Ethylenediamine → 5-[5-(4,5-dihydro-1H-imidazol-2-yl)-2-isopropyl-4-methoxy-phenoxy]-pyrimidine-2,4-diamine

HRID 38356Notes

Reaction equation

HRID 38356 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([NH2:8])[C:5]([O:9][C:10]2[C:11]([CH:20]([CH3:22])[CH3:21])=[CH:12][C:13]([O:18][CH3:19])=[C:14]([CH:17]=2)[C:15]#[N:16])=[CH:4][N:3]=1.[CH2:23](N)[CH2:24][NH2:25]>CO>[NH:16]1[CH2:23][CH2:24][N:25]=[C:15]1[C:14]1[C:13]([O:18][CH3:19])=[CH:12][C:11]([CH:20]([CH3:22])[CH3:21])=[C:10]([CH:17]=1)[O:9][C:5]1[C:6]([NH2:8])=[N:7][C:2]([NH2:1])=[N:3][CH:4]=1

Participants

4

Reactant 2

HCID 3301EthylenediamineHCID 445736915-(2,4-Diamino-pyrimidin-5-yloxy)-4-isopropyl-2-methoxy-benzonitrile

Product 1

HCID 445736965-[5-(4,5-dihydro-1H-imidazol-2-yl)-2-isopropyl-4-methoxy-phenoxy]-pyrimidine-2,4-diamine

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

To a cooled (0° C.) suspension of 5-(2,4-diamino-pyrimidin-5-yloxy)-4-isopropyl-2-methoxy-benzonitrile (0.138 g, 0.461 mmol) in dry methanol (15 ml) was bubbled with HCl gas for 10 minutes and refrigerated overnight. Solvent was evaporated under reduced pressure to give a yellow solid which was redissolved in dry methanol (10 ml). Ethylene diamine (0.034 ml, 0.509 mmol) was added and the reaction mixture was refluxed for 20 hours and concentrated under reduced pressure. The residue was purified by silica gel chromatography (gradient: 7-50% methanol in methylene chloride/0.1% concentrated NH4OH) to yield 5-[5-(4,5-dihydro-1H-imidazol-2-yl)-2-isopropyl-4-methoxy-phenoxy]-pyrimidine-2,4-diamine which was crystallized from methanol/ethyl acetate/ether as a white solid, (0.053 g, 33%).

Workup

  1. temperatureTo a cooled
  2. customwas bubbled with HCl gas for 10 minutes and refrigerated overnight
  3. customSolvent was evaporated under reduced pressure
  4. customto give a yellow solid which
  5. temperaturethe reaction mixture was refluxed for 20 hours
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by silica gel chromatography (gradient: 7-50% methanol in methylene chloride/0.1% concentrated NH4OH)

Sources & evidence

ORD record
ord-b6d46fa0b1a847ac8f25b3ba0c2b8bde
Source dataset
uspto-grants-2013_09
Patent number
US08524725B2

Reaction notes

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