Sodium Hydroxide → 5-(4-(azetidin-3-yloxy)-3-methoxyphenyl)-2-(4-chlorophenyl)thiazolo[5,4-c]pyridin-4(5H)-one

HRID 554845Notes

Reaction equation

HRID 554845 reaction equation
C(OC([N:8]1[CH2:11][CH:10]([O:12][C:13]2[CH:18]=[CH:17][C:16]([NH:19][C:20]([C:22]3[S:26][C:25]([C:27]4[CH:32]=[CH:31][C:30]([Cl:33])=[CH:29][CH:28]=4)=[N:24][C:23]=3[CH2:34][CH:35](OC)OC)=[O:21])=[CH:15][C:14]=2[O:40][CH3:41])[CH2:9]1)=O)(C)(C)C.O.C1(C)C=CC(S(O)(=O)=O)=CC=1.[OH-].[Na+]>C1(C)C=CC=CC=1>[NH:8]1[CH2:11][CH:10]([O:12][C:13]2[CH:18]=[CH:17][C:16]([N:19]3[CH:35]=[CH:34][C:23]4[N:24]=[C:25]([C:27]5[CH:32]=[CH:31][C:30]([Cl:33])=[CH:29][CH:28]=5)[S:26][C:22]=4[C:20]3=[O:21])=[CH:15][C:14]=2[O:40][CH3:41])[CH2:9]1

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 521998p-Toluenesulfonic acid monohydrateHCID 674612343-(4-{[2-(4-Chloro-phenyl)-4-(2,2-dimethoxy-ethyl)-thiazole-5-carbonyl]-amino}-2-methoxy-phenoxy)-azetidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 249907925-(4-(azetidin-3-yloxy)-3-methoxyphenyl)-2-(4-chlorophenyl)thiazolo[5,4-c]pyridin-4(5H)-oneYield 94.5%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
95 °C

Procedure

Dissolve 3-(4-{[2-(4-chloro-phenyl)-4-(2,2-dimethoxy-ethyl)-thiazole-5-carbonyl]-amino}-2-methoxy-phenoxy)-azetidine-1-carboxylic acid tert-butyl ester (18.9 g, 31.28 mmol) and p-toluenesulfonic acid monohydrate (19.7 g, 103.56 mmol) in dry toluene (460 mL) and stir mechanically at 95° C. overnight. Cool the reaction mixture and add 1 N NaOH. Stir the mixture vigorously at room temperature for one hour. Extract the aqueous layer with CH2Cl2 (2×700 mL). Combine the organic portions, wash with brine (700 mL), dry over MgSO4, and filter. Concentrate the filtrate in vacuo to give 13.0 g (85%) of 5-[4-(azetidin-3-yloxy)-3-methoxy-phenyl]-2-(4-chloro-phenyl)-5H-thiazolo[5,4-c]pyridin-4-one. ES/MS m/z 440.0 (35Cl) [M+1]+.

Workup

  1. temperatureCool the reaction mixture
  2. stirringStir the mixture vigorously at room temperature for one hour
  3. extractionExtract the aqueous layer with CH2Cl2 (2×700 mL)
  4. washCombine the organic portions, wash with brine (700 mL)
  5. dry with materialdry over MgSO4
  6. filtrationfilter
  7. concentrationConcentrate the filtrate in vacuo

Sources & evidence

ORD record
ord-8c8ae7550e454848b56b4495162659af
Source dataset
uspto-grants-2011_11
Patent number
US08049013B2

Reaction notes

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