Thionyl Chloride → HCID 86663607, compound

HRID 1520746Notes

Reaction equation

HRID 1520746 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.[C:17]([C:19]1[CH:20]=[C:21]([CH:23]=[CH:24][CH:25]=1)[NH2:22])#[CH:18].C(=O)(O)[O-].[Na+]>CN(C=O)C.CC(N(C)C)=O>[C:17]([C:19]1[CH:20]=[C:21]([NH:22][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:23]=[CH:24][CH:25]=1)#[CH:18]

Participants

7

Reactant 4

HCID 24386Thionyl ChlorideHCID 104682Benzenamine, 3-ethynyl-HCID 516892Sodium BicarbonateHCID 1354173706-fluoropyrido[3,4-d]pyrimidin-4-ol

Product 1

HCID 86663607HCID 86663607, compoundYield 99%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 31374DimethylacetamideSolvent

Procedure

A suspension of 6-fluoropyrido[3,4-d]pyrimidin-4(3H)-one (93) (6.64 g, 40.2 mmol), thionyl chloride (150 mL) and a catalytic amount of DMF (5 drops) was stirred under reflux for 30 min to give a homogeneous mixture which 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-ethynylaniline (6.56 g, 44.2 mmol) and dry DMA (40 mL). The reaction mixture was then stirred at room temperature for 40 min before a 5% solution of sodium bicarbonate (500 mL) was added and the resultant mixture was stirred at room temperature for 15 min. The solid was collected by filtration and washed several times with water and then hexane, respectively. The solid was then dried under vacuum over silica gel to give N-(3-ethynylphenyl)-6-fluoropyrido[3,4-d]pyrimidin-4-amine (164) (10.5 g, 99%), mp 225-227° C.; 1H NMR δ [(CD3)2SO] 10.06 (s, 1H), 8.96 (s, 1H), 8.74 (s, 1H), 8.28 (poorly resolved d, J=0.6 Hz, 1H), 8.10 (t, J=1.7 Hz, 1H), 7.95-7.90 (m, 1H), 7.46 (t, J=7.9 Hz, 1H), 7.32-7.27 (m, 1H), 4.22 (s, 1H). Anal. Calcd for C15H9BrFN4: C, 68.18; H, 3.43; N, 21.20%. Found C, 67.80; H, 3.50; N, 20.81%.

Workup

  1. temperatureunder reflux for 30 min
  2. customto give a homogeneous mixture which
  3. customwas evaporated under reduced pressure at 45° C. (bath temperature)
  4. customto give a light brown solid
  5. additionTo this solid was added
  6. additionwas added
  7. filtrationThe solid was collected by filtration
  8. washwashed several times with water
  9. customThe solid was then dried under vacuum over silica gel

Sources & evidence

ORD record
ord-13a0d53769da43b3bbe315d462c7dc49
Source dataset
uspto-grants-2015_07
Patent number
US09073916B2

Reaction notes

Loading…