Ammonia → 4-chloro-5-(trifluoromethyl)-5,6-dihydropyrido[2,3-d]pyrimidin-7(8H)-one

HRID 2088926Notes

Reaction equation

HRID 2088926 reaction equation
[Cl:1][C:2]1[C:7]([CH:8]([C:14]([F:17])([F:16])[F:15])[CH2:9][C:10](OC)=[O:11])=[C:6](Cl)[N:5]=[CH:4][N:3]=1.[NH3:19].C(O)(C)C>>[Cl:1][C:2]1[C:7]2[CH:8]([C:14]([F:17])([F:16])[F:15])[CH2:9][C:10](=[O:11])[NH:19][C:6]=2[N:5]=[CH:4][N:3]=1

Participants

4

Reactant 3

HCID 222AmmoniaHCID 3776IsopropanolHCID 86666569Methyl 3-(4,6-dichloropyrimidin-5-yl)-4,4,4-trifluorobutanoate

Product 1

HCID 866665794-chloro-5-(trifluoromethyl)-5,6-dihydropyrido[2,3-d]pyrimidin-7(8H)-oneYield 83%

Conditions

Temperature
120 °C

Procedure

Combine methyl 3-(4,6-dichloropyrimidin-5-yl)-4,4,4-trifluorobutanoate (501.0 g, 1.57 mol) and 2 M ammonia in isopropyl alcohol (1.57 L, 2.0 eq) in a pressure reactor. Heat at 120° C. for seven hours. Cool the mixture to room temperature, then concentrate in vacuo. Dilute with hexanes (1 L). Filter to give crude product. Triturate this solid with 10% isopropyl alcohol in water (600 mL) and water (1.3 L). Filter and dry at 70° C. to give 4-chloro-5-(trifluoromethyl)-5,6-dihydropyrido[2,3-d]pyrimidin-7(8H)-one (328.9 g, 83%) as a racemate. MS (ES) m/z=252 [M]+.

Workup

  1. temperatureCool the mixture to room temperature
  2. concentrationconcentrate in vacuo
  3. additionDilute with hexanes (1 L)
  4. filtrationFilter
  5. customto give crude product
  6. customTriturate this solid with 10% isopropyl alcohol in water (600 mL) and water (1.3 L)
  7. filtrationFilter
  8. customdry at 70° C.

Sources & evidence

ORD record
ord-8fce1ac684214a39a5d4fd3350efb924
Source dataset
uspto-grants-2013_05
Patent number
US08436002B2

Reaction notes

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