Dimethylformamide → 2-Ethyl-7-{[5-(trifluoromethyl)furan-2-yl]methoxy}thiazolo[4,5-c]quinolin-4-amine

HRID 913366Notes

Reaction equation

HRID 913366 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+].CN(C=O)C.Br[CH2:30][C:31]1[O:32][C:33]([C:36]([F:39])([F:38])[F:37])=[CH:34][CH:35]=1>ClCCl>[CH2:15]([C:13]1[S:14][C:10]2[C:9]3[CH:8]=[CH:7][C:6]([O:17][CH2:30][C:31]4[O:32][C:33]([C:36]([F:39])([F:38])[F:37])=[CH:34][CH:35]=4)=[CH:5][C:4]=3[N:3]=[C:2]([NH2:1])[C:11]=2[N:12]=1)[CH3:16]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 10796Cesium carbonateHCID 27946052-(Bromomethyl)-5-(trifluoromethyl)furanHCID 1363391164-Amino-2-ethylthiazolo[4,5-c]quinolin-7-ol

Product 1

HCID 589650262-Ethyl-7-{[5-(trifluoromethyl)furan-2-yl]methoxy}thiazolo[4,5-c]quinolin-4-amineYield 31.8%

Reagents, catalysts & solvents 1

HCID 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), and DMF (20 mL) was stirred at 75° C. for 10 minutes. 2-(Bromomethyl)-5-(trifluoromethyl)furan (252 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 (250 mL), stirred for 1 hour, and then filtered. The isolated solid was rinsed with water and then dried to provide a brown 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 200 mL. The resulting solid was recrystallized from acetonitrile to provide 125 mg of 2-ethyl-7-{[5-(trifluoromethyl)furan-2-yl]methoxy}thiazolo[4,5-c]quinolin-4-amine as an off-white solid, mp 152-154° C. MS (ESI) m/z 394 (M+H)+; Anal. calcd for C18H14F3N3O2S: C, 54.96; H, 3.59; N, 10.68. Found: C, 54.90; H, 3.46; N, 10.52.

Workup

  1. stirringThe reaction mixture was stirred for 1 hour
  2. customthe heat source was removed
  3. additionThe reaction mixture was diluted with water (250 mL)
  4. stirringstirred for 1 hour
  5. filtrationfiltered
  6. washThe isolated solid was rinsed with water
  7. customdried
  8. customto provide a brown powder
  9. custompurified by HPFC
  10. washeluting with a gradient of 0-15 CMA in chloroform 700 mL
  11. customThe resulting solid was recrystallized from acetonitrile

Sources & evidence

ORD record
ord-042892c89cd64fcd8591b90d7463e0bd
Source dataset
uspto-grants-2011_09
Patent number
US08026366B2

Reaction notes

Loading…