Sodium Carbonate → HCID 58998394, compound

HRID 1593079Notes

Reaction equation

HRID 1593079 reaction equation
[F:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][N:8]([C:13]3[CH:18]=[CH:17][C:16]([N+:19]([O-])=O)=[CH:15][CH:14]=3)[C:9]2=[O:12])=[CH:4][C:3]=1[NH:22][CH3:23].[Cl:24]N1C(=O)CCC1=O.[Sn](Cl)Cl.C(=O)([O-])[O-].[Na+].[Na+].C([O:43][C:44](=O)[NH:45][S:46]([C:49]1[S:50][C:51]([Cl:54])=[CH:52][CH:53]=1)(=[O:48])=[O:47])C>CN(C=O)C.C1(C)C=CC=CC=1>[Cl:54][C:51]1[S:50][C:49]([S:46]([NH:45][C:44]([NH:19][C:16]2[CH:17]=[CH:18][C:13]([N:8]3[CH:7]=[CH:6][C:5]4[C:10](=[CH:11][C:2]([F:1])=[C:3]([NH:22][CH3:23])[C:4]=4[Cl:24])[C:9]3=[O:12])=[CH:14][CH:15]=2)=[O:43])(=[O:48])=[O:47])=[CH:53][CH:52]=1

Participants

8

Reactant 5

HCID 10340Sodium CarbonateHCID 24479Stannous ChlorideHCID 31398ChlorosuccinimideHCID 24778122Ethyl ((5-chlorothiophen-2-yl)sulfonyl)carbamateHCID 58998407HCID 58998407, compound

Product 1

HCID 58998394HCID 58998394, compoundYield 6.4%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To a mixture of 7-Fluoro-6-methylamino-2-(4-nitro-phenyl)-2H-isoquinolin-1-one (100 mg, 0.27 mmol) (Example 104) in DMF (3 mL) was added N-chlorosuccinimide (76 mg, 0.57 mmol). After 18 hours all starting material was consumed. Tin dichloride dehydrate 244 mg (0.11 mmol) was added to the reaction mixture, and the reaction was heated to 80° C. for 2 hr. Upon cooling the reaction mixture was treated with 1 mL of 10% sodium carbonate and extracted 3 times with EtOAc. The combined organic layers were dried over Na2SO4 anhydrous and concentrated in vacuo to give a mixture of the 5-Cl and 4,5-dichloro anilines. This mixture was coupled directly with 76 mg (0.28 mmol) of (5-Chloro-thiophene-2-sulfonyl)-carbamic acid ethyl ester (Example 12) in toluene (0.54 mL) and refluxed for 4 h. The resulting mixture of monochloro and dichloro sulfonylureas were separated by preparative RP-HPLC to give 9.4 mg (6% yield overall) of 5-chloro-N-[({4-[5-chloro-7-fluoro-6-(methylamino)-1-oxoisoquinolin-2(1H)-yl]phenyl}amino)carbonyl]thiophene-2-sulfonamide. ES-MS (M+H)+=541.3 (2Cl).

Workup

  1. customAfter 18 hours all starting material was consumed
  2. temperatureUpon cooling the reaction mixture
  3. extractionextracted 3 times with EtOAc
  4. dry with materialThe combined organic layers were dried over Na2SO4 anhydrous
  5. concentrationconcentrated in vacuo
  6. customto give
  7. temperaturerefluxed for 4 h
  8. customwere separated by preparative RP-HPLC

Sources & evidence

ORD record
ord-a183d1bfa4974727b098b84b29d4435a
Source dataset
uspto-grants-2007_11
Patent number
US07294635B2

Reaction notes

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