Dichloromethane → 1-Cyclobutyl-4-{[1-(piperidin-1-ylacetyl)azetidin-3-yl]carbonyl}-1,4-diazepane

HRID 1402735Notes

Reaction equation

HRID 1402735 reaction equation
Cl[CH2:2][C:3]([N:5]1[CH2:8][CH:7]([C:9]([N:11]2[CH2:17][CH2:16][CH2:15][N:14]([CH:18]3[CH2:21][CH2:20][CH2:19]3)[CH2:13][CH2:12]2)=[O:10])[CH2:6]1)=[O:4].[NH:22]1[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]1.[CH2:28]([Cl:30])[Cl:29]>C1(C)C=CC=CC=1>[CH2:28]([Cl:30])[Cl:29].[CH3:3][OH:4].[NH3:5].[CH:18]1([N:14]2[CH2:15][CH2:16][CH2:17][N:11]([C:9]([CH:7]3[CH2:8][N:5]([C:3](=[O:4])[CH2:2][N:22]4[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]4)[CH2:6]3)=[O:10])[CH2:12][CH2:13]2)[CH2:21][CH2:20][CH2:19]1

Participants

6

Reactant 3

HCID 6344DichloromethaneHCID 8082PiperidineHCID 667393341-{[1-(Chloroacetyl)azetidin-3-yl]carbonyl}-4-cyclobutyl-1,4-diazepane

Product 2

HCID 21584172Ammonia methanol dichloromethaneHCID 468513191-Cyclobutyl-4-{[1-(piperidin-1-ylacetyl)azetidin-3-yl]carbonyl}-1,4-diazepaneYield 53%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A solution of 1-{[1-(chloroacetyl)azetidin-3-yl]carbonyl}-4-cyclobutyl-1,4-diazepane (40 mg, 0.13 mmol) and piperidine (38 μl, 0.38 mmol) in toluene (2 ml) was heated at 80° C. for 4 hrs in a sealed tube then cooled to RT. The reaction was diluted with DCM (30 ml), washed with a saturated aqueous solution of NaHCO3 (2×15 ml), dried (MgSO4), filtered and concentrated at reduced pressure. The residue was purified by silica FCC (using a gradient of eluents; DCM/MeOH/NH3 99:1:1 to 92:8:1) to give the title compound (25 mg, 53% yield) as a colourless oil.

Workup

  1. washwashed with a saturated aqueous solution of NaHCO3 (2×15 ml)
  2. dry with materialdried (MgSO4)
  3. filtrationfiltered
  4. concentrationconcentrated at reduced pressure
  5. customThe residue was purified by silica FCC (

Sources & evidence

ORD record
ord-d94c01dfbab6401088feab0f042d0515
Source dataset
uspto-grants-2014_12
Patent number
US08912176B2

Reaction notes

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