Dichloromethane → HCID 178462962, compound

HRID 717166Notes

Reaction equation

HRID 717166 reaction equation
Br[C:2]1[C:3]([CH3:19])=[N:4][C:5]([C:8]2[N:12]=[CH:11][N:10](C3CCCCO3)[N:9]=2)=[CH:6][CH:7]=1.B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.C([O-])(=O)C.[K+].C(=O)([O-])[O-].[K+].[K+].ClCCl.Br[C:53]1[N:58]=[C:57]2[N:59]([CH2:64][CH3:65])[C:60](=[O:63])[CH2:61][NH:62][C:56]2=[N:55][CH:54]=1>O1CCOCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].O>[CH2:64]([N:59]1[C:57]2=[N:58][C:53]([C:2]3[C:3]([CH3:19])=[N:4][C:5]([C:8]4[NH:12][CH:11]=[N:10][N:9]=4)=[CH:6][CH:7]=3)=[CH:54][N:55]=[C:56]2[NH:62][CH2:61][C:60]1=[O:63])[CH3:65]

Participants

10

Reactant 6

HCID 6344Dichloromethane2×HCID 11430Potassium CarbonateHCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 582983093-bromo-2-methyl-6-(1-(tetrahydro-2H-pyran-2-yl)-1H-1,2,4-triazol-3-yl)pyridineHCID 866542757-bromo-1-ethyl-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

Product 1

HCID 178462962HCID 178462962, compoundYield 57%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)Catalyst2×HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 3-Bromo-2-methyl-6-(1-(tetrahydro-2H-pyran-2-yl)-1H-1,2,4-triazol-3-yl)pyridine (1 equiv), bis(pinacolato)diboron (1.05 equiv), potassium acetate (2 equiv), potassium carbonate (3 equiv), [1,1′-bis(diphenylphosphino)-ferrocene]dichloropalladium(II), complex with dichloromethane (1:1) (0.1 equiv) in anhydrous dioxane was degassed and heated at 90° C. for 2 h. The mixture was cooled to <40° C. and 7-bromo-1-ethyl-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one (1 equiv), water and [1,1′-bis(diphenylphosphino)-ferrocene]dichloropalladium(II), complex with dichloromethane (1:1) (0.05 equiv) were added. The mixture was degassed and heated at 65-70° C. under nitrogen for 1 h. The mixture was cooled to <40° C., diluted with water and ethyl acetate. Standard ethyl acetate/water work up followed by flash column chromatography (0-5% methanol in dichloromethane) gave the title compound in 57% yield. 1H NMR (400 MHz, DMSO-d6) δ (ppm) 7.99 (s, 2H), 7.93 (s, 1H), 7.72 (s, 1H), 4.22 (s, 2H), 4.05 (q, J=6.77 Hz, 2H), 2.71 (s, 3H), 1.18 (t, J=7.03 Hz, 3H); MS (ESI) m/z 337.6 [M+1]+.

Workup

  1. customwas degassed
  2. temperatureThe mixture was cooled to <40° C.
  3. customThe mixture was degassed
  4. temperatureheated at 65-70° C. under nitrogen for 1 h
  5. temperatureThe mixture was cooled to <40° C.
  6. additiondiluted with water and ethyl acetate

Sources & evidence

ORD record
ord-2070d6a96d94444082be9758fdfc805f
Source dataset
uspto-grants-2015_11
Patent number
US09193692B2

Reaction notes

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