Acetic Acid → HCID 131729253, compound

HRID 554869Notes

Reaction equation

HRID 554869 reaction equation
[C:1]1(=O)[CH2:4][CH2:3][CH2:2]1.[NH:6]1[CH2:9][CH:8]([O:10][C:11]2[CH:16]=[CH:15][C:14]([N:17]3[CH:22]=[CH:21][C:20]4[N:23]=[C:24]([C:26]5[CH:31]=[CH:30][C:29]([Cl:32])=[CH:28][CH:27]=5)[S:25][C:19]=4[C:18]3=[O:33])=[CH:13][CH:12]=2)[CH2:7]1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].Cl.CCOCC>CO.ClCCl>[ClH:32].[Cl:32][C:29]1[CH:30]=[CH:31][C:26]([C:24]2[S:25][C:19]3[C:18](=[O:33])[N:17]([C:14]4[CH:15]=[CH:16][C:11]([O:10][CH:8]5[CH2:9][N:6]([CH:1]6[CH2:4][CH2:3][CH2:2]6)[CH2:7]5)=[CH:12][CH:13]=4)[CH:22]=[CH:21][C:20]=3[N:23]=2)=[CH:27][CH:28]=1

Participants

8

Reactant 5

HCID 176Acetic AcidHCID 14496CyclobutanoneHCID 5049666Sodium triacetoxyborohydrideHCID 10953452Ether hydrochlorideHCID 67459183HCID 67459183, compound

Product 1

HCID 131729253HCID 131729253, compoundYield 114.7%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

Add cyclobutanone (0.4 mL, 5.4 mmol) to a solution of 5-(4-(azetidin-3-yloxy)phenyl)-2-(4-chlorophenyl)thiazolo[5,4-c]pyridin-4(5H)-one (0.44 g, 1.08 mmol) in methanol (54 mL) and acetic acid (0.31 mL, 5.4 mmol). Stir the mixture at room temperature for one hour, add sodium triacetoxyborohydride (1.4 g, 6.48 mmol) and continue stirring at room temperature overnight. Dilute the mixture with dichloromethane, then wash with saturated NaHCO3 solution and water. Dry the organic portion over Na2SO4, filter, and concentrate. Purify the crude material by flash chromatography, using 0-10% MeOH/CH2Cl2 as eluent. Dissolve the solid with dichloromethane and add 1 M HCl/ether (1 eq). Stir the solution for 15 min. Concentrate the solid and filter with ether to give 0.31 g (58%) of the title compound. ES/MS m/z (35Cl) 464 [M+1]+.

Workup

  1. stirringcontinue stirring at room temperature overnight
  2. washwash with saturated NaHCO3 solution and water
  3. dry with materialDry the organic portion over Na2SO4
  4. filtrationfilter
  5. concentrationconcentrate
  6. customPurify the crude material by flash chromatography
  7. dissolutionDissolve the solid with dichloromethane
  8. stirringStir the solution for 15 min
  9. concentrationConcentrate the solid
  10. filtrationfilter with ether

Sources & evidence

ORD record
ord-a56e30b9c9194ec38e7f56078076f5cb
Source dataset
uspto-grants-2011_11
Patent number
US08049013B2

Reaction notes

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