Tri-o-tolylphosphine → HCID 59277553, compound

HRID 2097089Notes

Reaction equation

HRID 2097089 reaction equation
[CH2:1]([O:3][C:4]1[C:16]([CH:17]([CH3:19])[CH3:18])=[CH:15][CH:14]=[CH:13][C:5]=1[CH2:6][N:7]([CH3:12])[C:8](=[O:11])[CH:9]=[CH2:10])[CH3:2].C(N(C(C)C)CC)(C)C.Br[C:30]1[CH:50]=[N:49][C:33]2[NH:34][C:35](=[O:48])[CH2:36][N:37]([CH2:39][C:40]3[CH:45]=[CH:44][C:43]([O:46][CH3:47])=[CH:42][CH:41]=3)[CH2:38][C:32]=2[CH:31]=1.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]>[CH2:1]([O:3][C:4]1[C:16]([CH:17]([CH3:18])[CH3:19])=[CH:15][CH:14]=[CH:13][C:5]=1[CH2:6][N:7]([CH3:12])[C:8](=[O:11])/[CH:9]=[CH:10]/[C:30]1[CH:50]=[N:49][C:33]2[NH:34][C:35](=[O:48])[CH2:36][N:37]([CH2:39][C:40]3[CH:45]=[CH:44][C:43]([O:46][CH3:47])=[CH:42][CH:41]=3)[CH2:38][C:32]=2[CH:31]=1)[CH3:2]

Participants

8

Reactant 4

HCID 80271Tri-o-tolylphosphineHCID 81531DiisopropylethylamineHCID 59277600HCID 59277600, compoundHCID 594569197-Bromo-4-(4-methoxybenzyl)-1,3,4,5-tetrahydropyrido[2,3-e][1,4]diazepin-2-one

Product 1

HCID 59277553HCID 59277553, compoundYield 44.5%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolventHCID 7854PropionitrileSolvent

Procedure

A solution of N-(2-ethoxy-3-isopropylbenzyl)-N-methylacrylamide (0.281 g, 1.07 mmol) in propionitrile (4 mL) and DMF (0.8 mL) was deoxygenated with Ar for 20 min. The solution was treated with diisopropylethylamine (0.30 mL, 1.73 mmol) and 7-bromo-4-(4-methoxy-benzyl)-1,3,4,5-tetrahydro-pyrido[2,3-e][1,4]diazepin-2-one (0.300 g, 0.828 mmol). The solution was deoxygenated with Ar for 20 min. Pd(OAc)2 (0.018 g, 0.082 mmol) and P(o-tol)3 (0.050 g, 0.16 mmol) were then added and the solution was deoxygenated again with Ar for 10 min. The mixture was heated to reflux for 1.5 h, then allowed to cool. The mixture was diluted with H2O (100 mL) and then was washed with EtOAc (3×50 mL). The organic layer was washed with brine (2×100 mL), dried (Na2SO4) and concentrated to an orange oil. Purification by column chromatography (silica gel, CH2Cl2 to CH2Cl2/MeOH, 100 to 99.5:0.5) gave the title compound (0.20 g, 44%) as a light yellow solid and as a mixture of amide rotamers: 1H NMR (300 MHz, DMSO-d6) δ 10.43-10.41 (m, 1H), 8.55-8.49 (m, 1H), 8.10-8.01 (m, 1H), 7.55-7.50 (m, 1H), 7.35-7.17 (m, 4H), 7.12-7.04 (m, 1H), 6.91-6.85 (m, 3H), 4.80-4.66 (m, 2H), 3.83-3.70 (m, 7H), 3.65-3.62 (m, 2H), 3.41-3.38 (m, 2H), 3.29-3.90 (m, 1H), 2.56-2.51 (m, 3H), 1.39-1.37 (m, 3H), 1.25-1.11 (m, 6H); MS (ESI) m/e 543 (M+H)+.

Workup

  1. customThe solution was deoxygenated with Ar for 20 min
  2. customthe solution was deoxygenated again with Ar for 10 min
  3. temperatureThe mixture was heated
  4. temperatureto reflux for 1.5 h
  5. temperatureto cool
  6. additionThe mixture was diluted with H2O (100 mL)
  7. washwas washed with EtOAc (3×50 mL)
  8. washThe organic layer was washed with brine (2×100 mL)
  9. dry with materialdried (Na2SO4)
  10. concentrationconcentrated to an orange oil
  11. customPurification by column chromatography (silica gel, CH2Cl2 to CH2Cl2/MeOH, 100 to 99.5:0.5)

Sources & evidence

ORD record
ord-5dfd1af020e04e47935f22554845cee6
Source dataset
uspto-grants-2013_05
Patent number
US08450307B2

Reaction notes

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