Anisole → N2-(2,6-dimorpholinopyridin-4-yl)-N4-(1H-indazol-4-yl)pyrimidine-2,4-diamine

HRID 2237408ノート

反応式

HRID 2237408 の反応式
Cl[C:2]1[N:7]=[C:6]([NH:8][C:9]2[C:10]3[CH:11]=[N:12][N:13](CC4C=CC(OC)=CC=4)[C:14]=3[CH:15]=[CH:16][CH:17]=2)[CH:5]=[CH:4][N:3]=1.[O:27]1[CH2:32][CH2:31][N:30]([C:33]2[CH:38]=[C:37]([NH2:39])[CH:36]=[C:35]([N:40]3[CH2:45][CH2:44][O:43][CH2:42][CH2:41]3)[N:34]=2)[CH2:29][CH2:28]1.C1(OC)C=CC=CC=1>>[O:27]1[CH2:32][CH2:31][N:30]([C:33]2[CH:38]=[C:37]([NH:39][C:2]3[N:7]=[C:6]([NH:8][C:9]4[CH:17]=[CH:16][CH:15]=[C:14]5[C:10]=4[CH:11]=[N:12][NH:13]5)[CH:5]=[CH:4][N:3]=3)[CH:36]=[C:35]([N:40]3[CH2:41][CH2:42][O:43][CH2:44][CH2:45]3)[N:34]=2)[CH2:29][CH2:28]1

参加物

4

反応物 3

HCID 7519AnisoleHCID 575713742,6-Dimorpholin-4-ylpyridin-4-amineHCID 86626272N-(2-chloropyrimidin-4-yl)-1-(4-methoxybenzyl)-1H-indazol-4-amine

生成物 1

HCID 25138375N2-(2,6-dimorpholinopyridin-4-yl)-N4-(1H-indazol-4-yl)pyrimidine-2,4-diamine収率 34.5%

反応条件

温度
130 °C

実験手順

N-(2-chloropyrimidin-4-yl)-1-(4-methoxybenzyl)-1H-indazol-4-amine (400 mg, 1.09 mmol) and 2,6-dimorpholinopyridin-4-amine (289 mg, 1.09 mmol) were reacted according to procedure of Example 1. After filtration of the solids and evaporation of the solvents, the resulting gum was dissolved in TFA (8.2 mL) and anisole (0.594 mL, 5.47 mmol) and sealed into a microwave tube. The reaction was heated to 130° C. over a period of 30 minutes in a Personal Chemistry EMRYS™ Optimizer EXP microwave synthesisor. The reaction mixture was concentrated to dryness, diluted with dichloromethane (20 ml), washed with water (20 ml), brine (20 ml), dried over magnesium sulfate and concentrated. The crude product was purified by flash chromatography on silica gel eluting with 0 to 5% methanol in dichloromethane. The solvent was evaporated to dryness. The resulting solid was triturated with diethyl ether/petroleum ether (1/1), collected by filtration and dried under vacuum to give N2-(2,6-dimorpholinopyridin-4-yl)-N4-(1H-indazol-4-yl)pyrimidine-2,4-diamine (178 mg, 34.4%) as a pale beige solid. NMR Spectrum: (DMSOd6) 3.17 (bs, 8H), 3.61 (bs, 8H), 6.47 (s, 1H), 6.59 (s, 2H), 7.22 (s, 1H), 7.27 (s, 1H), 7.79 (s, 1H), 8.12 (s, 1H), 8.21 (s, 1H), 9.16 (s, 1H), 9.46 (s, 1H), 13.06 (s, 1H); Mass spectrum: MH+ 474.

後処理

  1. filtrationAfter filtration of the solids and evaporation of the solvents
  2. dissolutionthe resulting gum was dissolved in TFA (8.2 mL)
  3. concentrationThe reaction mixture was concentrated to dryness
  4. additiondiluted with dichloromethane (20 ml)
  5. washwashed with water (20 ml), brine (20 ml)
  6. dry with materialdried over magnesium sulfate
  7. concentrationconcentrated
  8. customThe crude product was purified by flash chromatography on silica gel eluting with 0 to 5% methanol in dichloromethane
  9. customThe solvent was evaporated to dryness
  10. customThe resulting solid was triturated with diethyl ether/petroleum ether (1/1)
  11. filtrationcollected by filtration
  12. customdried under vacuum

出典と根拠

ORDレコード
ord-9a14776d7b3f4a5e82b1aa18f3148f73
出典データセット
uspto-grants-2010_05
特許番号
US07718653B2

反応ノート

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