Cesium carbonate → 2-({3-[1-(cyclopentylamino)-4-hydroxy-2-oxo-1,2-dihydroquinolin-3-yl]-1,1-dioxido-4H-1,2,4-benzothiadiazin-7-yl}oxy)acetamide

HRID 601286Notes

Reaction equation

HRID 601286 reaction equation
[CH:1]1([NH:6][N:7]2[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[C:10]([OH:17])=[C:9]([C:18]3[NH:23][C:22]4[CH:24]=[CH:25][C:26]([OH:28])=[CH:27][C:21]=4[S:20](=[O:30])(=[O:29])[N:19]=3)[C:8]2=[O:31])[CH2:5][CH2:4][CH2:3][CH2:2]1.C(=O)([O-])[O-].[Cs+].[Cs+].Br[CH2:39][C:40]([NH2:42])=[O:41]>[I-].C([N+](CCCC)(CCCC)CCCC)CCC.CN(C)C=O>[CH:1]1([NH:6][N:7]2[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[C:10]([OH:17])=[C:9]([C:18]3[NH:23][C:22]4[CH:24]=[CH:25][C:26]([O:28][CH2:39][C:40]([NH2:42])=[O:41])=[CH:27][C:21]=4[S:20](=[O:29])(=[O:30])[N:19]=3)[C:8]2=[O:31])[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 696322-BromoacetamideHCID 1363741821-(cyclopentylamino)-4-hydroxy-3-(7-hydroxy-1,1-dioxido-4H-1,2,4-benzothiadiazin-3-yl)quinolin-2(1H)-one

Product 1

HCID 1363736512-({3-[1-(cyclopentylamino)-4-hydroxy-2-oxo-1,2-dihydroquinolin-3-yl]-1,1-dioxido-4H-1,2,4-benzothiadiazin-7-yl}oxy)acetamideYield 85%

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
165 °C

Procedure

The product of Example 305C (0.10 g, 0.23 mmol) was reacted with cesium carbonate (0.30 g, 0.92 mmol), 2-bromoacetamide (0.050 g, 0.37 mmol) and a catalytic amount of tetrabuylammonium iodide in N,N-dimethylformamide (5 mL) at 25° C. for 2 hours. The reaction was concentrated to half the volume under a stream of nitrogen warmed through a manifold heated to 165° C. The resulting solution was diluted with water and the precipitate was collected by filtration and dried to give the title compound (0.095 g, 85%). MS (ESI−) m/z 496 (M−H)−. The sodium salt of the title compound was prepared according to the procedure of Example 1D. 1H NMR (500 MHz, DMSO-d6) δ ppm 1.52 (m, 6 H) 1.76 (m, 2 H) 3.70 (m, 1 H) 4.47 (s, 2 H) 5.68 (d, J=4.88 Hz, 1 H) 7.03 (t, J=7.63 Hz, 1 H) 7.20 (m, 5 H) 7.46 (t, J=7.32 Hz, 1 H) 7.70 (d, J=8.54 Hz, 1 H) 8.06 (d, J=7.32 Hz, 1 H) 16.15 (s, 1 H).

Workup

  1. concentrationThe reaction was concentrated to half the volume under a stream of nitrogen
  2. temperaturewarmed through a manifold
  3. additionThe resulting solution was diluted with water
  4. filtrationthe precipitate was collected by filtration
  5. customdried

Sources & evidence

ORD record
ord-792105f2ce42484ba1028e49373e1b10
Source dataset
uspto-grants-2011_03
Patent number
US07902203B2

Reaction notes

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