Dimethylformamide → 8-[(3S,4S)-1-(2-cyclopropyl-acetyl)-4-phenyl-pyrrolidin-3-ylmethyl]-2-(4-methoxy-benzyl)-2,8-diaza-spiro[4.5]decan-1-one

HRID 1182170노트

반응식

HRID 1182170 반응식
[CH3:1][O:2][C:3]1[CH:32]=[CH:31][C:6]([CH2:7][N:8]2[CH2:12][CH2:11][C:10]3([CH2:17][CH2:16][N:15]([CH2:18][C@@H:19]4[C@@H:23]([C:24]5[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=5)[CH2:22][NH:21][CH2:20]4)[CH2:14][CH2:13]3)[C:9]2=[O:30])=[CH:5][CH:4]=1.[CH:33]1([CH2:36][CH2:37]C(O)=O)[CH2:35][CH2:34]1.CC(C)N=C=NC(C)C.CN(C=[O:54])C>CN(C1C=CN=CC=1)C>[CH:33]1([CH2:36][C:37]([N:21]2[CH2:22][C@H:23]([C:24]3[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=3)[C@@H:19]([CH2:18][N:15]3[CH2:16][CH2:17][C:10]4([C:9](=[O:30])[N:8]([CH2:7][C:6]5[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:32][CH:31]=5)[CH2:12][CH2:11]4)[CH2:13][CH2:14]3)[CH2:20]2)=[O:54])[CH2:34][CH2:35]1

참가 물질

6

반응물 4

HCID 6228DimethylformamideHCID 12734DiisopropylcarbodiimideHCID 27580133-Cyclopropylpropanoic acidHCID 114646642-(4-Methoxy-benzyl)-8-((3R,4S)-4-phenyl-pyrrolidin-3-ylmethyl)-2,8-diaza-spiro[4.5]decan-1-one

생성물 1

HCID 111915488-[(3S,4S)-1-(2-cyclopropyl-acetyl)-4-phenyl-pyrrolidin-3-ylmethyl]-2-(4-methoxy-benzyl)-2,8-diaza-spiro[4.5]decan-1-one수율 72%

시약·촉매·용매 1

HCID 142844-(Dimethylamino)pyridine촉매

실험 절차

To 100 mg (0.23 mmol) of 2-(4-methoxy-benzyl)-8-((3R,4S)-4-phenyl-pyrrolidin-3-ylmethyl)-2,8-diaza-spiro[4.5]decan-1-one in DMF (1 mL) was added cyclopropylmethylacetic acid (39 mg, 0.311 mmol), DIC (31 μL, 0.311 mmol) and DMAP (8 mg, 0.065 mmol) and the mixture was stirred overnight at room temperature. The reaction mixture was concentrated and purified by flash silica chromatography eluting first with ethyl acetate:hexanes (20%-100%) and then with methanol:dichloromethane (1:25) to give 116 mg (72%) of 8-[(3S,4S)-1-(2-cyclopropyl-acetyl)-4-phenyl-pyrrolidin-3-ylmethyl]-2-(4-methoxy-benzyl)-2,8-diaza-spiro[4.5]decan-1-one. The compound was then dissolved in methanol (2 mL) and HCl (aq., 0.2M, 3 mL) and stirred for 10 minutes. The solvent was removed in vacuo, and the solution lyophilized to give the Compound 117 (120 mg, 95%).

후처리

  1. concentrationThe reaction mixture was concentrated
  2. custompurified by flash silica chromatography
  3. washeluting first with ethyl acetate

출처 및 근거

ORD 기록
ord-1de0df9698c7460eb6b9b3dad3218d28
출처 데이터셋
uspto-grants-2007_10
특허 번호
US07288548B2

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