(S)-(+)-3-Hydroxytetrahydrofuran → (S)-6-(2-Chloro-4-((tetrahydrofuran-3-yl)oxy)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-2-methylbenzo[d]oxazole

HRID 529666Notes

Reaction equation

HRID 529666 reaction equation
[Cl:1][C:2]1[N:3]=[C:4](Cl)[C:5]2[C:10]([C:11]3[CH:20]=[CH:19][C:14]4[N:15]=[C:16]([CH3:18])[O:17][C:13]=4[CH:12]=3)=[CH:9][N:8]([CH2:21][O:22][CH2:23][CH2:24][Si:25]([CH3:28])([CH3:27])[CH3:26])[C:6]=2[N:7]=1.[O:30]1[CH2:34][CH2:33][C@H:32]([OH:35])[CH2:31]1.CC(C)([O-])C.[Na+]>O1CCOCC1>[Cl:1][C:2]1[N:3]=[C:4]([O:35][C@H:32]2[CH2:33][CH2:34][O:30][CH2:31]2)[C:5]2[C:10]([C:11]3[CH:20]=[CH:19][C:14]4[N:15]=[C:16]([CH3:18])[O:17][C:13]=4[CH:12]=3)=[CH:9][N:8]([CH2:21][O:22][CH2:23][CH2:24][Si:25]([CH3:28])([CH3:26])[CH3:27])[C:6]=2[N:7]=1

Participants

5

Reactant 3

HCID 2733227(S)-(+)-3-HydroxytetrahydrofuranHCID 23676156Sodium t-butoxideHCID 867264196-(2,4-Dichloro-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-2-methylbenzo[d]oxazole

Product 1

HCID 86726440(S)-6-(2-Chloro-4-((tetrahydrofuran-3-yl)oxy)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-2-methylbenzo[d]oxazoleYield 90%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
75 °C

Procedure

To a solution of 6-(2,4-dichloro-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-2-methylbenzo[d]oxazole (1 equiv), (S)-tetrahydrofuran-3-ol (1.1 equiv) in 1,4-dioxane (0.2 M) was added sodium tert-butoxide (1.1 equiv). The reaction was stirred at 75° C. for 5 h. The reaction mixture was quenched with saturated aqueous sodium chloride and then washed with ethyl acetate. The organic phase was combined and washed with saturated aqueous sodium chloride. The organic layer was dried (magnesium sulfate), filtered, and concentrated. The crude was purified by silica gel column chromatography (0-90%) ethyl acetate in hexane) to give the title compound (90% yield) as yellow solid; 1H NMR (400 MHz, DMSO-d6) δ ppm −0.07 (s, 9H) 0.84-0.90 (m, 2H) 1.99-2.10 (m, 1H) 2.26 (dtd, J=13.96, 8.25, 8.25, 6.25 Hz, 1 H) 2.63 (s, 3 H) 3.53-3.62 (m, 2 H) 3.73-3.81 (m, 2 H) 3.84 (d, J=10.54 Hz, 1 H) 3.93 (dd, J=10.54, 4.30 Hz, 1 H) 5.57 (s, 2 H) 5.72-5.80 (m, 1 H) 7.59-7.64 (m, 1 H) 7.66 (d, J=8.59 Hz, 1 H) 7.89 (s, 1 H) 7.91 (d, J=0.78 Hz, 1 H); MS (ESI) m/z 501.1 [M+1]+.

Workup

  1. customThe reaction mixture was quenched with saturated aqueous sodium chloride
  2. washwashed with ethyl acetate
  3. washwashed with saturated aqueous sodium chloride
  4. dry with materialThe organic layer was dried (magnesium sulfate)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude was purified by silica gel column chromatography (0-90%) ethyl acetate in hexane)

Sources & evidence

ORD record
ord-2ca41efeab854150ae7983f768bde9fa
Source dataset
uspto-grants-2016_05
Patent number
US09346812B2

Reaction notes

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