Hydrochloric Acid → N-[2-({1-[6-(methyloxy)-1,5-naphthyridin-4-yl]-3-pyrrolidinyl}thio)ethyl]-3-oxo-3,4-dihydro-2H-1,4-benzothiazine-6-sulfonamide

HRID 1992527Notes

Reaction equation

HRID 1992527 reaction equation
Cl.[CH3:2][O:3][C:4]1[N:5]=[C:6]2[C:11](=[CH:12][CH:13]=1)[N:10]=[CH:9][CH:8]=[C:7]2[N:14]1[CH2:18][CH2:17][CH:16]([S:19][CH2:20][CH2:21][NH2:22])[CH2:15]1.C(N(CC)CC)C.[O:30]=[C:31]1[NH:36][C:35]2[CH:37]=[C:38]([S:41](Cl)(=[O:43])=[O:42])[CH:39]=[CH:40][C:34]=2[S:33][CH2:32]1.C(=O)(O)[O-].[Na+]>C(Cl)Cl.CO.C(Cl)(Cl)Cl>[CH3:2][O:3][C:4]1[N:5]=[C:6]2[C:11](=[CH:12][CH:13]=1)[N:10]=[CH:9][CH:8]=[C:7]2[N:14]1[CH2:18][CH2:17][CH:16]([S:19][CH2:20][CH2:21][NH:22][S:41]([C:38]2[CH:39]=[CH:40][C:34]3[S:33][CH2:32][C:31](=[O:30])[NH:36][C:35]=3[CH:37]=2)(=[O:43])=[O:42])[CH2:15]1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 218737563-oxo-3,4-dihydro-2H-1,4-benzothiazine-6-sulfonyl chlorideHCID 58955135[2-({1-[6-(Methyloxy)-1,5-naphthyridin-4-yl]-3-pyrrolidinyl}thio)ethyl]amine

Product 1

HCID 11713493N-[2-({1-[6-(methyloxy)-1,5-naphthyridin-4-yl]-3-pyrrolidinyl}thio)ethyl]-3-oxo-3,4-dihydro-2H-1,4-benzothiazine-6-sulfonamideYield 61.2%

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 21226129Dichloromethane methanolSolvent

Conditions

Temperature
25 °C

Procedure

To the solution of HCl salt of [2-({1-[6-(methyloxy)-1,5-naphthyridin-4-yl]-3-pyrrolidinyl}thio)ethyl]amine (from Example 7b) (420 mg, 1.23 mmol) in DCM/MeOH (15 mL, 1:1) with triethylamine (0.86 mL, 6.1 mmol) was added 3-oxo-3,4-dihydro-2H-1,4-benzothiazine-6-sulfonyl chloride (388 mg, 1.48 mmol). After stirring at 25° C. for 12 h, the reaction mixture was diluted with chloroform and poured into saturated aqueous sodium bicarbonate solution. The aqueous layer was extracted with chloroform, and the combined organic layers were washed with brine, dried over magnesium sulfate, concentrated and purified by column chromatography (silica, 0-10% MeOH in CDCl3 (1% NH4OH) to afford the title compound as a white solid (400 mg, 61%): LC/MS m/z 532 (M+H)+; 1H NMR (CDCl3, 400 MHz) δ 9.05. (br, 1H), 8.34 (d, J=5.8 Hz, 1H), 8.23 (d, J=9.0 Hz, 1H), 7.57 (s, 1H), 7.55 (d, J=7.4 Hz, 1H), 7.48 (d, J=8.1 Hz, 1H), 7.07 (d, J=9.0 Hz, 1H), 6.45 (d, J=5.9 Hz, 1H), 6.2 (br, 1H), 4.38-4.43 (m, 1H), 3.93-4.18 (m, 6H), 3.52-3.61 (m, 1H), 3.47 (s, 2H), 3.22-3.28 (m, 2H), 2.82-02.87 (m, 2H), 2.4-2.47 (m, 1H), 1.99-2.08 (m, 1H).

Workup

  1. extractionThe aqueous layer was extracted with chloroform
  2. washthe combined organic layers were washed with brine
  3. dry with materialdried over magnesium sulfate
  4. concentrationconcentrated
  5. custompurified by column chromatography (silica, 0-10% MeOH in CDCl3 (1% NH4OH)

Sources & evidence

ORD record
ord-4c0bf1c52e684d9bb68a29c3aa092b20
Source dataset
uspto-grants-2010_01
Patent number
US07648984B2

Reaction notes

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