Pyridine → Benzyl 1-({[4-([2-[(phenoxycarbonyl)amino]pyridin-4-yl}oxy)-2,5-difluorophenyl]amino}carbonyl)cyclopropanecarboxylate

HRID 388520Notes

Reaction equation

HRID 388520 reaction equation
[NH2:1][C:2]1[CH:7]=[C:6]([O:8][C:9]2[C:14]([F:15])=[CH:13][C:12]([NH:16][C:17]([C:19]3([C:22]([O:24][CH2:25][C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=4)=[O:23])[CH2:21][CH2:20]3)=[O:18])=[C:11]([F:32])[CH:10]=2)[CH:5]=[CH:4][N:3]=1.N1C=CC=CC=1.Cl[C:40]([O:42][C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1)=[O:41].C(=O)([O-])O.[Na+]>O1CCCC1.CCCCCC>[O:42]([C:40]([NH:1][C:2]1[CH:7]=[C:6]([O:8][C:9]2[C:14]([F:15])=[CH:13][C:12]([NH:16][C:17]([C:19]3([C:22]([O:24][CH2:25][C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=4)=[O:23])[CH2:21][CH2:20]3)=[O:18])=[C:11]([F:32])[CH:10]=2)[CH:5]=[CH:4][N:3]=1)=[O:41])[C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1

Participants

7

Reactant 4

HCID 1049PyridineHCID 15891Phenyl chloroformateHCID 516892Sodium BicarbonateHCID 24788626Benzyl 1-[({4-[(2-aminopyridin-4-yl)oxy]-2,5-difluorophenyl}amino)carbonyl]cyclopropanecarboxylate

Product 1

HCID 24788625Benzyl 1-({[4-([2-[(phenoxycarbonyl)amino]pyridin-4-yl}oxy)-2,5-difluorophenyl]amino}carbonyl)cyclopropanecarboxylateYield 76%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8058HexaneSolvent

Procedure

Benzyl 1-[({4-[(2-aminopyridin-4-yl)oxy]-2,5-difluorophenyl}amino)carbonyl]cyclopropanecarboxylate (1.15 g) was dissolved in tetrahydrofuran (12 ml) under a nitrogen atmosphere. Pyridine (0.424 ml) and phenyl chloroformate (0.657 ml) were added at room temperature, and the mixture was stirred for 20 minutes. A saturated aqueous solution of sodium hydrogencarbonate (36 ml) and hexane (36 ml) were added to the mixture, and the mixture was stirred for 55 minutes. The precipitated solid was collected by filtration. The resultant solid was washed with hexane and dried under aeration and dried by hot air (60° C.) for 5 hours. Water (150 ml) was added to the solid, and the mixture was stirred for 2 hours, and the solid was collected by filtration, and the resultant solid was washed with water. The solid was dried by hot air (60° C.) for 3 days to give the title compound (1.117 g, 76%) as a white solid.

Workup

  1. stirringthe mixture was stirred for 55 minutes
  2. filtrationThe precipitated solid was collected by filtration
  3. washThe resultant solid was washed with hexane
  4. customdried under aeration
  5. customdried by hot air (60° C.) for 5 hours
  6. additionWater (150 ml) was added to the solid
  7. stirringthe mixture was stirred for 2 hours
  8. filtrationthe solid was collected by filtration
  9. washthe resultant solid was washed with water
  10. customThe solid was dried by hot air (60° C.) for 3 days

Sources & evidence

ORD record
ord-eef348e69af745ceaecdd5406f863899
Source dataset
uspto-grants-2013_02
Patent number
US08377938B2

Reaction notes

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