Triphenylphosphine → 7-chloro-5-[(4-methyl-1-piperazinyl)carbonylmethyl]-1-[2-methoxy-4-[N-[2-(2-methylphenoxy)ethyl]-N-trifluoroacetylamino]benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine

HRID 1249986Notes

Reaction equation

HRID 1249986 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]([C:12](=[O:28])[C:13]3[CH:18]=[CH:17][C:16]([NH:19][C:20](=[O:25])[C:21]([F:24])([F:23])[F:22])=[CH:15][C:14]=3[O:26][CH3:27])[CH2:10][CH2:9][CH2:8][CH:7]([CH2:29][C:30]([N:32]3[CH2:37][CH2:36][N:35]([CH3:38])[CH2:34][CH2:33]3)=[O:31])[C:6]=2[CH:39]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O[CH2:60][CH2:61][O:62][C:63]1[CH:68]=[CH:67][CH:66]=[CH:65][C:64]=1[CH3:69].N(C(OCC)=O)=NC(OCC)=O>O1CCCC1.O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]([C:12](=[O:28])[C:13]3[CH:18]=[CH:17][C:16]([N:19]([CH2:60][CH2:61][O:62][C:63]4[CH:68]=[CH:67][CH:66]=[CH:65][C:64]=4[CH3:69])[C:20](=[O:25])[C:21]([F:24])([F:23])[F:22])=[CH:15][C:14]=3[O:26][CH3:27])[CH2:10][CH2:9][CH2:8][CH:7]([CH2:29][C:30]([N:32]3[CH2:33][CH2:34][N:35]([CH3:38])[CH2:36][CH2:37]3)=[O:31])[C:6]=2[CH:39]=1

Participants

7

Reactant 4

HCID 11776TriphenylphosphineHCID 22539Ethanol, 2-(o-tolyloxy)-HCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 180010547-chloro-5-[(4-methyl-1-piperazinyl)carbonyl-methyl]-1-(2-methoxy-4-trifluoroacetylaminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine

Product 1

HCID 180010987-chloro-5-[(4-methyl-1-piperazinyl)carbonylmethyl]-1-[2-methoxy-4-[N-[2-(2-methylphenoxy)ethyl]-N-trifluoroacetylamino]benzoyl]-2,3,4,5-tetrahydro-1H-benzazepineYield 93%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 7-chloro-5-[(4-methyl-1-piperazinyl)carbonylmethyl]-1-(2-methoxy-4-trifluoroacetylaminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine (0.4 g) in dry tetrahydrofuran (20 ml) are added triphenylphosphine (0.54 g) and o-(2-hydroxyethoxy)toluene (0.29 g) at room temperature. To the mixture is added dropwise a solution of diethyl azodicarboxylate (0.32 ml) in dry tetrahydrofuran (5 ml), and the mixture is stirred at room temperature for 16 hours. To the mixture is added water, and the mixture is extracted with diethyl ether. The ether layer is dried, evaporated to remove the solvent, and the residue is purified by silica gel column chromatography (solvent; dichloromethane:methanol=50:1→30:1) to give 7-chloro-5-[(4-methyl-1-piperazinyl)carbonylmethyl]-1-[2-methoxy-4-{N-[2-(2-methylphenoxy)ethyl]-N-trifluoroacetylamino}benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine (0.46 g) as colorless amorphous.

Workup

  1. extractionthe mixture is extracted with diethyl ether
  2. dry with materialThe ether layer is dried
  3. customevaporated
  4. customto remove the solvent
  5. customthe residue is purified by silica gel column chromatography (solvent; dichloromethane:methanol=50:1→30:1)

Sources & evidence

ORD record
ord-0865670fd68a46278bb18c1a943f4530
Source dataset
uspto-grants-2002_01
Patent number
US06335327B1

Reaction notes

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