TFA dichloromethane water → HCID 59262912, compound

HRID 908340Notes

Reaction equation

HRID 908340 reaction equation
C([O:5][C:6]([C:8]1[S:31][C:11]2=[CH:12][CH:13]=[C:14]3[C:19]([N:18]=[C:17]([NH:20][C:21]4[CH:26]=[CH:25][CH:24]=[C:23]([S:27](=[O:30])(=[O:29])[NH2:28])[CH:22]=4)[N:16]=[CH:15]3)=[C:10]2[CH:9]=1)=[O:7])(C)(C)C.C(O)(C(F)(F)F)=O.ClCCl.O>>[S:27]([C:23]1[CH:22]=[C:21]([NH:20][C:17]2[N:16]=[CH:15][C:14]3[C:19](=[C:10]4[CH:9]=[C:8]([C:6]([OH:7])=[O:5])[S:31][C:11]4=[CH:12][CH:13]=3)[N:18]=2)[CH:26]=[CH:25][CH:24]=1)(=[O:30])(=[O:29])[NH2:28]

Participants

3

Reactant 2

HCID 18672661TFA dichloromethane waterHCID 592628832-(3-Sulfamoyl-phenylamino)-thieno[2,3-h]quinazoline-8-carboxylic acid tert-butyl ester

Product 1

HCID 59262912HCID 59262912, compoundYield 89.5%

Procedure

2-(3-Sulfamoyl-phenylamino)-thieno[2,3-h]quinazoline-8-carboxylic acid tert-butyl ester (1.84 g, 4.02 mmol) was placed in a 100 mL florentine and cooled in an ice-bath. Premixed TFA/dichloromethane/water (1:4:0.1, 9 mL TFA) was added in one portion and the resultant suspension was stirred at 0° C. for 10 minutes. After a further 2.5 hours at room temperature and 1.5 hours at 40° C. the reaction was concentrated under reduced pressure. The solid obtained was azeotroped with dry dichloromethane (3×10 mL), triturated with diethyl ether and isolated by filtration. The solid obtained was washed with diethyl ether (4×5 mL) and dried in a drying pistol at 40° C. overnight to afford the title compound as a yellow powder (1.44 g, 86% yield containing 1.24 eq. TFA). MS (ES+) 400. δH (d6 DMSO) 7.2-7.4 (2H, br s), 7.5 (1H, m), 7.6 (1H, m), 8.0 (3H, m), 8.7 (1H, s), 8.8-8.9 (1H, s), 9.4 (1H, s), 10.4-10.5 (1H, s), 13.4-13.8 (1H, br s).

Workup

  1. temperaturecooled in an ice-bath
  2. concentration1.5 hours at 40° C. the reaction was concentrated under reduced pressure
  3. customThe solid obtained
  4. customwas azeotroped with dry dichloromethane (3×10 mL)
  5. customtriturated with diethyl ether
  6. customisolated by filtration
  7. customThe solid obtained
  8. washwas washed with diethyl ether (4×5 mL)
  9. customdried in a drying pistol at 40° C. overnight

Sources & evidence

ORD record
ord-65e4676ef06646d0ad741d5599454da9
Source dataset
uspto-grants-2011_09
Patent number
US08017619B2

Reaction notes

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