Tri-o-tolylphosphine → HCID 16061423, compound

HRID 1362260Notes

Reaction equation

HRID 1362260 reaction equation
[CH2:1]([O:3][C:4]1[C:16]([O:17][C:18]([F:21])([F:20])[F:19])=[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:32]1[CH:45]=[N:44][C:35]2[NH:36][C:37](=[O:43])[C:38]([CH3:42])([CH3:41])[NH:39][CH2:40][C:34]=2[CH:33]=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]>[CH3:41][C:38]1([CH3:42])[C:37](=[O:43])[NH:36][C:35]2[N:44]=[CH:45][C:32](/[CH:10]=[CH:9]/[C:8]([N:7]([CH3:12])[CH2:6][C:5]3[CH:13]=[CH:14][CH:15]=[C:16]([O:17][C:18]([F:19])([F:20])[F:21])[C:4]=3[O:3][CH2:1][CH3:2])=[O:11])=[CH:33][C:34]=2[CH2:40][NH:39]1

Participants

8

Reactant 4

HCID 80271Tri-o-tolylphosphineHCID 81531DiisopropylethylamineHCID 59277573HCID 59277573, compoundHCID 594569147-Bromo-3,3-dimethyl-1,3,4,5-tetrahydropyrido[2,3-e][1,4]diazepin-2-one

Product 1

HCID 16061423HCID 16061423, compoundYield 45.7%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolventHCID 7854PropionitrileSolvent

Procedure

A solution of N-(2-ethoxy-3-trifluoromethoxybenzyl)-N-methylacrylamide (0.447 g, 1.47 mmol) in propionitrile (5 mL) and DMF (1 mL) was deoxygenated with Ar for 20 min and then treated with diisopropylethylamine (0.40 mL, 2.3 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 minutes. Pd(OAc)2 (0.024 g, 0.111 mmol) and P(o-tol)3 (0.067 g, 0.222 mmol) were added and the solution deoxygenated with Ar for 20 min. The mixture was heated to reflux for 18 h then, allowed to cool. The mixture was diluted with EtOAc (30 mL) and was washed with H2O (3×50 mL) and brine (2×50 mL), dried (Na2SO4) and concentrated to a yellow-orange solid. Purification by column chromatography (silica gel, CH2Cl2/MeOH, 100 to 98:2) gave the title compound (0.25 g, 31%) as an off-white solid and as a mixture of amide rotamers: 1H NMR (300 MHz, DMSO-d6) δ 9.80-9.78 (m, 1H), 8.40-8.37 (m, 1H), 8.01-7.93 (m, 1H), 7.56-7.49 (m, 1H), 7.36-7.09 (m, 4H), 4.87-4.68 (m, 2H), 4.06-3.83 (m, 4H), 3.31-2.88 (m, 4H), 1.36-1.29 (m, 9H).

Workup

  1. customThe solution was deoxygenated with Ar for 20 minutes
  2. customthe solution deoxygenated with Ar for 20 min
  3. temperatureThe mixture was heated
  4. temperatureto reflux for 18 h
  5. temperatureto cool
  6. additionThe mixture was diluted with EtOAc (30 mL)
  7. washwas washed with H2O (3×50 mL) and brine (2×50 mL)
  8. dry with materialdried (Na2SO4)
  9. concentrationconcentrated to a yellow-orange solid
  10. customPurification by column chromatography (silica gel, CH2Cl2/MeOH, 100 to 98:2)

Sources & evidence

ORD record
ord-d8f72e64d3104b24ad4e97106e3da2fa
Source dataset
uspto-grants-2011_02
Patent number
US07879872B2

Reaction notes

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