Dicyclohexylcarbodiimide → 4-(2-(4-methoxy-2-(trifluoromethyl)phenyl)acetamido)-N-(4-(5-(4'-methyl-[1,1'-biphenyl]-4-yl)-1,2,4-oxadiazol-3-yl)benzyl)-N-(2-(methylsulfonamido)-2-oxoethyl)benzamide

HRID 923616Notes

Reaction equation

HRID 923616 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([CH2:9][C:10]([NH:12][C:13]2[CH:50]=[CH:49][C:16]([C:17]([N:19]([CH2:45][C:46](O)=[O:47])[CH2:20][C:21]3[CH:26]=[CH:25][C:24]([C:27]4[N:31]=[C:30]([C:32]5[CH:37]=[CH:36][C:35]([C:38]6[CH:43]=[CH:42][C:41]([CH3:44])=[CH:40][CH:39]=6)=[CH:34][CH:33]=5)[O:29][N:28]=4)=[CH:23][CH:22]=3)=[O:18])=[CH:15][CH:14]=2)=[O:11])=[C:5]([C:51]([F:54])([F:53])[F:52])[CH:4]=1.[CH3:55][S:56]([NH2:59])(=[O:58])=[O:57].C1(N=C=NC2CCCCC2)CCCCC1>C(Cl)Cl>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([CH2:9][C:10]([NH:12][C:13]2[CH:14]=[CH:15][C:16]([C:17]([N:19]([CH2:20][C:21]3[CH:22]=[CH:23][C:24]([C:27]4[N:31]=[C:30]([C:32]5[CH:37]=[CH:36][C:35]([C:38]6[CH:39]=[CH:40][C:41]([CH3:44])=[CH:42][CH:43]=6)=[CH:34][CH:33]=5)[O:29][N:28]=4)=[CH:25][CH:26]=3)[CH2:45][C:46]([NH:59][S:56]([CH3:55])(=[O:58])=[O:57])=[O:47])=[O:18])=[CH:49][CH:50]=2)=[O:11])=[C:5]([C:51]([F:53])([F:54])[F:52])[CH:4]=1

Participants

5

Reactant 3

HCID 10868DicyclohexylcarbodiimideHCID 72879MethanesulfonamideHCID 711116302-(4-(2-(4-methoxy-2-(trifluoromethyl)phenyl)acetamido)-N-(4-(5-(4'-methyl-[1,1'-biphenyl]-4-yl)-1,2,4-oxadiazol-3-yl)benzyl)benzamido)acetic acid

Product 1

HCID 710781694-(2-(4-methoxy-2-(trifluoromethyl)phenyl)acetamido)-N-(4-(5-(4'-methyl-[1,1'-biphenyl]-4-yl)-1,2,4-oxadiazol-3-yl)benzyl)-N-(2-(methylsulfonamido)-2-oxoethyl)benzamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a stirred solution of 2-(4-(2-(4-methoxy-2-(trifluoromethyl)phenyl)acetamido)-N-(4-(5-(4′-methyl-[1,1′-biphenyl]-4-yl)-1,2,4-oxadiazol-3-yl)benzyl)benzamido)acetic acid 354 (15 mg, 0.02 mmol), methanesulfonamide (2.9 mg, 0.03 mmol) and N,N-dimethylaminopyridine (5 mg, 0.04 mmol) in anhydrous DCM (1 mL) was added dicylcohexylcarbodiimide (6.3 mg). The reaction mixture was stirred at room temperature for 12 h. The reaction was diluted with DCM (2 mL) and washed with saturated NaHCO3 solution (5 mL), brine (5 mL), dried over (MgSO4) then concentrated. The crude product was isolated by HPLC to afford 4-(2-(4-methoxy-2-(trifluoromethyl)phenyl)acetamido)-N-(4-(5-(4′-methyl-[1,1′-biphenyl]-4-yl)-1,2,4-oxadiazol-3-yl)benzyl)-N-(2-(methylsulfonamido)-2-oxoethyl)benzamide 493. LCMS-ESI (m/z) calculated for C42H36F3N5O7S: 812; no ion observed, tR=11.03 min (Method 2).

Workup

  1. washwashed with saturated NaHCO3 solution (5 mL), brine (5 mL)
  2. dry with materialdried over (MgSO4)
  3. concentrationthen concentrated
  4. customThe crude product was isolated by HPLC

Sources & evidence

ORD record
ord-ed6390369aa744628d65ecd02ab470e3
Source dataset
uspto-grants-2016_03
Patent number
US09278910B2

Reaction notes

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