Potassium Carbonate → methyl 2-chloro-6-({3-[4-hydroxy-1-(isobutylamino)-2-oxo-1,2-dihydroquinolin-3-yl]-1,1-dioxido-4H-1,2,4-benzothiadiazin-7-yl}oxy)isonicotinate

HRID 601394Notes

Reaction equation

HRID 601394 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-].[K+].[K+].[Cl:37][C:38]1[CH:39]=[C:40]([CH:45]=[C:46](Cl)[N:47]=1)[C:41]([O:43][CH3:44])=[O:42]>N1C=CC=CC=1.[Cu]=O>[Cl:37][C:38]1[CH:39]=[C:40]([CH:45]=[C:46]([O:28][C:26]2[CH:25]=[CH:24][C:22]3[NH:23][C:18]([C:3]4[C:4](=[O:17])[N:5]([NH:12][CH2:13][CH:14]([CH3:15])[CH3:16])[C:6]5[C:11]([C:2]=4[OH:1])=[CH:10][CH:9]=[CH:8][CH:7]=5)=[N:19][S:20](=[O:29])(=[O:30])[C:21]=3[CH:27]=2)[N:47]=1)[C:41]([O:43][CH3:44])=[O:42]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 93237Methyl 2,6-dichloroisonicotinateHCID 1363584044-hydroxy-3-(7-hydroxy-1,1-dioxido-4H-1,2,4-benzothiadiazin-3-yl)-1-(isobutylamino)quinolin-2(1H)-one

Product 1

HCID 136358432methyl 2-chloro-6-({3-[4-hydroxy-1-(isobutylamino)-2-oxo-1,2-dihydroquinolin-3-yl]-1,1-dioxido-4H-1,2,4-benzothiadiazin-7-yl}oxy)isonicotinate

Reagents, catalysts & solvents 2

HCID 14829Copper oxideCatalystHCID 1049PyridineSolvent

Conditions

Temperature
125 °C

Procedure

A mixture of the product of Example 321C (40.0 mg, 0.138 mmol), potassium carbonate (19.1 mg, 0.138 mmol), copper(II)oxide (18.4 mg, 0.23 mmol)and methyl 2,6-dichloroisonicotinate (28.4 mg, 0.138 mmol) in pyridine (0.2 mL) was stirred while heating at 125° C. in a microwave reactor for 100 minutes. After cooling to 25° C., the mixture was loaded directly onto silica gel gel and eluted with a 0-5% methanol in dichloromethane step gradient. The fractions containing the desired product were combined and concentrated. The title compound was isolated by recrystallization of the residue using ethyl acetate/hexane (4.3 mg, 68%). MS (ESI−) m/z 596 (M−H)−. 1H NMR (300 MHz, CDCl3) δ 1.13 (d, J=6.62 Hz, 6H) 2.00 (m, 1 H) 2.84 (br m, 2 H) 3.99 (s, 3 H) 5.73 (br s, 1 H) 7.43 (m, 4 H) 7.62 (d, J=8.46 Hz, 1 H) 7.80 (m, 2 H) 7.96 (d, J=8.46 Hz, 1 H) 8.28 (d, J=8.09 Hz, 1 H) 14.37 (s, 1 H) 15.04 (s, 1 H).

Workup

  1. temperatureAfter cooling to 25° C.
  2. washeluted with a 0-5% methanol in dichloromethane step gradient
  3. additionThe fractions containing the desired product
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-6ff02e34031b44409850cb6ee6f35066
Source dataset
uspto-grants-2011_03
Patent number
US07902203B2

Reaction notes

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