Potassium Phosphate, Tribasic → 8-(2-cyclopropylbenzyl)-2-(methylthio)pyrido[2,3-d]pyrimidin-7(8H)-one

HRID 1188716Notes

Reaction equation

HRID 1188716 reaction equation
Br[C:2]1[CH:21]=[CH:20][CH:19]=[CH:18][C:3]=1[CH2:4][N:5]1[C:10]2[N:11]=[C:12]([S:15][CH3:16])[N:13]=[CH:14][C:9]=2[CH:8]=[CH:7][C:6]1=[O:17].[CH:22]1(B(O)O)[CH2:24][CH2:23]1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>>[CH:22]1([C:2]2[CH:21]=[CH:20][CH:19]=[CH:18][C:3]=2[CH2:4][N:5]2[C:10]3[N:11]=[C:12]([S:15][CH3:16])[N:13]=[CH:14][C:9]=3[CH:8]=[CH:7][C:6]2=[O:17])[CH2:24][CH2:23]1

Participants

4

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 2760897Cyclopropylboronic acidHCID 667614708-(2-bromobenzyl)-2-(methylthio)pyrido[2,3-d]pyrimidin-7(8H)-one

Product 1

HCID 667608898-(2-cyclopropylbenzyl)-2-(methylthio)pyrido[2,3-d]pyrimidin-7(8H)-oneYield 66%

Conditions

Temperature
140 °C

Procedure

8-(2-bromobenzyl)-2-(methylthio)pyrido[2,3-d]pyrimidin-7(8H)-one (150 mg, 0.41 mmol, Example 30), cyclopropylboronic acid (107 mg, 1.25 mmol), K3PO4 (264 mg, 1.24 mmol) and PdCl2(Pcy3)2 (15 mg, 0.02 mmol) were mixed as solids and placed under argon. Argon was bubbled through a mixture of toluene:water (20:1, 1.5 mL) for 20 min. The solvent was added to the solid and the suspension was heated under microwave irradiation at 140° C. for 1.5 h. The reaction mixture was then diluted with toluene (10 mL) and water (1×5 mL), the two phases were separated, and the aqueous layer was extracted with toluene (1×10 mL). The combined organic layers were washed with water (1×10 mL) and evaporated to dryness. The crude compound was purified by silica gel column chromatography using dichloromethane:methanol (100:0.5) to yield 8-(2-cyclopropylbenzyl)-2-(methylthio)pyrido[2,3-d]pyrimidin-7(8H)-one as an off-white solid (88 mg, 0.27 mmol, 66%). ESMS m/z 324 (M+H)+.

Workup

  1. customArgon was bubbled through a mixture of toluene:water (20:1, 1.5 mL) for 20 min
  2. additionThe solvent was added to the solid
  3. additionThe reaction mixture was then diluted with toluene (10 mL) and water (1×5 mL)
  4. customthe two phases were separated
  5. extractionthe aqueous layer was extracted with toluene (1×10 mL)
  6. washThe combined organic layers were washed with water (1×10 mL)
  7. customevaporated to dryness
  8. customThe crude compound was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-06ac9b09e3024be595e45a5036079f60
Source dataset
uspto-grants-2014_03
Patent number
US08674095B2

Reaction notes

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