Formaldehyde → N-[(3'-{[(3S)-3,4-dimethyl-1-piperazinyl]methyl}-6-fluoro-3-biphenylyl)methyl]-3-[(1-methyl-4-piperidinyl)methyl]benzamide

HRID 2080327Notes

Reaction equation

HRID 2080327 reaction equation
[CH3:1][C@@H:2]1[N:7]([CH3:8])[CH2:6][CH2:5][N:4]([CH2:9][C:10]2[CH:11]=[C:12]([C:16]3[C:21]([F:22])=[CH:20][CH:19]=[C:18]([CH2:23][NH:24][C:25](=[O:39])[C:26]4[CH:31]=[CH:30][CH:29]=[C:28]([CH2:32][CH:33]5[CH2:38][CH2:37][NH:36][CH2:35][CH2:34]5)[CH:27]=4)[CH:17]=3)[CH:13]=[CH:14][CH:15]=2)[CH2:3]1.[CH2:40]=O.[BH4-].[Na+]>CO>[CH3:1][C@@H:2]1[N:7]([CH3:8])[CH2:6][CH2:5][N:4]([CH2:9][C:10]2[CH:11]=[C:12]([C:16]3[C:21]([F:22])=[CH:20][CH:19]=[C:18]([CH2:23][NH:24][C:25](=[O:39])[C:26]4[CH:31]=[CH:30][CH:29]=[C:28]([CH2:32][CH:33]5[CH2:34][CH2:35][N:36]([CH3:40])[CH2:37][CH2:38]5)[CH:27]=4)[CH:17]=3)[CH:13]=[CH:14][CH:15]=2)[CH2:3]1

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 4311764Sodium borohydrideHCID 11706395N-[(3'-{[(3S)-3,4-dimethyl-1-piperazinyl]methyl}-6-fluoro-3-biphenylyl)methyl]-3-(4-piperidinylmethyl)benzamide

Product 1

HCID 11656788N-[(3'-{[(3S)-3,4-dimethyl-1-piperazinyl]methyl}-6-fluoro-3-biphenylyl)methyl]-3-[(1-methyl-4-piperidinyl)methyl]benzamideYield 35.3%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of N-[(3′-{[(3S)-3,4-dimethyl-1-piperazinyl]methyl}-6-fluoro-3-biphenylyl)methyl]-3-(4-piperidinylmethyl)benzamide (165 mg, 0.313 mmol) in 3 mL of MeOH, was added dropwise formaldehyde (37%, 101 mg, 1.25 mmol). After stirring for 30 minutes, sodium borohydride (24 mg, 0.63 mmol) was added. After stirring of the resulting mixture at rt for 12 hours, the solvent was removed under vacuum and the residue was purified by loading onto a 2 g aminopropyl SPE cartridge and eluting sequentially with DCM (3×5 mL), EtOAc (3×5 mL), and MeOH (3×5 mL). The DCM factions were combined and evaporated to give the title compound as a white solid (60 mg, 35%). LC/MS: m/z, 543 (M+H), 1.18 min.

Workup

  1. stirringAfter stirring of the resulting mixture at rt for 12 hours
  2. customthe solvent was removed under vacuum
  3. customthe residue was purified
  4. washeluting sequentially with DCM (3×5 mL), EtOAc (3×5 mL), and MeOH (3×5 mL)
  5. customevaporated

Sources & evidence

ORD record
ord-d1cac5328ce8403f803c5eb9a385e122
Source dataset
uspto-grants-2011_04
Patent number
US07932247B2

Reaction notes

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