Ethanol → HCID 178515836, compound

HRID 1261991Notes

Reaction equation

HRID 1261991 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O1CCCC1.Br[C:26]1[N:34]2[C:29]([CH:30]=[N:31][C:32]([NH:35][C:36]3[CH:41]=[CH:40][C:39]([N:42]4[CH2:47][CH2:46][O:45][CH2:44][CH2:43]4)=[CH:38][CH:37]=3)=[N:33]2)=[CH:28][CH:27]=1.[OH:48][C:49]1[N:54]=[CH:53][C:52](B(O)O)=[CH:51][CH:50]=1.C(=O)([O-])[O-].[Na+].[Na+].O.C(O)C.[Cl-].[Na+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[N:42]1([C:39]2[CH:40]=[CH:41][C:36]([NH:35][C:32]3[N:31]=[CH:30][C:29]4=[CH:28][CH:27]=[C:26]([C:52]5[CH:51]=[CH:50][C:49]([OH:48])=[N:54][CH:53]=5)[N:34]4[N:33]=3)=[CH:37][CH:38]=2)[CH2:47][CH2:46][O:45][CH2:44][CH2:43]1

Participants

10

Reactant 8

HCID 702EthanolHCID 962WaterHCID 5234Sodium ChlorideHCID 8028TetrahydrofuranHCID 10340Sodium CarbonateHCID 11776TriphenylphosphineHCID 54578326(7-Bromo-pyrrolo[2,1-f][1,2,4]triazin-2-yl)-(4-morpholin-4-yl-phenyl)-amineHCID 178514836HCID 178514836, compound

Product 1

HCID 178515836HCID 178515836, compoundYield 5.2%

Reagents, catalysts & solvents 1

HCID 167845palladium(II) acetateCatalyst

Procedure

Palladium Acetate (0.018 g, 0.000080 mol) and Triphenylphosphine (0.026 g, 0.00010 mol) were dissolved in Tetrahydrofuran (1.2 mL, 0.015 mol) 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)-(4-morpholin-4-yl-phenyl)-amine (0.150 g, 0.000401 mol) was then added and the reaction was again allowed to stir for 10 minutes. 6-hydroxy-3-pyridine boronic acid (0.111 g, 0.000802 mol) was added followed by 0.9 M of Sodium carbonate in water (1 mL, 0.0009 mol) and Ethanol (1.2 mL, 0.021 mol). 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. Combined organics were dried over sodium sulfate, filtered and reduced en vacuo. The crude mixture was purified by Gilson prep HPLC to afford 8.16 mg of 5-[2-(4-Morpholin-4-yl-phenylamino)-pyrrolo[2,1-f][1,2,4]triazin-7-yl]-pyridin-2-ol as a lyophilized powder. (M+H)=389.7. 1H NMR (400 MHz, DMSO, d6) δ 9.27 (s, 1H), 8.89 (s, 1H), 8.42 (m, 1H), 8.13 (dd, 1H, J=2.60, 7.00 Hz), 7.58 (d, 2H, J=8.92 Hz), 7.06 (m, 3H), 6.90 (d, 1H, J=4.76 Hz), 6.52 (d, 1H, J=9.61 Hz), 3.77 (m, 4H), 3.11 (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
  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-bb59a199742d4bd396386b41399cef7c
Source dataset
uspto-grants-2013_06
Patent number
US08471005B2

Reaction notes

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