Diisopropylethylamine → (S)-tert-Butyl 1-(3-methyl-2-(phenylcarbamoyl)-1H-pyrrol-1-ylamino)-1-oxopropan-2-ylcarbamate

HRID 1052345Notes

Reaction equation

HRID 1052345 reaction equation
[NH2:1][N:2]1[CH:6]=[CH:5][C:4]([CH3:7])=[C:3]1[C:8]([NH:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)=[O:9].[C:17]([O:21][C:22]([NH:24][C@@H:25]([CH3:29])[C:26](O)=[O:27])=[O:23])([CH3:20])([CH3:19])[CH3:18].C(N(CC)C(C)C)(C)C.C(P1(=O)OP(CCC)(=O)OP(CCC)(=O)O1)CC>C(OCC)(=O)C.O>[CH3:7][C:4]1[CH:5]=[CH:6][N:2]([NH:1][C:26](=[O:27])[C@@H:25]([NH:24][C:22](=[O:23])[O:21][C:17]([CH3:19])([CH3:18])[CH3:20])[CH3:29])[C:3]=1[C:8](=[O:9])[NH:10][C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1

Participants

7

Reactant 4

HCID 81531Diisopropylethylamine2×HCID 85082Tert-butoxycarbonylalanine2×HCID 111923Propylphosphonic anhydride2×HCID 709224391-amino-3-methyl-N-phenyl-1H-pyrrole-2-carboxamide

Product 1

HCID 90200400(S)-tert-Butyl 1-(3-methyl-2-(phenylcarbamoyl)-1H-pyrrol-1-ylamino)-1-oxopropan-2-ylcarbamateYield 75.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent3×

Conditions

Temperature
0 °C

Procedure

1-Amino-3-methyl-N-phenyl-1H-pyrrole-2-carboxamide (5.30 g, 24.62 mmol) was dissolved in 35 mL ethyl acetate and (S)-2-((tert-butoxycarbonyl)amino)propanoic acid (6.50 g, 34.35 mmol) was added. The mixture was cooled in an ice bath and N,N-diisopropylethylamine (19.8 mL, 113.68 mmol) was added dropwise. After 15 min stirring, maintaining the reaction temperature at 0° C., T3P® (50% in ethyl acetate, 14.3 mL, 48.04 mmol) was added dropwise and the reaction was stirred at room temperature for 3 h. Further (S)-2-((tert-butoxycarbonyl)amino)propanoic acid (3.25 g, 17.17 mmol) was added and the mixture was stirred at room temperature overnight. Further N,N-diisopropylethylamine (20 mL, 114 mmol) and T3P® (50% in ethyl acetate, 14.3 mL, 48.04 mmol) were added dropwise at 0° C. and the reaction was stirred at room temperature overnight. The reaction was poured into water and extracted with ethyl acetate. The organic phase was dried over sodium sulphate, filtered and concentrated under reduced pressure. The residue was purified using Isolera® Purification System (0% to 60% hexane-ethyl acetate) to obtain 7.15 g (75% yield) of the desired product as a solid.

Workup

  1. temperatureThe mixture was cooled in an ice bath
  2. stirringthe reaction was stirred at room temperature for 3 h
  3. stirringthe mixture was stirred at room temperature overnight
  4. stirringthe reaction was stirred at room temperature overnight
  5. extractionextracted with ethyl acetate
  6. dry with materialThe organic phase was dried over sodium sulphate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified
  10. customIsolera® Purification System (0% to 60% hexane-ethyl acetate)

Sources & evidence

ORD record
ord-49a656bc7bb44791b61de8c15425af42
Source dataset
uspto-grants-2016_07
Patent number
US09388189B2

Reaction notes

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