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

HRID 554860Notes

Reaction equation

HRID 554860 reaction equation
[NH:1]1[CH2:4][CH:3]([O:5][C:6]2[CH:11]=[CH:10][C:9]([N:12]3[CH:17]=[CH:16][C:15]4[N:18]=[C:19]([C:21]5[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][CH:22]=5)[S:20][C:14]=4[C:13]3=[O:28])=[CH:8][C:7]=2[O:29][CH3:30])[CH2:2]1.[O:31]1[CH2:36][CH2:35][C:34](=O)[CH2:33][CH2:32]1.C(O)(=O)C.C([BH3-])#N.[Na+]>CO.ClCCl>[ClH:27].[Cl:27][C:24]1[CH:23]=[CH:22][C:21]([C:19]2[S:20][C:14]3[C:13](=[O:28])[N:12]([C:9]4[CH:10]=[CH:11][C:6]([O:5][CH:3]5[CH2:4][N:1]([CH:34]6[CH2:35][CH2:36][O:31][CH2:32][CH2:33]6)[CH2:2]5)=[C:7]([O:29][CH3:30])[CH:8]=4)[CH:17]=[CH:16][C:15]=3[N:18]=2)=[CH:26][CH:25]=1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 121599Tetrahydro-4H-pyran-4-oneHCID 5003444Sodium cyanoborohydrideHCID 249907925-(4-(azetidin-3-yloxy)-3-methoxyphenyl)-2-(4-chlorophenyl)thiazolo[5,4-c]pyridin-4(5H)-one

Product 1

HCID 1317292512-(4-Chloro-phenyl)-5-{3-methoxy-4-[1-(tetrahydro-pyran-4-yl)-azetidin-3-yloxy]-phenyl}-5H-thiazolo[5,4-c]pyridin-4-one, hydrochloride saltYield 165.4%

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent2×HCID 6344DichloromethaneSolvent

Procedure

Suspend 5-[4-(azetidin-3-yloxy)-3-methoxy-phenyl]-2-(4-chloro-phenyl)-5H-thiazolo[5,4-c]pyridin-4-one (50 mg, 0.11 mmol) in MeOH (5.68 mL). Add tetrahydro-4H-pyran-4-one (15.7 μL, 0.17 mmol) and acetic acid (9.8 μL, 0.17 mmol) and stir at room temperature for 10 min. Add sodium cyanoborohydride (7.1 mg, 0.11 mmol) and stir at room temperature for 6 h. Add dichloromethane to the reaction mixture to dissolve the solid material. Pour onto a 2 g SCX2 ion exchange column wet with MeOH and elute under gravity. Elute SCX cartridge with MeOH (approximately 3 volumes) under reduced pressure and discard. Elute SCX cartridge with 7N NH3 in MeOH:dichloromethane (1:1) (approximately 5 volumes) under reduced pressure and then concentrate in vacuo. Dissolve the resultant solid in dichloromethane (5 mL) and add 4 N HCl in dioxane solution (25 μL). Evaporate the solvent and suspend the solid in water. Freeze-dry to give (51 mg, 83%) of the title compound as a white solid. ES/MS m/z (35Cl) 524 [M+1]+.

Workup

  1. washelute under gravity
  2. concentrationElute SCX cartridge with 7N NH3 in MeOH:dichloromethane (1:1) (approximately 5 volumes) under reduced pressure and then concentrate in vacuo
  3. dissolutionDissolve the resultant solid in dichloromethane (5 mL)
  4. additionadd 4 N HCl in dioxane solution (25 μL)
  5. customEvaporate the solvent
  6. customFreeze-dry

Sources & evidence

ORD record
ord-f80022d0485441f98fadc0d5cefe6920
Source dataset
uspto-grants-2011_11
Patent number
US08049013B2

Reaction notes

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