1-Methylimidazole → HCID 58712131, compound

HRID 1909450Notes

Reaction equation

HRID 1909450 reaction equation
[CH3:1][C:2]([O:5][C:6]([NH:8][CH2:9][C:10]([OH:12])=O)=[O:7])([CH3:4])[CH3:3].CN1C=CN=C1.Cl.[CH3:20][O:21][C:22]1[CH:27]=[CH:26][C:25]([C:28]2[CH:29]=[N:30][O:31][C:32]=2[C:33]2[CH:38]=[C:37]([O:39][CH3:40])[C:36]([O:41][CH3:42])=[C:35]([O:43][CH3:44])[CH:34]=2)=[CH:24][C:23]=1[NH2:45]>C1COCC1>[C:2]([O:5][C:6](=[O:7])[NH:8][CH2:9][C:10](=[O:12])[NH:45][C:23]1[CH:24]=[C:25]([C:28]2[CH:29]=[N:30][O:31][C:32]=2[C:33]2[CH:34]=[C:35]([O:43][CH3:44])[C:36]([O:41][CH3:42])=[C:37]([O:39][CH3:40])[CH:38]=2)[CH:26]=[CH:27][C:22]=1[O:21][CH3:20])([CH3:1])([CH3:3])[CH3:4]

Participants

5

Reactant 3

HCID 13901-MethylimidazoleHCID 78288N-(tert-butoxycarbonyl)glycineHCID 66929481HCID 66929481, compound

Product 1

HCID 58712131HCID 58712131, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
45 °C

Procedure

To a solution of N-t-Boc-glycine (357 mg, 2 mmol) and N-methyl-imidazole (0.162 mL, 2 mmol) in THF (16 mL) cooled with ice methanesulfonyl chloride (0.158 mL, 2 mmol) was added. Ice batch was removed, compound 5 (0.4 g, 1 mmol) was added as a solid, followed by thriethylamine (0.144 mL, 2.02 mmol), and the reaction mixture was stirred at 40-50° C. overnight. A resulted solution was decanted from a solid, a flask rinsed with EtOAc, and a combined organic solution was washed with saturated ammonium chloride solution, then twice with water, brine and dried over anhydrous sodium sulfate. The solution was filtered out through a celite pad, concentrated and the residue was dissolved in 2-propanol (3 mL) with heating, and hexane (1-2 mL) was added drop-wise to start precipitation. In 1 hour a solid was filtered out, washed with 1:1 Hexane:ether mixture (10 ml×2) and vacuum-dried to give compound 6, 0.49 g (93.7%), LC purity 99%. 1H NMR (DMSO-d6): δ 9.11 (s, 1H), 8.81 (s, 1H), 8.22 (s, 1H), 7.24 (m, 1H), 7.20-7.15 (m, 2H), 6.91 (s, 2H), 3.87 (s, 3H), 3.73 (m, 2H), 3.70 (s, 3H), 3.66 (s, 6H). 1.40 (s, 9H).

Workup

  1. additionwas added
  2. customIce batch was removed
  3. customA resulted solution was decanted from a solid, a flask
  4. washrinsed with EtOAc
  5. washa combined organic solution was washed with saturated ammonium chloride solution
  6. dry with materialtwice with water, brine and dried over anhydrous sodium sulfate
  7. filtrationThe solution was filtered out through a celite pad
  8. concentrationconcentrated
  9. dissolutionthe residue was dissolved in 2-propanol (3 mL)
  10. temperaturewith heating
  11. additionhexane (1-2 mL) was added drop-wise
  12. customprecipitation
  13. filtrationIn 1 hour a solid was filtered out
  14. washwashed with 1:1 Hexane
  15. dry with materialether mixture (10 ml×2) and vacuum-dried

Sources & evidence

ORD record
ord-3fb60b9dc092473fbe1377245efa6a6f
Source dataset
uspto-grants-2013_12
Patent number
US08598366B2

Reaction notes

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