Methanesulfonamide → 2,5-dimethyl-N-[(1S)-1-(4-{[(methylsulfonyl)amino]carbonyl}phenyl)ethyl]-4-[4-(trifluoromethyl)benzyl]thiophene-3-carboxamide

HRID 870069Notes

Reaction equation

HRID 870069 reaction equation
[CH3:1][C:2]1[S:3][C:4]([CH3:32])=[C:5]([CH2:21][C:22]2[CH:27]=[CH:26][C:25]([C:28]([F:31])([F:30])[F:29])=[CH:24][CH:23]=2)[C:6]=1[C:7]([NH:9][C@H:10]([C:12]1[CH:20]=[CH:19][C:15]([C:16]([OH:18])=O)=[CH:14][CH:13]=1)[CH3:11])=[O:8].[CH3:33][S:34]([NH2:37])(=[O:36])=[O:35].Cl.CN(C)CCCN=C=NCC>C1COCC1.CN(C=O)C.CN(C)C1C=CN=CC=1>[CH3:1][C:2]1[S:3][C:4]([CH3:32])=[C:5]([CH2:21][C:22]2[CH:23]=[CH:24][C:25]([C:28]([F:30])([F:31])[F:29])=[CH:26][CH:27]=2)[C:6]=1[C:7]([NH:9][C@H:10]([C:12]1[CH:20]=[CH:19][C:15]([C:16]([NH:37][S:34]([CH3:33])(=[O:36])=[O:35])=[O:18])=[CH:14][CH:13]=1)[CH3:11])=[O:8]

Participants

7

Reactant 3

HCID 72879MethanesulfonamideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 249529274-{(1S)-1-[({2,5-dimethyl-4-[4-(trifluoromethyl)benzyl]-3-thienyl}carbonyl)amino]ethyl}benzoic acid

Product 1

HCID 249532812,5-dimethyl-N-[(1S)-1-(4-{[(methylsulfonyl)amino]carbonyl}phenyl)ethyl]-4-[4-(trifluoromethyl)benzyl]thiophene-3-carboxamide

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 4-{(1S)-1-[({2,5-dimethyl-4-[4-(trifluoromethyl)benzyl]-3-thienyl}carbonyl)amino]ethyl}benzoic acid from Example 12 (200 mg, 0.433 mmol) in a mixture of THF (5 mL) and DMF (2.5 mL), were successively added methanesulfonamide (52.0 mg, 0.542 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (166 mg, 0.866 mmol) and 4-dimethylaminopyridine (66.0 mg, 0.542 mmol). The mixture was stirred overnight at r.t. and quenched with acetic acid. After 10 min., the mixture was diluted with water and partitioned between 1N HCl and EtOAc. The organic layer was washed with 1N HCl (2×) and brine, dried and concentrated. The residue was purified by Combi Flash chromatography system (50% THF/CHCl3 in 13 min.) to afford the desired product as a white solid. MS (−APCI): m/z 537 (M−1)−.

Workup

  1. customquenched with acetic acid
  2. waitAfter 10 min.
  3. additionthe mixture was diluted with water
  4. custompartitioned between 1N HCl and EtOAc
  5. washThe organic layer was washed with 1N HCl (2×) and brine
  6. customdried
  7. concentrationconcentrated
  8. customThe residue was purified by Combi Flash chromatography system (50% THF/CHCl3 in 13 min.)

Sources & evidence

ORD record
ord-46743e004de1422eb1d64cf649dcf2cb
Source dataset
uspto-grants-2015_03
Patent number
US08969394B2

Reaction notes

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