Acetic Acid → HCID 136359783, compound

HRID 2360702Notes

Reaction equation

HRID 2360702 reaction equation
[CH3:1][C@H:2]1[CH2:7][NH:6][C@H:5]([CH3:8])[CH2:4][N:3]1[C:9]([C:11]1[CH:16]=[C:15]([C:17]2[CH:22]=[CH:21][C:20]([OH:23])=[CH:19][C:18]=2[F:24])[N:14]=[C:13]2[N:25]([CH:29]3[CH2:34][CH2:33][CH2:32][CH2:31][O:30]3)[N:26]=[C:27]([CH3:28])[C:12]=12)=[O:10].[N:35]1[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=1[CH:41]=O.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClC(Cl)C.O>[CH3:1][C@H:2]1[CH2:7][N:6]([CH2:41][C:36]2[CH:37]=[CH:38][CH:39]=[CH:40][N:35]=2)[C@H:5]([CH3:8])[CH2:4][N:3]1[C:9]([C:11]1[CH:16]=[C:15]([C:17]2[CH:22]=[CH:21][C:20]([OH:23])=[CH:19][C:18]=2[F:24])[N:14]=[C:13]2[N:25]([CH:29]3[CH2:34][CH2:33][CH2:32][CH2:31][O:30]3)[N:26]=[C:27]([CH3:28])[C:12]=12)=[O:10]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 142732-PyridinecarboxaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 136359784HCID 136359784, compound

Product 1

HCID 136359783HCID 136359783, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 63651,1-DichloroethaneSolvent

Conditions

Temperature
40 °C

Procedure

To a mixture of ((2S,5R)-2,5-Dimethyl-piperazin-1-yl)-[6-(2-fluoro-4-hydroxy-phenyl)-3-methyl-1-(tetrahydro-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl]-methanone (200 mg, precursor of example 543) and pyridine-2-carboxaldehyde (46 mg) in dichloroethane (5 mL) containing acetic acid (7.4 μL) was added sodium triacetoxy borohydride (136 mg) at r.t., then the mixture was stirred at 40° C. overnight. Water was added carefully and the mixture was extracted with dichloromethane. The combined organic phases were dried over magnesium sulfate and concentrated to dryness giving ((2S,5R)-2,5-Dimethyl-4-pyridin-2-ylmethyl-piperazin-1-yl)-[6-(2-fluoro-4-hydroxy-phenyl)-3-methyl-1-(tetrahydro-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridin-4-yl]-methanone. This was dissolved in THF (7 mL) containing conc. hydrochloric acid (1.5 mL) and stirred r.t. overnight. The precipitate formed was filtered off and dried in air. ((2S,5R)-2,5-Dimethyl-4-pyridin-2-ylmethyl-piperazin-1-yl)-[6-(2-fluoro-4-hydroxy-phenyl)-3-methyl-1H-pyrazolo[3,4-b]pyridin-4-yl]-methanone was obtained as a hydrochloride salt (263 mg, 100%).

Workup

  1. extractionthe mixture was extracted with dichloromethane
  2. dry with materialThe combined organic phases were dried over magnesium sulfate
  3. concentrationconcentrated to dryness

Sources & evidence

ORD record
ord-6724232c3a83452e885574963799dea5
Source dataset
uspto-grants-2014_04
Patent number
US08686150B2

Reaction notes

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