Dichloromethane → 7-(3,4-Diamino-5-methylphenyl)-1-((tetrahydro-2H-pyran-4-yl)methyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

HRID 717120Notes

Reaction equation

HRID 717120 reaction equation
[CH3:1][C:2]1[CH:7]=[C:6](B2OC(C)(C)C(C)(C)O2)[CH:5]=[C:4]([NH2:17])[C:3]=1[NH2:18].Br[C:20]1[N:25]=[C:24]2[N:26]([CH2:31][CH:32]3[CH2:37][CH2:36][O:35][CH2:34][CH2:33]3)[C:27](=[O:30])[CH2:28][NH:29][C:23]2=[N:22][CH:21]=1.ClCCl.C(=O)([O-])[O-].[Na+].[Na+]>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].C(O)(C)C.O1CCOCC1>[NH2:17][C:4]1[CH:5]=[C:6]([C:20]2[N:25]=[C:24]3[N:26]([CH2:31][CH:32]4[CH2:37][CH2:36][O:35][CH2:34][CH2:33]4)[C:27](=[O:30])[CH2:28][NH:29][C:23]3=[N:22][CH:21]=2)[CH:7]=[C:2]([CH3:1])[C:3]=1[NH2:18]

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 666077053-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzene-1,2-diamineHCID 866446427-bromo-1-((tetrahydro-2H-pyran-4-yl)methyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

Product 1

HCID 666070657-(3,4-Diamino-5-methylphenyl)-1-((tetrahydro-2H-pyran-4-yl)methyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-oneYield 99.1%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 3776IsopropanolSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

3-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzene-1,2-diamine (0.523 g, 2.109 mmol), 7-bromo-1-((tetrahydro-2H-pyran-4-yl)methyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one (0.600 g, 1.834 mmol), [1,1′-bis(diphenylphosphino)-ferrocene]dichloropalladium(II), complex with dichloromethane (1:1) (0.150 g, 0.183 mmol), sodium carbonate (1 M in water, 5.50 mmol), 1,4-dioxane (4.1 mL) and isopropanol (1.4 mL) were combined in a sealable vessel with a stirbar. The system was purged with nitrogen. The resulting mixture was sealed, stirred vigorously and heated at 100° C. for 3.5 h. The resulting mixture was diluted with 20% methanol in dichloromethane and all volatiles removed under reduced pressure. The residue was taken up in 20% methanol in dichloromethane and concentrated under reduced pressure with silica gel. The residue was purified using flash chromatography (1-10% methanol in dichloromethane) to give the desired product (0.669 g, 1.818 mmol, 99% yield) as a brown solid. MS (ESI) m/z 369.1 [M+1]+.

Workup

  1. customThe system was purged with nitrogen
  2. customThe resulting mixture was sealed
  3. additionThe resulting mixture was diluted with 20% methanol in dichloromethane
  4. customall volatiles removed under reduced pressure
  5. concentrationconcentrated under reduced pressure with silica gel
  6. customThe residue was purified

Sources & evidence

ORD record
ord-223e596f326743f281a0ad7b599be0c8
Source dataset
uspto-grants-2015_11
Patent number
US09193692B2

Reaction notes

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