Methane → 1-[(1R)-3-methyl-1-[1,3-dihydro-1-methyl-2-oxo-5-phenyl-2H-1,4-benzodiazepin-3-ylcarbamoyl]-butyl]-cyclopent-3-enecarboxylic amide

HRID 1635110Notes

Reaction equation

HRID 1635110 reaction equation
[CH2:1]([C:4]([CH2:35][CH:36]=C)([CH:8]([CH2:31][CH:32]([CH3:34])[CH3:33])[C:9]([NH:11][CH:12]1[C:18](=[O:19])[N:17]([CH3:20])[C:16]2[CH:21]=[CH:22][CH:23]=[CH:24][C:15]=2[C:14]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)=[N:13]1)=[O:10])[C:5]([NH2:7])=[O:6])[CH:2]=C.C>C1(C)C=CC=CC=1.C(Cl)Cl.Cl[Ru](=CC1C=CC=CC=1)([P](C1CCCCC1)(C1CCCCC1)C1CCCCC1)([P](C1CCCCC1)(C1CCCCC1)C1CCCCC1)Cl.C=CC1C=CC=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Ru]Cl>[CH3:34][CH:32]([CH3:33])[CH2:31][C@H:8]([C:4]1([C:5]([NH2:7])=[O:6])[CH2:35][CH:36]=[CH:2][CH2:1]1)[C:9](=[O:10])[NH:11][CH:12]1[N:13]=[C:14]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[C:15]2[CH:24]=[CH:23][CH:22]=[CH:21][C:16]=2[N:17]([CH3:20])[C:18]1=[O:19]

Participants

7

Reactant 2

HCID 297MethaneHCID 221352682,2-Diallyl-3-isobutyl-N4-(1-methyl-2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)-succinamide

Product 1

HCID 576061911-[(1R)-3-methyl-1-[1,3-dihydro-1-methyl-2-oxo-5-phenyl-2H-1,4-benzodiazepin-3-ylcarbamoyl]-butyl]-cyclopent-3-enecarboxylic amideYield 46.2%

Reagents, catalysts & solvents 4

HCID 60145889Benzylidene-bis(triphenylphosphine)ruthenium dichlorideCatalystHCID 178479819HCID 178479819, compoundCatalystHCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 31 (110 mg, 0.22 mmol) in 20 ml of toluene and CH2Cl2 (1:1) at 100 degree was added (bis(tricyclohexylphosphine)-benzylidine ruthenium (IV) dichloride) (24 mg, 0.029 mmol). The mixture was stirred at 100 degree for 4 hrs and another 24 mg Grubbs' catalyst was added. The mixture was then stirred at 100 degree for another 4 hrs. Then the solution was cooled to RT, after which 100 mg of charcoal was added. The mixture was filtered through ceslite to provide a slightly yellow solution, then concentrated. The residue was purified in silica gel chromatography with CH2Cl2/methanol (10:0.5) to give 48 mg of 32 (46%). 1H NMR (CDCl3) 0.97-0.90 (dd, 6H), 1.30-1.25 (m, 1H), 1.65-1.57 (m, 1H), 2.00-1.85 (m, 1H), 2.40-2.30 (d, 1H), 2.80-2.65 (m, 2H), 3.00-2.80 (d, 1H), 3.40-3.20 (m, 1H), 3.47 (s, 3H), 5.40-5.20 (s, 1H), 5.52-5.49 (d, 1H), 5.80-5.71 (m, 2H), 7.63-7.20 (m, 9H), 7.90 (s, 1H). API AP+ 473.1 (M+1).

Workup

  1. stirringThe mixture was then stirred at 100 degree for another 4 hrs
  2. filtrationThe mixture was filtered through ceslite
  3. customto provide a slightly yellow solution
  4. concentrationconcentrated
  5. customThe residue was purified in silica gel chromatography with CH2Cl2/methanol (10:0.5)

Sources & evidence

ORD record
ord-13c6eb48ef904ebcaa893dcd08d40692
Source dataset
uspto-grants-2003_01
Patent number
US06509333B2

Reaction notes

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