Cesium carbonate → 4-hydroxy-1-(isobutylamino)-3-{7-[(3-nitropyridin-2-yl)oxy]-1,1-dioxido-4H-1,2,4-benzothiadiazin-3-yl}quinolin-2(1H)-one

HRID 601374Notes

Reaction equation

HRID 601374 reaction equation
[OH:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]([NH:12][CH2:13][CH:14]([CH3:16])[CH3:15])[C:4](=[O:17])[C:3]=1[C:18]1[NH:23][C:22]2[CH:24]=[CH:25][C:26]([OH:28])=[CH:27][C:21]=2[S:20](=[O:30])(=[O:29])[N:19]=1.C(=O)([O-])[O-].[Cs+].[Cs+].Br[C:38]1[C:43]([N+:44]([O-:46])=[O:45])=[CH:42][CH:41]=[CH:40][N:39]=1>CS(C)=O>[OH:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]([NH:12][CH2:13][CH:14]([CH3:15])[CH3:16])[C:4](=[O:17])[C:3]=1[C:18]1[NH:23][C:22]2[CH:24]=[CH:25][C:26]([O:28][C:38]3[C:43]([N+:44]([O-:46])=[O:45])=[CH:42][CH:41]=[CH:40][N:39]=3)=[CH:27][C:21]=2[S:20](=[O:29])(=[O:30])[N:19]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 5550542-Bromo-3-nitropyridineHCID 1363584044-hydroxy-3-(7-hydroxy-1,1-dioxido-4H-1,2,4-benzothiadiazin-3-yl)-1-(isobutylamino)quinolin-2(1H)-one

Product 1

HCID 1363473564-hydroxy-1-(isobutylamino)-3-{7-[(3-nitropyridin-2-yl)oxy]-1,1-dioxido-4H-1,2,4-benzothiadiazin-3-yl}quinolin-2(1H)-oneYield 78.1%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
110 °C

Procedure

A mixture the product of Example 321C (10.0 mg, 0.02 mmol), cesium carbonate (27.7 mg, 0.09 mmol), and 2-bromo-3-nitropyridine (8.4 mg, 0.04 mmol) in dimethylsulfoxide (0.3 mL) was stirred while heating at 110° C. in a microwave reactor for 20 minutes. After cooling to 25° C., the mixture was partitioned between ethyl acetate and water. The aqueous layer was extracted with an additional portion of ethyl acetate. The combined organic layers were dried over sodium sulfate, filtered, concentrated under reduced pressure and purified by column chromatography on silica gel eluting with a 0-100% dichloromethane in hexane step gradient to give the title compound as a yellow solid (8.6 mg, 68%). MS (ESI−) m/z 549 (M−H)−. 1H NMR (300 MHz, CDCl3) δ 1.13 (d, J=6.62 Hz, 6 H) 2.00 (m, 1 H) 2.81 (m, 2 H) 5.73 (m, 1 H) 7.23 (m, 1 H) 7.40 (m, 2 H) 7.50 (dd, J=8.82, 2.57 Hz, 1 H) 7.82 (m, 2 H) 7.97 (m, 1 H) 8.27 (dd, J=8.09, 1.10 Hz, 1 H) 8.35 (dd, J=4.78, 1.84 Hz, 1 H) 8.42 (dd, J=8.09, 1.84 Hz, 1 H) 14.39 (s, 1 H) 15.02 (s, 1 H).

Workup

  1. temperatureAfter cooling to 25° C.
  2. customthe mixture was partitioned between ethyl acetate and water
  3. extractionThe aqueous layer was extracted with an additional portion of ethyl acetate
  4. dry with materialThe combined organic layers were dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. custompurified by column chromatography on silica gel eluting with a 0-100% dichloromethane in hexane step gradient

Sources & evidence

ORD record
ord-2e64e722bb034b759a32345bed452f69
Source dataset
uspto-grants-2011_03
Patent number
US07902203B2

Reaction notes

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