Potassium Iodide → Di-tert-butyl (3-(4-(3-chloro-2-(diphenylmethyleneamino)pyridin-4-yloxy)-3-fluorophenylcarbamoyl)-5-(4-fluorophenyl)-4-oxopyridin-1(4H)-yl)methyl phosphate

HRID 2380958Notes

Reaction equation

HRID 2380958 reaction equation
[Cl:1][C:2]1[C:3]([N:33]=[C:34]([C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=2)[C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)=[N:4][CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[CH:13][C:12]([NH:15][C:16]([C:18]2[C:23](=[O:24])[C:22]([C:25]3[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=3)=[CH:21][NH:20][CH:19]=2)=[O:17])=[CH:11][C:10]=1[F:32].C([O-])([O-])=O.[Cs+].[Cs+].[I-].[K+].[P:55]([O:67][CH2:68]Cl)([O:62][C:63]([CH3:66])([CH3:65])[CH3:64])([O:57][C:58]([CH3:61])([CH3:60])[CH3:59])=[O:56]>CN(C=O)C>[P:55]([O:67][CH2:68][N:20]1[CH:21]=[C:22]([C:25]2[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=2)[C:23](=[O:24])[C:18]([C:16](=[O:17])[NH:15][C:12]2[CH:13]=[CH:14][C:9]([O:8][C:7]3[CH:6]=[CH:5][N:4]=[C:3]([N:33]=[C:34]([C:41]4[CH:42]=[CH:43][CH:44]=[CH:45][CH:46]=4)[C:35]4[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=4)[C:2]=3[Cl:1])=[C:10]([F:32])[CH:11]=2)=[CH:19]1)([O:57][C:58]([CH3:61])([CH3:60])[CH3:59])([O:62][C:63]([CH3:64])([CH3:65])[CH3:66])=[O:56]

Participants

6

Reactant 4

HCID 4875Potassium IodideHCID 10796Cesium carbonateHCID 11701630Di-tert-butyl (chloromethyl) phosphateHCID 86650689N-(4-((3-Chloro-2-((diphenylmethylene)amino)pyridin-4-yl)oxy)-3-fluorophenyl)-5-(4-fluorophenyl)-4-oxo-1,4-dihydropyridine-3-carboxamide

Product 1

HCID 86650690Di-tert-butyl (3-(4-(3-chloro-2-(diphenylmethyleneamino)pyridin-4-yloxy)-3-fluorophenylcarbamoyl)-5-(4-fluorophenyl)-4-oxopyridin-1(4H)-yl)methyl phosphateYield 72.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of N-(4-(3-Chloro-2-(diphenylmethyleneamino)pyridin-4-yloxy)-3-fluorophenyl)-5-(4-fluorophenyl)-4-oxo-1,4-dihydropyridine-3-carboxamide (1.0 g, 1.58 mmol) in DMF (10 mL) at room temperature were added Cs2CO3 (1.3 g, 3.95 mmol), potassium iodide (525 mg, 3.16 mmol) and then di-tert-butyl chloromethyl phosphate (1.2 mL, 1.90 mmol: 2.0 M in DMF). The reaction mixture was stirred at room temperature for 26 h prior to being quenched by the addition of isopropyl acetate (10 mL) and cold water (50 mL). The organics were separated and washed with water (50 mL). The solvent was swapped into isopropanol (10 mL) by continuous distillation at 86° C. The solution was cooled to 20° C. and a solid precipitated. The solid was collected by filtration and dried under vacuum at 60° C. for 12 h to give the desired product (0.98 g, 72%) as an off-white solid. MS (ESI+) m/z 856 (M+H)+.

Workup

  1. customto being quenched by the addition of isopropyl acetate (10 mL) and cold water (50 mL)
  2. customThe organics were separated
  3. washwashed with water (50 mL)
  4. distillationThe solvent was swapped into isopropanol (10 mL) by continuous distillation at 86° C
  5. temperatureThe solution was cooled to 20° C.
  6. customa solid precipitated
  7. filtrationThe solid was collected by filtration
  8. customdried under vacuum at 60° C. for 12 h

Sources & evidence

ORD record
ord-ffb4760e54e34c5491e3cd55bd5cce5c
Source dataset
uspto-grants-2012_09
Patent number
US08258118B2

Reaction notes

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