1-Piperidinecarbonyl chloride → 1-Cyclobutyl-4-{[1-(piperidin-1-ylcarbonyl)azetidin-3-yl]carbonyl}-1,4-diazepane

HRID 1402731Notes

Reaction equation

HRID 1402731 reaction equation
[NH:1]1[CH2:4][CH:3]([C:5]([N:7]2[CH2:13][CH2:12][CH2:11][N:10]([CH:14]3[CH2:17][CH2:16][CH2:15]3)[CH2:9][CH2:8]2)=[O:6])[CH2:2]1.[N:18]1([C:24](Cl)=[O:25])[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]1>C(Cl)Cl>[CH:14]1([N:10]2[CH2:11][CH2:12][CH2:13][N:7]([C:5]([CH:3]3[CH2:2][N:1]([C:24]([N:18]4[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]4)=[O:25])[CH2:4]3)=[O:6])[CH2:8][CH2:9]2)[CH2:17][CH2:16][CH2:15]1

Participants

4

Reactant 2

HCID 2420851-Piperidinecarbonyl chlorideHCID 667393581-(Azetidin-3-ylcarbonyl)-4-cyclobutyl-1,4-diazepane

Product 1

HCID 468509941-Cyclobutyl-4-{[1-(piperidin-1-ylcarbonyl)azetidin-3-yl]carbonyl}-1,4-diazepaneYield 78%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred 0° C. solution of 1-(azetidin-3-ylcarbonyl)-4-cyclobutyl-1,4-diazepane (20 mg, 0.084 mmol) in DCM (1 ml) and TEA (0.023 ml, 0.17 mmol) was added dropwise piperidine-1-carbonyl chloride (14.9 mg, 0.013 ml, 0.10 mmol). The reaction was stirred for 1 h and then allowed to warm to RT and the progress monitored by LCMS. After 1 h the reaction was quenched with water (5 ml), extracted with DCM (2×10 ml), dried (MgSO4), filtered and concentrated at reduced pressure. Purification by silica FCC (eluting with 99:1 to 96:4 gradient of DCM/2M NH3 in MeOH) provided impure title compound (22 mg, 78%) as brown oil. Re-purification by preparative HPLC provided the title compound (3 mg, 10% yield) as a colourless oil.

Workup

  1. customAfter 1 h the reaction was quenched with water (5 ml)
  2. extractionextracted with DCM (2×10 ml)
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated at reduced pressure
  6. customPurification
  7. washby silica FCC (eluting with 99:1 to 96:4 gradient of DCM/2M NH3 in MeOH)

Sources & evidence

ORD record
ord-e8ca4fd837c94a3c8012e5194d3f99ba
Source dataset
uspto-grants-2014_12
Patent number
US08912176B2

Reaction notes

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