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 659709ノート

反応式

HRID 659709 の反応式
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

参加物

8

反応物 5

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

生成物 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

試薬・触媒・溶媒 2

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 8028Tetrahydrofuran溶媒

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-8460c7a31a044b79b2d89fae734e5775
出典データセット
uspto-grants-2011_12
特許番号
US08080546B2

反応ノート

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