Thionyl Chloride → HCID 10616889, compound

HRID 1520736Notes

Reaction equation

HRID 1520736 reaction equation
[F:1][C:2]1[N:12]=[CH:11][C:5]2[N:6]=[CH:7][NH:8][C:9](=O)[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[F:25])[NH2:21].C(=O)(O)[O-].[Na+]>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[F:25]

Participants

7

Reactant 4

HCID 24386Thionyl ChlorideHCID 516892Sodium BicarbonateHCID 27792863-Bromo-4-fluoroanilineHCID 1354173706-fluoropyrido[3,4-d]pyrimidin-4-ol

Product 1

HCID 10616889HCID 10616889, compoundYield 99.7%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 31374DimethylacetamideSolvent

Procedure

A heterogeneous mixture of 6-fluoropyrido[3,4-d]pyrimidin-4(3H)-one (93) (4.0 g, 24.2 mmol), thionyl chloride (100 mL) and a catalytic amount of DMF (3 drops) was stirred under reflux for 1 h. The resulting solution was evaporated under reduced pressure at 45° C. (bath temperature) to give a light brown solid. To this solid was added a mixture of 3-bromo-4-fluoroaniline (5.1 g, 26.8 mmol) and dry DMA (25 mL). The reaction mixture was stirred at room temperature for 40 min, then a 5% solution of sodium bicarbonate (250 mL) was added and the mixture was stirred at room temperature for 15 min. The precipitated solid was collected by filtration and washed successively with water and hexane several times, before being dried under vacuum over silica gel to give N-(3-bromo-4-fluorophenyl)-6-fluoropyrido[3,4-d]pyrimidin-4-amine (162) (8.13 g, 99%), mp 275-277° C. (literature mp 269-270° C.; Smaill et al. J Med Chem, 1999, 42, 1803-1815); 1H NMR δ [(CD3)2SO] 10.12 (s, 1H), 8.97 (s, 1H), 8.74 (s, 1H), 8.32 (dd, J=6.4, 2.6 Hz, 1H), 8.23 (poorly resolved d, J=0.8 Hz, 1H), 7.93-7.87 (m, 1H), 7.46 (t, J=8.8 Hz, 1H). Anal. Calcd for C13H7BrF2N4: C, 46.32; H, 2.09; N, 16.62%. Found C, 46.54; H, 3.33; N, 16.42%.

Workup

  1. temperatureunder reflux for 1 h
  2. customThe resulting solution was evaporated under reduced pressure at 45° C. (bath temperature)
  3. customto give a light brown solid
  4. additionTo this solid was added
  5. stirringthe mixture was stirred at room temperature for 15 min
  6. filtrationThe precipitated solid was collected by filtration
  7. washwashed successively with water and hexane several times
  8. custombefore being dried under vacuum over silica gel

Sources & evidence

ORD record
ord-19b37c5bfe5c47a399ea389f31deb046
Source dataset
uspto-grants-2015_07
Patent number
US09073916B2

Reaction notes

Loading…