Formaldehyde → 1,1-dimethylethyl 4-{[3-({[(3'-{[(3S)-3,4-dimethyl-1-piperazinyl]methyl}-6-fluoro-3-biphenylyl)methyl]amino}carbonyl)phenyl]methyl)-1-piperidinecarboxylate

HRID 2080322Notes

Reaction equation

HRID 2080322 reaction equation
[F:1][C:2]1[C:7]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([CH2:14][N:15]3[CH2:20][CH2:19][NH:18][C@@H:17]([CH3:21])[CH2:16]3)[CH:9]=2)=[CH:6][C:5]([CH2:22][NH:23][C:24]([C:26]2[CH:27]=[C:28]([CH2:32][CH:33]3[CH2:38][CH2:37][N:36]([C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])[CH2:35][CH2:34]3)[CH:29]=[CH:30][CH:31]=2)=[O:25])=[CH:4][CH:3]=1.[CH2:46]=O.[BH4-].[Na+]>CO>[CH3:21][C@@H:17]1[N:18]([CH3:46])[CH2:19][CH2:20][N:15]([CH2:14][C:10]2[CH:9]=[C:8]([C:7]3[C:2]([F:1])=[CH:3][CH:4]=[C:5]([CH2:22][NH:23][C:24]([C:26]4[CH:27]=[C:28]([CH2:32][CH:33]5[CH2:34][CH2:35][N:36]([C:39]([O:41][C:42]([CH3:44])([CH3:43])[CH3:45])=[O:40])[CH2:37][CH2:38]5)[CH:29]=[CH:30][CH:31]=4)=[O:25])[CH:6]=3)[CH:13]=[CH:12][CH:11]=2)[CH2:16]1

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 4311764Sodium borohydrideHCID 577304411,1-Dimethylethyl 4-{[3-({[(6-fluoro-3'-{[(3S)-3-methyl-1-piperazinyl]methyl}-3-biphenylyl)methyl]amino}carbonyl)phenyl]methyl}-1-piperidinecarboxylate

Product 1

HCID 577304331,1-dimethylethyl 4-{[3-({[(3'-{[(3S)-3,4-dimethyl-1-piperazinyl]methyl}-6-fluoro-3-biphenylyl)methyl]amino}carbonyl)phenyl]methyl)-1-piperidinecarboxylateYield 99%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of 1,1-dimethylethyl 4-{[3-({[(6-fluoro-3′-{[(3S)-3-methyl-1-piperazinyl]methyl}-3-biphenylyl)methyl]amino}carbonyl)phenyl]methyl}-1-piperidinecarboxylate (130 mg, 0.21 mmol) in MeOH (5 mL) was added formaldehyde (37% in water, 69 mg, 0.85 mmol). After 30 minutes stirring at rt, sodium borohydride (16 mg, 0.42 mmol) was added. After stirring at rt for additional 3 hours, the solvent was removed to give a residue which 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 dichloromethane and ethyl acetate fractions were combined and evaporated to give the title compound (130 mg, 99%). LC/MS: m/z, 629 (M+H), 1.97 min.

Workup

  1. stirringAfter stirring at rt for additional 3 hours
  2. customthe solvent was removed
  3. customto give a residue which
  4. customwas purified
  5. washeluting sequentially with DCM (3×5 mL), EtOAc (3×5 mL), and MeOH (3×5 mL)
  6. customevaporated

Sources & evidence

ORD record
ord-502a047f211d4805a88c2219eb8bd029
Source dataset
uspto-grants-2011_04
Patent number
US07932247B2

Reaction notes

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