Sodium hydride → 2-Chloro-5-iodo-4-((tetrahydro-2H-pyran-4-yl)oxy)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidine

HRID 529671Notes

Reaction equation

HRID 529671 reaction equation
[H-].[Na+].[O:3]1[CH2:8][CH2:7][CH:6]([OH:9])[CH2:5][CH2:4]1.[Cl:10][C:11]1[N:12]=[C:13](Cl)[C:14]2[C:19]([I:20])=[CH:18][N:17]([CH2:21][O:22][CH2:23][CH2:24][Si:25]([CH3:28])([CH3:27])[CH3:26])[C:15]=2[N:16]=1>C1COCC1>[Cl:10][C:11]1[N:12]=[C:13]([O:9][CH:6]2[CH2:7][CH2:8][O:3][CH2:4][CH2:5]2)[C:14]2[C:19]([I:20])=[CH:18][N:17]([CH2:21][O:22][CH2:23][CH2:24][Si:25]([CH3:28])([CH3:27])[CH3:26])[C:15]=2[N:16]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 74956Tetrahydro-4H-pyran-4-olHCID 866796212,4-dichloro-5-iodo-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo(2,3-d)pyrimidine

Product 1

HCID 867264332-Chloro-5-iodo-4-((tetrahydro-2H-pyran-4-yl)oxy)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidineYield 84%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a suspension of sodium hydride (1 equiv) in dry THF (0.42 M) under nitrogen atmosphere was added tetrahydro-2H-pyran-4-ol (1 equiv) at 0° C. The reaction mixture was stirred at room temperature for 30 min before a solution of 2,4-dichloro-5-iodo-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidine (0.67 equiv) in dry THF (0.75 M) was added at 0° C. The mixture was stirred at 0° C. for 1 h. The reaction was monitored by thin layer chromatography. Upon completion, the reaction mixture was quenched with water and extracted with ethyl acetate. The organic layers were combined, washed with brine, dried over sodium sulfate, filtered and concentrated. The crude product was purified by silica gel flash column chromatography (5% ethyl acetate in petroleum ether) to afford the title compound as a yellowish oil (84% yield). MS (ESI) m/z 510.1 [M+1]+.

Workup

  1. additionwas added at 0° C
  2. customUpon completion, the reaction mixture was quenched with water
  3. extractionextracted with ethyl acetate
  4. washwashed with brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude product was purified by silica gel flash column chromatography (5% ethyl acetate in petroleum ether)

Sources & evidence

ORD record
ord-859d67aa73a340f197f814f5e8437946
Source dataset
uspto-grants-2016_05
Patent number
US09346812B2

Reaction notes

Loading…