Triethylamine → HCID 178432648, compound

HRID 454341Notes

Reaction equation

HRID 454341 reaction equation
[CH:1]([N:4]1[C:9]2=[N:10][C:11]([C:14]3[C:15]([CH3:31])=[N:16][C:17]([C:20]4[N:24](C5CCCCO5)[CH:23]=[N:22][N:21]=4)=[CH:18][CH:19]=3)=[CH:12][N:13]=[C:8]2[NH:7][CH2:6][C:5]1=[O:32])([CH3:3])[CH3:2].BrC1C(C)=NC(C2N=CN(C3CCCCO3)N=2)=CC=1.C(N1C2=NC([Sn](C)(C)C)=CN=C2NCC1=O)(C)C.C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.C(N(CC)CC)C>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].CN(C)C=O>[CH:1]([N:4]1[C:9]2=[N:10][C:11]([C:14]3[C:15]([CH3:31])=[N:16][C:17]([C:20]4[NH:24][CH:23]=[N:22][N:21]=4)=[CH:18][CH:19]=3)=[CH:12][N:13]=[C:8]2[NH:7][CH2:6][C:5]1=[O:32])([CH3:3])[CH3:2]

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 80271Tri-o-tolylphosphineHCID 582983093-bromo-2-methyl-6-(1-(tetrahydro-2H-pyran-2-yl)-1H-1,2,4-triazol-3-yl)pyridineHCID 666075961-Isopropyl-7-(2-methyl-6-(4-(tetrahydro-2H-pyran-2-yl)-4H-1,2,4-triazol-3-yl)pyridin-3-yl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-oneHCID 666080081-Isopropyl-7-(trimethylstannyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

Product 1

HCID 178432648HCID 178432648, compoundYield 66.7%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

1-Isopropyl-7-(2-methyl-6-(4-(tetrahydro-2H-pyran-2-yl)-4H-1,2,4-triazol-3-yl)pyridin-3-yl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one. To a flask was added 3-Bromo-2-methyl-6-(1-(tetrahydro-2H-pyran-2-yl)-1H-1,2,4-triazol-3-yl)pyridine (0.446 g, 1.380 mmol), 1-isopropyl-7-(trimethylstannyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one (0.490 g, 1.380 mmol), tris(dibenzylideneacetone)dipalladium(0) (0.139 g, 0.152 mmol), tri-o-tolylphosphine (0.092 g, 0.304 mmol), triethylamine (0.577 mL, 4.14 mmol) and N,N-dimethylformamide (3 mL). Nitrogen gas was bubbled through the reaction mixture for 5 min and the mixture was heated to 100° C. for 1 h. After cooling to rt, the reaction mixture was filtered through Celite, rinsed with methanol and concentrated to dryness. The resulting residue was purified by silica gel flash column chromatography (0-80% ethyl acetate in hexanes, followed by 0-10% methanol in dichloromethane) to yield the desired product (0.40 g, 0.921 mmol, 66.7% yield). MS (ESI) m/z 435.5 [M+1]+.

Workup

  1. customNitrogen gas was bubbled through the reaction mixture for 5 min
  2. temperatureAfter cooling to rt
  3. filtrationthe reaction mixture was filtered through Celite
  4. washrinsed with methanol
  5. concentrationconcentrated to dryness
  6. customThe resulting residue was purified by silica gel flash column chromatography (0-80% ethyl acetate in hexanes, followed by 0-10% methanol in dichloromethane)

Sources & evidence

ORD record
ord-cb9fb7787b6a4ef098c6398343c80405
Source dataset
uspto-grants-2013_07
Patent number
US08492381B2

Reaction notes

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