Acetic Acid → HCID 90313992, compound

HRID 1524038Notes

Reaction equation

HRID 1524038 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:15]2[CH:20]=[CH:19][C:18]([C:21]([F:24])([F:23])[F:22])=[CH:17][C:16]=2[O:25]COCC[Si](C)(C)C)[CH:5]=[CH:6][C:7]=1[C:8]1[CH:9]=[N:10][C:11]([NH2:14])=[N:12][CH:13]=1.C(O)(=O)C.Cl>C1COCC1.C(OCC)(=O)C.O>[NH2:14][C:11]1[N:10]=[CH:9][C:8]([C:7]2[CH:6]=[CH:5][C:4]([C:15]3[C:16]([OH:25])=[CH:17][C:18]([C:21]([F:24])([F:22])[F:23])=[CH:19][CH:20]=3)=[CH:3][C:2]=2[F:1])=[CH:13][N:12]=1

Participants

7

Reactant 3

HCID 176Acetic AcidHCID 313Hydrochloric AcidHCID 90313481HCID 90313481, compound

Product 1

HCID 90313992HCID 90313992, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
65 °C

Procedure

To a stirred solution of 5-[3-fluoro-4′-(trifluoromethyl)-2′-{[2-(trimethylsilyl)ethoxy]-methoxy}-biphenyl-4-yl]pyrimidin-2-amine in 14 mL of THF were added water (1.40 mL), acetic acid (1.40 mL) and hydrochloric acid (0.43 mL, 6 N). The reaction was stirred overnight at 65° Celsius, before diluting with ethyl acetate (20 mL) and water (20 mL). The aqueous layer was extracted with ethyl acetate (3×30 mL) and the combined organic extracts dried over Na2SO4, and concentrated to dryness. The crude product was purified by FCC to provide the title compound. MS (ESI): mass calcd. for C17H11F4N3O, 349.08; m/z found, 350.1 [M+H]+. 1H NMR (500 MHz, CD3OD) δ 8.61 (s, 2H), 7.61-7.48 (m, 4H), 7.23-7.19 (dd, J=8.3, 1.8, 1H), 7.19-7.17 (d, J=1.6, 1H).

Workup

  1. extractionThe aqueous layer was extracted with ethyl acetate (3×30 mL)
  2. dry with materialthe combined organic extracts dried over Na2SO4
  3. concentrationconcentrated to dryness
  4. customThe crude product was purified by FCC

Sources & evidence

ORD record
ord-e7f293a9bb5747389086c8425a1e9dba
Source dataset
uspto-grants-2015_07
Patent number
US09079866B2

Reaction notes

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