Methanol → HCID 58826060, compound

HRID 1714853Notes

Reaction equation

HRID 1714853 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.Cl[Si](C)(C)C.[C:27](Cl)(=[O:31])[CH2:28][CH2:29][CH3:30].C[OH:34].N1C=[CH:39][CH:38]=[CH:37][CH:36]=1>ClCCl>[C:27]([NH:14][C:11]1[N:10]=[C:9]([NH:15][C:36](=[O:34])[CH2:37][CH2:38][CH3:39])[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:31])[CH2:28][CH2:29][CH3:30]

Participants

7

Reactant 5

HCID 887MethanolHCID 1049PyridineHCID 6397ChlorotrimethylsilaneHCID 8855Butyryl chlorideHCID 159538025-(5-Iodo-2-isopropyl-4-methoxyphenoxy)pyrimidine-2,4-diamine

Product 1

HCID 58826060HCID 58826060, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 5-(5-iodo-2-isopropyl-4-methoxy-phenoxy)-pyrimidine-2,4-diamine (1.0 g, 2.5 mmoles) in dichloromethane (80 ml) and pyridine (5 ml) at 0° C. was added chlorotrimethyl silane (3.2 ml, 25.2 mmoles). The mixture was stirred at room temperature for 2.5 hours, then cooled to at 0° C. and butyryl chloride (0.54 ml, 5.2 mmoles) was added. The reaction was stirred at 0° C. for 2.5 hours, and then methanol (20 ml) was added. The reaction was stirred at room temperature for 60 hours. The reaction mixture was concentrated under reduced pressure, and the residue was partitioned between dichloromethane and water. The organic phase was separated and washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel chromatography (0.5%, 1% methanol in dichloromethane with 0.1% concentrated ammonium hydroxide aqueous solution) to give crude N-[4-amino-5-(5-iodo-2-isopropyl-4-methoxy-phenoxy)-pyrimidin-2-yl]-butyramide and N-[2-butyrylamino-5-(5-iodo-2-isopropyl-4-methoxy-phenoxy)-pyrimidin-4-yl]-butyramide, which were loaded on preparative TLC plates separately, eluted with 5% methanol in dichloromethane to give pure N-[2-butyrylamino-5-(5-iodo-2-isopropyl-4-methoxy-phenoxy)-pyrimidin-4-yl]-butyramide (145 mgs), M+1: 541, and pure N-[4-amino-5-(5-iodo-2-isopropyl-4-methoxy-phenoxy)-pyrimidin-2-yl]-butyramide (425 mgs), MS (M+H)=471.

Workup

  1. additionwas added
  2. stirringThe reaction was stirred at 0° C. for 2.5 hours
  3. stirringThe reaction was stirred at room temperature for 60 hours
  4. concentrationThe reaction mixture was concentrated under reduced pressure
  5. customthe residue was partitioned between dichloromethane and water
  6. customThe organic phase was separated
  7. washwashed 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 (0.5%, 1% methanol in dichloromethane with 0.1% concentrated ammonium hydroxide aqueous solution)

Sources & evidence

ORD record
ord-029c9306981143b7837b6ba9b5b803ed
Source dataset
uspto-grants-2010_09
Patent number
US07799796B2

Reaction notes

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