Dimethyl Sulfoxide → methyl 3-{[5-(azetidin-1-ylcarbonyl)pyrazin-2-yl]oxy}-5-[(1S)-2-methoxy-1-methylethoxy]benzoate

HRID 658437Notes

Reaction equation

HRID 658437 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]([CH:9]=[C:10]([O:12][C@@H:13]([CH3:17])[CH2:14][O:15][CH3:16])[CH:11]=1)[C:5]([O:7][CH3:8])=[O:6].[N:18]1([C:22]([C:24]2[CH:29]=[N:28][C:27](Cl)=[CH:26][N:25]=2)=[O:23])[CH2:21][CH2:20][CH2:19]1.C(=O)([O-])[O-].[Cs+].[Cs+].CS(C)=O>O.C(OCC)(=O)C>[N:18]1([C:22]([C:24]2[N:25]=[CH:26][C:27]([O:1][C:2]3[CH:3]=[C:4]([CH:9]=[C:10]([O:12][C@@H:13]([CH3:17])[CH2:14][O:15][CH3:16])[CH:11]=3)[C:5]([O:7][CH3:8])=[O:6])=[N:28][CH:29]=2)=[O:23])[CH2:21][CH2:20][CH2:19]1

Participants

7

Reactant 4

HCID 679Dimethyl SulfoxideHCID 10796Cesium carbonateHCID 46870328(Azetidin-1-yl)(5-chloropyrazin-2-yl)methanoneHCID 59127146methyl 3-hydroxy-5-[(1S)-2-methoxy-1-methylethoxy]benzoate

Product 1

HCID 49765464methyl 3-{[5-(azetidin-1-ylcarbonyl)pyrazin-2-yl]oxy}-5-[(1S)-2-methoxy-1-methylethoxy]benzoateYield 93%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
45 °C

Procedure

To a flask fitted with overhead stirrer, condenser, thermometer and nitrogen line was added methyl 3-hydroxy-5-[(1S)-2-methoxy-1-methylethoxy]benzoate (1.0 eq), 2-(azetidin-1-ylcarbonyl)-5-chloropyrazine (1.05 eq), cesium carbonate (1.5 eq) and dimethylsulfoxide (10 vols) under a nitrogen atmosphere. The contents of the flask were heated to 45° C. for 1.5 hours, then cooled to 22° C. Ethyl acetate (6 vols) and water (6 vols) were added to the flask, the mixture was agitated for 15 minutes, then the layers were separated. Water (3 vols) was added to the organic layer, the batch agitated for 15 minutes, then the layers were separated. This process was repeated with water (3 vols) then saturated brine (6 vols), then with water (6 vols). The organic layer was evaporated on the rotary evaporator to yield the title compound as an oil (93% yield corrected for assay). 1H NMR δ (400 MHz) DMSO: 8.62 (s, 1H), 8.50 (s, 1H), 7.34 (s, 1H), 7.30 (s, 1H), 7.17 (s, 1H), 4.68-4.64 (m, 1H), 4.54-4.49 (t, 2H), 4.07-4.03 (t, 2H), 3.81 (s, 3H), 3.49-3.41 (m, 2H), 3.25 (s, 3H), 2.29-2.22 (m, 2H), 1.20-1.18 (d, 3H).

Workup

  1. customTo a flask fitted with overhead stirrer, condenser
  2. temperaturecooled to 22° C
  3. customthe layers were separated
  4. additionWater (3 vols) was added to the organic layer
  5. stirringthe batch agitated for 15 minutes
  6. customthe layers were separated
  7. customThe organic layer was evaporated on the rotary evaporator

Sources & evidence

ORD record
ord-f959fa8e695c4e03bc4653ca7062f969
Source dataset
uspto-grants-2011_12
Patent number
US08076481B2

Reaction notes

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