Sodium Carbonate → [4-(2-Methoxy-pyrimidin-5-yl)-phenyl]-(2-(S)-pyrrolidin-1-ylmethyl-pyrrolidin-1-yl)-methanone

HRID 1867812노트

반응식

HRID 1867812 반응식
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]([N:10]2[CH2:14][CH2:13][CH2:12][C@H:11]2[CH2:15][N:16]2[CH2:20][CH2:19][CH2:18][CH2:17]2)=[O:9])=[CH:4][CH:3]=1.C(=O)([O-])[O-].[Na+].[Na+].[CH3:27][O:28][C:29]1[N:34]=[CH:33][C:32](B(O)O)=[CH:31][N:30]=1>C1(C)C=CC=CC=1.O.C(O)C.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH3:27][O:28][C:29]1[N:34]=[CH:33][C:32]([C:2]2[CH:7]=[CH:6][C:5]([C:8]([N:10]3[CH2:14][CH2:13][CH2:12][C@H:11]3[CH2:15][N:16]3[CH2:20][CH2:19][CH2:18][CH2:17]3)=[O:9])=[CH:4][CH:3]=2)=[CH:31][N:30]=1

참가 물질

8

반응물 3

HCID 10340Sodium CarbonateHCID 27367782-Methoxypyrimidine-5-boronic acidHCID 11965129Pyrrolidine, 1-(4-bromobenzoyl)-2-(1-pyrrolidinylmethyl)-, (2S)-

생성물 1

HCID 57980080[4-(2-Methoxy-pyrimidin-5-yl)-phenyl]-(2-(S)-pyrrolidin-1-ylmethyl-pyrrolidin-1-yl)-methanone수율 47%

시약·촉매·용매 4

HCID 11979704Tetrakis(triphenylphosphine)palladium촉매HCID 702Ethanol용매HCID 962Water용매HCID 1140Toluene용매

실험 절차

Procedure SS: To a stirred solution of (4-bromo-phenyl)-(2-(S)-pyrrolidin-1-ylmethyl-pyrrolidin-1-yl)-methanone (100 mg, 0.297 mmol), sodium carbonate (94.4 mg, 0.890 mmol) and 2-Methoxy-5-pyrimidine boronic acid (230 mg, 1.48 mmol) in toluene (5 ml), water (1 ml) and ethanol (1.5 ml) under nitrogen was added Tetrakis (triphenylphosphine) palladium (0) (34.3 mg, 0.030 mmol). The reaction was then heated to reflux for 48 h. The reaction was allowed to cool and bound to a SCX-2 cartridge (5 g). The cartridge washed with two cartridge volumes of dimethylformamide and one volume of methanol. The product was eluted using 2M ammonia in methanol. The ammonia/methanol solution was evaporated on a Genevac HT4. The sample was further purified by prep-LCMS. The resulting acetonitrile/water fractions were combined and evaporated using a Genevac to give 51 mg of a colourless oil (47%). MS (ES+) 367.3

후처리

  1. temperatureThe reaction was then heated
  2. temperatureto reflux for 48 h
  3. temperatureto cool
  4. washThe cartridge washed with two cartridge volumes of dimethylformamide and one volume of methanol
  5. washThe product was eluted
  6. customThe ammonia/methanol solution was evaporated on a Genevac HT4
  7. customThe sample was further purified by prep-LCMS
  8. customevaporated

출처 및 근거

ORD 기록
ord-cbfb0561e93b429381a7c749ff6b8116
출처 데이터셋
uspto-grants-2009_12
특허 번호
US07632857B2

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