Acetic Anhydride → HCID 69319692, compound

HRID 270730Notes

Reaction equation

HRID 270730 reaction equation
[F:1][C:2]1[CH:27]=[C:26]([F:28])[CH:25]=[CH:24][C:3]=1[O:4][C:5]1[C:21](=[O:22])[N:20]([CH3:23])[C:8]2[N:9]=[C:10]([NH:13][CH:14]3[CH2:19][CH2:18][O:17][CH2:16][CH2:15]3)[N:11]=[CH:12][C:7]=2[CH:6]=1.C(N(CC)C(C)C)(C)C.[C:38](OC(=O)C)(=[O:40])[CH3:39].CCCCCC>CC(C)=O>[F:1][C:2]1[CH:27]=[C:26]([F:28])[CH:25]=[CH:24][C:3]=1[O:4][C:5]1[C:21](=[O:22])[N:20]([CH3:23])[CH:8]2[N:9]=[C:10]([N:13]([CH:14]3[CH2:19][CH2:18][O:17][CH2:16][CH2:15]3)[C:38](=[O:40])[CH3:39])[N:11]=[CH:12][CH:7]2[CH:6]=1

Participants

6

Reactant 4

HCID 7918Acetic AnhydrideHCID 8058HexaneHCID 81531DiisopropylethylamineHCID 114065906-(2,4-Difluorophenoxy)-8-methyl-2-(tetrahydro-2H-pyran-4-ylamino)pyrido[2,3-d]pyrimidin-7(8H)-one

Product 1

HCID 69319692HCID 69319692, compound

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Conditions

Temperature
125 °C

Procedure

A mixture of 6-(2,4-difluorophenoxy)-8-methyl-2-(tetrahydro-2H-pyran-4-ylamino)pyrido[2,3-d]pyrimidin-7(8H)-one (Example 23) (1.0 g, 2.57 mmol), N,N-diisopropylethylamine (0.498 g, 0.67 mL, 3.86 mmol) in acetic anhydride (1.42 g, 1.02 mL, 13.9 mmol) was heated to 123-127° C. for 2 hours. The volatiles were evaporated at 60° C. to provide a thick residue which was dissolved in 4 mL of acetone at 67-70° C. To the resulting solution was added 5 mL of hexane maintaining a temperature of 53-55° C. This mixture was allowed to cool to ambient temperature over 18 hours. The resulting solid was filtered and washed with 3×3 mL of 1:2 acetone:hexane. The rinsed solid was suspended in 5 mL of hexane and heated to reflux for 45 minutes. After cooling to ambient temperature, the slurry was filtered and the solid washed with hexane and dried under vacuum. (0.903 g, mass spec. M+1=431, MP=185.3-186.9° C.).

Workup

  1. customThe volatiles were evaporated at 60° C.
  2. customto provide a thick residue which
  3. temperatureto cool to ambient temperature over 18 hours
  4. filtrationThe resulting solid was filtered
  5. washwashed with 3×3 mL of 1:2 acetone
  6. temperatureheated
  7. temperatureto reflux for 45 minutes
  8. temperatureAfter cooling to ambient temperature
  9. filtrationthe slurry was filtered
  10. washthe solid washed with hexane
  11. customdried under vacuum

Sources & evidence

ORD record
ord-99589d97bcd949c2b3ff9ade9fb5c76f
Source dataset
uspto-grants-2008_11
Patent number
US07449581B2

Reaction notes

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