Methanol → HCID 58826024, compound

HRID 1714858Notes

Reaction equation

HRID 1714858 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.N1[CH:27]=[CH:26]C=CC=1.C[Si](Cl)(C)C.[C:33](Cl)(=[O:35])[CH3:34].C[OH:38]>C(Cl)Cl>[NH2:15][C:9]1[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]=[C:11]([NH:14][C:33](=[O:35])[CH3:34])[N:10]=1.[C:33]([NH:14][C:11]1[N:10]=[C:9]([NH:15][C:26](=[O:38])[CH3:27])[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])[CH3:34]

Participants

8

Reactant 5

HCID 887MethanolHCID 1049PyridineHCID 6367Acetyl chlorideHCID 6397ChlorotrimethylsilaneHCID 159538025-(5-Iodo-2-isopropyl-4-methoxyphenoxy)pyrimidine-2,4-diamine

Product 2

HCID 58826024HCID 58826024, compoundHCID 58826039HCID 58826039, 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 CH2Cl2 (80 ml) cooled at 0° C. was added pyridine (2.6 g, 36 mmole) and trimethylsilylchloride (2.70 g, 25 mmole). The reaction mixture was stirred at room temperature for two hours, then recooled to 0° C. and acetyl chloride (0.22 g, 2.75 mmole) was added dropwise. After stirring at 0° C. for 90 minutes, methanol (20 ml) was added and stirring was continued for 16 hours. Solvent was removed under reduced pressure and the residue was treated with water (400 ml). The white insoluble material was collected by filtration and subject to flash chromatography on silica gel, eluting with 2% CH3OH, 0.1% NH4OH in CH2Cl2 to give N-[4-amino-5-(5-iodo-2-isopropyl-4-methoxy-phenoxy)-pyrimidin-2-yl]-acetamide (0.094 g, MS (M+H)=443), N-[2-Acetylamino-5-(5-iodo-2-isopropyl-4-methoxy-phenoxy)-pyrimidin-4-yl]-acetamide (0.187 g, MS (M+H)=485), and a third fraction containing a mixture of N-[4-amino-5-(5-iodo-2-isopropyl-4-methoxy-phenoxy)-pyrimidin-2-yl]-acetamide and N-[2-Acetylamino-5-(5-iodo-2-isopropyl-4-methoxy-phenoxy)-pyrimidin-4-yl]-acetamide (0.524 g).

Workup

  1. customrecooled to 0° C.
  2. stirringAfter stirring at 0° C. for 90 minutes
  3. stirringstirring
  4. waitwas continued for 16 hours
  5. customSolvent was removed under reduced pressure
  6. additionthe residue was treated with water (400 ml)
  7. filtrationThe white insoluble material was collected by filtration
  8. washeluting with 2% CH3OH, 0.1% NH4OH in CH2Cl2

Sources & evidence

ORD record
ord-2314ab7c9cc04933a6e42aeddb47ca3b
Source dataset
uspto-grants-2010_09
Patent number
US07799796B2

Reaction notes

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