Tri-o-tolylphosphine → HCID 16659664, compound

HRID 1362298Notes

Reaction equation

HRID 1362298 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:44]=[N:43][C:34]2[NH:35][C:36](=[O:42])[C:37]([CH3:41])([CH3:40])[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]>[CH3:40][C:37]1([CH3:41])[C:36](=[O:42])[NH:35][C:34]2[N:43]=[CH:44][C:31](/[CH:12]=[CH:11]/[C:10]([N:9]([CH2:8][C:7]3[CH:15]=[CH:16][CH:17]=[C:18]([O:19][CH3:20])[C:6]=3[O:5][CH2:1][CH:2]([CH3:3])[CH3:4])[CH3:14])=[O:13])=[CH:32][C:33]=2[CH2:39][NH:38]1

Participants

8

Reactant 4

HCID 80271Tri-o-tolylphosphineHCID 81531DiisopropylethylamineHCID 59277527N-(2-Isobutoxy-3-methoxybenzyl)-N-methylacrylamideHCID 594569147-Bromo-3,3-dimethyl-1,3,4,5-tetrahydropyrido[2,3-e][1,4]diazepin-2-one

Product 1

HCID 16659664HCID 16659664, compoundYield 36.7%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolventHCID 7854PropionitrileSolvent

Procedure

A solution of N-(2-isobutoxy-3-methoxybenzyl)-N-methylacrylamide (0.407 g, 1.47 mmol) in propionitrile (5 mL) and DMF (1 mL) was deoxygenated with Ar for 20 min. The solution was treated with diisopropylethylamine (0.40 mL, 2.33 mmol) and 7-bromo-3,3-dimethyl-1,3,4,5-tetrahydro-pyrido[2,3-e][1,4]diazepin-2-one (0.300 g, 1.11 mmol). The solution was deoxygenated with Ar for 20 min. Pd(OAc)2 (0.024 g, 0.11 mmol) and P(o-tol)3 (0.067 g, 0.22 mmol) were then added and the solution was deoxygenated with Ar for 20 min. The solution was heated to reflux for 18 h, then allowed to cool. The solution was diluted with EtOAc (30 mL) and was washed with H2O (3×50 mL). The organic layer was washed with brine (2×50 mL), dried (Na2SO4) and concentrated to an orange oil. Purification by column chromatography (silica gel, CH2Cl2/MeOH, 100 to 98:2) gave the title compound (0.19 g, 32%) as an off-white solid and as a mixture of amide rotamers: 1H NMR (300 MHz, DMSO-d6) δ 9.79-9.77 (m, 1H), 8.40-8.35 (m, 1H), 8.00-7.92 (m, 1H), 7.54-7.48 (m, 1H), 7.29-7.22 (m, 1H), 7.04-6.96 (m, 2H), 6.66-6.63 (m, 1H), 4.79-4.64 (m, 2H), 3.89-3.83 (m, 2H), 3.79 (s, 3H), 3.72-3.67 (m, 2H), 3.11-2.87 (m, 4H), 2.04-1.99 (m, 1H), 1.31-1.29 (m, 6H), 1.00-0.97 (m, 6H).

Workup

  1. customThe solution was deoxygenated with Ar for 20 min
  2. customthe solution was 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 EtOAc (30 mL)
  7. washwas washed with H2O (3×50 mL)
  8. washThe organic layer was washed with brine (2×50 mL)
  9. dry with materialdried (Na2SO4)
  10. concentrationconcentrated to an orange oil
  11. customPurification by column chromatography (silica gel, CH2Cl2/MeOH, 100 to 98:2)

Sources & evidence

ORD record
ord-795f1e7d8b7c4673b4c75ef1bcfabc34
Source dataset
uspto-grants-2011_02
Patent number
US07879872B2

Reaction notes

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