tert-Butanol → HCID 78323975, compound

HRID 2170155Notes

Reaction equation

HRID 2170155 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:29]#[N:30])=[N:11]3)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C([OH:36])(C)(C)C.CC(C)([O-])C.[K+]>>[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:29]([NH2:30])=[O:36])=[N:11]3)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

4

Reactant 3

HCID 6386tert-ButanolHCID 23665647Potassium tert-butoxideHCID 90386268HCID 90386268, compound

Product 1

HCID 78323975HCID 78323975, compoundYield 44.7%

Conditions

Temperature
90 °C

Procedure

To a solution of 5-(5-phenyl-4-((pyridin-2-ylmethyl)amino)pyrrolo[2,1-f][1,2,4]triazin-2-yl)nicotinonitrile (45.0 mg, 0.112 mmol) in t-butanol (5.00 mL, 502 mmol) was added potassium tert-butoxide (125 mg, 1.12 mmol) and the contents were heated to 90° C. for 12 h. The reaction mixture was allowed to cool and the solvents were removed under reduced pressure. The residue was dissolved in CH2Cl2 (25 mL) and washed with 1.5 N HCl (20 mL). The organic layer was separated and dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to give a brown solid. The solid was purified by preparative HPLC (Condition B-64 as described in general methods) to give 5-(5-phenyl-4-((pyridin-2-ylmethyl)amino)pyrrolo[2,1-f][1,2,4]triazin-2-yl)nicotinamide (21.0 mg, 44.7%) as a brown solid. LCMS Condition B-12: retention time 2.07 min, [M+1]=422.2. HPLC Condition B-1: retention time=6.85 min, Purity=96.30%. 1H NMR (400 MHz, DMSO-d6) δ ppm 4.96 (d, J=4.4 Hz, 2H), 6.84 (d, J=2.8 Hz, 1H), 7.25-7.53 (m, 8H), 7.58-7.72 (m, 3H), 7.93 (d, J=2.8 Hz, 1H), 8.31 (s, 1H), 8.92 (s, 1H), 9.12 (s, 1H), 9.51 (s, 1H).

Workup

  1. temperatureto cool
  2. customthe solvents were removed under reduced pressure
  3. dissolutionThe residue was dissolved in CH2Cl2 (25 mL)
  4. washwashed with 1.5 N HCl (20 mL)
  5. customThe organic layer was separated
  6. dry with materialdried over anhydrous Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customto give a brown solid
  10. customThe solid was purified by preparative HPLC (Condition B-64 as described in general methods)

Sources & evidence

ORD record
ord-185af89016854f159f81b59560d42d3d
Source dataset
uspto-grants-2015_06
Patent number
US09050345B2

Reaction notes

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