Trifluoroacetic acid → 2-(3-Sulfamoyl-phenylamino)-thieno[2,3-h]quinazoline-8-carboxylic acid (2-amino-ethyl)-amide

HRID 908342Notes

Reaction equation

HRID 908342 reaction equation
C(OC(=O)[NH:7][CH2:8][CH2:9][NH:10][C:11]([C:13]1[S:36][C:16]2=[CH:17][CH:18]=[C:19]3[C:24]([N:23]=[C:22]([NH:25][C:26]4[CH:31]=[CH:30][CH:29]=[C:28]([S:32](=[O:35])(=[O:34])[NH2:33])[CH:27]=4)[N:21]=[CH:20]3)=[C:15]2[CH:14]=1)=[O:12])(C)(C)C.C(O)(C(F)(F)F)=O.ClCCl.O.C(O)(C(F)(F)F)=O>>[NH2:7][CH2:8][CH2:9][NH:10][C:11]([C:13]1[S:36][C:16]2=[CH:17][CH:18]=[C:19]3[C:24]([N:23]=[C:22]([NH:25][C:26]4[CH:31]=[CH:30][CH:29]=[C:28]([S:32](=[O:34])(=[O:35])[NH2:33])[CH:27]=4)[N:21]=[CH:20]3)=[C:15]2[CH:14]=1)=[O:12]

Participants

4

Reactant 3

HCID 6422Trifluoroacetic acidHCID 18672661TFA dichloromethane waterHCID 59262928(2-{[2-(3-Sulfamoyl-phenylamino)-thieno[2,3-h]quinazoline-8-carbonyl]amino}-ethyl)-carbamic acid tert-butyl ester

Product 1

HCID 592629422-(3-Sulfamoyl-phenylamino)-thieno[2,3-h]quinazoline-8-carboxylic acid (2-amino-ethyl)-amideYield 95%

Procedure

(2-{[2-(3-Sulfamoyl-phenylamino)-thieno[2,3-h]quinazoline-8-carbonyl]-amino}-ethyl)-carbamic acid tert-butyl ester (138.1 mg, 0.25 mmol) was placed in a 50 mL florentine and cooled in an ice-bath. Premixed TFA/dichloromethane/water (1:4:0.1, 0.5 mL TFA) was added in one portion and the resultant suspension was stirred at 0° C. for 35 minutes. After a further 1.75 hours at room temperature the solution was concentrated under reduced pressure to give a yellow solid. This solid was azeotroped with dichloromethane (3×10 mL), triturated with diethyl ether and isolated by filtration. The solid collected was washed with diethyl ether (3×5 mL) and pentane (3×5 mL) and placed in a drying pistol at 40° C. overnight giving a yellow powder (145.5 mg, 95% yield containing ˜1.5 eq. TFA). MS (ES+) 442. δH (d6 DMSO) 3.0-3.1 (2H, m), 3.5-3.7 (2H, m), 7.3-7.4 (2H, br s), 7.5 (1H, m), 7.6 m), 7.8-8.1 (5H, m), 8.2-8.3 (1H, m), 8.7-8.9 (3H, m), 9.4 (1H, s), 10.5 (1H, s).

Workup

  1. temperaturecooled in an ice-bath
  2. concentrationAfter a further 1.75 hours at room temperature the solution was concentrated under reduced pressure
  3. customto give a yellow solid
  4. customThis solid was azeotroped with dichloromethane (3×10 mL)
  5. customtriturated with diethyl ether
  6. customisolated by filtration
  7. customThe solid collected
  8. washwas washed with diethyl ether (3×5 mL) and pentane (3×5 mL)
  9. customgiving

Sources & evidence

ORD record
ord-2cba7035cd124fe0bc203f43816c6a45
Source dataset
uspto-grants-2011_09
Patent number
US08017619B2

Reaction notes

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