Dimethylformamide → benzyl 3-(1-[(tert-butoxycarbonyl)amino]-5-cyano-1H-pyrrol-2-yl]azetidine-1-carboxylate

HRID 1972944Notes

Reaction equation

HRID 1972944 reaction equation
ClS([N:5]=[C:6]=O)(=O)=O.[C:8]([O:12][C:13]([NH:15][N:16]1[CH:20]=[CH:19][CH:18]=[C:17]1[CH:21]1[CH2:24][N:23]([C:25]([O:27][CH2:28][C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)=[O:26])[CH2:22]1)=[O:14])([CH3:11])([CH3:10])[CH3:9].CN(C=O)C>C(#N)C>[C:8]([O:12][C:13]([NH:15][N:16]1[C:20]([C:6]#[N:5])=[CH:19][CH:18]=[C:17]1[CH:21]1[CH2:22][N:23]([C:25]([O:27][CH2:28][C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)=[O:26])[CH2:24]1)=[O:14])([CH3:11])([CH3:9])[CH3:10]

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 70918Chlorosulfonyl isocyanateHCID 58529958benzyl 3-(1-[(tert-butoxycarbonyl)amino]-1H-pyrrol-2-yl}azetidine-1-carboxylate

Product 1

HCID 58529525benzyl 3-(1-[(tert-butoxycarbonyl)amino]-5-cyano-1H-pyrrol-2-yl]azetidine-1-carboxylateYield 36%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of chlorosulfonylisocyanate (541 μL, 6.22 mmol) in acetonitrile (5 mL) was added dropwise to a cooled (0° C.) solution of benzyl 3-{1-[(tert-butoxycarbonyl)amino]-1H-pyrrol-2-yl}azetidine-1-carboxylate (2.10 g, 5.65 mmol) in acetonitrile (15 mL). The mixture was stirred at 0° C. for 30 min and was warmed to rt. After 1 h, the mixture was recooled (0° C.) and DMF was added dropwise. The reaction was allowed to warm to rt. After 30 min, the mixture was poured onto crushed ice (100 g) and was allowed to warm to rt. The aqueous mixture was extracted with EtOAc (3×75 mL) and the combined organic layers were washed with brine, dried (Na2SO4), and concentrated. The crude material was purified by ISCO® chromatography using a gradient of 50 to 75% ethyl acetate in hexanes to obtain 800 mg (36%) of the desired product, which was used without further characterization.

Workup

  1. temperaturewas warmed to rt
  2. waitAfter 1 h
  3. additionwas added dropwise
  4. temperatureto warm to rt
  5. waitAfter 30 min
  6. additionthe mixture was poured
  7. temperatureto warm to rt
  8. extractionThe aqueous mixture was extracted with EtOAc (3×75 mL)
  9. washthe combined organic layers were washed with brine
  10. dry with materialdried (Na2SO4)
  11. concentrationconcentrated
  12. customThe crude material was purified by ISCO® chromatography

Sources & evidence

ORD record
ord-c152d18b134f46dabdfe5458ad652afc
Source dataset
uspto-grants-2013_04
Patent number
US08431695B2

Reaction notes

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