1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 4-((1-((4-chlorophenyl)(phenyl)methyl)azetidin-3-yl)methoxy)-5-cyclopropyl-2-fluoro-N-(methylsulfonyl)benzamide

HRID 1849878Notes

Reaction equation

HRID 1849878 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[N:9]2[CH2:12][CH:11]([CH2:13][O:14][C:15]3[C:23]([CH:24]4[CH2:26][CH2:25]4)=[CH:22][C:18]([C:19](O)=[O:20])=[C:17]([F:27])[CH:16]=3)[CH2:10]2)=[CH:4][CH:3]=1.[CH3:34][S:35]([NH2:38])(=[O:37])=[O:36].CCN=C=NCCCN(C)C>CN(C1C=CN=CC=1)C.C(Cl)Cl.CCOC(C)=O>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[N:9]2[CH2:12][CH:11]([CH2:13][O:14][C:15]3[C:23]([CH:24]4[CH2:26][CH2:25]4)=[CH:22][C:18]([C:19]([NH:38][S:35]([CH3:34])(=[O:37])=[O:36])=[O:20])=[C:17]([F:27])[CH:16]=3)[CH2:10]2)=[CH:4][CH:3]=1

Participants

7

Reactant 3

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 72879MethanesulfonamideHCID 86703763HCID 86703763, compound

Product 1

HCID 725489054-((1-((4-chlorophenyl)(phenyl)methyl)azetidin-3-yl)methoxy)-5-cyclopropyl-2-fluoro-N-(methylsulfonyl)benzamideYield 19%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
25 °C

Procedure

A mixture of 4-((1-((4-chlorophenyl)(phenyl)methyl)azetidin-3-yl)-methoxy)-5-cyclopropyl-2-fluorobenzoic acid (50 mg, 0.11 mmol), methanesulfonamide (15 mg, 0.16 mmol), EDCI (31 mg, 0.16 mmol) and DMAP (20 mg, 0.16 mmol) in DCM (20 mL) was stirred at 25° C. for 16 h. The reaction mixture was diluted with EtOAc (100 mL), washed with HCl (2.0 M, 20 mL) and brine (50×2 mL), dried over anhydrous sodium sulfate, filtered and concentrated. The residue was purified by reverse phase Combiflash (35%-38% MeCN in 0.5% NH4HCO3) to give the target product (11.0 mg, 19%) as an off-white solid. LCMS (ESI) Method A: RT=5.83 min, m/z: 543.5 [M+H]+. 1H-NMR (500 MHz, MeOH-d4): δ 7.31-7.29 (m, 4H), 7.23-7.19 (m, 5H), 7.14-7.11 (m, 1H), 6.69-6.66 (m, 1H), 4.51 (s, 1H), 4.08 (d, J=6.5 Hz, 2H), 3.39-3.34 (m, 2H), 3.32-3.13 (m, 5H), 2.94-2.90 (m, 1H), 1.99-1.96 (m, 1H), 0.84-0.80 (m, 2H), 0.58-0.54 (m, 2H).

Workup

  1. washwashed with HCl (2.0 M, 20 mL) and brine (50×2 mL)
  2. dry with materialdried over anhydrous sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue was purified by reverse phase Combiflash (35%-38% MeCN in 0.5% NH4HCO3)

Sources & evidence

ORD record
ord-3aacc7d379374799b0beb4b5d425250c
Source dataset
uspto-grants-2015_02
Patent number
US08952169B2

Reaction notes

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