Isobutylamine → tert-butyl (4S)-4-[4-((2-methylpropyl)methylcarbamoyl)piperidin-1-yl]azepane-1-carboxylate

HRID 714549Notes

Reaction equation

HRID 714549 reaction equation
CO[C:3]([CH:5]1[CH2:10][CH2:9][N:8]([C@H:11]2[CH2:17][CH2:16][CH2:15][N:14]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:13][CH2:12]2)[CH2:7][CH2:6]1)=[O:4].[CH2:25]([NH2:29])[CH:26]([CH3:28])[CH3:27].[CH3:30]N(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C>[CH3:27][CH:26]([CH3:28])[CH2:25][N:29]([CH3:30])[C:3]([CH:5]1[CH2:6][CH2:7][N:8]([C@H:11]2[CH2:17][CH2:16][CH2:15][N:14]([C:18]([O:20][C:21]([CH3:23])([CH3:22])[CH3:24])=[O:19])[CH2:13][CH2:12]2)[CH2:9][CH2:10]1)=[O:4]

Participants

6

Reactant 4

HCID 6558IsobutylamineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 89590036(S)-tert-Butyl 4-(4-(methoxycarbonyl)piperidin-1-yl)azepane-1-carboxylate

Product 1

HCID 131734061tert-butyl (4S)-4-[4-((2-methylpropyl)methylcarbamoyl)piperidin-1-yl]azepane-1-carboxylateYield 35%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

tert-butyl (4S)-4-[4-(methoxycarbonyl)piperidin-1-yl]azepane-1-carboxylate (0.3 g, 0.92 mmol) was dissolved in DMF (4 mL) and isobutylamine (0.14 g, 0.18 mL, 1.84 mmol), HATU (0.53 g, 1.38 mmol) and DIPEA (0.36 g, 0.48 mL, 2.76 mmol) were added. The reaction mixture was stirred at rt for 48 h and the solvents were removed in vacuo. The residue was partitioned between DCM and sat. NaHCO3 sol., the organic layer was washed with sat. NaCl sol. and dried (MgSO4). The solvents were removed in vacuo, and the residue was purified by column chromatography (normal phase, [Biotage SNAP cartridge KP-sil 10 g, 40-63 μm, 60 Å, 12 mL per min, gradient 0% to 10% MeOH in DCM]) to give tert-butyl (4S)-4-[4-((2-methylpropyl)methylcarbamoyl)piperidin-1-yl]azepane-1-carboxylate (0.12 g, 35%) as a pale yellow gum.

Workup

  1. customthe solvents were removed in vacuo
  2. customThe residue was partitioned between DCM and sat. NaHCO3 sol.
  3. washthe organic layer was washed with sat. NaCl sol.
  4. dry with materialdried (MgSO4)
  5. customThe solvents were removed in vacuo
  6. customthe residue was purified by column chromatography (normal phase, [Biotage SNAP cartridge KP-sil 10 g, 40-63 μm, 60 Å, 12 mL per min, gradient 0% to 10% MeOH in DCM])

Sources & evidence

ORD record
ord-d07718dcd4a948549a633147b7ea0660
Source dataset
uspto-grants-2015_11
Patent number
US09187451B2

Reaction notes

Loading…