Triethylamine → (E)-[2-(3-{4-[(2-Morpholin-4-yl-ethoxy)-(4-trifluoromethyl-phenylcarbamoyl)-methyl]-phenyl}-acryloylamino)-phenyl]-carbamic acid tert-butyl ester

HRID 1714166Notes

Reaction equation

HRID 1714166 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([CH:8]([O:22][CH2:23][CH2:24][N:25]2[CH2:30][CH2:29][O:28][CH2:27][CH2:26]2)[C:9]([NH:11][C:12]2[CH:17]=[CH:16][C:15]([C:18]([F:21])([F:20])[F:19])=[CH:14][CH:13]=2)=[O:10])=[CH:4][CH:3]=1.[C:31]([O:35][C:36](=[O:49])[NH:37][C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][C:39]=1[NH:44][C:45](=[O:48])[CH:46]=[CH2:47])([CH3:34])([CH3:33])[CH3:32].C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.C(N(CC)CC)C.[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:31]([O:35][C:36](=[O:49])[NH:37][C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][C:39]=1[NH:44][C:45](=[O:48])/[CH:46]=[CH:47]/[C:2]1[CH:3]=[CH:4][C:5]([CH:8]([O:22][CH2:23][CH2:24][N:25]2[CH2:26][CH2:27][O:28][CH2:29][CH2:30]2)[C:9](=[O:10])[NH:11][C:12]2[CH:17]=[CH:16][C:15]([C:18]([F:21])([F:19])[F:20])=[CH:14][CH:13]=2)=[CH:6][CH:7]=1)([CH3:34])([CH3:32])[CH3:33]

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 25517Ammonium ChlorideHCID 80271Tri-o-tolylphosphineHCID 20786195HCID 20786195, compoundHCID 578200612-(4-bromo-phenyl)-2-(2-morpholin-4-yl-ethoxy)-N-(4-trifluoromethyl-phenyl)-acetamide

Product 1

HCID 57820106(E)-[2-(3-{4-[(2-Morpholin-4-yl-ethoxy)-(4-trifluoromethyl-phenylcarbamoyl)-methyl]-phenyl}-acryloylamino)-phenyl]-carbamic acid tert-butyl esterYield 24.6%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6228DimethylformamideSolvent

Procedure

A mixture of 2-(4-bromo-phenyl)-2-(2-morpholin-4-yl-ethoxy)-N-(4-trifluoromethyl-phenyl)-acetamide (481 mg, 0.720 mmol), (2-acryloylamino-phenyl)-carbamic acid tert-butyl ester (240 mg, 0.920 mmol), tri-o-tolyl-phosphine (51 mg, 0.17 mmol), triethylamine (421 mg, 4.16 mmol) and Pd2(dba)3 (76 mg, 0.08 mmol) in DMF (4 mL) was heated at 105 degrees Celcius for 1 hr under N2 atmosphere, and then at 95 degrees Celcius overnight. After cooling to room temperature, the mixture was poured into a saturated aqueous solution of NH4Cl and extracted with ethyl acetate four times. The organic layer was washed with brine, dried over Na2SO4, filtered, concentrated in vacuo, and purified by flash column chromatography (dichloromethane/methanol 500:1-100:1) to obtain a brown solid (118 mg, 24.6%). MS: calc'd 669 (MH+), exp 669 (MH+).

Workup

  1. temperaturewas heated at 105 degrees Celcius for 1 hr under N2 atmosphere
  2. customat 95 degrees
  3. customCelcius overnight
  4. extractionextracted with ethyl acetate four times
  5. washThe organic layer was washed with brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. custompurified by flash column chromatography (dichloromethane/methanol 500:1-100:1)

Sources & evidence

ORD record
ord-74b50571f3c4450d897d7438cb7974cd
Source dataset
uspto-grants-2010_09
Patent number
US07795315B2

Reaction notes

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