Trifluoroacetic acid → HCID 71229333, compound

HRID 1473107Notes

Reaction equation

HRID 1473107 reaction equation
[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

Participants

6

Reactant 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

Product 1

HCID 71229333HCID 71229333, compoundYield 42%

Reagents, catalysts & solvents 1

HCID 64092,2,2-TrifluoroethanolSolvent

Procedure

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]+.

Workup

  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.)

Sources & evidence

ORD record
ord-12db92d9e0f341cd86ad1111e3e24434
Source dataset
uspto-grants-2015_04
Patent number
US09012461B2

Reaction notes

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