(S)-(-)-3-Acetamidopyrrolidine → N-((S)-1-[2-([(S)-1-(4-fluorophenyl)ethyl]amino)-6-(pyrazin-2-ylamino)pyridin-4-yl]pyrrolidin-3-yl)acetamide

HRID 1187698노트

반응식

HRID 1187698 반응식
Cl[C:2]1[CH:7]=[C:6]([NH:8][C:9]2[CH:14]=[N:13][CH:12]=[CH:11][N:10]=2)[N:5]=[C:4]([NH:15][C@H:16]([C:18]2[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=2)[CH3:17])[CH:3]=1.[NH:25]1[CH2:29][CH2:28][C@H:27]([NH:30][C:31](=[O:33])[CH3:32])[CH2:26]1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.CC(C)([O-])C.[Na+]>C(OCC)(=O)C.C1(C)C=CC=CC=1>[F:24][C:21]1[CH:22]=[CH:23][C:18]([C@@H:16]([NH:15][C:4]2[CH:3]=[C:2]([N:25]3[CH2:29][CH2:28][C@H:27]([NH:30][C:31](=[O:33])[CH3:32])[CH2:26]3)[CH:7]=[C:6]([NH:8][C:9]3[CH:14]=[N:13][CH:12]=[CH:11][N:10]=3)[N:5]=2)[CH3:17])=[CH:19][CH:20]=1

참가 물질

7

반응물 4

HCID 7021471(S)-(-)-3-AcetamidopyrrolidineHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 23676156Sodium t-butoxideHCID 56602199(S)-4-Chloro-N2-[1-(4-fluorophenyl)ethyl]-N6-(pyrazin-2-yl)pyridine-2,6-diamine

생성물 1

HCID 56599595N-((S)-1-[2-([(S)-1-(4-fluorophenyl)ethyl]amino)-6-(pyrazin-2-ylamino)pyridin-4-yl]pyrrolidin-3-yl)acetamide수율 90.8%

시약·촉매·용매 2

HCID 1140Toluene용매HCID 8857Ethyl Acetate용매

반응 조건

온도
100 °C

실험 절차

100 mg of (S)-4-chloro-N2-[1-(4-fluorophenyl)ethyl]-N6-(pyrazin-2-yl)pyridine-2,6-diamine (Reference Example 2), 112 mg of (S)—N-(pyrrolidin-3-yl)acetamide, 69 mg of 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl, 92 mg of sodium t-butoxide and 30 mg of tris (dibenzylideneacetone)(chloroform)dipalladium were added in turn to 6 ml of degassed toluene, and the mixture was stirred at 100° C. for 2 hours under argon atmosphere. The reaction solution was diluted with ethyl acetate. The solution was washed in turn with water and brine and then dried over magnesium sulfate. The solvent was distilled off under reduced pressure, and then the obtained residue was purified by silica gel column chromatography to obtain 115 mg of N-{(S)-1-[2-{[(S)-1-(4-fluorophenyl)ethyl]amino}-6-(pyrazin-2-ylamino)pyridin-4-yl]pyrrolidin-3-yl}acetamide as pale brown powder. The obtained compound was subjected to hydrochlorination using a conventional method to obtain 67 mg of the objective compound as brown powder.

후처리

  1. washThe solution was washed in turn with water and brine
  2. dry with materialdried over magnesium sulfate
  3. distillationThe solvent was distilled off under reduced pressure
  4. customthe obtained residue was purified by silica gel column chromatography

출처 및 근거

ORD 기록
ord-89f7386344964609b83de701509f4b0d
출처 데이터셋
uspto-grants-2014_03
특허 번호
US08673891B2

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