Potassium Phosphate, Tribasic → 1-{2-[3-(5,6-Dihydro-8H-[1,2,4]triazolo[4,3-a]pyrazin-7-yl)-phenyl]-5H-pyrrolo[2,3-b]pyrazin-7-yl}-2,2-dimethyl-propan-1-one

HRID 1677432Notes

Reaction equation

HRID 1677432 reaction equation
[CH3:1][C:2]([CH3:46])([CH3:45])[C:3]([C:5]1[C:13]2[C:8](=[N:9][CH:10]=[C:11]([C:14]3[CH:15]=[C:16](OS(C(F)(F)C(F)(F)C(F)(F)C(F)(F)F)(=O)=O)[CH:17]=[CH:18][CH:19]=3)[N:12]=2)[N:7](COCC[Si](C)(C)C)[CH:6]=1)=[O:4].[N:47]1[N:48]=[CH:49][N:50]2[CH2:55][CH2:54][NH:53][CH2:52][C:51]=12.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[N:47]1[N:48]=[CH:49][N:50]2[CH2:55][CH2:54][N:53]([C:16]3[CH:15]=[C:14]([C:11]4[N:12]=[C:13]5[C:5]([C:3](=[O:4])[C:2]([CH3:45])([CH3:1])[CH3:46])=[CH:6][NH:7][C:8]5=[N:9][CH:10]=4)[CH:19]=[CH:18][CH:17]=3)[CH2:52][C:51]=12

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 179987185H,6H,7H,8H-(1,2,4)triazolo(4,3-a)pyrazineHCID 595406441,1,2,2,3,3,4,4,4-nonafluoro-butane-1-sulfonic acid 3-[7-(2,2-dimethyl-propionyl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-phenyl ester

Product 1

HCID 595407051-{2-[3-(5,6-Dihydro-8H-[1,2,4]triazolo[4,3-a]pyrazin-7-yl)-phenyl]-5H-pyrrolo[2,3-b]pyrazin-7-yl}-2,2-dimethyl-propan-1-one

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
115 °C

Procedure

A mixture of 1,1,2,2,3,3,4,4,4-nonafluoro-butane-1-sulfonic acid 3-[7-(2,2-dimethyl-propionyl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-phenyl ester (0.175 g, 0.25 mmol, see the experimental below preparation of this compound), 5,6,7,8-Tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine (0.061 g, 0.5 mmol), Pd2(dba)3 (0.041 g, 0.41 mmol), XANPHOS (0.046 g, 0.08 mmol) and K3PO4 in toluene (2 mL) were heated in a microwave oven under an argon atmosphere at 115° C. for 1 h. After cooling to room temperature, the reaction mixture was directly purified by flash column chromatography on silica gel with a mixture of 28% aqueous ammonium hydroxide:methanol:DCM (1:10:60) in DCM (20% to 80% gradient over 30 min) to give 20 mg of the desired product as a yellow foam. 1H NMR (CDCl3, 400 MHz): δ 8.84 (s, 1H), 8.47 (s, 1H), 8.23 (s, 1H), 7.95 (s, 1H), 7.71 (d, J=7.7 Hz, 1H), 7.52 (t, J=8.0 Hz, 1H), 7.13 (d, J=8.2 Hz, 1H), 5.74 (s, 2H), 4.77 (s, 2H), 4.30 (t, J=5.3 Hz, 2H), 3.88 (t, J=5.4 Hz, 2H), 3.65 (t, J=8.2 Hz, 2H), 1.62 (s, 9H), 0 (s, 9H); MS [M+H]+: 532.

Workup

  1. temperatureAfter cooling to room temperature
  2. customthe reaction mixture was directly purified by flash column chromatography on silica gel with a mixture of 28% aqueous ammonium hydroxide:methanol:DCM (1:10:60) in DCM (20% to 80% gradient over 30 min)

Sources & evidence

ORD record
ord-9769acb5f5444f46a171bfc62eb2593b
Source dataset
uspto-grants-2011_08
Patent number
US08008298B2

Reaction notes

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