MeOH tetrahydrofuran → (+/-)-1-(3-Amino-4-cyano-benzyl)-4-(6-chloro-benzo[b]thiophene-2-sulfonyl)-6-oxo-piperazine-2-carboxylic acid

HRID 1432944Notes

Reaction equation

HRID 1432944 reaction equation
C[O:2][C:3]([CH:5]1[CH2:10][N:9]([S:11]([C:14]2[S:18][C:17]3[CH:19]=[C:20]([Cl:23])[CH:21]=[CH:22][C:16]=3[CH:15]=2)(=[O:13])=[O:12])[CH2:8][C:7](=[O:24])[N:6]1[CH2:25][C:26]1[CH:31]=[CH:30][C:29]([C:32]#[N:33])=[C:28]([NH2:34])[CH:27]=1)=[O:4].C1COCC1.CO>O>[NH2:34][C:28]1[CH:27]=[C:26]([CH:31]=[CH:30][C:29]=1[C:32]#[N:33])[CH2:25][N:6]1[C:7](=[O:24])[CH2:8][N:9]([S:11]([C:14]2[S:18][C:17]3[CH:19]=[C:20]([Cl:23])[CH:21]=[CH:22][C:16]=3[CH:15]=2)(=[O:12])=[O:13])[CH2:10][CH:5]1[C:3]([OH:4])=[O:2]

Participants

5

Reactant 2

HCID 21899815MeOH tetrahydrofuranHCID 54383939(+/-)-1-(3-Amino-4-cyano-benzyl)-4-(6-chloro-benzo[b]thiophene-2-sulfonyl)-6-oxo-piperazine-2-carboxylic acid methyl ester

Product 1

HCID 17985171(+/-)-1-(3-Amino-4-cyano-benzyl)-4-(6-chloro-benzo[b]thiophene-2-sulfonyl)-6-oxo-piperazine-2-carboxylic acidYield 39.6%

Reagents, catalysts & solvents 2

HCID 962WaterCatalystHCID 962WaterSolvent

Procedure

Water (5 drops) is added to a solution containing (±)-1-(3-amino-4-cyano-benzyl)-4-(6-chloro-benzo[b]thiophene-2-sulfonyl)-6-oxo-piperazine-2-carboxylic acid methyl ester (30 mg, 0.05 mmol), EXAMPLE 99, in a 1:1 mixture of THF/MeOH (2 mL). At ambient temperature, LiOH monohydrate (7 mg, 1.66 mmol) is then added. After 16 h, the reaction mixture is diluted with water and purified by reverse-phase HPLC [Buffer A: water w/0.1% TFA; Buffer B: CH3CN w/0.1% TFA; Gradient: 0% B to 60% B over 30 min] to provide 10 mg (34%) of the title compound as a white solid. 1H NMR (300 MHz, d6-DMSO) δ3.18 (dd, J=12.1, 3.5 Hz, 1H), 3.61 (d, J=16.0 Hz, 1H), 3.77 (d, J=16.0 Hz, 1H), 3.95 (d, J=16.0 Hz, 1H), 4.06 (d, J=12.1 Hz, 1H), 4.14 (m, 1H), 6.40 (d, J=8.0 Hz, 1H), 6.54 (s, 1H), 7.21 (d, J=8.0 Hz, 1H), 7.57 (dd, J=8.6, 1.9 Hz, 1H), 8.06 (d, J=8.6 Hz, 1H), 8.18 (s, 1H), 8.33 (s, 1H) ppm; MS (ISP loop): m/z 505 (M+H).

Workup

  1. custompurified by reverse-phase HPLC [Buffer A: water

Sources & evidence

ORD record
ord-af064c5bff5743cbbefcf225823258c9
Source dataset
uspto-grants-2009_11
Patent number
US07612075B2

Reaction notes

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