1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → N-{[1-(4-Benzo[1,3]-dioxol-5-yl-cyclohex-3-enyl)-azetidin-3-ylcarbamoyl]-methyl}-3-trifluoromethyl-benzamide

HRID 1893220Notes

Reaction equation

HRID 1893220 reaction equation
OC(C(F)(F)F)=O.[O:8]1[C:12]2[CH:13]=[CH:14][C:15]([C:17]3[CH2:22][CH2:21][CH:20]([N:23]4[CH2:26][CH:25]([NH2:27])[CH2:24]4)[CH2:19][CH:18]=3)=[CH:16][C:11]=2[O:10][CH2:9]1.[F:28][C:29]([F:44])([F:43])[C:30]1[CH:31]=[C:32]([CH:40]=[CH:41][CH:42]=1)[C:33]([NH:35][CH2:36][C:37](O)=[O:38])=[O:34].CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1>C(Cl)Cl>[O:8]1[C:12]2[CH:13]=[CH:14][C:15]([C:17]3[CH2:22][CH2:21][CH:20]([N:23]4[CH2:26][CH:25]([NH:27][C:37]([CH2:36][NH:35][C:33](=[O:34])[C:32]5[CH:40]=[CH:41][CH:42]=[C:30]([C:29]([F:44])([F:28])[F:43])[CH:31]=5)=[O:38])[CH2:24]4)[CH2:19][CH:18]=3)=[CH:16][C:11]=2[O:10][CH2:9]1

Participants

6

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 2777432((3-(Trifluoromethyl)benzoyl)amino)acetic acidHCID 866466771-(4-benzo[1,3]dioxol-5-yl-cyclohex-3-enyl)-azetidin-3-ylamine TFA salt

Product 1

HCID 56680600N-{[1-(4-Benzo[1,3]-dioxol-5-yl-cyclohex-3-enyl)-azetidin-3-ylcarbamoyl]-methyl}-3-trifluoromethyl-benzamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 1-(4-benzo[1,3]dioxol-5-yl-cyclohex-3-enyl)-azetidin-3-ylamine TFA salt (as prepared in the previous step, 550 mg, 1.10 mmol) and (3-trifluoromethyl-benzoylamino)-acetic acid (Bionet, 272 mg, 1.10 mmol) in DCM (10 mL) was treated with TEA (770 μL, 5.5 mmol) at room temperature. The mixture was treated with EDCI (Aldrich, 252 mg, 1.32 mmol), HOBT (Aldrich 149 mg, 1.10 mmol), and the reaction was stirred at room temperature for additional 6 hours. The reaction was partitioned between DCM and water. The organic layer was washed with brine, dried over anhydrous Na2SO4, filtered and concentrated to give the crude product, which was then purified by CombiFlash® system using ethyl acetate and 7N NH3 in MeOH as eluent (from pure ethyl acetate to 5% 7N NH3 in MeOH in ethyl acetate) to afford the title compound as a white solid.

Workup

  1. customThe reaction was partitioned between DCM and water
  2. washThe organic layer was washed with brine
  3. dry with materialdried over anhydrous Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto give the crude product, which
  7. customwas then purified by CombiFlash® system

Sources & evidence

ORD record
ord-05127522e4e04b57a9914f19da637ea9
Source dataset
uspto-grants-2013_08
Patent number
US08513229B2

Reaction notes

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