Sodium Carbonate → 5-(2-Chloro-primidin-4-yl)-2-((S)-3-fluoro-pyrrolidin-1-yl)-nicotinonitrile

HRID 55862노트

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HRID 55862 반응식
[F:1][C@H:2]1[CH2:6][CH2:5][N:4]([C:7]2[N:14]=[CH:13][C:12](B3OC(C)(C)C(C)(C)O3)=[CH:11][C:8]=2[C:9]#[N:10])[CH2:3]1.BC1C=NC(N2CC[C@H](F)C2)=C(C=1)C#N.[Cl:39][C:40]1[N:45]=[C:44](Cl)[CH:43]=[CH:42][N:41]=1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.O.CCOC(C)=O.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:39][C:40]1[N:45]=[C:44]([C:12]2[CH:13]=[N:14][C:7]([N:4]3[CH2:5][CH2:6][C@H:2]([F:1])[CH2:3]3)=[C:8]([CH:11]=2)[C:9]#[N:10])[CH:43]=[CH:42][N:41]=1

참가 물질

9

반응물 4

HCID 10340Sodium CarbonateHCID 775312,4-DichloropyrimidineHCID 903571482-((S)-3-Fluoro-pyrrolidin-1-yl)-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-nicotinonitrileHCID 178419157HCID 178419157, 화합물

생성물 1

HCID 903695215-(2-Chloro-primidin-4-yl)-2-((S)-3-fluoro-pyrrolidin-1-yl)-nicotinonitrile수율 55%

시약·촉매·용매 4

HCID 178418397HCID 178418397, 화합물촉매HCID 962Water용매HCID 8857Ethyl Acetate용매HCID 218864351,4-Dioxane--water (1/1)용매

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온도
120 °C

실험 절차

A mixture of 2-((S)-3-Fluoro-pyrrolidin-1-yl)-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-nicotinonitrile and 5-boranyl-2-((S)-3-fluoro-pyrrolidin-1-yl)-nicotinonitrile (7) (2.64 g, ˜9.6 mmol), 2,4-dichloropyrimidine (1.2 g, 9.6 mmol), tetrakis(triphenylphosphine)palladium(0) (1.1 g, 1.0 mmol) and Na2CO3 (3.1 g, 28.8 mmol) were dissolved in 1:1 1,4-dioxane-H2O (40 mL) and the mixture was stirred at 120° C. in the microwave (250 W, stirring) for 30 minutes. The mixture was diluted with EtOAc (130 mL) and H2O (40 mL) and the layers separated. The organic phase was washed with saturated brine solution (50 mL), then dried (MgSO4), filtered and the solvent evaporated in vacuo. The crude product was purified by column chromatography (40-63 mesh silica gel, 1:1 isohexane-EtOAc) to provide the title compound as a pale yellow solid (1.6 g, 55%); LCMS, Rt=2.80 min (MeOH-FA method), m/z 304 (MH+).

후처리

  1. customthe layers separated
  2. washThe organic phase was washed with saturated brine solution (50 mL)
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. customthe solvent evaporated in vacuo
  6. customThe crude product was purified by column chromatography (40-63 mesh silica gel, 1:1 isohexane-EtOAc)

출처 및 근거

ORD 기록
ord-f7689369cac64b7fa4a9f547d206a9f9
출처 데이터셋
uspto-grants-2016_09
특허 번호
US09433622B2

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