Formaldehyde → HCID 178482103, 화합물

HRID 336857노트

반응식

HRID 336857 반응식
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:13]=[C:12]3[N:14](C(OC(C)(C)C)=O)[N:15]=[C:16]([CH3:17])[C:11]3=[C:10]([C:25]3[CH:30]=[CH:29][C:28]([N:31]4[CH2:36][CH2:35][N:34]([C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])[CH2:33][CH2:32]4)=[CH:27][CH:26]=3)[C:9]=2[C:44]#[N:45])=[C:4]([F:46])[CH:3]=1.[CH3:47][O-].[Na+].C=O.[BH4-].[Na+]>CO.O>[C:44]([C:9]1[C:10]([C:25]2[CH:30]=[CH:29][C:28]([N:31]3[CH2:36][CH2:35][N:34]([C:37]([O:39][C:40]([CH3:43])([CH3:41])[CH3:42])=[O:38])[CH2:33][CH2:32]3)=[CH:27][CH:26]=2)=[C:11]2[C:16]([CH3:17])=[N:15][NH:14][C:12]2=[N:13][C:8]=1[C:5]1[CH:6]=[CH:7][C:2]([NH:1][CH3:47])=[CH:3][C:4]=1[F:46])#[N:45]

참가 물질

7

반응물 4

HCID 712FormaldehydeHCID 4311764Sodium borohydrideHCID 10942334Sodium MethoxideHCID 67074167HCID 67074167, 화합물

생성물 1

HCID 178482103HCID 178482103, 화합물수율 20.8%

시약·촉매·용매 2

HCID 887Methanol용매HCID 962Water용매

실험 절차

To a solution of 0.20 g (0.32 mmol) of tert-butyl 6-(4-amino-2-fluorophenyl)-4-(4-(4-(tert-butoxycarbonyl)piperazin-1-yl)phenyl)-5-cyano-3-methyl-1H-pyrazolo[3,4-b]pyridine-1-carboxylate in 40 ml of MeOH are added 0.16 mg (2.9 mmol) of sodium methoxide and 0.10 g (3.2 mmol) of paraformaldehyde. The reaction mixture is refluxed for 2 h. The mixture is then cooled, 0.24 g (6.34 mmol) of sodium borohydride is added, and the mixture is refluxed for 1 h. The mixture is then cooled, diluted with iced water, then extracted with dichloromethane. The organic phase is dried over magnesium sulfate, filtered, and concentrated. The solid obtained is then purified by chromatography on silica (methanol gradient in dichloromethane: 1 to 2%) to give 0.036 g (18%) of tert-butyl 4-(4-(5-cyano-6-(2-fluoro-4-(methylamino)phenyl)-3-methyl-1H-pyrazolo[3,4-b]pyridin-4-yl)phenyl)piperazine-1-carboxylate in the form of yellow crystals. Deprotection of the piperazine following general procedure E2 gives 0.02 g (68%) of 6-(2-fluoro-4-(methylamino)phenyl)-3-methyl-4-(4-(piperazine-1-yl)phenyl)-1H-pyrazolo[3,4-b]pyridine-5-carbonitrile hydrochloride in the form of orange crystals.

후처리

  1. temperatureThe reaction mixture is refluxed for 2 h
  2. temperatureThe mixture is then cooled
  3. temperaturethe mixture is refluxed for 1 h
  4. temperatureThe mixture is then cooled
  5. extractionextracted with dichloromethane
  6. dry with materialThe organic phase is dried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe solid obtained
  10. customis then purified by chromatography on silica (methanol gradient in dichloromethane: 1 to 2%)

출처 및 근거

ORD 기록
ord-993262b2bc4d44a58fab938369a19f63
출처 데이터셋
uspto-grants-2014_11
특허 번호
US08889711B2

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