Lithium hydroxide, monohydrate → 2-(2-(2-(2-((6-(1-(tert-Butoxycarbonyl)piperidin-4-yl)pyridin-3-yl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)acetic acid

HRID 1779006Notes

Reaction equation

HRID 1779006 reaction equation
O[Li].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:24]=[CH:25][C:26]([CH: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)=[N:27][CH:28]=2)[N:13]=1>O.C1COCC1>[C:38]([O:37][C:35]([N:32]1[CH2:31][CH2:30][CH:29]([C:26]2[N: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]([OH: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]

Participants

5

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 86712661tert-Butyl 4-(5-((4-(2-(2-methoxy-2-oxoethyl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)pyridin-2-yl)piperidine-1-carboxylate

Product 1

HCID 867126622-(2-(2-(2-((6-(1-(tert-Butoxycarbonyl)piperidin-4-yl)pyridin-3-yl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)acetic acid

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
40 °C

Procedure

LiOH.H2O (297 mg, 7.1 mmol) was added to a stirred solution of tert-butyl 4-(5-((4-(2-(2-methoxy-2-oxoethyl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)pyridin-2-yl)piperidine-1-carboxylate (A45) (85 mg, 0.14 mmol) in H2O (2 mL) and THF (20 mL) and the resulting mixture heated at 40° C. for 18 hours. The volatiles were removed in vacuo and the residue was partitioned between EtOAc (100 mL), and aqueous 2 M HCl (50 mL). The layers were separated and the organics washed with water (100 mL), brine (50 mL) and dried over MgSO4. The volatiles were removed in vacuo to give the title compound A46 as an orange foam (74 mg, 89%); 1H NMR (400 MHz, d4-MeOH) δ 9.00 (d, J=1.8 Hz, 1H), 8.66 (s, 1H), 8.36 (dd, J=8.7, 2.6 Hz, 1H), 7.54 (d, J=8.7 Hz, 1H), 7.28-7.10 (m, 4H), 4.25 (d, J=13.4 Hz, 2H), 3.72 (s, 2H), 3.19-3.09 (m, 4H), 3.07-2.83 (m, 3H), 1.94 (d, J=12.7 Hz, 2H), 1.72 (m, 2H), 1.48 (s, 9H). LCMS-A: rt 5.707 min; m/z 586 [M+H]+.

Workup

  1. customThe volatiles were removed in vacuo
  2. customthe residue was partitioned between EtOAc (100 mL), and aqueous 2 M HCl (50 mL)
  3. customThe layers were separated
  4. washthe organics washed with water (100 mL), brine (50 mL)
  5. dry with materialdried over MgSO4
  6. customThe volatiles were removed in vacuo

Sources & evidence

ORD record
ord-fc0e012a3a3e48e8802c8ce6b8d7c2c9
Source dataset
uspto-grants-2016_02
Patent number
US09266864B2

Reaction notes

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