Propargyl alcohol → N-(4-Chlorobenzyl)-2-(hydroxymethyl)-8-(4-morpholinylmethyl)-6-oxo-6H-pyrrolo[3,2,1-ij]quinoline-5-carboxamide

HRID 1060599Notes

Reaction equation

HRID 1060599 reaction equation
[Cl:1][C:2]1[CH:30]=[CH:29][C:5]([CH2:6][NH:7][C:8]([C:10]2[CH:11]=[N:12][C:13]3[C:18]([C:19]=2[OH:20])=[CH:17][C:16]([CH2:21][N:22]2[CH2:27][CH2:26][O:25][CH2:24][CH2:23]2)=[CH:15][C:14]=3I)=[O:9])=[CH:4][CH:3]=1.[CH2:31]([OH:34])[C:32]#[CH:33]>C(NCC)C.C(Cl)Cl.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:30]=[CH:29][C:5]([CH2:6][NH:7][C:8]([C:10]2[C:19](=[O:20])[C:18]3[C:13]4=[C:14]([CH:33]=[C:32]([CH2:31][OH:34])[N:12]4[CH:11]=2)[CH:15]=[C:16]([CH2:21][N:22]2[CH2:27][CH2:26][O:25][CH2:24][CH2:23]2)[CH:17]=3)=[O:9])=[CH:4][CH:3]=1

Participants

7

Reactant 2

HCID 7859Propargyl alcoholHCID 178522928N-(4-chlorobenzyl)-4-hydroxy-8-iodo-6-(4-morpholinylmethyl)-3-quinolinecarboxamide

Product 1

HCID 491952N-(4-Chlorobenzyl)-2-(hydroxymethyl)-8-(4-morpholinylmethyl)-6-oxo-6H-pyrrolo[3,2,1-ij]quinoline-5-carboxamideYield 23%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6344DichloromethaneSolventHCID 8021DiethylamineSolvent

Procedure

To a solution of N-(4-chlorobenzyl) -4-hydroxy-8-iodo-6-(4-morpholinylmethyl)-3-quinolinecarboxamide (0.15 g), PdCl2(PPh3)2 (0.0098 g) and CuI (0.0027 g) in diethylamine (5.2 mL) and CH2Cl2 (5 mL) is added propargyl alcohol (0.016 mL). The reaction is stirred at room temperature overnight, then concentrated. The crude residue is partitioned between CH2Cl2 and water. The aqueous layer is extracted with CH2Cl2 (3×). The combined organic layers are dried over Na2SO4 and condensed. The crude product is adsorbed onto silica and chromatographed (Biotage flash 40S, gradient from CH2Cl2 to 2.5% MeOH/ICH2Cl2) Product containing fractions are combined and concentrated. The resulting solid is triturated with CH2Cl2/hexanes, filtered and dried to yield 0.029 g (23%) of N-(4-chlorobenzyl)-2-(hydroxymethyl)-8-(4-morpholinylmethyl)-6-oxo-6H-pyrrolo[3,2,1-ij]quinoline-5-carboxamide, m.p. 210-212° C.

Workup

  1. concentrationconcentrated
  2. customThe crude residue is partitioned between CH2Cl2 and water
  3. extractionThe aqueous layer is extracted with CH2Cl2 (3×)
  4. dry with materialThe combined organic layers are dried over Na2SO4 and condensed
  5. customchromatographed (Biotage flash 40S, gradient from CH2Cl2 to 2.5% MeOH/ICH2Cl2) Product
  6. additioncontaining fractions
  7. concentrationconcentrated
  8. customThe resulting solid is triturated with CH2Cl2/hexanes
  9. filtrationfiltered
  10. customdried

Sources & evidence

ORD record
ord-358036f669754caa9ce87e29920cb40d
Source dataset
uspto-grants-2003_02
Patent number
US06525049B2

Reaction notes

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