Formaldehyde → HCID 178482103, compound

HRID 336857Notes

Reaction equation

HRID 336857 reaction equation
[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]

Participants

7

Reactant 4

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

Product 1

HCID 178482103HCID 178482103, compoundYield 20.8%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

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.

Workup

  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%)

Sources & evidence

ORD record
ord-993262b2bc4d44a58fab938369a19f63
Source dataset
uspto-grants-2014_11
Patent number
US08889711B2

Reaction notes

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