Methanesulfonamide → HCID 68006725, compound

HRID 2401905Notes

Reaction equation

HRID 2401905 reaction equation
[C:1]([C:3]1[C:4]([CH2:17][C:18]2[CH:23]=[CH:22][C:21]([Cl:24])=[C:20]([Cl:25])[CH:19]=2)=[C:5]([C:14](O)=[O:15])[S:6][C:7]=1[N:8]1[CH2:13][CH2:12][O:11][CH2:10][CH2:9]1)#[N:2].[CH3:26][S:27]([NH2:30])(=[O:29])=[O:28].Cl.CN(C)CCCN=C=NCC>C(Cl)Cl.Cl.O>[C:1]([C:3]1[C:4]([CH2:17][C:18]2[CH:23]=[CH:22][C:21]([Cl:24])=[C:20]([Cl:25])[CH:19]=2)=[C:5]([C:14]([NH:30][S:27]([CH3:26])(=[O:29])=[O:28])=[O:15])[S:6][C:7]=1[N:8]1[CH2:13][CH2:12][O:11][CH2:10][CH2:9]1)#[N:2]

Participants

7

Reactant 3

HCID 72879MethanesulfonamideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 66747861HCID 66747861, compound

Product 1

HCID 68006725HCID 68006725, compoundYield 20.2%

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a mixture of 4-cyano-3-(3,4-dichlorobenzyl)-5-morpholinothiophene-2-carboxylic acid (291 mg, 0.732 mmol), in DCM (5.0 mL) was added methanesulfonamide (87.1 mg, 0.916 mmol), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (176 mg, 0.916 mmol), and N,N-dimethylaminopyridine (103 mg, 0.842 mmol) and the resulting solution was stirred at room temperature overnight. The reaction was diluted with DCM (10 mL), 1N HCl (3 mL) and with water (3 mL). The organic layer was dried, filtered and concentrated in vacuo. The residue was purified by silica gel chromatography (MeOH/DCM=0/100→20/80) to give 250 mg of crude product. This material was purified by preparative reverse phase chromatography to give 70 mg (20% yield) of the title compound as a white solid. LC/MS (FA) ES+ 474, 476. 1H NMR (400 MHz, MeOH-d4) δ: 7.45 (d, 1H, J=2.0 Hz)), 7.38 (d, 1H, J=8.4 Hz), 7.25 (dd, 1H, J=8.0, 2.0 Hz), 4.38 (s, 2H), 3.82-3.80 (m, 4H), 3.57-3.55 (m, 4H), 3.18 (s, 3H).

Workup

  1. customThe organic layer was dried
  2. filtrationfiltered
  3. concentrationconcentrated in vacuo
  4. customThe residue was purified by silica gel chromatography (MeOH/DCM=0/100→20/80)
  5. customto give 250 mg of crude product
  6. customThis material was purified by preparative reverse phase chromatography

Sources & evidence

ORD record
ord-25e99d2a21fb4e308fb1f89af29e76f2
Source dataset
uspto-grants-2014_08
Patent number
US08796268B2

Reaction notes

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