Dimethylformamide → 7-[2-(3,5-dimethyl-1H-pyrazol-4-yl)ethoxy]-2-ethylthiazolo[4,5-c]quinolin-4-amine

HRID 913369Notes

Reaction equation

HRID 913369 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][CH2:31][C:32]1[C:33]([CH3:38])=[N:34][NH:35][C:36]=1[CH3:37]>ClCCl>[CH3:38][C:33]1[C:32]([CH2:31][CH2:30][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)=[C:36]([CH3:37])[NH:35][N:34]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 10796Cesium carbonateHCID 5728794-(2-Bromoethyl)-3,5-dimethyl-1H-pyrazoleHCID 1363391164-Amino-2-ethylthiazolo[4,5-c]quinolin-7-ol

Product 1

HCID 589650407-[2-(3,5-dimethyl-1H-pyrazol-4-yl)ethoxy]-2-ethylthiazolo[4,5-c]quinolin-4-amineYield 55.8%

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. 4-(Bromoethyl)-3,5-dimethyl-1H-pyrazole (223 mg, 1.1 mmol) was added in portions over a period of 30 minutes. The reaction mixture was stirred for 20 minutes and then the heat source was removed. The reaction mixture was diluted with water (250 mL), stirred overnight, and then filtered. The isolated solid was rinsed with water and then dried to provide a tan powder. This material was dissolved in dichloromethane and then purified by HPFC eluting with a gradient of 0-30% CMA in chloroform 700 mL and then with 30% CMA in chloroform over 200 mL. The resulting solid was recrystallized from 50:1 acetonitrile:methanol (40 mL) to provide 205 mg of 7-[2-(3,5-dimethyl-1H-pyrazol-4-yl)ethoxy]-2-ethylthiazolo[4,5-c]quinolin-4-amine as an off white solid, mp 195.0-197.0° C. MS (APCI) m/z 368 (M+H)+; Anal. calcd for C19H21N5OS: C, 62.10; H, 5.764; N, 19.06. Found C, 61.95; H, 5.53; N, 19.09.

Workup

  1. stirringThe reaction mixture was stirred for 20 minutes
  2. customthe heat source was removed
  3. additionThe reaction mixture was diluted with water (250 mL)
  4. stirringstirred overnight
  5. filtrationfiltered
  6. washThe isolated solid was rinsed with water
  7. customdried
  8. customto provide a tan powder
  9. custompurified by HPFC
  10. washeluting with a gradient of 0-30% CMA in chloroform 700 mL
  11. customThe resulting solid was recrystallized from 50:1 acetonitrile

Sources & evidence

ORD record
ord-94da886fb5d8468f83018991a4d092c4
Source dataset
uspto-grants-2011_09
Patent number
US08026366B2

Reaction notes

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