Trifluoroacetic acid → 5-[4-(Azetidin-3-yloxy)-3-methoxy-phenyl]-2-(4-chloro-phenyl)-6,7-dihydro-5H-thiazolo[5,4-c]pyridin-4-one, hydrochloride salt

HRID 554871Notes

Reaction equation

HRID 554871 reaction equation
C(OC([N:8]1[CH2:11][CH:10]([O:12][C:13]2[CH:18]=[CH:17][C:16]([N:19]3[CH2:24][CH2:23][C:22]4[N:25]=[C:26]([C:28]5[CH:33]=[CH:32][C:31]([Cl:34])=[CH:30][CH:29]=5)[S:27][C:21]=4[C:20]3=[O:35])=[CH:15][C:14]=2[O:36][CH3:37])[CH2:9]1)=O)(C)(C)C.FC(F)(F)C(O)=O.[OH-].[Na+].Cl.O1CCOCC1>C(Cl)Cl.C(Cl)(Cl)Cl>[ClH:34].[NH:8]1[CH2:11][CH:10]([O:12][C:13]2[CH:18]=[CH:17][C:16]([N:19]3[CH2:24][CH2:23][C:22]4[N:25]=[C:26]([C:28]5[CH:29]=[CH:30][C:31]([Cl:34])=[CH:32][CH:33]=5)[S:27][C:21]=4[C:20]3=[O:35])=[CH:15][C:14]=2[O:36][CH3:37])[CH2:9]1

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 14798Sodium HydroxideHCID 204431481,4-Dioxane hydrochlorideHCID 59238512HCID 59238512, compound

Product 1

HCID 1317292545-[4-(Azetidin-3-yloxy)-3-methoxy-phenyl]-2-(4-chloro-phenyl)-6,7-dihydro-5H-thiazolo[5,4-c]pyridin-4-one, hydrochloride saltYield 21.4%

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 6344DichloromethaneSolvent

Procedure

Dissolve 3-{4-[2-(4-chloro-phenyl)-4-oxo-6,7-dihydro-4H-thiazolo[5,4-c]pyridin-5-yl]-2-methoxy-phenoxy}-azetidine-1-carboxylic acid tert-butyl ester (3.33 g, 6.16 mmol) in CH2Cl2 (21 mL) and add trifluoroacetic acid (7.25 mL). Stir for one hour at room temperature and then add 1 N NaOH to adjust to pH=8-10. Extract with EtOAc (3×50 mL) and wash with water (2×50 mL). Collect an off-white solid via vacuum filtration (2.15 g, 79%). Re-dissolve a portion of the crude material (300 mg, 0.68 mmol) in CHCl3 and add 4 N HCl/dioxane solution (about 200 μL). Remove the organic solvent via reduced pressure to dryness to give 316 mg of the titled compound. ES/MS m/z (35Cl) 442.0 [M+1]+.

Workup

  1. extractionExtract with EtOAc (3×50 mL)
  2. washwash with water (2×50 mL)
  3. customCollect an off-white solid
  4. filtrationvia vacuum filtration (2.15 g, 79%)
  5. customRemove the organic solvent via reduced pressure to dryness

Sources & evidence

ORD record
ord-ab833eb9d0b84addb5f8af02c43fdc21
Source dataset
uspto-grants-2011_11
Patent number
US08049013B2

Reaction notes

Loading…