Toluene → 4-(3-Aza-bicyclo[3.2.2]non-3-yl)-N-(6-fluoro-quinolin-3-yl)-benzamide

HRID 1944554Notes

Reaction equation

HRID 1944554 reaction equation
C[Al](C)C.C1(C)C=CC=CC=1.[F:12][C:13]1[CH:14]=[C:15]2[C:20](=[CH:21][CH:22]=1)[N:19]=[CH:18][C:17]([NH2:23])=[CH:16]2.C([O:26][C:27](=O)[C:28]1[CH:33]=[CH:32][C:31]([N:34]2[CH2:40][CH:39]3[CH2:41][CH2:42][CH:36]([CH2:37][CH2:38]3)[CH2:35]2)=[CH:30][CH:29]=1)C>ClCCCl.ClCCl.CO>[CH:39]12[CH2:38][CH2:37][CH:36]([CH2:42][CH2:41]1)[CH2:35][N:34]([C:31]1[CH:30]=[CH:29][C:28]([C:27]([NH:23][C:17]3[CH:18]=[N:19][C:20]4[C:15]([CH:16]=3)=[CH:14][C:13]([F:12])=[CH:22][CH:21]=4)=[O:26])=[CH:33][CH:32]=1)[CH2:40]2

Participants

8

Reactant 4

HCID 1140TolueneHCID 16682925TrimethylaluminumHCID 224587126-Fluoroquinolin-3-amineHCID 668161774-(3-Aza-bicyclo[3.2.2]non-3-yl)-benzoic acid ethyl ester

Product 1

HCID 601143134-(3-Aza-bicyclo[3.2.2]non-3-yl)-N-(6-fluoro-quinolin-3-yl)-benzamide

Reagents, catalysts & solvents 3

HCID 111,2-DichloroethaneSolventHCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

In a sealed tube, a solution of trimethylaluminum in toluene (3N, 0.41 mL, 1.23 mmol) was added to a solution of 6-fluoro-quinolin-3-ylamine (90 mg, 0.56 mmol) and 4-(3-aza-bicyclo[3.2.2]non-3-yl)-benzoic acid ethyl ester (180 mg, 0.65 mmol) in 1,2-dichloroethane (2 mL). The solution was allowed to stir at room temperature for 15 minutes, and then heated at 83° C. for 16 hours. The tube was cooled and carefully opened. Methanol (0.5 mL) was added and the resultant mixture was allowed to stir at room temperature for several hours. The mixture was diluted with dichloromethane and preabsorbed onto silica gel. Flash chromatography, using a gradient of methanol (0% to 3%) in dichloromethane as the eluant, gave the product, 60 mg (28%), as a colorless solid. MS: m/z 390.0 (MH+). 1HNMR (DMSO-d6): δ 1.67 (m, 8 H), 2.14 (m, 2 H), 3.56 (d, 2 H), 6.97 (d, 2 H), 7.54 (d of t, 1 H), 7.77 (d of d, 1 H), 7.92 (d, 2 H), 8.04 (d of d, 1 H), 8.85 (d, 1 H), 9.13 (d, 1 H) and 10.3 (s, 1 H).

Workup

  1. temperatureheated at 83° C. for 16 hours
  2. temperatureThe tube was cooled
  3. stirringto stir at room temperature for several hours
  4. custompreabsorbed onto silica gel
  5. customgave the product, 60 mg (28%)

Sources & evidence

ORD record
ord-fb3d24a0b2ac452d8e8f42706e3a8812
Source dataset
uspto-grants-2013_03
Patent number
US08394828B2

Reaction notes

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