Tri-o-tolylphosphine → (E)-3-(3,3-Dimethyl-2-oxo-2,3,4,5-tetrahydro-1H-pyrido[2,3-e][1,4]diazepin-7-yl)-N-(3-methoxy-2-propoxybenzyl)-N-methylacrylamide

HRID 2097073Notes

Reaction equation

HRID 2097073 reaction equation
Br[C:2]1[CH:15]=[N:14][C:5]2[NH:6][C:7](=[O:13])[C:8]([CH3:12])([CH3:11])[NH:9][CH2:10][C:4]=2[CH:3]=1.[CH3:16][O:17][C:18]1[C:19]([O:31][CH2:32][CH2:33][CH3:34])=[C:20]([CH:28]=[CH:29][CH:30]=1)[CH2:21][N:22]([CH3:27])[C:23](=[O:26])[CH:24]=[CH2:25].C(N(C(C)C)C(C)C)C.CC1C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C>C(#N)CC.CN(C=O)C.CCOCC.CCOC(C)=O.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH3:11][C:8]1([CH3:12])[C:7](=[O:13])[NH:6][C:5]2[N:14]=[CH:15][C:2](/[CH:25]=[CH:24]/[C:23]([N:22]([CH2:21][C:20]3[CH:28]=[CH:29][CH:30]=[C:18]([O:17][CH3:16])[C:19]=3[O:31][CH2:32][CH2:33][CH3:34])[CH3:27])=[O:26])=[CH:3][C:4]=2[CH2:10][NH:9]1

Participants

10

Reactant 4

HCID 80271Tri-o-tolylphosphineHCID 81531DiisopropylethylamineHCID 57742093N-(3-Methoxy-2-propoxybenzyl)-N-methylacrylamideHCID 594569147-Bromo-3,3-dimethyl-1,3,4,5-tetrahydropyrido[2,3-e][1,4]diazepin-2-one

Product 1

HCID 16659984(E)-3-(3,3-Dimethyl-2-oxo-2,3,4,5-tetrahydro-1H-pyrido[2,3-e][1,4]diazepin-7-yl)-N-(3-methoxy-2-propoxybenzyl)-N-methylacrylamideYield 60.3%

Reagents, catalysts & solvents 5

HCID 167845palladium(II) acetateCatalystHCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolventHCID 7854PropionitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

A suspension of 7-bromo-3,3-dimethyl-1,3,4,5-tetrahydro-pyrido[2,3-e][1,4]diazepin-2-one (0.30 g, 1.1 mmol) and N-(3-methoxy-2-propoxybenzyl)-N-methylacrylamide (0.35 g, 1.3 mmol) in propionitrile (5 mL) and DMF (1.3 mL) was de-oxygenated with Ar for 5 min. The mixture was treated with (i-Pr)2EtN (0.41 mL, 2.4 mmol) and was de-oxygenated with Ar for 10 min. Pd(OAc)2 (25 mg, 0.11 mmol) and P(o-tol)3 (69 mg, 0.23 mmol) were added simultaneously, and the mixture was de-oxygenated a third time for 5 min. The mixture was heated to reflux overnight, then allowed to cool. The mixture was diluted with Et2O (50 mL) and EtOAc (25 mL), washed with H2O (25 mL), dried over Na2SO4, filtered and concentrated to an orange residue. Purification by flash column chromatography (silica gel, CH2Cl2/MeOH, 98:2 to 97:3) gave the title compound (0.30 g, 60%) as an off-white solid: MS (ESI) m/e 453 (M+H)+.

Workup

  1. waitwas de-oxygenated with Ar for 10 min
  2. customfor 5 min
  3. temperatureThe mixture was heated
  4. temperatureto reflux overnight
  5. temperatureto cool
  6. washwashed with H2O (25 mL)
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated to an orange residue
  10. customPurification by flash column chromatography (silica gel, CH2Cl2/MeOH, 98:2 to 97:3)

Sources & evidence

ORD record
ord-ce263ceaaf9b461f8bb00918bb2e6865
Source dataset
uspto-grants-2013_05
Patent number
US08450307B2

Reaction notes

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