4-Amino-N-methylbenzenemethanesulfonamide → N-methyl-[4-(6-methoxy-4-phenylamino-quinazolin-2-ylamino)-phenyl]-methanesulfonamide

HRID 1603423Notes

Reaction equation

HRID 1603423 reaction equation
Cl[C:2]1[N:11]=[C:10]([NH:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([O:19][CH3:20])[CH:8]=2)[N:3]=1.[CH3:21][NH:22][S:23]([CH2:26][C:27]1[CH:32]=[CH:31][C:30]([NH2:33])=[CH:29][CH:28]=1)(=[O:25])=[O:24]>C(O)CC(C)C.CO>[CH3:21][NH:22][S:23]([CH2:26][C:27]1[CH:32]=[CH:31][C:30]([NH:33][C:2]2[N:11]=[C:10]([NH:12][C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[C:9]3[C:4](=[CH:5][CH:6]=[C:7]([O:19][CH3:20])[CH:8]=3)[N:3]=2)=[CH:29][CH:28]=1)(=[O:24])=[O:25]

Participants

5

Reactant 2

HCID 27781314-Amino-N-methylbenzenemethanesulfonamideHCID 226398172-Chloro-6-methoxy-4-phenylamino-quinazoline

Product 1

HCID 22639807N-methyl-[4-(6-methoxy-4-phenylamino-quinazolin-2-ylamino)-phenyl]-methanesulfonamide

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 31260Isoamyl AlcoholSolvent

Procedure

A solution of 2-chloro-6-methoxy-4-phenylamino-quinazoline (1.15 g) and N-methyl-(4-aminophenyl)-methanesulfonamide (prepared as described in Tetrahedron Letters 1992, 33, 8011) (0.89 g) in 5 mL of isopentylalcohol is stirred under nitrogen at 180° C. for 20 min in a sealed vessel. The warm reaction mixture is diluted with methanol and the hydrochloride salt, which is crystallizing on cooling, is filtered off. The crude product is redissolved in ethylacetate and aqueous sodium carbonate solution and extracted with ethylacetate. The organic extracts are dried and evaporated and the solid residue is titurated with diethylether to give N-methyl-[4-(6-methoxy-4-phenylamino-quinazolin-2-ylamino)-phenyl]-methanesulfonamide as light yellow crystals melting at 212-215° C.; (Rf (A2) 0.16. Recrystallisation from methanolic hydrogen chloride and diethylether yields N-methyl-[4-(6-methoxy-4-phenylamino-quinazolin-2-ylamino)-phenyl]-methanesulfonamide hydrochloride as light yellow crystals melting at 264-268° C.; Rf (A2) 0.16, FAB-MS: (M+H)+ =450. Analytical data: C23H23N5O3S+HCl.

Workup

  1. customThe warm reaction mixture
  2. customthe hydrochloride salt, which is crystallizing
  3. temperatureon cooling
  4. filtrationis filtered off
  5. dissolutionThe crude product is redissolved in ethylacetate
  6. extractionaqueous sodium carbonate solution and extracted with ethylacetate
  7. customThe organic extracts are dried
  8. customevaporated

Sources & evidence

ORD record
ord-2262df47f1c44c0baaa00d73d46fcecc
Source dataset
uspto-grants-1999_11
Patent number
US05989920

Reaction notes

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