Sodium Methoxide → 3-Amino-4-(4-chlorophenyl)-N-(5-(cyclopropylcarbamoyl)-2-methylphenyl)thiophene-2-carboxamide

HRID 1951273Notes

Reaction equation

HRID 1951273 reaction equation
C[O-].[Na+].[CH:4]1([NH:7][C:8](=[O:21])[C:9]2[CH:14]=[CH:13][C:12]([CH3:15])=[C:11]([NH:16][C:17](=[O:20])[CH2:18][SH:19])[CH:10]=2)[CH2:6][CH2:5]1.C1(S(O[CH:32]=[C:33]([C:36]2[CH:41]=[CH:40][C:39]([Cl:42])=[CH:38][CH:37]=2)[C:34]#[N:35])(=O)=O)C=CC=CC=1>CO>[NH2:35][C:34]1[C:33]([C:36]2[CH:37]=[CH:38][C:39]([Cl:42])=[CH:40][CH:41]=2)=[CH:32][S:19][C:18]=1[C:17]([NH:16][C:11]1[CH:10]=[C:9]([C:8](=[O:21])[NH:7][CH:4]2[CH2:6][CH2:5]2)[CH:14]=[CH:13][C:12]=1[CH3:15])=[O:20]

Participants

5

Reactant 3

HCID 10942334Sodium MethoxideHCID 59761419N-Cyclopropyl-3-(2-mercaptoacetamido)-4-methylbenzamideHCID 866215342-(4-Chlorophenyl)-2-cyanovinyl benzenesulfonate

Product 1

HCID 597614253-Amino-4-(4-chlorophenyl)-N-(5-(cyclopropylcarbamoyl)-2-methylphenyl)thiophene-2-carboxamide

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

To MeOH (4 mL) at rt was added a 25% (w/w) solution of NaOMe in MeOH followed by addition of N-cyclopropyl-3-(2-mercaptoacetamido)-4-methylbenzamide a (200 mg, 10.8 mmol). After stirring at rt for 15 min, 200 mg (10.6 mmol) of 2-(4-chlorophenyl)-2-cyanovinyl benzenesulfonate (prepared as described in J. Med. Chem., 6(47):1448 (2004)) was added and the resulting solution was warmed to 60° C. for 2 h then allowed to cool to rt and stir for an additional 15 h. The mixture was concentrated under vacuum to remove the MeOH then water (20 mL) was added and the solution was extracted with EtOAc (200 mL). The organic extract was washed with water, brine, then dried over anhyd Na2SO4, filtered, and concentrated under vacuum to afford 300 mg of an orange solid as the crude product. This material was purified by reverse-phase preparative HPLC to afford 50 mg of a light yellow solid as the title compound (Example 209). HPLC Ret time=3.57 min. LCMS [M+H]+ 426.17.

Workup

  1. temperaturethe resulting solution was warmed to 60° C. for 2 h
  2. temperatureto cool to rt
  3. stirringstir for an additional 15 h
  4. concentrationThe mixture was concentrated under vacuum
  5. customto remove the MeOH
  6. additionwater (20 mL) was added
  7. extractionthe solution was extracted with EtOAc (200 mL)
  8. extractionThe organic extract
  9. washwas washed with water, brine
  10. dry with materialdried over anhyd Na2SO4
  11. filtrationfiltered
  12. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-9c80202afb1f432998bacc13ca254c7d
Source dataset
uspto-grants-2013_03
Patent number
US08404689B2

Reaction notes

Loading…