2-(5-(Trimethylstannyl)pyridin-2-yl)propan-2-ol → 7-(6-(2-Hydroxypropan-2-yl)pyridin-3-yl)-1-(2-methoxyethyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

HRID 1401225Notes

Reaction equation

HRID 1401225 reaction equation
Br[C:2]1[N:7]=[C:6]2[N:8]([CH2:13][CH2:14][O:15][CH3:16])[C:9](=[O:12])[CH2:10][NH:11][C:5]2=[N:4][CH:3]=1.C[Sn](C)(C)[C:19]1[CH:20]=[CH:21][C:22]([C:25]([OH:28])([CH3:27])[CH3:26])=[N:23][CH:24]=1>CN(C)C=O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[OH:28][C:25]([C:22]1[N:23]=[CH:24][C:19]([C:2]2[N:7]=[C:6]3[N:8]([CH2:13][CH2:14][O:15][CH3:16])[C:9](=[O:12])[CH2:10][NH:11][C:5]3=[N:4][CH:3]=2)=[CH:20][CH:21]=1)([CH3:27])[CH3:26]

Participants

5

Reactant 2

HCID 666077842-(5-(Trimethylstannyl)pyridin-2-yl)propan-2-olHCID 866446527-Bromo-1-(2-methoxyethyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

Product 1

HCID 582983337-(6-(2-Hydroxypropan-2-yl)pyridin-3-yl)-1-(2-methoxyethyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-oneYield 38%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
140 °C

Procedure

7-Bromo-1-(2-methoxyethyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one (1 equiv), 2-(5-(trimethylstannyl)pyridin-2-yl)propan-2-ol (See Example 5.E) (1 equiv) and dichlorobis(triphenylphosphine)-palladium(II) (0.2 equiv) were suspended in dimethylformamide. The reaction was purged with nitrogen and was heated to 140° C. for 2 h. The reaction was cooled to room temperature, filtered through Celite and washed with ethyl acetate. Volatiles were removed under reduced pressure and the resulting purple slurry was purified using silica gel column chromatography (0-100% (5% methanol in ethyl acetate) in hexanes). The desired fractions were combined and organic volatiles removed under reduced pressure. The solid was triturated in 5% ethyl acetate in hexanes and washed with hexanes to afford the desired product in 38% yield. 1H NMR (400 MHz, DMSO-d6) δ (ppm) 9.02 (d, J=1.6 Hz, 1H), 8.27 (s, 1H), 8.24 (dd, J=8.6, 2.3 Hz, 1H), 7.71 (d, J=0.8 Hz, 1H), 7.69 (s, 1H), 5.25 (s, 1H), 4.28 (t, J=6.2 Hz, 2H), 4.20 (d, 2H), 3.60 (t, J=6.2 Hz, 2H), 3.26 (s, 3H), 1.46 (s, 6H); MS (ESI) m/z 344.3 [M+1]+.

Workup

  1. customThe reaction was purged with nitrogen
  2. temperatureThe reaction was cooled to room temperature
  3. filtrationfiltered through Celite
  4. washwashed with ethyl acetate
  5. customVolatiles were removed under reduced pressure
  6. customthe resulting purple slurry was purified
  7. customorganic volatiles removed under reduced pressure
  8. customThe solid was triturated in 5% ethyl acetate in hexanes
  9. washwashed with hexanes

Sources & evidence

ORD record
ord-5c4692a363ca4cbe9e1370de4ecdbbb2
Source dataset
uspto-grants-2014_12
Patent number
US08907087B2

Reaction notes

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