Hydrochloric Acid → HCID 118014508, compound

HRID 1472941Notes

Reaction equation

HRID 1472941 reaction equation
N1C2C=CC=CC=2N=N1.[CH3:10][C:11]1[CH:19]=[CH:18][C:14]([C:15](Cl)=[O:16])=[CH:13][CH:12]=1.[C:20]([NH:23][C@H:24]([C:27]([OH:29])=[O:28])[CH2:25][SH:26])(=[O:22])[CH3:21].CN1CCOCC1.Cl>O1CCCC1>[C:20]([NH:23][CH:24]([CH2:25][S:26][C:15](=[O:16])[C:14]1[CH:18]=[CH:19][C:11]([CH3:10])=[CH:12][CH:13]=1)[C:27]([OH:29])=[O:28])(=[O:22])[CH3:21]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 79724-MethylmorpholineHCID 12035N-Acetyl-L-CysteineHCID 134054-Methylbenzoyl ChlorideHCID 178418385HCID 178418385, compound

Product 1

HCID 118014508HCID 118014508, compoundYield 60%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of benzotriazole (9.91 g, 83.2 mmol) in tetrahydrofuran (80 mL) was added 4-methylbenzoyl chloride (5.0 mL, 37.8 mmol) (5 g, 95%). After 2 hours, the resulting slurry was filtered and the solid was rinsed with tetrahydrofuran (25 mL). The filtrates were combined and added to a solution of N-acetyl-L-cysteine (5.55 g, 34.0 mmol) and N-methylmorpholine (3.74 mL, 34.0 mmol) in tetrahydrofuran (50 mL) at 0° C. The resulting mixture was allowed to warm to ambient temperature over 16 hours. Aqueous hydrochloric acid (1 M, 100 mL) was added to the mixture and the resulting mixture was concentrated at reduced pressure to a volume of approximately 125 mL. Additional aqueous hydrochloric acid (80 mL) was added and the mixture was extracted with dichloromethane (180 mL then 80 mL). The combined organic extracts were combined, dried over sodium sulfate, filtered and concentrated at reduced pressure. Ethyl acetate (100 mL) was added and the resulting slurry was stirred for 2 hours. The resulting slurry was filtered and dried to give a white solid (5.7 g, 60%). 1H NMR (300 MHz, DMSO) δ=12.94 (s, 1H), 8.34 (d, J=7.9 Hz, 1H), 7.86-7.74 (m, 2H), 7.35 (d, J=8.5 Hz, 2H), 4.43 (dt, J=5.0, 8.4 Hz, 1H), 3.53 (dd, J=5.0, 13.8 Hz, 1H), 3.21 (dd, J=8.5, 13.8 Hz, 1H), 2.37 (s, 3H), 1.83 (s, 3H). MS (ESI) m/z 282 (M+1)+.

Workup

  1. filtrationthe resulting slurry was filtered
  2. washthe solid was rinsed with tetrahydrofuran (25 mL)
  3. concentrationthe resulting mixture was concentrated at reduced pressure to a volume of approximately 125 mL
  4. additionAdditional aqueous hydrochloric acid (80 mL) was added
  5. extractionthe mixture was extracted with dichloromethane (180 mL
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated at reduced pressure
  9. additionEthyl acetate (100 mL) was added
  10. filtrationThe resulting slurry was filtered
  11. customdried

Sources & evidence

ORD record
ord-34f0c2a92aa3415e8a3751cc2e4a530b
Source dataset
uspto-grants-2015_04
Patent number
US09012674B1

Reaction notes

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