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

HRID 923252노트

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HRID 923252 반응식
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

참가 물질

7

반응물 4

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

생성물 1

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

시약·촉매·용매 2

HCID 178418397HCID 178418397, 화합물촉매HCID 80711,2-Dimethoxyethane용매

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온도
130 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-6c6208d1cf794eaea28dba199ceb9deb
출처 데이터셋
uspto-grants-2016_03
특허 번호
US09278969B2

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