Sodium Carbonate → 6-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)-4'-fluorobiphenyl-3-carbonitrile

HRID 76871ノート

反応式

HRID 76871 の反応式
Br[C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[CH:10]1[N:14]2[CH:15]=[N:16][CH:17]=[C:13]2[CH2:12][CH2:11]1)[C:5]#[N:6].[F:18][C:19]1[CH:24]=[CH:23][C:22](B(O)O)=[CH:21][CH:20]=1.C([O-])([O-])=O.[Na+].[Na+].[OH-].[K+]>COCCOC.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:17]1[N:16]=[CH:15][N:14]2[CH:10]([C:9]3[C:2]([C:22]4[CH:23]=[CH:24][C:19]([F:18])=[CH:20][CH:21]=4)=[CH:3][C:4]([C:5]#[N:6])=[CH:7][CH:8]=3)[CH2:11][CH2:12][C:13]=12

参加物

7

反応物 4

HCID 10340Sodium CarbonateHCID 14797Potassium HydroxideHCID 2856454-Fluorophenylboronic acidHCID 588270573-bromo-4-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)benzonitrile

生成物 1

HCID 588271906-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)-4'-fluorobiphenyl-3-carbonitrile

試薬・触媒・溶媒 2

HCID 178418397HCID 178418397、化合物触媒HCID 80711,2-Dimethoxyethane溶媒

反応条件

温度
130 °C

実験手順

To a solution of 3-bromo-4-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)benzonitrile (0.100 g, 0.347 mmol) and 4-fluorophenylboronic acid (0.158 g, 1.04 mmol) in DME (2 mL), aqueous solutions of Na2CO3 (0.69 mL, 2 M) and KOH (0.17 mL, 2 M) are added. After degassing with nitrogen, Pd(PPh3)4 (0.040 g, 0.035 mmol) is added. Mixture is heated in a microwave reactor at 130° C., for 20 minutes. LCMS showed consumption of starting material. The solution is then diluted with ethyl acetate and saturated aqueous sodium bicarbonate. The resulting aqueous layer is extracted further with ethyl acetate (3×). The combined organic layers are washed with brine and dried over anhydrous sodium sulfate. After concentration, crude product is purified by flash chromatography (Hexane/EtOAc, and then 10% MeOH/DCM) followed by preparative HPLC (0-50% acetonitrile with 0.1% TEA in 21 minutes). After concentration and free basing, 6-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)-4′-fluorobiphenyl-3-carbonitrile is obtained as a white powder. MS (ESI) m/z 304.0 (M+H); 1H NMR (400 MHz, CDCl3) δ ppm 2.38-2.54 (m, 1H), 2.76-3.03 (m, 3H), 5.33 (app t, J=6.7 Hz, 1H), 6.79 (s, 1H), 7.01 (d, J=8.1 Hz, 1H), 7.15-7.24 (m, 3H), 7.29 (dd, J=13.4, 5.1 Hz, 2H), 7.54-7.65 (m, 2H).

後処理

  1. additionis added
  2. customconsumption of starting material
  3. additionThe solution is then diluted with ethyl acetate and saturated aqueous sodium bicarbonate
  4. extractionThe resulting aqueous layer is extracted further with ethyl acetate (3×)
  5. washThe combined organic layers are washed with brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationAfter concentration, crude product
  8. customis purified by flash chromatography (Hexane/EtOAc
  9. customfollowed by preparative HPLC (0-50% acetonitrile with 0.1% TEA in 21 minutes)
  10. concentrationAfter concentration and free basing

出典と根拠

ORDレコード
ord-81fc5ab075e743dfb6dd58f09a9413cf
出典データセット
uspto-grants-2014_09
特許番号
US08835646B2

反応ノート

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