Potassium Carbonate → (R)-3-cyclopentyl-3-[4-(2-methoxy-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]propanenitrile

HRID 403191ノート

反応式

HRID 403191 の反応式
Cl[C:2]1[C:3]2[CH:12]=[CH:11][NH:10][C:4]=2[N:5]=[C:6]([O:8][CH3:9])[N:7]=1.[CH:13]1([C@H:18]([N:22]2[CH:26]=[C:25](B3OC(C)(C)C(C)(C)O3)[CH:24]=[N:23]2)[CH2:19][C:20]#[N:21])[CH2:17][CH2:16][CH2:15][CH2:14]1.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.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>[CH:13]1([C@H:18]([N:22]2[CH:26]=[C:25]([C:2]3[C:3]4[CH:12]=[CH:11][NH:10][C:4]=4[N:5]=[C:6]([O:8][CH3:9])[N:7]=3)[CH:24]=[N:23]2)[CH2:19][C:20]#[N:21])[CH2:17][CH2:16][CH2:15][CH2:14]1

参加物

7

反応物 3

HCID 11430Potassium CarbonateHCID 61402294-chloro-2-methoxy-7H-pyrrolo[2,3-d]pyrimidineHCID 58221004(betaR)-beta-Cyclopentyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-propanenitrile

生成物 1

HCID 58221013(R)-3-cyclopentyl-3-[4-(2-methoxy-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]propanenitrile

試薬・触媒・溶媒 3

HCID 178418397HCID 178418397、化合物触媒HCID 962Water溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
100 °C

実験手順

4-Chloro-2-methoxy-7H-pyrrolo[2,3-d]pyrimidine (0.4 g, 2.18 mmol, Toronto Research Chemicals) and (R)-3-cyclopentyl-3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]propanenitrile (0.824 g, 2.61 mmol, prepared as described in Org. Lett., 2009, 11(9), 1999-2002.) were dissolved in 1,4-dioxane (4 mL) and potassium carbonate (0.903 g, 6.54 mmol) in water (2 mL) was added. The mixture was degassed and tetrakis(triphenylphosphine)palladium(0) (0.126 g, 0.109 mmol) was added. The reaction mixture was heated to 100° C. for 16 h. The reaction mixture was partitioned between water and ethyl acetate. The aqueous layer was extracted with ethyl acetate three times. The combined extracts were dried over sodium sulfate, decanted and concentrated. Flash column chromatography, eluting with a gradient from 0-10% MeOH in methylene chloride was used to purify the product (670 mg, 91%). 1H NMR (300 MHz, CD3OD): δ 8.59 (s, 1H), 8.35 (s, 1H), 7.24 (d, 1H), 6.81 (d, 1H), 4.47 (dt, 1H), 4.04 (s, 3H), 3.21 (dd, 1H), 3.10 (dd, 1H), 2.62-2.44 (m, 1H), 2.02-1.86 (m, 1H), 1.81-1.20 (m, 7H); LCMS (M+H)+: 337.0.

後処理

  1. customThe mixture was degassed
  2. customThe reaction mixture was partitioned between water and ethyl acetate
  3. extractionThe aqueous layer was extracted with ethyl acetate three times
  4. dry with materialThe combined extracts were dried over sodium sulfate
  5. customdecanted
  6. concentrationconcentrated
  7. washFlash column chromatography, eluting with a gradient from 0-10% MeOH in methylene chloride
  8. customto purify the product (670 mg, 91%)

出典と根拠

ORDレコード
ord-c1c785850b784723bac36610ebdcf785
出典データセット
uspto-grants-2014_06
特許番号
US08748401B2

反応ノート

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