Toluene → HCID 57389674, compound

HRID 533699Notes

Reaction equation

HRID 533699 reaction equation
[CH3:1][S:2]([CH2:5][CH2:6][NH:7][CH2:8][C:9]1[O:13][C:12]([C:14]2[CH:15]=[C:16]3[C:21](=[CH:22][CH:23]=2)[N:20]=[CH:19][N:18]=[C:17]3O)=[CH:11][CH:10]=1)(=[O:4])=[O:3].P(Cl)(Cl)(O[Cl:28])=O.C1(C)C=CC=CC=1.C(N(CC)CC)C>CCCCCC.C(OCC)(=O)C>[Cl:28][C:17]1[C:16]2[C:21](=[CH:22][CH:23]=[C:14]([C:12]3[O:13][C:9]([CH2:8][NH:7][CH2:6][CH2:5][S:2]([CH3:1])(=[O:4])=[O:3])=[CH:10][CH:11]=3)[CH:15]=2)[N:20]=[CH:19][N:18]=1

Participants

6

Reactant 4

HCID 1140TolueneHCID 8471TriethylamineHCID 86587839PhosphoryloxychlorideHCID 178504890HCID 178504890, compound2×

Product 1

HCID 57389674HCID 57389674, compound

Reagents, catalysts & solvents 1

HCID 21226206Ethyl acetate hexaneSolvent

Procedure

In a 4-neck glass flask provided with a mechanical stirrer, condenser and thermometer, the entirety having been previously dried, 63.8 g of 6-[5-({[2-(methylsulfonyl)ethyl]amino}methyl)furan-2-yl] quinazoline-4-ol of formula (VI) (0.184 moles), 33.7 g (20.1 mL) of phosphoryl oxychloride (POCl3; 0.220 moles) and 150 mL of toluene were introduced, under nitrogen. Stirring was carried out at ambient temperature for 10 minutes then 22.3 g (30.7 mL) of triethylamine (0.220 moles) was dosed, maintaining the T below 30° C. After introduction heating was carried out at 75° C. for 3 hours. The reaction was controlled by means of TLC using the Hexane/Ethyl acetate mixture (4:6) as eluent. Cooling was carried out at 0° C. and stirring was carried out for an hour at such temperature. The suspension was filtered washing the solid with 100 mL of toluene. The product was dried at 50° C. for 7-8 hours under vacuum. 63.8 g of product was added with a molar yield equivalent to 95%.

Workup

  1. customIn a 4-neck glass flask provided with a mechanical stirrer, condenser
  2. customthermometer, the entirety having been previously dried
  3. temperaturemaintaining the T below 30° C
  4. temperatureAfter introduction heating
  5. waitwas carried out at 75° C. for 3 hours
  6. temperatureCooling
  7. customwas carried out at 0° C.
  8. stirringstirring
  9. waitwas carried out for an hour at such temperature
  10. filtrationThe suspension was filtered
  11. washwashing the solid with 100 mL of toluene
  12. customThe product was dried at 50° C. for 7-8 hours under vacuum
  13. addition63.8 g of product was added with a molar yield equivalent to 95%

Sources & evidence

ORD record
ord-7c4a1b2fe4c14b06825a5cbe2ce2b6e8
Source dataset
uspto-grants-2014_10
Patent number
US08853396B2

Reaction notes

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