Thionyl Chloride → N-(3-bromo-4-chlorophenyl)-6-fluoropyrido[3,4-d]pyrimidin-4-amine

HRID 511803Notes

Reaction equation

HRID 511803 reaction equation
[F:1][C:2]1[N:12]=[CH:11][C:5]2[NH:6][C:7](=O)[N:8]=[CH:9][C:4]=2[CH:3]=1.S(Cl)(Cl)=O.[Br:17][C:18]1[CH:19]=[C:20]([CH:22]=[CH:23][C:24]=1[Cl:25])[NH2:21]>CN(C=O)C.CC(N(C)C)=O>[Br:17][C:18]1[CH:19]=[C:20]([NH:21][C:9]2[C:4]3[CH:3]=[C:2]([F:1])[N:12]=[CH:11][C:5]=3[N:6]=[CH:7][N:8]=2)[CH:22]=[CH:23][C:24]=1[Cl:25]

Participants

6

Reactant 3

HCID 24386Thionyl ChlorideHCID 128437223-Bromo-4-chloroanilineHCID 66823511HCID 66823511, compound

Product 1

HCID 68158622N-(3-bromo-4-chlorophenyl)-6-fluoropyrido[3,4-d]pyrimidin-4-amineYield 99.6%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 31374DimethylacetamideSolvent

Procedure

A heterogeneous mixture of 6-fluoropyrido[3,4-d]pyrimidin-4(3H)-one (200) (1.50 g, 9.09 mmol), thionyl chloride (20 mL) and a catalytic amount of DMF (2 drops) was stirred under reflux for 3 h to give a homogeneous mixture. It was evaporated under reduced pressure at 40° C. (bath temperature) to give a light brown solid. To this solid was added a solution of 3-bromo-4-chloroaniline (2.07 g, 10.0 mmol) in dry DMA (15 mL). The residue of 3-bromo-4-chloroaniline was washed down with more DMA (2×2 mL). The reaction mixture was stirred at room temperature for 19 h. It was poured into water (200 mL). The pH was adjusted to ca. 8 using an aqueous solution of Na2CO3 at room temperature. Petroleum ether (300 mL) was added and stirred at room temperature for 30 min. The petroleum ether layer was decanted. It was repeated once more with petroleum ether. The solid was collected by filtration and washed with water (4×20 mL). It was dried in vacuum over silica gel/KOH overnight to give N-(3-bromo-4-chlorophenyl)-6-fluoropyrido[3,4-d]pyrimidin-4-amine (205) (3.20 g, 99%) as a yellow/orange solid, mp 271-275° C.; 1H NMR δ [(CD3)2SO] 10.15 (s, 1H), 8.99 (s, 1H), 8.79 (s, 1H), 8.45 (d, J=2.5 Hz, 1H), 8.26 (br s, 1H), 7.98 (dd, J=8.8, 2.5 Hz, 1H), 7.69 (d, J=8.8 Hz, 11-1). Anal. Calcd for C13N7BrClFN4: C, 44.16; H, 2.00; N, 15.85. Found C, 44.21; H, 1.87; N, 15.98.

Workup

  1. temperatureunder reflux for 3 h
  2. customto give a homogeneous mixture
  3. customIt was evaporated under reduced pressure at 40° C. (bath temperature)
  4. customto give a light brown solid
  5. washThe residue of 3-bromo-4-chloroaniline was washed down with more DMA (2×2 mL)
  6. additionIt was poured into water (200 mL)
  7. customat room temperature
  8. additionPetroleum ether (300 mL) was added
  9. stirringstirred at room temperature for 30 min
  10. customThe petroleum ether layer was decanted
  11. filtrationThe solid was collected by filtration
  12. washwashed with water (4×20 mL)
  13. customIt was dried in vacuum over silica gel/KOH overnight

Sources & evidence

ORD record
ord-baf631126d5d4242a7547db34612c278
Source dataset
uspto-grants-2015_08
Patent number
US09101632B2

Reaction notes

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