Sodium Carbonate → 3-(6-methyl-1H-benzo[d]imidazol-2-yl)-5-(1,4-dioxaspiro[4.5]dec-7-en-8-yl)pyrazin-2-amine

HRID 1959349Notes

Reaction equation

HRID 1959349 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.[O:19]1[C:23]2([CH2:28][CH2:27][C:26](B(O)O)=[CH:25][CH2:24]2)[O:22][CH2:21][CH2:20]1.C(P(CC)CC)C.C([O-])([O-])=O.[Na+].[Na+]>CN(C=O)C.Cl[Pd]Cl.CCOC(C)=O>[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]([C:26]4[CH2:27][CH2:28][C:23]5([O:22][CH2:21][CH2:20][O:19]5)[CH2:24][CH:25]=4)[N:3]=3)[NH:13][C:12]=2[CH:14]=1

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 27365TriethylphosphineHCID 441187651,4-Dioxaspiro[4.5]dec-7-en-8-ylboronic acidHCID 580842975-bromo-3-(6-methyl-1H-benzo[d]imidazol-2-yl)pyrazin-2-amine

Product 1

HCID 461992483-(6-methyl-1H-benzo[d]imidazol-2-yl)-5-(1,4-dioxaspiro[4.5]dec-7-en-8-yl)pyrazin-2-amineYield 63%

Reagents, catalysts & solvents 3

HCID 24290Palladium ChlorideCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 5-bromo-3-(6-methyl-1H-benzimidazol-2-yl)pyrazin-2-amine (150 mg, 0.4932 mmol), 1,4-dioxaspiro[4.5]dec-7-en-8-ylboronic acid (181.5 mg, 0.9864 mmol), dichloropalladium; triethylphosphane (10.20 mg, 0.02466 mmol) and Na2CO3 (740.0 μL of 2 M, 1.480 mmol) were heated in DMF (1.500 mL) at 130° C. in a microwave for 30 min. EtOAc was added and the organic phase washed with saturated aqueous Na2CO3, dried (MgSO4) and concentrated in vacuo. The resulting oil was purified by reverse phase preparative HPLC [Waters Sunfire C18, 10 uM, 100A 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 a yellow solid (113 mg, 63% Yield). 1H NMR (400.0 MHz, DMSO) d 1.86 (t, J=6.4 Hz, 2H), 2.45 (m, 5H), 2.76 (s, 2H), 3.95 (s, 4H), 6.61 (t, J=3.9 Hz, 1H), 7.07 (dd, J=1.3, 8.3 Hz, 1H), 7.38 (s, 1H), 7.48 (d, J=8.2 Hz, 1H), 7.54 (s, 1H), 7.62 (d, J=8.3 Hz, 1H), 8.31 (d, J=4.0 Hz, 1H) and 8.37 (s, 1H) ppm; MS (ES+) 364

Workup

  1. washthe organic phase washed with saturated aqueous Na2CO3
  2. dry with materialdried (MgSO4)
  3. concentrationconcentrated in vacuo
  4. customThe resulting oil was purified by reverse phase preparative HPLC [Waters Sunfire C18, 10 uM, 100A column, gradient 10%-95% B (solvent A: 0.05% TFA in water, solvent B: CH3CN) over 16 minutes at 25 mL/min]
  5. customThe fractions were collected
  6. customfreeze-dried

Sources & evidence

ORD record
ord-aef46d874dc847bb8510c8eb93f8b16e
Source dataset
uspto-grants-2013_04
Patent number
US08410112B2

Reaction notes

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