Propargyl bromide → 2-(3-ethynyl-quinolin-6-yloxy)-N-(1-methyl-2-prop-2-ynyloxy-1-prop-2-ynyloxymethyl-ethyl)-2-methylsulfanyl-acetamide

HRID 1962878Notes

Reaction equation

HRID 1962878 reaction equation
[H-].[Na+].[C:3]([C:5]1[CH:6]=[N:7][C:8]2[C:13]([CH:14]=1)=[CH:12][C:11]([O:15][CH:16]([S:29][CH3:30])[C:17]([NH:19][C:20]([CH3:28])([CH2:23][O:24][CH2:25][C:26]#[CH:27])[CH2:21][OH:22])=[O:18])=[CH:10][CH:9]=2)#[CH:4].[CH2:31]1[CH2:35]OC[CH2:32]1.C(Br)C#C>C(OCC)(=O)C.O>[C:3]([C:5]1[CH:6]=[N:7][C:8]2[C:13]([CH:14]=1)=[CH:12][C:11]([O:15][CH:16]([S:29][CH3:30])[C:17]([NH:19][C:20]([CH3:28])([CH2:21][O:22][CH2:35][C:31]#[CH:32])[CH2:23][O:24][CH2:25][C:26]#[CH:27])=[O:18])=[CH:10][CH:9]=2)#[CH:4]

Participants

7

Reactant 4

HCID 7842Propargyl bromideHCID 8028TetrahydrofuranHCID 24758Sodium hydrideHCID 595654102-(3-ethynyl-quinolin-6-yloxy)-N-(2-hydroxy-1-methyl-1-prop-2-ynyloxymethyl-ethyl)-2-methylsulfanyl-acetamide

Product 1

HCID 595652862-(3-ethynyl-quinolin-6-yloxy)-N-(1-methyl-2-prop-2-ynyloxy-1-prop-2-ynyloxymethyl-ethyl)-2-methylsulfanyl-acetamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

Sodium hydride (55% in dispersion in oil) (0.097 g) was added portionwise to a solution of 2-(3-ethynyl-quinolin-6-yloxy)-N-(2-hydroxy-1-methyl-1-prop-2-ynyloxymethyl-ethyl)-2-methylsulfanyl-acetamide (0.4 g) from Example 12b, Stage 3 described above in dry THF (20 ml) at 0° C. The reaction mixture was stirred at room temperature for 0.5 h. Propargyl bromide (0.166 ml) was added dropwise at 0° C. and the resulting mixture was stirred at room temperature for 23 hrs. The reaction mixture was diluted with ethyl acetate and water was added dropwise. The two phases were separated and the aqueous layer was extracted thrice with ethyl acetate. The organic layers were combined, washed once with brine dried over sodium sulphate, filtered and evaporated to give a dark orange oil which was purified by column chromatography (hexane/ethyl acetate 4:2, 1:1) to yield 2-(3-ethynyl-quinolin-6-yloxy)-N-(1-methyl-2-prop-2-ynyloxy-1-prop-2-ynyloxymethyl-ethyl)-2-methylsulfanyl-acetamide as a white solid (m.p.: 95-100° C.). 1H NMR (CDCl3) δ ppm: 8.84 (1H, d); 8.22 (1H, d); 8.04 (1H, d); 7.49 (1H, dd); 7.21 (1H, d); 6.98 (1H, s br); 5.61 (1H, s); 4.19-4.16 (4H, m); 3.82-3.61 (2H, dd); 3.73 (2H, s); 3.29 (1H, s); 2.47-2.43 (2H, m); 2.21 (3H, s); 1.46 (3H, s).

Workup

  1. stirringthe resulting mixture was stirred at room temperature for 23 hrs
  2. additionwas added dropwise
  3. customThe two phases were separated
  4. extractionthe aqueous layer was extracted thrice with ethyl acetate
  5. washwashed once with brine
  6. dry with materialdried over sodium sulphate
  7. filtrationfiltered
  8. customevaporated
  9. customto give a dark orange oil which
  10. customwas purified by column chromatography (hexane/ethyl acetate 4:2, 1:1)

Sources & evidence

ORD record
ord-9c70448e89474238943b0f0e2b94bc6c
Source dataset
uspto-grants-2013_04
Patent number
US08415272B2

Reaction notes

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