Toluene → HCID 178516287, compound

HRID 1068950Notes

Reaction equation

HRID 1068950 reaction equation
[NH2:1][CH2:2][C:3]1[CH:4]=[C:5]([NH:9][C:10]2[C:18]3[C:13](=[N:14][CH:15]=[N:16][C:17]=3[NH:19][C:20]3[CH:25]=[CH:24][CH:23]=[C:22]([Cl:26])[CH:21]=3)[NH:12][N:11]=2)[CH:6]=[CH:7][CH:8]=1.C1(C)C=CC=CC=1.[C:34]1(=O)[O:39][C:37](=[O:38])[CH2:36][CH2:35]1.C(N(CC)CC)C>C(OCC)C>[Cl:26][C:22]1[CH:21]=[C:20]([NH:19][C:17]2[N:16]=[CH:15][N:14]=[C:13]3[NH:12][N:11]=[C:10]([NH:9][C:5]4[CH:6]=[CH:7][CH:8]=[C:3]([CH2:2][N:1]5[C:37](=[O:38])[CH2:36][CH2:35][C:34]5=[O:39])[CH:4]=4)[C:18]=23)[CH:25]=[CH:24][CH:23]=1

Participants

6

Reactant 4

HCID 1140TolueneHCID 7922Succinic anhydride2×HCID 8471Triethylamine2×HCID 178509838HCID 178509838, compound

Product 1

HCID 178516287HCID 178516287, compound

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 200 mg (0.537 mmol) of 3(3-aminomethyl-phenylamino)-4-(3-chloro-phenylamino)-1H-pyrazolo[3,4-d]pyrimidine (water content: 1.79%; see Step 90.5) and 10 ml of toluene is concentrated by evaporation in vacuo for the purpose of removing water and, after repetition of that operation, the residue is taken up in 10 ml of toluene. After the addition of 59 mg (0.59 mmol) of succinic anhydride and 0.082 ml (0.59 mmol) of triethylamine, the reaction mixture is heated for 1 hour at 80° C. and for 18 hours under reflux. A further 21 mg (0.21 mmol) of succinic anhydride and 0.041 ml (0.2949 mmol) of triethylamine are added to the reaction mixture which is heated for a further 6 hours under reflux, then cooled to room temperature and 10 ml of diethyl ether are added. Filtration, purification of the filter residue by flash chromatography (silica gel having a particle size of 0.04-0.06 mm; eluant: ethyl acetate), concentration of the product-containing fractions by evaporation in vacuo and recrystallization of the residue from methanol yield 4-(3-chloro-phenylamino)-3-(3-[succinimido-methyl]-phenylamino)-1H-pyrazolo[3,4-d]pyrimidine having a water content of 7.72%; m.p. 140-142° C.; ESI-MS: (M−H)−=446.

Workup

  1. concentrationis concentrated by evaporation in vacuo for the purpose of removing water
  2. temperatureunder reflux
  3. temperatureis heated for a further 6 hours
  4. temperatureunder reflux
  5. temperaturecooled to room temperature
  6. filtrationFiltration, purification of the filter residue by flash chromatography (silica gel having a particle size of 0.04-0.06 mm
  7. customeluant: ethyl acetate), concentration of the product-containing fractions by evaporation
  8. customin vacuo and recrystallization of the residue from methanol

Sources & evidence

ORD record
ord-ace00f67536e4700a1aa3527ef9bb841
Source dataset
uspto-grants-2001_06
Patent number
US06251911B1

Reaction notes

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