Diisopropylethylamine → Tert-butyl 4-{4-methoxy-4-[(1-methylcyclobutyl)carbamoyl]piperidin-1-yl}azepane-1-carboxylate

HRID 714539Notes

Reaction equation

HRID 714539 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:14][CH2:13][CH2:12][CH:11]([N:15]2[CH2:20][CH2:19][C:18]([O:24][CH3:25])([C:21]([OH:23])=O)[CH2:17][CH2:16]2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.[CH3:27][C:28]1([NH2:32])[CH2:31][CH2:30][CH2:29]1.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>[CH3:25][O:24][C:18]1([C:21](=[O:23])[NH:32][C:28]2([CH3:27])[CH2:31][CH2:30][CH2:29]2)[CH2:17][CH2:16][N:15]([CH:11]2[CH2:12][CH2:13][CH2:14][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[CH2:9][CH2:10]2)[CH2:20][CH2:19]1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 183324491-Methylcyclobutan-1-amine hydrochlorideHCID 1176784071-[1-(Tert-butoxycarbonyl)azepan-4-yl]-4-methoxypiperidine-4-carboxylic acid

Product 1

HCID 117678314Tert-butyl 4-{4-methoxy-4-[(1-methylcyclobutyl)carbamoyl]piperidin-1-yl}azepane-1-carboxylateYield 13.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

1-[1-(tert-butoxycarbonyl)azepan-4-yl]-4-methoxypiperidine-4-carboxylic acid (0.163 g, 0.44 mmol) was dissolved in DMF (5 mL) and (1-methyl)cyclobutylamine hydrochloride (0.08 g, 0.66 mmol), HATU (0.25 g, 0.66 mmol) and DIPEA (0.284 g, 0.38 mL, 2.20 mmol) were added. The reaction mixture was stirred at rt overnight under nitrogen. The solvents were removed in vacuo, and the residue was partitioned between DCM and sat. NaHCO3 sol., organic layer washed with sat. NaCl sol. and dried over 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, 50 mL per min, gradient 1% to 6% MeOH in DCM]) to give tert-butyl 4-{4-methoxy-4-[(1-methylcyclobutyl)carbamoyl]piperidin-1-yl}azepane-1-carboxylate (0.025 g, 13.4%) as a pale yellow oil.

Workup

  1. customThe solvents were removed in vacuo
  2. customthe residue was partitioned between DCM and sat. NaHCO3 sol., organic layer
  3. washwashed with sat. NaCl sol.
  4. dry with materialdried over 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, 50 mL per min, gradient 1% to 6% MeOH in DCM])

Sources & evidence

ORD record
ord-6a61081f339d47549529a2e7c4e0de3d
Source dataset
uspto-grants-2015_11
Patent number
US09187451B2

Reaction notes

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