Hydrochloric Acid → HCID 66780490, compound

HRID 1958031Notes

Reaction equation

HRID 1958031 reaction equation
[CH3:1][O:2][CH2:3][CH2:4][C:5](Cl)=O.[Cl:8][C:9]1[C:10]([CH3:31])=[C:11]([CH2:15][NH:16][C:17]2[N:18]=[C:19]([N:25]3[CH2:30][CH2:29][O:28][CH2:27][CH2:26]3)[S:20][C:21]=2[C:22]([NH2:24])=[O:23])[CH:12]=[CH:13][CH:14]=1.[OH-].[Na+].Cl>COCCOC>[Cl:8][C:9]1[C:10]([CH3:31])=[C:11]([CH2:15][N:16]2[C:17]3[N:18]=[C:19]([N:25]4[CH2:26][CH2:27][O:28][CH2:29][CH2:30]4)[S:20][C:21]=3[C:22](=[O:23])[N:24]=[C:5]2[CH2:4][CH2:3][O:2][CH3:1])[CH:12]=[CH:13][CH:14]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 27597283-Methoxypropanoyl chlorideHCID 66779830HCID 66779830, compound

Product 1

HCID 66780490HCID 66780490, compound

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent2×

Procedure

3-methoxypropionyl chloride (66.8 mg, 0.545 mmol) in 1,2-Dimethoxyethane (DME) (400 μl) was added to a solution of 4-{[(3-chloro-2-methylphenyl)methyl]amino}-2-(4-morpholinyl)-1,3-thiazole-5-carboxamide (100 mg, 0.273 mmol) in 1,2-Dimethoxyethane (DME) (1000 μl). The mixture was stirred at room temperature overnight, then quenched with methanol and concentrated. To the residue was added methanol (1 mL) followed by 6N NaOH (1 equiv.). The mixture was stirred at room temperature for 3 h, neutralized (pH ˜8) with 6N HCl, and concentrated. The residue was partitioned between dichloromethane and water. The organic layer was dried (sodium sulfate), filtered, and concentrated. The crude product was purified by reversed-phase HPLC and the fractions were neutralized with sat. aq. sodium bicarbonate. The combined fractions were concentrated to remove acetonitrile and the remaining water was extracted with dichloromethane. The organic layer was dried (sodium sulfate), filtered, and concentrated to provide 4-[(3-chloro-2-methylphenyl)methyl]-5-[2-(methyloxy)ethyl]-2-(4-morpholinyl)[1,3]thiazolo[4,5-d]pyrimidin-7(4H)-one. (14 mg, 12%); LC/MS: MS (ES+) m/e 435 (MH+); 1H NMR (400 MHz, DMSO-d6) δ ppm 2.44 (s, 3H), 2.80 (t, J=6.7 Hz, 2H), 3.19 (s, 3H), 3.52 (m, 4H), 3.62-3.72 (m, 6H), 5.57 (s, 2H), 6.51 (d, J=7.6 Hz, 1H), 7.16 (m, 1H), 7.39 (d, J=7.8 Hz, 1H).

Workup

  1. customquenched with methanol
  2. concentrationconcentrated
  3. additionTo the residue was added methanol (1 mL)
  4. stirringThe mixture was stirred at room temperature for 3 h
  5. concentrationconcentrated
  6. customThe residue was partitioned between dichloromethane and water
  7. dry with materialThe organic layer was dried (sodium sulfate)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe crude product was purified by reversed-phase HPLC
  11. concentrationThe combined fractions were concentrated
  12. customto remove acetonitrile
  13. extractionthe remaining water was extracted with dichloromethane
  14. dry with materialThe organic layer was dried (sodium sulfate)
  15. filtrationfiltered
  16. concentrationconcentrated

Sources & evidence

ORD record
ord-092effa2ac11489e91db36813fc4f18b
Source dataset
uspto-grants-2013_04
Patent number
US08410095B2

Reaction notes

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