5-Isocyanato-1,3-dioxaindane → N-({1-[4-(3-Benzo[1,3]dioxol-5-yl-ureido)-cyclohexyl]-azetidin-3-ylcarbamoyl}-methyl)-3-trifluoromethyl-benzamide

HRID 2188584Notes

Reaction equation

HRID 2188584 reaction equation
[N:1]([C:4]1[CH:12]=[CH:11][C:7]2[O:8][CH2:9][O:10][C:6]=2[CH:5]=1)=[C:2]=[O:3].OC(C(F)(F)F)=O.[NH2:20][CH:21]1[CH2:26][CH2:25][CH:24]([N:27]2[CH2:30][CH:29]([NH:31][C:32]([CH2:34][NH:35][C:36](=[O:47])[C:37]3[CH:42]=[CH:41][CH:40]=[C:39]([C:43]([F:46])([F:45])[F:44])[CH:38]=3)=[O:33])[CH2:28]2)[CH2:23][CH2:22]1>CN(C=O)C>[O:8]1[C:7]2[CH:11]=[CH:12][C:4]([NH:1][C:2](=[O:3])[NH:20][CH:21]3[CH2:22][CH2:23][CH:24]([N:27]4[CH2:30][CH:29]([NH:31][C:32]([CH2:34][NH:35][C:36](=[O:47])[C:37]5[CH:42]=[CH:41][CH:40]=[C:39]([C:43]([F:44])([F:45])[F:46])[CH:38]=5)=[O:33])[CH2:28]4)[CH2:25][CH2:26]3)=[CH:5][C:6]=2[O:10][CH2:9]1

Participants

4

Reactant 2

HCID 52232135-Isocyanato-1,3-dioxaindaneHCID 86646662N-{[1-(4-Amino-cyclohexyl)-azetidin-3-ylcarbamoyl]-methyl}-3-trifluoromethyl-benzamide TFA salt

Product 1

HCID 49763338N-({1-[4-(3-Benzo[1,3]dioxol-5-yl-ureido)-cyclohexyl]-azetidin-3-ylcarbamoyl}-methyl)-3-trifluoromethyl-benzamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

5-Isocyanato-benzo[1,3]dioxole (Aldrich, 50 mg, 0.302 mmol) was added into a solution of N-{[1-(4-amino-cyclohexyl)-azetidin-3-ylcarbamoyl]-methyl}-3-trifluoromethyl-benzamide TFA salt (150 mg, 0.302 mmol) and TEA (127 μL, 0.906 mmol) in DMF (3 mL) at room temperature. The reaction was stirred overnight and quenched with saturated sodium bicarbonate. The reaction was then partitioned between DCM and water. The organic layer was separated and the aqueous layer was extracted 3 times with a chloroform/IPA “cocktail” (˜3:1, v/v). The combined organic layers were dried over anhydrous Na2SO4, filtered and concentrated to give the crude product, which was then purified by a 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 white solid.

Workup

  1. customquenched with saturated sodium bicarbonate
  2. customThe reaction was then partitioned between DCM and water
  3. customThe organic layer was separated
  4. extractionthe aqueous layer was extracted 3 times with a chloroform/IPA “cocktail” (˜3:1
  5. dry with materialThe combined organic layers were dried over anhydrous Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto give the crude product, which
  9. customwas then purified by a CombiFlash® system

Sources & evidence

ORD record
ord-c420370e899d4d12ac1be46e9aea3e48
Source dataset
uspto-grants-2012_12
Patent number
US08324186B2

Reaction notes

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