Hydrochloric Acid → HCID 118092936, compound

HRID 2207371Notes

Reaction equation

HRID 2207371 reaction equation
Cl.[CH3:2][C:3]1[CH:4]=[C:5]([C:20]2[CH:25]=[CH:24][N:23]=[C:22]([C:26]3([OH:36])[CH2:35][CH2:34][C:29]4(OCC[O:30]4)[CH2:28][CH2:27]3)[CH:21]=2)[CH:6]=[C:7]([NH:9][C:10]2[N:15]=[C:14]([C:16]([F:19])([F:18])[F:17])[CH:13]=[CH:12][N:11]=2)[CH:8]=1.C(=O)(O)[O-].[Na+]>C1COCC1>[OH:36][C:26]1([C:22]2[CH:21]=[C:20]([C:5]3[CH:6]=[C:7]([NH:9][C:10]4[N:15]=[C:14]([C:16]([F:19])([F:18])[F:17])[CH:13]=[CH:12][N:11]=4)[CH:8]=[C:3]([CH3:2])[CH:4]=3)[CH:25]=[CH:24][N:23]=2)[CH2:35][CH2:34][C:29](=[O:30])[CH2:28][CH2:27]1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 516892Sodium BicarbonateHCID 118092542HCID 118092542, compound

Product 1

HCID 118092936HCID 118092936, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Hydrochloric acid (1.75 mL, 10.5 mmol, 6.0 M in dioxane) was added to a solution of 8-[4-(3-Methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyridin-2-yl]-1,4-dioxaspiro[4.5]decan-8-ol (255 mg, 0.524 mmol) in THF (3 mL). The reaction mixture was stirred for 1 hour at room temperature, then brought to pH 8 with saturated aqueous sodium bicarbonate. The reaction mixture was extracted with EtOAc (3×), and the combined organic layers were washed with saturated aqueous sodium bicarbonate. The organic layer was dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by silica gel chromatography (ethyl acetate/hexanes) to afford 4-hydroxy-4-[4-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyridin-2-yl]cyclohexanone as a white foam. MS ESI calc'd for C23H22F3N4O2 [M+H]+ 443. found 443. 1H NMR (500 MHz, DMSO-d6) δ 10.30 (s, 1H), 8.83 (d, J=4.9 Hz, 1H), 8.56 (d, J=5.1 Hz, 1H), 8.05 (s, 1H), 8.00 (d, J=1.1 Hz, 1H), 7.62 (s, 1H), 7.49 (dd, J=5.1, 1.8 Hz, 1H), 7.29-7.26 (m, 2H), 5.68 (s, 1H), 2.77 (td, J=14.1, 6.2 Hz, 2H), 2.46-2.36 (m, 2H), 2.37 (s, 3H), 2.18 (d, J=14.5 Hz, 2H), 2.02-1.91 (m, 2H).

Workup

  1. extractionThe reaction mixture was extracted with EtOAc (3×)
  2. washthe combined organic layers were washed with saturated aqueous sodium bicarbonate
  3. dry with materialThe organic layer was dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by silica gel chromatography (ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-7dd628222d7244c4bd61509be6dfe883
Source dataset
uspto-grants-2016_06
Patent number
US09376418B2

Reaction notes

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