Hydrochloric Acid → HCID 58826034, compound

HRID 1714857Notes

Reaction equation

HRID 1714857 reaction equation
[I:1][C:2]1[C:3]([O:20][CH3:21])=[CH:4][C:5]([CH:17]([CH3:19])[CH3:18])=[C:6]([CH:16]=1)[O:7][C:8]1[C:9]([NH2:15])=[N:10][C:11]([NH2:14])=[N:12][CH:13]=1.C([NH:29][CH:30]([C:34](O)=[O:35])[CH:31]([CH3:33])[CH3:32])(OC(C)(C)C)=O.C1(N=C=NC2CCCCC2)CCCCC1.Cl>CN(C)C1C=CN=CC=1.ClCCl.C(OCC)C>[NH2:29][CH:30]([CH:31]([CH3:33])[CH3:32])[C:34]([NH:14][C:11]1[N:10]=[C:9]([NH2:15])[C:8]([O:7][C:6]2[CH:16]=[C:2]([I:1])[C:3]([O:20][CH3:21])=[CH:4][C:5]=2[CH:17]([CH3:19])[CH3:18])=[CH:13][N:12]=1)=[O:35]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 10868DicyclohexylcarbodiimideHCID 270655Boc-DL-valineHCID 159538025-(5-Iodo-2-isopropyl-4-methoxyphenoxy)pyrimidine-2,4-diamine

Product 1

HCID 58826034HCID 58826034, compoundYield 9.6%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 3283Diethyl EtherSolvent2×HCID 6344DichloromethaneSolvent2×

Procedure

To a suspension of compound 5-(5-iodo-2-isopropyl-4-methoxy-phenoxy)-pyrimidine-2,4-diamine (1.0 g, 2.5 mmoles), Boc-DL-valine (1.22 g, 5.6 mmoles), and 4-dimethylaminopyridine (1.0 g, 8.2 mmoles) in dichloromethane, was added 1,3-dicyclohexylcarbodiimide (2.4 g, 11.6 mmoles). The mixture was stirred at room temperature for 60 hours, and solids were filtered off. The filtrate was evaporated and the residue was dissolved in a mixture of concentrated aqueous ammonium hydroxide and methanol (5 ml/45 ml) and stirred at room temperature for 5 hours. Solvent was evaporated under reduced pressure and the residue was partitioned between dichloromethane and 0.5 N aqueous HCl. The organic phase was washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography (30% ethyl acetate in hexane) to give Boc-protected 2-Amino-N-[4-amino-5-(5-iodo-2-isopropyl-4-methoxy-phenoxy)-pyrimidin-2-yl]-3-methyl-butyramide as a white foam (0.2 g), MS (M+H)=600. This Boc compound was dissolved in dichloromethane (3 ml) and 1M HCl in diethyl ether (10 ml) was added. The mixture was stirred for 4 hours at room temperature, and 10 ml of additional diethyl ether was added. The resulting solid precipitate was collected and crystallized from isopropanol and ether to give 2-amino-N-[4-amino-5-(5-iodo-2-isopropyl-4-methoxy-phenoxy)-pyrimidin-2-yl]-3-methyl-butyramide as white solid (0.12 g), MS (M+H)=500.

Workup

  1. filtrationsolids were filtered off
  2. customThe filtrate was evaporated
  3. dissolutionthe residue was dissolved in a mixture of concentrated aqueous ammonium hydroxide and methanol (5 ml/45 ml)
  4. stirringstirred at room temperature for 5 hours
  5. customSolvent was evaporated under reduced pressure
  6. customthe residue was partitioned between dichloromethane and 0.5 N aqueous HCl
  7. washThe organic phase was washed with brine
  8. dry with materialdried over anhydrous sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customThe residue was purified by silica gel chromatography (30% ethyl acetate in hexane)
  12. customto give Boc-protected 2-Amino-N-[4-amino-5-(5-iodo-2-isopropyl-4-methoxy-phenoxy)-pyrimidin-2-yl]-3-methyl-butyramide as a white foam (0.2 g), MS (M+H)=600
  13. stirringThe mixture was stirred for 4 hours at room temperature
  14. customThe resulting solid precipitate was collected
  15. customcrystallized from isopropanol and ether

Sources & evidence

ORD record
ord-0db67ebac4b94d608fed296906f3a9e5
Source dataset
uspto-grants-2010_09
Patent number
US07799796B2

Reaction notes

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