Sodium Carbonate → Ethyl 4-amino-7-(3-fluorophenyl)-5-{4-[({[4-(trifluoromethyl)pyridin-2-yl]amino}carbonyl)amino]phenyl}-pyrrolo[2,1-f][1,2,4]triazine-6-carboxylate

HRID 1094882ノート

反応式

HRID 1094882 の反応式
[C:1]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C[CH:2]=1.[NH2:20][C:21]1[C:26]2=[C:27]([C:34]3[CH:39]=[CH:38][C:37]([NH:40][C:41]([NH:43][C:44]4[CH:49]=[C:48]([C:50]([F:53])([F:52])[F:51])[CH:47]=[CH:46][N:45]=4)=[O:42])=[CH:36][CH:35]=3)[C:28]([C:31]([O-:33])=[O:32])=[C:29](Br)[N:25]2[N:24]=[CH:23][N:22]=1.[F:54][C:55]1[CH:56]=[C:57](B(O)O)[CH:58]=[CH:59][CH:60]=1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[NH2:20][C:21]1[C:26]2=[C:27]([C:34]3[CH:39]=[CH:38][C:37]([NH:40][C:41]([NH:43][C:44]4[CH:49]=[C:48]([C:50]([F:53])([F:52])[F:51])[CH:47]=[CH:46][N:45]=4)=[O:42])=[CH:36][CH:35]=3)[C:28]([C:31]([O:33][CH2:1][CH3:2])=[O:32])=[C:29]([C:59]3[CH:58]=[CH:57][CH:56]=[C:55]([F:54])[CH:60]=3)[N:25]2[N:24]=[CH:23][N:22]=1

参加物

7

反応物 4

HCID 10340Sodium CarbonateHCID 11776TriphenylphosphineHCID 27339863-Fluorophenylboronic acidHCID 866357834-Amino-7-bromo-5-{4-[({[4-(trifluoromethyl)pyridin-2-yl]amino}carbonyl)amino]phenyl}pyrrolo[2,1-f][1,2,4-]triazine-6-carboxylate

生成物 1

HCID 57955236Ethyl 4-amino-7-(3-fluorophenyl)-5-{4-[({[4-(trifluoromethyl)pyridin-2-yl]amino}carbonyl)amino]phenyl}-pyrrolo[2,1-f][1,2,4]triazine-6-carboxylate収率 383.5%

試薬・触媒・溶媒 2

HCID 167845palladium(II) acetate触媒HCID 312751,4-Dioxane溶媒

反応条件

温度
80 °C

実験手順

Palladium(II)acetate (0.002 g, 0.009 mmol) was dissolved in dioxane (0.5 mL), and treated with triphenylphosphine (0.009 g, 0.035 mmol). The mixture was degassed twice before adding ethyl Intermediate AY (4-amino-7-bromo-5-{4-[({[4-(trifluoromethyl)pyridin-2-yl]amino}carbonyl)amino]phenyl}pyrrolo[2,1-f][1,2,4-]triazine-6-carboxylate (0.05 g, 0.009 mmol)), 3-fluorophenylboronic acid (0.014 g, 0.097 mmol) and aq. Na2CO3 solution (0.11 mL, 0.22 mmol, 2M). The mixture was heated to 80° C. overnight. The reaction was then cooled and filtered through silica. The filtrate was concentrated then triturated with EtOAc. The product was collected by filtration to give 20 mg of a tan solid (39%). 1H-NMR (THF-d8) δ 10.59 (bs, 1H) 9.08 (s, 1H), 8.47 (d, J=5.1, 1H), 7.79 (s, 1H), 7.73-7.68 (m, 3H), 7.41-7.37 (m, 5H), 7.23 (d, J=5.2, 1H), 7.13-7.08 (m, 1H), 3.94 (q, J=7.1, 2H), 0.90 (t, J=7.1, 3H); MS [M+H]+=580.0; LCMS RT=3.41.

後処理

  1. customThe mixture was degassed twice
  2. temperatureThe reaction was then cooled
  3. filtrationfiltered through silica
  4. concentrationThe filtrate was concentrated
  5. customthen triturated with EtOAc
  6. filtrationThe product was collected by filtration

出典と根拠

ORDレコード
ord-d0121405b2dc484cb5fd70fbfe4e58aa
出典データセット
uspto-grants-2012_03
特許番号
US08133995B2

反応ノート

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