Lithium Hydroxide → (S)-3-(4-Amino-6-((1-(5-methyl-4-oxo-3-phenyl-3,4-dihydropyrrolo[2,1-f][1,2,4]triazin-2-yl)ethyl)amino)pyrimidin-5-yl)-5-hydroxybenzoic acid

HRID 1052668Notes

Reaction equation

HRID 1052668 reaction equation
[NH2:1][C:2]1[C:7]([C:8]2[CH:9]=[C:10]([CH:15]=[C:16]([OH:18])[CH:17]=2)[C:11]([O:13]C)=[O:12])=[C:6]([NH:19][C@H:20]([C:22]2[N:27]([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)[C:26](=[O:34])[C:25]3=[C:35]([CH3:38])[CH:36]=[CH:37][N:24]3[N:23]=2)[CH3:21])[N:5]=[CH:4][N:3]=1.[OH-].[Li+]>O1CCCC1.O>[NH2:1][C:2]1[C:7]([C:8]2[CH:9]=[C:10]([CH:15]=[C:16]([OH:18])[CH:17]=2)[C:11]([OH:13])=[O:12])=[C:6]([NH:19][C@H:20]([C:22]2[N:27]([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)[C:26](=[O:34])[C:25]3=[C:35]([CH3:38])[CH:36]=[CH:37][N:24]3[N:23]=2)[CH3:21])[N:5]=[CH:4][N:3]=1

Participants

5

Reactant 2

HCID 3939Lithium HydroxideHCID 131736113(S)-Methyl 3-(4-amino-6-((1-(5-methyl-4-oxo-3-phenyl-3,4-dihydropyrrolo[2,1-f][1,2,4]triazin-2-yl)ethyl)amino)pyrimidin-5-yl)-5-hydroxybenzoate

Product 1

HCID 73776790(S)-3-(4-Amino-6-((1-(5-methyl-4-oxo-3-phenyl-3,4-dihydropyrrolo[2,1-f][1,2,4]triazin-2-yl)ethyl)amino)pyrimidin-5-yl)-5-hydroxybenzoic acidYield 72%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

(S)-Methyl 3-(4-amino-6-((1-(5-methyl-4-oxo-3-phenyl-3,4-dihydropyrrolo[2,1-f][1,2,4]triazin-2-yl)ethyl)amino)pyrimidin-5-yl)-5-hydroxybenzoate (35 mg, 0.07 mmol) was dissolved in 5 mL tetrahydrofuran. Lithium hydroxide in 5 mL water was added and the mixture was stirred at 50° C. for 4 h. The solvent was evaporated and the residue was re-dissolved in dichloromethane. The aqueous phase was acidified with 2N hydrochloric acid. The aqueous was further extracted with dichloromethane and was washed with water and brine, dried over sodium sulphate, filtered and evaporated under reduced pressure. The residue was purified by reverse phase using SP1 ® Purification System to obtain 25 mg (72% yield) of the title compound as a white solid. Purity 97%.

Workup

  1. customThe solvent was evaporated
  2. dissolutionthe residue was re-dissolved in dichloromethane
  3. extractionThe aqueous was further extracted with dichloromethane
  4. washwas washed with water and brine
  5. dry with materialdried over sodium sulphate
  6. filtrationfiltered
  7. customevaporated under reduced pressure
  8. customThe residue was purified by reverse phase
  9. custom® Purification System

Sources & evidence

ORD record
ord-9357ae05949f4d57a44df4b6d5edf399
Source dataset
uspto-grants-2016_07
Patent number
US09388189B2

Reaction notes

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