Trifluoroacetic acid → HCID 71229333, 화합물

HRID 1473107노트

반응식

HRID 1473107 반응식
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[O:13][CH2:12][CH2:11][N:10]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:9]2)=[CH:4][CH:3]=1.CS([C:25]1[N:30]=[C:29]([CH2:31][CH2:32][C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=2[CH2:39][C:40]([O:42][CH3:43])=[O:41])[C:28]([C:44]([F:47])([F:46])[F:45])=[CH:27][N:26]=1)(=O)=O.C(O)(C(F)(F)F)=O.CC(OC(OC(OC(C)(C)C)=O)=O)(C)C>C(O)C(F)(F)F>[CH3:43][O:42][C:40](=[O:41])[CH2:39][C:34]1[CH:35]=[CH:36][CH:37]=[CH:38][C:33]=1[CH2:32][CH2:31][C:29]1[C:28]([C:44]([F:47])([F:45])[F:46])=[CH:27][N:26]=[C:25]([NH:1][C:2]2[CH:7]=[CH:6][C:5]([CH:8]3[O:13][CH2:12][CH2:11][N:10]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:9]3)=[CH:4][CH:3]=2)[N:30]=1

참가 물질

6

반응물 4

HCID 6422Trifluoroacetic acidHCID 90495Di-tert-butyl dicarbonateHCID 58315596tert-Butyl 2-(4-aminophenyl)morpholine-4-carboxylateHCID 68282869Methyl 2-(2-(2-(2-(methylsulfonyl)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)acetate

생성물 1

HCID 71229333HCID 71229333, 화합물수율 42%

시약·촉매·용매 1

HCID 64092,2,2-Trifluoroethanol용매

실험 절차

tert-Butyl 2-(4-aminophenyl)morpholine-4-carboxylate (I88) (50 mg, 0.18 mmol) and methyl 2-(2-(2-(2-(methylsulfonyl)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)acetate (I67) (72 mg, 0.18 mmol) were heated in trifluoroethanol (1.2 mL) and TFA (0.12 mL) under microwave irradiation (100° C./20 minutes). The mixture was concentrated, evaporated from toluene and loaded onto a 5 g SCX cartridge in methanol (1 mL). The cartridge was washed with methanol (50 mL), and then eluted with 1% methylamine/methanol (50 mL). The basic eluent was concentrated, and taken up in dichloromethane (5 mL). Boc anhydride (0.062 mL, 0.27 mmol) was added, and the mixture stirred at room temperature for 18 hours. The mixture was evaporated onto silica gel, and chromatographed (12 g silica cartridge, 0-60% ethyl acetate/petroleum benzine 40-60° C.) to give the title compound (I89) (46 mg, 42% yield) as a pale yellow oil; 1H NMR (400 MHz, CDCl3) 8.55 (s, 1H), 7.64 (d, J=8.6 Hz, 2H), 7.47 (s, 1H), 7.37 (d, J=8.5 Hz, 2H), 7.29-7.18 (m, overlaps with CHCl3), 4.41 (d, J=8.4 Hz, 1H), 4.08 (m, 3H), 3.76 (s, 2H), 3.73-3.64 (m, 4H), 3.16-2.98 (m, 5H), 2.85 (s, 1H), 1.51-1.47 (m, 9H). LCMS Method C: rt 6.88 min; m/z 601.1 [M+H]+, 545.1 [M−tBu+2H]+.

후처리

  1. concentrationThe mixture was concentrated
  2. customevaporated from toluene
  3. washThe cartridge was washed with methanol (50 mL)
  4. washeluted with 1% methylamine/methanol (50 mL)
  5. concentrationThe basic eluent was concentrated
  6. customThe mixture was evaporated onto silica gel
  7. customchromatographed (12 g silica cartridge, 0-60% ethyl acetate/petroleum benzine 40-60° C.)

출처 및 근거

ORD 기록
ord-12db92d9e0f341cd86ad1111e3e24434
출처 데이터셋
uspto-grants-2015_04
특허 번호
US09012461B2

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