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 527066노트

반응식

HRID 527066 반응식
[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]

참가 물질

5

반응물 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, 화합물2회

생성물 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

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

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 (0) (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).

후처리

  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)

출처 및 근거

ORD 기록
ord-eb908ba874834a86a42c787977a2e9bc
출처 데이터셋
uspto-grants-2016_05
특허 번호
US09345708B2

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