Cesium carbonate → Tert-butyl [3-({4-carbamoyl-5-[(2-fluoro-4-iodophenyl)amino]pyridin-3-yl}oxy)phenyl]carbamate

HRID 2167222Notes

Reaction equation

HRID 2167222 reaction equation
F[C:2]1[CH:10]=[N:9][CH:8]=[C:7]([NH:11][C:12]2[CH:17]=[CH:16][C:15]([I:18])=[CH:14][C:13]=2[F:19])[C:3]=1[C:4]([NH2:6])=[O:5].[OH:20][C:21]1[CH:22]=[C:23]([NH:27][C:28](=[O:34])[O:29][C:30]([CH3:33])([CH3:32])[CH3:31])[CH:24]=[CH:25][CH:26]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C>[C:4]([C:3]1[C:7]([NH:11][C:12]2[CH:17]=[CH:16][C:15]([I:18])=[CH:14][C:13]=2[F:19])=[CH:8][N:9]=[CH:10][C:2]=1[O:20][C:21]1[CH:22]=[C:23]([NH:27][C:28](=[O:34])[O:29][C:30]([CH3:32])([CH3:31])[CH3:33])[CH:24]=[CH:25][CH:26]=1)(=[O:5])[NH2:6]

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 312485tert-butyl N-(3-hydroxyphenyl)carbamateHCID 675154073-Fluoro-5-[(2-fluoro-4-iodophenyl)amino]isonicotinamide

Product 1

HCID 56970468Tert-butyl [3-({4-carbamoyl-5-[(2-fluoro-4-iodophenyl)amino]pyridin-3-yl}oxy)phenyl]carbamate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

31 mg of 3-fluoro-5-[(2-fluoro-4-iodophenyl)amino]isonicotinamide (0.083 mmol, 1. eq.) and 17 mg of tert-butyl (3-hydroxyphenyl)carbamate (0.083 mmol, 1 eq.) were dissolved in 1 ml of DMF, then 81 mg of cesium carbonate (0.248 mmol, 3 eq.) were added. The resulting mixture was stirred at room temperature for 18 hours. Since the reaction was not complete, the mixture was stirred for another 3 days at 50° C. bath temperature. The mixture was then partitioned between aq. NH4Cl solution (10 ml) and dichloromethane (10 ml). The phases were separated and the aqueouse layer was reextracted twice with dichloromethane (10 ml each). The combined organic layers were washed with brine (20 ml), dried over a silicone filter and concentrated in vacuo. The residue was purified by flash chromatography to yield 17 mg (0.03 mmol, 30%) of the analytically pure target compound.

Workup

  1. stirringthe mixture was stirred for another 3 days at 50° C. bath temperature
  2. customThe mixture was then partitioned between aq. NH4Cl solution (10 ml) and dichloromethane (10 ml)
  3. customThe phases were separated
  4. washThe combined organic layers were washed with brine (20 ml)
  5. dry with materialdried over a silicone
  6. filtrationfilter
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by flash chromatography
  9. customto yield 17 mg (0.03 mmol, 30%) of the analytically pure target compound

Sources & evidence

ORD record
ord-de9292e96c6b488fb330c3e466ce4272
Source dataset
uspto-grants-2015_06
Patent number
US09045429B2

Reaction notes

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