Hydrochloric Acid → 6-Trifluoromethyl-4-[8-(4-morpholin-4-ylphenylamino)imidazo[1,2-a]pyrazin-5-yl]-1H-pyridin-2-one

HRID 1921785Notes

Reaction equation

HRID 1921785 reaction equation
C(OC(=O)[N:7]([C:20]1[C:21]2[N:22]([CH:37]=[CH:38][N:39]=2)[C:23]([C:26]2[CH:31]=[C:30]([C:32]([F:35])([F:34])[F:33])[N:29]=[C:28](F)[CH:27]=2)=[CH:24][N:25]=1)[C:8]1[CH:13]=[CH:12][C:11]([N:14]2[CH2:19][CH2:18][O:17][CH2:16][CH2:15]2)=[CH:10][CH:9]=1)(C)(C)C.CC([O-:45])(C)C.[K+].Cl>C1COCC1.O>[F:33][C:32]([F:35])([F:34])[C:30]1[NH:29][C:28](=[O:45])[CH:27]=[C:26]([C:23]2[N:22]3[CH:37]=[CH:38][N:39]=[C:21]3[C:20]([NH:7][C:8]3[CH:13]=[CH:12][C:11]([N:14]4[CH2:19][CH2:18][O:17][CH2:16][CH2:15]4)=[CH:10][CH:9]=3)=[N:25][CH:24]=2)[CH:31]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 23665647Potassium tert-butoxideHCID 58228824[5-(2-Fluoro-6-trifluoromethyl-pyridin-4-yl)imidazo[1,2-a]pyrazin-8-yl]-(4-morpholin-4-yl-phenyl)carbamic acid tert-butyl ester

Product 1

HCID 590231036-Trifluoromethyl-4-[8-(4-morpholin-4-ylphenylamino)imidazo[1,2-a]pyrazin-5-yl]-1H-pyridin-2-oneYield 17.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of [5-(2-fluoro-6-trifluoromethyl-pyridin-4-yl)imidazo[1,2-a]pyrazin-8-yl]-(4-morpholin-4-yl-phenyl)carbamic acid tert-butyl ester (92 mg, 0.12 mmol) in THF (0.5 mL) is added KOtBu (26 mg, 0.23 mmol) and the mixture is stirred at rt for 20 min. HCl (12 M aq., 0.1 mL) is added and the mixture is diluted with water (10 mL) and concentrated under reduced pressure. The residue is dissolved in THF (5 mL) and HCl (12 M aq., 0.5 mL) is added and the mixture is stirred at rt for 5 h. NaHCO3 (sat. aq.) is added until the pH is 7 and the mixture is extracted with DCM (3×10 mL). The extracts are dried over Na2SO4 and evaporated under reduced pressure to afford a pale orange solid. This is purified by preparative HPLC to afford the title compound as a yellow solid (9.5 mg). LCMS: Rt=1.04 min (100%), m/z (ESI) 457 (M+H)+.

Workup

  1. concentrationconcentrated under reduced pressure
  2. dissolutionThe residue is dissolved in THF (5 mL)
  3. additionHCl (12 M aq., 0.5 mL) is added
  4. stirringthe mixture is stirred at rt for 5 h
  5. additionNaHCO3 (sat. aq.) is added until the pH is 7
  6. extractionthe mixture is extracted with DCM (3×10 mL)
  7. dry with materialThe extracts are dried over Na2SO4
  8. customevaporated under reduced pressure
  9. customto afford a pale orange solid
  10. customThis is purified by preparative HPLC

Sources & evidence

ORD record
ord-fab0f0b736d948d39a12648fd0e4b3bf
Source dataset
uspto-grants-2012_05
Patent number
US08173656B2

Reaction notes

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