Water → N-(4-Methoxy-7-morpholin-4-yl-benzothiazol-2-yl)-2-methyl-isonicotinamide

HRID 8348

Reaction equation

HRID 8348 reaction equation
[N:1]1[CH:6]=[CH:5]C=[CH:3][CH:2]=1.CN(C)[CH:9]=[O:10].[C:12](Cl)(=[O:16])[C:13](Cl)=O.[NH2:18][C:19]1[S:20][C:21]2[CH:27]=[CH:26][CH:25]=[CH:24][C:22]=2[N:23]=1.C([N:30]([CH:34]([CH3:36])[CH3:35])[CH:31]([CH3:33])C)C.[OH2:37]>ClCCl>[CH3:9][O:10][C:24]1[C:22]2[N:23]=[C:19]([NH:18][C:12](=[O:16])[C:13]3[CH:33]=[CH:31][N:30]=[C:34]([CH3:35])[CH:36]=3)[S:20][C:21]=2[C:27]([N:1]2[CH2:2][CH2:3][O:37][CH2:5][CH2:6]2)=[CH:26][CH:25]=1

Participants

8

Reactant 6

HCID 962Water2×HCID 1049PyridineHCID 6228DimethylformamideHCID 8706Benzo(d)thiazol-2-amineHCID 65578Oxalyl chlorideHCID 81531Diisopropylethylamine

Product 1

HCID 10200037N-(4-Methoxy-7-morpholin-4-yl-benzothiazol-2-yl)-2-methyl-isonicotinamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

20.0 g Pyridine acid (115 mmol) were suspended at RT in 100 ml dichloromethane. 0.5 ml Dimethylformamide (6.5 mmol) was added, and after 0.2 h, 14.9 g oxalyl chloride (10.2 ml, 115 mmol) were added over 2 min. The dropping funnel was rinsed with 4 ml dichloromethane. The brown suspension was stirred at RT for 3 h. Then 200 ml tetrahydrofuran were added causing the acid chloride to partially precipitate. After 0.2 h, 24.3 g aminobenzothiazole (IA) (92 mmol) were added in one portion at RT. Directly afterwards, 56.0 ml N-ethyldiisopropylamine (42 g, 321 mmol) were added over 0.1 h., and the reaction mixture was stirred at RT overnight (˜17 h). The contents were heated to reflux (˜60° C.), and 300 ml water were added whilst maintaining ca. constant volume throughout a distillation process until the internal temperature reached 90° C. Once all the water was added, heating was increased to 110° C. and a total of 280 ml of distillate was collected. A further 320 ml water was added in one portion, and the temperature was increased to 120° C. whereby the internal and distillate temperature rose to ˜70° C.

Workup

  1. washThe dropping funnel was rinsed with 4 ml dichloromethane
  2. additionThen 200 ml tetrahydrofuran were added
  3. customto partially precipitate
  4. waitAfter 0.2 h
  5. stirringthe reaction mixture was stirred at RT overnight (˜17 h)
  6. temperatureThe contents were heated
  7. additionwere added
  8. temperaturewhilst maintaining ca. constant volume throughout a distillation process until the internal temperature
  9. customreached 90° C
  10. temperatureheating
  11. temperaturewas increased to 110° C.
  12. distillationa total of 280 ml of distillate was collected
  13. additionA further 320 ml water was added in one portion
  14. temperaturethe temperature was increased to 120° C. whereby the internal and distillate temperature
  15. customrose to ˜70° C.

Sources & evidence

ORD record
ord-8178b2b12697448ba91a6d555ccc7cb6
Source dataset
uspto-grants-2006_08
Patent number
US07087761B2

Linked notes

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