Sodium Carbonate → 3-(6-methyl-1H-benzimidazol-2-yl)-5-[(E)-prop-1-enyl]pyrazin-2-amine

HRID 1853137Notes

Reaction equation

Br[C:2]1[N:3]=[C:4]([C:9]2[NH:13][C:12]3[CH:14]=[C:15]([CH3:18])[CH:16]=[CH:17][C:11]=3[N:10]=2)[C:5]([NH2:8])=[N:6][CH:7]=1.[CH:19](B(O)O)=[CH:20][CH3:21].C(P(CC)CC)C.C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.Cl[Pd]Cl>[CH3:18][C:15]1[CH:16]=[CH:17][C:11]2[N:10]=[C:9]([C:4]3[C:5]([NH2:8])=[N:6][CH:7]=[C:2](/[CH:19]=[CH:20]/[CH3:21])[N:3]=3)[NH:13][C:12]=2[CH:14]=1

Participants

Conditions

Temperature: 120 °C

Procedure

A mixture of 5-bromo-3-(6-methyl-1H-benzimidazol-2-yl)pyrazin-2-amine (50 mg, 0.1644 mmol), prop-1-enylboronic acid (15.53 mg, 0.1808 mmol), dichloropalladium; triethylphosphane (6.800 mg, 0.01644 mmol) and disodium carbonate (164.4 μL of 2 M, 0.3288 mmol) was dissolved in 1,2-dimethoxyethane (2 mL) and heated at 120° C. under microwave conditions 30 minutes. The residual solids were removed by filtration and the filtrate purified by reverse phase preparative HPLC [Waters Sunfire C18, 10 mM, 100 Å column, gradient 10%-95% B (solvent A: 0.05% TFA in water; solvent B: CH3CN) over 16 minutes at 25 mL/min]. The fractions were collected and freeze-dried to give the title compound as an orange solid (13.7 mg, 31% Yield). 1H NMR (400.0 MHz, DMSO) δ 1.95 (3H, d), 2.45 (3H, s), 6.45-6.55 (1H, m), 6.8-6.9 (1H, m), 6.95 (0.5H, m), 7.05-7.15 (2H, m), 7.22 (0.5H, s), 7.45 (1H, br s), 7.55-7.6 (1H, m), 8.1 (1H, s), 13.15 (1H, vbr s) ppm; MS (ES+) 266.0.

Workup

customThe residual solids were removed by filtration
customthe filtrate purified by reverse phase preparative HPLC [Waters Sunfire C18, 10 mM, 100 Å column, gradient 10%-95% B (solvent A: 0.05% TFA in water; solvent B: CH3CN) over 16 minutes at 25 mL/min]
customThe fractions were collected
customfreeze-dried

Sources & evidence

ORD record: ord-6bc97e86fe474574b8129135c04f3520
Source dataset: uspto-grants-2015_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08962631B2

Reaction notes

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