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

HRID 228113Notes

Reaction equation

HRID 228113 reaction equation
Cl.[NH2:2][C@H:3]([CH2:23][C:24]1[CH:29]=[CH:28][C:27]([Cl:30])=[CH:26][CH:25]=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[C:18]([N:20]([CH3:22])[CH3:21])=[O:19])[CH2:8][CH2:7]1)=[O:5].[N:31]1([C:44]([O:46][C:47]([CH3:50])([CH3:49])[CH3:48])=[O:45])[CH2:40][C:39]2[C:34](=[CH:35][CH:36]=[CH:37][CH:38]=2)[CH2:33][C@H:32]1[C:41](O)=[O:42].C1C=NC2N(O)N=NC=2C=1.C(Cl)CCl.CCN(C(C)C)C(C)C>>[CH3:21][N:20]([CH3:22])[C:18]([C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=1[N:9]1[CH2:8][CH2:7][N:6]([C:4](=[O:5])[C@H:3]([NH:2][C:41]([C@@H:32]2[CH2:33][C:34]3[C:39](=[CH:38][CH:37]=[CH:36][CH:35]=3)[CH2:40][N:31]2[C:44]([O:46][C:47]([CH3:50])([CH3:49])[CH3:48])=[O:45])=[O:42])[CH2:23][C:24]2[CH:29]=[CH:28][C:27]([Cl:30])=[CH:26][CH:25]=2)[CH2:11][CH2:10]1)=[O:19]

Participants

6

Reactant 5

HCID 111,2-DichloroethaneHCID 81531DiisopropylethylamineHCID 181649HOAtHCID 664088(3S)-2-((tert-butoxy)carbonyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acidHCID 69075714(2-{4-[(2R)-2-Amino-3-(4-chlorophenyl)propanoyl]-piperazinyl}phenyl)-N,N-dimethylcarboxamide HCl salt

Product 1

HCID 69072944Tert-butyl 3-[n-((1r)-2-{4-[2-(n,n-dimethylcarbamoyl)-phenyl]piperazinyl}-1-[(4-chlorophenyl)methyl]-2-oxoethyl)carbamoyl](3s)-1,2,3,4-tetrahydro-isoquinoline-2-carboxylate

Procedure

tert-Butyl 3-[N-((1R)-2-{4-[2-(N,N-dimethylcarbamoyl)-phenyl]piperazinyl}-1-[(4-chlorophenyl)methyl]-2-oxoethyl)carbamoyl](3S)-1,2,3,4-tetrahydro-isoquinoline-2-carboxylate was prepared according to the procedure described in Preparation V by using (2-{4-[(2R)-2-amino-3-(4-chlorophenyl)-propanoyl]-piperazinyl}phenyl)-N,N-dimethylcarboxamide HCl salt (Step 5) (230 mg, 0.50 mmol), Boc-L-Tic-OH (Bachem Company) (150 mg, 0.55 mmol), HOAT (Aldrich) (68 mg, 0. 50 mmol), EDC (Aldrich) (190 mg, 1.00 mmol) and DIEA (Aldrich) (87 μL, 0.50 mmol). The compound was isolated and purified by column chromatography (CH2Cl2: 1.5% 2 M NH3 in MeOH). (255 mg). MS (ESI, pos. ion) m/z: 674 (M+H). Calc'd for C37H44ClN5O5: 674.23.

Workup

  1. customdescribed in Preparation V
  2. customThe compound was isolated
  3. custompurified by column chromatography (CH2Cl2: 1.5% 2 M NH3 in MeOH)

Sources & evidence

ORD record
ord-2b398475a3d74568aceac22a5f7f55c9
Source dataset
uspto-grants-2009_07
Patent number
US07560460B2

Reaction notes

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