1,2-Dichloroethane → 4-(4-methyl-1-phenyl-3,4-dihydro-1H-isoquinolin-2-yl)-4-oxo-N-[[3-(trifluoromethyl)phenyl]methyl]butyric acid amide

HRID 383997

Reaction equation

HRID 383997 reaction equation
C(Cl)CCl.CCN(C(C)C)C(C)C.C1C=CC2N(O)N=NC=2C=1.[O:24]=[C:25]([NH:31][CH2:32][C:33]1[CH:38]=[CH:37][CH:36]=[C:35]([C:39]([F:42])([F:41])[F:40])[CH:34]=1)[CH2:26][CH2:27][C:28]([OH:30])=O.[CH3:43][CH:44]1[C:53]2[C:48](=[CH:49][CH:50]=[CH:51][CH:52]=2)[CH:47]([C:54]2[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=2)[NH:46][CH2:45]1>C(Cl)Cl.CCCCCC>[CH3:43][CH:44]1[C:53]2[C:48](=[CH:49][CH:50]=[CH:51][CH:52]=2)[CH:47]([C:54]2[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=2)[N:46]([C:28](=[O:30])[CH2:27][CH2:26][C:25]([NH:31][CH2:32][C:33]2[CH:38]=[CH:37][CH:36]=[C:35]([C:39]([F:42])([F:41])[F:40])[CH:34]=2)=[O:24])[CH2:45]1

Participants

8

Reactant 5

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 146126774-Methyl-1-phenyl-1,2,3,4-tetrahydroisoquinolineHCID 433971044-Oxo-4-(3-(trifluoromethyl)benzylamino)butyric acid

Product 1

HCID 468297314-(4-methyl-1-phenyl-3,4-dihydro-1H-isoquinolin-2-yl)-4-oxo-N-[[3-(trifluoromethyl)phenyl]methyl]butyric acid amideYield 72%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8058HexaneSolvent

Procedure

384 mg (2.0 mmol) of EDC, 306 μl (1.8 mmol) of DIPEA and 135 mg (1.0 mmol) of HOBt were added to a solution of 275 mg (1.0 mmol) of 4-oxo-4-(3-(trifluoromethyl)benzylamino)butyric acid (intermediate VVV01) in DCM (13 ml) and the mixture was stirred for 5 min at RT. Then 268 mg (1.2 mmol) of 4-methyl-1-phenyl-1,2,3,4-tetrahydroisoquinoline were added and the mixture was stirred for a further 2 h at RT. It was then diluted with DCM and washed successively with a 10% aqueous hydrochloric acid, a saturated aqueous Na2CO3 solution, a saturated aqueous NH4Cl solution and brine. The organic phase was dried over Na2SO4, filtered and concentrated to small volume under vacuum. Column chromatography (hexane/EE 7:3) of the residue produced 346 mg (0.72 mmol, 72%) of 4-(4-methyl-1-phenyl-3,4-dihydro-1H-isoquinolin-2-yl)-4-oxo-N-[[3-(trifluoromethyl)phenyl]methyl]butyric acid amide. MS: m/z 481.2 [M+H]+.

Workup

  1. stirringthe mixture was stirred for a further 2 h at RT
  2. washwashed successively with a 10% aqueous hydrochloric acid
  3. dry with materialThe organic phase was dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated to small volume under vacuum

Sources & evidence

ORD record
ord-63d4ef374ee74e1e8037e93e414887c8
Source dataset
uspto-grants-2013_02
Patent number
US08367700B2

Linked notes

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