Isobutylamine → Ethyl 4-(4-((2-methylpropyl)carbamoyl)piperidin-1-yl)azepane-1-carboxylate

HRID 714546Notes

Reaction equation

HRID 714546 reaction equation
[CH2:1]([O:3][C:4]([N:6]1[CH2:12][CH2:11][CH2:10][CH:9]([N:13]2[CH2:18][CH2:17][CH:16]([C:19]([OH:21])=O)[CH2:15][CH2:14]2)[CH2:8][CH2:7]1)=[O:5])[CH3:2].[CH2:22]([NH2:26])[CH:23]([CH3:25])[CH3:24].CN(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>[CH3:24][CH:23]([CH3:25])[CH2:22][NH:26][C:19]([CH:16]1[CH2:15][CH2:14][N:13]([CH:9]2[CH2:10][CH2:11][CH2:12][N:6]([C:4]([O:3][CH2:1][CH3:2])=[O:5])[CH2:7][CH2:8]2)[CH2:18][CH2:17]1)=[O:21]

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 895794231-(1-(Ethoxycarbonyl)azepan-4-yl)piperidine-4-carboxylic acid

Product 1

HCID 71569978Ethyl 4-(4-((2-methylpropyl)carbamoyl)piperidin-1-yl)azepane-1-carboxylateYield 5.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

1-(1-(ethoxycarbonyl)azepan-4-yl)piperidine-4-carboxylic acid (0.26 g assumed 0.89 mmol) was dissolved in DMF (4 mL) and isobutylamine (0.81 g, 1.1 mL, 11.0 mmol), HATU (0.51 g, 1.34 mmol) and DIPEA (0.46 g, 0.62 mL, 3.56 mmol) were added. The reaction mixture was stirred at rt overnight 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 25 g, 40-63 μm, 60 Å, 25 mL per min, gradient 0% to 3% MeOH in DCM]) to give ethyl 4-(4-((2-methylpropyl)carbamoyl)piperidin-1-yl)azepane-1-carboxylate (17 mg, 2%) 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 25 g, 40-63 μm, 60 Å, 25 mL per min, gradient 0% to 3% MeOH in DCM])

Sources & evidence

ORD record
ord-7fc69d5b57bf43d789e9abb4ddd8f0f1
Source dataset
uspto-grants-2015_11
Patent number
US09187451B2

Reaction notes

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