Lithium hydroxide, monohydrate → 4-{1-hydroxy-1-[1-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1H-pyrazol-4-yl]ethyl}benzoic acid

HRID 595301Notes

Reaction equation

HRID 595301 reaction equation
[OH:1][C:2]([C:27]1[CH:36]=[CH:35][C:30]([C:31]([O:33]C)=[O:32])=[CH:29][CH:28]=1)([C:4]1[CH:5]=[N:6][N:7]([C:9]2[CH:14]=[C:13]([NH:15][C:16]3[N:21]=[C:20]([C:22]([F:25])([F:24])[F:23])[CH:19]=[CH:18][N:17]=3)[CH:12]=[C:11]([CH3:26])[CH:10]=2)[CH:8]=1)[CH3:3].O.[OH-].[Li+].C(=O)(O)[O-].[Na+]>O1CCOCC1.O>[OH:1][C:2]([C:27]1[CH:36]=[CH:35][C:30]([C:31]([OH:33])=[O:32])=[CH:29][CH:28]=1)([C:4]1[CH:5]=[N:6][N:7]([C:9]2[CH:14]=[C:13]([NH:15][C:16]3[N:21]=[C:20]([C:22]([F:24])([F:23])[F:25])[CH:19]=[CH:18][N:17]=3)[CH:12]=[C:11]([CH3:26])[CH:10]=2)[CH:8]=1)[CH3:3]

Participants

6

Reactant 3

HCID 168937Lithium hydroxide, monohydrateHCID 516892Sodium BicarbonateHCID 118208752methyl 4-{1-hydroxy-1-[1-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1H-pyrazol-4-yl]ethyl}benzoate

Product 1

HCID 1182084974-{1-hydroxy-1-[1-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1H-pyrazol-4-yl]ethyl}benzoic acid

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of methyl 4-{1-hydroxy-1-[1-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1H-pyrazol-4-yl]ethyl}benzoate (isomer 1, early eluting) (100 mg, 0.2 mmol) and lithium hydroxide monohydrate (26 mg, 0.6 mmol) in 1,4-dioxane (2 mL) and water (0.5 mL) was stirred at 60° C. for 3 hours. After being cooled to 0° C., the mixture was adjusted to pH 7 with aqueous sodium bicarbonate solution. Then the mixture was extracted with ethyl acetate and washed by brine. The organic layer was concentrated and the residue was purified by reverse phase chromatography to afford 4-{1-hydroxy-1-[1-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1H-pyrazol-4-yl]ethyl}benzoic acid (Example 19.7). MS ESI calc'd. for C24H21F3N5O3 [M+H]+ 484. found 484. 1H NMR (400 MHz, DMSO-d6): δ 11.11 (s, 1H), 9.66 (s, 1H), 8.99 (s, 1H), 8.93 (s, 1H), 8.69-8.71 (m, 2H), 8.42-8.44 (m, 3H), 8.24 (s, 1H), 8.10-8.11 (m, 2H), 6.67 (s, 1H), 3.16 (s, 3H), 2.64 (s, 3H).

Workup

  1. temperatureAfter being cooled to 0° C.
  2. extractionThen the mixture was extracted with ethyl acetate
  3. washwashed by brine
  4. concentrationThe organic layer was concentrated
  5. customthe residue was purified by reverse phase chromatography

Sources & evidence

ORD record
ord-6b4ebfee6b654f36b85c1561042e95c7
Source dataset
uspto-grants-2016_01
Patent number
US09242984B2

Reaction notes

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