تفاعل #68659

معادلة التفاعل

DIEA

1-(3-fluoro-5-(1-methyl-1H-pyrazol-4-yl)pyridin-2-yl)hydrazine

methyl 2,2-difluoro-2-(quinolin-6-yl)acetate

triphenylphosphine

2,2,2-trichloroacetonitrile

→

6-(Difluoro(8-fluoro-6-(1-methyl-1H-pyrazol-4-yl)-[1,2,4]-triazolo[4,3-a]pyridin-3-yl)methyl)quinoline

المذيبات

DCM

ظروف التفاعل

المعالجة

1. 1
   أخرىThe reaction vessel was then appropriately sealed
2. 2
   تركيزThe reaction was then concentrated onto dry silica under reduced pressure and product
3. 3
   أخرىpurified on silica (40 g)
4. 4
   غسيلeluting with 1-4% of 2 M NH3 in MeOH/DCM
5. 5
   أخرىThe product was then further purified by RP-HPLC
6. 6
   غسيلeluting with water/ACN (0.1% TFA)
7. 7
   أخرىCollected
8. 8
   تركيزfractions concentrated under reduced pressure
9. 9
   workup.DISSOLUTIONdissolved in MeOH/DCM (5 mL)
10. 10
    أخرىSolids were then removed by filtration
11. 11
    غسيلwashed with MeOH (3×1 mL)
12. 12
    تركيزThe filtrate was then concentrated under reduced pressure, and product
13. 13
    أخرىisolated as an off white solid

الإجراء التجريبي

To a stirring suspension of 1-(3-fluoro-5-(1-methyl-1H-pyrazol-4-yl)pyridin-2-yl)hydrazine (190 mg, 917 μmol), methyl 2,2-difluoro-2-(quinolin-6-yl)acetate (218 mg, 917 μmol), triphenylphosphine polymer supported (241 mg, 917 μmol), DIEA (200 μl, 1146 μmol) in DCM (4 mL) was added 2,2,2-trichloroacetonitrile (92 μl, 917 μmol). The reaction vessel was then appropriately sealed and heated to 150° C. with microwaves for 15 min. The reaction was then concentrated onto dry silica under reduced pressure and product purified on silica (40 g) eluting with 1-4% of 2 M NH3 in MeOH/DCM. The product was then further purified by RP-HPLC eluting with water/ACN (0.1% TFA). Collected fractions concentrated under reduced pressure, dissolved in MeOH/DCM (5 mL) and stirred with Si-Carbonated (300 mg; 0.2 mmol) for 30 min at 23° C. Solids were then removed by filtration, and washed with MeOH (3×1 mL). The filtrate was then concentrated under reduced pressure, and product isolated as an off white solid. MS (ESI pos. ion) m/z: 395 (MH+). Calc'd exact mass for C20H13F3N6: 394.

المصدر