Cesium carbonate → 2-(1-(6-(3,5-dimethyl-1H-1,2,4-triazol-1-yl)-2-methylpyrimidin-4-yl)azetidin-3-yl)-1-methyl-1H-benzo[d]imidazole

HRID 2202819Notes

Reaction equation

HRID 2202819 reaction equation
Cl[C:2]1[CH:7]=[C:6]([N:8]2[C:12]([CH3:13])=[N:11][C:10]([CH3:14])=[N:9]2)[N:5]=[C:4]([CH3:15])[N:3]=1.[NH:16]1[CH2:19][CH:18]([C:20]2[N:24]([CH3:25])[C:23]3[CH:26]=[CH:27][CH:28]=[CH:29][C:22]=3[N:21]=2)[CH2:17]1.C([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C>[CH3:14][C:10]1[N:11]=[C:12]([CH3:13])[N:8]([C:6]2[N:5]=[C:4]([CH3:15])[N:3]=[C:2]([N:16]3[CH2:19][CH:18]([C:20]4[N:24]([CH3:25])[C:23]5[CH:26]=[CH:27][CH:28]=[CH:29][C:22]=5[N:21]=4)[CH2:17]3)[CH:7]=2)[N:9]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 624817454-chloro-6-(3,5-dimethyl-1H-1,2,4-triazol-1-yl)-2-methylpyrimidineHCID 894881762-(azetidin-3-yl)-1-methyl-1H-1,3-benzodiazole

Product 1

HCID 715508042-(1-(6-(3,5-dimethyl-1H-1,2,4-triazol-1-yl)-2-methylpyrimidin-4-yl)azetidin-3-yl)-1-methyl-1H-benzo[d]imidazoleYield 78%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

Intermediate 2 (0.15 g, 0.67 mmol), Intermediate 1 (0.13 g, 0.67 mmol), and Cs2CO3 (0.66 g, 2.01 mmol) were suspended in DMF (6.7 mL) in a microwave vial. The vial was then capped and heated in the microwave at 100° C. for 30 min. After cooling to room temperature, the reaction was filtered and the filtrate was purified by reverse phase chromatography (acetonitrile/water/0.1% TFA). The fractions containing the product were partitioned between EtOAc and saturated NaHCO3. The organic layer was washed with brine, dried over Na2SO4 and concentrated to provide Example 1 (0.17 g, 78%) as a white solid. 1H NMR: (500 MHz, CD3OD) δ 7.63 (d, J=8 Hz, 1H), 7.5 (d, J=8 Hz, 1H), 7.28 (m, 2H), 6.66 (s, 1H), 4.66 (m, 2H), 4.53 (m, 3H), 3.83 (s, 3H), 2.84 (s, 3H), 2.51 (s, 3H), 2.36 (s, 3H). MS: m/z=375.4 (M+H).

Workup

  1. customThe vial was then capped
  2. temperatureAfter cooling to room temperature
  3. filtrationthe reaction was filtered
  4. customthe filtrate was purified by reverse phase chromatography (acetonitrile/water/0.1% TFA)
  5. additionThe fractions containing the product
  6. customwere partitioned between EtOAc and saturated NaHCO3
  7. washThe organic layer was washed with brine
  8. dry with materialdried over Na2SO4
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-7d7907bc92004eb39c43b875041a2121
Source dataset
uspto-grants-2016_06
Patent number
US09365562B2

Reaction notes

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