1,2-Diaminocyclohexane, trans- → 4-Amino-N-(4-(3-(2-(methylamino)pyrimidin-4-yl)pyridin-2-yloxy)phenyl)benzamide

HRID 1361680Notes

Reaction equation

HRID 1361680 reaction equation
I[C:2]1[CH:22]=[CH:21][C:5]([O:6][C:7]2[C:12]([C:13]3[CH:18]=[CH:17][N:16]=[C:15]([NH:19][CH3:20])[N:14]=3)=[CH:11][CH:10]=[CH:9][N:8]=2)=[CH:4][CH:3]=1.[NH2:23][C:24]1[CH:32]=[CH:31][C:27]([C:28]([NH2:30])=[O:29])=[CH:26][CH:25]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].N[C@@H]1CCCC[C@H]1N>[Cu]I.C(OCC)(=O)C.O1CCOCC1>[NH2:23][C:24]1[CH:32]=[CH:31][C:27]([C:28]([NH:30][C:2]2[CH:22]=[CH:21][C:5]([O:6][C:7]3[C:12]([C:13]4[CH:18]=[CH:17][N:16]=[C:15]([NH:19][CH3:20])[N:14]=4)=[CH:11][CH:10]=[CH:9][N:8]=3)=[CH:4][CH:3]=2)=[O:29])=[CH:26][CH:25]=1

Participants

8

Reactant 4

HCID 438061,2-Diaminocyclohexane, trans-HCID 62657Potassium Phosphate, TribasicHCID 760794-AminobenzamideHCID 585885464-(2-(4-iodophenoxy)pyridin-3-yl)-N-methylpyrimidin-2-amine

Product 1

HCID 585879594-Amino-N-(4-(3-(2-(methylamino)pyrimidin-4-yl)pyridin-2-yloxy)phenyl)benzamide

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

In a manner analogous to that described in Klappars, A.; Antilla, J. C.; Huang, X.; Buchwald, S. L. J. Am. Chem. Soc. 2001, 123, 7727, 4-(2-(4-iodophenoxy)pyridin-3-yl)-N-methylpyrimidin-2-amine (202 mg, 0.500 mmol), 4-aminobenzamide (102 mg, 0.750 mmol), finely ground CuI (4.8 mg, 0.0250 mmol, 5 mol %), and anhydrous potassium phosphate (212 mg, 1 mmol) were added into a screw cap test tube. The tube was purged with argon for 5 minutes. Then trans-1,2-diaminocyclohexane (15.0 mL, 0.100 mmol, 10 mol %) and dioxane were added into the reaction mixture via syringe. The tube was sealed and placed in a preheated oil bath at 110° C. After a day, the reaction was cooled to room temperature. The reaction mixture was passed through a pad of celite with the aid of ethyl acetate. The filtrate was concentrated under reduced pressure. The product was purified by column chromatography using 10:90 Hex:EtOAc. 4-Amino-N-(4-(3-(2-(methylamino)pyrimidin-4-yl)pyridin-2-yloxy)phenyl)benzamide was obtained as an off-white solid.

Workup

  1. customcap test tube
  2. customThe tube was purged with argon for 5 minutes
  3. customThe tube was sealed
  4. customplaced in a preheated oil bath at 110° C
  5. waitAfter a day
  6. concentrationThe filtrate was concentrated under reduced pressure
  7. customThe product was purified by column chromatography

Sources & evidence

ORD record
ord-074e749a32a94282929a6cf1255d1ad4
Source dataset
uspto-grants-2011_02
Patent number
US07880000B2

Reaction notes

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