2-Methyltetrahydrofuran → (R)-methyl 3-((5-fluoro-2-(5-fluoro-1-tosyl-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4-yl)amino)-4,4-dimethylpentanoate

HRID 1055038ノート

反応式

HRID 1055038 の反応式
CC1OCCC1.[F:7][C:8]1[CH:9]=[C:10]2[C:16](B3OC(C)(C)C(C)(C)O3)=[CH:15][N:14]([S:26]([C:29]3[CH:34]=[CH:33][C:32]([CH3:35])=[CH:31][CH:30]=3)(=[O:28])=[O:27])[C:11]2=[N:12][CH:13]=1.Cl[C:37]1[N:42]=[C:41]([NH:43][C@@H:44]([C:50]([CH3:53])([CH3:52])[CH3:51])[CH2:45][C:46]([O:48][CH3:49])=[O:47])[C:40]([F:54])=[CH:39][N:38]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>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].O>[F:54][C:40]1[C:41]([NH:43][C@@H:44]([C:50]([CH3:53])([CH3:52])[CH3:51])[CH2:45][C:46]([O:48][CH3:49])=[O:47])=[N:42][C:37]([C:16]2[C:10]3[C:11](=[N:12][CH:13]=[C:8]([F:7])[CH:9]=3)[N:14]([S:26]([C:29]3[CH:30]=[CH:31][C:32]([CH3:35])=[CH:33][CH:34]=3)(=[O:28])=[O:27])[CH:15]=2)=[N:38][CH:39]=1

参加物

8

反応物 5

HCID 73012-MethyltetrahydrofuranHCID 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 86714731methyl (3R)-3-[(2-chloro-5-fluoropyrimidin-4-yl)amino]-4,4-dimethylpentanoate

生成物 1

HCID 71247937(R)-methyl 3-((5-fluoro-2-(5-fluoro-1-tosyl-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4-yl)amino)-4,4-dimethylpentanoate

試薬・触媒・溶媒 2

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

反応条件

温度
115 °C

実験手順

A 2-MeTHF (253 mL)/water (56 mL) solution of 5-fluoro-1-(p-tolylsulfonyl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrrolo[2,3-b]pyridine, 7a, (24.3 g, 58.3 mmol), methyl (R)-methyl 3-((2-chloro-5-fluoropyrimidin-4-yl)amino)-4,4-dimethylpentanoate, 6a, (14.1 g, 48.6 mmol) and K3PO4 (30.9 g, 146 mmol) was purged with nitrogen for 0.75 h. XPhos (2.8 g, 5.8 mmol) and Pd2(dba)3 (1.1 g, 1.2 mmol) were added and the reaction mixture was stirred at 115° C. in a sealed tube for 2 h. The reaction mixture was cooled and the aqueous phase was removed. The organic phase was filtered through a pad of Celite and the mixture was concentrated to dryness. The residue was purified on silica gel (EA/Hex) to provide the desired product, 8a, (23.2 g): LCMS Gradient 10-90%, 0.1% formic acid, 5 min, C18/ACN, RT=2.18 minutes (M+H) 245.28.

後処理

  1. temperatureThe reaction mixture was cooled
  2. customthe aqueous phase was removed
  3. filtrationThe organic phase was filtered through a pad of Celite
  4. concentrationthe mixture was concentrated to dryness
  5. customThe residue was purified on silica gel (EA/Hex)

出典と根拠

ORDレコード
ord-bb683614ef9e429d9cbdb471afd7169a
出典データセット
uspto-grants-2016_07
特許番号
US09394302B2

反応ノート

読み込み中…