Hydrochloric Acid → HCID 58456271, compound

HRID 410632Notes

Reaction equation

HRID 410632 reaction equation
[OH:1][C:2]1([C:6]2[S:7][C:8]([C:11]3[CH:12]=[C:13]([NH:18][C:19]4[N:24]=[C:23]([O:25][CH:26]5[CH2:31][CH2:30][CH:29]([C:32]([O:34]CC)=[O:33])[CH2:28][CH2:27]5)[CH:22]=[CH:21][N:20]=4)[CH:14]=[C:15]([CH3:17])[CH:16]=3)=[CH:9][N:10]=2)[CH2:5][CH2:4][CH2:3]1.CO.[OH-].[Na+].Cl>O1CCCC1.O>[OH:1][C:2]1([C:6]2[S:7][C:8]([C:11]3[CH:12]=[C:13]([NH:18][C:19]4[N:24]=[C:23]([O:25][CH:26]5[CH2:31][CH2:30][CH:29]([C:32]([OH:34])=[O:33])[CH2:28][CH2:27]5)[CH:22]=[CH:21][N:20]=4)[CH:14]=[C:15]([CH3:17])[CH:16]=3)=[CH:9][N:10]=2)[CH2:3][CH2:4][CH2:5]1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 887MethanolHCID 14798Sodium HydroxideHCID 67261264HCID 67261264, compound

Product 1

HCID 58456271HCID 58456271, compoundYield 100%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of ethyl 4-{[2-({3-[2-(1-hydroxycyclobutyl)-1,3-thiazol-5-yl]-5-methylphenyl}-amino)pyrimidin-4-yl]oxy}cyclohexanecarboxylate (Example 94A-16, 40 mg, 0.08 mmol) in tetrahydrofuran (0.52 mL), water (0.13 mL), and methanol (0.13 mL) was added aqueous sodium hydroxide (1.0 M in H2O, 0.2 mL, 0.2 mmol). The mixture was stirred at room temperature until complete. The reaction was then quenched with aqueous hydrochloric acid (1.0 M in H2O, 0.22 mL, 0.22 mmol). The resulting mixture was extracted with dichloromethane. The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure to provide 4-{[2-({3-[2-(1-hydroxycyclobutyl)-1,3-thiazol-5-yl]-5-methylphenyl}amino)pyrimidin-4-yl]oxy}cyclohexanecarboxylic acid (37 mg, 0.08 mmol, 99%) as a pale yellow solid. MS ESI: [M+H]+ m/z 480.8. 1H NMR (500 MHz, DMSO-d6) δ 12.12 (s, 1H), 9.52 (s, 1H), 8.19 (m, 1H), 7.97 (s, 1H), 7.88 (s, 1H), 7.73-7.39 (m, 2H), 7.08 (s, 1H), 6.63-6.41 (m, 1H), 6.36-6.15 (m, 1H), 5.38-4.87 (m, 2H), 2.57-2.50 (m, 1H), 2.40-2.26 (m, 4H), 2.19-2.06 (m, 1H), 1.97-1.79 (m, 3H), 1.79-1.68 (m, 2H), 1.67-1.58 (m, 1H), 1.51-1.36 (m, 1H), 1.30-0.74 (m, 2H). rhSyk activity=+++.

Workup

  1. extractionThe resulting mixture was extracted with dichloromethane
  2. dry with materialThe organic layer was dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-07e99913bbec414a8468e8b8bfa40a82
Source dataset
uspto-grants-2014_06
Patent number
US08759366B2

Reaction notes

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