Lithium Hexamethyldisilazide → N-(3-(2-Methyl-9-(tetrahydro-2H-pyran-2-YL)-9H-purin-6-YL)-5-(4-(methylsulfonyl)benzyl)pyridin-2-YL)-1-(tetrahydro-2H-pyran-2-YL)-1H-indazol-4-amine

HRID 1621481노트

반응식

HRID 1621481 반응식
F[C:2]1[C:7]([C:8]2[N:16]=[C:15]([CH3:17])[N:14]=[C:13]3[C:9]=2[N:10]=[CH:11][N:12]3[CH:18]2[CH2:23][CH2:22][CH2:21][CH2:20][O:19]2)=[CH:6][C:5]([CH2:24][C:25]2[CH:30]=[CH:29][C:28]([S:31]([CH3:34])(=[O:33])=[O:32])=[CH:27][CH:26]=2)=[CH:4][N:3]=1.[O:35]1[CH2:40][CH2:39][CH2:38][CH2:37][CH:36]1[N:41]1[C:49]2[CH:48]=[CH:47][CH:46]=[C:45]([NH2:50])[C:44]=2[CH:43]=[N:42]1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C>C1COCC1>[CH3:17][C:15]1[N:14]=[C:13]2[C:9]([N:10]=[CH:11][N:12]2[CH:18]2[CH2:23][CH2:22][CH2:21][CH2:20][O:19]2)=[C:8]([C:7]2[C:2]([NH:50][C:45]3[C:44]4[CH:43]=[N:42][N:41]([CH:36]5[CH2:37][CH2:38][CH2:39][CH2:40][O:35]5)[C:49]=4[CH:48]=[CH:47][CH:46]=3)=[N:3][CH:4]=[C:5]([CH2:24][C:25]3[CH:30]=[CH:29][C:28]([S:31]([CH3:34])(=[O:33])=[O:32])=[CH:27][CH:26]=3)[CH:6]=2)[N:16]=1

참가 물질

5

반응물 3

HCID 2733832Lithium HexamethyldisilazideHCID 441182321-(Oxan-2-yl)-1H-indazol-4-amineHCID 595482776-(2-fluoro-5-(4-(methylsulfonyl)benzyl)pyridin-3-yl)-2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purine

생성물 1

HCID 66611958N-(3-(2-Methyl-9-(tetrahydro-2H-pyran-2-YL)-9H-purin-6-YL)-5-(4-(methylsulfonyl)benzyl)pyridin-2-YL)-1-(tetrahydro-2H-pyran-2-YL)-1H-indazol-4-amine수율 115.7%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

실험 절차

A mixture of 6-(2-fluoro-5-(4-(methylsulfonyl)benzyl)pyridin-3-yl)-2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purine (78.5 mg, 0.163 mmol) and 1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-4-amine (45.5 mg, 0.209 mmol) in THF (1.0 mL) was cooled in an ice/salt bath and treated dropwise with LiHMDS (0.627 mL of a 1.0 M solution in THF). The mixture was stirred for 20 min and then quenched with water (0.1 mL). The mixture was stirred for 3 min and then extracted into EtOAc from saturated aqueous NaHCO3. The EtOAc extracts were dried (MgSO4) and concentrated to give a dark yellow solid (128 mg). This was taken on to the next step without further purification.

후처리

  1. temperaturewas cooled in an ice/salt bath
  2. customquenched with water (0.1 mL)
  3. stirringThe mixture was stirred for 3 min
  4. extractionextracted into EtOAc from saturated aqueous NaHCO3
  5. dry with materialThe EtOAc extracts were dried (MgSO4)
  6. concentrationconcentrated

출처 및 근거

ORD 기록
ord-cfece1fd9c084d49a3e2159ff8906db2
출처 데이터셋
uspto-grants-2014_07
특허 번호
US08772480B2

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