Hydrochloric Acid → 4-{1-Hydroxy-1-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]ethyl}-1-methylcyclohexanecarboxylic acid

HRID 928137Notes

Reaction equation

HRID 928137 reaction equation
[OH:1][C:2]([CH:27]1[CH2:32][CH2:31][C:30]([CH3:37])([C:33]([O:35]C)=[O:34])[CH2:29][CH2:28]1)([C:4]1[S:5][C:6]([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:7][N:8]=1)[CH3:3].[OH-].[Na+].Cl>O1CCCC1.CO>[OH:1][C:2]([CH:27]1[CH2:32][CH2:31][C:30]([CH3:37])([C:33]([OH:35])=[O:34])[CH2:29][CH2:28]1)([C:4]1[S:5][C:6]([C:9]2[CH:14]=[C:13]([NH:15][C:16]3[N:21]=[C:20]([C:22]([F:23])([F:25])[F:24])[CH:19]=[CH:18][N:17]=3)[CH:12]=[C:11]([CH3:26])[CH:10]=2)=[CH:7][N:8]=1)[CH3:3]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 86720198Methyl 4-{1-hydroxy-1-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]ethyl}-1-methylcyclohexanecarboxylate

Product 1

HCID 709835664-{1-Hydroxy-1-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]ethyl}-1-methylcyclohexanecarboxylic acid

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of methyl 4-{1-hydroxy-1-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]ethyl}-1-methylcyclohexanecarboxylate (37.8 mg, 0.071 mmol) in tetrahydrofuran (0.6 mL) and methanol (1.2 mL) was added sodium hydroxide (1.0 M in water, 0.283 mL, 0.283 mmol). The reaction mixture was irradiated to 160° C. for 5 min in a microwave oven. After cooling to room temperature, hydrochloric acid (2.0 M in water, 0.145 mL, 0.290 mmol) was added. The mixture was partitioned between 10% IPA:CHCl3 and brine, and then the layers were separated. The aqueous layer was extracted with 10% IPA:CHCl3, and the combined organic layers were dried over sodium sulfate, filtered and concentrated under reduced pressure to yield 4-{1-hydroxy-1-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]ethyl}-1-methylcyclohexanecarboxylic acid. MS ESI calc'd. for C25H27F3N4O3S [M+H]+ 521. found 521. 1H NMR (500 MHz, DMSO-d6) δ 11.99 (s, 1H), 10.24 (s, 1H), 8.83 (d, J=4.9 Hz, 1H), 7.95 (s, 2H), 7.45 (s, 1H), 7.27 (d, J=4.9 Hz, 1H), 7.14 (s, 1H), 5.83 (s, 1H), 2.31 (s, 3H), 1.70-1.38 (m, 6H), 1.48 (s, 3H), 1.36-1.28 (m, 1H), 1.26-1.16 (m, 2H), 1.02 (s, 3H). rhSyk (isomer 3)=+++

Workup

  1. customThe reaction mixture was irradiated to 160° C. for 5 min in a microwave oven
  2. customThe mixture was partitioned between 10% IPA
  3. customCHCl3 and brine, and then the layers were separated
  4. extractionThe aqueous layer was extracted with 10% IPA
  5. dry with materialCHCl3, and the combined organic layers were dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-569337efee534730a9c3a0f7165c44cc
Source dataset
uspto-grants-2016_03
Patent number
US09290490B2

Reaction notes

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