Trimethylaluminum → cis-5-Methoxy-1-[4-(1-methylpiperidin-4-yl)-1-naphthoyl]-6-(3,4,5-trimethylpiperazin-1-yl)indoline

HRID 352371Notes

Reaction equation

HRID 352371 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][C:11]=1[N:12]1[CH2:17][C@H:16]([CH3:18])[N:15]([CH3:19])[C@H:14]([CH3:20])[CH2:13]1)[NH:8][CH2:7][CH2:6]2.C[Al](C)C.[CH3:25][N:26]1[CH2:31][CH2:30][CH:29]([C:32]2[C:41]3[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=3)[C:35]([C:42](OC)=[O:43])=[CH:34][CH:33]=2)[CH2:28][CH2:27]1>C1(C)C=CC=CC=1>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][C:11]=1[N:12]1[CH2:13][C@H:14]([CH3:20])[N:15]([CH3:19])[C@H:16]([CH3:18])[CH2:17]1)[N:8]([C:42]([C:35]1[C:36]3[C:41](=[CH:40][CH:39]=[CH:38][CH:37]=3)[C:32]([CH:29]3[CH2:30][CH2:31][N:26]([CH3:25])[CH2:27][CH2:28]3)=[CH:33][CH:34]=1)=[O:43])[CH2:7][CH2:6]2

Participants

5

Reactant 3

HCID 16682925TrimethylaluminumHCID 22711881Methyl 4-(1-methylpiperidin-4-yl)-1-naphthoateHCID 69836129cis-5-Methoxy-6-(3,4,5-trimethylpiperazin-1-yl)indoline

Product 1

HCID 69836444cis-5-Methoxy-1-[4-(1-methylpiperidin-4-yl)-1-naphthoyl]-6-(3,4,5-trimethylpiperazin-1-yl)indolineYield 35.3%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent3×

Procedure

A stirred solution of D3 (58 mg, 0.21 mmole) in toluene (5 ml) under argon was treated with 2M trimethylaluminium in toluene (0.13 ml, 0.25 mmole), then stirred at room temperature for 0.75 h. A solution of D9 (60 mg, 0.21 mmole) in toluene (5 ml) was added and the mixture was heated under reflux for 3.5 h, then allowed to cool to room temperature. The mixture was added to a 5 g silica gel column and eluted with 0-10% MeOH/DCM to afford a yellow oil. This was further purified by preparative plate TLC on silica gel eluting with 9:1:0.1 DCM/MeOH/0.88 NH3 to afford the title compound as a white solid (39 mg, 35%). MH+ 527.

Workup

  1. temperaturethe mixture was heated
  2. temperatureunder reflux for 3.5 h
  3. temperatureto cool to room temperature
  4. additionThe mixture was added to a 5 g silica gel column
  5. washeluted with 0-10% MeOH/DCM
  6. customto afford a yellow oil
  7. customThis was further purified by preparative plate TLC on silica gel eluting with 9:1:0.1 DCM/MeOH/0.88 NH3

Sources & evidence

ORD record
ord-2e2e1ec855b04b47b7da6ff5467efba2
Source dataset
uspto-grants-2004_06
Patent number
US06747030B1

Reaction notes

Loading…