Lithium Hydroxide → HCID 86712703, compound

HRID 1779059Notes

Reaction equation

HRID 1779059 reaction equation
[Li+].[OH-].C[O:4][C:5](=[O:49])[CH2:6][C:7]1[C:44]([C:45]([F:48])([F:47])[F:46])=[CH:43][CH:42]=[CH:41][C:8]=1[CH2:9][CH2:10][C:11]1[C:16]([C:17]([F:20])([F:19])[F:18])=[CH:15][N:14]=[C:13]([NH:21][C:22]2[CH:27]=[CH:26][C:25]([CH:28]3[CH2:33][CH2:32][N:31]([C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[CH2:30][CH2:29]3)=[CH:24][CH:23]=2)[N:12]=1>C1COCC1.CO.O>[C:37]([O:36][C:34]([N:31]1[CH2:30][CH2:29][CH:28]([C:25]2[CH:24]=[CH:23][C:22]([NH:21][C:13]3[N:12]=[C:11]([CH2:10][CH2:9][C:8]4[CH:41]=[CH:42][CH:43]=[C:44]([C:45]([F:46])([F:48])[F:47])[C:7]=4[CH2:6][C:5]([OH:49])=[O:4])[C:16]([C:17]([F:18])([F:20])[F:19])=[CH:15][N:14]=3)=[CH:27][CH:26]=2)[CH2:33][CH2:32]1)=[O:35])([CH3:40])([CH3:38])[CH3:39]

Participants

6

Reactant 2

HCID 3939Lithium Hydroxide2×HCID 86712702HCID 86712702, compound

Product 1

HCID 86712703HCID 86712703, compound

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolvent3×HCID 8028TetrahydrofuranSolvent

Procedure

LiOH (31 mg, 1.3 mmol) was added to a solution of tert-butyl 4-(4-((4-(2-(2-methoxy-2-oxoethyl)-3-(trifluoromethyl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate (A95) (0.106 g, 0.159 mmol) in THF (2.0 mL), MeOH (1.0 mL) and water (1.0 mL) and the resulting mixture was stirred at room temperature for 16 hours. Water (20 mL) was added and the mixture extracted with EtOAc (2×20 mL). The combined organic extracts were concentrated under reduced pressure and the residue taken up in THF (2.0 mL), MeOH (1.0 mL) and water (1.0 mL). LiOH (0.103 g, 4.30 mmol) was added and the resulting mixture stirred for 136 hours at room temperature. The mixture was diluted with water (30 mL) then extracted with EtOAc (3×30 mL). The combined organic extracts were passed through a phase separation cartridge then concentrated under reduced pressure to give the title compound A96 (0.104 g, 99%); 1H NMR (400 MHz, d6-DMSO) δ 10.27 (bs, 1H), 8.65 (s, 1H), 7.64 (d, J=8.6 Hz, 2H), 7.45 (d, J=7.7 Hz, 1H), 7.38 (d, J=7.6 Hz, 1H), 7.25 (dd, J=7.6, 7.6 Hz, 1H), 7.19 (d, J=8.6 Hz, 2H), 4.06 (m, 2H), 3.48 (s, 2H), 3.14 (m, 2H), 3.05 (m, 2H), 2.80 (m, 2H), 2.61 (m, 1H), 1.74 (m, 2H), 1.48 (m, 2H), 1.42 (s, 9H). LCMS-A: rt 6.78 min; m/z 653.3 [M+H]+.

Workup

  1. extractionthe mixture extracted with EtOAc (2×20 mL)
  2. concentrationThe combined organic extracts were concentrated under reduced pressure
  3. stirringthe resulting mixture stirred for 136 hours at room temperature
  4. extractionthen extracted with EtOAc (3×30 mL)
  5. customThe combined organic extracts were passed through a phase separation cartridge
  6. concentrationthen concentrated under reduced pressure

Sources & evidence

ORD record
ord-c57ac420c75c4b0ca243144633e20037
Source dataset
uspto-grants-2016_02
Patent number
US09266864B2

Reaction notes

Loading…