Lithium hydroxide, monohydrate → Lithium 2-(2-(2-(2-((4-(4-(tert-butoxycarbonyl)piperazin-1-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)acetate

HRID 1473019Notes

Reaction equation

HRID 1473019 reaction equation
O[Li:2].O.C[O:5][C:6](=[O:46])[CH2:7][C:8]1[CH:45]=[CH:44][CH:43]=[CH:42][C:9]=1[CH2:10][CH2:11][C:12]1[C:17]([C:18]([F:21])([F:20])[F:19])=[CH:16][N:15]=[C:14]([NH:22][C:23]2[CH:28]=[CH:27][C:26]([N:29]3[CH2:34][CH2:33][N:32]([C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH2:31][CH2:30]3)=[CH:25][CH:24]=2)[N:13]=1>C1COCC1.O.CO>[C:38]([O:37][C:35]([N:32]1[CH2:31][CH2:30][N:29]([C:26]2[CH:27]=[CH:28][C:23]([NH:22][C:14]3[N:13]=[C:12]([CH2:11][CH2:10][C:9]4[CH:42]=[CH:43][CH:44]=[CH:45][C:8]=4[CH2:7][C:6]([O-:46])=[O:5])[C:17]([C:18]([F:19])([F:20])[F:21])=[CH:16][N:15]=3)=[CH:24][CH:25]=2)[CH2:34][CH2:33]1)=[O:36])([CH3:41])([CH3:39])[CH3:40].[Li+:2]

Participants

6

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 68282913tert-Butyl 4-(4-((4-(2-(2-methoxy-2-oxoethyl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperazine-1-carboxylate

Product 1

HCID 68282842Lithium 2-(2-(2-(2-((4-(4-(tert-butoxycarbonyl)piperazin-1-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)acetateYield 96%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
40 °C

Procedure

LiOH.H2O (0.044 g, 1.06 mmol) was added to tert-butyl 4-(4-((4-(2-(2-methoxy-2-oxoethyl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperazine-1-carboxylate (I6) (0.211 g, 0.352 mmol) in THF (10 mL), water (2.5 mL) and methanol (1 mL). The resulting mixture was allowed to stir for 3 hours at 40° C. The volatiles were removed in vacuo and the residue was diluted with EtOAc (100 mL) and 2 M aq. NaOH (100 mL). The layers were separated and the aqueous layer was extracted with EtOAc (70 mL), the organic layers were combined, washed with brine (100 mL), dried (MgSO4), filtered and concentrated under reduced pressure to give the title compound (I7) (0.195 g, 96% yield) as a yellow solid; 1H NMR (400 MHz, d6-DMSO) δ 10.02 (s, 1H), 8.61 (s, 1H), 7.64-7.55 (m, 2H), 7.26-7.14 (m, 4H), 6.97-6.91 (m, 2H), 3.65 (s, 2H), 3.50-3.41 (m, 4H), 3.10-2.93 (m, 8H), 1.42 (s, 9H). LCMS Method C: rt 6.32 min; m/z 586.3 [M+H]+.

Workup

  1. customThe volatiles were removed in vacuo
  2. additionthe residue was diluted with EtOAc (100 mL) and 2 M aq. NaOH (100 mL)
  3. customThe layers were separated
  4. extractionthe aqueous layer was extracted with EtOAc (70 mL)
  5. washwashed with brine (100 mL)
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-0b3c0afc82624336b50873877e4ec64f
Source dataset
uspto-grants-2015_04
Patent number
US09012461B2

Reaction notes

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