Morpholine → 1-(4-fluoro-phenyl)-1H-pyrazolo[3,4-c]pyridine-4-carboxylic acid [1-(6-morpholin-4-yl-pyridin-3-yl)-cyclopropyl]-amide

HRID 2172981Notes

Reaction equation

HRID 2172981 reaction equation
Br[C:2]1[N:7]=[CH:6][C:5]([C:8]2([NH:11][C:12]([C:14]3[C:15]4[CH:22]=[N:21][N:20]([C:23]5[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=5)[C:16]=4[CH:17]=[N:18][CH:19]=3)=[O:13])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.[NH:30]1[CH2:35][CH2:34][O:33][CH2:32][CH2:31]1>CS(C)=O.CCOC(C)=O>[N:30]1([C:2]2[N:7]=[CH:6][C:5]([C:8]3([NH:11][C:12]([C:14]4[C:15]5[CH:22]=[N:21][N:20]([C:23]6[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=6)[C:16]=5[CH:17]=[N:18][CH:19]=4)=[O:13])[CH2:10][CH2:9]3)=[CH:4][CH:3]=2)[CH2:35][CH2:34][O:33][CH2:32][CH2:31]1

Participants

5

Reactant 2

HCID 8083MorpholineHCID 52916799HCID 52916799, compound

Product 1

HCID 529175031-(4-fluoro-phenyl)-1H-pyrazolo[3,4-c]pyridine-4-carboxylic acid [1-(6-morpholin-4-yl-pyridin-3-yl)-cyclopropyl]-amide

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 1-(4-fluoro-phenyl)-1H-pyrazolo[3,4-c]pyridine-4-carboxylic acid [1-(6-bromo-pyridin-3-yl)-cyclopropyl]-amide (35 mg, 0.077 mmol) and morpholine (68 μL, 0.77 mmol) in DMSO (1 mL) is heated in a pressure tube at 160° C. After 40 hours, the mixture is cooled to room temperature, diluted with EtOAc (50 mL) and washed with saturated aqueous ammonium chloride (2×50 mL), saturated aqueous sodium bicarbonate (50 mL), brine (50 mL), dried over MgSO4, filtered and concentrated. The resulting solid is purified by silica gel chromatography eluting with a gradient of 0-5% methanol in dichloromethane to give a solid, which is triturated with ether (5 mL), filtered and dried to afford the title compound.

Workup

  1. washwashed with saturated aqueous ammonium chloride (2×50 mL), saturated aqueous sodium bicarbonate (50 mL), brine (50 mL)
  2. dry with materialdried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe resulting solid is purified by silica gel chromatography
  6. washeluting with a gradient of 0-5% methanol in dichloromethane
  7. customto give a solid, which
  8. customis triturated with ether (5 mL)
  9. filtrationfiltered
  10. customdried

Sources & evidence

ORD record
ord-8daae4d9bdc645339ec1d543b611e020
Source dataset
uspto-grants-2015_06
Patent number
US09056858B2

Reaction notes

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