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Morpholine → N-[3-Fluoro-4-({6-{(morpholin-4-ylcarbonyl)amino}pyrimidin-4-yl}oxy)phenyl]-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide

HRID 2265658
Notes
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Reaction equation

HRID 2265658 reaction equation
C1(O[C:8](=[O:40])[NH:9][C:10]2[CH:15]=[C:14]([O:16][C:17]3[CH:22]=[CH:21][C:20]([NH:23][C:24]([C:26]4([C:29](=[O:38])[NH:30][C:31]5[CH:36]=[CH:35][C:34]([F:37])=[CH:33][CH:32]=5)[CH2:28][CH2:27]4)=[O:25])=[CH:19][C:18]=3[F:39])[N:13]=[CH:12][N:11]=2)C=CC=CC=1.[NH:41]1[CH2:46][CH2:45][O:44][CH2:43][CH2:42]1>CN(C)C=O>[F:39][C:18]1[CH:19]=[C:20]([NH:23][C:24]([C:26]2([C:29]([NH:30][C:31]3[CH:36]=[CH:35][C:34]([F:37])=[CH:33][CH:32]=3)=[O:38])[CH2:27][CH2:28]2)=[O:25])[CH:21]=[CH:22][C:17]=1[O:16][C:14]1[CH:15]=[C:10]([NH:9][C:8]([N:41]2[CH2:46][CH2:45][O:44][CH2:43][CH2:42]2)=[O:40])[N:11]=[CH:12][N:13]=1
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

4

Reactant 2

HCID 8083MorpholineHCID 59596966[6-(2-Fluoro-4-{[1-(4-fluorophenylcarbamoyl)cyclopropanecarbonyl]amino}phenoxy)pyrimidin-4-yl]carbamic acid phenyl ester

Product 1

HCID 59596971N-[3-Fluoro-4-({6-{(morpholin-4-ylcarbonyl)amino}pyrimidin-4-yl}oxy)phenyl]-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamideYield 82.9%

Reagents, catalysts & solvents 1

HCID 6228Dimethylformamide
Solvent

Procedure

[6-(2-Fluoro-4-{[1-(4-fluorophenylcarbamoyl)cyclopropanecarbonyl]amino}phenoxy)pyrimidin-4-yl]carbamic acid phenyl ester (40 mg) was dissolved in N,N-dimethylformamide (1.0 ml), and morpholine (0.045 ml) was added thereto, followed by stirring for 26 hr. The reaction mixture was partitioned between ethyl acetate (50 ml) and a saturated aqueous solution of ammonium chloride (20 ml). The organic layer was washed with a saturated aqueous solution of ammonium chloride (20 ml), water (20 ml) and brine (20 ml) in this order, and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure, and the resultant residue was purified by silica gel column chromatography (Fuji Silysia NH, eluent; heptane:ethyl acetate=1:5, then ethyl acetate). Fractions containing the target compound were concentrated under reduced pressure, and the resultant residue was suspended in diethyl ether (2 ml) and hexane (4 ml). The solid was collected by filtration and dried under aeration to provide the titled compound as white powder (18.3 mg, 82.9%).

Workup

  1. customThe reaction mixture was partitioned between ethyl acetate (50 ml)
  2. washThe organic layer was washed with a saturated aqueous solution of ammonium chloride (20 ml), water (20 ml) and brine (20 ml) in this order
  3. dry with materialdried over anhydrous sodium sulfate
  4. customThe solvent was removed under reduced pressure
  5. customthe resultant residue was purified by silica gel column chromatography (Fuji Silysia NH, eluent
  6. additionFractions containing the target compound
  7. concentrationwere concentrated under reduced pressure
  8. filtrationThe solid was collected by filtration
  9. customdried under aeration

Sources & evidence

ORD record
ord-46177e7b1b0a4511b87e3ffc3f4d4350
Source dataset
uspto-grants-2010_12
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US07855290B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes