Ammonium Chloride → N-cyclopropyl-3-(1-(3-fluorophenyl)-7-methyl-6-oxo-6,7-dihydro-1H-pyrazolo[3,4-b]pyridin-4-ylamino)-4-methylbenzamide

HRID 659709Notes

Reaction equation

HRID 659709 reaction equation
Cl[C:2]1[C:3]2[CH:12]=[N:11][N:10]([C:13]3[CH:18]=[CH:17][CH:16]=[C:15]([F:19])[CH:14]=3)[C:4]=2[N:5]([CH3:9])[C:6](=[O:8])[CH:7]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2N(C)C)CCCCC1.[NH2:48][C:49]1[CH:50]=[C:51]([CH:58]=[CH:59][C:60]=1[CH3:61])[C:52]([NH:54][CH:55]1[CH2:57][CH2:56]1)=[O:53].[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[Cl-].[NH4+]>C1COCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH:55]1([NH:54][C:52](=[O:53])[C:51]2[CH:58]=[CH:59][C:60]([CH3:61])=[C:49]([NH:48][C:2]3[C:3]4[CH:12]=[N:11][N:10]([C:13]5[CH:18]=[CH:17][CH:16]=[C:15]([F:19])[CH:14]=5)[C:4]=4[N:5]([CH3:9])[C:6](=[O:8])[CH:7]=3)[CH:50]=2)[CH2:56][CH2:57]1

Participants

8

Reactant 5

HCID 25517Ammonium ChlorideHCID 2733832Lithium HexamethyldisilazideHCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenylHCID 119838543-amino-N-cyclopropyl-4-methylbenzamideHCID 57708073HCID 57708073, compound

Product 1

HCID 25242389N-cyclopropyl-3-(1-(3-fluorophenyl)-7-methyl-6-oxo-6,7-dihydro-1H-pyrazolo[3,4-b]pyridin-4-ylamino)-4-methylbenzamide

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8028TetrahydrofuranSolvent

Procedure

In a glass tube, a mixture of 4-chloro-1-(3-fluorophenyl)-7-methyl-1H-pyrazolo[3,4-b]pyridin-6(7H)-one (76 mg, 0.27 mmol), tris(dibenzylideneacetone)dipalladium (0) (12 mg), 2-dicyclohexylphosphino-2′-(N,N-dimethylamino)biphenyl (Dave-Phos, 12 mg), 3-amino-N-cyclopropyl-4-methylbenzamide (78 mg, 0.41 mmol) in THF (2 mL) was de-gassed slightly under reduced pressure or a vacuum. LiHMDS (0.82 mL of 1.0 M in THF solution, 821 mmol) was added slowly. The glass tube was sealed and placed in an oil bath at 60° C. for 1 h. The mixture was cooled to RT and treated with saturated ammonium chloride solution, then extracted twice with EtOAc. The combined EtOAc layers were washed with brine, dried and concentrated. The resulting crude material was purified by silica gel chromatography (80-100% EtOAc in hexanes) to provide the title compound as a tan crystalline solid. MS (ESI, pos.ion) m/z: 432.0 (M+1).

Workup

  1. customwas de-gassed slightly under reduced pressure
  2. customThe glass tube was sealed
  3. extractionextracted twice with EtOAc
  4. washThe combined EtOAc layers were washed with brine
  5. customdried
  6. concentrationconcentrated
  7. customThe resulting crude material was purified by silica gel chromatography (80-100% EtOAc in hexanes)

Sources & evidence

ORD record
ord-8460c7a31a044b79b2d89fae734e5775
Source dataset
uspto-grants-2011_12
Patent number
US08080546B2

Reaction notes

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