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

HRID 1849886Notes

Reaction equation

HRID 1849886 reaction equation
[CH:1]([N:14]1[CH2:19][CH2:18][CH:17]([CH2:20][O:21][C:22]2[C:30]([CH:31]3[CH2:33][CH2:32]3)=[CH:29][C:25]([C:26](O)=[O:27])=[C:24]([F:34])[CH:23]=2)[CH2:16][CH2:15]1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:35][S:36]([NH2:39])(=[O:38])=[O:37].CCN=C=NCCCN(C)C>CN(C1C=CN=CC=1)C.C(Cl)Cl>[CH:1]([N:14]1[CH2:19][CH2:18][CH:17]([CH2:20][O:21][C:22]2[C:30]([CH:31]3[CH2:33][CH2:32]3)=[CH:29][C:25]([C:26]([NH:39][S:36]([CH3:35])(=[O:38])=[O:37])=[O:27])=[C:24]([F:34])[CH:23]=2)[CH2:16][CH2:15]1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 72879MethanesulfonamideHCID 867037654-((1-Benzhydrylpiperidin-4-yl)methoxy) 5-cyclopropyl-2-fluorobenzoic acid

Product 1

HCID 725491354-((1-benzhydrylpiperidin-4-yl)methoxy)-5-cyclopropyl-2-fluoro-N-(methylsulfonyl)benzamideYield 5%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

A solution of 4-((1-benzhydrylpiperidin-4-yl)methoxy)-5-cyclopropyl-2-fluorobenzoic acid (270 mg, 0.59 mmol), methanesulfonamide (84 mg, 0.88 mmol), EDCI (169 mg, 0.88 mmol) and DMAP (107 mg, 0.88 mmol) in DCM (5 mL) was stirred at room temperature for 16 h. The reaction was quenched with water (5 mL) then adjusted pH to 1 with HCl (1 M). The resulting mixture was extracted with DCM (5 mL×3), dried over anhydrous sodium sulfate, filtered and concentrated. The resulting residue was purified by reverse phase Combiflash (20%-50% CH3CN/H2O in 0.1% NH4HCO3) to afford the target compound (15 mg, 5%) as a white solid. LCMS (ESI) Method A: RT=6.10 min, m/z: 537.2 [M+H]+. 1H-NMR (500 MHz, MeOD-d4,): δ 7.40-7.42 (m, 4H), 7.15-7.30 (m, 7H), 6.67 (d, J=13 Hz, 1H), 4.30 (s, 1H), 3.87 (d, J=6 Hz, 2H), 2.82 (s, 3H), 1.73-1.98 (m, 7H), 1.37-1.40 (m, 3H), 0.83-0.86 (m, 2H), 0.50-0.53 (m, 2H).

Workup

  1. customThe reaction was quenched with water (5 mL)
  2. extractionThe resulting mixture was extracted with DCM (5 mL×3)
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe resulting residue was purified by reverse phase Combiflash (20%-50% CH3CN/H2O in 0.1% NH4HCO3)

Sources & evidence

ORD record
ord-650f49a2cc6c40e19115f0baa760b6de
Source dataset
uspto-grants-2015_02
Patent number
US08952169B2

Reaction notes

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