Water → HCID 5328397, compound

HRID 1358295Notes

Reaction equation

HRID 1358295 reaction equation
Cl[C:2]1[C:3]2[C:14]3[C:9](=[CH:10][CH:11]=[C:12]([O:15][CH3:16])[CH:13]=3)[NH:8][C:4]=2[N:5]=[CH:6][N:7]=1.[Br:17][C:18]1[CH:19]=[C:20]([CH:22]=[CH:23][CH:24]=1)[NH2:21].CN(C)C(=O)C.O>Cl.CC(O)C>[Br:17][C:18]1[CH:19]=[C:20]([CH:22]=[CH:23][CH:24]=1)[NH:21][C:2]1[C:3]2[C:14]3[C:9](=[CH:10][CH:11]=[C:12]([O:15][CH3:16])[CH:13]=3)[NH:8][C:4]=2[N:5]=[CH:6][N:7]=1

Participants

7

Reactant 4

HCID 962WaterHCID 115623-BromoanilineHCID 31374DimethylacetamideHCID 10823553HCID 10823553, compound

Product 1

HCID 5328397HCID 5328397, compoundYield 28.5%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 3776IsopropanolSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 4-chloro-6-methoxyindolo-[2,3-d]pyrimidine (107 mg, 0.37 mmol, 80% pure), 3-bromoaniline (0.15 mL, 1.4 mmol), N,N-dimethylacetamide (1 mL), and 1 drop of a solution of 2-propanol that is 8.5 molar in HCl is heated under N2 at 120° C. for 5 h. The solution is concentrated in vacuo to an oily solid that is triturated in 5% aqueous sodium bicarbonate. The solids are collected by filtration, then washed successively with H2O and EtOAc. The solids are warmed in a small volume of N,N-dimethylformamide and filtered. The filtrate is purified by thick layer silica gel chromatography eluting with 3:2 dichloromethane:EtOAc. The product band is collected and sonicated in EtOAc. The mixture is filtered and the filtrate is concentrated to a solid that is sonicated in MeOH. The solids are collected, washed with MeOH, and dried to give pure 4-(3-bromoanilino)-6-methoxyindolo[2,3-d]pyrimidine (39 mg, 28%) hydrated with 0.7 equivalent of H2O. 1H NMR (DMSO): δ11.99 (1H, br s, exchanges with D2O), 8.97 (1H, br s, exchanges with D2O), 8.44 (1H, s), 8.02 (1H, s), 7.91 (1H, d, J=2.4 Hz), 7.76 (1H, d, J=8.0 Hz), 7.42 (1H, d, J=8.7 Hz), 7.36-7.24 (2H, m), 7.08 (1H,dd, J=8.7, 2.2 Hz), 3.87 (3H, s).

Workup

  1. concentrationThe solution is concentrated in vacuo to an oily solid
  2. customthat is triturated in 5% aqueous sodium bicarbonate
  3. filtrationThe solids are collected by filtration
  4. washwashed successively with H2O and EtOAc
  5. temperatureThe solids are warmed in a small volume of N,N-dimethylformamide
  6. filtrationfiltered
  7. customThe filtrate is purified by thick layer silica gel chromatography
  8. washeluting with 3:2 dichloromethane
  9. customThe product band is collected
  10. customsonicated in EtOAc
  11. filtrationThe mixture is filtered
  12. concentrationthe filtrate is concentrated to a solid
  13. customthat is sonicated in MeOH
  14. customThe solids are collected
  15. washwashed with MeOH
  16. customdried

Sources & evidence

ORD record
ord-e468e802621d4b449c15451f1cd3f56e
Source dataset
uspto-grants-2003_07
Patent number
US06596726B1

Reaction notes

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