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

HRID 1500702ノート

反応式

HRID 1500702 の反応式
[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]

参加物

7

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 2

HCID 11186Zinc cyanide (Zn(CN)2)触媒HCID 178418397HCID 178418397、化合物触媒

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-f1514c0efade4c4a99e1f2bc50752913
出典データセット
uspto-grants-2015_12
特許番号
US09206174B2

反応ノート

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