Sodium Carbonate → Racemic methyl-3-[[2-[5-chloro-1-(p-tolylsulfonyl)pyrrolo[2,3-b]pyridin-3-yl]-5-fluoro-pyrimidin-4-yl]amino]-2-hydroxy-1-methyl-cyclohexanecarboxylate

HRID 75027ノート

反応式

HRID 75027 の反応式
[CH3:1][O:2][C:3]([C:5]1([CH3:21])[CH2:10][CH2:9][CH2:8][CH:7]([NH:11][C:12]2[C:17]([F:18])=[CH:16][N:15]=[C:14](Cl)[N:13]=2)[CH:6]1[OH:20])=[O:4].[Cl:22][C:23]1[CH:24]=[C:25]2[C:31](B3OC(C)(C)C(C)(C)O3)=[CH:30][N:29]([S:41]([C:44]3[CH:49]=[CH:48][C:47]([CH3:50])=[CH:46][CH:45]=3)(=[O:43])=[O:42])[C:26]2=[N:27][CH:28]=1.C([O-])([O-])=O.[Na+].[Na+]>C1COCC1>[CH3:1][O:2][C:3]([C:5]1([CH3:21])[CH2:10][CH2:9][CH2:8][CH:7]([NH:11][C:12]2[C:17]([F:18])=[CH:16][N:15]=[C:14]([C:31]3[C:25]4[C:26](=[N:27][CH:28]=[C:23]([Cl:22])[CH:24]=4)[N:29]([S:41]([C:44]4[CH:49]=[CH:48][C:47]([CH3:50])=[CH:46][CH:45]=4)(=[O:42])=[O:43])[CH:30]=3)[N:13]=2)[CH:6]1[OH:20])=[O:4]

参加物

5

反応物 3

HCID 10340Sodium CarbonateHCID 575977475-Chloro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-tosyl-1H-pyrrolo[2,3-b]pyridineHCID 87339124HCID 87339124、化合物2 回

生成物 1

HCID 67285771Racemic methyl-3-[[2-[5-chloro-1-(p-tolylsulfonyl)pyrrolo[2,3-b]pyridin-3-yl]-5-fluoro-pyrimidin-4-yl]amino]-2-hydroxy-1-methyl-cyclohexanecarboxylate

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

To a solution of racemic methyl-3-[(2-chloro-5-fluoro-pyrimidin-4-yl)amino]-2-hydroxy-1-methyl-cyclohexanecarboxylate, 66e, (0.65 g, 2.05 mmol) and 5-chloro-1-(p-tolylsulfonyl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrrolo[2,3-b]pyridine (1.32 g, 3.05 mmol) in THF (20 mL) was added aqueous Na2CO3 (3.52 mL of 2 M solution, 7.04 mmol). The solution was degassed with N2 for 20 minutes. Tetrakis triphenylphosphane palladium (O) (0.14 g, 0.12 mmol) was added and the mixture was refluxed overnight. LCMS showed good conversion, but some starting materials remained. More degassed 2 N Na2CO3 was added followed by another portion of Tetrakis triphenylphosphane palladium (0.14 g, 0.12 mmol). The reaction was refluxed for another 4 hours. The mixture was cooled to room temperature, extracted with EtOAc. The organic phase was washed by brine and dried over Na2SO4. After evaporation of solvent the crude mixture was purified by silica gel chromatography (Hexanes/EtOAc 100/0 to 0/100) to provide 1.0 g of racemic methyl-3-[[2-[5-chloro-1-(p-tolylsulfonyl)pyrrolo[2,3-b]pyridin-3-yl]-5-fluoro-pyrimidin-4-yl]amino]-2-hydroxy-1-methyl-cyclohexanecarboxylate, 66f. LCMS: 588.26 (M+1).

後処理

  1. customThe solution was degassed with N2 for 20 minutes
  2. temperaturethe mixture was refluxed overnight
  3. customMore degassed 2 N Na2CO3
  4. additionwas added
  5. temperatureThe reaction was refluxed for another 4 hours
  6. extractionextracted with EtOAc
  7. washThe organic phase was washed by brine
  8. dry with materialdried over Na2SO4
  9. customAfter evaporation of solvent the crude mixture
  10. customwas purified by silica gel chromatography (Hexanes/EtOAc 100/0 to 0/100)

出典と根拠

ORDレコード
ord-dea9074ce9514b5481b7205706cd2b6e
出典データセット
uspto-grants-2014_09
特許番号
US08829007B2

反応ノート

読み込み中…