Potassium Phosphate, Tribasic → N-((1R,3S)-3-(5-fluoro-2-(5-fluoro-1-tosyl-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4-ylamino)cyclohexyl)pyrrolidine-1-carboxamide

HRID 75031

反応式

HRID 75031 の反応式
Cl[C:2]1[N:7]=[C:6]([NH:8][C@H:9]2[CH2:14][CH2:13][CH2:12][C@@H:11]([NH:15][C:16]([N:18]3[CH2:22][CH2:21][CH2:20][CH2:19]3)=[O:17])[CH2:10]2)[C:5]([F:23])=[CH:4][N:3]=1.[F:24][C:25]1[CH:26]=[C:27]2[C:33](B3OC(C)(C)C(C)(C)O3)=[CH:32][N:31]([S:43]([C:46]3[CH:51]=[CH:50][C:49]([CH3:52])=[CH:48][CH:47]=3)(=[O:45])=[O:44])[C:28]2=[N:29][CH:30]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1>O.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]>[F:23][C:5]1[C:6]([NH:8][C@H:9]2[CH2:14][CH2:13][CH2:12][C@@H:11]([NH:15][C:16]([N:18]3[CH2:22][CH2:21][CH2:20][CH2:19]3)=[O:17])[CH2:10]2)=[N:7][C:2]([C:33]2[C:27]3[C:28](=[N:29][CH:30]=[C:25]([F:24])[CH:26]=3)[N:31]([S:43]([C:46]3[CH:51]=[CH:50][C:49]([CH3:52])=[CH:48][CH:47]=3)(=[O:44])=[O:45])[CH:32]=2)=[N:3][CH:4]=1

参加物

7

反応物 4

HCID 62657Potassium Phosphate, TribasicHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 672856905-fluoro-1-((4-methylphenyl)sulfonyl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo(2,3-b)pyridineHCID 86667450N-((1R,3S)-3-((2-Chloro-5-fluoropyrimidin-4-yl)amino)cyclohexyl)pyrrolidine-1-carboxamide2 回

生成物 1

HCID 68008350N-((1R,3S)-3-(5-fluoro-2-(5-fluoro-1-tosyl-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4-ylamino)cyclohexyl)pyrrolidine-1-carboxamide

試薬・触媒・溶媒 2

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 962Water溶媒

反応条件

温度
125 °C

実験手順

A solution of N-((1R,3S)-3-(2-chloro-5-fluoropyrimidin-4-ylamino)cyclohexyl)-pyrrolidine-1-carboxamide, 67e, (6.8 g, 20.0 mmol), 5-fluoro-1-(p-tolylsulfonyl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrrolo[2,3-b]pyridine, 44a, (12.5 g, 30.0 mmol) and K3PO4 (17.0 g, 80.0 mmol) in 2-methyl THF (180 mL) and water (20 mL) was degassed under nitrogen for 30 min. To the mixture was added dicyclohexyl-[2-(2,4,6-triisopropylphenyl)phenyl]phosphane (XPhos) (1.1 g, 2.4 mmol) and Pd2(dba)3 (0.5 g, 0.5 mmol). The reaction mixture was heated in a pressure bottle at 125° C. for 2.5 hr. The reaction mixture was filtered through celite, the solvent was removed under reduced pressure. The resulting residue was purified by silica gel chromatography (8% MeOH/CH2Cl2) to afford 11.5 g of the desired product.

後処理

  1. filtrationThe reaction mixture was filtered through celite
  2. customthe solvent was removed under reduced pressure
  3. customThe resulting residue was purified by silica gel chromatography (8% MeOH/CH2Cl2)

出典と根拠

ORDレコード
ord-a6251a2de8cd4d0f92b20896e24b1b05
出典データセット
uspto-grants-2014_09
特許番号
US08829007B2

関連ノート

読み込み中…