1-(2,2-dimethyl-2H-chromen-6-yl)-1-ethanone -Drug Synthesis Database

【结构式】

【分子编号】28706

【品名】1-(2,2-dimethyl-2H-chromen-6-yl)-1-ethanone

【CA登记号】

【分子式】C₁₃H₁₄O₂

【分子量】202.25296

【元素组成】C 77.2% H 6.98% O 15.82%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(III)

The cyclization of 4-hydroxyacetophenone (I) with 3-chloro-3-methyl-1-butyne (II) gives 6-acetyl-2,2-dimethyl-2H-1-benzopyran (III), which is enantioselectively epoxidized by means of Mn+3 salen catalysts, yielding the chiral epoxide (IV). The cleavage of the epoxide ring of (IV) with ammonia in ethanol affords the (3R,4S)-trans-aminoalcohol (V). The acylation of (V) with 3-chloro-4-fluorobenzoyl chloride (VI) and triethylamine yields the (3R,4S)-trans-amide (VII). The cyclization of (VII) by means of diethylaminosulfur trifluoride (DAST) in dichloromethane affords the (3aS-cis)-oxazoline (VIII), which is finally treated with 5N H2SO4.

参考文献中间体

合成目标

【1】 Chan, W.N.; et al.; Synthesis of novel trans-4-(substituted-benzamido)-3, 4-dihydro-2H-benzo[b]-pyran-3-ol derivatives as potential anticonvulsant agents with a distinctive binding profile. J Med Chem 1996, 39, 23, 4537.
【2】 Castañer, J.; Leeson, P.; Rabasseda, X.; Tonabersat. Drugs Fut 1999, 24, 10, 1078.
【3】 Chan, W.N.; Morgan, H.K.A.; Thompson, M.; Evans, J.M. (SmithKline Beecham plc); Benzopyrans and their use as therapeutic agents. EP 0764157; JP 1998501251; US 5760074; WO 9534545 .
【4】 Thompson, M.; Evans, J.M.; Upton, N.; Chan, W.N.; Vong, K.K.; Willette, R.N. (SmithKline Beecham plc); Bicyclic cpds. with pharmaceutical activity. EP 0673373; JP 1996505132; US 5908860; WO 9413656 .
【5】 Attrill, R.P.; Bell, D.; Miller, D. (SmithKline Beecham plc); Chiral catalysts and epoxidation reactions catalyzed thereby. WO 9403271 .

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)	18123	1-(4-hydroxyphenyl)-1-ethanone; 4'-Hydroxyacetophenone	99-93-4	C₈H₈O₂	详情	详情
(II)	22416	3-chloro-3-methyl-1-butyne	1111-97-3	C₅H₇Cl	详情	详情
(III)	28706	1-(2,2-dimethyl-2H-chromen-6-yl)-1-ethanone		C₁₃H₁₄O₂	详情	详情
(IV)	28707	1-[(1aR,7bR)-2,2-dimethyl-1a,7b-dihydro-2H-oxireno[2,3-c]chromen-6-yl]-1-ethanone		C₁₃H₁₄O₃	详情	详情
(V)	28708	1-[(3R,4S)-4-amino-3-hydroxy-2,2-dimethyl-3,4-dihydro-2H-chromen-6-yl]-1-ethanone		C₁₃H₁₇NO₃	详情	详情
(VI)	24370	3-chloro-4-fluorobenzoyl chloride	65055-17-6	C₇H₃Cl₂FO	详情	详情
(VII)	28709	N-[(3R,4S)-6-acetyl-3-hydroxy-2,2-dimethyl-3,4-dihydro-2H-chromen-4-yl]-3-chloro-4-fluorobenzamide		C₂₀H₁₉ClFNO₄	详情	详情
(VIII)	28713	1-[(3aS,9bS)-2-(3-chloro-4-fluorophenyl)-4,4-dimethyl-3a,9b-dihydro-4H-chromeno[4,3-d][1,3]oxazol-8-yl]-1-ethanone		C₂₀H₁₇ClFNO₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(III)

The cyclization of 4-hydroxyacetophenone (I) with 3-chloro-3-methyl-1-butyne (II) gives 5-acetyl-2,2-dimethyl-2H-1-benzopyran (III), which is enantioselectively epoxidized catalyzed by chiral salen Mn(III) catalysts to yield the (3R,4R)-epoxide (IV). The reaction of (IV) with ammonia in ethanol affords the (3R,4S)-aminoalcohol (V), which is finally acylated with 4-fluorobenzoyl chloride (VI) and TEA in dichloromethane to provide the target amide. Alternatively, the target amide can also be obtained by direct cleavage of the epoxide ring of (IV) with 4-fluorobenzamide (VII) by means of tBu-OK in tert-butanol.

参考文献中间体

合成目标

【1】 Chan, W.N.; et al.; Synthesis of novel trans-4-(substituted-benzamido)-3, 4-dihydro-2H-benzo[b]-pyran-3-ol derivatives as potential anticonvulsant agents with a distinctive binding profile. J Med Chem 1996, 39, 23, 4537.

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)	18123	1-(4-hydroxyphenyl)-1-ethanone; 4'-Hydroxyacetophenone	99-93-4	C₈H₈O₂	详情	详情
(II)	22416	3-chloro-3-methyl-1-butyne	1111-97-3	C₅H₇Cl	详情	详情
(III)	28706	1-(2,2-dimethyl-2H-chromen-6-yl)-1-ethanone		C₁₃H₁₄O₂	详情	详情
(IV)	28707	1-[(1aR,7bR)-2,2-dimethyl-1a,7b-dihydro-2H-oxireno[2,3-c]chromen-6-yl]-1-ethanone		C₁₃H₁₄O₃	详情	详情
(V)	28708	1-[(3R,4S)-4-amino-3-hydroxy-2,2-dimethyl-3,4-dihydro-2H-chromen-6-yl]-1-ethanone		C₁₃H₁₇NO₃	详情	详情
(VI)	17263	4-fluorobenzoyl chloride	403-43-0	C₇H₄ClFO	详情	详情
(VII)	37090	4-fluorobenzamide	824-75-9	C₇H₆FNO	详情	详情

Extended Information