Pyridine → n-[4-(Thiazol-2-ylsulfamoyl)-phenyl]-2-(8-trifluoromethyl-quinolin-4-yloxy)-acetamide

HRID 219549

Reaction equation

HRID 219549 reaction equation
[F:1][C:2]([F:19])([F:18])[C:3]1[CH:4]=[CH:5][CH:6]=[C:7]2[C:12]=1[N:11]=[CH:10][CH:9]=[C:8]2[O:13][CH2:14][C:15]([OH:17])=O.C(Cl)(=O)C(Cl)=O.[CH:26]1[C:31]([NH2:32])=[CH:30][CH:29]=[C:28]([S:33]([NH:36][C:37]2[S:41][CH:40]=[CH:39][N:38]=2)(=[O:35])=[O:34])[CH:27]=1.N1C=CC=CC=1>C(Cl)Cl>[S:41]1[CH:40]=[CH:39][N:38]=[C:37]1[NH:36][S:33]([C:28]1[CH:27]=[CH:26][C:31]([NH:32][C:15](=[O:17])[CH2:14][O:13][C:8]2[C:7]3[C:12](=[C:3]([C:2]([F:1])([F:19])[F:18])[CH:4]=[CH:5][CH:6]=3)[N:11]=[CH:10][CH:9]=2)=[CH:30][CH:29]=1)(=[O:35])=[O:34]

Participants

6

Reactant 4

HCID 1049PyridineHCID 5340SulfathiazoleHCID 65578Oxalyl chlorideHCID 534209752-((8-(Trifluoromethyl)quinolin-4-yl)oxy)acetic acid

Product 1

HCID 57936440n-[4-(Thiazol-2-ylsulfamoyl)-phenyl]-2-(8-trifluoromethyl-quinolin-4-yloxy)-acetamideYield 69.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

(8-Trifluoromethylquinolin-4-yloxy)-acetic acid (0.50 g, 1.84 mmol) was suspended in 20 mL DCM with rapid stirring. At rt, oxalyl chloride (0.19 mL, 1.2 equiv) was added dropwise and stirring continued for 4 h. Solvent and excess oxalyl chloride were removed in vacuo, the white residue was re-suspended in DCM, and the mixture cooled to 0° C. N′-(2-thiazolyl)sulfanilamide (0.47 g, 1.0 equiv) was added followed by pyridine (0.30 mL, 2.0 equiv). The mixture was allowed to warm to rt overnight. The solid was collected and rinsed with fresh DCM. Further purification was effected by suspending the solid in 20 mL methanol, stirring vigorously for 4 h, and filtration. After drying under vacuum, white solid 0.65 g (69%) was obtained. 1H-NMR (DMSO-d6) 5.11 (s, 2H), 6.79 (d, J=4.8 Hz, 1H), 7.12 (d, J=5.2 Hz, 1H), 7.22 (d, J=4.8 Hz, 1H), 7.71 (t, J=8.0 Hz, 1H), 8.17 (d, J=8.0 Hz, 1H), 8.55 (d, J=8.0 Hz, 1H), 8.85 (d, J=5.2 Hz, 1H); 13C-NMR (DMSO-d6) 68.0, 103.6, 108.8, 120.0, 122.0, 124.8 (q, J=270 Hz), 125.1, 125.4, 126.4 (q, J=33 Hz), 127.7, 127.8, 129.2, 137.7, 142.1, 145.6, 153.2, 161.2, 166.5, 169.4 LC/MS (10-99%) M/Z: M+1 obs=509.5; tR=3.13 min.

Workup

  1. customSolvent and excess oxalyl chloride were removed in vacuo
  2. temperatureto warm to rt overnight
  3. customThe solid was collected
  4. washrinsed with fresh DCM
  5. customFurther purification
  6. stirringstirring vigorously for 4 h
  7. filtrationfiltration
  8. customAfter drying under vacuum

Sources & evidence

ORD record
ord-9365a5b5bb7c4446b37894b84f0e84da
Source dataset
uspto-grants-2012_06
Patent number
US08202861B2

Linked notes

Loading…