(S)-2-(7-chloro-1-oxo-1H-isoquinolin-2-yl)-butyric acid → (S,S)-3-[2-(7-chloro-1-oxo-1H-isoquinolin-2-yl)-butyrylamino]-4-oxo-5-(2,3,5,6-tetrafluoro-phenoxy)-pentanoic Acid

HRID 1091440Notes

Reaction equation

HRID 1091440 reaction equation
[Cl:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][N:8]([C@@H:13]([CH2:17][CH3:18])[C:14]([OH:16])=O)[C:9]2=[O:12])=[CH:4][CH:3]=1.C([O:23][C:24](=[O:42])[CH2:25][C@H:26]([NH2:41])[CH:27]([OH:40])[CH2:28][O:29][C:30]1[C:35]([F:36])=[C:34]([F:37])[CH:33]=[C:32]([F:38])[C:31]=1[F:39])(C)(C)C>>[Cl:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][N:8]([C@@H:13]([CH2:17][CH3:18])[C:14]([NH:41][C@H:26]([C:27](=[O:40])[CH2:28][O:29][C:30]3[C:35]([F:36])=[C:34]([F:37])[CH:33]=[C:32]([F:38])[C:31]=3[F:39])[CH2:25][C:24]([OH:42])=[O:23])=[O:16])[C:9]2=[O:12])=[CH:4][CH:3]=1

Participants

3

Reactant 2

HCID 11565197(S)-2-(7-chloro-1-oxo-1H-isoquinolin-2-yl)-butyric acidHCID 44604220(3S)-3-Amino-4-hydroxy-5-(2,3,5,6-tetrafluoro-phenoxy)-pentanoic Acid Tert-Butyl Ester

Product 1

HCID 9850339(S,S)-3-[2-(7-chloro-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-(7-chloro-1-oxo-1H-isoquinolin-2-yl)-butyric acid (prepared as 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 product was isolated as a white solid (94% last step). IR (solid) 1639.3, 1618.8, 1593.2, 1516.4, 1485.6, 1219.4, 1168.1, 1106.7, 932.6, 830.2 cm−1; 1H NMR (400 MHz, DMSO-d6) δ 0.80 (3H, t), 1.94-2.12 (2H, m), 2.55-2.61 (1H, m), 2.74-2.80 (1H, m), 4.58-4.63 (1H, m), 5.12-5.76 (3H, m), 6.70 (1H, d), 7.51-7.78 (4H, m), 8.11-8.12 (1H, m), 8.60-8.95 (1H, 2×d) ppm; 13C NMR (100 MHz, d6-DMSO) δ 23.8, 24.5, 32.9, 34.6, 47.8, 52.8, 55.2, 58.2, 58.9, 74.4, 75.6, 100.1, 100.3, 100.5, 101.0, 101.2, 104.6, 126.5, 136.6, 131.3, 131.4, 133.0, 135.6, 135.6, 139.0, 139.1, 141.4, 141.6, 144.6, 144.8, 144.9, 147.1, 147.1, 160.7, 170.4, 172.0, 173.0, 202.2; 19F NMR (376 MHz, d6-DMSO) (proton decoupled) δ −140.57, −140.60, −140.64, −140.66, −141.00, −141.03, −141.06, −141.09, −156.78, −156.80, −156.84, −156.86, −156.96, −156.98, −157.02, −157.04; MS ES (+) 543.20 (M+H).

Workup

  1. customThis compound was prepared
  2. customThe product was isolated as a white solid (94% last step)

Sources & evidence

ORD record
ord-85070aef2f4c4b658cab56cbb89497e6
Source dataset
uspto-grants-2012_03
Patent number
US08129381B2

Reaction notes

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