Trimethylsilyl iodide → HCID 178518776, compound

HRID 1947006Notes

Reaction equation

HRID 1947006 reaction equation
C[Si](I)(C)C.C[O:7][C:8]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[N:10]([C:17]2[CH:22]=[CH:21][N:20]=[C:19]([NH:23][C@H:24]3[CH2:29][CH2:28][C@H:27]([OH:30])[CH2:26][CH2:25]3)[N:18]=2)[N:9]=1>C(Cl)(Cl)Cl>[OH:30][C@H:27]1[CH2:28][CH2:29][C@H:24]([NH:23][C:19]2[N:18]=[C:17]([N:10]3[C:11]4[C:16](=[CH:15][CH:14]=[CH:13][CH:12]=4)[C:8](=[O:7])[NH:9]3)[CH:22]=[CH:21][N:20]=2)[CH2:25][CH2:26]1

Participants

4

Reactant 2

HCID 85247Trimethylsilyl iodide2×HCID 178494301HCID 178494301, compound

Product 1

HCID 178518776HCID 178518776, compoundYield 31.2%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

Trimethylsilyliodide (0.80 mL, 5.6 mmol) was added under N2 to a suspension of trans-4-[4-(3-methoxyindazol-1-yl)-pyrimidin-2-ylamino]-cyclohexanol (251 mg, 0.7 mmol) in chloroform (10 mL). The reaction mixture immediately became homogeneous, but within 1 hour a suspension formed, and the resulting mixture was stirred for 3 days. An additional aliquot of trimethylsilyliodide (2 mL, 14 mmol) was added, and the resulting mixture was heated to reflux overnight and stirred at RT for one day. The reaction mixture was then poured onto ice water and extracted with DCM. The insoluble solids were filtered and dissolved in a mixture of MeOH and DCM, the combined organic layers dried over Na2SO4, filtered and concentrated under reduced pressure onto silica gel. The residue was purified by flash chromatography (MeOH/DCM, gradient from 3:97 to 5:95) to give trans-1-[2-(4-hydroxycyclohexylamino)-pyrimidin-4-yl]-1,2-dihydroindazol-3-one (71 mg, 30% yield) as an off-white solid. MS=326 [M+H]+; MP=263.5-264.4° C.

Workup

  1. customThe reaction mixture immediately became homogeneous, but within 1 hour a suspension formed
  2. temperaturethe resulting mixture was heated
  3. temperatureto reflux overnight
  4. stirringstirred at RT for one day
  5. additionThe reaction mixture was then poured onto ice water
  6. extractionextracted with DCM
  7. filtrationThe insoluble solids were filtered
  8. dissolutiondissolved in a mixture of MeOH and DCM
  9. dry with materialthe combined organic layers dried over Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure onto silica gel
  12. customThe residue was purified by flash chromatography (MeOH/DCM, gradient from 3:97 to 5:95)

Sources & evidence

ORD record
ord-3434eb5f09e94602a17726351d12372e
Source dataset
uspto-grants-2013_03
Patent number
US08399462B2

Reaction notes

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