Phenylacetyl chloride → N-{(3R*,4S*)-1-Benzyl4-[(isopropyl-phenylacetyl-amino)-methyl]-pyrrolidin-3-ylmethyl}-N-isopropyl-4-methoxy-3-(3-methoxy-propoxy)-benzamide

HRID 1158486노트

반응식

HRID 1158486 반응식
[CH2:1]([N:8]1[CH2:12][C@@H:11]([CH2:13][NH:14][CH:15]([CH3:17])[CH3:16])[C@@H:10]([CH2:18][N:19]([CH:36]([CH3:38])[CH3:37])[C:20](=[O:35])[C:21]2[CH:26]=[CH:25][C:24]([O:27][CH3:28])=[C:23]([O:29][CH2:30][CH2:31][CH2:32][O:33][CH3:34])[CH:22]=2)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.[C:46]1([CH2:52][C:53](Cl)=[O:54])[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=1.[OH-].[Na+]>CN(C1C=CN=CC=1)C.C(Cl)Cl>[CH2:1]([N:8]1[CH2:12][C@@H:11]([CH2:13][N:14]([CH:15]([CH3:17])[CH3:16])[C:53](=[O:54])[CH2:52][C:46]2[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=2)[C@@H:10]([CH2:18][N:19]([CH:36]([CH3:38])[CH3:37])[C:20](=[O:35])[C:21]2[CH:26]=[CH:25][C:24]([O:27][CH3:28])=[C:23]([O:29][CH2:30][CH2:31][CH2:32][O:33][CH3:34])[CH:22]=2)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

참가 물질

7

반응물 4

HCID 7679Phenylacetyl chlorideHCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 59512319N-[(3R*,4R*)-1-Benzyl-4-(isopropylamino-methyl)-pyrrolidin-3-ylmethyl]-N-isopropyl-4-methoxy-3-(3-methoxy-propoxy)-benzamide

생성물 1

HCID 59512431N-{(3R*,4S*)-1-Benzyl4-[(isopropyl-phenylacetyl-amino)-methyl]-pyrrolidin-3-ylmethyl}-N-isopropyl-4-methoxy-3-(3-methoxy-propoxy)-benzamide

시약·촉매·용매 2

HCID 142844-(Dimethylamino)pyridine촉매HCID 6344Dichloromethane용매2회

실험 절차

To a solution of N-[(3R*,4R*)-1-benzyl-4-(isopropylamino-methyl)-pyrrolidin-3-ylmethyl]-N-isopropyl-4-methoxy-3-(3-methoxy-propoxy)-benzamide (0.19 g, 0.36 mmol), triethyl-amine (0.15 mL, 1.09 mmol), and DMAP (0.013 g, 0.11 mmol) in CH2Cl2, is added dropwise phenyl-acetyl chloride (0.058 mL, 0.44 mmol) at 0° C. under a nitrogen atmosphere. The solution is stirred overnight at room temperature. The mixture is added an aqueous solution of NaOH 0.1N (50 mL) and CH2Cl2 (50 mL). The organic layer is separated and the aqueous phase extracted twice with CH2Cl2, dried over MgSO4, filtered, and concentrated in vacuo. The crude product is purified by flash chromatography on silica gel (eluent: CH2Cl2/MeOH 90:10) to give the title product. TLC, Rf (CH2Cl2/MeOH 9:1)=0.23. MS (LC-MS): [M+H]+; 644.4 tR (HPLC, C18 column, 10-100% CH3CN/H2O/5 min, 100% CH3CN/2.5 min, CH3CN and H2O containing 0.1% TFA, flow: 1.5 mL/min): 5.95 min.

후처리

  1. customThe organic layer is separated
  2. extractionthe aqueous phase extracted twice with CH2Cl2
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude product is purified by flash chromatography on silica gel (eluent: CH2Cl2/MeOH 90:10)

출처 및 근거

ORD 기록
ord-a3a44da3faab43cdba812024fbb28899
출처 데이터셋
uspto-grants-2010_10
특허 번호
US07807709B2

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