Methanol → HCID 68282902, compound

HRID 1485199Notes

Reaction equation

HRID 1485199 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([C:8]2[CH:9]=[C:10]([NH:14][C:15]3[N:20]=[C:19]([CH2:21][CH2:22][C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=4[CH2:29][C:30]([O:32]C)=[O:31])[C:18]([C:34]([F:37])([F:36])[F:35])=[CH:17][N:16]=3)[CH:11]=[CH:12][CH:13]=2)[CH2:4][CH2:3]1.O[Li].O.O.CO>C1COCC1>[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([C:8]2[CH:9]=[C:10]([NH:14][C:15]3[N:20]=[C:19]([CH2:21][CH2:22][C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=4[CH2:29][C:30]([OH:32])=[O:31])[C:18]([C:34]([F:36])([F:35])[F:37])=[CH:17][N:16]=3)[CH:11]=[CH:12][CH:13]=2)[CH2:4][CH2:3]1

Participants

6

Reactant 4

HCID 887MethanolHCID 962WaterHCID 168937Lithium hydroxide, monohydrateHCID 68282860HCID 68282860, compound

Product 1

HCID 68282902HCID 68282902, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Methyl 2-(2-(2-(2-((3-(4-methylpiperazin-1-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)acetate (I67) (150 mg, 292 μmol) was dissolved in a THF (10 mL), then LiOH.H2O (36.7 mg, 876 μmol) was added. Water (2 mL) then MeOH (1 mL) was added. The resulting mixture was stirred at room temperature for 16 hours then the volatiles were removed by evaporation under reduced pressure. The residue was dissolved in MeOH (3 mL) then acidified with concentrated HCl to pH 2-3. The volatiles were evaporated under reduced pressure to give an orange residue. The residue was chromatographed on silica gel (0-20% MeOH/DCM) to give the title compound (I68) (120 mg, 82%) as a yellow crystalline solid; 1H NMR (400 MHz, d6-DMSO) δ 11.04 (bs, 1H), 10.12 (s, 1H), 8.68 (s, 1H), 7.44 (m, 1H), 7.35 (m, 1H), 7.24-7.18 (m, 5H), 6.72 (m, 1H), 3.77-3.74 (m, partially obscured by residual water signal), 3.44 (m, 3H), 3.17-3.03 (m, 8H), 2.78 (s, 3H). LCMS Method C: rt 4.92 min; m/z 500.3 (M+1), 498.2 (M−1), 454.3 (M-COOH).

Workup

  1. customthe volatiles were removed by evaporation under reduced pressure
  2. dissolutionThe residue was dissolved in MeOH (3 mL)
  3. customThe volatiles were evaporated under reduced pressure
  4. customto give an orange residue
  5. customThe residue was chromatographed on silica gel (0-20% MeOH/DCM)

Sources & evidence

ORD record
ord-702add73d9694ef4bd94eb18555d450f
Source dataset
uspto-grants-2016_08
Patent number
US09421205B2

Reaction notes

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