合成路线1
该中间体在本合成路线中的序号:
(XXI) Treatment of cyclopropane-1,1-dicarboxylic acid (IX) with one equivalent of SOCl2 in the presence of Et3N in THF at 0 °C, followed by condensation of the activated intermediate with 4-fluoroaniline (X), provides the monoamide (XI) , which is optionally chlorinated to (VIII) by treatment with oxalyl chloride in cold THF .
Reaction of 3,4-difluoronitrobenzene (XII) with sodium benzylate prepared from benzyl alcohol and NaH in dimethylacetamide gives 1-benzyloxy-2-fluoro-4-nitrobenzene (XIII) as the main product. Subsequent reduction of compound (XIII) by means of iron and ammonium formate in refluxing toluene leads to the corresponding aniline (XIV), which is subsequently coupled with carboxylic acid (XI) using EDC in CH2Cl2 to afford the diamide (XV). Finally, debenzylation of diamide (XV) by transfer hydrogenation with 1,4-cyclohexadiene and Pd/C in boiling EtOH provides the target intermediate (I) . Scheme 2. Alternatively, acid chloride (VIII) can be directly condensed with 4-amino-2-fluorophenol (XVI) in the presence of 2,6-lutidine in cold THF to give diamide (I) .
【1】
Bannen, L.C., Chan, D.S.-M., Chen, J. (Exelixis, Inc.). c-Met modulators and methods of use. EP 1673085, EP 2210607, EP 2213661, JP 2007506777, JP 2010235631, JP 2010235632, WO 2005030140. |
【2】
Forsyth, T.P., Mac, M.B., Leahy, J.W., Nuss, J.M., Xu, W.(Exelixis, Inc.). c-Met modulators and methods of use. EP 1874759, JP 2008537748, US 2008161305, WO 2006108059. |
中间体序号 |
中间体编号 |
品名 |
CAS号 |
分子式 |
供应商 |
用于合成 |
(II) |
69103 |
7-(benzyloxy)-6-methoxyquinolin-4-yl trifluoromethanesulfonate |
|
C18H14F3NO5S |
详情 | 详情
|
(XVII) |
22604 |
1-(4-hydroxy-3-methoxyphenyl)-1-ethanone;Acetovanillone;4’-hydroxy-3’-methoxyacetophenone;1-(4-hydroxy-3-methoxyphenyl)ethanone |
498-02-2 |
C9H10O3 |
详情 | 详情
|
(XVIII) |
69112 |
1-(4-(benzyloxy)-3-methoxyphenyl)ethanone;3'-Methoxy-4'-(benzyloxy)acetophenone;4'-(Benzyloxy)-3'-methoxyacetophenone;Acetovanillone benzyl ether;1-(3-Methoxy-4-phenylmethoxyphenyl)ethanone |
1835-11-6 |
C16H16O3 |
详情 | 详情
|
(XIX) |
69113 |
1-(4-(benzyloxy)-5-methoxy-2-nitrophenyl)ethanone;4’-benzyloxy-5’-methoxy-2’-nitroacetophenone |
|
C16H15NO5 |
详情 | 详情
|
(XX) |
69114 |
1-(2-amino-4-(benzyloxy)-5-methoxyphenyl)ethanone |
|
C16H17NO3 |
详情 | 详情
|
(XXI) |
16602 |
ethyl formate
|
109-94-4 |
C3H6O2 |
详情 | 详情
|
(XXII) |
67631 |
7-(benzyloxy)-6-methoxyquinolin-4-ol |
|
C17H15NO3 |
详情 | 详情
|
合成路线2
该中间体在本合成路线中的序号:
(VI) The condensation of 6-methylpyridine-3-carboxaldehyde (I) with malonic acid (II) by means of piperidine in refluxing pyridine gives 3-(6-methyl-3-pyridyl)acrylic acid (III), which is esterified with ethanol and H2SO4 as usual to afford ethyl 3-(6-methyl-3-pyridyl)acrylate (IV). The reduction of (IV) with H2 over Pd/C in ethanol affords ethyl 3-(6-methyl-3-pyridyl)propionate (V), which is cyclized with ethyl formate (VI) and thiourea (VII) by means of Na in ether-ethanol yielding 5-(6-methyl-3-pyridylmethyl)-2-thiouracil (VIII). The methylation of (VIII) with methyl iodide and NaOH in hot water gives 5-(6-methyl-3-pyridyl-methyl)-2-methylthio-4-pyrimidone (IX), which is finally condensed with 2-[(5-dimethylaminomethylfuran-2-yl)methylthio]ethylamine (X) in refluxing pyridine.
【1】
Brown, T.H.; Ife, R.J. (SmithKline Beecham plc); Pyrimidine compounds. DD 140252; EP 0003677; ES 477667; US 4234588; US 4649141 .
|
【2】
de Angelis, L.; Serradell, M.N.; Castaner, J.; Blancafort, P.; SKF-93,479. Drugs Fut 1982, 7, 3, 175.
|
中间体序号 |
中间体编号 |
品名 |
CAS号 |
分子式 |
供应商 |
用于合成 |
(I) |
22949 |
6-methylnicotinaldehyde
|
|
C7H7NO |
详情 |
详情
|
(II) |
12963 |
Malonic acid
|
141-82-2 |
C3H4O4 |
详情 | 详情
|
(III) |
22950 |
(E)-3-(6-methyl-3-pyridinyl)-2-propenoic acid
|
|
C9H9NO2 |
详情 |
详情
|
(IV) |
36446 |
ethyl (E)-3-(6-methyl-3-pyridinyl)-2-propenoate
|
|
C11H13NO2 |
详情 |
详情
|
(V) |
22951 |
ethyl 3-(6-methyl-3-pyridinyl)propanoate
|
|
C11H15NO2 |
详情 |
详情
|
(VI) |
16602 |
ethyl formate
|
109-94-4 |
C3H6O2 |
详情 | 详情
|
(VII) |
10180 |
Thiourea
|
62-56-6 |
CH4N2S |
详情 | 详情
|
(VIII) |
36447 |
5-[(6-methyl-3-pyridinyl)methyl]-2-thioxo-2,3-dihydro-4(1H)-pyrimidinone
|
|
C11H11N3OS |
详情 |
详情
|
(IX) |
36448 |
5-[(6-methyl-3-pyridinyl)methyl]-2-(methylsulfanyl)-4(3H)-pyrimidinone
|
|
C12H13N3OS |
详情 |
详情
|
(X) |
13851 |
2-[([5-[(Dimethylamino)methyl]-2-furyl]methyl)sulfanyl]-1-ethanamine; N-[(5-[[(2-Aminoethyl)sulfanyl]methyl]-2-furyl)methyl]-N,N-dimethylamine
|
|
C10H18N2OS |
详情 |
详情
|
合成路线3
该中间体在本合成路线中的序号:
(A) The reaction of dl-l-phenylethylamine (I) with ethyl chloroacetate (II) by means of triethylamine in DMF gives dl-N-[(ethoxycarbonyl)methyl]-1-phenylethylamine (III), which is then treated with formic acid in refluxing xylene yielding dl-N-formyl-N-[(ethoxycarbonyl)methyl]-1-phenylethylamine (IV). The reaction of (IV) with sodium ethoxide and ethyl formate (A) in THF affords dl-N-formyl-N-[(ethoxycarbonyl)-2-hydroxyvinyl]-1-phenylethylamine (V), which, without purification, is treated with potassium thiocyanate and HCl in diisopropyl ether to give dl-l-(phenylethyl)-2-mercapto-5-ethoxycarbonylimidazole (VI). This product is finally treated with nitric acid and sodium nitrate at room temperature. The optical active drugs can be obtained starting the synthesis with the optically active amine (I).
中间体序号 |
中间体编号 |
品名 |
CAS号 |
分子式 |
供应商 |
用于合成 |
(A) |
16602 |
ethyl formate
|
109-94-4 |
C3H6O2 |
详情 | 详情
|
(I) |
10039 |
(1R)-1-Phenylethylamine; (1R)-1-Phenyl-1-ethanamine.; L-alpha-Phenylethylamine
|
3886-69-9 |
C8H11N |
详情 | 详情
|
(II) |
16601 |
ethyl chloroacetate; ethyl 2-chloroacetate
|
105-39-5 |
C4H7ClO2 |
详情 | 详情
|
(III) |
34103 |
ethyl 2-[[(1R)-1-phenylethyl]amino]acetate
|
|
C12H17NO2 |
详情 |
详情
|
(IV) |
34104 |
ethyl 2-[formyl[(1R)-1-phenylethyl]amino]acetate
|
|
C13H17NO3 |
详情 |
详情
|
(V) |
34105 |
ethyl (Z)-2-[formyl[(1R)-1-phenylethyl]amino]-3-hydroxy-2-propenoate
|
|
C14H17NO4 |
详情 |
详情
|
(VI) |
34106 |
ethyl 1-[(1R)-1-phenylethyl]-2-sulfanyl-1H-imidazole-5-carboxylate
|
|
C14H16N2O2S |
详情 |
详情
|
合成路线4
该中间体在本合成路线中的序号:
(B) 4) By reaction of the nitrile (I) with ethyl formate (B) by means of NaOEt in ethanol to give alpha-formyl-2,6-dichlorophenylacetonitrile (III), which is condensed with guanidine hydrochloride (A) by means of NaOEt in ethanol to yield alpha-(guanidinomethylene)-2,6-dichlorophenylacetonitrile (IV); this product is finally hydrolyzed and rearranged by means of HCl.
【1】
Arrigoni-Martelli, E.; Castaner, J.; BS 100-141. Drugs Fut 1976, 1, 4, 167.
|
【2】
Bream, J.B.; et al.; Verfahren zur Herstellung von Acylguanidinen. CH 511816 .
|
【3】
Bream, J.B.; et al.; Verfahren zur Herstellung von Acylguanidinen. CH 518910 .
|
中间体序号 |
中间体编号 |
品名 |
CAS号 |
分子式 |
供应商 |
用于合成 |
(A) |
14790 |
Guanidine
|
113-00-8 |
CH5N3 |
详情 | 详情
|
(B) |
16602 |
ethyl formate
|
109-94-4 |
C3H6O2 |
详情 | 详情
|
(I) |
18202 |
2-(2,6-dichlorophenyl)acetonitrile; 2,6-Dichlorophenylacetonitrile
|
3215-64-3 |
C8H5Cl2N |
详情 | 详情
|
(III) |
40331 |
2-(2,6-dichlorophenyl)-2-hydroxyacetonitrile
|
|
C8H5Cl2NO |
详情 |
详情
|
(IV) |
40332 |
N''-[(Z)-2-cyano-2-(2,6-dichlorophenyl)ethenyl]guanidine
|
|
C10H8Cl2N4 |
详情 |
详情
|
合成路线5
该中间体在本合成路线中的序号:
(II) The cyclization of the imidazolyl riboside (I) with [13C]-formic acid ethyl ester (II) by means of sodium ethoxide in refluxing ethanol gives labeled inosine (III), which is acetylated with Ac2O and pyridine yielding the triacetate (IV). The nitration of (IV) with ammonium nitrate and trifluoroacetic anhydride affords the 1-nitroinosine (V), which is rearranged with 15NH4Cl in acetonitrile/water to provide the doubly labeled inosine (VI). The reaction of (VI) with SOCl2 gives the chloropurine (VII), which is condensed with the dideuterated 2-aminocyclopentanol (rac-trans)-(VIII) (obtained by hydrogenation of the unsaturated analogue (rac-trans)-(IX)) by means of NaHCO3 in isopropanol providing a diastereomeric mixture (X). The deacetylation of (X) with tert-butylamine in methanol furnishes a mixture of the target compound along with its diastereomer, which is separated by preparative HPLC.
【1】
Wadsworth, A.H.; et al.; Synthesis of isotopically labelled versions of adenosine agonist GR79236. J Label Compd Radiopharm 2000, 43, 1, 11.
|
中间体序号 |
中间体编号 |
品名 |
CAS号 |
分子式 |
供应商 |
用于合成 |
(IV),(VI) |
38014 |
(2R,3R,4R,5R)-4-(acetoxy)-2-[(acetoxy)methyl]-5-(6-oxo-1,6-dihydro-9H-purin-9-yl)tetrahydro-3-furanyl acetate
|
|
C16H18N4O8 |
详情 |
详情
|
(I) |
37427 |
5-amino-1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]-1H-imidazole-4-carboxamide
|
|
C9H14N4O5 |
详情 |
详情
|
(II) |
16602 |
ethyl formate
|
109-94-4 |
C3H6O2 |
详情 | 详情
|
(II) |
45175 |
ethyl formate
|
|
C3H6O2 |
详情 |
详情
|
(III) |
38013 |
9-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]-1,9-dihydro-6H-purin-6-one
|
|
C10H12N4O5 |
详情 |
详情
|
(III) |
45176 |
9-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]-1,9-dihydro-6H-purin-6-one
|
|
C10H12N4O5 |
详情 |
详情
|
(IV) |
45177 |
(2R,3R,4R,5R)-4-(acetoxy)-2-[(acetoxy)methyl]-5-(6-oxo-1,6-dihydro-9H-purin-9-yl)tetrahydro-3-furanyl acetate
|
|
C16H18N4O8 |
详情 |
详情
|
(V) |
38015 |
(2R,3R,4R,5R)-4-(acetoxy)-2-[(acetoxy)methyl]-5-(1-nitro-6-oxo-1,6-dihydro-9H-purin-9-yl)tetrahydro-3-furanyl acetate
|
|
C16H17N5O10 |
详情 |
详情
|
(V) |
45178 |
(2R,3R,4R,5R)-4-(acetoxy)-2-[(acetoxy)methyl]-5-(1-nitro-6-oxo-1,6-dihydro-9H-purin-9-yl)tetrahydro-3-furanyl acetate
|
|
C16H17N5O10 |
详情 |
详情
|
(VI) |
45179 |
(2R,3R,4R,5R)-4-(acetoxy)-2-[(acetoxy)methyl]-5-(6-oxo-1,6-dihydro-9H-purin-9-yl)tetrahydro-3-furanyl acetate
|
|
C16H18N4O8 |
详情 |
详情
|
(VII) |
38016 |
(2R,3R,4R,5R)-4-(acetoxy)-2-[(acetoxy)methyl]-5-(6-chloro-9H-purin-9-yl)tetrahydro-3-furanyl acetate
|
|
C16H17ClN4O7 |
详情 |
详情
|
(VII) |
45180 |
(2R,3R,4R,5R)-4-(acetoxy)-2-[(acetoxy)methyl]-5-(6-chloro-9H-purin-9-yl)tetrahydro-3-furanyl acetate
|
|
C16H17ClN4O7 |
详情 |
详情
|
(VIII) |
38010 |
(1S,2S)-2-aminocyclopentanol
|
|
C5H11NO |
详情 |
详情
|
(VIII) |
45181 |
(1S,2S)-2-aminocyclopentanol
|
|
C5H11NO |
详情 |
详情
|
(IX) |
38017 |
(1S,2S)-2-amino-3-cyclopenten-1-ol
|
|
C5H9NO |
详情 |
详情
|
(X) |
38018 |
(2R,3R,4R,5R)-4-(acetoxy)-2-[(acetoxy)methyl]-5-(6-[[(1S,2S)-2-hydroxycyclopentyl]amino]-9H-purin-9-yl)tetrahydro-3-furanyl acetate
|
|
C21H27N5O8 |
详情 |
详情
|
(X) |
45182 |
(2R,3R,4R,5R)-4-(acetoxy)-2-[(acetoxy)methyl]-5-(6-[[(1S,2S)-2-hydroxycyclopentyl]amino]-9H-purin-9-yl)tetrahydro-3-furanyl acetate
|
|
C21H27N5O8 |
详情 |
详情
|
合成路线6
该中间体在本合成路线中的序号:
(B) The condensation of cyclohexene-epoxide (I) with pyrrolidine (II) gives trans-2-(1-pyrrolidinyl)cyclohexanol (III), which by reaction with NaH and methanesulfonyl chloride, and then with benzylamine is converted into trans-2-(1-pyrrolidinyl)-N-benzylcyclohexylamine (IV). The debenzylation of (IV) by hydrogenolysis with H2 over Pd/C affords trans-2-(1-pyrrolidinyl)cyclohexylamine (V), which is formylated with ethyl formate to the corresponding N-formyl-trans-2-(1-pyrrolidinyl)cyclohexylamine (VI). The reduction of (VI) with LiAlH4 in refluxing ether gives trans-N-methyl-2-(1-pyrrolidinyl)cyclohexylamine (VII), which is finally condensed with 3,4-dichlorophenylacetic acid (VIII) by means of carbonyl diimidazole (IX) in THF.
中间体序号 |
中间体编号 |
品名 |
CAS号 |
分子式 |
供应商 |
用于合成 |
(A) |
15147 |
Benzylamine; Phenylmethanamine
|
100-46-9 |
C7H9N |
详情 | 详情
|
(B) |
16602 |
ethyl formate
|
109-94-4 |
C3H6O2 |
详情 | 详情
|
(I) |
17986 |
7-oxabicyclo[4.1.0]heptane; cyclohexene oxide
|
286-20-4 |
C6H10O |
详情 | 详情
|
(II) |
11376 |
Pyrrolidine
|
123-75-1 |
C4H9N |
详情 | 详情
|
(III) |
14637 |
(1R,2R)-2-(1-pyrrolidinyl)cyclohexanol
|
|
C10H19NO |
详情 |
详情
|
(IV) |
37038 |
N-phenyl-N-[(1R,2R)-2-(1-pyrrolidinyl)cyclohexyl]amine; N-[(1R,2R)-2-(1-pyrrolidinyl)cyclohexyl]aniline
|
|
C16H24N2 |
详情 |
详情
|
(V) |
37040 |
(1R,2R)-2-(1-pyrrolidinyl)cyclohexylamine; (1R,2R)-2-(1-pyrrolidinyl)cyclohexanamine
|
|
C10H20N2 |
详情 |
详情
|
(VI) |
37011 |
1-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-quinoxalinyl)-2-propen-1-one
|
|
C15H20N2O |
详情 |
详情
|
(VII) |
31357 |
N-methyl-N-[(1R,2R)-2-(1-pyrrolidinyl)cyclohexyl]amine; (1R,2R)-N-methyl-2-(1-pyrrolidinyl)cyclohexanamine
|
|
C11H22N2 |
详情 |
详情
|
(VIII) |
30414 |
2-(3,4-dichlorophenyl)acetic acid;2-(3,4-Dichlorophenyl)acetic acid |
5807-30-7 |
C8H6Cl2O2 |
详情 | 详情
|
(IX) |
11353 |
1,1'-Carbonyldiimidazole; Di(1H-imidazol-1-yl)methanone; N,N-Carbonyldiimidazole; 1,1'-Carbonylbis(1H-imidazole)
|
530-62-1 |
C7H6N4O |
详情 | 详情
|
(X) |
37039 |
7-azabicyclo[4.1.0]heptane
|
|
C6H11N |
详情 |
详情
|
合成路线7
该中间体在本合成路线中的序号:
(XVIII) The thiazolyl carbonate (XI) has been synthesized as follows:
The reaction of formamide (XIV) with P2S5 in ethyl ether gives thioformamide (XV), which is cyclized with 2-chloro-3-oxopropionic acid ethyl ester (XVI) [obtained by condensation of ethyl chloroacetate (XVII) with ethyl formate (XVIII) by means of t-BuOK in THF] yielding thiazol-5-carboxylic acid ethyl ester (XIX). The reduction of (XIX) with LiAlH4 in THF affords 5-thiazolylmethanol (XX), which is then esterified with 4-nitrophenyl chloroformate (XXI) by means of 4-methylmorpholine (MPH) in dichloromethane to give the desired product (XI).
【1】
Graul, A.; Castañer, J.; Ritonavir. Drugs Fut 1996, 21, 7, 700.
|
【2】
Kempf, D.J.; Norbeck, D.W.; Sham, H.L.; Zhao, C.; Sowin, T.J.; Reno, D.S.; Haight, A.R.; Cooper, A.J. (Abbott Laboratories Inc.); Retroviral protease inhibiting cpds. EP 0674513; EP 0727419; JP 1996505844; JP 1997118679; JP 1998087639; WO 9414436 .
|
【3】
Al-Razzak, L.; Marsh, K.C.; Manning, L.P.; Kaul, D. (Abbott Laboratories Inc.); Pharmaceutical compsns. containing HIV protease inhibitors. EP 0732923; US 5484801; WO 9520384 .
|
【4】
Flentge, C.; Kempf, D.; Marsh, K.; et al.; Symmetry-based inhibitors of HIV protease with high oral bioavailability. 207th ACS Natl Meet (March 13-17, San Diego) 1994, Abst MEDI 35.
|
中间体序号 |
中间体编号 |
品名 |
CAS号 |
分子式 |
供应商 |
用于合成 |
(XI) |
16595 |
4-nitrophenyl 1,3-thiazol-5-ylmethyl carbonate
|
144163-97-3 |
C11H8N2O5S |
详情 | 详情
|
(XIV) |
16598 |
Formamide
|
75-12-7 |
CH3NO |
详情 | 详情
|
(XV) |
16599 |
Thioformamide
|
|
CH3NS |
详情 |
详情
|
(XVI) |
16600 |
ethyl 2-chloro-3-oxopropanoate
|
|
C5H7ClO3 |
详情 |
详情
|
(XVII) |
16601 |
ethyl chloroacetate; ethyl 2-chloroacetate
|
105-39-5 |
C4H7ClO2 |
详情 | 详情
|
(XVIII) |
16602 |
ethyl formate
|
109-94-4 |
C3H6O2 |
详情 | 详情
|
(XIX) |
16603 |
ethyl 1,3-thiazole-5-carboxylate
|
32955-22-9 |
C6H7NO2S |
详情 | 详情
|
(XX) |
16604 |
1,3-thiazol-5-ylmethanol;5-thiazolylmethanol;Thiazole-5-methanol |
38585-74-9 |
C4H5NOS |
详情 | 详情
|
(XXI) |
16605 |
4-Nitrophenyl chloroformate; 1-[(Chlorocarbonyl)oxy]-4-nitrobenzene
|
7693-46-1 |
C7H4ClNO4 |
详情 | 详情
|
合成路线8
该中间体在本合成路线中的序号:
(II) The reaction of ethyl chloroacetate (I) with ethyl formate (II) by means of potassium tert-butoxide in diisopropyl ether gives the 2-formylchloroacetate (III), which is cyclized with 6-methylpyridine-2-amine (IV) by means of conc. H2SO4, yielding 5-methylimidazo[1,2-a]pyridine-3-carboxylic acid ethyl ester (V). The chlorination of (V) with NCS in THF affords the chloromethyl derivative (VI), which is condensed with the monoprotected diamine (VII) by means of TEA to provide the adduct (VIII). The cyclization of (VIII) by means of NaOMe, TEA and NaI in DMF gives 4-[4-(benzyloxycarbonylamino)butyl]-4,5-dihydro-3H-1,4,8b-triazaacenaphthylen-3-one (IX), which is deprotected with H2 over Pd/C in MeOH, yielding the butylamine derivative (X). Finally, this compound is sulfonated with N-phenyltrifluoromethylsulfonimide (XI) and TEA in DMF.
【1】
Ikemoto, T.; et al.; A practical synthesis of the chronic renal disease agent, 4,5-dihydro-3H-1,4,8b-triazaacenaphthylen-3-one derivatives, using regioselective chlorination of ethyl 5-methylimidazo[1,2-a]pyridine-3-carboxy with N-chlorosuccinimide. Tetrahedron 2000, 56, 40, 7915. |
【2】
Takatani, M.; Shibouta, Y.; Tomimatsu, K.; Kawamoto, T. (Takeda Chemical Industries, Ltd.); Tricyclic cpds., their production and use. EP 0771319; JP 1996081467; WO 9602542 .
|
中间体序号 |
中间体编号 |
品名 |
CAS号 |
分子式 |
供应商 |
用于合成 |
(I) |
10257 |
methyl 2-chloroacetate; methyl chloroacetate
|
96-34-4 |
C3H5ClO2 |
详情 | 详情
|
(II) |
16602 |
ethyl formate
|
109-94-4 |
C3H6O2 |
详情 | 详情
|
(III) |
16600 |
ethyl 2-chloro-3-oxopropanoate
|
|
C5H7ClO3 |
详情 |
详情
|
(IV) |
19678 |
6-methyl-2-pyridinamine; 6-methyl-2-pyridinylamine; 6-amino-2-picoline; 2-Amino-6-methylpyridine
|
1824-81-3 |
C6H8N2 |
详情 | 详情
|
(V) |
42075 |
ethyl 5-methylimidazo[1,2-a]pyridine-3-carboxylate
|
|
C11H12N2O2 |
详情 |
详情
|
(VI) |
42076 |
ethyl 5-(chloromethyl)imidazo[1,2-a]pyridine-3-carboxylate
|
|
C11H11ClN2O2 |
详情 |
详情
|
(VII) |
42077 |
benzyl 4-aminobutylcarbamate
|
62146-62-7 |
C12H18N2O2 |
详情 | 详情
|
(VIII) |
42078 |
ethyl 5-[[(4-[[(benzyloxy)carbonyl]amino]butyl)amino]methyl]imidazo[1,2-a]pyridine-3-carboxylate
|
|
C23H28N4O4 |
详情 |
详情
|
(IX) |
42079 |
benzyl 4-(3-oxo-3,5-dihydro-4H-1,4,8b-triazaacenaphthylen-4-yl)butylcarbamate
|
|
C21H22N4O3 |
详情 |
详情
|
(X) |
42080 |
4-(4-aminobutyl)-4,5-dihydro-3H-1,4,8b-triazaacenaphthylen-3-one
|
|
C13H16N4O |
详情 |
详情
|
(XI) |
17573 |
N-Phenyltrifluoromethanesulfonimide; Trifluoro-N-phenyl-N-[(trifluoromethyl)sulfonyl]methanesulfonamide
|
37595-74-7 |
C8H5F6NO4S2 |
详情 | 详情
|
合成路线9
该中间体在本合成路线中的序号:
Claisen condensation of 3-beta-acetyloxypregna-5,16-dien-20-one (I) with ethyl formate in the presence of NaOMe in pyridine, with simultaneous deacetylation, provided the corresponding 21-formyl derivative (II). Subsequent treatment of (II) with hydroxylamine yielded isoxazole (III) as the only regioisomer. Finally, Oppenauer oxidation of (III) with cyclohexanone and aluminum isopropoxide gave rise to the target alpha,beta-unsaturated ketone.
【1】
Ling, Y.; et al.; 17-Imidazolyl, pyrazolyl, and isoxazolyl androstene derivatives, novel steroidal inhibitors of human cytochrome C17,20-lyase (P45017alpha). J Med Chem 1997, 40, 20, 3297.
|
中间体序号 |
中间体编号 |
品名 |
CAS号 |
分子式 |
供应商 |
用于合成 |
|
16602 |
ethyl formate
|
109-94-4 |
C3H6O2 |
详情 | 详情
|
(I) |
32586 |
(3S,8R,9S,10R,13S,14S)-17-acetyl-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15-dodecahydro-1H-cyclopenta[a]phenanthren-3-yl acetate
|
979-02-2 |
C23H32O3 |
详情 | 详情
|
(II) |
32587 |
(Z)-3-hydroxy-1-[(3S,8R,9S,10R,13S,14S)-3-hydroxy-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15-dodecahydro-1H-cyclopenta[a]phenanthren-17-yl]-2-propen-1-one
|
|
C22H30O3 |
详情 |
详情
|
(III) |
32588 |
(3S,8R,9S,10R,13S,14S)-17-(5-isoxazolyl)-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15-dodecahydro-1H-cyclopenta[a]phenanthren-3-ol
|
|
C22H29NO2 |
详情 |
详情
|
合成路线10
该中间体在本合成路线中的序号:
Keto oxime (IV) was converted to the syn amino alcohol (XII) by palladium-catalyzed hydrogenation. Subsequent N-methylation of (XII) to give (XIV) was then achieved via formylation of the primary amine to formamide (XIII) in refluxing ethyl formate, followed by borane reduction. Acylation of the secondary amine (XIV) with N-(benzyloxycarbonyl)piperidine-4-carbonyl chloride (XV) provided amide (XVI). After Swern oxidation of the alcohol group of (XVI), the keto amide (XVII) was cyclized to the desired imidazole (VIII) in boiling ammonium formate.
【1】
Claiborne, C.F.; et al.; An efficient synthesis of tetrasubstituted imidazoles from N-(2-oxo)-amides. Tetrahedron Lett 1998, 39, 49, 8939.
|
中间体序号 |
中间体编号 |
品名 |
CAS号 |
分子式 |
供应商 |
用于合成 |
|
16602 |
ethyl formate
|
109-94-4 |
C3H6O2 |
详情 | 详情
|
(IV) |
35155 |
1-(2-fluoro-4-pyridinyl)-2-[3-(trifluoromethyl)phenyl]-1,2-ethanedione 1-oxime
|
|
C14H8F4N2O2 |
详情 |
详情
|
(VIII) |
35159 |
benzyl 4-[5-(2-fluoro-4-pyridinyl)-1-methyl-4-[3-(trifluoromethyl)phenyl]-1H-imidazol-2-yl]-1-piperidinecarboxylate
|
|
C29H26F4N4O2 |
详情 |
详情
|
(XII) |
35162 |
(1S,2R)-2-amino-2-(2-fluoro-4-pyridinyl)-1-[3-(trifluoromethyl)phenyl]-1-ethanol
|
|
C14H12F4N2O |
详情 |
详情
|
(XIII) |
35163 |
(1R,2S)-1-(2-fluoro-4-pyridinyl)-2-hydroxy-2-[3-(trifluoromethyl)phenyl]ethylformamide
|
|
C15H12F4N2O2 |
详情 |
详情
|
(XIV) |
35164 |
(1S,2R)-2-(2-fluoro-4-pyridinyl)-2-(methylamino)-1-[3-(trifluoromethyl)phenyl]-1-ethanol
|
|
C15H14F4N2O |
详情 |
详情
|
(XV) |
35165 |
benzyl 4-(chlorocarbonyl)-1-piperidinecarboxylate
|
|
C14H16ClNO3 |
详情 |
详情
|
(XVI) |
35166 |
benzyl 4-[[[(1R,2S)-1-(2-fluoro-4-pyridinyl)-2-hydroxy-2-[3-(trifluoromethyl)phenyl]ethyl](methyl)amino]carbonyl]-1-piperidinecarboxylate
|
|
C29H29F4N3O4 |
详情 |
详情
|
(XVII) |
35167 |
benzyl 4-[[[(1R)-1-(2-fluoro-4-pyridinyl)-2-oxo-2-[3-(trifluoromethyl)phenyl]ethyl](methyl)amino]carbonyl]-1-piperidinecarboxylate
|
|
C29H27F4N3O4 |
详情 |
详情
|
合成路线11
该中间体在本合成路线中的序号:
(XII) Alternatively, the desired compound can be obtained as follows: Treatment of diethyl cyanomethyl phosphonate (VII) with NaH in dimethoxyethane (DME) followed by reaction with 3,3'-difluorobenzophenone (VIII) gives alkene derivative (IX), which is then hydrogenated over Pd(OH)2 to provide compound (X). Reduction of the cyano moiety of (X) by means of B2H6-THF followed by treatment with refluxing HCl yields substituted propylamine (XI), which is then converted into formamide (XIII) by treatment with refluxing ethyl formate (XII). Compound (XIII) is then reduced by means of borane-methyl sulfide in refluxing THF and finally treated with HCl. Propylamine (XI) can also be obtained following these steps: Treatment of benzophenone derivative (VIII) with n-BuLi and acetonitrile in THF affords cyano derivative (XIV), which is then hydrogenated over Ni/Al and NaOH in EtOH to furnish amine (XV). Elimination of the tertiary alcohol (XV) by refluxing with HCl in EtOH gives substituted diphenylpropenamine hydrochloride (XVI), which is hydrogenated over Pd/C in EtOH and finally subjected to hydrochloride salt neutralization.
【1】
Moe, S.T.; Mueller, A.L.; Vanwagenen, B.C.; Barmore, R.M.; Delmar, E.G.; Artman, L.D.; Balandrin, M.F.; Smith, D.L. (NPS Pharmaceuticals, Inc.); Cpds. active at a novel site on receptor-operated calcium channels useful for treatment of neurological disorders and diseases. WO 9746511 . |
【2】
Barmore, R.M.; DelMar, E.G.; Balandrin, M.F.; VanWagenen, B.C.; Artman, L.D.; Mueller, A.L.; Moe, S.T. (NPS Pharmaceuticals, Inc.); Cpds. active at a novel site on receptor-operated calcium channels useful for treatment of neurological disorders and diseases. US 6071970 . |
中间体序号 |
中间体编号 |
品名 |
CAS号 |
分子式 |
供应商 |
用于合成 |
(VII) |
10045 |
Diethyl cyanomethylphosphonate
|
2537-48-6 |
C6H12NO3P |
详情 | 详情
|
(VIII) |
35077 |
bis(3-fluorophenyl)methanone
|
345-70-0 |
C13H8F2O |
详情 | 详情
|
(IX) |
35078 |
3,3-bis(3-fluorophenyl)acrylonitrile
|
|
C15H9F2N |
详情 |
详情
|
(X) |
35079 |
3,3-bis(3-fluorophenyl)propanenitrile
|
|
C15H11F2N |
详情 |
详情
|
(XI) |
48851 |
3,3-bis(3-fluorophenyl)-1-propanamine; 3,3-bis(3-fluorophenyl)propylamine
|
|
C15H15F2N |
详情 |
详情
|
(XII) |
16602 |
ethyl formate
|
109-94-4 |
C3H6O2 |
详情 | 详情
|
(XIII) |
48852 |
3,3-bis(3-fluorophenyl)propylformamide
|
|
C16H15F2NO |
详情 |
详情
|
(XIV) |
37211 |
3,3-bis(3-fluorophenyl)-3-hydroxypropanenitrile
|
|
C15H11F2NO |
详情 |
详情
|
(XV) |
37212 |
3-amino-1,1-bis(3-fluorophenyl)-1-propanol
|
|
C15H15F2NO |
详情 |
详情
|
(XVI) |
37213 |
3,3-bis(3-fluorophenyl)-2-propen-1-amine; 3,3-bis(3-fluorophenyl)-2-propenylamine
|
|
C15H13F2N |
详情 |
详情
|
合成路线12
该中间体在本合成路线中的序号:
(II) Claisen reaction between ethyl caproate (I) and ethyl formate (II) in the presence of NaOEt affords formyl derivative (III), which is then condensed with O-benzyl hydroxylamine hydrochloride (IV) by means of NaOAc in EtOH/H2O to yield derivative (V). Hydrolysis of the ethyl ester moiety of (V) by treatment with aqueous NaOH in MeOH provides carboxylic acid (VI), which is coupled to tert-leucine N,N-dimethylamide (VII) by means of EDC and HOAt to furnish compound (VIII). Reduction of the oxime moiety of (VIII) with NaCNBH3 in HOAc affords a mixture of diastereoisomers from which (R)-(IX) is separated by flash chromatography.
Finally, treatment of (R)-(IX) with N-formyl-benzotriazole (HCOBt) in THF provides formamide (X), whose benzyl group is then removed by hydrogenation over Pd/C in MeOH.
【1】
Spavold, Z.M.; Launchbury, S.; Clements, J.M.; Hunter, M.G.; Davies, S.J.; Pratt, L.M.; Beckett, R.P.; Whittaker, M. (British Biotech Pharmaceuticals Ltd.); Antibacterial agents. WO 9939704 .
|
中间体序号 |
中间体编号 |
品名 |
CAS号 |
分子式 |
供应商 |
用于合成 |
(VIIIa) |
45887 |
(2R)-2-[[(benzyloxy)imino]methyl]-N-[(1S)-1-[(dimethylamino)carbonyl]-2,2-dimethylpropyl]hexanamide
|
|
C22H35N3O3 |
详情 |
详情
|
(VIIIb) |
45890 |
(2S)-2-[[(benzyloxy)imino]methyl]-N-[(1S)-1-[(dimethylamino)carbonyl]-2,2-dimethylpropyl]hexanamide
|
|
C22H35N3O3 |
详情 |
详情
|
(I) |
51702 |
Ethyl caproate; Ethyl n-Caproate; Caproic acid ethyl ester; n-Caproic acid ethylester; Capronic Ether; Isoamyl acetate; Hexanoic acid ethyl ester; Ethyl hexanoate
|
123-66-0 |
C8H16O2 |
详情 | 详情
|
(II) |
16602 |
ethyl formate
|
109-94-4 |
C3H6O2 |
详情 | 详情
|
(III) |
45886 |
(2S)-2-amino-N,N,3,3-tetramethylbutanamide
|
|
C8H18N2O |
详情 |
详情
|
(IV) |
14640 |
O-benzylhydroxylamine; 1-[(aminooxy)methyl]benzene
|
622-33-3 |
C7H9NO |
详情 | 详情
|
(V) |
45884 |
ethyl 2-[[(benzyloxy)imino]methyl]hexanoate
|
|
C16H23NO3 |
详情 |
详情
|
(VI) |
45885 |
2-[[(benzyloxy)imino]methyl]hexanoic acid
|
|
C14H19NO3 |
详情 |
详情
|
(VII) |
45886 |
(2S)-2-amino-N,N,3,3-tetramethylbutanamide
|
|
C8H18N2O |
详情 |
详情
|
(IX) |
45888 |
(2R)-2-[[(benzyloxy)amino]methyl]-N-[(1S)-1-[(dimethylamino)carbonyl]-2,2-dimethylpropyl]hexanamide
|
|
C22H37N3O3 |
详情 |
详情
|
(X) |
45889 |
(2R)-2-[[(benzyloxy)(formyl)amino]methyl]-N-[(1S)-1-[(dimethylamino)carbonyl]-2,2-dimethylpropyl]hexanamide
|
|
C23H37N3O4 |
详情 |
详情
|
合成路线13
该中间体在本合成路线中的序号:
(V) The chiral intermediate (X) is prepared by two methods. Treatment of lactonitrile (I) with HCl/EtOH affords imidate (II), which is further reacted with ethanolic ammonia to produce amidine (III). Claisen condensation between ethyl acetate (IV) and ethyl formate (V) in the presence of NaH provides the sodium salt of ethyl 3-hydroxyacrylate (VI). Cyclization of (VI) with amidine (III) then furnishes the racemic pyrimidinone (VII). Kinetic resolution of (VII) is accomplished by acylation with vinyl butyrate (VIII) in the presence of lipase P30 to yield a mixture of unreacted (S)-alcohol (IX) and the desired (R)-butyrate ester (X), which can be separated by partition between CH2Cl2 and H2O.
【1】
Mylari, B.L.; Zembrowski, W.J.; Murry, J.A.; Chu-Moyer, M.Y. (Pfizer Products Inc.); Aminopyrimidines as sorbitol dehydrogenase inhibitors. EP 1185275; US 6414149; WO 0059510 .
|
中间体序号 |
中间体编号 |
品名 |
CAS号 |
分子式 |
供应商 |
用于合成 |
(I) |
64060 |
2-hydroxypropanenitrile
|
|
C3H5NO |
详情 |
详情
|
(II) |
64061 |
ethyl 2-hydroxypropanimidoate
|
|
C5H11NO2 |
详情 |
详情
|
(III) |
64062 |
2-hydroxypropanimidamide
|
|
C3H8N2O |
详情 |
详情
|
(IV) |
17491 |
ethyl acetate
|
141-78-6 |
C4H8O2 |
详情 | 详情
|
(V) |
16602 |
ethyl formate
|
109-94-4 |
C3H6O2 |
详情 | 详情
|
(VI) |
64063 |
sodium (E)-3-ethoxy-3-oxo-1-propen-1-olate
|
|
C5H7NaO3 |
详情 |
详情
|
(VII) |
64064 |
2-(1-hydroxyethyl)-4(3H)-pyrimidinone
|
|
C6H8N2O2 |
详情 |
详情
|
(VIII) |
53263 |
n-Butyric acid vinyl ester; Vinyl n-butyrate; Vinyl butyrate
|
123-20-6 |
C6H10O2 |
详情 | 详情
|
(IX) |
64065 |
2-[(1S)-1-hydroxyethyl]-4(3H)-pyrimidinone
|
|
C6H8N2O2 |
详情 |
详情
|
(X) |
64066 |
(1R)-1-(6-oxo-1,6-dihydro-2-pyrimidinyl)ethyl butyrate
|
|
C10H14N2O3 |
详情 |
详情
|
合成路线14
该中间体在本合成路线中的序号:
(I)
【1】
Khamar BM, Modi IA, Shukla MC, et aL. 2006. A process for the preparation of zaleplon. W0 2006070244 |
中间体序号 |
中间体编号 |
品名 |
CAS号 |
分子式 |
供应商 |
用于合成 |
(I) |
16602 |
ethyl formate
|
109-94-4 |
C3H6O2 |
详情 | 详情
|
(II) |
66968 |
1-(3-bromophenyl)ethanone |
2142-63-4 |
C8H7BrO |
详情 | 详情
|
(III) |
66969 |
sodium 1-(3-bromophenyl)-1,3-dioxopropan-2-ide |
|
C9H6BrNaO2 |
详情 | 详情
|
(IV) |
11987 |
3-Amino-4-pyrazolecarbonitrile; 3-Amino-1H-pyrazole-4-carbonitrile; 3-Amino-4-cyanopyrazole
|
16617-46-2 |
C4H4N4 |
详情 | 详情
|
(V) |
66970 |
7-(3-bromophenyl)pyrazolo[1,5-a]pyrimidine-3-carbonitrile |
933054-30-9 |
C13H7BrN4 |
详情 | 详情
|
(VI) |
66971 |
N-(3-(3-cyanopyrazolo[1,5-a]pyrimidin-7-yl)phenyl)acetamide |
115931-01-6 |
C15H11N5O |
详情 | 详情
|
合成路线15
该中间体在本合成路线中的序号:
(I)
【1】
Horns S. 2003. Method for producing N-ethyl-N-[3-(3-cyanopyrazolo [1, 5α] pyrimidin-7-yl) phenyl] acetamide (zaleplon). W0 2003068775 |
中间体序号 |
中间体编号 |
品名 |
CAS号 |
分子式 |
供应商 |
用于合成 |
(I) |
16602 |
ethyl formate
|
109-94-4 |
C3H6O2 |
详情 | 详情
|
(II) |
66973 |
N-(3-acetylphenyl)-N-ethylacetamide |
|
C12H15NO2 |
详情 | 详情
|
(III) |
66974 |
sodium 1-(3-(N-ethylacetamido)phenyl)-1,3-dioxopropan-2-ide |
|
C13H14NaNO3 |
详情 | 详情
|
(IV) |
11987 |
3-Amino-4-pyrazolecarbonitrile; 3-Amino-1H-pyrazole-4-carbonitrile; 3-Amino-4-cyanopyrazole
|
16617-46-2 |
C4H4N4 |
详情 | 详情
|
合成路线16
该中间体在本合成路线中的序号:
(XVIII) Condensation of 4-hydroxy-3-methoxyacetophenone (XIII) with mesylate (XIV) by means of K2CO3 in DMF at 100 °C yields the aryl ether (XV), which by nitration using HNO3 in AcOH gives the corresponding o-nitroaryl ketone (XVI). Reduction of the nitro group in compound (XVI) using Fe and NH4Cl in refluxing EtOH/H2O gives amine (XVII). Friedlaender cyclization of the o-aminoaryl ketone (XVII) with ethyl formate (XVIII) and NaOMe in DME affords a 4-hydroxyquinoline derivative, which without isolation is chlorinated using POCl3 to produce the corresponding chloride (XIX). Condensation of the aryl chloride (XIX) with 6-hydroxy-N-methyl-1-naphthamide (V) in the presence of DMAP in refluxing dioxane gives adduct (XX), whose methyl ester is hydrolyzed with NaOH in refluxing MeOH to afford acid (XXI). Activation of acid (XXI) with i-BuOCOCl in the presence of DIEA in acetone and subsequent substitution of the obtained mixed anhydride with NaN3 produces azide (XXII), which is finally treated with PhCH2OH in refluxing toluene .
中间体序号 |
中间体编号 |
品名 |
CAS号 |
分子式 |
供应商 |
用于合成 |
(V) |
67629 |
6-hydroxy-N-methyl-1-naphthamide |
|
C12H11NO2 |
详情 | 详情
|
(XIII) |
22604 |
1-(4-hydroxy-3-methoxyphenyl)-1-ethanone;Acetovanillone;4’-hydroxy-3’-methoxyacetophenone;1-(4-hydroxy-3-methoxyphenyl)ethanone |
498-02-2 |
C9H10O3 |
详情 | 详情
|
(XIV) |
67637 |
1-(4-hydroxy-3-methoxyphenyl)ethanone |
|
C7H12O5S |
详情 | 详情
|
(XV) |
67638 |
methyl 1-((4-acetyl-2-methoxyphenoxy)methyl)cyclopropanecarboxylate |
|
C15H18O5 |
详情 | 详情
|
(XVI) |
67639 |
methyl 1-((4-acetyl-2-methoxy-5-nitrophenoxy)methyl)cyclopropanecarboxylate |
|
C15H17NO7 |
详情 | 详情
|
(XVII) |
67640 |
methyl 1-((4-acetyl-5-amino-2-methoxyphenoxy)methyl)cyclopropanecarboxylate |
|
C15H19NO5 |
详情 | 详情
|
(XVIII) |
16602 |
ethyl formate
|
109-94-4 |
C3H6O2 |
详情 | 详情
|
(XIX) |
67641 |
methyl 1-(((4-chloro-6-methoxyquinolin-7-yl)oxy)methyl)cyclopropanecarboxylate |
|
C16H16ClNO4 |
详情 | 详情
|
(XX) |
67642 |
methyl 1-(((6-methoxy-4-((5-(methylcarbamoyl)naphthalen-1-yl)oxy)quinolin-7-yl)oxy)methyl)cyclopropanecarboxylate |
|
C28H26N2O6 |
详情 |
详情
|
(XXI) |
67643 |
1-(((6-methoxy-4-((5-(methylcarbamoyl)naphthalen-1-yl)oxy)quinolin-7-yl)oxy)methyl)cyclopropanecarboxylic acid |
|
C27H24N2O6 |
详情 | 详情
|
(XXII) |
67644 |
1-(((6-methoxy-4-((5-(methylcarbamoyl)naphthalen-1-yl)oxy)quinolin-7-yl)oxy)methyl)cyclopropanecarbonyl azide |
|
C27H23N5O5 |
详情 | 详情
|
合成路线17
该中间体在本合成路线中的序号:
(XXI) Alkylation of 4’-hydroxy-3’-methoxyacetophenone (XVII) with benzyl bromide by means of K2CO3 in DMF gives benzyl ether (XVIII), which is reacted with fuming HNO3 and concentrated H2SO4 in cold CH2Cl2 to afford 4’-benzyloxy-5’-methoxy-2’-nitroacetophenone (XIX). After reduction of the nitro group of compound (XIX) using iron powder and ammonium formate in refluxing H2O/toluene, the resulting 2-aminoacetophenone derivative (XX) cyclizes with ethyl formate (XXI) in the presence of NaOEt in DME, providing 7-benzyloxy-6-methoxy-4-quinolinol (XXII). Finally, quinolinol (XXII) is treated with trifluoromethanesulfonyl chloride in the presence of DMAP and 2,6-lutidine in cold CH2Cl2 .
【1】
Deschamps, N.M., Martin, M.T., Monteith, M.J., Zhou, X. (GlaxoSmithKline Inc.). Preparation of a quinolinyloxydiphenylcyclopropanedicarboxamide. US 2010081805, WO 010036831. |
【2】
Wilson, J., Zuberi, S., Naganathan, S., Goldman, E., Kanter, J. (Exelixis, Inc.). Methods of preparing quinoline derivatives. WO 2010056960. |
中间体序号 |
中间体编号 |
品名 |
CAS号 |
分子式 |
供应商 |
用于合成 |
(XXIVa) |
22605 |
4-(3-Chloropropoxy)-3-Methoxyacetophenone;3-(4-Acetyl-2-methoxyphenoxy)propyl chloride;1-(4-(3-chloropropoxy)-3-methoxyphenyl)ethanone;1-[4-(3-chloropropoxy)-3-methoxyphenyl]-1-ethanone |
58113-30-7 |
C12H15ClO3 |
详情 | 详情
|
(XXIVb) |
69115 |
1-(4-(3-bromopropoxy)-3-methoxyphenyl)ethanone |
|
C12H15BrO3 |
详情 | 详情
|
(XXVa) |
69117 |
1-(4-(3-chloropropoxy)-5-methoxy-2-nitrophenyl)ethanone |
|
C12H14ClNO5 |
详情 | 详情
|
(XXVb) |
69116 |
1-(4-(3-bromopropoxy)-5-methoxy-2-nitrophenyl)ethanone |
|
C12H14BrNO5 |
详情 |
详情
|
(VI) |
69105 |
4-chloro-6-methoxy-7-(3-morpholinopropoxy)quinoline;4-(3-((4-chloro-6-methoxyquinolin-7-yl)oxy)propyl)morpholine |
|
C17H21ClN2O3 |
详情 | 详情
|
(XVII) |
22604 |
1-(4-hydroxy-3-methoxyphenyl)-1-ethanone;Acetovanillone;4’-hydroxy-3’-methoxyacetophenone;1-(4-hydroxy-3-methoxyphenyl)ethanone |
498-02-2 |
C9H10O3 |
详情 | 详情
|
(XXI) |
16602 |
ethyl formate
|
109-94-4 |
C3H6O2 |
详情 | 详情
|
(XXIII) |
10358 |
1-Bromo-3-chloropropane
|
109-70-6 |
C3H6BrCl |
详情 | 详情
|
(XXVI) |
10388 |
Morpholine
|
110-91-8 |
C4H9NO |
详情 | 详情
|
(XXVII) |
69118 |
1-(5-methoxy-4-(3-morpholinopropoxy)-2-nitrophenyl)ethanone |
|
C16H22N2O6 |
详情 | 详情
|
(XXVIII) |
56891 |
1,3-propanediol cyclic sulfate;1,3,2-dioxathiane 2,2-dioxide;1,3-Propylene sulfate |
1073-05-8 |
C3H6O4S |
详情 | 详情
|
(XXIX) |
69119 |
4’-(morpholinopropoxy)acetophenone;1-(3-methoxy-4-(3-morpholinopropoxy)phenyl)ethanone |
|
C16H23NO4 |
详情 | 详情
|
(XXX) |
69120 |
1-(2-amino-5-methoxy-4-(3-morpholinopropoxy)phenyl)ethanone |
|
C16H24N2O4 |
详情 | 详情
|
(XXXI) |
69121 |
6-methoxy-7-(3-morpholinopropoxy)quinolin-4-ol |
|
C17H22N2O4 |
详情 | 详情
|
(XXXII) |
20360 |
methyl(phenyl)formamide;N-Methylformanilide;N-Formyl-N-methylaniline;Methylphenylformamide;N-methyl-N-phenylformamide;N-Methyl-N-formylaniline;N-Formyl-N-methylaniline |
93-61-8 |
C8H9NO |
详情 | 详情
|