Trifluoroacetic acid → 4-(3-furanyl)-2-methyl-1-{[2-methyl-3-(trifluoromethyl)phenyl]methyl}-6-(4-morpholinyl)-1H-benzimidazole

HRID 44563

반응식

HRID 44563 반응식
Br[C:2]1[C:10]2[N:9]=[C:8]([CH3:11])[N:7]([CH2:12][C:13]3[CH:18]=[CH:17][CH:16]=[C:15]([C:19]([F:22])([F:21])[F:20])[C:14]=3[CH3:23])[C:6]=2[CH:5]=[C:4]([N:24]2[CH2:29][CH2:28][O:27][CH2:26][CH2:25]2)[CH:3]=1.[O:30]1[CH:34]=[CH:33][C:32](B(O)O)=[CH:31]1.C(=O)([O-])[O-].[Na+].[Na+].C(O)(C(F)(F)F)=O>COCCOC.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl.C(#N)C>[O:30]1[CH:34]=[CH:33][C:32]([C:2]2[C:10]3[N:9]=[C:8]([CH3:11])[N:7]([CH2:12][C:13]4[CH:18]=[CH:17][CH:16]=[C:15]([C:19]([F:22])([F:21])[F:20])[C:14]=4[CH3:23])[C:6]=3[CH:5]=[C:4]([N:24]3[CH2:25][CH2:26][O:27][CH2:28][CH2:29]3)[CH:3]=2)=[CH:31]1

참가 물질

9

반응물 4

HCID 6422Trifluoroacetic acidHCID 10340Sodium CarbonateHCID 2734358Furan-3-boronic acidHCID 569605424-(7-bromo-2-methyl-3-(2-methyl-3-(trifluoromethyl)benzyl)-3H-benzo[d]imidazol-5-yl)morpholine

생성물 1

HCID 669768194-(3-furanyl)-2-methyl-1-{[2-methyl-3-(trifluoromethyl)phenyl]methyl}-6-(4-morpholinyl)-1H-benzimidazole수율 14.11%

시약·촉매·용매 4

HCID 178418807HCID 178418807, 화합물촉매HCID 962Water용매3회HCID 6342Acetonitrile용매HCID 80711,2-Dimethoxyethane용매

실험 절차

A mixture of 4-bromo-2-methyl-1-{[2-methyl-3-(trifluoromethyl)phenyl]methyl}-6-(4-morpholinyl)-1H-benzimidazole, prepared as described in Example 62 (200 mg, 0.427 mmol), 3-furanyl boronic acid (47.8 mg, 0.427 mmol), sodium carbonate (91 mg, 0.854 mmol) and PdCl2(dppf)-CH2Cl2 adduct (34.9 mg, 0.043 mmol) in 1,2-Dimethoxyethane (DME) (2.5 mL) and Water (0.5 mL) was irradiated in a microwave reactor for 1 h at 100° C. The mixture was poured into water and extracted with EtOAc. The organic phase was washed with brine, dried over Na2SO4 and evaporated. Only partial conversion (ca. 50%) was observed by LC/MS analysis. The residue was purified by RP-HPLC (Gilson, 25-65% Acetonitrile in water plus 0.1% TFA) to the desired product (28 mg, 0.060 mmol, 14.11% yield) as a white powder (separation from impurity was difficult. The head of the peak was discarded decreasing the overall yield, in addition to the partial conversion observed). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 8.57 (s, 1H), 7.58 (d, J=7.58 Hz, 1H), 7.55 (t, J=1.52 Hz, 1H), 7.09-7.15 (m, 2H), 7.02 (d, J=1.26 Hz, 1H), 6.52 (d, J=7.83 Hz, 1H), 6.48 (d, J=2.02 Hz, 1H), 5.29 (s, 2H), 3.80-3.97 (m, 4H), 3.07-3.21 (m, 4H), 2.57 (s, 3H), 2.52 (s, 3H). MS (ES+) m/e 456.0 [M+H]+

후처리

  1. customprepared
  2. customwas irradiated in a microwave reactor for 1 h at 100° C
  3. extractionextracted with EtOAc
  4. washThe organic phase was washed with brine
  5. dry with materialdried over Na2SO4
  6. customevaporated

출처 및 근거

ORD 기록
ord-292140d775a4480ea10b5e9d67dc2106
출처 데이터셋
uspto-grants-2013_09
특허 번호
US08541411B2

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