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 73688노트

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HRID 73688 반응식
[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

참가 물질

7

반응물 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

생성물 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-carboxylate수율 383.5%

시약·촉매·용매 2

HCID 167845palladium(II) acetate촉매HCID 312751,4-Dioxane용매

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온도
80 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-fb345404fca04ef98a97520baa4d32d1
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08829185B2

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