N,N-Dimethylpropargylamine → HCID 5278409, compound

HRID 2086602Notes

Reaction equation

HRID 2086602 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][CH: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][N:33]([CH2:35][C:36]#[CH:37])[CH3:34]>C(NCC)C.[Cu](I)I.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>[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:37]#[C:36][CH2:35][N:33]([CH3:34])[CH3:32])[CH:15]=[C:16]([CH2:21][CH: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

6

Reactant 2

HCID 81643N,N-DimethylpropargylamineHCID 22724547HCID 22724547, compound

Product 1

HCID 5278409HCID 5278409, compoundYield 70%

Reagents, catalysts & solvents 3

HCID 83717Copper iodideCatalystHCID 178418476HCID 178418476, compoundCatalystHCID 8021DiethylamineSolvent

Procedure

A solution of N-(4-chlorobenzyl)-8-iodo-1-methyl-4-oxo-6-(tetrahydro-2H-pyran-4-ylmethyl)-1,4-dihydro-3-quinolinecarboxamide (0.070 g), copper iodide (0.013 g), Pd(PPh3)2Cl2 (0.007 g) and N,N-dimethylpropargylamine (0.020 mL) in 7 mL diethylamine is stirred at room temperature for 3 days. The reaction is partitioned between CH2Cl2 and H2O. The aqueous layer is extracted 3×with CH2Cl2. The organics are combined, dried over Na2SO4, filtered and concentrated. The residue is dissolved in CH2Cl2 and adsorbed onto silica. Purification by Biotage Flash 40S (eluent CH2Cl2 (1L), 1% MeOH/CH2Cl2 (1L), 2% MeOH/CH2Cl2 (1L), 3% MeOH/CH2Cl2 (1L), 4% MeOH/CH2Cl2 (1L), 5% MeOH/CH2Cl2 (1L)) affords the product as a tan residue. Recrystallization with CH2Cl2/hexanes affords the desired product (0.046 g, 70%).

Workup

  1. customThe reaction is partitioned between CH2Cl2 and H2O
  2. extractionThe aqueous layer is extracted 3×with CH2Cl2
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. dissolutionThe residue is dissolved in CH2Cl2
  7. customPurification by Biotage Flash 40S (eluent CH2Cl2 (1L), 1% MeOH/CH2Cl2 (1L), 2% MeOH/CH2Cl2 (1L), 3% MeOH/CH2Cl2 (1L), 4% MeOH/CH2Cl2 (1L), 5% MeOH/CH2Cl2 (1L))
  8. customaffords the product as a tan residue
  9. customRecrystallization with CH2Cl2/hexanes

Sources & evidence

ORD record
ord-f8849defaf8a4efe9d69061d10377216
Source dataset
uspto-grants-2004_04
Patent number
US06727248B2

Reaction notes

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