1,2-Dichloroethane → 2-methyl-N-(methylsulfonyl)-6-(4-morpholinyl)-1-(1-naphthalenylmethyl)-1H-benzimidazole-4-carboxamide

HRID 44520Notes

Reaction equation

HRID 44520 reaction equation
[CH3:1][C:2]1[N:6]([CH2:7][C:8]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[CH:11]=[CH:10][CH:9]=2)[C:5]2[CH:18]=[C:19]([N:25]3[CH2:30][CH2:29][O:28][CH2:27][CH2:26]3)[CH:20]=[C:21]([C:22]([OH:24])=O)[C:4]=2[N:3]=1.C(Cl)CCl.[CH3:35][S:36]([NH2:39])(=[O:38])=[O:37]>CN(C)C=O.CN(C1C=CN=CC=1)C>[CH3:1][C:2]1[N:6]([CH2:7][C:8]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[CH:11]=[CH:10][CH:9]=2)[C:5]2[CH:18]=[C:19]([N:25]3[CH2:30][CH2:29][O:28][CH2:27][CH2:26]3)[CH:20]=[C:21]([C:22]([NH:39][S:36]([CH3:35])(=[O:38])=[O:37])=[O:24])[C:4]=2[N:3]=1

Participants

6

Reactant 3

HCID 111,2-DichloroethaneHCID 72879MethanesulfonamideHCID 569595312-methyl-6-(4-morpholinyl)-1-(1-naphthalenylmethyl)-1H-benzimidazole-4-carboxylic acid

Product 1

HCID 569601262-methyl-N-(methylsulfonyl)-6-(4-morpholinyl)-1-(1-naphthalenylmethyl)-1H-benzimidazole-4-carboxamideYield 39%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent2×

Conditions

Temperature
60 °C

Procedure

To the mixture of 2-methyl-6-(4-morpholinyl)-1-(1-naphthalenylmethyl)-1H-benzimidazole-4-carboxylic acid, prepared as described in Example 20 (100 mg, 0.249 mmol) in N,N-Dimethylformamide (DMF) (2 mL) in a 20 mL vial was added EDC (57.3 mg, 0.299 mmol), methane sulfonamide (47.4 mg, 0.498 mmol) and DMAP (21.30 mg, 0.174 mmol). The mixture was stirred at 60° C. and monitored by LC/MS. After stirring for 5 days the DMF was removed in-vacuo and the remaining residue was dissolved in 2 mL of DMSO and purified by reverse phase chromatography with 2 injections eluting with a 27% to 57% AcCN/H2O gradient over 12 minutes. The fractions containing the desired compound, as determined by LC/MS, were combined and concentrated in-vacuo to provide the desired compound (47 mg, 0.097 mmol, 39.0% yield) as bright yellow solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 2.52 (s, 3H), 3.12 (t, 4H), 3.50 (s, 3H), 3.73 (t, 4H), 6.15 (s, 2H), 6.38 (d, 1H), 7.35 (t, aH), 7.50 (s. 1H), 7.51-7.75 (m, 2H), 7.88 (d, 1H), 8.05 (d, 1H), 8.25 (2, 1H), 8.35 (s, 1H), 12.8 (br. s, 1H); LC-MS: m/e=480 [M+1]+

Workup

  1. customprepared
  2. customwas removed in-vacuo
  3. dissolutionthe remaining residue was dissolved in 2 mL of DMSO
  4. custompurified by reverse phase chromatography with 2 injections
  5. washeluting with a 27% to 57% AcCN/H2O gradient over 12 minutes
  6. additionThe fractions containing the desired compound
  7. concentrationconcentrated in-vacuo

Sources & evidence

ORD record
ord-f6615d73345349e8b76653d8ba858752
Source dataset
uspto-grants-2013_09
Patent number
US08541411B2

Reaction notes

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