Hydrochloric Acid → HCID 178493321, compound

HRID 347439Notes

Reaction equation

HRID 347439 reaction equation
[C:1]([C:3]1[CH:4]=[N:5][C:6]2[C:11]([C:12]=1[OH:13])=[C:10]([O:14][CH:15]1[CH2:20][CH2:19][N:18]([CH3:21])[CH2:17][CH2:16]1)[CH:9]=[C:8](F)[CH:7]=2)#[N:2].CO.C[C:26](C)([O-:28])C.[K+].Cl>CS(C)=O.O>[C:1]([C:3]1[CH:4]=[N:5][C:6]2[C:11]([C:12]=1[OH:13])=[C:10]([O:14][CH:15]1[CH2:20][CH2:19][N:18]([CH3:21])[CH2:17][CH2:16]1)[CH:9]=[C:8]([O:28][CH3:26])[CH:7]=2)#[N:2]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 887MethanolHCID 23665647Potassium tert-butoxideHCID 178480503HCID 178480503, compound

Product 1

HCID 178493321HCID 178493321, compoundYield 73%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of 3-cyano-7-fluoro-4-hydroxy-5-[(1-methylpiperidin-4-yl)oxy]quinoline (600 mg), methanol (0.40 ml) and potassium tert-butoxide (1.0M solution in tetrahydrofuran; 10.0 ml) in anhydrous dimethyl sulphoxide (20 ml) was heated at 70° C. for 16 hours. The solution was cooled and then diluted with water (100 ml). Dilute hydrochloric acid was added until pH6 was reached and the by-product precipitate (3-cyano-4-hydroxy-5,7-dimethoxyquinoline) was filtered off. The filtrate was pumped onto a cation exchange cartridge (Waters Oasis MCX 6.0 g) and washed on with water. The column was flushed successively with water (200 ml), methanol/water (1:1; 200 ml) and methanol (200 ml). The product was eluted off the column with methanol containing triethylamine (1%). The fractions containing the product were combined and evaporated. This gave the title compound as an white solid (460 mg, 73%); NMR spectrum: (DMSOd6) 1.67 (m, 2H), 1.83 (m, 2H), 2.12 (m, 2H), 2.15 (s, 3H), 2.64 (m, 2H), 4.31 (m, 1H), 6.31 (d, 1H), 6.56 (d, 1H), 8.16 (s, 1H); Mass spectrum: M+H+ 314.

Workup

  1. temperatureThe solution was cooled
  2. filtrationthe by-product precipitate (3-cyano-4-hydroxy-5,7-dimethoxyquinoline) was filtered off
  3. washwashed on with water
  4. customThe column was flushed successively with water (200 ml), methanol/water (1:1; 200 ml) and methanol (200 ml)
  5. washThe product was eluted off the column with methanol
  6. additioncontaining triethylamine (1%)
  7. additionThe fractions containing the product
  8. customevaporated

Sources & evidence

ORD record
ord-f0fb9303f26b4e78a09306e5e7acf8ad
Source dataset
uspto-grants-2007_02
Patent number
US07173135B2

Reaction notes

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