Triethylamine → (E)-[2-(3-{4-[1-(4-Chloro-phenylcarbamoyl)-2-(3-diethylamino-pyrrolidin-1-yl)-ethyl]-phenyl}-acryloylamino)-phenyl]-carbamic acid tert-butyl ester

HRID 220194Notes

Reaction equation

HRID 220194 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([CH:8]([CH2:19][N:20]2[CH2:24][CH2:23][CH2:22][CH:21]2N(CC)CC)[C:9]([NH:11][C:12]2[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][CH:13]=2)=[O:10])=[CH:4][CH:3]=1.[C:30]([O:34][C:35](=[O:48])[NH:36][C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][C:38]=1[NH:43][C:44](=[O:47])[CH:45]=[CH2:46])([CH3:33])([CH3:32])[CH3:31].C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.[CH2:71]([N:73](CC)[CH2:74][CH3:75])[CH3:72].[NH4+].[Cl-]>CN(C=O)C.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:30]([O:34][C:35](=[O:48])[NH:36][C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][C:38]=1[NH:43][C:44](=[O:47])/[CH:45]=[CH:46]/[C:2]1[CH:3]=[CH:4][C:5]([CH:8]([C:9](=[O:10])[NH:11][C:12]2[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][CH:13]=2)[CH2:19][N:20]2[CH2:24][CH2:23][CH:22]([N:73]([CH2:74][CH3:75])[CH2:71][CH3:72])[CH2:21]2)=[CH:6][CH:7]=1)([CH3:33])([CH3:31])[CH3:32]

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 25517Ammonium ChlorideHCID 80271Tri-o-tolylphosphineHCID 20786195HCID 20786195, compoundHCID 672315242-(4-Bromo-phenyl)-N-(4-chloro-phenyl)-3-(diethylamino-pyrrolidin-1-yl)-propionamide

Product 1

HCID 59238288(E)-[2-(3-{4-[1-(4-Chloro-phenylcarbamoyl)-2-(3-diethylamino-pyrrolidin-1-yl)-ethyl]-phenyl}-acryloylamino)-phenyl]-carbamic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6228DimethylformamideSolvent

Procedure

A mixture of 2-(4-bromo-phenyl)-N-(4-chloro-phenyl)-3-(diethylamino-pyrrolidin-1-yl)-propionamide (826 mg, 1.72 mmol), (2-acryloylamino-phenyl)-carbamic acid tert-butyl ester (452 mg, 1.72 mmol), Pd2(dba)3 (47.3 mg, 0.051 mmol), tri-o-tolylphosphine (62.8 mg, 0.017 mmol) and triethylamine (694 mg, 6.88 mmol) in DMF (10 mL) was stirred at 100 degrees Celsius under N2 for 4 hours. After cooling to room temperature, the mixture was poured into a saturated aqueous solution of NH4Cl, and extracted with EtOAc (80 mL). The organic layer was washed with brine, dried over Na2SO4, filtered, concentrated in vacuo, and used directly without further purification. MS: calc'd 660 (MH+), exp 660 (MH+).

Workup

  1. extractionextracted with EtOAc (80 mL)
  2. washThe organic layer was washed with brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customused directly without further purification

Sources & evidence

ORD record
ord-76f732d0837145c1899ce89c0dd660e2
Source dataset
uspto-grants-2012_06
Patent number
US08202866B2

Reaction notes

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