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Dimethylformamide → N-(4-chlorobenzyl)-8-[3-(1,1-dioxido-4-thiomorpholinyl)-1-propynyl]-1-methyl-6-(4-morpholinylmethyl)-4-oxo-1,4-dihydro-3-quinolinecarboxamide

HRID 2086617
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HRID 2086617 반응식
[Cl:1][C:2]1[CH:31]=[CH:30][C:5]([CH2:6][NH:7][C:8]([C:10]2[C:19](=[O:20])[C:18]3[C:13](=[C:14](I)[CH:15]=[C:16]([CH2:21][N:22]4[CH2:27][CH2:26][O:25][CH2:24][CH2:23]4)[CH:17]=3)[N:12]([CH3:29])[CH:11]=2)=[O:9])=[CH:4][CH:3]=1.[CH2:32]([N:35]1[CH2:40][CH2:39][S:38](=[O:42])(=[O:41])[CH2:37][CH2:36]1)[C:33]#[CH:34].CN(C=O)C>N(CC)CC.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I>[Cl:1][C:2]1[CH:31]=[CH:30][C:5]([CH2:6][NH:7][C:8]([C:10]2[C:19](=[O:20])[C:18]3[C:13](=[C:14]([C:34]#[C:33][CH2:32][N:35]4[CH2:36][CH2:37][S:38](=[O:42])(=[O:41])[CH2:39][CH2:40]4)[CH:15]=[C:16]([CH2:21][N:22]4[CH2:27][CH2:26][O:25][CH2:24][CH2:23]4)[CH:17]=3)[N:12]([CH3:29])[CH:11]=2)=[O:9])=[CH:4][CH:3]=1
참가 물질실험 절차후처리출처 및 근거반응 노트

참가 물질

7

반응물 3

HCID 6228DimethylformamideHCID 27772654-(Prop-2-yn-1-yl)-1lambda~6~,4-thiazinane-1,1-dioneHCID 12095879N-(4-chlorobenzyl)-8-iodo-1-methyl-6-(4-morpholinylmethyl)-4-oxo-1,4-dihydro-3-quinolinecarboxamide

생성물 1

HCID 5278416N-(4-chlorobenzyl)-8-[3-(1,1-dioxido-4-thiomorpholinyl)-1-propynyl]-1-methyl-6-(4-morpholinylmethyl)-4-oxo-1,4-dihydro-3-quinolinecarboxamide수율 27%

시약·촉매·용매 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)촉매
HCID 178418476HCID 178418476, 화합물촉매
HCID 8021Diethylamine용매

실험 절차

To a solution of N-(4-chlorobenzyl)-8-iodo-1-methyl-6-(4-morpholinylmethyl)-4-oxo-1,4-dihydro-3-quinolinecarboxamide (300 mg), PdCl2(PPh3)2 (19.1 mg), and CuI (5.2 mg) in Et2NH (6.2 mL) is added 4-propargylthiomorpholine-1,1-dioxide (103.8 mg). Anhydrous DMF (18 mL) is added to help solubilize the reactants (also requires sonication). The reaction is stirred at room temperature overnight, then condensed. The resulting residue is placed under high vac to remove residual DMF. The crude product is dissolved in CH2Cl2 and partitioned between CH2Cl2 and H2O. The aqueous layer is extracted with CH2Cl2 (2×). The combined organic layers are dried over Na2SO4, filtered, and condensed. The crude product is adsorbed onto silica and chromatographed (eluent 100% CH2Cl2 (1L), 0.5% MeOH in CH2Cl2 (1L), 1% MeOH in CH2Cl2 (1L), 1.5% MeOH in CH2Cl2 (1L), and 2% MeOH in CH2Cl2 (4L), and 2.5% MeOH in CH2Cl2 (3L)). Product-containing fractions are combined, concentrated, and further purified by HPLC. The product is recrystallized from hot acetonitrile to afford 86.1 mg (27%) of the desired product as a white solid.

후처리

  1. customalso requires sonication)
  2. customcondensed
  3. customto remove residual DMF
  4. dissolutionThe crude product is dissolved in CH2Cl2
  5. custompartitioned between CH2Cl2 and H2O
  6. extractionThe aqueous layer is extracted with CH2Cl2 (2×)
  7. dry with materialThe combined organic layers are dried over Na2SO4
  8. filtrationfiltered
  9. customcondensed
  10. customchromatographed (eluent 100% CH2Cl2 (1L), 0.5% MeOH in CH2Cl2 (1L), 1% MeOH in CH2Cl2 (1L), 1.5% MeOH in CH2Cl2 (1L), and 2% MeOH in CH2Cl2 (4L), and 2.5% MeOH in CH2Cl2 (3L))
  11. concentrationconcentrated
  12. customfurther purified by HPLC
  13. customThe product is recrystallized from hot acetonitrile

출처 및 근거

ORD 기록
ord-9e927ba8bca84265a186323c94d066bf
출처 데이터셋
uspto-grants-2004_04
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US06727248B2

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