4,5-Dichlorothiophene-2-sulfonyl chloride → 4,5-dichloro-N-{3-[4-hydroxy-1-(3-methylbutyl)-2-oxo-1,2-dihydro-1,8-naphthyridin-3-yl]-1,1-dioxido-4H-1,2,4-benzothiadiazin-7-yl}thiophene-2-sulfonamide

HRID 601378Notes

Reaction equation

HRID 601378 reaction equation
[NH2:1][C:2]1[CH:30]=[CH:29][C:5]2[NH:6][C:7]([C:12]3[C:13](=[O:28])[N:14]([CH2:23][CH2:24][CH:25]([CH3:27])[CH3:26])[C:15]4[C:20]([C:21]=3[OH:22])=[CH:19][CH:18]=[CH:17][N:16]=4)=[N:8][S:9](=[O:11])(=[O:10])[C:4]=2[CH:3]=1.[Cl:31][C:32]1[S:33][C:34]([S:38](Cl)(=[O:40])=[O:39])=[CH:35][C:36]=1[Cl:37]>N1C=CC=CC=1.C(OCC)(=O)C>[Cl:37][C:36]1[CH:35]=[C:34]([S:38]([NH:1][C:2]2[CH:30]=[CH:29][C:5]3[NH:6][C:7]([C:12]4[C:13](=[O:28])[N:14]([CH2:23][CH2:24][CH:25]([CH3:27])[CH3:26])[C:15]5[C:20]([C:21]=4[OH:22])=[CH:19][CH:18]=[CH:17][N:16]=5)=[N:8][S:9](=[O:11])(=[O:10])[C:4]=3[CH:3]=2)(=[O:40])=[O:39])[S:33][C:32]=1[Cl:31]

Participants

5

Reactant 2

HCID 5186224,5-Dichlorothiophene-2-sulfonyl chlorideHCID 1354307103-(7-Amino-1,1-dioxido-4H-1,2,4-benzothiadiazin-3-yl)-4-hydroxy-1-(3-methylbutyl)-1,8-naphthyridin-2(1H)-one

Product 1

HCID 1363585024,5-dichloro-N-{3-[4-hydroxy-1-(3-methylbutyl)-2-oxo-1,2-dihydro-1,8-naphthyridin-3-yl]-1,1-dioxido-4H-1,2,4-benzothiadiazin-7-yl}thiophene-2-sulfonamideYield 50%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

To the product of Example 205 (0.020 g, 0.047 mmol) in pyridine (0.2 mL) was added 2,3-dichlorothiophene-5-sulfonyl chloride (0.015 g, 0.056 mmol). The reaction mixture was heated in a microwave reactor at 100° C. for 15 minutes. The reaction was diluted with ethyl acetate (40 mL), washed with 1 N hydrochloric acid, water, and brine. The organic layer was dried over magnesium sulfate, filtered and concentrated. The residue was chromatographed on silica gel eluting with 99:1 dichloromethane:methanol to give the title compound (14.8 mg, 50%). 1H NMR (300 MHz, DMSO-d6) δ 0.98 (d, J=6.25 Hz, 6 H) 1.56 (m, 2 H) 1.69 (m, 1 H) 4.47 (m, 2 H) 7.50 (m, 2 H) 7.56 (s, 1 H) 7.71 (d, J=8.82 Hz, 1 H) 7.76 (s, 1 H) 8.55 (dd, J=7.91, 2.02 Hz, 1 H) 8.88 (dd, J=4.60, 1.65 Hz, 1 H) 11.28 (s, 1 H) 14.19 (br s, 1 H). MS (ESI−) m/z 640 (M−H)−.

Workup

  1. washwashed with 1 N hydrochloric acid, water, and brine
  2. dry with materialThe organic layer was dried over magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue was chromatographed on silica gel eluting with 99:1 dichloromethane

Sources & evidence

ORD record
ord-b4b8aa4c150642789de4229da30d533e
Source dataset
uspto-grants-2011_03
Patent number
US07902203B2

Reaction notes

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