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

HRID 55862ノート

反応式

HRID 55862 の反応式
[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

参加物

9

反応物 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、化合物

生成物 1

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

試薬・触媒・溶媒 4

HCID 178418397HCID 178418397、化合物触媒HCID 962Water溶媒HCID 8857Ethyl Acetate溶媒HCID 218864351,4-Dioxane--water (1/1)溶媒

反応条件

温度
120 °C

実験手順

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+).

後処理

  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)

出典と根拠

ORDレコード
ord-f7689369cac64b7fa4a9f547d206a9f9
出典データセット
uspto-grants-2016_09
特許番号
US09433622B2

反応ノート

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