Sodium triacetoxyborohydride → N-{[6-fluoro-3'-(1-piperazinylmethyl)-3-biphenylyl]methyl}-3-(4-piperidinylmethyl)benzamide

HRID 2080348Notes

Reaction equation

HRID 2080348 reaction equation
[F:1][C:2]1[C:7]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([CH:14]=O)[CH:9]=2)=[CH:6][C:5]([CH2:16][NH:17][C:18]([C:20]2[CH:21]=[C:22]([CH2:26][CH:27]3[CH2:32][CH2:31][N:30](C(OC(C)(C)C)=O)[CH2:29][CH2:28]3)[CH:23]=[CH:24][CH:25]=2)=[O:19])=[CH:4][CH:3]=1.C[C@H:41]1[CH2:46][NH:45][CH2:44][CH2:43][N:42]1C(OC(C)(C)C)=O.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>C(Cl)Cl>[F:1][C:2]1[C:7]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([CH2:14][N:42]3[CH2:43][CH2:44][NH:45][CH2:46][CH2:41]3)[CH:9]=2)=[CH:6][C:5]([CH2:16][NH:17][C:18](=[O:19])[C:20]2[CH:25]=[CH:24][CH:23]=[C:22]([CH2:26][CH:27]3[CH2:28][CH2:29][NH:30][CH2:31][CH2:32]3)[CH:21]=2)=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 5049666Sodium triacetoxyborohydrideHCID 10081508tert-Butyl (2S)-2-methylpiperazine-1-carboxylateHCID 577366931,1-Dimethylethyl 4-{[3-({[(6-fluoro-3'-formyl-3-biphenylyl)methyl]amino}carbonyl)phenyl]methyl}-1-piperidinecarboxylate

Product 1

HCID 11627458N-{[6-fluoro-3'-(1-piperazinylmethyl)-3-biphenylyl]methyl}-3-(4-piperidinylmethyl)benzamideYield 27.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of 1,1-dimethylethyl 4-{[3-({[(6-fluoro-3′-formyl-3-biphenylyl)methyl]amino}carbonyl)phenyl]methyl}-1-piperidinecarboxylate (74 mg, 0.14 mmol) in CH2Cl2 (5 mL) was mixed with 1,1-dimethylethyl (2S)-2-methyl-1-piperazinecarboxylate (26 mg, 0.14 mmol) and NaB(OAc)3H (45 mg, 0.21 mmol). The resulting mixture was stirred for 16 hours, diluted with dichloromethane (30 mL) and washed with brine (10 mL). The organic layer was collected, dried over Na2SO4 and concentrated under vacuum. The residue was purified by loading onto a 2 g amminopropyl SPE cartridge, eluting sequentially with DCM (3×5 mL), EtOAc (3×5 mL), and MeOH (3×5 mL). The DCM fractions were combined, and mixed with 2 mL of TFA. After stirring for 1 h, the mixture was concentrated under vacuum, and the residue thus obtained was purified by Gilson reverse phase HPLC, eluting with acetonitrile/water/0.1% TFA (10/90 to 70/30, v/v, over 12 min), to give the title compound (19 mg, 27%). LC/MS: m/z, 501 (M+H), 1.35 min.

Workup

  1. washwashed with brine (10 mL)
  2. customThe organic layer was collected
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated under vacuum
  5. customThe residue was purified
  6. washeluting sequentially with DCM (3×5 mL), EtOAc (3×5 mL), and MeOH (3×5 mL)
  7. additionmixed with 2 mL of TFA
  8. stirringAfter stirring for 1 h
  9. concentrationthe mixture was concentrated under vacuum
  10. customthe residue thus obtained
  11. customwas purified by Gilson reverse phase HPLC
  12. washeluting with acetonitrile/water/0.1% TFA (10/90 to 70/30, v/v, over 12 min)

Sources & evidence

ORD record
ord-5dca35b8c68548939d90e39768e9b6bc
Source dataset
uspto-grants-2011_04
Patent number
US07932247B2

Reaction notes

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