Sodium Chloride → [7-(3-Fluoro-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(3-morpholin-4-yl-phenyl)-amine

HRID 1261939Notes

Reaction equation

HRID 1261939 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.Br[C:21]1[N:29]2[C:24]([CH:25]=[N:26][C:27]([NH:30][C:31]3[CH:36]=[CH:35][CH:34]=[C:33]([N:37]4[CH2:42][CH2:41][O:40][CH2:39][CH2:38]4)[CH:32]=3)=[N:28]2)=[CH:23][CH:22]=1.[F:43][C:44]1[CH:45]=[C:46](B(O)O)[CH:47]=[CH:48][CH:49]=1.C(=O)([O-])[O-].[Na+].[Na+].[Cl-].[Na+]>O1CCCC1.O.C(O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[F:43][C:44]1[CH:49]=[C:48]([C:21]2[N:29]3[C:24]([CH:25]=[N:26][C:27]([NH:30][C:31]4[CH:36]=[CH:35][CH:34]=[C:33]([N:37]5[CH2:42][CH2:41][O:40][CH2:39][CH2:38]5)[CH:32]=4)=[N:28]3)=[CH:23][CH:22]=2)[CH:47]=[CH:46][CH:45]=1

Participants

10

Reactant 5

HCID 5234Sodium ChlorideHCID 10340Sodium CarbonateHCID 11776TriphenylphosphineHCID 27339863-Fluorophenylboronic acidHCID 66711115(7-Bromo-pyrrolo[2,1-f][1,2,4]triazin-2-yl)-(3-morpholin-4-yl-phenyl)-amine

Product 1

HCID 66711229[7-(3-Fluoro-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(3-morpholin-4-yl-phenyl)-amineYield 16.2%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

Palladium Acetate (0.029 g, 0.00013 mol) and Triphenylphosphine (0.042 g, 0.00016 mol) were dissolved in Tetrahydrofuran (2.0 mL) and the mixture was allowed to stir at room temperature for 10 minutes. (7-Bromo-pyrrolo[2,1-f][1,2,4]triazin-2-yl)-(3-morpholin-4-yl-phenyl)-amine (0.240 g, 0.000641 mol) was then added and the reaction was again allowed to stir for 10 minutes. 3-fluorophenylboronic acid (0.179 g, 0.00128 mol) was added followed by 0.9 M of Sodium carbonate in water (2 mL) and Ethanol (2.0 mL). The reaction mixture was then heated at 80° C. and was allowed to stir overnight. The reaction mixture was poured over saturated sodium chloride, and organics were extracted with ethyl acetate/dichloromethane. Combined organics were dried over sodium sulfate, filtered and reduced en vacuo. The crude mixture was purified by Gilson prep HPLC to afford 40.32 mg of [7-(3-Fluoro-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-(3-morpholin-4-yl-phenyl)-amine as a lyophilated powder. (M+H)=390.14. 1H NMR (400 MHz, CDCl3) δ 8.67 (s, 1H), 7.93 (m, 1H), 7.83 (m, 1H), 7.35-7.55 (m, 5H), 7.18 (m, 3H), 6.99 (m, 1H), 3.92 (m, 4H), 3.26 (m, 4H).

Workup

  1. stirringto stir for 10 minutes
  2. temperatureThe reaction mixture was then heated at 80° C.
  3. stirringto stir overnight
  4. extractionorganics were extracted with ethyl acetate/dichloromethane
  5. dry with materialCombined organics were dried over sodium sulfate
  6. filtrationfiltered
  7. customThe crude mixture was purified by Gilson prep HPLC

Sources & evidence

ORD record
ord-88fb8c9917d54060beaaae0556d40ac0
Source dataset
uspto-grants-2013_06
Patent number
US08471005B2

Reaction notes

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