Chloroacetonitrile → HCID 73603535, compound

HRID 1500302Notes

Reaction equation

HRID 1500302 reaction equation
[Cl:1][CH:2]([Cl:24])[C:3]([NH:5][C@H:6]([CH2:22][F:23])[C@H:7]([OH:21])[C:8]1[CH:13]=[CH:12][C:11]([C:14]2[CH:19]=[CH:18][NH:17][C:16](=[O:20])[CH:15]=2)=[CH:10][CH:9]=1)=[O:4].C(=O)([O-])[O-].[Cs+].[Cs+].Cl[CH2:32][C:33]#[N:34]>CN(C)C=O.O>[Cl:24][CH:2]([Cl:1])[C:3]([NH:5][C@H:6]([CH2:22][F:23])[C@@H:7]([C:8]1[CH:9]=[CH:10][C:11]([C:14]2[CH:19]=[CH:18][N:17]([CH2:32][C:33]#[N:34])[C:16](=[O:20])[CH:15]=2)=[CH:12][CH:13]=1)[OH:21])=[O:4]

Participants

6

Reactant 3

HCID 7856ChloroacetonitrileHCID 10796Cesium carbonateHCID 86713190HCID 86713190, compound

Product 1

HCID 73603535HCID 73603535, compoundYield 58.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
65 °C

Procedure

A microwave tube is charged with the product of step 2, Example 20 (185 mg, 0.496 mmol) in dimethylformamide (4.9 mL), cesium carbonate (194 mg, 0.595 mmol) and chloroacetonitrile (313.7 uL, 4.957 mmol) were added under nitrogen, and the tube is capped. The reaction mixture is heated at 65° C. for 2.5 hours using the microwave (max power—100 W). The mixture is diluted with water (20 mL), extracted with ethylacetate (2×20 mL), and the combined organic phase is washed with water (3×15 mL), brine (15 mL), dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. Purification by silica gel chromatography (40 g, 50-90% ethyl acetate/hexanes) gave the title compound (120 mg): 1H NMR (300 MHz, DMSO) δ 4.25 (m, 1.5H), 4.44 (m, 0.5H), 4.53 (m, 0.5H), 4.72 (m, 0.5H), 4.91 (m, 1H), 5.02 (s, 2H), 6.01 (d, 1H), 6.51 (s, 1H), 6.72 (dd, 1H), 6.77 (m, 1H), 7.47 (d, 2H), 7.70 (d, 2H), 7.83 (d, 1H), 8.60 (bd, 1H). MS (ESI+) m/z 412 [M+H].

Workup

  1. additionwere added under nitrogen
  2. customthe tube is capped
  3. extractionextracted with ethylacetate (2×20 mL)
  4. washthe combined organic phase is washed with water (3×15 mL), brine (15 mL)
  5. dry with materialdried over anhydrous magnesium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customPurification by silica gel chromatography (40 g, 50-90% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-5cd9fad83599491fb445a493f1f3a875
Source dataset
uspto-grants-2015_12
Patent number
US09206126B2

Reaction notes

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