Methanol → HCID 78323976, compound

HRID 2170156Notes

Reaction equation

HRID 2170156 reaction equation
[C:1]1([C:7]2[CH:8]=[CH:9][N:10]3[C:15]=2[C:14]([NH:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][N:19]=2)=[N:13][C:12]([C:24]2[CH:25]=[N:26][CH:27]=[C:28]([CH:31]=2)C#N)=[N:11]3)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH3:32][OH:33].[OH-:34].[K+]>O1CCOCC1.O.C(Cl)(Cl)Cl>[C:1]1([C:7]2[CH:8]=[CH:9][N:10]3[C:15]=2[C:14]([NH:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][N:19]=2)=[N:13][C:12]([C:24]2[CH:25]=[N:26][CH:27]=[C:28]([CH:31]=2)[C:32]([OH:34])=[O:33])=[N:11]3)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

7

Reactant 3

HCID 887MethanolHCID 14797Potassium HydroxideHCID 90386268HCID 90386268, compound

Product 1

HCID 78323976HCID 78323976, compoundYield 49%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6212ChloroformSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
95 °C

Procedure

To a stirred solution of 5-(5-phenyl-4-((pyridin-2-ylmethyl)amino)pyrrolo[2,1-f][1,2,4]triazin-2-yl)nicotinonitrile (50.0 mg, 0.124 mmol) in dioxane (5 mL)/MeOH (2 mL) was added KOH (34.8 mg, 0.620 mmol) dissolved in water (2 mL) in a pressure tube. The contents were heated at 95° C. for 12 h. The reaction mixture was allowed to cool and concentrated under reduced pressure to give a white solid. The solid was dissolved in CHCl3 and washed with 1.5 N HCl (5 mL) and the organic layer was separated and dried over anhydrous Na2SO4, filtered and concentrated to give 5-(5-phenyl-4-((pyridin-2-ylmethyl)amino)pyrrolo[2,1-f][1,2,4]triazin-2-yl)nicotinic acid (24.0 mg, 49.0%) as an off-white solid. LCMS Condition B-23: retention time 1.64, [M+1]=423.2. HPLC Condition B-1: retention time 5.80 min, purity 98.80%. 1H NMR (400 MHz, DMSO-d6) δ ppm 4.94 (d, J=4.4 Hz, 2H), 6.83 (d, J=2.8 Hz, 1H), 7.21-7.52 (m, 8H), 7.89 (t, J=1.7 Hz, 1H), 7.96 (d, J=2.8 Hz, 1H), 8.38 (br s, 1H), 8.98 (s, 1H), 9.19 (s, 1H), 9.52 (s, 1H).

Workup

  1. temperatureto cool
  2. concentrationconcentrated under reduced pressure
  3. customto give a white solid
  4. washwashed with 1.5 N HCl (5 mL)
  5. customthe organic layer was separated
  6. dry with materialdried over anhydrous Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-247014e4678542b0835f0c5b7e40d79a
Source dataset
uspto-grants-2015_06
Patent number
US09050345B2

Reaction notes

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