4,5-Dichlorophthalic anhydride → 2-({[2-[(4-{[(Tert-butoxycarbonyl)amino]methyl}phenyl)amino]-5-(trifluoromethyl)phenyl]amino}carbonyl)-4,5-dichlorobenzoic acid

HRID 585039

Reaction equation

HRID 585039 reaction equation
[NH2:1][C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[CH:4][C:3]=1[NH:12][C:13]1[CH:27]=[CH:26][C:16]([CH2:17][NH:18][C:19](=[O:25])[O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[CH:15][CH:14]=1.[Cl:28][C:29]1[CH:30]=[C:31]2[C:36](=[O:37])[O:35][C:33](=[O:34])[C:32]2=[CH:38][C:39]=1[Cl:40]>C(Cl)(Cl)Cl>[C:21]([O:20][C:19]([NH:18][CH2:17][C:16]1[CH:26]=[CH:27][C:13]([NH:12][C:3]2[CH:4]=[CH:5][C:6]([C:8]([F:11])([F:10])[F:9])=[CH:7][C:2]=2[NH:1][C:33]([C:32]2[CH:38]=[C:39]([Cl:40])[C:29]([Cl:28])=[CH:30][C:31]=2[C:36]([OH:37])=[O:35])=[O:34])=[CH:14][CH:15]=1)=[O:25])([CH3:23])([CH3:24])[CH3:22]

Participants

4

Reactant 2

HCID 703344,5-Dichlorophthalic anhydrideHCID 22339357Tert-butyl 4-{[2-amino-4-(trifluoromethyl)phenyl]amino}benzylcarbamate

Product 1

HCID 223393592-({[2-[(4-{[(Tert-butoxycarbonyl)amino]methyl}phenyl)amino]-5-(trifluoromethyl)phenyl]amino}carbonyl)-4,5-dichlorobenzoic acid

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

Tert-butyl 4-{[2-amino-4-(trifluoromethyl)phenyl]amino}benzylcarbamate (216 mg, 0.56 mmol), and 4,5-dichlorophthalic anhydride (110 mg, 0.51 mmol) are added to a 7 ml vial. After diluting with chloroform (4 mL), the reaction vial is placed on an orbit shaker at 40° C. After 18 hr, the reaction mixture is concentrated. Recrystallization gives 2-({[2-[(4-{[(tert-butoxycarbonyl)amino]methyl}phenyl)amino]-5-(trifluoromethyl)phenyl]amino}carbonyl)-4,5-dichlorobenzoic acid, which is dissolved in ethyl acetate (10 mL). After cooling to 0° C., ethyl acetate saturated with HCl (10 mL) is added. After 2 hr the reaction mixture is concentrated and purified by recrystallization to give 2-({[2-{[4-(aminomethyl)phenyl]amino}-5-(trifluoromethyl)phenyl]amino}carbonyl)-4,5-dichlorobenzoic acid hydrochloride. The yield is 92 mg (34%). 1H NMR (400 MHz, DMSO-d6) 13.91 (s, 1H), 10.24 (s, 1H), 8.25 (s, 3H), 8.09 (s, 1H), 8.02 (s, 1H), 7.95, (s, 1H), 7.83 (m, 1H), 7.49 (m, 1 H), 7.43 (d, 2H), 7.36 (m, 1H), 7.21 (d, 2H), 3.97 (m, 2H); HRMS for C22H16Cl2F3N3O3 498.0584 (M+H)+.

Workup

  1. customthe reaction
  2. customvial is placed on an orbit shaker at 40° C
  3. concentrationthe reaction mixture is concentrated
  4. customRecrystallization

Sources & evidence

ORD record
ord-c7046d49292d476b88455985716e58e2
Source dataset
uspto-grants-2005_08
Patent number
US06930106B2

Linked notes

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