Hydrochloric Acid → HCID 58456405, compound

HRID 410506Notes

Reaction equation

HRID 410506 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([C:19]2[S:23][C:22]([C:24]3([OH:34])[CH2:33][CH2:32][C:27]4(OCC[O:28]4)[CH2:26][CH2:25]3)=[N:21][CH:20]=2)[CH:5]=[C:6]([NH:8][C:9]2[N:14]=[C:13]([C:15]([F:18])([F:17])[F:16])[CH:12]=[CH:11][N:10]=2)[CH:7]=1.Cl.C(=O)(O)[O-].[Na+]>C1COCC1>[OH:34][C:24]1([C:22]2[S:23][C:19]([C:4]3[CH:5]=[C:6]([NH:8][C:9]4[N:14]=[C:13]([C:15]([F:17])([F:18])[F:16])[CH:12]=[CH:11][N:10]=4)[CH:7]=[C:2]([CH3:1])[CH:3]=3)=[CH:20][N:21]=2)[CH2:33][CH2:32][C:27](=[O:28])[CH2:26][CH2:25]1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 516892Sodium BicarbonateHCID 67262258HCID 67262258, compound

Product 1

HCID 58456405HCID 58456405, compoundYield 87.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of 8-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]-1,4-dioxaspiro[4.5]decan-8-ol (Example 4B-15, 785 mg, 1.59 mmol) in THF (6 mL) was added HCl (6 M, 5.3 mL, 32 mmol) and the reaction was left to stir for 6 h. The mixture was brought to pH 8 with saturated aqueous sodium bicarbonate, extracted with ethyl acetate (×3), and the combined organic portion was washed with saturated aqueous sodium bicarbonate. The solution was dried over Na2SO4, filtered, concentrated, and purified by flash chromatography to afford 4-hydroxy-4-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]cyclohexanone (625 mg, 1.39 mmol) as a white foam. APCI: [M+H]+ m/z 449.1. 1H NMR (600 MHz, CDCl3) δ 8.64 (d, J=4.9, 1H), 7.90 (s, 1H), 7.86 (s, 1H), 7.46 (s, 1H), 7.26 (s, 1H), 7.06 (s, 1H), 7.04 (d, J=4.9, 1H), 2.92-2.82 (m, 2H), 2.49-2.29 (m, 6H), 2.38 (s, 3H). rhSYK activity=+++

Workup

  1. waitthe reaction was left
  2. extractionextracted with ethyl acetate (×3)
  3. washthe combined organic portion was washed with saturated aqueous sodium bicarbonate
  4. dry with materialThe solution was dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. custompurified by flash chromatography

Sources & evidence

ORD record
ord-ef6ee8557055401b8e97ce383b1d5c98
Source dataset
uspto-grants-2014_06
Patent number
US08759366B2

Reaction notes

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