Tri-o-tolylphosphine → HCID 16659986, compound

HRID 1362328Notes

Reaction equation

HRID 1362328 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][N:17]([CH2:22][C:23]1[N:24]([CH3:32])[C:25]2[C:30]([CH:31]=1)=[CH:29][CH:28]=[CH:27][CH:26]=2)[C:18](=[O:21])[CH:19]=[CH2:20].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.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:20]=[CH:19]/[C:18]([N:17]([CH3:16])[CH2:22][C:23]3[N:24]([CH3:32])[C:25]4[C:30]([CH:31]=3)=[CH:29][CH:28]=[CH:27][CH:26]=4)=[O:21])=[CH:3][C:4]=2[CH2:10][NH:9]1

Participants

9

Reactant 4

HCID 80271Tri-o-tolylphosphineHCID 81531DiisopropylethylamineHCID 20752825N-Methyl-N-[(1-methyl-2-indolyl)methyl]acrylamideHCID 594569147-Bromo-3,3-dimethyl-1,3,4,5-tetrahydropyrido[2,3-e][1,4]diazepin-2-one

Product 1

HCID 16659986HCID 16659986, compoundYield 52.3%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 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-methyl-N-(1-methyl-1H-indol-2-ylmethyl)acrylamide (0.35 g, 1.3 mmol) in propionitrile (5 mL) and DMF (1.3 mL) was de-oxygenated with Ar for 10 min. The mixture was treated with (i-Pr)2EtN (0.41 mL, 2.4 mmol) and was de-oxygenated with Ar for 5 min. Pd(OAc)2 (25 mg, 0.11 mmol) and P(o-tol)3 (70 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 EtOAc (100 mL), washed with H2O (50 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 (0.24 g, 51%) as a light pink solid: MS (ESI) m/e 418 (M+H)+.

Workup

  1. waitwas de-oxygenated with Ar for 5 min
  2. customfor 5 min
  3. temperatureThe mixture was heated
  4. temperatureto reflux overnight
  5. temperatureto cool
  6. washwashed with H2O (50 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-1d4fb734d62442da8fb7665dd55ce7e9
Source dataset
uspto-grants-2011_02
Patent number
US07879872B2

Reaction notes

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