Sodium Carbonate → HCID 58547178, compound

HRID 1850358Notes

Reaction equation

HRID 1850358 reaction equation
Cl.[NH:2]1[CH2:5][CH:4]([C:6]2[C:11]([O:12][C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=3[O:19][CH3:20])=[N:10][CH:9]=[CH:8][N:7]=2)[CH2:3]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH:45]1[C:49]2[CH:50]=[CH:51][CH:52]=[CH:53][C:48]=2[N:47]=[C:46]1[C:54](O)=[O:55].C([O-])([O-])=O.[Na+].[Na+]>C(Cl)Cl.O.CC#N>[NH:45]1[C:49]2[CH:50]=[CH:51][CH:52]=[CH:53][C:48]=2[N:47]=[C:46]1[C:54]([N:2]1[CH2:3][CH:4]([C:6]2[C:11]([O:12][C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=3[O:19][CH3:20])=[N:10][CH:9]=[CH:8][N:7]=2)[CH2:5]1)=[O:55]

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 2332402-Benzimidazolecarboxylic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 67469212HCID 67469212, compound

Product 1

HCID 58547178HCID 58547178, compoundYield 27%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 18373917Acetonitrile--water (1/1)Solvent

Procedure

The mixture of 2-azetidin-3-yl-3-(2-methoxy-phenoxy)-pyrazine hydrochloride (108 mg, 0.37 mmol), HATU (280 mg, 0.74 mmol) and TEA (130 mg, 1.3 mmol) in dry DCM (10 mL) was stirred at RT for 30 min, then 1H-benzoimidazole-2-carboxylic acid was added to the solution. The solution was heated to 80° C. overnight. The mixture was poured into saturated aqueous Na2CO3 and extracted with DCM (50 mL×2). The organic layer was washed with brine, dried over Na2SO4 and concentrated to give the crude compound, which was purified by ISCO silica gel column (10% to 80% EtOAc in petroleum ether) and followed by reverse phase prep. HPLC (10% to 80% water/MeCN) to give (1H-benzoimidazol-2-yl)-{3-[3-(2-methoxy-phenoxy)-pyrazin-2-yl]-azetidin-1-yl}-methanone (40 mg, 0.11 mmol, yield 27%).

Workup

  1. temperatureThe solution was heated to 80° C. overnight
  2. extractionextracted with DCM (50 mL×2)
  3. washThe organic layer was washed with brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated
  6. customto give the crude compound, which
  7. customwas purified by ISCO silica gel column (10% to 80% EtOAc in petroleum ether)

Sources & evidence

ORD record
ord-58c85570a15a4b49ab5e74eabce18bb9
Source dataset
uspto-grants-2015_02
Patent number
US08957073B2

Reaction notes

Loading…