Methanesulfonamide → HCID 52933067, compound

HRID 1665251Notes

Reaction equation

HRID 1665251 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([F:9])=[CH:4][C:3]=1[C:10]1[CH:15]=[CH:14][C:13]([O:16][CH2:17][C:18]2[CH:19]=[C:20]([CH:29]=[CH:30][CH:31]=2)[C:21]([N:23]([CH2:25][C:26]([OH:28])=O)[CH3:24])=[O:22])=[CH:12][CH:11]=1.[CH3:32][S:33]([NH2:36])(=[O:35])=[O:34]>CN1C(=O)CCC1>[CH3:32][S:33]([NH:36][C:26](=[O:28])[CH2:25][N:23]([CH3:24])[C:21](=[O:22])[C:20]1[CH:29]=[CH:30][CH:31]=[C:18]([CH2:17][O:16][C:13]2[CH:14]=[CH:15][C:10]([C:3]3[CH:4]=[C:5]([F:9])[C:6]([F:8])=[CH:7][C:2]=3[F:1])=[CH:11][CH:12]=2)[CH:19]=1)(=[O:35])=[O:34]

Participants

4

Reactant 2

HCID 72879Methanesulfonamide2×HCID 52933304HCID 52933304, compound

Product 1

HCID 52933067HCID 52933067, compoundYield 38.6%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

1,1-Carbonyldiimidazole (671 mg, 4.14 mmol) was added to a stirred solution of {[3-(2′,4′,5′-trifluoro-biphenyl-4-yloxymethyl)-benzoyl]-methyl-amino}-acetic acid (1.1 g, 3.07 mmol) in 5 mL NMP in an ice bath under argon for 3 hrs. To this mixture was added methanesulfonamide (437 mg, 4.6 mmol) and 1,8-diazobicyclo[5.4.0]undec-7-ene (0.684 mL, 4.6 mmol). The reaction was stirred at RT overnight. An additional 0.5 equiv. each of 1,1-carbonyldiimidazole (335 mg, 2.07 mmol), methanesulfonamide (197 mg, 2.07 mmol) and 1,8-diazobicyclo[5.4.0]undec-7-ene (0.34 mL, 2.07 mmol) were added and let stir over the weekend. The reaction mixture was concentrated, dissolved in 250 mL ethyl acetate, washed with H2O and concentrated. The crude product was purified by flash chromatography with a 0-25% gradient of ethyl acetate/MeOH/AcOH (95:5:1) in CH2Cl2 and lyophilized to yield 153 mg (38.6%) of N-(2-methanesulfonylamino-2-oxo-ethyl)-N-methyl-3-(2′,4′,5′-trifluoro-biphenyl-4-yloxymethyl)-benzamide as an amorphous solid. LC-MS (ES) calculated for C24H21F2NO5S, 506.50; found m/z 507 [M+H]+.

Workup

  1. stirringlet stir over the weekend
  2. concentrationThe reaction mixture was concentrated
  3. dissolutiondissolved in 250 mL ethyl acetate
  4. washwashed with H2O
  5. concentrationconcentrated
  6. customThe crude product was purified by flash chromatography with a 0-25% gradient of ethyl acetate/MeOH/AcOH (95:5:1) in CH2Cl2

Sources & evidence

ORD record
ord-b3ddda68c9114fd3a34abfb59476eb12
Source dataset
uspto-grants-2011_10
Patent number
US08039495B2

Reaction notes

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