Triethylamine → (S)-2-(1-((6-Amino-5-(3-fluoro-4-hydroxyphenyl)pyrimidin-4-yl)amino)ethyl)-3-phenylpyrrolo[2,1-f][1,2,4]triazin-4(3H)-one

HRID 1052656Notes

Reaction equation

HRID 1052656 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]([NH:8][C@H:9]([C:11]2[N:16]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[C:15](=[O:23])[C:14]3=[C:24](Br)[CH:25]=[CH:26][N:13]3[N:12]=2)[CH3:10])[C:3]=1[C:28]1[CH:33]=[CH:32][C:31]([OH:34])=[C:30]([F:35])[CH:29]=1.C(N(CC)CC)C.[H][H]>CO.CN(C)C=O.[Pd]>[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]([NH:8][C@H:9]([C:11]2[N:16]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[C:15](=[O:23])[C:14]3=[CH:24][CH:25]=[CH:26][N:13]3[N:12]=2)[CH3:10])[C:3]=1[C:28]1[CH:33]=[CH:32][C:31]([OH:34])=[C:30]([F:35])[CH:29]=1

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 118433808(S)-2-(1-((6-Amino-5-(3-fluoro-4-hydroxyphenyl)pyrimidin-4-yl)amino)ethyl)-5-bromo-3-phenylpyrrolo[2,1-f][1,2,4]triazin-4(3H)-oneHCID 178418361HCID 178418361, compound

Product 1

HCID 73775104(S)-2-(1-((6-Amino-5-(3-fluoro-4-hydroxyphenyl)pyrimidin-4-yl)amino)ethyl)-3-phenylpyrrolo[2,1-f][1,2,4]triazin-4(3H)-oneYield 4%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Procedure

(S)-2-(1-((6-Amino-5-(3-fluoro-4-hydroxyphenyl)pyrimidin-4-yl)amino)ethyl)-5-bromo-3-phenylpyrrolo[2,1-f][1,2,4]triazin-4(3H)-one (150 mg, 0.28 mol) was dissolved in 10 mL methanol and 2 mL dimethylformamide. Triethylamine and palladium on carbon were added under nitrogen atmosphere and the mixture was submitted at 30 psi of hydrogen conditions for 4 h. Further catalyst was added and the mixture was hydrogenated at 30 psi for 48 h. The reaction mixture was filtered off and evaporated to dryness. The residue was purified by reverse phase using SP1® Purification System and then was purified by normal phase (0% to 100%, hexane-ethyl acetate) to give 5 mg (4%) of the title compound as a solid. Purity 99%.

Workup

  1. additionFurther catalyst was added
  2. filtrationThe reaction mixture was filtered off
  3. customevaporated to dryness
  4. customThe residue was purified by reverse phase
  5. custom® Purification System
  6. customwas purified by normal phase (0% to 100%, hexane-ethyl acetate)

Sources & evidence

ORD record
ord-3a7640d345234edeabab603e7470f552
Source dataset
uspto-grants-2016_07
Patent number
US09388189B2

Reaction notes

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