Tri-o-tolylphosphine → HCID 16659982, compound

HRID 1362320Notes

Reaction equation

HRID 1362320 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.[CH2:16]([C:18]1[C:22]2[CH:23]=[CH:24][CH:25]=[CH:26][C:21]=2[O:20][C:19]=1[CH2:27][N:28]([CH3:33])[C:29](=[O:32])[CH:30]=[CH2:31])[CH3:17].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.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:31]=[CH:30]/[C:29]([N:28]([CH2:27][C:19]3[O:20][C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=4[C:18]=3[CH2:16][CH3:17])[CH3:33])=[O:32])=[CH:3][C:4]=2[CH2:10][NH:9]1

Participants

8

Reactant 4

HCID 80271Tri-o-tolylphosphineHCID 81531DiisopropylethylamineHCID 59277547HCID 59277547, compoundHCID 594569147-Bromo-3,3-dimethyl-1,3,4,5-tetrahydropyrido[2,3-e][1,4]diazepin-2-one

Product 1

HCID 16659982HCID 16659982, compoundYield 20.3%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolventHCID 7854PropionitrileSolvent

Procedure

To 7-bromo-3,3-dimethyl-1,3,4,5-tetrahydro-pyrido[2,3-e][1,4]diazepin-2-one (400 mg, 1.48 mmol) in propionitrile (40 mL) and DMF (10 mL) was added N-(3-ethyl-benzofuran-2-ylmethyl)-N-methylacrylamide (410 mg, 1.62 mmol), (i-Pr)2EtN (0.51 mL, 2.96 mmol), Pd(OAc)2 (332 mg, 0.148 mmol) and P(o-tol)3 (90.1 mg, 0.296 mmol), and the mixture was de-oxygenated with argon for 15 min. The mixture was heated to reflux overnight, allowed to cool and then filtered. The filtrate was concentrated and the residue was dissolved in CH2Cl2 (150 mL). The organic solution was washed with water and brine, dried (Na2SO4) and the solvent was removed in vacuo. Purification by column chromatography (silica gel, CH2Cl2/MeOH, 20:1) gave the title compound (130 mg, 20%) as an off-white solid: MS m/z 433 (M+H)+.

Workup

  1. temperatureThe mixture was heated
  2. temperatureto reflux overnight
  3. temperatureto cool
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated
  6. dissolutionthe residue was dissolved in CH2Cl2 (150 mL)
  7. washThe organic solution was washed with water and brine
  8. dry with materialdried (Na2SO4)
  9. customthe solvent was removed in vacuo
  10. customPurification by column chromatography (silica gel, CH2Cl2/MeOH, 20:1)

Sources & evidence

ORD record
ord-d23873e96d2c438cbb5030e2d8c978d1
Source dataset
uspto-grants-2011_02
Patent number
US07879872B2

Reaction notes

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