(2S)-N-[(1S)-2-amino-1-benzyl-2-oxoethyl]-2-{[(2R)-2-aminopropanoyl]amino}-3-(4-fluorophenyl)propanamide -Drug Synthesis Database

【结构式】

【分子编号】61045

【品名】(2S)-N-[(1S)-2-amino-1-benzyl-2-oxoethyl]-2-{[(2R)-2-aminopropanoyl]amino}-3-(4-fluorophenyl)propanamide

【CA登记号】

【分子式】C₂₁H₂₅FN₄O₃

【分子量】400.4530632

【元素组成】C 62.99% H 6.29% F 4.74% N 13.99% O 11.99%

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：(VIII)

The title compound has been prepared by solid-phase peptide synthesis on a Knorr resin. N-Fmoc-L-Phenylalanine (I) is attached to the resin by means of BOP and HOBt, producing resin (II). Deprotection of the N-Fmoc group of (II) with piperidine in DMF gives the phenylalanine-bound resin (III). Subsequent coupling with N-Fmoc-L-p-fluorophenylalanine (IV) yields the dipeptide resin (V), which is further deprotected to (VI) with piperidine in DMF. Further coupling-deprotection cycles with N-Fmoc-D-alanine (VII) and N-Fmoc-O-tert-butyl-L-tyrosine (IX) provide the peptide resins (VIII) and (X) respectively. Finally, simultaneous cleavage from the resin and side chain deprotection is accomplished by treatment with trifluoroacetic acid.

参考文献中间体

合成目标

【1】 Wang, W. (AstraZeneca plc); Novel opioid peptides. EP 0845003; JP 1999512086; US 6337319; WO 9707130 .

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)	19030	(2S)-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]-3-phenylpropionic acid; N-((9H-fluoren-9-ylmethoxy)carbonyl)-phenylalanine	35661-40-6	C₂₄H₂₁NO₄	详情	详情
(II)	19031	9H-fluoren-9-ylmethyl (1S)-2-amino-1-benzyl-2-oxoethylcarbamate		C₂₄H₂₂N₂O₃	详情	详情
(III)	19032	(2S)-2-amino-3-phenylpropanamide	5241-58-7	C₉H₁₂N₂O	详情	详情
(IV)	61042	(2S)-2-{[(9H-fluoren-9-ylmethoxy)carbonyl]amino}-3-(4-fluorophenyl)propanoic acid		C₂₄H₂₀FNO₄	详情	详情
(V)	61043	9H-fluoren-9-ylmethyl (1S)-2-{[(1S)-2-amino-1-benzyl-2-oxoethyl]amino}-1-(4-fluorobenzyl)-2-oxoethylcarbamate		C₃₃H₃₀FN₃O₄	详情	详情
(VI)	61044	(2S)-2-amino-N-[(1S)-2-amino-1-benzyl-2-oxoethyl]-3-(4-fluorophenyl)propanamide		C₁₈H₂₀FN₃O₂	详情	详情
(VII)	19926	(2S)-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]propionic acid		C₁₈H₁₇NO₄	详情	详情
(VIII)	61045	(2S)-N-[(1S)-2-amino-1-benzyl-2-oxoethyl]-2-{[(2R)-2-aminopropanoyl]amino}-3-(4-fluorophenyl)propanamide		C₂₁H₂₅FN₄O₃	详情	详情
(IX)	18858	(2S)-3-[4-(tert-butoxy)phenyl]-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]propionic acid		C₂₈H₂₉NO₅	详情	详情
(X)	61046	(2S)-2-amino-N-((1R)-2-{[(1S)-2-{[(1S)-2-amino-1-benzyl-2-oxoethyl]amino}-1-(4-fluorobenzyl)-2-oxoethyl]amino}-1-methyl-2-oxoethyl)-3-[4-(tert-butoxy)phenyl]propanamide		C₃₄H₄₂FN₅O₅	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XI)

N-Cbz-D-Alanine (VIII) is activated as the mixed anhydride (IX) and subsequently coupled to the dipeptide amide (VII), producing (X). Deprotection of the N-Cbz group of tripeptide (X) by hydrogenolysis over Pd/C yields (XI). The mixed anhydride (XIII) (prepared from N-Cbz-L-tyrosine (XII) and isobutyl chloroformate) is then coupled to tripeptide (XI), producing (XIV). Finally, removal of the N-Cbz group of (XIV) by catalytic hydrogenolysis furnishes the title compound.

参考文献中间体

合成目标

【1】 Franzen, H. (AstraZeneca plc); Process for the preparation of a tetrapeptide. WO 9947548 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(VII)	61044	(2S)-2-amino-N-[(1S)-2-amino-1-benzyl-2-oxoethyl]-3-(4-fluorophenyl)propanamide	C₁₈H₂₀FN₃O₂	详情	详情
(VIII)	61209	CBZ-L-Alanine; (2S)-2-[[(Benzyloxy)carbonyl]amino]propionic acid; N-((Phenylmethoxy)carbonyl)-alanine; Carbobenzyloxy-L-alanine	C₁₁H₁₃NO₄	详情	详情
(IX)	61210		C₁₆H₂₁NO₆	详情	详情
(X)	61211	benzyl (1R)-2-{[(1S)-2-{[(1S)-2-amino-1-benzyl-2-oxoethyl]amino}-1-(4-fluorobenzyl)-2-oxoethyl]amino}-1-methyl-2-oxoethylcarbamate	C₂₉H₃₁FN₄O₅	详情	详情
(XI)	61045	(2S)-N-[(1S)-2-amino-1-benzyl-2-oxoethyl]-2-{[(2R)-2-aminopropanoyl]amino}-3-(4-fluorophenyl)propanamide	C₂₁H₂₅FN₄O₃	详情	详情
(XII)	39328	(2S)-2-[[(benzyloxy)carbonyl]amino]-3-(4-hydroxyphenyl)propionic acid	C₁₇H₁₇NO₅	详情	详情
(XIII)	61212		C₂₂H₂₅NO₇	详情	详情
(XIV)	61213	(1R)-2-{[(1S)-2-{[(1S)-2-amino-1-benzyl-2-oxoethyl]amino}-1-(4-fluorobenzyl)-2-oxoethyl]amino}-1-methyl-2-oxoethyl (2S)-2-{[(benzyloxy)carbonyl]amino}-3-(4-hydroxyphenyl)propanoate	C₃₈H₃₉FN₄O₈	详情	详情

Extended Information