Triethylamine → (1H-benzoimidazol-2-yl)-[3-(3-chloro-pyrazin-2-yl)-azetidin-1-yl]-methanone

HRID 1850304Notes

Reaction equation

HRID 1850304 reaction equation
[NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[C:10]([OH:12])=O.Cl.[NH:14]1[CH2:17][CH:16]([C:18]2[C:23]([Cl:24])=[N:22][CH:21]=[CH:20][N:19]=2)[CH2:15]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(CC)CC.C([O-])([O-])=O.[Na+].[Na+]>C(Cl)Cl.O.CC#N>[NH:3]1[C:4]2[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=2[N:1]=[C:2]1[C:10]([N:14]1[CH2:17][CH:16]([C:18]2[C:23]([Cl:24])=[N:22][CH:21]=[CH:20][N:19]=2)[CH2:15]1)=[O:12]

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 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 717437842-(Azetidin-3-YL)-3-chloropyrazine hydrochloride

Product 1

HCID 58546731(1H-benzoimidazol-2-yl)-[3-(3-chloro-pyrazin-2-yl)-azetidin-1-yl]-methanoneYield 34%

Reagents, catalysts & solvents 2

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

Procedure

A mixture of 1H-benzoimidazole-2-carboxylic acid (19) (100 mg, 0.47 mmol), 2-azetidin-3-yl-3-chloro-pyrazine hydrochloride (8) (96 mg, 0.47 mmol), HATU (540 mg, 1.3 mmol) and Et3N (101 mg, 1 mmol) in dry DCM (10 mL) was stirred at RT overnight. Then the mixture reaction was poured into saturated aqueous Na2CO3 and extracted with DCM (50 mL×3), 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 afford pure (1H-benzoimidazol-2-yl)-[3-(3-chloro-pyrazin-2-yl)-azetidin-1-yl]-methanone (84) (50 mg, 0.16 mmol, yield 34%).

Workup

  1. customThen the mixture reaction
  2. extractionextracted with DCM (50 mL×3)
  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-c773eac875b04b21ab59ec1418c7778d
Source dataset
uspto-grants-2015_02
Patent number
US08957073B2

Reaction notes

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