trans-2-Phenylcyclopropanecarboxylic acid → (8-Bromo-5-fluoro-3,4-dihydro-1H-isoquinolin-2-yl)-((1R,2R)-2-phenyl-cyclopropyl)-methanone

HRID 1773958Notes

Reaction equation

HRID 1773958 reaction equation
Cl.[Br:2][C:3]1[CH:4]=[CH:5][C:6]([F:13])=[C:7]2[C:12]=1[CH2:11][NH:10][CH2:9][CH2:8]2.[C:14]1([C@@H:20]2[CH2:22][C@H:21]2[C:23](O)=[O:24])[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.Cl.CN(C)CCCN=C=NCC>CN(C=O)C.CN(C)C1C=CN=CC=1.CCOC(C)=O>[Br:2][C:3]1[CH:4]=[CH:5][C:6]([F:13])=[C:7]2[C:12]=1[CH2:11][N:10]([C:23]([C@@H:21]1[CH2:22][C@H:20]1[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)=[O:24])[CH2:9][CH2:8]2

Participants

7

Reactant 3

HCID 237413trans-2-Phenylcyclopropanecarboxylic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 896484578-Bromo-5-fluoro-1,2,3,4-tetrahydroisoquinoline hydrochloride

Product 1

HCID 89648804(8-Bromo-5-fluoro-3,4-dihydro-1H-isoquinolin-2-yl)-((1R,2R)-2-phenyl-cyclopropyl)-methanone

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 8-bromo-5-fluoro-1,2,3,4-tetrahydro-isoquinoline hydrochloride (200 mg, 0.75 mmol, 1.0 eq.) and the acid (1R,2R)-2-phenyl-cyclopropanecarboxylic acid (122 mg, 0.75 mmol, 1.0 eq.) in DMF (9 mL) was treated with 4-(dimethylamino)pyridine (367 mg, 3.00 mmol, 4.0 eq.) and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (216 mg, 1.13 mmol, 1.5 eq.) and the resulting solution was stirred at r.t. for 18 hours. The reaction mixture was diluted with AcOEt (70 mL). The diluted solution was washed with 1N aq. HCl (3×30 mL), sat. aq. NaCl soln. (1×30 mL), dried over MgSO4, filtered, and concentrated in vacuo to give the desired compound as a pale yellow oil. The product was used without further purification.

Workup

  1. washThe diluted solution was washed with 1N aq. HCl (3×30 mL), sat. aq. NaCl soln
  2. dry with material(1×30 mL), dried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-4024b6914dc043e2b2e21d678db69627
Source dataset
uspto-grants-2016_02
Patent number
US09255090B2

Reaction notes

Loading…