Cesium carbonate → 4-{1-Methyl-2-[2-(2-(r)-methyl-pyrrolidin-1-yl)-ethyl]-1h-indol-5-yl}-benzonitrile

HRID 10413

반응식

HRID 10413 반응식
C([O-])([O-])=O.[Cs+].[Cs+].[F-].[Cs+].[C:9]([C:11]1[CH:16]=[CH:15][C:14](B(O)O)=[CH:13][CH:12]=1)#[N:10].Br[C:21]1[CH:22]=[C:23]2[C:27](=[CH:28][CH:29]=1)[N:26]([CH3:30])[C:25]([CH2:31][CH2:32][N:33]1[CH2:37][CH2:36][CH2:35][CH:34]1[CH3:38])=[CH:24]2>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(C)C=CC=CC=1.O>[CH3:30][N:26]1[C:27]2[C:23](=[CH:22][C:21]([C:14]3[CH:15]=[CH:16][C:11]([C:9]#[N:10])=[CH:12][CH:13]=3)=[CH:29][CH:28]=2)[CH:24]=[C:25]1[CH2:31][CH2:32][N:33]1[CH2:37][CH2:36][CH2:35][C@H:34]1[CH3:38]

참가 물질

8

반응물 4

HCID 10796Cesium carbonateHCID 25953Cesium fluorideHCID 27343264-Cyanophenylboronic acidHCID 219799955-Bromo-1-methyl-2-[2-(2-methyl-pyrrolidin-1-yl)-ethyl]-1H-indole2회

생성물 1

HCID 113023334-{1-Methyl-2-[2-(2-(r)-methyl-pyrrolidin-1-yl)-ethyl]-1h-indol-5-yl}-benzonitrile수율 44.8%

시약·촉매·용매 3

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 962Water용매HCID 1140Toluene용매

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온도
65 °C

실험 절차

A reaction flask was charged with Cs2CO3 (1.14 g, 3.5 mmol), CsF (0.38 g, 2.5 mmol), 4-cyanophenylboronic acid (425 mg, 2.5 mmol), and H2O (10 mL) followed by a toluene solution (10 mL) of 5-bromo-1-methyl-2-[2-(2-methyl-pyrrolidin-1-yl)-ethyl]-1H-indole (320 mg, 1.0 mmol). The resulting mixture was purged with nitrogen. To the reaction mixture was then added Cy2PPh2(5-bromo-2-[2-(R)-methyl-pyrrolidin-1-yl)-ethyl]-1H-indole) (35 mg, 0.1 mmol) and Pd2(dba)3 (46 mg, 0.05 mmol). The resulting reaction mixture was then heated to 65° C. overnight under nitrogen. HPLC indicated that all of the 5-bromo-1-methyl-2-[2-(2-methyl-pyrrolidin-1-yl)-ethyl]-1H-indole was consumed. The reaction mixture was cooled to room temperature and IPAc (20 mL) was added. The organic layer was separated and concentrated. The residue was purified by column chromatograph eluting with heptane/acetone/CH2Cl2/Et3N (600 mL/40/mL/5 mL/2 mL). The fractions containing product were combined and concentrated under reduced pressure to provide the title compound as a semisolid (154 mg). 1H NMR (400 MHz, CDCl3) δ 7.57–7.66 (m, 5H), 7.30 (dd, J=1.7, 8.6Hz, 1H), 7.25 (d, J=8.51 Hz, 1H), 6.27 (S, 1H), 3.63 (S, 1H), 3.21–3.25 (m, 1H), 3.06–3.13 (m, 1H), 2.87–2.93 (m, 2H), 2.33–2.40 (m, 2H), 2.16 (q, J=8.78 Hz, 1H), 1.84–1.91 (m, 1H), 1.65–1.76 (m, 2H), 1.36–1.44 (m, 1H), 1.07 (d, J=6.1 Hz, 3H). 13C NMR (400 MHz, CDCl3) δ 146.80, 140.39, 137.11, 132.04, 130.19, 128.11, 127.27, 119.86, 119.08, 118.43, 109.18, 99.37, 60.15, 54.19, 53.24, 32.89, 29.91, 26.85, 21.98, 19.32. [M+H]+ at m/z 344.

후처리

  1. customThe resulting mixture was purged with nitrogen
  2. customThe resulting reaction mixture
  3. customwas consumed
  4. temperatureThe reaction mixture was cooled to room temperature
  5. additionIPAc (20 mL) was added
  6. customThe organic layer was separated
  7. concentrationconcentrated
  8. customThe residue was purified by column chromatograph
  9. washeluting with heptane/acetone/CH2Cl2/Et3N (600 mL/40/mL/5 mL/2 mL)
  10. additionThe fractions containing product
  11. concentrationconcentrated under reduced pressure

출처 및 근거

ORD 기록
ord-e374225418be4187b8abb583b3fe848e
출처 데이터셋
uspto-grants-2006_08
특허 번호
US07094790B2

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