Dimethylformamide → 7-[(6-Chloropyridin-2-yl)methoxy]-2-ethylthiazolo[4,5-c]quinolin-4-amine

HRID 913368Notes

Reaction equation

HRID 913368 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.C(=O)([O-])[O-].[Cs+].[Cs+].[CH3:24]N(C=O)C.[Cl:29][C:30]1[CH:35]=[CH:34][C:33](CCl)=[CH:32][N:31]=1>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.ClCCl>[Cl:29][C:30]1[N:31]=[C:32]([CH2:24][O:17][C:6]2[CH:7]=[CH:8][C:9]3[C:10]4[S:14][C:13]([CH2:15][CH3:16])=[N:12][C:11]=4[C:2]([NH2:1])=[N:3][C:4]=3[CH:5]=2)[CH:33]=[CH:34][CH:35]=1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 10796Cesium carbonateHCID 1554792-Chloro-5-(chloromethyl)pyridineHCID 1363391164-Amino-2-ethylthiazolo[4,5-c]quinolin-7-ol

Product 1

HCID 589650417-[(6-Chloropyridin-2-yl)methoxy]-2-ethylthiazolo[4,5-c]quinolin-4-amine

Reagents, catalysts & solvents 2

HCID 74236Tetrabutylammonium BromideCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
75 °C

Procedure

A mixture of 4-amino-2-ethylthiazolo[4,5-c]quinolin-7-ol (245 mg, 1.0 mmol), cesium carbonate (1.3 g, 4.0 mmol), tetrabutylammonium bromide (322 mg, 1.0 mmol), and DMF (15 mL) was stirred at 75° C. for 10 minutes. 2-Chloro-5-(chloromethyl)pyridine (178 mg, 1.1 mmol) was added in portions over a period of 30 minutes. The reaction mixture was stirred for 1 hour and then the heat source was removed. The reaction mixture was diluted with water (200 mL) and then filtered. The isolated solid was rinsed with water and then dried to provide an off white powder. This material was dissolved in dichloromethane and then purified by HPFC eluting with a gradient of 0-15 CMA in chloroform 700 mL and then with 15% CMA in chloroform over 600 mL. The resulting solid was slurried with hot 10:1 acetonitrile:methanol to provide 216 mg of 7-[(6-chloropyridin-2-yl)methoxy]-2-ethylthiazolo[4,5-c]quinolin-4-amine as a pale yellow solid, mp 229.0-230.0° C. MS (APCI) m/z 371 (M+H)+; Anal. calcd for C18H15ClN4OS.0.1CHCl3: C, 57.06; H, 4.32; N, 14.63. Found C, 56.79; H, 3.98; N, 14.63.

Workup

  1. stirringThe reaction mixture was stirred for 1 hour
  2. customthe heat source was removed
  3. additionThe reaction mixture was diluted with water (200 mL)
  4. filtrationfiltered
  5. washThe isolated solid was rinsed with water
  6. customdried
  7. customto provide an off white powder
  8. custompurified by HPFC
  9. washeluting with a gradient of 0-15 CMA in chloroform 700 mL

Sources & evidence

ORD record
ord-26f41febbc714c72bca481704d490ba1
Source dataset
uspto-grants-2011_09
Patent number
US08026366B2

Reaction notes

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