Dimethylformamide → HCID 58965018, compound

HRID 913365Notes

Reaction equation

HRID 913365 reaction equation
[C:1]([O:4][C:5]1[CH:6]=[CH:7][C:8]2[C:9]3[S:18][C:17]([CH2:19][CH2:20][CH3:21])=[N:16][C:10]=3[C:11]([NH2:15])=[N:12][C:13]=2[CH:14]=1)(=O)[CH3:2].C(=O)([O-])[O-].[Cs+].[Cs+].CN(C=O)C.ClC[C:35]1[C:36](C)=[N:37][O:38][C:39]=1[CH3:40]>ClCCl>[CH3:35][C:36]1[C:2]([CH2:1][O:4][C:5]2[CH:6]=[CH:7][C:8]3[C:9]4[S:18][C:17]([CH2:19][CH2:20][CH3:21])=[N:16][C:10]=4[C:11]([NH2:15])=[N:12][C:13]=3[CH:14]=2)=[C:39]([CH3:40])[O:38][N:37]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 10796Cesium carbonate2×HCID 88246Isoxazole, 4-(chloromethyl)-3,5-dimethyl-2×HCID 67393211HCID 67393211, compound

Product 1

HCID 58965018HCID 58965018, compoundYield 42.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
75 °C

Procedure

A mixture of 4-amino-2-propylthiazolo[4,5-c]quinolin-7-ol acetate (318 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-(Chloromethyl)-3,5-dimethylisoxazole (160 mg, 1.1 mmol) was added dropwise over a period of 10 minutes. After 3 hours an additional equivalent of cesium carbonate was added in a single portion followed by the dropwise addition of an equivalent of 4-(chloromethyl)-3,5-dimethylisoxazole. After 1 additional hour 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 0-5% methanol in dichloromethane for over 1000 mL and then with 5% methanol in dichloromethane over 400 mL. The resulting solid was recrystallized from acetonitrile to provide 156 mg of 7-[(3,5-dimethylisoxazol-4-yl)methoxy]-2-propylthiazolo[4,5-c]quinolin-4-amine as an off-white solid, mp 178.0-180.0° C. MS (ESI) m/z 369 (M+H)+; Anal. calcd for C19H20N4O2S: C, 61.94; H, 5.47; N, 15.21. Found C, 61.98; H, 5.25; N, 15.26.

Workup

  1. customAfter 1 additional hour the heat source was removed
  2. additionthe reaction mixture was diluted with water (250 mL)
  3. stirringstirred for 1 hour
  4. filtrationfiltered
  5. washThe isolated solid was rinsed with water
  6. customdried
  7. customto provide a brown powder
  8. custompurified by HPFC
  9. washeluting with a gradient of 0-5% methanol in dichloromethane for over 1000 mL
  10. customThe resulting solid was recrystallized from acetonitrile

Sources & evidence

ORD record
ord-2c60e0481d7f45d584efdf20e5233965
Source dataset
uspto-grants-2011_09
Patent number
US08026366B2

Reaction notes

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