HOAt → tert-butyl (3s)-3-(n-[(1S)-1-[(4-chlorophenyl)methyl]-2-(4-{2-[(methylsulfonyl)amino]phenyl}piperazinyl)-2-oxoethyl]carbamoyl)-1,2,3,4-tetrahydroisoquinoline-2-carboxylate

HRID 228088Notes

Reaction equation

HRID 228088 reaction equation
[NH2:1][C@@H:2]([CH2:22][C:23]1[CH:28]=[CH:27][C:26]([Cl:29])=[CH:25][CH:24]=1)[C:3]([N:5]1[CH2:10][CH2:9][N:8]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=2[NH:17][S:18]([CH3:21])(=[O:20])=[O:19])[CH2:7][CH2:6]1)=[O:4].[N:30]1([C:43]([O:45][C:46]([CH3:49])([CH3:48])[CH3:47])=[O:44])[CH2:39][C:38]2[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=2)[CH2:32][C@H:31]1[C:40](O)=[O:41].CCN=C=NCCCN(C)C.CI.C1C=NC2N(O)N=NC=2C=1>CN(C=O)C>[Cl:29][C:26]1[CH:25]=[CH:24][C:23]([CH2:22][C@H:2]([NH:1][C:40]([C@@H:31]2[CH2:32][C:33]3[C:38](=[CH:37][CH:36]=[CH:35][CH:34]=3)[CH2:39][N:30]2[C:43]([O:45][C:46]([CH3:49])([CH3:48])[CH3:47])=[O:44])=[O:41])[C:3]([N:5]2[CH2:6][CH2:7][N:8]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=3[NH:17][S:18]([CH3:21])(=[O:19])=[O:20])[CH2:9][CH2:10]2)=[O:4])=[CH:28][CH:27]=1

Participants

6

Reactant 4

HCID 181649HOAtHCID 664088(3S)-2-((tert-butoxy)carbonyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acidHCID 10236463N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide methyliodideHCID 69074863(2s)-2-Amino-3-(4-chlorophenyl)-1-(4-{2-[(methylsulfonyl)amino]phenyl}-piperazinyl)propan-1-one

Product 1

HCID 90865346tert-butyl (3s)-3-(n-[(1S)-1-[(4-chlorophenyl)methyl]-2-(4-{2-[(methylsulfonyl)amino]phenyl}piperazinyl)-2-oxoethyl]carbamoyl)-1,2,3,4-tetrahydroisoquinoline-2-carboxylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

tert-Butyl (3S)-3-(N-[(1S)-1-[(4-chlorophenyl)methyl]-2-(4-{2-[(methylsulfonyl)amino]phenyl}piperazinyl)-2-oxoethyl]carbamoyl)-1,2,3,4-tetrahydroisoquinoline-2-carboxylate was prepared from (2S)-2-amino-3-(4-chlorophenyl)-1-(4-{2-[(methylsulfonyl)amino]phenyl}-piperazinyl)propan-1-one (Step 2) (380 mg, 0.87 mmol), according to the procedure for Preparation XIX using Boc-L-Tic-OH (250 mg, 0.91 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide methiodide (540 mg, 1.8 mmol), HOAT (140 mg, 1.0 mmol), and DMF (25 mL). Crude material was obtained in a quantitative yield and used without further purification. MS (ESI, pos. ion) m/z: 696 (M+H), (ESI, neg. ion) m/z: 694 (M−H). Calc'd for C35H42ClN5O6S: 695.25.

Workup

  1. customCrude material was obtained in a quantitative yield
  2. customused without further purification

Sources & evidence

ORD record
ord-097713c964bc4dbcb4671624dff1caa0
Source dataset
uspto-grants-2009_07
Patent number
US07560460B2

Reaction notes

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