Acetic Acid → HCID 131729411, compound

HRID 423422Notes

Reaction equation

HRID 423422 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:30][C:11]3[C:12](=[O:29])[N:13]([C:16]4[CH:17]=[N:18][C:19]([O:22][CH:23]5[CH2:28][CH2:27][NH:26][CH2:25][CH2:24]5)=[CH:20][CH:21]=4)[CH:14]=[CH:15][C:10]=3[CH:9]=2)=[CH:4][CH:3]=1.[C:31](O)(=O)C.C=O.C([BH3-])#N.[Na+].[Cl-].[NH4+]>CO.CO.C(Cl)Cl>[ClH:1].[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[S:30][C:11]3[C:12](=[O:29])[N:13]([C:16]4[CH:17]=[N:18][C:19]([O:22][CH:23]5[CH2:28][CH2:27][N:26]([CH3:31])[CH2:25][CH2:24]5)=[CH:20][CH:21]=4)[CH:14]=[CH:15][C:10]=3[CH:9]=2)=[CH:6][CH:7]=1

Participants

8

Reactant 5

HCID 176Acetic AcidHCID 712FormaldehydeHCID 25517Ammonium Chloride2×HCID 5003444Sodium cyanoborohydrideHCID 59152452HCID 59152452, compound

Product 1

HCID 131729411HCID 131729411, compoundYield 187.9%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 21226129Dichloromethane methanolSolvent

Conditions

Temperature
0 °C

Procedure

Combine 2-(4-chloro-phenyl)-6-[6-(piperidin-4-yloxy)-pyridin-3-yl]-6H-thieno[2,3-c]pyridin-7-one (500 mg, 1.14 mmol) with acetic acid (0.33 mL, 5.71 mmol) in methanol (40 mL). Cool to 0° C., add formaldehyde (0.25 mL, 3.42 mmol, 37% aqueous solution) and stir for 5 min. Then add sodium cyanoborohydride (179 mg, 2.85 mmol) and warm the reaction to RT with stirring overnight. Concentrate the solution in vacuo and dilute with dichloromethane, saturated aqueous NaHCO3, and water. Separate the organic layer and extract the aqueous layer with dichloromethane. Combine the organic extracts, dry over MgSO4, filter, and concentrate in vacuo. Chromatograph the residue (silica gel, eluting with 0-10% MeOH (2N NH3)/CH2Cl2 to yield the free base. Add 1 equivalent of ammonium chloride to a solution of the free base in 1:1 methanol/CH2Cl2 and sonicate the solution until complete dissolution of NH4Cl. Concentrate in vacuo to yield 523 mg (99%) of the title compound. MS/ES m/z (35Cl) 452.0 [M+H+].

Workup

  1. customthe reaction to RT
  2. stirringwith stirring overnight
  3. concentrationConcentrate the solution in vacuo
  4. additiondilute with dichloromethane, saturated aqueous NaHCO3, and water
  5. customSeparate the organic layer
  6. extractionextract the aqueous layer with dichloromethane
  7. dry with materialdry over MgSO4
  8. filtrationfilter
  9. concentrationconcentrate in vacuo
  10. washChromatograph the residue (silica gel, eluting with 0-10% MeOH (2N NH3)/CH2Cl2
  11. customto yield the free base
  12. customsonicate the solution
  13. concentrationConcentrate in vacuo

Sources & evidence

ORD record
ord-cd94fc70dcb94a7b9af70dab576ed462
Source dataset
uspto-grants-2012_01
Patent number
US08101764B2

Reaction notes

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