Potassium Carbonate → HCID 58711997、化合物

HRID 2374960ノート

反応式

HRID 2374960 の反応式
Br[C:2]1[CH:3]=[C:4]([C:8]2[N:16]3[C:11]([CH:12]=[N:13][C:14]([NH:17][C:18]4[CH:23]=[C:22]([O:24][CH3:25])[C:21]([O:26][CH3:27])=[C:20]([O:28][CH3:29])[CH:19]=4)=[N:15]3)=[C:10]([CH3:30])[N:9]=2)[CH:5]=[CH:6][CH:7]=1.[C:31]1(/[CH:37]=[CH:38]/[C:39]([NH2:41])=[O:40])[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1.C(=O)([O-])[O-].[K+].[K+].C(N(C(C)C)CC)(C)C>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O1CCOCC1>[CH3:30][C:10]1[N:9]=[C:8]([C:4]2[CH:3]=[C:2](/[C:37](/[C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=3)=[CH:38]\[C:39]([NH2:41])=[O:40])[CH:7]=[CH:6][CH:5]=2)[N:16]2[C:11]=1[CH:12]=[N:13][C:14]([NH:17][C:18]1[CH:23]=[C:22]([O:24][CH3:25])[C:21]([O:26][CH3:27])=[C:20]([O:28][CH3:29])[CH:19]=1)=[N:15]2

参加物

8

反応物 4

HCID 11430Potassium CarbonateHCID 81531DiisopropylethylamineHCID 5273472trans-CinnamamideHCID 112135557-(3-bromophenyl)-5-methyl-N-(3,4,5-trimethoxyphenyl)-imidazo[5,1-f][1,2,4]triazin-2-amine

生成物 1

HCID 58711997HCID 58711997、化合物収率 19.7%

試薬・触媒・溶媒 3

HCID 74236Tetrabutylammonium Bromide触媒HCID 11979704Tetrakis(triphenylphosphine)palladium触媒HCID 312751,4-Dioxane溶媒

反応条件

温度
110 °C

実験手順

To a mixture of 7-(3-bromophenyl)-5-methyl-N-(3,4,5-trimethoxyphenyl)imidazo[5,1-f][1,2,4]triazin-2-amine (Example 9) (40 mg, 0.085 mmol), (2E)-3-phenylprop-2-enamide (15.0 mg, 0.10 mmol), tetrakis(triphenylphosphine) palladium (0) (5.0 mg, 0.004 mmol) and potassium carbonate (17.6 mg, 0.127 mmol) was added 1,4-dioxane (1.0 mL). In a sealed reaction vessel, the mixture was heated with microwave radiation at 110° C. for 20 minutes. Analysis by LCMS indicated that no reaction occurred. To the mixture was added diisopropylethylamine (0.044 mL, 0.255 mmol), Combiphos catalyst POPd (Dihydrogen dichlorobis(di-tert-butylphosphinito-κP)palladate(2-)) (5.0 mg, 0.01 mmol) and tetrabutylammonium bromide (5.0 mg, 0.015 mmol) and heated with microwave radiation at 130° C. for 70 minutes. After cooling to room temperature, removed solvent under reduced pressure, dissolved residue in methanol (25 mL), and added silica gel (200 mg). Following evaporation of the volatiles under reduced pressure, the pre-adsorbed solids were loaded into a solid loading cartridge and subjected to a gradient elution using ethylacetate:methanol (100:0 to 80:20) using a RediSep silica gel cartridge (4.2 g; ISCO). The appropriate fractions were combined and concentrated under reduced pressure to give a gold oil. Added diethyl ether (15 mL) to precipitate, and vacuum filtered to give (2Z)-3-(3-{5-methyl-2-[(3,4,5-trimethoxyphenyl)amino]imidazo[5,1-f][1,2,4]triazin-7-yl}phenyl)-3-phenylprop-2-enamide (0.009 g) as a yellow solid. 1H NMR (CDCl3): δ8.80 (s, 1H), 8.48-8.46 (m, 1H), 7.40-7.28 (m, 7H), 7.17-7.15 (m, 1H), 7.02 (s, 1H), 6.89-6.86 (m, 2H), 6.44 (m, 1H), 5.34 (s, 2H), 3.83-3.79 (m, 9H), 2.60-2.57 (m, 3H). MS m/z 537 (M+1).

後処理

  1. customIn a sealed reaction vessel
  2. temperatureheated with microwave radiation at 130° C. for 70 minutes
  3. temperatureAfter cooling to room temperature
  4. customremoved solvent under reduced pressure
  5. dissolutiondissolved residue in methanol (25 mL)
  6. additionadded silica gel (200 mg)
  7. customevaporation of the volatiles under reduced pressure
  8. washsubjected to a gradient elution
  9. concentrationconcentrated under reduced pressure
  10. customto give a gold oil
  11. customAdded diethyl ether (15 mL) to precipitate
  12. filtrationvacuum filtered

出典と根拠

ORDレコード
ord-2dddf95097204a269eb4ac7bae26a82f
出典データセット
uspto-grants-2008_12
特許番号
US07462614B2

反応ノート

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