Dimethylformamide → N-(4-fluorobenzyl)-5-isocyanato-N-(4-(pyridin-3-yl)benzyl)thiazol-2-amine

HRID 624229Notes

Reaction equation

HRID 624229 reaction equation
[F:1][C:2]1[CH:30]=[CH:29][C:5]([CH2:6][N:7]([CH2:16][C:17]2[CH:22]=[CH:21][C:20]([C:23]3[CH:24]=[N:25][CH:26]=[CH:27][CH:28]=3)=[CH:19][CH:18]=2)[C:8]2[S:9][C:10](C(O)=O)=[CH:11][N:12]=2)=[CH:4][CH:3]=1.C(Cl)(=O)C(Cl)=O.C[N:38](C)[CH:39]=[O:40].C[Si](N=[N+]=[N-])(C)C>ClCCl>[F:1][C:2]1[CH:30]=[CH:29][C:5]([CH2:6][N:7]([CH2:16][C:17]2[CH:18]=[CH:19][C:20]([C:23]3[CH:24]=[N:25][CH:26]=[CH:27][CH:28]=3)=[CH:21][CH:22]=2)[C:8]2[S:9][C:10]([N:38]=[C:39]=[O:40])=[CH:11][N:12]=2)=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 78378AzidotrimethylsilaneHCID 687536802-((4-Fluorobenzyl)(4-(pyridin-3-yl)benzyl)amino)thiazole-5-carboxylic acid

Product 1

HCID 86665087N-(4-fluorobenzyl)-5-isocyanato-N-(4-(pyridin-3-yl)benzyl)thiazol-2-amine

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a 50 mL round-bottomed flask was added 2-((4-fluorobenzyl)(4-(pyridin-3-yl)benzyl)amino)thiazole-5-carboxylic acid (850 mg, 2.026 mmol) in dichloromethane (10.100 ml) and the solution was cooled to 0° C. Oxalyl chloride (0.266 ml, 3.04 mmol) and dimethylformamide (0.016 ml, 0.203 mmol) were added and some bubbling occurred. The solution was warmed to room temperature and stirred for 1 hour. The mixture was cooled to 0° C., and trimethylsilyl azide (0.538 ml, 4.05 mmol) was added. The mixture was warmed to room temperature, stirred for 30 minutes and concentrated under vacuum. Toluene (5 ml) was added and the mixture was heated to 95° C. for 2.5 hours. The toluene was removed and the resulting solid was triturated/sonicated with ether and filtered with ether washes to provide the title compound.

Workup

  1. temperatureThe solution was warmed to room temperature
  2. temperatureThe mixture was cooled to 0° C.
  3. temperatureThe mixture was warmed to room temperature
  4. stirringstirred for 30 minutes
  5. concentrationconcentrated under vacuum
  6. additionToluene (5 ml) was added
  7. temperaturethe mixture was heated to 95° C. for 2.5 hours
  8. customThe toluene was removed
  9. customthe resulting solid was triturated/sonicated with ether
  10. filtrationfiltered with ether

Sources & evidence

ORD record
ord-e981703853f44ba6ae5c378eb5bb28c2
Source dataset
uspto-grants-2016_04
Patent number
US09302989B2

Reaction notes

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