Diisopropylethylamine → (S)-N-((1H-Pyrazol-4-yl)ethyl)-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-carboxamide

HRID 1052728Notes

Reaction equation

HRID 1052728 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]([OH:32])=O)=[CH:28][NH:27][C:23]=3[N:24]=[CH:25][N:26]=1)[CH3:19])=[N:6]2.[NH:33]1[CH:37]=[C:36]([CH2:38]N)[CH:35]=[N:34]1.[CH:40]([N:43](C(C)C)CC)(C)C.C(P1(=O)OP(CCC)(=O)OP(CCC)(=O)O1)CC>CN(C=O)C>[NH:34]1[CH:35]=[C:36]([CH2:38][CH2:40][NH:43][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:32])[CH:37]=[N:33]1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 111923Propylphosphonic anhydrideHCID 230055831H-pyrazol-4-ylmethanamineHCID 90102798HCID 90102798, compound

Product 1

HCID 118433956(S)-N-((1H-Pyrazol-4-yl)ethyl)-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-carboxamideYield 2.6%

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 (50 mg, 0.12 mmol), (1H-pyrazol-4-yl)methanamine (11 mg, 0.11 mmol) and diisopropylethylamine (163 μl, 0.94 mmol) were dissolved in DMF (2 ml) and stirred for 30 min. The reaction flask was then sealed and T3P® (50% in DMF, 270 μl, 0.46 mmol) was added dropwise and the reaction mixture stirred overnight at room temperature. The mixture was poured into ice-water 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 10% DCM/MeOH) to give 1.5 mg (2% 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. extractionextracted with ethyl acetate
  4. washThe resulting organic solution was washed with water and brine
  5. dry with materialdried over magnesium sulphate
  6. filtrationfiltered
  7. customthe solvents were removed under reduced pressure
  8. customThe product was purified by flash chromatography
  9. customSP1® Purification System (0% to 10% DCM/MeOH)

Sources & evidence

ORD record
ord-122880d3969648d1a27dd16332800bd4
Source dataset
uspto-grants-2016_07
Patent number
US09388189B2

Reaction notes

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