Dimethylformamide → HCID 10228404, compound

HRID 2086614Notes

Reaction equation

HRID 2086614 reaction equation
[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.[CH3:32][C@@H:33]([OH:36])[C:34]#[CH:35].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:35]#[C:34][C@@H:33]([OH:36])[CH3:32])[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

Participants

7

Reactant 3

HCID 6228DimethylformamideHCID 638102(2R)-but-3-yn-2-olHCID 12095879N-(4-chlorobenzyl)-8-iodo-1-methyl-6-(4-morpholinylmethyl)-4-oxo-1,4-dihydro-3-quinolinecarboxamide

Product 1

HCID 10228404HCID 10228404, compoundYield 34%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 8021DiethylamineSolvent

Procedure

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 (R)-(+)-3-butyn-2-ol (0.047 mL, 0.599 mmol). Anhydrous DMF (10 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)). Product-containing fractions are combined, concentrated, and recrystallized from hot acetonitrile to afford 90.7 mg (34%) of the desired product as a white solid.

Workup

  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))
  11. concentrationconcentrated
  12. customrecrystallized from hot acetonitrile

Sources & evidence

ORD record
ord-3245717293a04c61827d41a413437ac6
Source dataset
uspto-grants-2004_04
Patent number
US06727248B2

Reaction notes

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