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

HRID 228101Notes

Reaction equation

HRID 228101 reaction equation
[NH2:1][C@H:2]([CH2:26][C:27]1[CH:32]=[CH:31][C:30]([Cl:33])=[CH:29][CH:28]=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[N:17]([CH2:22][CH:23]2[CH2:25][CH2:24]2)[S:18]([CH3:21])(=[O:20])=[O:19])[CH2:7][CH2:6]1)=[O:4].[N:34]1([C:47]([O:49][C:50]([CH3:53])([CH3:52])[CH3:51])=[O:48])[CH2:43][C:42]2[C:37](=[CH:38][CH:39]=[CH:40][CH:41]=2)[CH2:36][C@H:35]1[C:44](O)=[O:45].CCN=C=NCCCN(C)C.CI.C1C=NC2N(O)N=NC=2C=1>CN(C=O)C>[Cl:33][C:30]1[CH:29]=[CH:28][C:27]([CH2:26][C@@H:2]([NH:1][C:44]([C@@H:35]2[CH2:36][C:37]3[C:42](=[CH:41][CH:40]=[CH:39][CH:38]=3)[CH2:43][N:34]2[C:47]([O:49][C:50]([CH3:53])([CH3:52])[CH3:51])=[O:48])=[O:45])[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[N:17]([CH2:22][CH:23]3[CH2:24][CH2:25]3)[S:18]([CH3:21])(=[O:19])=[O:20])[CH2:9][CH2:10]2)=[O:4])=[CH:32][CH:31]=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 69073190(2R)-2-Amino-3-(4-chlorophenyl)-1-(4-{2-[(cyclopropylmethyl) (methylsulfonyl)amino]phenyl}piperazinyl)propan-1-one

Product 1

HCID 69078318Tert-butyl 3-{n-[(1r)-1-[(4-chlorophenyl)methyl]-2-(4-{2-[(cyclopropylmethyl) (methylsulfonyl)amino]phenyl}piperazinyl)-2-oxoethyl]carbamoyl}(3s)-1,2,3,4-tetrahydroisoquinoline-2-carboxylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

tert-Butyl 3-{N-[(1R)-1-[(4-chlorophenyl)methyl]-2-(4-{2-[(cyclopropylmethyl)(methylsulfonyl)amino]phenyl}piperazinyl)-2-oxoethyl]carbamoyl}(3S)-1,2,3,4-tetrahydroisoquinoline-2-carboxylate was prepared from (2R)-2-amino-3-(4-chlorophenyl)-1-(4-{2-[(cyclopropylmethyl)(methylsulfonyl)amino]phenyl}-piperazinyl) propan-1-one (Example 58, Step 3) (224 mg, 0.457 mmol), according to the procedure for Preparation XIX using Boc-L-Tic-OH (135 mg, 0.487 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide methiodide (285 mg, 0.959 mmol), HOAT (68 mg, 0.50 mmol), and DMF (7 mL). The compound was isolated (339 mg). MS (ESI, pos. ion) m/z: 750 (M+H), (ESI, neg. ion) m/z: 748 (M−H). Calc'd for C39H48ClN5O6S: 750.35.

Workup

  1. customThe compound was isolated (339 mg)

Sources & evidence

ORD record
ord-c6c7fab21131467fbec8ff00c9442488
Source dataset
uspto-grants-2009_07
Patent number
US07560460B2

Reaction notes

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