3-Bromoaniline → 4-N-(3-bromophenyl)-9H-pyrimido[4,5-b]indole-2,4-diamine

HRID 1358299Notes

Reaction equation

HRID 1358299 reaction equation
Cl.[NH2:2][C:3]1[N:4]=[C:5](Cl)[C:6]2[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[NH:9][C:7]=2[N:8]=1.[Br:17][C:18]1[CH:19]=[C:20]([CH:22]=[CH:23][CH:24]=1)[NH2:21]>CC(O)C.CO>[NH2:2][C:3]1[N:4]=[C:5]([NH:21][C:20]2[CH:22]=[CH:23][CH:24]=[C:18]([Br:17])[CH:19]=2)[C:6]2[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[NH:9][C:7]=2[N:8]=1

Participants

5

Reactant 2

HCID 115623-BromoanilineHCID 181843672-Amino-4-chloroindolo[2,3-d]pyrimidine hydrochloride

Product 1

HCID 53283964-N-(3-bromophenyl)-9H-pyrimido[4,5-b]indole-2,4-diamineYield 17%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 3776IsopropanolSolvent2×

Procedure

A mixture of 2-amino-4-chloroindolo[2,3-d]pyrimidine hydrochloride (123 mg, 0.6 mmol) and 3-bromoaniline (0.3 mL, 2.8 mmol) in 2-propanol (6 mL) is heated at reflux for 4 hr, filtered through a celite pad, and concentrated in vacuo. The residue is partitioned between ethyl acetate (25 mL) and water (25 mL). The aqueous phase is extracted with further ethyl acetate (2×20 mL), followed by washing the combined extracts with 1% aqueous sodium hydroxide (25 mL), water (2×40 mL) , saturated brine (40 mL), and drying (Na2SO4). The solution is evaporated to dryness under reduced pressure to afford 105 mg crude product as a tan powder. The solid is dissolved in a minimum amount of methanol, filtered, and further purified by preparative plate chromatography (SiO2; 1:1, EtOAc:CH2Cl2; Rf=0.40). After extraction of the product from the silica gel with ethyl acetate, the volume of the warm solution is reduced to minimum, an d it is filtered through celite, and the solvent is removed under reduced pressure. The oily solid thus obtained is dissolved in a minimum amount of 2-propanol and allowed to crystallize at 3 C. over an 18 h period. The crystals are collected by suction filtration, washed with a small amount of cold 2-propanol, and dried in vacuo to give 2-amino-4-(3-bromoanilino)indolo[2,3-d]pyrimidine (34 mg, 17%). 1HNMR, (DMSO): δbrs), 8.57 (1H, s), 8.11 (1H, d, J=8.0 Hz), 8.01 (1H, s), 7.94 (1H, d, J=8.2 Hz), 7.34-7.12 (5H, m), 6.41 (2H, brs).

Workup

  1. temperatureis heated
  2. temperatureat reflux for 4 hr
  3. filtrationfiltered through a celite pad
  4. concentrationconcentrated in vacuo
  5. customThe residue is partitioned between ethyl acetate (25 mL) and water (25 mL)
  6. extractionThe aqueous phase is extracted with further ethyl acetate (2×20 mL)
  7. washby washing the combined extracts with 1% aqueous sodium hydroxide (25 mL), water (2×40 mL) , saturated brine (40 mL)
  8. dry with materialdrying (Na2SO4)
  9. customThe solution is evaporated to dryness under reduced pressure
  10. customto afford 105 mg crude product as a tan powder
  11. filtrationfiltered
  12. customfurther purified by preparative plate chromatography (SiO2; 1:1, EtOAc:CH2Cl2; Rf=0.40)
  13. extractionAfter extraction of the product from the silica gel with ethyl acetate
  14. filtrationan d it is filtered through celite
  15. customthe solvent is removed under reduced pressure
  16. customThe oily solid thus obtained
  17. customto crystallize at 3 C
  18. filtrationThe crystals are collected by suction filtration
  19. washwashed with a small amount of cold 2-propanol
  20. customdried in vacuo

Sources & evidence

ORD record
ord-c2d1c2ac566e40cbb37288babb979e94
Source dataset
uspto-grants-2003_07
Patent number
US06596726B1

Reaction notes

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