Potassium Carbonate → (R)-4-[(S)-1-(6-cyano-3,3-dimethyl-2,3-dihydro-indole-1-carbonyl)-propyl]-2-methyl-piperazine-1-carboxylic acid tert-butyl ester

HRID 1475534노트

반응식

HRID 1475534 반응식
Cl[C@H:2]([CH2:18][CH3:19])[C:3]([N:5]1[C:13]2[C:8](=[CH:9][CH:10]=[C:11]([C:14]#[N:15])[CH:12]=2)[C:7]([CH3:17])([CH3:16])[CH2:6]1)=[O:4].[C:20]([O:24][C:25]([N:27]1[CH2:32][CH2:31][NH:30][CH2:29][C@H:28]1[CH3:33])=[O:26])([CH3:23])([CH3:22])[CH3:21].C(=O)([O-])[O-].[K+].[K+]>C(#N)C.C(OCC)(=O)C>[C:20]([O:24][C:25]([N:27]1[CH2:32][CH2:31][N:30]([C@H:2]([C:3]([N:5]2[C:13]3[C:8](=[CH:9][CH:10]=[C:11]([C:14]#[N:15])[CH:12]=3)[C:7]([CH3:17])([CH3:16])[CH2:6]2)=[O:4])[CH2:18][CH3:19])[CH2:29][C@H:28]1[CH3:33])=[O:26])([CH3:23])([CH3:21])[CH3:22]

참가 물질

6

반응물 3

HCID 11430Potassium CarbonateHCID 10262201tert-Butyl (2R)-2-methylpiperazine-1-carboxylateHCID 86724047(R)-1-(2-chlorobutanoyl)-3,3-dimethylindoline-6-carbonitrile

생성물 1

HCID 70981673(R)-4-[(S)-1-(6-cyano-3,3-dimethyl-2,3-dihydro-indole-1-carbonyl)-propyl]-2-methyl-piperazine-1-carboxylic acid tert-butyl ester수율 14.5%

시약·촉매·용매 2

HCID 6342Acetonitrile용매HCID 8857Ethyl Acetate용매

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온도
50 °C

실험 절차

To a suspension of (R)-1-(2-chlorobutanoyl)-3,3-dimethylindoline-6-carbonitrile (0.1 g, 0.36 mmol), (R)-2-methyl-piperazine-1-carboxylic acid tert-butyl ester (0.072 g, 0.36 mmol) in acetonitrile (2.5 mL) was added potassium carbonate (0.049 g, 0.36 mmol) and the reaction heated to 50° C. for 48 h followed by 80° C. for 24 h and 60° C. for 36 h. The reaction mixture was then diluted with ethyl acetate and washed with water. The organics were separated, dried with sodium sulfate and concentrated. The residue was purified by flash column chromatography on silica gel; eluting with 20-30% ethyl acetate in heptane to give (R)-4-[(S)-1-(6-cyano-3,3-dimethyl-2,3-dihydro-indole-1-carbonyl)-propyl]-2-methyl-piperazine-1-carboxylic acid tert-butyl ester (0.023 g). MS: [M+H]+=441.

후처리

  1. washwashed with water
  2. customThe organics were separated
  3. dry with materialdried with sodium sulfate
  4. concentrationconcentrated
  5. customThe residue was purified by flash column chromatography on silica gel
  6. washeluting with 20-30% ethyl acetate in heptane

출처 및 근거

ORD 기록
ord-d1e78516d6b64755b484878cdbf28048
출처 데이터셋
uspto-grants-2015_04
특허 번호
US09018214B2

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