1,2,3,4-Tetrahydroisoquinoline → N-[4-(3,4-Dihydro-1H-isoquinolin-2-yl)-2,6-dimethoxy-phenyl]-3,3-dimethyl-butanamide

HRID 2067831Notes

Reaction equation

HRID 2067831 reaction equation
Br[C:2]1[CH:7]=[C:6]([O:8][CH3:9])[C:5]([NH:10][C:11](=[O:17])[CH2:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[C:4]([O:18][CH3:19])[CH:3]=1.[CH2:20]1[C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[CH2:23][CH2:22][NH:21]1.CC(C)([O-])C.[K+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd]>[CH2:20]1[C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[CH2:23][CH2:22][N:21]1[C:2]1[CH:7]=[C:6]([O:8][CH3:9])[C:5]([NH:10][C:11](=[O:17])[CH2:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[C:4]([O:18][CH3:19])[CH:3]=1

Participants

5

Reactant 3

HCID 70461,2,3,4-TetrahydroisoquinolineHCID 23665647Potassium tert-butoxideHCID 58097361HCID 58097361, compound

Product 1

HCID 24937454N-[4-(3,4-Dihydro-1H-isoquinolin-2-yl)-2,6-dimethoxy-phenyl]-3,3-dimethyl-butanamide

Reagents, catalysts & solvents 1

HCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladiumCatalyst

Procedure

Toluene (6 mL) was degassed with nitrogen for 15 min in a 10 mL of microwave tube, then N-(4-bromo-2,6-dimethoxy phenyl)-3,3-dimethyl butanamide (200 mg, 0.6 mmol) and 1,2,3,4-tetrahydroisoquinoline (96 mg, 0.72 mmol) was added, followed by potassium tert-butoxide (101 mg, 0.9 mmol), bis(dibenzylidene acetone)palladium (17 mg, 0.03 mmol), and 2-dicyclohexyphosphino-2-(N,N-dimethylamino)biphenyl (24 mg, 0.06 mmol). The reaction tube was sealed and reacted in microwave at 100° C. for 2 hours. The reaction mixture was purified by silica gel column (ISCO, hexane/EtOAc, 0-40%, 40 min) to give pure compound as a white solid. 1H-NMR (DMSO-d6, 400 MHz): δ 8.36 (brs, 1H, exchangeable with D2O), 7.20 (m, 4H), 6.25 (s, 2H), 4.41 (s, 2H), 3.72 (s, 6H), 3.55 (t, J=6.0 Hz, 2H), 2.95 (t, J=6.0 Hz, 2H), 2.07 (s, 2H), 1.03 (s, 9H). MS: 383 (M+1).

Workup

  1. customToluene (6 mL) was degassed with nitrogen for 15 min in a 10 mL of microwave tube
  2. customThe reaction tube was sealed
  3. customreacted in microwave at 100° C. for 2 hours
  4. customThe reaction mixture was purified by silica gel column (ISCO, hexane/EtOAc, 0-40%, 40 min)
  5. customto give pure compound as a white solid

Sources & evidence

ORD record
ord-8050f5d1f48143b19fd3d6362bd3e8c2
Source dataset
uspto-grants-2012_10
Patent number
US08293911B2

Reaction notes

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