Diisopropylethylamine → HCID 73438532, compound

HRID 1777298Notes

Reaction equation

HRID 1777298 reaction equation
[CH2:1]([O:3][C:4]([N:6]1[CH2:23][CH2:22][C:8]2([CH2:11][CH:10]([N:12]3[CH2:17][CH2:16][C:15]([F:21])([C:18](O)=[O:19])[CH2:14][CH2:13]3)[CH2:9]2)[CH2:7]1)=[O:5])[CH3:2].Cl.[CH3:25][C:26]1([NH2:30])[CH2:29][CH2:28][CH2:27]1.CCN(C(C)C)C(C)C>S(Cl)(Cl)=O>[F:21][C:15]1([C:18](=[O:19])[NH:30][C:26]2([CH3:25])[CH2:29][CH2:28][CH2:27]2)[CH2:16][CH2:17][N:12]([CH:10]2[CH2:11][C:8]3([CH2:22][CH2:23][N:6]([C:4]([O:3][CH2:1][CH3:2])=[O:5])[CH2:7]3)[CH2:9]2)[CH2:13][CH2:14]1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 183324491-Methylcyclobutan-1-amine hydrochlorideHCID 90079597HCID 90079597, compound

Product 1

HCID 73438532HCID 73438532, compoundYield 28%

Reagents, catalysts & solvents 1

HCID 24386Thionyl ChlorideSolvent

Conditions

Temperature
90 °C

Procedure

Crude 1-[6-(ethoxycarbonyl)-6-azaspiro[3.4]oct-2-yl]-4-fluoropiperidine-4-carboxylic acid was suspended in thionyl chloride (3 mL) and the reaction was stirred at 90° C. for 2 h. The reaction mixture was cooled to rt and concentrated in vacuo. The residue was dissolved in DCM (5 mL) and (1-methylcyclobutyl)amine hydrochloride (0.196 g, 1.62 mmol) and DIPEA (0.523 g, 0.71 mL, 4.05 mmol) were added, the reaction mixture was stirred overnight at rt. The reaction mixture was partitioned between DCM and sat. NaHCO3 sol., organic layer washed with sat. NaCl sol. and dried over MgSO4. The residue was purified by column chromatography (normal phase, [Biotage SNAP cartridge KP-sil 25 g, 40-63 μm, 60 A, 12 mL per min, gradient 0% to 6% MeOH in DCM]) to give ethyl 2-{4-fluoro-4-[(1-methylcyclobutyl)carbamoyl]piperidin-1-yl}-6-azaspiro[3.4]octane-6-carboxylate (0.09 g, 28%) as a pale yellow gum as a mixture of diastereomers.

Workup

  1. temperatureThe reaction mixture was cooled to rt
  2. concentrationconcentrated in vacuo
  3. dissolutionThe residue was dissolved in DCM (5 mL)
  4. stirringthe reaction mixture was stirred overnight at rt
  5. customThe reaction mixture was partitioned between DCM and sat. NaHCO3 sol., organic layer
  6. washwashed with sat. NaCl sol.
  7. dry with materialdried over MgSO4
  8. customThe residue was purified by column chromatography (normal phase, [Biotage SNAP cartridge KP-sil 25 g, 40-63 μm, 60 A, 12 mL per min, gradient 0% to 6% MeOH in DCM])

Sources & evidence

ORD record
ord-3b88fa041e46478c84955b1765bdc0fa
Source dataset
uspto-grants-2016_02
Patent number
US09266857B2

Reaction notes

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