3-(Trifluoromethyl)phenyl isocyanate → acetic acid 4-[4-fluoro-2-methyl-1-(3-trifluoromethyl-phenylcarbamoyl)-1H-indol-5-yloxy]-pyrimidin-2-ylmethyl ester

HRID 45125

반응식

HRID 45125 반응식
[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[C:11]([O:14][CH2:15][C:16]1[N:21]=[C:20]([O:22][C:23]2[C:24]([F:33])=[C:25]3[C:29](=[CH:30][CH:31]=2)[NH:28][C:27]([CH3:32])=[CH:26]3)[CH:19]=[CH:18][N:17]=1)(=[O:13])[CH3:12].[N:34]([C:37]1[CH:42]=[CH:41][CH:40]=[C:39]([C:43]([F:46])([F:45])[F:44])[CH:38]=1)=[C:35]=[O:36].[NH4+].[Cl-]>C1COCC1.O>[F:33][C:24]1[C:23]([O:22][C:20]2[CH:19]=[CH:18][N:17]=[C:16]([CH2:15][O:14][C:11](=[O:13])[CH3:12])[N:21]=2)=[CH:31][CH:30]=[C:29]2[C:25]=1[CH:26]=[C:27]([CH3:32])[N:28]2[C:35](=[O:36])[NH:34][C:37]1[CH:42]=[CH:41][CH:40]=[C:39]([C:43]([F:44])([F:46])[F:45])[CH:38]=1

참가 물질

7

반응물 4

HCID 94833-(Trifluoromethyl)phenyl isocyanateHCID 25517Ammonium ChlorideHCID 2733832Lithium HexamethyldisilazideHCID 67433093(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)pyrimidin-2-yl)methyl acetate

생성물 1

HCID 59394198acetic acid 4-[4-fluoro-2-methyl-1-(3-trifluoromethyl-phenylcarbamoyl)-1H-indol-5-yloxy]-pyrimidin-2-ylmethyl ester

시약·촉매·용매 2

HCID 962Water용매HCID 8028Tetrahydrofuran용매

실험 절차

LHMDS (1.0 M in THF, 7.68 mL, 7.68 mmol) is added over 1 min to a solution of (4-(4-fluoro-2-methyl-1H-indol-5-yloxy)pyrimidin-2-yl)methyl acetate (1.21 g, 3.84 mmol) and 1-isocyanato-3-(trifluoromethyl)benzene (0.70 mL, 5.08 mmol) in THF (40 mL) at −78° C. for 40 min. Saturated aqueous NH4Cl (100 mL) and water (20 mL) are added and the mixture is extracted with EtOAc (3×60 mL). The combined organic layers are washed with brine (30 mL), dried (Na2SO4), and concentrated. The residue is purified by silica gel chromatography (0-100% EtOAc/heptane) to give acetic acid 4-[4-fluoro-2-methyl-1-(3-trifluoromethyl-phenylcarbamoyl)-1H-indol-5-yloxy]-pyrimidin-2-ylmethyl ester. MS (ESI) m/z 503.0 (M+1); 1H NMR (400 MHz, DMSO-d6) δ ppm 10.99 (s, 1 H)8.68 (d, J=5.81 Hz, 1 H)8.12 (s, 1 H)7.92 (d, J=7.83 Hz, 1 H)7.66 (t, J=8.08 Hz, 1 H)7.51-7.55 (m, 2 H)7.11-7.18 (m, 2 H)6.64 (s, 1 H)5.02 (s, 2 H)2.59 (s, 3 H)1.88 (s, 3H).

후처리

  1. extractionthe mixture is extracted with EtOAc (3×60 mL)
  2. washThe combined organic layers are washed with brine (30 mL)
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated
  5. customThe residue is purified by silica gel chromatography (0-100% EtOAc/heptane)

출처 및 근거

ORD 기록
ord-71430e405ea54840a01187dc3729b864
출처 데이터셋
uspto-grants-2013_09
특허 번호
US08541432B2

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