Cyclohexanecarboxylic acid → 1-Cyclobutyl-4-{[1-(cyclohexylcarbonyl)azetidin-3-yl]carbonyl}-1,4-diazepane

HRID 1402732Notes

Reaction equation

HRID 1402732 reaction equation
[CH:1]1([C:7]([OH:9])=O)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.[NH:31]1[CH2:34][CH:33]([C:35]([N:37]2[CH2:43][CH2:42][CH2:41][N:40]([CH:44]3[CH2:47][CH2:46][CH2:45]3)[CH2:39][CH2:38]2)=[O:36])[CH2:32]1.CCN(C(C)C)C(C)C>C(Cl)Cl.CN(C=O)C.C(Cl)Cl>[CH:44]1([N:40]2[CH2:41][CH2:42][CH2:43][N:37]([C:35]([CH:33]3[CH2:32][N:31]([C:7]([CH:1]4[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]4)=[O:9])[CH2:34]3)=[O:36])[CH2:38][CH2:39]2)[CH2:47][CH2:46][CH2:45]1

Participants

8

Reactant 5

HCID 7413Cyclohexanecarboxylic acidHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 667393581-(Azetidin-3-ylcarbonyl)-4-cyclobutyl-1,4-diazepane

Product 1

HCID 468509961-Cyclobutyl-4-{[1-(cyclohexylcarbonyl)azetidin-3-yl]carbonyl}-1,4-diazepaneYield 82.2%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 22350042dichloromethane N,N-dimethylformamideSolvent

Procedure

To a stirred solution of cyclohexanecarboxylic acid (10.8 mg, 0.084 mmol) in DCM/DMF (1.1 ml) was added HOBt (11.4 mg, 0.084 mmol) and EDCI (16.1 mg, 0.084 mmol). After 10 mins a solution of 1-(azetidin-3-ylcarbonyl)-4-cyclobutyl-1,4-diazepane (20 mg, 0.084 mmol) in DCM (1 ml) and DIPEA (0.01 ml, 0.084 mmol) was added dropwise. After 15 h the solvent was evaporated at reduced pressure and purified by silica FCC (eluting with 99:1 to 95:5 gradient of DCM/2M NH3 in MeOH) to give the title compound (24 mg, 82% yield) as brown oil.

Workup

  1. customAfter 15 h the solvent was evaporated at reduced pressure
  2. custompurified by silica FCC (eluting with 99:1 to 95:5 gradient of DCM/2M NH3 in MeOH)

Sources & evidence

ORD record
ord-d996836a5ba045b0be7cc5657fc748ad
Source dataset
uspto-grants-2014_12
Patent number
US08912176B2

Reaction notes

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