Triethylamine → 2-[3-(S)-(6-Chloro-benzo[b]thiophene-2-sulfonylamino)-2-oxopyrrolidin-1-ylmethyl]-pyrrolo[2,3-c]pyridine-1-carboxylic acid tert-butyl ester

HRID 651663Notes

Reaction equation

HRID 651663 reaction equation
[C:1]([O:5][C:6](=[O:15])[NH:7][C:8]1[CH:9]=[N:10][CH:11]=[CH:12][C:13]=1I)([CH3:4])([CH3:3])[CH3:2].[O:16]=[C:17]1[C@@H:21]([NH:22][S:23]([C:26]2[S:30][C:29]3[CH:31]=[C:32]([Cl:35])[CH:33]=[CH:34][C:28]=3[CH:27]=2)(=[O:25])=[O:24])[CH2:20][CH2:19][N:18]1[CH2:36][C:37]#[CH:38].C(N(CC)CC)C.C1CCN2C(=NCCC2)CC1>CN(C=O)C.CCOC(C)=O.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)I>[C:1]([O:5][C:6]([N:7]1[C:8]2=[CH:9][N:10]=[CH:11][CH:12]=[C:13]2[CH:38]=[C:37]1[CH2:36][N:18]1[CH2:19][CH2:20][C@H:21]([NH:22][S:23]([C:26]2[S:30][C:29]3[CH:31]=[C:32]([Cl:35])[CH:33]=[CH:34][C:28]=3[CH:27]=2)(=[O:25])=[O:24])[C:17]1=[O:16])=[O:15])([CH3:4])([CH3:3])[CH3:2]

Participants

9

Reactant 4

HCID 8471TriethylamineHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 15366413(4-Iodo-pyridin-3-YL)-carbamic acid tert-butyl esterHCID 538925226-Chloro-benzo[b]thiophene-2-sulfonic acid (2-oxo-1-prop-2-ynyl-pyrrolidin-3-(s)-yl)amide

Product 1

HCID 700232832-[3-(S)-(6-Chloro-benzo[b]thiophene-2-sulfonylamino)-2-oxopyrrolidin-1-ylmethyl]-pyrrolo[2,3-c]pyridine-1-carboxylic acid tert-butyl esterYield 49.1%

Reagents, catalysts & solvents 4

HCID 83717Copper iodideCatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of (4-iodo-pyridin-3-yl)-carbamic acid tert-butyl ester (0.85 g, 2.65 mmol), 6-chlorobenzo[b]thiophene-2-sulfonic acid (2-oxo-1-prop-2-ynyl-pyrrolidin-3-(S)-yl)-amide (0.98 g, 2.65 mmol), Pd(PPh3)2Cl2 (95 mg), copper iodide (18 mg) and triethylamine (1.45 mL) in 8 ml of DMF is heated at 100° C. for 1.5 hours. The reaction mixture is cooled to 50° C. and DBU is added. The resulting mixture is heated at 50° C. for 1.5 hours. After cooling, the crude mixture is diluted with EtOAc and washed with saturated NH4Cl solution, water and saturated NaCl. The organic layer is dried over MgSO4, filtered and concentrated. The crude product is purified by column chromatography eluting with a gradient of 1% MeOH/CH2Cl2 to 4% MeOH/CH2Cl2 to afford the title compound (0.73 g, 1.3 mmol) as a tan solid.

Workup

  1. temperatureThe reaction mixture is cooled to 50° C.
  2. temperatureThe resulting mixture is heated at 50° C. for 1.5 hours
  3. temperatureAfter cooling
  4. washwashed with saturated NH4Cl solution, water and saturated NaCl
  5. dry with materialThe organic layer is dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude product is purified by column chromatography
  9. washeluting with a gradient of 1% MeOH/CH2Cl2 to 4% MeOH/CH2Cl2

Sources & evidence

ORD record
ord-351faa11779b49f08326ce8eeeb8afe6
Source dataset
uspto-grants-2001_08
Patent number
US06281227B1

Reaction notes

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