Acetic Acid → HCID 24803423, compound

HRID 2384909Notes

Reaction equation

HRID 2384909 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:32][C:11]3[C:12](=[O:31])[N:13]([C:16]4[CH:21]=[CH:20][C:19]([O:22][C@@H:23]5[CH2:28][CH2:27][CH2:26][NH:25][CH2:24]5)=[C:18]([O:29][CH3:30])[CH:17]=4)[CH:14]=[CH:15][C:10]=3[CH:9]=2)=[CH:4][CH:3]=1.C=O.[C:35](O)(=O)C.C([BH3-])#N.[Na+]>CO>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:32][C:11]3[C:12](=[O:31])[N:13]([C:16]4[CH:21]=[CH:20][C:19]([O:22][C@@H:23]5[CH2:28][CH2:27][CH2:26][N:25]([CH3:35])[CH2:24]5)=[C:18]([O:29][CH3:30])[CH:17]=4)[CH:14]=[CH:15][C:10]=3[CH:9]=2)=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 712FormaldehydeHCID 5003444Sodium cyanoborohydrideHCID 24803256HCID 24803256, compound

Product 1

HCID 24803423HCID 24803423, compoundYield 34.2%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Stir a solution of 2-(4-chloro-phenyl)-6-[3-methoxy-4-((R)-piperidin-3-yloxy)-phenyl]-6H-thieno[2,3-c]pyridine-7-one (446 mg, 0.96 mmol), formaldehyde (0.38 mL, 37% aqueous solution), and acetic acid (0.22 mL, 3.84 mmol) in methanol (34 mL) at room temperature for 5 min. Add sodium cyanoborohydride (150 mg, 2.4 mmol) to this solution and stir the reaction for 2 h. Concentrate the mixture in vacuo and partition the residue between dichloromethane (20 mL) and saturated sodium bicarbonate (20 mL). Separate the organic portion and extract the aqueous portion with dichloromethane (2×10 mL). Dry the combined organics (Na2SO4), filter, and concentrate in vacuo. Purify by chromatography (dichloromethane to 5% 2 M ammonia in methanol/dichloromethane) to afford 158 mg (34%) of 2-(4-chloro-phenyl)-6-[3-methoxy-4-((R)-1-methyl-piperidin-3-yloxy)-phenyl]-6H-thieno[2,3-c]pyridin-7-one.

Workup

  1. customthe reaction for 2 h
  2. concentrationConcentrate the mixture in vacuo
  3. custompartition the residue between dichloromethane (20 mL) and saturated sodium bicarbonate (20 mL)
  4. customSeparate the organic portion
  5. extractionextract the aqueous portion with dichloromethane (2×10 mL)
  6. dry with materialDry the combined organics (Na2SO4)
  7. filtrationfilter
  8. concentrationconcentrate in vacuo
  9. customPurify by chromatography (dichloromethane to 5% 2 M ammonia in methanol/dichloromethane)

Sources & evidence

ORD record
ord-43476785f4bd4af38b4d6fcb4916bbcd
Source dataset
uspto-grants-2012_09
Patent number
US08263772B2

Reaction notes

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