Methanol → 5-Cyano-3-(2-fluoro-4-trimethylsilanyl-phenylamino)-pyrazine-2-carboxylic acid methyl ester

HRID 2064007노트

반응식

HRID 2064007 반응식
[CH3:1][O:2][C:3]([C:5]1[C:10]([NH:11][C:12]2[CH:17]=[CH:16][C:15]([Si:18]([CH3:21])([CH3:20])[CH3:19])=[CH:14][C:13]=2[F:22])=[N:9][C:8](Cl)=[CH:7][N:6]=1)=[O:4].C(OCC)(=O)C.CO.[CH3:32][N:33](C)C=O>[C-]#N.[Zn+2].[C-]#N.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:1][O:2][C:3]([C:5]1[C:10]([NH:11][C:12]2[CH:17]=[CH:16][C:15]([Si:18]([CH3:21])([CH3:20])[CH3:19])=[CH:14][C:13]=2[F:22])=[N:9][C:8]([C:32]#[N:33])=[CH:7][N:6]=1)=[O:4]

참가 물질

7

반응물 4

HCID 887MethanolHCID 6228DimethylformamideHCID 8857Ethyl AcetateHCID 591401805-Chloro-3-(2-fluoro-4-trimethylsilanyl-phenylamino)-pyrazine-2-carboxylic acid methyl ester

생성물 1

HCID 591401375-Cyano-3-(2-fluoro-4-trimethylsilanyl-phenylamino)-pyrazine-2-carboxylic acid methyl ester수율 99.8%

시약·촉매·용매 2

HCID 11186Zinc cyanide (Zn(CN)2)촉매HCID 178418397HCID 178418397, 화합물촉매

실험 절차

A degassed suspension of 5-chloro-3-(2-fluoro-4-trimethylsilanyl-phenylamino)-pyrazine-2-carboxylic acid methyl ester (1.35 g, 3.82 mmol), zinc (II) cyanide (492.8 mg, 4.2 mmol, 1.1 eq.), and Pd(PPh3)4 (551.0 mg, 0.48 mmol, 0.12 eq.) in anhydrous dimethylformamide (30 mL) was subjected to microwave irradiation at 150° C. for 18 minutes. The reaction mixture was poured into ethyl acetate and then filtered through a pad of Celite®. The pad was rinsed well with ethyl acetate (2×). The combined filtrates were washed with 50% brine (2×) and brine (1×), dried (Na2SO4), filtered and concentrated in vacuo. The crude residue was purified by column chromotagraphy (Si-PPC, gradient 0 to 30% ethyl acetate in hexane) to give a brown oil. Trituration with MeOH afforded the desired compound as an orange solid (1.31 g, 99.8%). 1H NMR (CDCl3, 400 MHz) δ ppm 10.56 (s, 1H), 8.36 (s, 1H), 8.29 (t, J=7.82 Hz, 1H), 7.37-7.27 (m, 2H), 4.10 (s, 3H), 0.29 (s, 9H); LCMS (method D1): RT=1.28 min, [M+H]+=345.

후처리

  1. customirradiation at 150° C. for 18 minutes
  2. filtrationfiltered through a pad of Celite®
  3. washThe pad was rinsed well with ethyl acetate (2×)
  4. washThe combined filtrates were washed with 50% brine (2×) and brine (1×)
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude residue was purified by column chromotagraphy (Si-PPC, gradient 0 to 30% ethyl acetate in hexane)
  9. customto give a brown oil

출처 및 근거

ORD 기록
ord-841b6de63c31459987dbde426a99cbca
출처 데이터셋
uspto-grants-2012_10
특허 번호
US08288408B2

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