반응 #68659

반응 방정식

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

용매

DCM

반응 조건

후처리

1. 1
   기타The reaction vessel was then appropriately sealed
2. 2
   농축The reaction was then concentrated onto dry silica under reduced pressure and product
3. 3
   기타purified on silica (40 g)
4. 4
   세척eluting with 1-4% of 2 M NH3 in MeOH/DCM
5. 5
   기타The product was then further purified by RP-HPLC
6. 6
   세척eluting with water/ACN (0.1% TFA)
7. 7
   기타Collected
8. 8
   농축fractions concentrated under reduced pressure
9. 9
   workup.DISSOLUTIONdissolved in MeOH/DCM (5 mL)
10. 10
    기타Solids were then removed by filtration
11. 11
    세척washed with MeOH (3×1 mL)
12. 12
    농축The filtrate was then concentrated under reduced pressure, and product
13. 13
    기타isolated as an off white solid

실험 절차

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.

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