Sodium Carbonate → 4-(8-(Cyclobutylamino)-[1,2,4]triazolo[1,5-a]pyrazin-5-yl)furan-2-carboxamide

HRID 1093961Notes

Reaction equation

Br[C:2]1[N:7]2[N:8]=[CH:9][N:10]=[C:6]2[C:5]([NH:11][CH:12]2[CH2:15][CH2:14][CH2:13]2)=[N:4][CH:3]=1.CC1(C)C(C)(C)OB([C:24]2[CH:25]=[C:26]([C:29]([NH2:31])=[O:30])[O:27][CH:28]=2)O1.C(=O)([O-])[O-].[Na+].[Na+]>C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Pd].[Pd].[Pd].[Pd].O1CCOCC1>[CH:12]1([NH:11][C:5]2[C:6]3[N:7]([N:8]=[CH:9][N:10]=3)[C:2]([C:24]3[CH:25]=[C:26]([C:29]([NH2:31])=[O:30])[O:27][CH:28]=3)=[CH:3][N:4]=2)[CH2:15][CH2:14][CH2:13]1

Participants

Conditions

Temperature: 90 °C

Procedure

The product of Step 1 (900 mg, 3.35 mmol), Intermediate 5 (4-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-furan-2-carboxylic acid amide, 1.8 g, 4.02 mmol), tetrakis palladium triphenylphosphine (970 mg, 0.84 mmol), sodium carbonate solution (1.5 M, 18 mL, 26.8 mmol) and dioxane (20 mL) are combined in a flask. The mixture is degassed with nitrogen for 10 min then sealed and heated at 90° C. for 18 h. The reaction mixture is cooled and the precipitate collected by filtration. The precipitate is washed with 2% methanol: dichloromethane (2 mL) to give the title compound as a white solid (910 mg, 91%). 1H-NMR (400 MHz, d6-DMSO) =1.74-1.76 (m, 2H), 2.22-2.26 (m, 2H), 2.32 (brs, 2H), 4.70 (brd, 1H, J=7.6), 7.58 (s, 1H), 7.86 (s, 1H), 7.97 (s, 1H), 8.12 (s, 1H), 8.35 (d, 1H, J=7.2), 8.69 (d, 11H, J=9.6). LCMS: Rt 2.63 min (90.4%), m/z (APCI) 299 (M+H)+.

Workup

customThe mixture is degassed with nitrogen for 10 min
customthen sealed
temperatureThe reaction mixture is cooled
filtrationthe precipitate collected by filtration
washThe precipitate is washed with 2% methanol

Sources & evidence

ORD record: ord-5fe68fceb45e4aa9983e0f7c82f52b11
Source dataset: uspto-grants-2012_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08133895B2

Reaction notes

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