Sodium Bicarbonate → Benzyl 1-[({2,5-difluoro-4-[(2-{[(3-hydroxyazetidin-1-yl)carbonyl]amino}pyridin-4-yl)oxy]phenyl}amino)carbonyl]cyclopropanecarboxylate

HRID 1712679Notes

Reaction equation

HRID 1712679 reaction equation
O([C:8]([NH:10][C:11]1[CH:16]=[C:15]([O:17][C:18]2[C:23]([F:24])=[CH:22][C:21]([NH:25][C:26]([C:28]3([C:31]([O:33][CH2:34][C:35]4[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=4)=[O:32])[CH2:30][CH2:29]3)=[O:27])=[C:20]([F:41])[CH:19]=2)[CH:14]=[CH:13][N:12]=1)=[O:9])C1C=CC=CC=1.Cl.[OH:43][CH:44]1[CH2:47][NH:46][CH2:45]1.C(=O)([O-])O.[Na+]>CCCCCC.C(N(CC)CC)C.CN(C)C=O>[F:41][C:20]1[CH:19]=[C:18]([O:17][C:15]2[CH:14]=[CH:13][N:12]=[C:11]([NH:10][C:8]([N:46]3[CH2:47][CH:44]([OH:43])[CH2:45]3)=[O:9])[CH:16]=2)[C:23]([F:24])=[CH:22][C:21]=1[NH:25][C:26]([C:28]1([C:31]([O:33][CH2:34][C:35]2[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=2)=[O:32])[CH2:29][CH2:30]1)=[O:27]

Participants

7

Reactant 3

HCID 516892Sodium BicarbonateHCID 27592903-Hydroxyazetidine hydrochloride2×HCID 24788625Benzyl 1-({[4-([2-[(phenoxycarbonyl)amino]pyridin-4-yl}oxy)-2,5-difluorophenyl]amino}carbonyl)cyclopropanecarboxylate

Product 1

HCID 24788565Benzyl 1-[({2,5-difluoro-4-[(2-{[(3-hydroxyazetidin-1-yl)carbonyl]amino}pyridin-4-yl)oxy]phenyl}amino)carbonyl]cyclopropanecarboxylateYield 45.1%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8058HexaneSolventHCID 8471TriethylamineSolvent2×

Procedure

Triethylamine (0.100 ml) was added to a mixture of benzyl 1-({[4-({2-[(phenoxycarbonyl)amino]pyridin-4-yl}oxy)-2,5-difluorophenyl]amino}carbonyl)cyclopropanecarboxylate (200 mg), 3-hydroxyazetidine hydrochloride (39.1 mg) and N,N-dimethylformamide (4.0 ml) at room temperature under a nitrogen atmosphere, and the mixture was stirred for 6 hours and 10 minutes. 3-Hydroxyazetidine hydrochloride (10.0 mg) and triethylamine (0.025 ml) were added at room temperature, and the mixture was stirred for 1 hour and 20 minutes. A saturated aqueous solution of sodium hydrogencarbonate (16 ml) and hexane (5 ml) were added to the mixture, and the precipitated solid was collected by filtration. The solid was washed with water (2 ml, three times), and dried under aeration. The resultant solid was purified by silica gel column chromatography (Fuji Silysia NH, eluent; ethyl acetate, then ethyl acetate:methanol=10:1). The fractions containing the target compound was concentrated under reduced pressure to give the title compound (86.7 mg, 45%) as a white solid.

Workup

  1. stirringthe mixture was stirred for 1 hour and 20 minutes
  2. filtrationthe precipitated solid was collected by filtration
  3. washThe solid was washed with water (2 ml, three times)
  4. customdried under aeration
  5. customThe resultant solid was purified by silica gel column chromatography (Fuji Silysia NH, eluent
  6. additionThe fractions containing the target compound
  7. concentrationwas concentrated under reduced pressure

Sources & evidence

ORD record
ord-512e938976444a07881aa0587bff22e1
Source dataset
uspto-grants-2010_09
Patent number
US07790885B2

Reaction notes

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