Hydrochloric Acid → HCID 66780337, compound

HRID 1958033Notes

Reaction equation

HRID 1958033 reaction equation
[Cl:1][C:2]1[C:3]([CH3:24])=[C:4]([CH2:8][NH:9][C:10]2[N:11]=[C:12]([N:18]3[CH2:23][CH2:22][O:21][CH2:20][CH2:19]3)[S:13][C:14]=2[C:15]([NH2:17])=[O:16])[CH:5]=[CH:6][CH:7]=1.[C:25](OCC(Cl)=O)(=[O:27])[CH3:26].[OH-].[Na+].Cl>COCCOC.CO>[Cl:1][C:2]1[C:3]([CH3:24])=[C:4]([CH2:8][N:9]2[C:10]3[N:11]=[C:12]([N:18]4[CH2:19][CH2:20][O:21][CH2:22][CH2:23]4)[S:13][C:14]=3[C:15](=[O:16])[N:17]=[C:26]2[CH2:25][OH:27])[CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 26297Acetoxyacetyl chlorideHCID 66779830HCID 66779830, compound

Product 1

HCID 66780337HCID 66780337, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

To a solution of 4-{[(3-chloro-2-methylphenyl)methyl]amino}-2-(4-morpholinyl)-1,3-thiazole-5-carboxamide (1 g, 2.73 mmol) in 1,2-Dimethoxyethane (DME) (20 ml) at 0° C. was added acetoxyacetyl chloride (0.586 ml, 5.45 mmol). The mixture was stirred at room temperature for 2 h, then stirred at 50° C. overnight. The mixture was quenched with methanol and concentrated. To the resulting residue in Methanol (12 ml) was added 6N NaOH (0.9 mL, 5.45 mmol). The mixture was stirred at room temperature for 60 min, then acidified (˜pH 5) with 1N HCl. The solvent was removed and the residue was partitioned between dichloromethane and water. The organic layer was dried (sodium sulfate), filtered, and concentrated. Reversed-phase HPLC purification provided 4-[(3-chloro-2-methylphenyl)methyl]-5-(hydroxymethyl)-2-(4-morpholinyl)[1,3]thiazolo[4,5-d]pyrimidin-7(4H)-one. (250 mg, 22%); LC/MS: MS (ES+) m/e 407 (MH+); 1H NMR (400 MHz, DMSO-d6) δ ppm 2.43 (s, 3H), 3.51 (m, 4H), 3.67 (m, 4H), 4.32 (d, J=5.6 Hz, 2H), 5.57 (s, 2H), 5.64 (t, J=5.6 Hz, 1H, OH), 6.51 (d, J=7.6 Hz, 1H), 7.14 (m, 1H), 7.37 (d, J=7.8 Hz, 1H).

Workup

  1. stirringstirred at 50° C. overnight
  2. customThe mixture was quenched with methanol
  3. concentrationconcentrated
  4. stirringThe mixture was stirred at room temperature for 60 min
  5. customThe solvent was removed
  6. customthe residue was partitioned between dichloromethane and water
  7. dry with materialThe organic layer was dried (sodium sulfate)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customReversed-phase HPLC purification

Sources & evidence

ORD record
ord-e2b343ee659748509db75ddabb059b25
Source dataset
uspto-grants-2013_04
Patent number
US08410095B2

Reaction notes

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