Water → 5-(4-Amino-2-ethylamino-pyrimidin-5-yloxy)-4-isopropyl-2-methoxy-benzonitrile

HRID 38403Notes

Reaction equation

HRID 38403 reaction equation
[CH2:1]([NH:3][C:4]1[N:9]=[C:8]([NH2:10])[C:7]([O:11][C:12]2[CH:17]=[C:16](I)[C:15]([O:19][CH3:20])=[CH:14][C:13]=2[CH:21]([CH3:23])[CH3:22])=[CH:6][N:5]=1)[CH3:2].[C:24]([Cu])#[N:25].O>CN(C=O)C>[NH2:10][C:8]1[C:7]([O:11][C:12]2[C:13]([CH:21]([CH3:23])[CH3:22])=[CH:14][C:15]([O:19][CH3:20])=[C:16]([CH:17]=2)[C:24]#[N:25])=[CH:6][N:5]=[C:4]([NH:3][CH2:1][CH3:2])[N:9]=1

Participants

5

Reactant 3

HCID 962WaterHCID 59598707HCID 59598707, compoundHCID 178418546HCID 178418546, compound

Product 1

HCID 595985715-(4-Amino-2-ethylamino-pyrimidin-5-yloxy)-4-isopropyl-2-methoxy-benzonitrileYield 71%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of N2-Ethyl-5-(5-iodo-2-isopropyl-4-methoxy-phenoxy)-pyrimidine-2,4-diamine (1.65 g, 4.12 mmol) in anhydrous DMF (10 ml) was added CuCN, and the reaction mixture was heated to 120° C. for 3 hrs. The reaction mixture was poured into water (200 ml) and the insoluble portion was collected by filtration. The solid was triturated with 10% MeOH/methylene chloride/0.1% NH4OH solution (100 ml) and filtered again. The filtrate was concentrated and flash chromatographed on silica (3% MeOH in methylene chloride with 0.1% NH4OH) to give 5-(4-Amino-2-ethylamino-pyrimidin-5-yloxy)-4-isopropyl-2-methoxy-benzonitrile (0.87 g, 71%) as a white solid.

Workup

  1. filtrationthe insoluble portion was collected by filtration
  2. customThe solid was triturated with 10% MeOH/methylene chloride/0.1% NH4OH solution (100 ml)
  3. filtrationfiltered again
  4. concentrationThe filtrate was concentrated
  5. customflash chromatographed on silica (3% MeOH in methylene chloride with 0.1% NH4OH)

Sources & evidence

ORD record
ord-e8f8d6a3da55492fbfae62659ca3f31a
Source dataset
uspto-grants-2013_09
Patent number
US08524725B2

Reaction notes

Loading…