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

HRID 554856Notes

Reaction equation

HRID 554856 reaction equation
[C:1]([OH:8])(=[O:7])/[CH:2]=[CH:3]/[C:4]([OH:6])=[O:5].[Cl:9][C:10]1[CH:15]=[CH:14][C:13]([C:16]2[S:17][C:18]3[C:19](=[O:39])[N:20]([C:25]4[CH:30]=[CH:29][C:28]([O:31][CH:32]5[CH2:35][N:34]([CH3:36])[CH2:33]5)=[C:27]([O:37][CH3:38])[CH:26]=4)[CH:21]=[CH:22][C:23]=3[N:24]=2)=[CH:12][CH:11]=1>CO>[C:1]([OH:8])(=[O:7])/[CH:2]=[CH:3]/[C:4]([OH:6])=[O:5].[Cl:9][C:10]1[CH:15]=[CH:14][C:13]([C:16]2[S:17][C:18]3[C:19](=[O:39])[N:20]([C:25]4[CH:30]=[CH:29][C:28]([O:31][CH:32]5[CH2:33][N:34]([CH3:36])[CH2:35]5)=[C:27]([O:37][CH3:38])[CH:26]=4)[CH:21]=[CH:22][C:23]=3[N:24]=2)=[CH:12][CH:11]=1

Participants

4

Reactant 2

HCID 444972Fumaric Acid2×HCID 249907962-(4-Chloro-phenyl)-5-[3-methoxy-4-(1-methyl-azetidin-3-yloxy)-phenyl]-5H-thiazolo[5,4-c]pyridin-4-one

Product 1

HCID 1317292502-(4-Chloro-phenyl)-5-[3-methoxy-4-(1-methyl-azetidin-3-yloxy)-phenyl]-5H-thiazolo[5,4-c]pyridin-4-one, fumarate saltYield 89%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
60 °C

Procedure

Dissolve fumaric acid (59.41 g, 0.5118 mol) methanol/water (1900 mL, 1/1) by heating to 60° C. In a separate vessel dissolve 2-(4-chloro-phenyl)-5-[3-methoxy-4-(1-methyl-azetidin-3-yloxy)-phenyl]-5H-thiazolo[5,4-c]pyridin-4-one (200.0 g, 0.4406 mol) in methanol (2000 mL) and heat to 65° C. Add fumaric acid solution hot as quickly as possible. Allow the temperature to recover to 65° C. and hold for 15 min. Cool to 25° C. at 0.25° C./min and hold for one hour. Filter and wash the reactor twice with methanol (100 mL), and rinse the filter cake twice with methanol (250 mL) each. Dry under vacuum at 40° C. until constant weight to provide 223 g (89%) of the title compound.

Workup

  1. temperatureheat to 65° C
  2. customto recover to 65° C.
  3. temperatureCool to 25° C. at 0.25° C./min
  4. waithold for one hour
  5. filtrationFilter
  6. washwash the reactor twice with methanol (100 mL)
  7. washrinse the filter cake twice with methanol (250 mL) each
  8. customDry under vacuum at 40° C. until constant weight

Sources & evidence

ORD record
ord-db8e329f5f3d4dc9848c74d43de06d13
Source dataset
uspto-grants-2011_11
Patent number
US08049013B2

Reaction notes

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