Triethylamine → 2-[3-(S)-Benzyloxycarbonylamino-2-oxo-pyrrolidin-1-ylmethyl)-pyrrolo[3,2-c]pyridine-1-carboxylic acid tert-butyl ester

HRID 651671Notes

Reaction equation

HRID 651671 reaction equation
C(N(CC)CC)C.[CH2:8]([O:15][C:16](=[O:27])[NH:17][C@H:18]1[CH2:22][CH2:21][N:20]([CH2:23][C:24]#[CH:25])[C:19]1=[O:26])[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.[C:28]([O:32][C:33](=[O:42])[NH:34][C:35]1[CH:40]=[CH:39][N:38]=[CH:37][C:36]=1I)([CH3:31])([CH3:30])[CH3:29].C1CCN2C(=NCCC2)CC1>CN(C=O)C.C(OCC)(=O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I>[C:28]([O:32][C:33]([N:34]1[C:35]2[CH:40]=[CH:39][N:38]=[CH:37][C:36]=2[CH:25]=[C:24]1[CH2:23][N:20]1[CH2:21][CH2:22][C@H:18]([NH:17][C:16]([O:15][CH2:8][C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=2)=[O:27])[C:19]1=[O:26])=[O:42])([CH3:31])([CH3:29])[CH3:30]

Participants

9

Reactant 4

HCID 8471TriethylamineHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 10903275(3-Iodo-pyridin-4-yl)-carbamic acid tert-butyl esterHCID 54281442(2-Oxo-1-prop2-ynyl-pyrrolidin-3-(s)-yl)-carbamic acid benzyl ester

Product 1

HCID 697099132-[3-(S)-Benzyloxycarbonylamino-2-oxo-pyrrolidin-1-ylmethyl)-pyrrolo[3,2-c]pyridine-1-carboxylic acid tert-butyl esterYield 74.1%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

Pd(PPh3)2Cl2 (0.49 g, 0.70 mmol), CuI (0.08 g, 0.42 mmol) followed by triethylamine (7.8 mL, 56.0 mmol) is added to a solution of (2-oxo-1-prop-2-ynyl-pyrrolidin-3-(S)-yl)-carbamic acid benzyl ester (3.81 g, 13.9 mmol) and (3-iodo-pyridin-4-yl)-carbamic acid tert-butyl ester (4.48 g, 14.0 mmol) in DMF (50 mL) at room temperature. The mixture is heated to 100° C. and stirred for 1.5 h. The reaction mixture is then cooled to 50° C. and DBU (4.2 mL, 28.1 mmol) is added. After 30 min the solution is cooled to room temperature, diluted with ethyl acetate and washed with saturated ammonium chloride, water and brine. The organic layer is dried over MgSO4, filtered and concentrated to dryness in vacuo. The resulting solid is purified by column chromatography eluting with a gradient of 2% MeOH/CH2Cl2 to 5% MeOH/CH2Cl2 to give the product (4.79 g, 10.3 mmol) as a white solid.

Workup

  1. temperatureThe reaction mixture is then cooled to 50° C.
  2. temperatureAfter 30 min the solution is cooled to room temperature
  3. washwashed with saturated ammonium chloride, water and brine
  4. dry with materialThe organic layer is dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated to dryness in vacuo
  7. customThe resulting solid is purified by column chromatography
  8. washeluting with a gradient of 2% MeOH/CH2Cl2 to 5% MeOH/CH2Cl2

Sources & evidence

ORD record
ord-4285ee82627c494995a3bf587e81953a
Source dataset
uspto-grants-2001_08
Patent number
US06281227B1

Reaction notes

Loading…