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

HRID 1944554노트

반응식

HRID 1944554 반응식
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

참가 물질

8

반응물 4

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

생성물 1

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

시약·촉매·용매 3

HCID 111,2-Dichloroethane용매HCID 887Methanol용매HCID 6344Dichloromethane용매

실험 절차

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).

후처리

  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%)

출처 및 근거

ORD 기록
ord-fb3d24a0b2ac452d8e8f42706e3a8812
출처 데이터셋
uspto-grants-2013_03
특허 번호
US08394828B2

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