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

HRID 601283Notes

Reaction equation

HRID 601283 reaction equation
[CH:1]1([NH:5][N:6]2[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[C:9]([OH:16])=[C:8]([C:17]3[NH:22][C:21]4[CH:23]=[CH:24][C:25]([OH:27])=[CH:26][C:20]=4[S:19](=[O:29])(=[O:28])[N:18]=3)[C:7]2=[O:30])[CH2:4][CH2:3][CH2:2]1.C(=O)([O-])[O-].[Cs+].[Cs+].Br[CH2:38][C:39]([NH2:41])=[O:40]>CN(C)C=O.[I-].C([N+](CCCC)(CCCC)CCCC)CCC>[CH:1]1([NH:5][N:6]2[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[C:9]([OH:16])=[C:8]([C:17]3[NH:22][C:21]4[CH:23]=[CH:24][C:25]([O:27][CH2:38][C:39]([NH2:41])=[O:40])=[CH:26][C:20]=4[S:19](=[O:28])(=[O:29])[N:18]=3)[C:7]2=[O:30])[CH2:2][CH2:3][CH2:4]1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 696322-BromoacetamideHCID 1363741731-(cyclobutylamino)-4-hydroxy-3-(7-hydroxy-1,1-dioxido-4H-1,2,4-benzothiadiazin-3-yl)quinolin-2(1H)-one

Product 1

HCID 1354412162-({3-[1-(cyclobutylamino)-4-hydroxy-2-oxo-1,2-dihydroquinolin-3-yl]-1,1-dioxido-4H-1,2,4-benzothiadiazin-7-yl}oxy)acetamideYield 37.6%

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
165 °C

Procedure

The product of Example 304I (0.048 g, 0.11 mmol) in N,N-dimethylformamide (2 mL) was reacted with cesium carbonate (0.15 g, 0.45 mmol), bromoacetamide (0.026 mL, 0.18 mmol), and a catalytic amount of tetrabutylammonium iodide at 25° C. for 3 hours. The reaction was concentrated under a stream of nitrogen stream of nitrogen warmed through a manifold heated to 165° C. and the resulting residue was triturated with water, filtered and dried. The resulting solid was triturated in hot ethyl acetate, filtered, and dried to give the title compound (0.020 g, 37%). MS (ESI−) m/z 482 (M−H)−. 1H NMR (300 MHz, DMSO-d6) δ ppm 1.59 (m, 2 H) 1.99 (m, 4 H) 3.60 (m, 1 H) 4.49 (s, 2 H) 6.08 (d, J=6.62 Hz, 1 H) 7.05 (t, J=7.17 Hz, 1 H) 7.20 (m, 3 H) 7.40 (s, 1 H) 7.50 (m, 1 H) 7.65 (m, 2 H) 8.05 (d, J=7.72 Hz, 1 H) 16.25 (s, 1 H). The sodium salt of the title compound was prepared according to the procedure of Example 1D. 1H NMR (300 MHz, DMSO-d6) δ ppm 1.59 (m, 1 H) 1.99 (m, 4 H) 3.61 (m, 2 H) 4.49 (s, 2 H) 6.08 (d, J=6.62 Hz, 1 H) 7.05 (m, 1 H) 7.21 (m, 2 H) 7.40 (s, 2 H) 7.50 (m, 1 H) 7.64 (m, 2 H) 8.06 (dd, J=7.91, 1.29 Hz, 1 H) 8.32 (s, 1 H).

Workup

  1. concentrationThe reaction was concentrated under a stream of nitrogen stream of nitrogen
  2. temperaturewarmed through a manifold
  3. customthe resulting residue was triturated with water
  4. filtrationfiltered
  5. customdried
  6. customThe resulting solid was triturated in hot ethyl acetate
  7. filtrationfiltered
  8. customdried

Sources & evidence

ORD record
ord-83a5dfe7e4f04e2f82d6e9ee93652496
Source dataset
uspto-grants-2011_03
Patent number
US07902203B2

Reaction notes

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