Pyridine → HCID 22599567, compound

HRID 1267192Notes

Reaction equation

HRID 1267192 reaction equation
[CH3:1][N:2]1[C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=2[C:6](=O)[NH:5][CH2:4][C:3]1=[O:14].N1C=CC=CC=1.FC(F)(F)S(OS(C(F)(F)F)(=O)=O)(=O)=O.[CH2:36]([SH:38])[CH3:37]>ClCCl>[CH2:36]([S:38][C:6]1[C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=2[N:2]([CH3:1])[C:3](=[O:14])[CH2:4][N:5]=1)[CH3:37]

Participants

6

Reactant 4

HCID 1049PyridineHCID 6343EthanethiolHCID 67749Trifluoromethanesulfonic anhydrideHCID 35623871-Methyl-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione

Product 1

HCID 22599567HCID 22599567, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-51 °C

Procedure

A solution of 1.0 mmol of 3,4-dihydro-1-methyl-1H-1,4-benzodiazepin-2,5-dione (Tett. Lett. 1994, 50(30), 9051) in 8mL dry dichloromethane (Aldrich Sure Seal), in an oven-dried round bottom flask under nitrogen cover, is treated with 1.1 equivalents of anhydrous pyridine (Mallinkrodt). The reaction is cooled to −51° C. in a dry ice/acetone bath and treated, dropwise via syringe over three minutes, with 1.1 equivalents of trifluoromethanesulfonic anhydride (Aldrich; sealed ampules). The reaction mixture is allowed to stir twenty minutes while maintaining a reaction temperature between −47 and −35° C. The temperature is brought to 0° C. over 1-2 minutes and then maintained at that temperature for one hour. Ethanethiol (3.4 equivalents) is introduced via syringe and the mixture allowed to stir overnight, still immersed in an ice water-filled Dewar. The temperature had risen to 16° C. by morning. The reaction mixture is partitioned between methylene chloride and aqueous sodium bicarbonate. The aqueous portion is further extracted three times with methylene chloride and the combined extracts dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to give a yellow oil. Purification is effected by flash chromatography (silica gel; gradient elution using methylene chloride/ethyl acetate in 100/1, 95/5, 90/10 and 85/15. The title compound is obtained as a colorless oil which crystallizes on standing.

Workup

  1. temperaturewhile maintaining a reaction temperature between −47 and −35° C
  2. temperaturemaintained at that temperature for one hour
  3. stirringto stir overnight
  4. additionfilled Dewar
  5. customhad risen to 16° C. by morning
  6. customThe reaction mixture is partitioned between methylene chloride and aqueous sodium bicarbonate
  7. extractionThe aqueous portion is further extracted three times with methylene chloride
  8. dry with materialthe combined extracts dried over anhydrous sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customto give a yellow oil
  12. customPurification
  13. washgradient elution

Sources & evidence

ORD record
ord-af1aa82cafe343d29718a6ebaf9d2c2c
Source dataset
uspto-grants-2003_04
Patent number
US06552013B1

Reaction notes

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