Lithium Hexamethyldisilazide → 1-(4'-(Cyclopropylmethyl)-2-(4-(methylsulfonyl)phenylamino)-4,5'-bipyrimidin-2'-ylamino)-2-methylpropan-2-ol

HRID 1397162노트

반응식

HRID 1397162 반응식
[S:1](=[C:4]1[CH:10]=[CH:9][C:7]([NH2:8])=[CH:6][CH2:5]1)(=[O:3])=[O:2].[Li+].[CH3:12][Si]([N-][Si](C)(C)C)(C)C.[CH:21]1([CH2:24][C:25]2[C:30]([C:31]3[CH:36]=[CH:35][N:34]=[C:33](S(C)=O)[N:32]=3)=[CH:29][N:28]=[C:27]([NH:40][CH2:41][C:42]([CH3:45])([OH:44])[CH3:43])[N:26]=2)[CH2:23][CH2:22]1>C1COCC1>[CH:21]1([CH2:24][C:25]2[C:30]([C:31]3[CH:36]=[CH:35][N:34]=[C:33]([NH:8][C:7]4[CH:6]=[CH:5][C:4]([S:1]([CH3:12])(=[O:3])=[O:2])=[CH:10][CH:9]=4)[N:32]=3)=[CH:29][N:28]=[C:27]([NH:40][CH2:41][C:42]([CH3:45])([OH:44])[CH3:43])[N:26]=2)[CH2:22][CH2:23]1

참가 물질

5

반응물 3

HCID 2733832Lithium HexamethyldisilazideHCID 204326224-SulfonylanilineHCID 679836401-(4'-(Cyclopropylmethyl)-2-(methylsulfinyl)-4,5'-bipyrimidin-2'-ylamino)-2-methylpropan-2-ol

생성물 1

HCID 679839941-(4'-(Cyclopropylmethyl)-2-(4-(methylsulfonyl)phenylamino)-4,5'-bipyrimidin-2'-ylamino)-2-methylpropan-2-ol수율 17%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

To a solution of 4-sulfonylaniline (71.1 mg, 0.415 mmol) in THF (277 μl) cooled to −78° C. under nitrogen, LiHMDS (69.4 mg, 0.415 mmol) was added dropwise. The reaction mixture was warmed up to rt, then was stirred for 30 minutes. To the reaction mixture cooled back to −78° C., 1-(4′-(cyclopropylmethyl)-2-(methylsulfinyl)-4,5′-bipyrimidin-2′-ylamino)-2-methylpropan-2-ol (5-3) (50 mg, 0.138 mmol) was added, and the reaction mixture was warmed up to rt, then was stirred for additional 1 hour. According to LC/MS, the reaction was complete. The crude product was purified by reverse-phase HPLC [30-100% organic phase over 15 minutes] followed by Biotage™ silica gel chromatography [10 g SNAP column, 100% DCM to 12% MeOH/DCM] to obtain the desired product (11 mg, 17%).

후처리

  1. temperatureTo the reaction mixture cooled back to −78° C.
  2. temperaturethe reaction mixture was warmed up to rt
  3. stirringwas stirred for additional 1 hour
  4. customThe crude product was purified by reverse-phase HPLC [30-100% organic phase over 15 minutes]

출처 및 근거

ORD 기록
ord-a609201e053b45409a7c14702278ace5
출처 데이터셋
uspto-grants-2014_12
특허 번호
US08901147B2

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