Diisopropylethylamine → Tert-butyl 2-{4-[(1-methylcyclobutyl)carbamoyl]piperidin-1-yl}-6-azaspiro[3.4]octane-6-carboxylate

HRID 1777305Notes

Reaction equation

HRID 1777305 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:24][CH2:23][C:10]2([CH2:13][CH:12]([N:14]3[CH2:19][CH2:18][CH:17]([C:20]([OH:22])=O)[CH2:16][CH2:15]3)[CH2:11]2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.[CH3:26][C:27]1([NH2:31])[CH2:30][CH2:29][CH2:28]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>[CH3:26][C:27]1([NH:31][C:20]([CH:17]2[CH2:16][CH2:15][N:14]([CH:12]3[CH2:13][C:10]4([CH2:23][CH2:24][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])[CH2:9]4)[CH2:11]3)[CH2:19][CH2:18]2)=[O:22])[CH2:30][CH2:29][CH2:28]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 1183062081-[6-(Tert-butoxycarbonyl)-6-azaspiro[3.4]oct-2-yl]piperidine-4-carboxylic acid

Product 1

HCID 90089500Tert-butyl 2-{4-[(1-methylcyclobutyl)carbamoyl]piperidin-1-yl}-6-azaspiro[3.4]octane-6-carboxylateYield 76.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

1-[6-(tert-Butoxycarbonyl)-6-azaspiro[3.4]oct-2-yl]piperidine-4-carboxylic acid was dissolved in DMF (5 mL) and (1-methylcyclobutyl)amine hydrochloride (0.37 g, 3.03 mmol), HATU (0.844 g, 2.22 mmol) and DIPEA (1.305 g, 10.1 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 50 g, 40-63 μm, 60 A, 50 mL per min, gradient 0% to 10% MeOH in DCM]) to give tert-butyl 2-{4-[(1-methylcyclobutyl)carbamoyl]piperidin-1-yl}-6-azaspiro[3.4]octane-6-carboxylate (0.627 g, 76.7%) as a white foam.

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 50 g, 40-63 μm, 60 A, 50 mL per min, gradient 0% to 10% MeOH in DCM])

Sources & evidence

ORD record
ord-432e75df1acd46c389ce166a8f85cacf
Source dataset
uspto-grants-2016_02
Patent number
US09266857B2

Reaction notes

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