Benzenesulfonic Acid → Benzenesulfonic Acid

HRID 1754443노트

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HRID 1754443 반응식
[NH2:1][C:2]1[C:3]([F:26])=[CH:4][C:5]([O:15][CH2:16][CH2:17][O:18][Si](C(C)(C)C)(C)C)=[C:6]([N:8]2[C:12](=[O:13])[N:11]([CH3:14])[N:10]=[N:9]2)[CH:7]=1.Cl[C:28]1[N:33]=[C:32]([NH:34][C@@H:35]2[CH2:43][C@H:42]3[N:38]([CH2:39][CH2:40][CH2:41]3)[C:37]([CH3:45])([CH3:44])[CH2:36]2)[C:31]([C:46]#[N:47])=[CH:30][N:29]=1.[C:48]1([S:54]([OH:57])(=[O:56])=[O:55])[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=1>CC(O)C>[CH3:44][C:37]1([CH3:45])[CH2:36][C@H:35]([NH:34][C:32]2[C:31]([C:46]#[N:47])=[CH:30][N:29]=[C:28]([NH:1][C:2]3[CH:7]=[C:6]([N:8]4[C:12](=[O:13])[N:11]([CH3:14])[N:10]=[N:9]4)[C:5]([O:15][CH2:16][CH2:17][OH:18])=[CH:4][C:3]=3[F:26])[N:33]=2)[CH2:43][C@H:42]2[N:38]1[CH2:39][CH2:40][CH2:41]2.[C:48]1([S:54]([OH:57])(=[O:56])=[O:55])[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=1

참가 물질

6

반응물 3

HCID 7371Benzenesulfonic AcidHCID 86704483(7R,8aS)-N-(2-chloro-5-cyanopyrimidin-4-yl)-octahydro-5,5-dimethylindolizin-7-amineHCID 867044861-(5-amino-2-(2-(tert-butyldimethylsilyl)oxyethoxy)-4-fluorophenyl)-4-methyl-1H-tetrazol-5(4H)-one

생성물 2

HCID 7371Benzenesulfonic AcidHCID 718115574-((7R,8aS)-octahydro-5,5-dimethylindolizin-7-ylamino)-2-(4-(2-hydroxyethoxy)-2-fluoro-5-(4,5-dihydro-4-methyl-5-oxotetrazol-1-yl)phenylamino)pyrimidine-5-carbonitrile

시약·촉매·용매 1

HCID 3776Isopropanol용매

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온도
80 °C

실험 절차

A mixture of 1-(5-amino-2-(2-(tert-butyldimethylsilyl)oxyethoxy)-4-fluorophenyl)-4-methyl-1H-tetrazol-5(4H)-one (200 mg), (7R,8aS)—N-(2-chloro-5-cyanopyrimidin-4-yl)-octahydro-5,5-dimethylindolizin-7-amine (120 mg), and benzenesulfonic acid (120 mg) in IPA (2 mL) was heated to 80° C. overnight. After cooling to ambient temperature, the crude mixture was concentrated to dryness. The crude product was absorbed onto silica gel and purified by CombiFlash chromatography (2N NH3 in MeOH/CH2Cl2=0-20%) to give desired product with benzenesulfonic acid. The methanol solution of the salt was passed through an ion-exchange resin column to remove acid to give the free base of compound 78 (120 mg, 57%).

후처리

  1. temperatureAfter cooling to ambient temperature
  2. concentrationthe crude mixture was concentrated to dryness
  3. customThe crude product was absorbed onto silica gel
  4. custompurified by CombiFlash chromatography (2N NH3 in MeOH/CH2Cl2=0-20%)

출처 및 근거

ORD 기록
ord-50f98e2a38074d1da4b11d78c8cc9a28
출처 데이터셋
uspto-grants-2015_10
특허 번호
US09169249B2

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