Dichloromethane → HCID 178423526, compound

HRID 1640302Notes

Reaction equation

[CH3:1][C:2]1[CH:7]=[C:6]([C:8]2[N:12](C3CCCCO3)[CH:11]=[N:10][N:9]=2)[CH:5]=[CH:4][C:3]=1[C:19]1[N:24]=[C:23]2[NH:25][C:26](=[O:29])[CH2:27][NH:28][C:22]2=[N:21][CH:20]=1.CC1C=C(C2N(C3CCCCO3)C=NN=2)C=CC=1B1OC(C)(C)C(C)(C)O1.FC(F)(F)C(O)=O.BrC1N=C2NC(=O)CNC2=NC=1.[Cl:76]CCl.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>[ClH:76].[CH3:1][C:2]1[CH:7]=[C:6]([C:8]2[NH:12][CH:11]=[N:10][N:9]=2)[CH:5]=[CH:4][C:3]=1[C:19]1[N:24]=[C:23]2[NH:25][C:26](=[O:29])[CH2:27][NH:28][C:22]2=[N:21][CH:20]=1

Participants

Conditions

Temperature: 100 °C

Procedure

7-(2-Methyl-4-(4-(tetrahydro-2H-pyran-2-yl)-4H-1,2,4-triazol-3-yl)phenyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one. 3-(3-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-4-(tetrahydro-2H-pyran-2-yl)-4H-1,2,4-triazole (See Example 2.C) (0.465 g, 1.259 mmol), 7-bromo-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one trifluoroacetate (0.432 g, 1.259 mmol), [1,1′-bis(diphenylphosphino)-ferrocene]dichloropalladium(II), complex with dichloromethane (1:1) (0.103 g, 0.126 mmol), sodium carbonate (1 M in water, 3.78 mL, 3.78 mmol), 1,4-dioxane (2.5 mL) and isopropanol (1 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 70 min. The resulting mixture was diluted with water and dichloromethane and filtered through a fitted funnel. Solids were washed with 20% methanol in dichloromethane. Filtrate and wash were combined and the solvent was removed under reduced pressure. The residue was triturated with acetonitrile. Water was added. Solids were collected by vacuum filtration and washed thoroughly with water and diethyl ether. Solids were washed with 20% methanol in dichloromethane. Filtrate and wash were combined and the solvent was removed under reduced pressure. The residue was taken up in hot DMSO and methanol, filtered and purified using reverse-phase preparatory HPLC (20-65% acetonitrile+0.1% TFA in water+0.1% TFA, over 30 min). Fractions containing the desired product were combined, neutralized with saturated aqueous sodium bicarbonate and concentrated nearly to dryness under reduced pressure. Solids were collected by vacuum filtration, washed with water and dried under high vacuum to give the desired product (0.072 g, 0.184 mmol, 15% yield) as an off-white solid. MS (ESI) m/z 392.1 [M+1]+.

Workup

customThe system was purged with nitrogen
customThe resulting mixture was sealed
additionThe resulting mixture was diluted with water and dichloromethane
filtrationfiltered through a fitted funnel
washSolids were washed with 20% methanol in dichloromethane
washFiltrate and wash
customthe solvent was removed under reduced pressure
customThe residue was triturated with acetonitrile
additionWater was added
filtrationSolids were collected by vacuum filtration
washwashed thoroughly with water and diethyl ether
washSolids were washed with 20% methanol in dichloromethane
washFiltrate and wash
customthe solvent was removed under reduced pressure
filtrationmethanol, filtered
custompurified
customreverse-phase preparatory HPLC (20-65% acetonitrile+0.1% TFA in water+0.1% TFA, over 30 min)
additionFractions containing the desired product
concentrationconcentrated nearly to dryness under reduced pressure
filtrationSolids were collected by vacuum filtration
washwashed with water
customdried under high vacuum

Sources & evidence

ORD record: ord-3a35b31b769f4ac6b8936720997d7bce
Source dataset: uspto-grants-2012_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08110578B2

Reaction notes

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