Potassium Carbonate → 4-(3-(4-(2-(Benzhydrylamino)-3-chloropyridin-4-yloxy)-3-fluorophenylcarbamoyl)-5-(4-fluorophenyl)-4-oxopyridin-1(4H)-yl)methyl 1-tert-butyl piperidine-1,4-dicarboxylate

HRID 2380955Notes

Reaction equation

HRID 2380955 reaction equation
[CH:1]([NH:14][C:15]1[C:20]([Cl:21])=[C:19]([O:22][C:23]2[CH:28]=[CH:27][C:26]([NH:29][C:30]([C:32]3[C:37](=[O:38])[C:36]([C:39]4[CH:44]=[CH:43][C:42]([F:45])=[CH:41][CH:40]=4)=[CH:35][NH:34][CH:33]=3)=[O:31])=[CH:25][C:24]=2[F:46])[CH:18]=[CH:17][N:16]=1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([O-])([O-])=O.[K+].[K+].[N:53]1([C:64]([O:66][C:67]([CH3:70])([CH3:69])[CH3:68])=[O:65])[CH2:58][CH2:57][CH:56]([C:59]([O:61][CH2:62]Cl)=[O:60])[CH2:55][CH2:54]1>CN(C=O)C.C(Cl)Cl>[N:53]1([C:64]([O:66][C:67]([CH3:70])([CH3:69])[CH3:68])=[O:65])[CH2:54][CH2:55][CH:56]([C:59]([O:61][CH2:62][N:34]2[CH:35]=[C:36]([C:39]3[CH:40]=[CH:41][C:42]([F:45])=[CH:43][CH:44]=3)[C:37](=[O:38])[C:32]([C:30](=[O:31])[NH:29][C:26]3[CH:27]=[CH:28][C:23]([O:22][C:19]4[CH:18]=[CH:17][N:16]=[C:15]([NH:14][CH:1]([C:2]5[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=5)[C:8]5[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=5)[C:20]=4[Cl:21])=[C:24]([F:46])[CH:25]=3)=[CH:33]2)=[O:60])[CH2:57][CH2:58]1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 101075661-Tert-butyl 4-chloromethyl piperidine-1,4-dicarboxylateHCID 66772473N-(4-(2-(Benzhydrylamino)-3-chloropyridin-4-yloxy)-3-fluorophenyl)-5-(4-fluorophenyl)-4-oxo-1,4-dihydropyridine-3-carboxamide

Product 1

HCID 667724004-(3-(4-(2-(Benzhydrylamino)-3-chloropyridin-4-yloxy)-3-fluorophenylcarbamoyl)-5-(4-fluorophenyl)-4-oxopyridin-1(4H)-yl)methyl 1-tert-butyl piperidine-1,4-dicarboxylateYield 87.5%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of N-(4-(2-(benzhydrylamino)-3-chloropyridin-4-yloxy)-3-fluorophenyl)-5-(4-fluorophenyl)-4-oxo-1,4-dihydropyridine-3-carboxamide (120 mg, 0.189 mmol), K2CO3 (104 mg, 0.756 mmol) and 1-tert-butyl 4-chloromethyl piperidine-1,4-dicarboxylate (157 mg, 0.567 mmol) in DMF (2 mL) was stirred at rt for 3 h. The reaction mixture was then diluted with DCM and the solid that formed was filtered off. The residue was washed with sat. aq. KH2PO4 solution. The organic layer was dried over MgSO4 and the desired product was purified by flash column chromatography (SiO2, eluting with a DCM/EtOAc gradient) to give the desired compound (145 mg) as a white solid. MS (ESI+) m/z 876 (M+H)+.

Workup

  1. customthe solid that formed
  2. filtrationwas filtered off
  3. washThe residue was washed with sat. aq. KH2PO4 solution
  4. dry with materialThe organic layer was dried over MgSO4
  5. customthe desired product was purified by flash column chromatography (SiO2
  6. washeluting with a DCM/EtOAc gradient)

Sources & evidence

ORD record
ord-4b5752bbd9244072b529bfbfd00c4b09
Source dataset
uspto-grants-2012_09
Patent number
US08258118B2

Reaction notes

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