Hydrochloric Acid → N-(4-(3-(2-(methylamino)pyrimidin-4-yl)pyridin-2-yloxy)phenyl)-2-(phenylamino)nicotinamide

HRID 1361683Notes

Reaction equation

HRID 1361683 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O1CCCC1.F[C:14]1[N:43]=[CH:42][CH:41]=[CH:40][C:15]=1[C:16]([NH:18][C:19]1[CH:24]=[CH:23][C:22]([O:25][C:26]2[C:31]([C:32]3[CH:37]=[CH:36][N:35]=[C:34]([NH:38][CH3:39])[N:33]=3)=[CH:30][CH:29]=[CH:28][N:27]=2)=[CH:21][CH:20]=1)=[O:17].Cl>C[Si]([N-][Si](C)(C)C)(C)C.[Li+].CCOC(C)=O.O.O>[CH3:39][NH:38][C:34]1[N:33]=[C:32]([C:31]2[C:26]([O:25][C:22]3[CH:23]=[CH:24][C:19]([NH:18][C:16](=[O:17])[C:15]4[CH:40]=[CH:41][CH:42]=[N:43][C:14]=4[NH:1][C:2]4[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=4)=[CH:20][CH:21]=3)=[N:27][CH:28]=[CH:29][CH:30]=2)[CH:37]=[CH:36][N:35]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 6115AnilineHCID 8028TetrahydrofuranHCID 66970630HCID 66970630, compound

Product 1

HCID 58588424N-(4-(3-(2-(methylamino)pyrimidin-4-yl)pyridin-2-yloxy)phenyl)-2-(phenylamino)nicotinamide

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 2733832Lithium HexamethyldisilazideSolventHCID 22728543Water ethylacetateSolvent

Conditions

Temperature
70 °C

Procedure

To a brown solution of aniline (0.18 ml, 1.9 mmol) in lithium bis(trimethylsilyl)amide, 11.0m solution in tetrahydrofuran (1.9 ml, 1.9 mmol) was added 2-fluoro-N-(4-(3-(2-(methylamino)pyrimidin-4-yl)pyridin-2-yloxy)phenyl)nicotinamide (0.200 g, 0.48 mmol). The mixture was sealed and heated to 70° C. After 2 h, the reaction was cooled to ambient temperature. Water was added, and the pH was adjusted with 6N HCl until slightly acidic. Add to EtOAc/water. Wash the mixture 1× with brine. The organic layer was dried over anhyd. sodium sulfate, filtered, and concentrated to give a brown solid. This material was purified by silica gel chromatography using 90/10 dichloromethane/methanol as eluent to give a yellow solid. Further purification was performed by trituration with dichloromethane and methanol to give N-(4-(3-(2-(methylamino)pyrimidin-4-yl)pyridin-2-yloxy)phenyl)-2-(phenylamino)nicotinamide as a yellow solid. MS m/z=490 [M+1]+. Calc'd for C28H23N7O2: 489.53.

Workup

  1. customThe mixture was sealed
  2. temperaturethe reaction was cooled to ambient temperature
  3. washWash the mixture 1× with brine
  4. customThe organic layer was dried over anhyd
  5. filtrationsodium sulfate, filtered
  6. concentrationconcentrated
  7. customto give a brown solid
  8. customThis material was purified by silica gel chromatography
  9. customto give a yellow solid
  10. customFurther purification

Sources & evidence

ORD record
ord-3456534c7ae44967acaae88af616135a
Source dataset
uspto-grants-2011_02
Patent number
US07880000B2

Reaction notes

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