Diisopropylethylamine → ((3s)(3-1,2,3,4-tetrahydroisoquinolyl))-n-[(1S)-1-[(4-chlorophenyl)methyl]-2-(4-{2-[(methylsulfonyl)amino]phenyl}piperazinyl)-2-oxoethyl]carboxamide

HRID 228087Notes

Reaction equation

HRID 228087 reaction equation
Cl.[CH3:2][S:3]([NH:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[N:13]1[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]1)(=[O:5])=[O:4].[C:19]([NH:26][C@H:27]([C:36]([OH:38])=[O:37])[CH2:28][C:29]1[CH:34]=[CH:33][C:32]([Cl:35])=[CH:31][CH:30]=1)([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20].CC[N:41]([CH:45]([CH3:47])C)[CH:42]([CH3:44])C.CCN=C=NCCCN(C)C.CI.[CH:61]1[CH:66]=N[C:64]2N(O)N=N[C:63]=2[CH:62]=1>CN(C=O)C>[Cl:35][C:32]1[CH:33]=[CH:34][C:29]([CH2:28][C@H:27]([NH:26][C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[C:36]([N:16]2[CH2:17][CH2:18][N:13]([C:8]3[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=3[NH:6][S:3]([CH3:2])(=[O:4])=[O:5])[CH2:14][CH2:15]2)=[O:37])=[CH:30][CH:31]=1.[CH2:45]1[C:47]2[C:66](=[CH:61][CH:62]=[CH:63][CH:64]=2)[CH2:44][C@@H:42]([C:19]([NH:26][C@@H:27]([CH2:28][C:29]2[CH:30]=[CH:31][C:32]([Cl:35])=[CH:33][CH:34]=2)[C:36]([N:16]2[CH2:17][CH2:18][N:13]([C:8]3[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=3[NH:6][S:3]([CH3:2])(=[O:4])=[O:5])[CH2:14][CH2:15]2)=[O:38])=[O:21])[NH:41]1

Participants

8

Reactant 5

HCID 81531DiisopropylethylamineHCID 181649HOAtHCID 2734499N-(tert-Butoxycarbonyl)-4-chloro-L-phenylalanineHCID 10236463HCID 10236463, compoundHCID 21283546N-(2-(Piperazin-1-yl)phenyl)methanesulfonamide hydrochloride

Product 2

HCID 10145280((3s)(3-1,2,3,4-tetrahydroisoquinolyl))-n-[(1S)-1-[(4-chlorophenyl)methyl]-2-(4-{2-[(methylsulfonyl)amino]phenyl}piperazinyl)-2-oxoethyl]carboxamideYield 117.9%HCID 21060096n-[(1S)-1-[(4-chlorophenyl)methyl]-2-(4-{2-[(methylsulfonyl)amino]phenyl}piperazinyl)-2-oxoethyl](tert-butoxy)carboxamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

N-[(1S)-1-[(4-Chlorophenyl)methyl]-2-(4-{2-[(methylsulfonyl)amino]phenyl}piperazinyl)-2-oxoethyl](tert-butoxy)carboxamide was prepared according to the procedure for Preparation XIX using (methylsulfonyl)(2-piperazinylphenyl)amine hydrochloride (913 mg, 3.13 mmol), N-Boc-4-chloro-L-phenylalanine (960 mg, 3.2 mmol) (Bachem), DIEA (550 μl, 3.16 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide methiodide (1.9 g, 6.5 mmol), HOAT (440 mg, 3.2 mmol) and DMF (30 mL). The crude was purified by flash chromatography (SiO2, 1:1 hexane:EtOAc) to afford the desired compound (1.1 g). MS (ESI, pos. ion) m/z: 537 (M+H), (ESI, neg. ion) m/z: 535 (M−H). Calc'd for C25H33ClN4O5S: 536.19.

Workup

  1. customThe crude was purified by flash chromatography (SiO2, 1:1 hexane:EtOAc)

Sources & evidence

ORD record
ord-b6d388b80270418a82c2e5d7a4daf0cc
Source dataset
uspto-grants-2009_07
Patent number
US07560460B2

Reaction notes

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