Tri-o-tolylphosphine → HCID 16660146, compound

HRID 2097091Notes

Reaction equation

HRID 2097091 reaction equation
[CH2:1]([O:5][C:6]1[C:18]([O:19][CH3:20])=[CH:17][CH:16]=[CH:15][C:7]=1[CH2:8][N:9]([CH3:14])[C:10](=[O:13])[CH:11]=[CH2:12])[CH:2]([CH3:4])[CH3:3].C(N(C(C)C)CC)(C)C.Br[C:31]1[CH:42]=[N:41][C:34]2[NH:35][C:36](=[O:40])[CH2:37][NH:38][CH2:39][C:33]=2[CH:32]=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:5][C:6]1[C:18]([O:19][CH3:20])=[CH:17][CH:16]=[CH:15][C:7]=1[CH2:8][N:9]([CH3:14])[C:10](=[O:13])/[CH:11]=[CH:12]/[C:31]1[CH:42]=[N:41][C:34]2[NH:35][C:36](=[O:40])[CH2:37][NH:38][CH2:39][C:33]=2[CH:32]=1)[CH:2]([CH3:3])[CH3:4]

Participants

8

Reactant 4

HCID 80271Tri-o-tolylphosphineHCID 81531DiisopropylethylamineHCID 59277527N-(2-Isobutoxy-3-methoxybenzyl)-N-methylacrylamideHCID 594569547-Bromo-4,5-dihydro-1H-pyrido[2,3-e][1,4]diazepin-2(3H)-one

Product 1

HCID 16660146HCID 16660146, compoundYield 23%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolventHCID 7854PropionitrileSolvent

Procedure

A solution of N-(2-isobutoxy-3-methoxybenzyl)-N-methylacrylamide (0.387 g, 1.40 mmol) in propionitrile (5 mL) and DMF (1 mL) was deoxygenated with Ar for 20 min. Then treated with diisopropylethylamine (0.39 mL, 2.25 mmol) and 7-bromo-1,3,4,5-tetrahydro-pyrido[2,3-e][1,4]diazepin-2-one (0.300 g, 1.07 mmol). The solution was deoxygenated with Ar for 20 min. Then Pd(OAc)2 (0.024 g, 0.10 mmol) and P(o-tol)3 (0.065 g, 0.21 mmol) were added and the solution deoxygenated with Ar for 20 min. The solution was heated to reflux for 18 h, then allowed to cool. The solution was diluted with H2O (30 mL) and was washed with EtOAc (3×50 mL). The organics were washed with brine (2×100 mL), dried over Na2SO4, filtered and concentrated to an orange-brown semi-solid. Purification by column chromatography (silica gel, CH2Cl2 to CH2Cl2/MeOH, 100 to 95:5) gave the title compound (0.10 g, 23%) as an yellow-orange solid and as a mixture of amide rotamers: 1H NMR (300 MHz, DMSO-d6) δ 10.08-10.06 (m, 1H), 8.44-8.39 (m, 1H), 8.02-7.95 (m, 1H), 7.53-7.48 (m, 1H), 7.30-7.25 (m, 1H), 7.04-6.93 (m, 2H), 6.66-6.41 (m, 1H), 4.79-4.64 (m, 2H), 3.91-3.87 (m, 2H), 3.79 (s, 3H), 3.71-3.61 (m, 4H), 3.11-2.87 (m, 4H), 2.03-1.99 (m, 1H), 1.00-0.97 (m, 6H); MS (ESI) m/e 439 (M+H)+.

Workup

  1. customThe solution was deoxygenated with Ar for 20 min
  2. customthe solution deoxygenated with Ar for 20 min
  3. temperatureThe solution was heated
  4. temperatureto reflux for 18 h
  5. temperatureto cool
  6. additionThe solution was diluted with H2O (30 mL)
  7. washwas washed with EtOAc (3×50 mL)
  8. washThe organics were washed with brine (2×100 mL)
  9. dry with materialdried over Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated to an orange-brown semi-solid
  12. customPurification by column chromatography (silica gel, CH2Cl2 to CH2Cl2/MeOH, 100 to 95:5)

Sources & evidence

ORD record
ord-8c2629ce756d4eec840eac4a8b535502
Source dataset
uspto-grants-2013_05
Patent number
US08450307B2

Reaction notes

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