Potassium tert-butoxide → HCID 90386249, compound

HRID 2170200Notes

Reaction equation

HRID 2170200 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]([CH:24]2[CH2:26][CH:25]2[C:27]#[N:28])=[N:11]3)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CC([O-:33])(C)C.[K+]>C(O)(C)(C)C>[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]([CH:24]2[CH2:26][CH:25]2[C:27]([NH2:28])=[O:33])=[N:11]3)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

4

Reactant 2

HCID 23665647Potassium tert-butoxideHCID 90386185HCID 90386185, compound

Product 1

HCID 90386249HCID 90386249, compoundYield 22.5%

Reagents, catalysts & solvents 1

HCID 6386tert-ButanolSolvent2×

Procedure

To a solution of (±)-2-(5-phenyl-4-((pyridin-2-ylmethyl)amino)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclopropanecarbonitrile (550 mg, 1.50 mmol) in t-butanol (30 mL) was added KOtBu (842 mg, 7.51 mmol). The reaction mixture was heated to reflux at 90° C. for 12 h. t-Butanol was evaporated under reduced pressure and water (25 mL) was added to the reaction mixture. The aqueous layer was acidified with aqueous citric acid solution and extracted with DCM (3×50 mL). The combined organic extracts were washed with brine (25 mL), dried over sodium sulfate and concentrated. The residue was purified by preparative HPLC (Condition B-108 as described in general methods) to obtain (±)-2-(5-phenyl-4-((pyridin-2-ylmethyl)amino)pyrrolo[2,1-f][1,2,4]triazin-2-yl)cyclopropanecarboxamide (130 mg, 22.0%) which was resolved by chiral HPLC (Condition B-109 as described in general methods) to obtain enantiomer-1 (42 mg) and enantiomer-2 (46 mg).

Workup

  1. temperatureThe reaction mixture was heated
  2. customwas evaporated under reduced pressure and water (25 mL)
  3. additionwas added to the reaction mixture
  4. extractionextracted with DCM (3×50 mL)
  5. washThe combined organic extracts were washed with brine (25 mL)
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated
  8. customThe residue was purified by preparative HPLC (Condition B-108 as described in general methods)

Sources & evidence

ORD record
ord-f040ce7f25cb4c7eb31107e0404e44cb
Source dataset
uspto-grants-2015_06
Patent number
US09050345B2

Reaction notes

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