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

HRID 1944554ノート

反応式

HRID 1944554 の反応式
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

参加物

8

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 3

HCID 111,2-Dichloroethane溶媒HCID 887Methanol溶媒HCID 6344Dichloromethane溶媒

実験手順

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).

後処理

  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%)

出典と根拠

ORDレコード
ord-fb3d24a0b2ac452d8e8f42706e3a8812
出典データセット
uspto-grants-2013_03
特許番号
US08394828B2

反応ノート

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