Potassium Carbonate → tert-butyl 2-[3-(bis(tert-butoxycarbonyl)amino)-6-(1-tert-butoxycarbonyl-3,6-dihydro-2H-pyridin-4-yl)pyrazin-2-yl]benzimidazole-1-carboxylate

HRID 1959408Notes

Reaction equation

HRID 1959408 reaction equation
[C:1]([O:5][C:6]([N:8]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[C:9]1[C:10]([C:16]2[N:20]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[C:19]3[CH:28]=[CH:29][CH:30]=[CH:31][C:18]=3[N:17]=2)=[N:11][C:12](Br)=[CH:13][N:14]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CC1(C)C(C)(C)OB([C:47]2[CH2:48][CH2:49][N:50]([C:53]([O:55][C:56]([CH3:59])([CH3:58])[CH3:57])=[O:54])[CH2:51][CH:52]=2)O1.C(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)(C)C.C([O-])([O-])=O.[K+].[K+]>C1(C)C=CC=CC=1.O.Cl[Pd]Cl>[C:1]([O:5][C:6]([N:8]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[C:9]1[C:10]([C:16]2[N:20]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[C:19]3[CH:28]=[CH:29][CH:30]=[CH:31][C:18]=3[N:17]=2)=[N:11][C:12]([C:47]2[CH2:52][CH2:51][N:50]([C:53]([O:55][C:56]([CH3:59])([CH3:58])[CH3:57])=[O:54])[CH2:49][CH:48]=2)=[CH:13][N:14]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 4642098Tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine-1-carboxylateHCID 11714598(4-(N,N-Dimethylamino)phenyl)di-tert-butyl phosphineHCID 86662069Tert-butyl 2-(3-(bis(tert-butoxycarbonyl)amino)-6-bromopyrazin-2-yl)-1H-benzo[d]imidazole-1-carboxylate

Product 1

HCID 66745281tert-butyl 2-[3-(bis(tert-butoxycarbonyl)amino)-6-(1-tert-butoxycarbonyl-3,6-dihydro-2H-pyridin-4-yl)pyrazin-2-yl]benzimidazole-1-carboxylateYield 85.6%

Reagents, catalysts & solvents 3

HCID 24290Palladium ChlorideCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

A mixture of tert-butyl 2-[3-[bis(tert-butoxycarbonyl)amino]-6-bromo-pyrazin-2-yl]benzimidazole-1-carboxylate (1.7068 g, 1.734 mmol), tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,6-dihydro-2H-pyridine-1-carboxylate (643.5 mg, 2.081 mmol), 4-ditert-butylphosphanyl-N,N-dimethyl-aniline; dichloropalladium (12.28 mg, 0.01734 mmol) and K2CO3 (479.3 mg, 3.468 mmol) in toluene (9.216 mL) and water (1.024 mL) was heated to 100° C. for 16 hours. The reaction mixture was allowed to cool to RT and partitioned between DCM and water. The organic layer was washed with 1M NaOH solution, dried (Na2SO4), filtered and concentrated in vacuo to give a brown oil. This was purified by column chromatography (ISCO Companion™, 40 g column, 0-20% EtOAc/Petrol) to afford the title compound as a yellow oil (1.028 g, 60% Yield). MS (ES+) 693.38

Workup

  1. custompartitioned between DCM and water
  2. washThe organic layer was washed with 1M NaOH solution
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customto give a brown oil
  7. customThis was purified by column chromatography (ISCO Companion™, 40 g column, 0-20% EtOAc/Petrol)

Sources & evidence

ORD record
ord-9d621c2ba32c4a4f9255cb67f0384693
Source dataset
uspto-grants-2013_04
Patent number
US08410112B2

Reaction notes

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