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 1094882Notes

Reaction equation

HRID 1094882 reaction equation
[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

Participants

7

Reactant 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

Product 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-carboxylateYield 383.5%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-d0121405b2dc484cb5fd70fbfe4e58aa
Source dataset
uspto-grants-2012_03
Patent number
US08133995B2

Reaction notes

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