Silanamine, 1,1,1-trimethyl-N-(trimethylsilyl)-, potassium salt → HCID 178453660, compound

HRID 577710Notes

Reaction equation

HRID 577710 reaction equation
[Cl:1][C:2]1[N:3]=[C:4](Cl)[C:5]2[C:10]([I:11])=[CH:9][N:8]([CH2:12][O:13][CH2:14][CH2:15][Si:16]([CH3:19])([CH3:18])[CH3:17])[C:6]=2[N:7]=1.[C:21]([O:25][C:26](=[O:34])[NH:27][CH2:28][C@H:29]1[CH2:32][C@H:31]([OH:33])[CH2:30]1)([CH3:24])([CH3:23])[CH3:22].C[Si](C)(C)N[Si](C)(C)C.[K]>C1COCC1>[Cl:1][C:2]1[N:3]=[C:4]([O:33][C@H:31]2[CH2:32][C@H:29]([CH2:28][NH:27][C:26](=[O:34])[O:25][C:21]([CH3:23])([CH3:22])[CH3:24])[CH2:30]2)[C:5]2[C:10]([I:11])=[CH:9][N:8]([CH2:12][O:13][CH2:14][CH2:15][Si:16]([CH3:19])([CH3:18])[CH3:17])[C:6]=2[N:7]=1

Participants

5

Reactant 3

HCID 45051783Silanamine, 1,1,1-trimethyl-N-(trimethylsilyl)-, potassium saltHCID 866796212,4-dichloro-5-iodo-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo(2,3-d)pyrimidineHCID 178453656HCID 178453656, compound

Product 1

HCID 178453660HCID 178453660, compoundYield 80%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 2,4-dichloro-5-iodo-7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidine (416 mg, 0.94 mmol), as prepared in Example 5, step 1, in THF (10 mL) was added tert-butyl(trans-3-hydroxycyclobutyl)methylcarbamate (175 mg, 0.94 mmol) and potassium hexamethyldisilazane (560 mg, 2.8 mmol, 3.0 mol eq) and the reaction was stirred at ambient temperature for 20 hrs. The reaction was then quenched with brine (3 mL) and stirred for 10 min, and diluted with ethyl acetate (60 mL) and water (10 mL). The organic layer was separated, washed with brine (10 mL), dried over Na2SO4, filtered and evaporated to give an oil which was purified via flash chromatography (eluting with a gradient of 0 iodobenzene diacetate 100% EtOAc in heptanes) to give the title compound (452 mg, 80% yield) as a colorless oil. 1H NMR (400 MHz, DMSO-d6) δ ppm 7.80 (s, 1H) 5.48 (s, 2H) 5.38 (t, J=6.54 Hz, 1H) 4.86 (br. s., 1H) 3.44-3.59 (m, 2H) 2.81 (s, 3H) 2.61-2.74 (m, 2H) 2.27-2.43 (m, 2H) 1.40 (s, 9H) 0.71-0.97 (m, 2H) −0.08 (s, 9H). m/z (APCI+) for C22H34ClIN4O4Si 509.0 (M+H)+.

Workup

  1. customThe reaction was then quenched with brine (3 mL)
  2. stirringstirred for 10 min
  3. additiondiluted with ethyl acetate (60 mL) and water (10 mL)
  4. customThe organic layer was separated
  5. washwashed with brine (10 mL)
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. customevaporated
  9. customto give an oil which
  10. customwas purified via flash chromatography (
  11. washeluting with a gradient of 0 iodobenzene diacetate 100% EtOAc in heptanes)

Sources & evidence

ORD record
ord-c4dd663bbef34c1eb994f5a368af7fe5
Source dataset
uspto-grants-2015_05
Patent number
US09040547B2

Reaction notes

Loading…