Dichloromethane → 7-(2-Amino-4-methyl-1H-benzo[d]imidazol-6-yl)-1-((tetrahydro-2H-pyran-4-yl)Methyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one

HRID 2361207Notes

Reaction equation

HRID 2361207 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([C:10]2[N:15]=[C:14]3[N:16]([CH2:21][CH:22]4[CH2:27][CH2:26][O:25][CH2:24][CH2:23]4)[C:17](=[O:20])[CH2:18][NH:19][C:13]3=[N:12][CH:11]=2)[CH:5]=[C:6]([CH3:9])[C:7]=1[NH2:8].CC1C=C(B2OC(C)(C)C(C)(C)O2)C=[C:31]([NH2:44])C=1N.BrC1N=C2N(CC3CCOCC3)C(=O)CNC2=NC=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>[NH2:44][C:31]1[NH:1][C:2]2[CH:3]=[C:4]([C:10]3[N:15]=[C:14]4[N:16]([CH2:21][CH:22]5[CH2:27][CH2:26][O:25][CH2:24][CH2:23]5)[C:17](=[O:20])[CH2:18][NH:19][C:13]4=[N:12][CH:11]=3)[CH:5]=[C:6]([CH3:9])[C:7]=2[N:8]=1

Participants

9

Reactant 5

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 666070657-(3,4-Diamino-5-methylphenyl)-1-((tetrahydro-2H-pyran-4-yl)methyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-oneHCID 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 582983117-(2-Amino-4-methyl-1H-benzo[d]imidazol-6-yl)-1-((tetrahydro-2H-pyran-4-yl)Methyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-oneYield 99%

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

7-(3,4-Diamino-5-methylphenyl)-1-((tetrahydro-2H-pyran-4-yl)methyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one. 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-0dad02f9051f4924859e929dfe78d536
Source dataset
uspto-grants-2014_04
Patent number
US08686135B2

Reaction notes

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