Triethylamine → HCID 10906711, compound

HRID 1432919Notes

Reaction equation

HRID 1432919 reaction equation
C(N(CC)CC)C.[CH2:8]([O:15][C:16]([N:18]1[CH2:23][CH2:22][N:21]([CH2:24][C:25]#[CH:26])[C:20](=[O:27])[CH2:19]1)=[O:17])[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:26]=[C:25]1[CH2:24][N:21]1[CH2:22][CH2:23][N:18]([C:16]([O:15][CH2:8][C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=2)=[O:17])[CH2:19][C:20]1=[O:27])=[O:42])([CH3:31])([CH3:29])[CH3:30]

Participants

9

Reactant 4

HCID 8471TriethylamineHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 10891001Benzyl 3-oxo-4-(prop-2-yn-1-yl)piperazine-1-carboxylateHCID 10903275(3-Iodo-pyridin-4-yl)-carbamic acid tert-butyl ester

Product 1

HCID 10906711HCID 10906711, compoundYield 76.7%

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 (0.29 g, 0.41 mmol), CuI (0.05 g, 0.25 mmol) and triethylamine (4.6 mL, 3.29 mmol) is added to a solution of 3-oxo-4-prop-2-ynylpiperazine-1-carboxylic acid benzyl ester (2.24 g, 8.23 mmol) and (3-iodopyridin-4-yl)-carbamic acid tert-butyl ester (2.63 g, 8.23 mmol) in DMF (30 mL) at room temperature. The mixture is heated to 100° C. and stirred for 1.5 hours. The reaction mixture is then cooled to 50° C. and DBU (2.5 mL, 16.5 mmol) is added. After 30 minutes 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 in vacuo. The resulting solid is purified by column chromatography eluting with a gradient of 2% MeOH/CH2Cl2to 5% MeOH/CH2Cl2to give the product (2.93 g, 6.31 mmol) as a white solid. 1H NMR (CDCl3, 300 MHz) δ8.75 (s, 1H), 8.4 (d, 1H), 7.85 (d, 1H), 7.35 (m, 5H), 6.38 (s, 1H), 5.2 (s, 2H), 5.00 (s, 2H), 4.29 (s, 2H), 3.85 (m, 2H), 3.52 (m, 2H), 1.7 (s, 9H). Ion spray MS, [M+H]+=465.

Workup

  1. temperatureThe reaction mixture is then cooled to 50° C.
  2. temperatureAfter 30 minutes 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 in vacuo
  7. customThe resulting solid is purified by column chromatography
  8. washeluting with a gradient of 2% MeOH/CH2Cl2to 5% MeOH/

Sources & evidence

ORD record
ord-14df01b481304d4d9cba82da8576722d
Source dataset
uspto-grants-2009_11
Patent number
US07612075B2

Reaction notes

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