(3S)-3-Amino-4-hydroxy-5-(2,3,5,6-tetrafluoro-phenoxy)-pentanoic Acid Tert-Butyl Ester → (S,S)-3-[2-(6,7-dichloro-1-oxo-1H-isoquinolin-2-yl)-butyrylamino]-4-oxo-5-(2,3,5,6-tetrafluoro-phenoxy)-pentanoic Acid

HRID 1987879Notes

Reaction equation

HRID 1987879 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[Cl:12])[C:8](=[O:13])[N:7]([C@@H:14]([CH2:18][CH3:19])[C:15]([OH:17])=O)[CH:6]=[CH:5]2.ClC1C(Cl)=CC(C(O)=O)=C(C=O)C=1.C([O:37][C:38](=[O:56])[CH2:39][C@H:40]([NH2:55])[CH:41]([OH:54])[CH2:42][O:43][C:44]1[C:49]([F:50])=[C:48]([F:51])[CH:47]=[C:46]([F:52])[C:45]=1[F:53])(C)(C)C>>[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[Cl:12])[C:8](=[O:13])[N:7]([C@@H:14]([CH2:18][CH3:19])[C:15]([NH:55][C@H:40]([C:41](=[O:54])[CH2:42][O:43][C:44]1[C:49]([F:50])=[C:48]([F:51])[CH:47]=[C:46]([F:52])[C:45]=1[F:53])[CH2:39][C:38]([OH:56])=[O:37])=[O:17])[CH:6]=[CH:5]2

Participants

4

Reactant 3

HCID 44604220(3S)-3-Amino-4-hydroxy-5-(2,3,5,6-tetrafluoro-phenoxy)-pentanoic Acid Tert-Butyl EsterHCID 66593918(S)-2-(6,7-dichloro-1-oxo-1H-isoquinolin-2-yl)-butyric acidHCID 865917864,5-Dichloro-2-formylbenzoic acid

Product 1

HCID 10076879(S,S)-3-[2-(6,7-dichloro-1-oxo-1H-isoquinolin-2-yl)-butyrylamino]-4-oxo-5-(2,3,5,6-tetrafluoro-phenoxy)-pentanoic Acid

Procedure

This compound was prepared using (S)-2-(6,7-dichloro-1-oxo-1H-isoquinolin-2-yl)-butyric acid (synthesized from 4,5-dichloro-2-formyl-benzoic acid [prepared as described in methods Q-S] using procedures similar to those described in methods A-E) and (3S)-3-amino-4-hydroxy-5-(2,3,5,6-tetrafluoro-phenoxy)-pentanoic acid tert-butyl ester (prepared as described in methods N-P) using procedures similar to those described in methods F, G and E. The title compound was isolated as a white solid (94% last step). IR (solid) 1784.5, 1734.7, 1650.1, 1610.2, 1585.4, 1515.7, 1490.8, 1426.0, 1216.9, 1172.1, 1092.5, 933.1 cm−1; 1H NMR (400 MHz, d6-DMSO) δ 0.80 (3H, t), 1.90-1.98 (1H, m), 2.04-2.12 (1H, m), 2.55-2.79 (2H, m), 4.56-4.71 (1H, m), 5.08-5.41 (3H, m), 6.67 (1H, d), 7.56-7.59 (2H, m), 8.07 (1H, brd s), 8.25 (1H, d), 8.85-8.95 (1H, 2×d), 12.73 (1H, brd s) ppm; 19F NMR (376 MHz, d6-DMSO) (proton decoupled) δ −140.93, −140.95, −140.99, −141.01, −141.04, −141.07, −141.10, −156.76, −156.79, −156.82, −156.85, −156.89, −156.91; MS ES (+): 577.14 (M+H).

Workup

  1. customThis compound was prepared

Sources & evidence

ORD record
ord-a39e846228524028b0f49f999b8703c6
Source dataset
uspto-grants-2009_06
Patent number
US07553852B2

Reaction notes

Loading…