1,2-Dichloroethane → Tert-butyl 3-(n-{(1r)-1-[(4-chlorophenyl)methyl]-2-[4-(2-nitrophenyl) piperazinyl]-2-oxoethyl}carbamoyl)(3s)-1,2,3,4-tetrahydroisoquinoline-2-carboxylate

HRID 1242732Notes

Reaction equation

HRID 1242732 reaction equation
Cl.[NH2:2][C@H:3]([CH2:21][C:22]1[CH:27]=[CH:26][C:25]([Cl:28])=[CH:24][CH:23]=1)[C:4]([N:6]1[CH2:11][CH2:10][N:9]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[N+:18]([O-:20])=[O:19])[CH2:8][CH2:7]1)=[O:5].[N:29]1([C:42]([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=[O:43])[CH2:38][C:37]2[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=2)[CH2:31][C@H:30]1[C:39](O)=[O:40].C1C=NC2N(O)N=NC=2C=1.C(Cl)CCl.CCN(C(C)C)C(C)C>CN(C=O)C>[Cl:28][C:25]1[CH:24]=[CH:23][C:22]([CH2:21][C@@H:3]([NH:2][C:39]([C@@H:30]2[CH2:31][C:32]3[C:37](=[CH:36][CH:35]=[CH:34][CH:33]=3)[CH2:38][N:29]2[C:42]([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=[O:43])=[O:40])[C:4]([N:6]2[CH2:11][CH2:10][N:9]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=3[N+:18]([O-:20])=[O:19])[CH2:8][CH2:7]2)=[O:5])=[CH:27][CH:26]=1

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 81531DiisopropylethylamineHCID 181649HOAtHCID 664088(3S)-2-((tert-butoxy)carbonyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acidHCID 69080220(2R)-2-amino-3-(4-chlorophenyl)-1-[4-(2-nitrophenyl)piperazinyl]propan-1-one hydrochloride

Product 1

HCID 58714297Tert-butyl 3-(n-{(1r)-1-[(4-chlorophenyl)methyl]-2-[4-(2-nitrophenyl) piperazinyl]-2-oxoethyl}carbamoyl)(3s)-1,2,3,4-tetrahydroisoquinoline-2-carboxylateYield 85%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Using the procedure described for the synthesis of Preparation V, tert-butyl 3-(N-{(1R)-1-[(4-chlorophenyl)methyl]-2-[4-(2-nitrophenyl) piperazinyl]-2-oxoethyl{carbamoyl)(3S)-1,2,3,4-tetrahydroisoquinoline-2-carboxylate was prepared from (2R)-2-amino-3-(4-chlorophenyl)-1-[4-(2-nitrophenyl)piperazinyl]propan-1-one hydrochloride (570 mg, 1.3 mmol) in DMF (10 mL), Boc-L-Tic-OH (Bachem) (410, 1.5 mmol), HOAT (Aldrich) (180 mg, 1.4 mmol), EDC (Aldrich) (520 mg, 2.70 mmol), and DIEA (Aldrich) (240 μL, 1.4 mmol). The crude material was purified by column chromatography (1:1 hexanes-EtOAc) to give the title compound as a white foam (716 mg). MS (ESI, pos. ion) m/z: 648 (M+H). Calc'd for C34H38ClN5O6: 647.25.

Workup

  1. customdescribed for the synthesis of Preparation V, tert-butyl 3-(N-{(1R)-1-[(4-chlorophenyl)methyl]-2-[4-(2-nitrophenyl) piperazinyl]-2-oxoethyl{carbamoyl)(3S)-1,2,3,4-tetrahydroisoquinoline-2-carboxylate
  2. customThe crude material was purified by column chromatography (1:1 hexanes-EtOAc)

Sources & evidence

ORD record
ord-56211b3a5d9d4f38bd0b6a71b84fe358
Source dataset
uspto-grants-2006_10
Patent number
US07115607B2

Reaction notes

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