Trifluoroacetic acid → HCID 71229333、化合物

HRID 1473107ノート

反応式

HRID 1473107 の反応式
[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

参加物

6

反応物 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

生成物 1

HCID 71229333HCID 71229333、化合物収率 42%

試薬・触媒・溶媒 1

HCID 64092,2,2-Trifluoroethanol溶媒

実験手順

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]+.

後処理

  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.)

出典と根拠

ORDレコード
ord-12db92d9e0f341cd86ad1111e3e24434
出典データセット
uspto-grants-2015_04
特許番号
US09012461B2

反応ノート

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