Acetic Acid → 2-(4-Chloro-phenyl)-5-[3-methoxy-4-(1-methyl-azetidin-3-yloxy)-phenyl]-5H-thiazolo[5,4-c]pyridin-4-one

HRID 554848Notes

Reaction equation

HRID 554848 reaction equation
Cl.[NH:2]1[CH2:5][CH:4]([O:6][C:7]2[CH:12]=[CH:11][C:10]([N:13]3[CH:18]=[CH:17][C:16]4[N:19]=[C:20]([C:22]5[CH:27]=[CH:26][C:25]([Cl:28])=[CH:24][CH:23]=5)[S:21][C:15]=4[C:14]3=[O:29])=[CH:9][C:8]=2[O:30][CH3:31])[CH2:3]1.[C:32](O)(=O)C.C([BH3-])#N.[Na+].C=O.C([O-])(O)=O.[Na+]>CO.O>[Cl:28][C:25]1[CH:24]=[CH:23][C:22]([C:20]2[S:21][C:15]3[C:14](=[O:29])[N:13]([C:10]4[CH:11]=[CH:12][C:7]([O:6][CH:4]5[CH2:5][N:2]([CH3:32])[CH2:3]5)=[C:8]([O:30][CH3:31])[CH:9]=4)[CH:18]=[CH:17][C:16]=3[N:19]=2)=[CH:27][CH:26]=1

Participants

8

Reactant 5

HCID 176Acetic AcidHCID 712FormaldehydeHCID 516892Sodium BicarbonateHCID 5003444Sodium cyanoborohydrideHCID 1317292485-[4-(Azetidin-3-yloxy)-3-methoxy-phenyl]-2-(4-chloro-phenyl)-5H-thiazolo[5,4-c]pyridin-4-one, hydrochloride salt

Product 1

HCID 249907962-(4-Chloro-phenyl)-5-[3-methoxy-4-(1-methyl-azetidin-3-yloxy)-phenyl]-5H-thiazolo[5,4-c]pyridin-4-oneYield 81%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Conditions

Temperature
5 °C

Procedure

Cool a mixture of 5-[4-(azetidin-3-yloxy)-3-methoxy-phenyl]-2-(4-chloro-phenyl)-5H-thiazolo[5,4-c]pyridin-4-one, hydrochloride salt (20 g, 42.0 mmol) in methanol (600 mL) to 15° C. Add acetic acid (12.1 mL, 211.6 mmol) and sodium cyanoborohydride (7 g, 111 mmol). Add formaldehyde (10.2 mL, 136.45 mmol, as a solution in water to the thick mixture and stir for 15 h at room temperature. Cool the mixture to 5° C., add saturated aqueous NaHCO3 (320 mL), and stir the mixture for one hour at room temperature. Extract the mixture with CHCl3 (3×1 L). Combine the organic solutions and wash with brine, then dry, filter, and concentrate. Dissolve the residue in CHCl3 (240 mL) and dilute with tert-butyl methyl ether (700 mL). Collect the precipitate by filtration and rinse the solids with additional tert-butyl methyl ether. Dry the solid under vacuum for 5 h at room temperature to obtain 5.4 g (81%) of the title compound. ES/MS m/z (35Cl) 454 [M+1]+.

Workup

  1. temperatureCool
  2. extractionExtract the mixture with CHCl3 (3×1 L)
  3. washCombine the organic solutions and wash with brine
  4. customdry
  5. filtrationfilter
  6. concentrationconcentrate
  7. dissolutionDissolve the residue in CHCl3 (240 mL)
  8. additiondilute with tert-butyl methyl ether (700 mL)
  9. customCollect the precipitate
  10. filtrationby filtration
  11. washrinse the solids with additional tert-butyl methyl ether
  12. customDry the solid under vacuum for 5 h at room temperature

Sources & evidence

ORD record
ord-e57b24799fe8463898f6775f23a1b261
Source dataset
uspto-grants-2011_11
Patent number
US08049013B2

Reaction notes

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