Acetic Acid → 2-(4-Chloro-phenyl)-5-{3-methoxy-4-[1-(3,3,3-trifluoro-propyl)-azetidin-3-yloxy]-phenyl}-5H-thiazolo[5,4-c]pyridin-4-one, hydrochloride salt

HRID 554861Notes

Reaction equation

HRID 554861 reaction equation
[F:1][C:2]([F:7])([F:6])[CH2:3][CH:4]=O.[NH:8]1[CH2:11][CH:10]([O:12][C:13]2[CH:18]=[CH:17][C:16]([N:19]3[CH:24]=[CH: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.C(O)(=O)C.C([BH3-])#N.[Na+].C([O-])(O)=O.[Na+].Cl.CCOCC>CO.C(Cl)(Cl)Cl>[ClH:34].[Cl:34][C:31]1[CH:32]=[CH:33][C:28]([C:26]2[S:27][C:21]3[C:20](=[O:35])[N:19]([C:16]4[CH:17]=[CH:18][C:13]([O:12][CH:10]5[CH2:9][N:8]([CH2:4][CH2:3][C:2]([F:7])([F:6])[F:1])[CH2:11]5)=[C:14]([O:36][CH3:37])[CH:15]=4)[CH:24]=[CH:23][C:22]=3[N:25]=2)=[CH:29][CH:30]=1

Participants

9

Reactant 6

HCID 176Acetic AcidHCID 680283,3,3-TrifluoropropanalHCID 516892Sodium BicarbonateHCID 5003444Sodium cyanoborohydrideHCID 10953452Ether hydrochlorideHCID 249907925-(4-(azetidin-3-yloxy)-3-methoxyphenyl)-2-(4-chlorophenyl)thiazolo[5,4-c]pyridin-4(5H)-one

Product 1

HCID 1317292522-(4-Chloro-phenyl)-5-{3-methoxy-4-[1-(3,3,3-trifluoro-propyl)-azetidin-3-yloxy]-phenyl}-5H-thiazolo[5,4-c]pyridin-4-one, hydrochloride saltYield 14.5%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6212ChloroformSolvent

Procedure

Add 3,3,3-trifluoropropanal (120 mg, 1.06 mmol) to a suspension of 5-[4-(azetidin-3-yloxy)-3-methoxy-phenyl]-2-(4-chloro-phenyl)-5H-thiazolo[5,4-c]pyridin-4-one (390 mg, 0.89 mmol) in MeOH (2.96 mL). Add acetic acid (0.254 mL, 4.43 mmol) and stir vigorously. Add sodium cyanoborohydride (146.6 mg, 2.22 mmol). Stir overnight at room temperature. Add saturated NaHCO3 (10 mL) and stir for 30 min. Extract the mixture with CH2Cl2 (2×10 mL). Combine the organic layer and wash with water (5 mL). Dry, filter, and concentrate the organic solution. Purify the crude material by flash chromatography, using 0-40% THF (1% NH3/MeOH) in heptane as eluent, to give a white solid. Redissolve in CHCl3 and add HCl/Et2O (0.32 mL). Filter the HCl salt to provide 37 mg (7%) of the title compound. ES/MS m/z 536.0 (35Cl) [M+1]+.

Workup

  1. extractionExtract the mixture with CH2Cl2 (2×10 mL)
  2. washCombine the organic layer and wash with water (5 mL)
  3. customDry
  4. filtrationfilter
  5. concentrationconcentrate the organic solution
  6. customPurify the crude material by flash chromatography
  7. customto give a white solid
  8. filtrationFilter the HCl salt

Sources & evidence

ORD record
ord-0ec986f300db45d995e5bbd1997c2b74
Source dataset
uspto-grants-2011_11
Patent number
US08049013B2

Reaction notes

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