Cesium carbonate → Methyl 6-[(4-amino-2-ethyl[1,3]thiazolo[4,5-c]quinolin-7-yl)oxy]nicotinate

HRID 913373Notes

Reaction equation

HRID 913373 reaction equation
[NH2:1][C:2]1[C:11]2[N:12]=[C:13]([CH2:15][CH3:16])[S:14][C:10]=2[C:9]2[CH:8]=[CH:7][C:6]([OH:17])=[CH:5][C:4]=2[N:3]=1.Cl[C:19]1[CH:28]=[CH:27][C:22]([C:23]([O:25][CH3:26])=[O:24])=[CH:21][N:20]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1>[NH2:1][C:2]1[C:11]2[N:12]=[C:13]([CH2:15][CH3:16])[S:14][C:10]=2[C:9]2[CH:8]=[CH:7][C:6]([O:17][C:19]3[CH:28]=[CH:27][C:22]([C:23]([O:25][CH3:26])=[O:24])=[CH:21][N:20]=3)=[CH:5][C:4]=2[N:3]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 254249Methyl 6-chloropyridine-3-carboxylateHCID 1363391164-Amino-2-ethylthiazolo[4,5-c]quinolin-7-ol

Product 1

HCID 67392673Methyl 6-[(4-amino-2-ethyl[1,3]thiazolo[4,5-c]quinolin-7-yl)oxy]nicotinate

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

A round bottom flask was charged with 4-amino-2-ethylthiazolo[4,5-c]quinolin-7-ol (1.0 eq., 2.0 mmol), methyl 6-chloronicotinate (1.0 eq., 2.0 mmol), cesium carbonate (3.0 eq. 6.0 mmol), and anhydrous 1,4-dioxane (45 mL). The mixture was heated to reflux for 24 hours. The reaction was monitored by HPLC. The reaction mixture was concentrated to dryness. The resulting solid was then dissolved in methanol and adsorbed onto silica gel (6 g) for purification by HPFC (0-15% CMA in chloroform, 1440 mL). Pure fractions were combined and concentrated; the resulting solid was recrystallized from acetonitrile to provide methyl 6-[(4-amino-2-ethyl[1,3]thiazolo[4,5-c]quinolin-7-yl)oxy]nicotinate as a light peach colored crystalline solid, mp 213-214° C. MS (APCI) m/z 381 (M+H)+. Anal. calcd for C19H16N4O3S: C, 59.99; H, 4.24; N, 14.73. Found: C, 59.76; H, 4.19; N, 14.71.

Workup

  1. temperatureThe mixture was heated
  2. temperatureto reflux for 24 hours
  3. concentrationThe reaction mixture was concentrated to dryness
  4. dissolutionThe resulting solid was then dissolved in methanol
  5. customadsorbed onto silica gel (6 g) for purification by HPFC (0-15% CMA in chloroform, 1440 mL)
  6. concentrationconcentrated
  7. customthe resulting solid was recrystallized from acetonitrile

Sources & evidence

ORD record
ord-071a683036b34a9598374beeabbf71d8
Source dataset
uspto-grants-2011_09
Patent number
US08026366B2

Reaction notes

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