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4-Fluoro-N-methylaniline → N-(2-(dimethylamino)ethyl)-8-(1-((4-fluorophenyl)(methyl)amino)ethyl)-2-morpholino-4-oxo-4H-chromene-6-carboxamide

HRID 572739
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HRID 572739 반응식
Br.Br[CH:3]([C:5]1[CH:6]=[C:7]([C:22]([NH:24][CH2:25][CH2:26][N:27]([CH3:29])[CH3:28])=[O:23])[CH:8]=[C:9]2[C:14]=1[O:13][C:12]([N:15]1[CH2:20][CH2:19][O:18][CH2:17][CH2:16]1)=[CH:11][C:10]2=[O:21])[CH3:4].[F:30][C:31]1[CH:38]=[CH:37][C:34]([NH:35][CH3:36])=[CH:33][CH:32]=1>CN1C(=O)CCC1>[CH3:28][N:27]([CH3:29])[CH2:26][CH2:25][NH:24][C:22]([C:7]1[CH:8]=[C:9]2[C:14](=[C:5]([CH:3]([N:35]([C:34]3[CH:37]=[CH:38][C:31]([F:30])=[CH:32][CH:33]=3)[CH3:36])[CH3:4])[CH:6]=1)[O:13][C:12]([N:15]1[CH2:20][CH2:19][O:18][CH2:17][CH2:16]1)=[CH:11][C:10]2=[O:21])=[O:23]
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참가 물질

4

반응물 2

HCID 680244-Fluoro-N-methylanilineHCID 671039198-(1-bromoethyl)-N-(2-(dimethylamino)ethyl)-2-morpholino-4-oxo-4H-chromene-6-carboxamide hydrobromide

생성물 1

HCID 58235058N-(2-(dimethylamino)ethyl)-8-(1-((4-fluorophenyl)(methyl)amino)ethyl)-2-morpholino-4-oxo-4H-chromene-6-carboxamide수율 53.1%

시약·촉매·용매 1

HCID 13387N-methyl-2-pyrrolidone용매

실험 절차

A solution of 8-(1-bromoethyl)-N-(2-(dimethylamino)ethyl)-2-morpholino-4-oxo-4H-chromene-6-carboxamide hydrobromide (85 mg, 0.16 mmol) and 4-fluoro-N-methylaniline (0.077 mL, 0.64 mmol) in NMP (1 mL) was stirred at room temperature for 4 h then at 45° C. for 1 h. The reaction mixture was allowed to cool to room temperature and purified by preparative HPLC using a Waters X-Bridge reverse-phase column (C-18, 5 microns silica, 19 mm diameter, 100 mm length, flow rate of 40 mL/minute) and decreasingly polar mixtures of water (containing 0.2% ammonium carbonate) and acetonitrile as eluent. The fractions containing the desired compound were evaporated to dryness. The residue was triturated in diethyl ether, collected by filtration and dried to afford N-(2-(dimethylamino)ethyl)-8-(1-((4-fluorophenyl)(methyl)amino)ethyl)-2-morpholino-4-oxo-4H-chromene-6-carboxamide (42.0 mg, 53.1%) as a white solid. Mass Spectrum: M+H+ 497. NMR Spectrum: (CDCl3) 1.66 (d, 3H), 2.33 (s, 6H), 2.33 (bs, 2H), 2.60 (bs, 2H), 2.61 (s, 3H), 3.09-3.24 (m, 4H), 3.44-3.57 (m, 4H), 3.57-3.66 (m, 2H), 5.36 (q, 1H), 5.48 (s, 1H), 6.75 (dd, 2H), 6.77 (dd, 2H), 7.14 (bs, 1H), 8.33 (s, 1H), 8.44 (s, 1H).

후처리

  1. custompurified by preparative HPLC
  2. additionThe fractions containing the desired compound
  3. customwere evaporated to dryness
  4. customThe residue was triturated in diethyl ether
  5. filtrationcollected by filtration
  6. customdried

출처 및 근거

ORD 기록
ord-a0d71e654139401cb57cf85abfcb7096
출처 데이터셋
uspto-grants-2015_05
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09029374B2

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