Diethylamine → HCID 59134101, compound

HRID 1994412Notes

Reaction equation

HRID 1994412 reaction equation
[Cl:1][C:2]1[CH:59]=[CH:58][C:5]([CH2:6][CH:7]2[N:12]3[C:13](=[O:53])[CH:14]([NH:28][C:29]([CH:31]4[CH2:35][CH2:34][CH2:33][N:32]4C(OCC4C5C=CC=CC=5C5C4=CC=CC=5)=O)=[O:30])[CH2:15][N:16]([S:17]([C:20]4[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][C:21]=4[Cl:27])(=[O:19])=[O:18])[CH:11]3[CH2:10][N:9]([CH:54]([CH3:56])[CH3:55])[C:8]2=[O:57])=[CH:4][CH:3]=1.C(NCC)C>C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][CH:7]2[N:12]3[C:13](=[O:53])[CH:14]([NH:28][C:29]([CH:31]4[CH2:35][CH2:34][CH2:33][NH:32]4)=[O:30])[CH2:15][N:16]([S:17]([C:20]4[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][C:21]=4[Cl:27])(=[O:19])=[O:18])[CH:11]3[CH2:10][N:9]([CH:54]([CH3:56])[CH3:55])[C:8]2=[O:57])=[CH:58][CH:59]=1

Participants

4

Reactant 2

HCID 8021DiethylamineHCID 68695242HCID 68695242, compound

Product 1

HCID 59134101HCID 59134101, compoundYield 67.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of 50 mg (0.089 mmol) of 3-amino-6-(4-chlorobenzyl)-1-(2,4-dichlorobenzenesulfonyl)-8-isopropylhexahydropyrazino[1,2-a]pyrimidine-4,7-dione, 1 ml of DCM, 23 mg (0.178 mmol) of DIEA and 32 mg (0.090 mmol) of Fmoc-Pro-Cl was stirred at room temperature for 1 hour. The mixture was purified by chromatography on 2 g of SiO2 (elution with EtOAc/DCM, gradient 0-20%). 72 mg of the intermediate 9H-fluoren-9-ylmethyl 2-[6-(4-chlorobenzyl)-1-(2,4-dichlorobenzenesulfonyl)-8-isopropyl-4,7-dioxooctahydropyrazino[1,2-a]pyrimidin-3-ylcarbamoyl]pyrrolidine-1-carboxylate were obtained. LC/MS: (calculated, monoisotopic MW=877, measured value (M+H)=878) A mixture of 60 mg (0.068 mmol) of 9H-fluoren-9-ylmethyl 2-[6-(4-chlorobenzyl)-1-(2,4-dichlorobenzenesulfonyl)-8-isopropyl-4,7-dioxooctahydropyrazino[1,2-a]pyrimidin-3-ylcarbamoyl]pyrrolidine-1-carboxylate and 2 ml of 15% strength diethylamine in DCM was stirred at room temperature overnight. The mixture was concentrated and subjected to a flash chromatography on 2 g of SiO2 (elution with DCM, EtOAc and then with 10% methanol/EtOAc). The amine was converted into the hydrochloride salt. 30 mg of solid were obtained. This was further purified by preparative reverse phase (RP)HPLC. 17 mg of the desired compound were obtained. LC/MS (calculated, monoisotopic MW=655.12; measured value (M+H)=656)

Workup

  1. concentrationThe mixture was concentrated
  2. washelution with DCM, EtOAc

Sources & evidence

ORD record
ord-db7cf6f01d304ecb9aeec40ebc048aaf
Source dataset
uspto-grants-2010_01
Patent number
US07652007B2

Reaction notes

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