1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → Benzyl 3-[(4-cyclobutyl-1,4-diazepan-1-yl)carbonyl]azetidine-1-carboxylate

HRID 1402729Notes

Reaction equation

HRID 1402729 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:14][CH:13]([C:15]([OH:17])=O)[CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.[CH:39]1([N:43]2[CH2:49][CH2:48][CH2:47][NH:46][CH2:45][CH2:44]2)[CH2:42][CH2:41][CH2:40]1>CN(C=O)C.C(Cl)Cl.C(Cl)Cl>[CH:39]1([N:43]2[CH2:49][CH2:48][CH2:47][N:46]([C:15]([CH:13]3[CH2:12][N:11]([C:9]([O:8][CH2:1][C:2]4[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=4)=[O:10])[CH2:14]3)=[O:17])[CH2:45][CH2:44]2)[CH2:42][CH2:41][CH2:40]1

Participants

7

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 109882141-[(Benzyloxy)carbonyl]azetidine-3-carboxylic acidHCID 574239531-Cyclobutyl-[1,4]diazepane

Product 1

HCID 46843044Benzyl 3-[(4-cyclobutyl-1,4-diazepan-1-yl)carbonyl]azetidine-1-carboxylateYield 60%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 22350042dichloromethane N,N-dimethylformamideSolvent

Procedure

To a stirred solution of 1-[(benzyloxy)carbonyl]azetidine-3-carboxylic acid (500 mg, 2.13 mmol) in DMF/DCM (1:10) (11 ml) was added HOBt (287 mg, 2.13 mmol) and EDCI (490 mg, 2.56 mmol). The resulting suspension was stirred at RT for 10 mins before dropwise addition of 1-cyclobutyl-1,4-diazepane (328 mg, 2.13 mmol) in DCM (3 ml). After stirring for 16 h at RT the reaction was shown to be complete by TLC and the solvent was evaporated at reduced pressure. The residue was treated with saturated aqueous NaHCO3 (10 ml) and the resulting aqueous extracted with EtOAc (3×7.5 ml). The combined organic phases were dried (MgSO4), filtered and concentrated at reduced pressure. Purification by silica FCC (eluting with 99:1 to 97:3 gradient of DCM/2M NH3 in MeOH) provided the title compound (475 mg, 60% yield) as a yellow oil.

Workup

  1. customthe solvent was evaporated at reduced pressure
  2. additionThe residue was treated with saturated aqueous NaHCO3 (10 ml)
  3. extractionthe resulting aqueous extracted with EtOAc (3×7.5 ml)
  4. dry with materialThe combined organic phases were dried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated at reduced pressure
  7. customPurification
  8. washby silica FCC (eluting with 99:1 to 97:3 gradient of DCM/2M NH3 in MeOH)

Sources & evidence

ORD record
ord-928d3fa4785047bd9ce6e9f26b51c278
Source dataset
uspto-grants-2014_12
Patent number
US08912176B2

Reaction notes

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