Sodium Carbonate → N-tert-butyl-2-(isoquinolin-8-yl)-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide

HRID 246714Notes

Reaction equation

Br[C:2]1[N:7]=[C:6]2[C:8]([C:11]([NH:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])=[CH:9][NH:10][C:5]2=[N:4][CH:3]=1.[CH:18]1[C:27]2[C:22](=[CH:23][CH:24]=[CH:25][C:26]=2B(O)O)[CH:21]=[CH:20][N:19]=1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:14]([NH:13][C:11]([C:8]1[C:6]2=[N:7][C:2]([C:26]3[CH:25]=[CH:24][CH:23]=[C:22]4[C:27]=3[CH:18]=[N:19][CH:20]=[CH:21]4)=[CH:3][N:4]=[C:5]2[NH:10][CH:9]=1)=[O:12])([CH3:17])([CH3:16])[CH3:15]

Participants

Conditions

Temperature: 90 °C

Procedure

A mixture of 2-bromo-N-tert-butyl-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide (0.1 g, 0.337 mmol), isoquinolin-8-ylboronic acid (64 mg, 0.37 mmol), Pd2 dba3 (77 mg, 0.067 mmol), X-Phos (64 mg, 0.135 mmol) and Na2CO3 (107 mg, 1.01 mmol) in dioxane (20 mL) and water (5 mL) was heated to 90° C. for 16 hours under N2 atmosphere. Reaction mixture was concentrated and the residue was purified by preparative-TLC (methanol:dichloromethane=1:10) to afford N-tert-butyl-2-(isoquinolin-8-yl)-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide (76 mg, 66%) as a white solid. 1H NMR (300 MHz, CDCl3): δ 11.77 (s, 1H), 9.95 (s, 1H), 8.89 (s, 1H), 8.69 (d, 1H, J=5.7 Hz), 8.45 (s, 1H), 8.41 (s, 1H), 8.01-7.84 (m, 4H), 1.46 (s, 9H). LCMS: (M+H)+=346.

Workup

customReaction mixture
concentrationwas concentrated
customthe residue was purified by preparative-TLC (methanol:dichloromethane=1:10)

Sources & evidence

ORD record: ord-9acac12570744773a8ef781aab1fc93f
Source dataset: uspto-grants-2014_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08658646B2

Reaction notes

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