3-Aminophenol → N-(3-hydroxyphenyl)-4-[[(1S)-1-(5-methyl-4-oxo-3-phenylpyrrolo[2,1-f][1,2,4]triazin-2-yl)ethyl]amino]-7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide

HRID 1052722Notes

Reaction equation

HRID 1052722 reaction equation
[CH3:1][C:2]1[CH:3]=[CH:4][N:5]2[C:10]=1[C:9](=[O:11])[N:8]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[C:7]([C@@H:18]([NH:20][C:21]1[C:22]3[C:29]([C:30](O)=[O:31])=[CH:28][NH:27][C:23]=3[N:24]=[CH:25][N:26]=1)[CH3:19])=[N:6]2.[NH2:33][C:34]1[CH:35]=[C:36]([OH:40])[CH:37]=[CH:38][CH:39]=1.C(N(C(C)C)CC)(C)C.C(P1(=O)OP(CCC)(=O)OP(CCC)(=O)O1)CC>CN(C=O)C>[OH:40][C:36]1[CH:35]=[C:34]([NH:33][C:30]([C:29]2[C:22]3[C:21]([NH:20][C@H:18]([C:7]4[N:8]([C:12]5[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=5)[C:9](=[O:11])[C:10]5=[C:2]([CH3:1])[CH:3]=[CH:4][N:5]5[N:6]=4)[CH3:19])=[N:26][CH:25]=[N:24][C:23]=3[NH:27][CH:28]=2)=[O:31])[CH:39]=[CH:38][CH:37]=1

Participants

6

Reactant 4

HCID 115683-AminophenolHCID 81531DiisopropylethylamineHCID 111923Propylphosphonic anhydrideHCID 90102798HCID 90102798, compound

Product 1

HCID 73775934N-(3-hydroxyphenyl)-4-[[(1S)-1-(5-methyl-4-oxo-3-phenylpyrrolo[2,1-f][1,2,4]triazin-2-yl)ethyl]amino]-7H-pyrrolo[2,3-d]pyrimidine-5-carboxamideYield 6.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

(S)-4-((1-(5-Methyl-4-oxo-3-phenyl-3,4-dihydropyrrolo[2,1-f][1,2,4]triazin-2-yl)ethyl)amino)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxylic acid (25 mg, 0.06 mmol), 3-aminophenol (7 mg, 0.07 mmol) and diisopropylethylamine (41 μl, 0.23 mmol) were dissolved in DMF (1.5 ml) and stirred for 30 min. The reaction flask was then sealed and T3P® (50% in DMF, 140 μl, 0.24 mmol) was added dropwise and the reaction mixture stirred overnight at room temperature. The mixture was poured into ice and extracted with ethyl acetate. The resulting organic solution was washed with water and brine, dried over magnesium sulphate, filtered and the solvents were removed under reduced pressure. The product was purified by flash chromatography using SP1® Purification System (0% to 5% DCM/MeOH) to give 2 mg (6% yield) of the title compound as a white solid.

Workup

  1. customThe reaction flask was then sealed
  2. stirringthe reaction mixture stirred overnight at room temperature
  3. additionThe mixture was poured into ice
  4. extractionextracted with ethyl acetate
  5. washThe resulting organic solution was washed with water and brine
  6. dry with materialdried over magnesium sulphate
  7. filtrationfiltered
  8. customthe solvents were removed under reduced pressure
  9. customThe product was purified by flash chromatography
  10. customSP1® Purification System (0% to 5% DCM/MeOH)

Sources & evidence

ORD record
ord-eb18c437329a49d2a0a19004d47f26a8
Source dataset
uspto-grants-2016_07
Patent number
US09388189B2

Reaction notes

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