Anisole → HCID 10640427, compound

HRID 1520738Notes

Reaction equation

HRID 1520738 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:11]3[CH:19]=[C:18]([NH:20]CC4C=CC(OC)=CC=4)[N:17]=[CH:16][C:12]=3[N:13]=[CH:14][N:15]=2)[CH:5]=[CH:6][C:7]=1[F:8].C1(OC)C=CC=CC=1>FC(F)(F)C(O)=O>[Br:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:11]3[CH:19]=[C:18]([NH2:20])[N:17]=[CH:16][C:12]=3[N:13]=[CH:14][N:15]=2)[CH:5]=[CH:6][C:7]=1[F:8]

Participants

4

Reactant 2

HCID 7519AnisoleHCID 10647359HCID 10647359, compound

Product 1

HCID 10640427HCID 10640427, compoundYield 99%

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Procedure

To a stirred homogeneous solution of compound 165 (15.9 g, 34.9 mmol) in trifluoroacetic acid (80 mL) was added anisole (7.58 mL, 69.8 mmol). The mixture was then stirred at room temperature for 20 h. Most of the trifluoroacetic acid was evaporated under reduced pressure at 35° C. (bath temperature). The resultant red-brown oil was stirred with petroleum ether (400 mL) at room temperature for ca. 10 min. The petroleum ether layer was then decanted and the process was repeated with more petroleum ether (2×300 mL). The residue was then stirred with 5M NH3 at 0° C. for 5 min, then at room temperature for another 45 min. The solid thus obtained was collected by filtration and washed with water (3×60 mL) before being dried in vacuo. The solid was then stirred with warm acetone (500 mL) for 30 min. Water (800 mL) was added and the suspension was stirred at room temperature for 1 h. The solid was again collected by filtration and washed successively with water (6×70 mL) and then petroleum ether/ethyl acetate (3:1, 4×100 mL) before being dried under reduced pressure, to give N4-(3-bromo-4-fluorophenyl)pyrido[3,4-d]pyrimidine-4,6-diamine (159) (11.5 g, 99%), mp 269-271° C. (literature mp 268-270° C.). 1H NMR identical with that reported (Smaill et al. J Med Chem, 1999, 42, 1803-1815).

Workup

  1. customMost of the trifluoroacetic acid was evaporated under reduced pressure at 35° C. (bath temperature)
  2. stirringThe resultant red-brown oil was stirred with petroleum ether (400 mL) at room temperature for ca. 10 min
  3. customThe petroleum ether layer was then decanted
  4. stirringThe residue was then stirred with 5M NH3 at 0° C. for 5 min
  5. waitat room temperature for another 45 min
  6. customThe solid thus obtained
  7. filtrationwas collected by filtration
  8. washwashed with water (3×60 mL)
  9. custombefore being dried in vacuo
  10. stirringThe solid was then stirred with warm acetone (500 mL) for 30 min
  11. additionWater (800 mL) was added
  12. stirringthe suspension was stirred at room temperature for 1 h
  13. filtrationThe solid was again collected by filtration
  14. washwashed successively with water (6×70 mL)
  15. dry with materialpetroleum ether/ethyl acetate (3:1, 4×100 mL) before being dried under reduced pressure

Sources & evidence

ORD record
ord-55ba56a7cf2744c3b17a4431941aa6c3
Source dataset
uspto-grants-2015_07
Patent number
US09073916B2

Reaction notes

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