4-Fluoro-3-(tributylstannyl)pyridine → 2-Amino-5-(2,6-diethyl-pyridin-4-yl)-5-[4-fluoro-3-(4-fluoropyridin-3-yl)-phenyl]-3-methyl-3,5-dihydro-imidazol-4-one

HRID 271121

反応式

HRID 271121 の反応式
[NH2:1][C:2]1[N:6]([CH3:7])[C:5](=[O:8])[C:4]([C:19]2[CH:24]=[CH:23][C:22]([F:25])=[C:21](Br)[CH:20]=2)([C:9]2[CH:14]=[C:13]([CH2:15][CH3:16])[N:12]=[C:11]([CH2:17][CH3:18])[CH:10]=2)[N:3]=1.[F:27][C:28]1[CH:33]=[CH:32][N:31]=[CH:30][C:29]=1[Sn](CCCC)(CCCC)CCCC>CN(C=O)C.C1(P([Pd-](Cl)P(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[NH2:1][C:2]1[N:6]([CH3:7])[C:5](=[O:8])[C:4]([C:9]2[CH:14]=[C:13]([CH2:15][CH3:16])[N:12]=[C:11]([CH2:17][CH3:18])[CH:10]=2)([C:19]2[CH:24]=[CH:23][C:22]([F:25])=[C:21]([C:29]3[CH:30]=[N:31][CH:32]=[CH:33][C:28]=3[F:27])[CH:20]=2)[N:3]=1

参加物

5

反応物 2

HCID 164271514-Fluoro-3-(tributylstannyl)pyridineHCID 598345582-Amino-5-(3-bromo-4-fluorophenyl)-5-(2,6-diethyl-pyridin-4-yl)-3-methyl-3,5-dihydro-imidazol-4-one

生成物 1

HCID 598345772-Amino-5-(2,6-diethyl-pyridin-4-yl)-5-[4-fluoro-3-(4-fluoropyridin-3-yl)-phenyl]-3-methyl-3,5-dihydro-imidazol-4-one収率 10%

試薬・触媒・溶媒 2

HCID 178479804HCID 178479804、化合物触媒HCID 6228Dimethylformamide溶媒

反応条件

温度
150 °C

実験手順

A mixture of 2-amino-5-(3-bromo-4-fluorophenyl)-5-(2,6-diethyl-pyridin-4-yl)-3-methyl-3,5-dihydro-imidazol-4-one (0.170 g, 0.405), 4-fluoropyridin-3-yl(tributly)tin (0.235 g, 0.608 mmol) and bis(triphenylphosphino)palladium(II) chloride (0.023 g, 0.032 mmol) in DMF (5 mL) was degassed and heated at 150° C. for 1 h. The mixture was cooled to room temperature and diluted with ethyl acetate (50 mL) and 2% aqueous lithium chloride (20 mL). The organic layer was separated, washed with 2% aqueous lithium chloride, dried over sodium sulfate, filtered, and concentrated. Purification of the resultant residue by flash chromatography (silica, 95:5:0.25 methylene chloride/methanol/concentrated ammonium hydroxide) afforded the title product (0.017 g, 10%) as a white solid, mp 92-100° C.; 1H NMR (300 MHz, CD3OD) δ 8.55-8.45 (m, 2H), 7.56-7.19 (m, 4H), 7.09 (s, 2H), 3.10 (s, 3H), 2.68 (q, J=7.5 Hz, 4H), 1.15 (t, J=7.5 Hz, 6H); ESI MS m/z 436 [C24H23F2N5O+OH]+.

後処理

  1. customwas degassed
  2. temperatureThe mixture was cooled to room temperature
  3. additiondiluted with ethyl acetate (50 mL) and 2% aqueous lithium chloride (20 mL)
  4. customThe organic layer was separated
  5. washwashed with 2% aqueous lithium chloride
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customPurification of the resultant residue by flash chromatography (silica, 95:5:0.25 methylene chloride/methanol/concentrated ammonium hydroxide)

出典と根拠

ORDレコード
ord-6486f40020e549b890f08825eb036461
出典データセット
uspto-grants-2008_11
特許番号
US07452885B2

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