Tri-o-tolylphosphine → HCID 16662046, compound

HRID 2097012Notes

Reaction equation

HRID 2097012 reaction equation
[CH3:1][N:2]([CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[C:10]([O:14][C:15]([F:18])([F:17])[F:16])[C:9]=1[O:19][CH2:20][CH2:21][CH3:22])[C:3](=[O:6])[CH:4]=[CH2:5].C(N(C(C)C)CC)(C)C.Br[C:33]1[CH:46]=[N:45][C:36]2[NH:37][C:38](=[O:44])[C:39]([CH3:43])([CH3:42])[NH:40][CH2:41][C:35]=2[CH:34]=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]>[CH3:42][C:39]1([CH3:43])[C:38](=[O:44])[NH:37][C:36]2[N:45]=[CH:46][C:33](/[CH:5]=[CH:4]/[C:3]([N:2]([CH3:1])[CH2:7][C:8]3[CH:13]=[CH:12][CH:11]=[C:10]([O:14][C:15]([F:18])([F:16])[F:17])[C:9]=3[O:19][CH2:20][CH2:21][CH3:22])=[O:6])=[CH:34][C:35]=2[CH2:41][NH:40]1

Participants

8

Reactant 4

HCID 80271Tri-o-tolylphosphineHCID 81531DiisopropylethylamineHCID 59277578HCID 59277578, compoundHCID 594569147-Bromo-3,3-dimethyl-1,3,4,5-tetrahydropyrido[2,3-e][1,4]diazepin-2-one

Product 1

HCID 16662046HCID 16662046, compoundYield 44.5%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolventHCID 7854PropionitrileSolvent

Procedure

A solution of N-methyl-N-(2-propoxy-3-trifluoromethoxybenzyl)acrylamide (0.468 g, 1.47 mmol) in propionitrile (5 mL) and DMF (1 mL) was deoxygenated with Ar for 20 min. The solution was treated sequentially 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 min. 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 was deoxygenated with Ar for 20 minutes. The mixture was heated to reflux for 18 h, then allowed to cool. The mixture was diluted with EtOAc (30 mL) and then washed with H2O (3×50 mL) and brine (2×100 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), 8.41-8.36 (m, 1H), 8.01-7.92 (m, 1H), 7.56-7.49 (m, 1H), 7.36-7.08 (m, 4H), 4.87-4.69 (m, 2H), 3.96-3.83 (m, 4H), 3.16-2.88 (m, 4H), 1.78-1.71 (m, 2H), 1.31-1.29 (m, 6H), 1.03-0.98 (m, 3H); MS (ESI) m/e 507 (M+H)+.

Workup

  1. customThe solution was deoxygenated with Ar for 20 min
  2. customthe solution was deoxygenated with Ar for 20 minutes
  3. temperatureThe mixture was heated
  4. temperatureto reflux for 18 h
  5. temperatureto cool
  6. additionThe mixture was diluted with EtOAc (30 mL)
  7. washwashed with H2O (3×50 mL) and brine (2×100 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-e80b96d803fc48849207bdb8edb54ad8
Source dataset
uspto-grants-2013_05
Patent number
US08450307B2

Reaction notes

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