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

HRID 1487598Notes

Reaction equation

HRID 1487598 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.[O:21]1[CH2:26][CH2:25][CH:24]([OH:27])[CH2:23][CH2:22]1.CC(C)([O-])C.[Na+]>O1CCOCC1>[Cl:1][C:2]1[N:3]=[C:4]([O:27][CH:24]2[CH2:25][CH2:26][O:21][CH2:22][CH2:23]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 74956Tetrahydro-4H-pyran-4-olHCID 23676156Sodium t-butoxideHCID 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 86%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
70 °C

Procedure

2,4-Dichloro-5-iodo-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidine (1 equiv), tetrahydro-2H-pyran-4-ol (1.05 equiv), sodium tert-butoxide (1.05 equiv) and 1,4-dioxane (0.56 M) were combined and heated at 70° C. for 5 h. The reaction mixture was concentrated and extracted with ethyl acetate/H2O. The organic layers were combined, evaporated under reduced pressure and purified by silica-gel chromatography (0-50% hexane:ethyl acetate over 800 mL) followed by 5-15% (DCM:MeOH over 800 mL). Pure fractions were combined, evaporated under reduced pressure and dried under high vacuum to give the title compound (86% yield) as a yellow oil. 1H NMR (400 MHz, METHANOL-d4) δ ppm 7.57 (s, 1H), 5.62-5.70 (m, 1H), 5.59 (s, 2H), 4.11-4.19 (m, 2H), 3.74-3.82 (m, 2H), 3.62 (d, J=8.20 Hz, 2H), 2.15-2.24 (m, 2H), 1.91-2.01 (m, 2H), 0.90-0.98 (m, 2H), 0.00 (s, 9H); MS (ESI) m/z 510.2 [M+1]+.

Workup

  1. concentrationThe reaction mixture was concentrated
  2. extractionextracted with ethyl acetate/H2O
  3. customevaporated under reduced pressure
  4. custompurified by silica-gel chromatography (0-50% hexane:ethyl acetate over 800 mL)
  5. customevaporated under reduced pressure
  6. customdried under high vacuum

Sources & evidence

ORD record
ord-879be9e7d923420b996e5b09956e9a8b
Source dataset
uspto-grants-2016_08
Patent number
US09428509B2

Reaction notes

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