Triethylamine → HCID 178495835, compound

HRID 1890883Notes

Reaction equation

HRID 1890883 reaction equation
[CH3:1][O:2][CH2:3][CH2:4][N:5]1[C:10]2=[N:11][C:12]([Sn](C)(C)C)=[CH:13][N:14]=[C:9]2[NH:8][CH2:7][C:6]1=[O:19].Br[C:21]1[C:22]([CH3:38])=[N:23][C:24]([C:27]2[N:31]=[CH:30][N:29](C3CCCCO3)[N:28]=2)=[CH:25][CH:26]=1.C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.C(N(CC)CC)C>CN(C)C=O>[CH3:1][O:2][CH2:3][CH2:4][N:5]1[C:10]2=[N:11][C:12]([C:21]3[C:22]([CH3:38])=[N:23][C:24]([C:27]4[NH:31][CH:30]=[N:29][N:28]=4)=[CH:25][CH:26]=3)=[CH:13][N:14]=[C:9]2[NH:8][CH2:7][C:6]1=[O:19]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 80271Tri-o-tolylphosphineHCID 582983093-bromo-2-methyl-6-(1-(tetrahydro-2H-pyran-2-yl)-1H-1,2,4-triazol-3-yl)pyridineHCID 666080181-(2-Methoxyethyl)-7-(trimethylstannyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

Product 1

HCID 178495835HCID 178495835, compoundYield 10.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
130 °C

Procedure

1-(2-Methoxyethyl)-7-(trimethylstannyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one (0.5 g, 1.348 mmol), 3-bromo-2-methyl-6-(1-(tetrahydro-2H-pyran-2-yl)-1H-1,2,4-triazol-3-yl)pyridine (0.436 g, 1.348 mmol), tris(dibenzylidineacetone)dipalladium(0) (0.123 g, 0.135 mmol), tri-o-tolylphosphine (0.082 g, 0.270 mmol), triethylamine (0.584 mL, 4.04 mmol) and N,N-dimethylformamide (10 mL) were combined in a 75 mL sealable flask, the atmosphere in the flask was removed and replaced with nitrogen. The mixture was stirred at 130° C. for 3 h. The resulting mixture was cooled to room temperature and filtered. The organic layer was concentrated under reduced pressure. The resulting residue was diluted with methanol and dimethylsulfoxide, filtered and purified using reverse-phase preparatory HPLC (10-30% acetonitrile+0.1% TFA in water+0.1% TFA, over 30 min). Fractions containing clean product were passed through a Phenomenex Strata-X-C solid phase extraction column. The column was washed successively with water, acetonitrile, methanol and 5% ammonium hydroxide in methanol. The product eluted with the 5% ammonium hydroxide in methanol eluent and was concentrated under reduced pressure. The residue was triturated with ethyl ether in hexane to make a fine powder and dried under vacuum at 50° C. to give the desired product (0.05 g, 0.136 mmol, 10% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ (ppm) 8.10 (br. s., 1H), 7.98 (br. s., 1H), 7.94 (s, 1H), 7.73 (br. s., 1H), 4.13-4.28 (m, 4H), 3.55 (t, J=6.25 Hz, 2H), 3.24 (s, 3H), 2.70 (br. s., 3H); MS (ESI) m/z 367.2[M+1]+.

Workup

  1. customthe atmosphere in the flask was removed
  2. temperatureThe resulting mixture was cooled to room temperature
  3. filtrationfiltered
  4. concentrationThe organic layer was concentrated under reduced pressure
  5. additionThe resulting residue was diluted with methanol and dimethylsulfoxide
  6. filtrationfiltered
  7. custompurified
  8. customreverse-phase preparatory HPLC (10-30% acetonitrile+0.1% TFA in water+0.1% TFA, over 30 min)
  9. additionFractions containing clean product
  10. extractionwere passed through a Phenomenex Strata-X-C solid phase extraction column
  11. washThe column was washed successively with water, acetonitrile, methanol and 5% ammonium hydroxide in methanol
  12. washThe product eluted with the 5% ammonium hydroxide in methanol eluent
  13. concentrationwas concentrated under reduced pressure
  14. customThe residue was triturated with ethyl ether in hexane
  15. customdried under vacuum at 50° C.

Sources & evidence

ORD record
ord-1ea341e78ddc491cb7e570f80c0db5f5
Source dataset
uspto-grants-2013_08
Patent number
US08507492B2

Reaction notes

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