Bromoacetonitrile → HCID 178441288, compound

HRID 76307Notes

Reaction equation

HRID 76307 reaction equation
[CH2:1]([C:5]1=[CH:6][N:7]([C:21]([CH3:24])([CH3:23])[CH3:22])[S:8]/[C:9]/1=[N:10]\[C:11](=[O:20])[C:12]1[CH:17]=[C:16]([Cl:18])[CH:15]=[CH:14][C:13]=1[OH:19])[CH2:2][CH2:3][CH3:4].[H-].[Na+].Br[CH2:28][C:29]#[N:30]>C1COCC1.CN(C=O)C>[CH2:1]([C:5]1=[CH:6][N:7]([C:21]([CH3:23])([CH3:22])[CH3:24])[S:8]/[C:9]/1=[N:10]\[C:11](=[O:20])[C:12]1[CH:17]=[C:16]([Cl:18])[CH:15]=[CH:14][C:13]=1[O:19][CH2:28][C:29]#[N:30])[CH2:2][CH2:3][CH3:4]

Participants

5

Reactant 3

HCID 11534BromoacetonitrileHCID 24758Sodium hydrideHCID 178441284HCID 178441284, compound

Product 1

HCID 178441288HCID 178441288, compoundYield 4.5%

Reagents, catalysts & solvents 1

HCID 21974620tetrahydrofuran N,N-dimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of Example 135 (300 mg, 0.82 mmol) in THF/DMF (1:1, 4 mL) were added sodium hydride (39.2 mg, 0.98 mmol) and 2-bromoacetonitrile (65 μL, 0.98 mmol). The reaction was stirred at 40° C. for 4 hrs and at 80° C. for overnight. The reaction mixture was cooled to room temperature, quenched with saturated NaHCO3 (10 mL) and extracted with ethyl acetate (3×20 mL). The combined organic extracts were dried (Na2SO4), filtered and concentrated. The residue was purified by column chromatography using an Analogix® Intelliflash280™ (SiO2, 0-50% ethyl acetate in dichloromethane) to afford 15 mg of the title compound. 1H NMR (300 MHz, DMSO-d6) δ ppm 0.93 (t, J=7.3 Hz, 3 H), 1.20-1.48 (m, 2 H), 1.53-1.77 (m, 2 H), 1.63 (s, 9 H), 2.62-2.82 (m, 2 H), 5.22 (s, 2 H), 7.29 (d, J=9.1 Hz, 1 H), 7.58 (dd, J=8.7, 2.8 Hz, 1 H), 7.86 (d, J=2.8 Hz, 1 H), 8.67 (s, 1 H); MS (ESI+) m/z 406 (M+H)+; Anal. Calculated C20H24ClN3O2S: C, 59.17; H, 5.96; N, 10.35. Found: C, 59.18; H, 5.78; N, 10.37.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. customquenched with saturated NaHCO3 (10 mL)
  3. extractionextracted with ethyl acetate (3×20 mL)
  4. dry with materialThe combined organic extracts were dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by column chromatography

Sources & evidence

ORD record
ord-aa3137a1df364a8ba7134fade765e948
Source dataset
uspto-grants-2014_09
Patent number
US08835475B2

Reaction notes

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