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

HRID 529661Notes

Reaction equation

HRID 529661 reaction equation
[Cl:1][C:2]1[N:3]=[C:4]([O:20][CH:21]2[CH2:26][CH2:25][O:24][CH2:23][CH2:22]2)[C:5]2[C:10](I)=[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.[N:27]1[CH:32]=[CH:31][C:30](B(O)O)=[CH:29][CH:28]=1.O1CCOCC1.C(=O)([O-])[O-].[Na+].[Na+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>[Cl:1][C:2]1[N:3]=[C:4]([O:20][CH:21]2[CH2:26][CH2:25][O:24][CH2:23][CH2:22]2)[C:5]2[C:10]([C:30]3[CH:31]=[CH:32][N:27]=[CH:28][CH:29]=3)=[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

7

Reactant 4

HCID 10340Sodium CarbonateHCID 312751,4-DioxaneHCID 2734379(Pyridin-4-yl)boronic acidHCID 867264332-Chloro-5-iodo-4-((tetrahydro-2H-pyran-4-yl)oxy)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidine

Product 1

HCID 867264362-Chloro-5-(pyridin-4-yl)-4-((tetrahydro-2H-pyran-4-yl)oxy)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidineYield 50.5%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
75 °C

Procedure

To a solution of 2-chloro-5-iodo-4-((tetrahydro-2H-pyran-4-yl)oxy)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidine (1 equiv), pyridin-4-ylboronic acid (1.1 equiv), tetrakis(triphenylphosphine)palladium(0) (0.1 equiv) in a 5:1 mixture of 1,4-dioxane and water (0.17 M) was added sodium carbonate (2.1 equiv). The reaction was stirred at 75° C. for 3 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 product was purified by silica gel column chromatography (0-90%) ethyl acetate (with 10% 1N ammonia in methanol) in hexane) to give the title compound (50.5% yield) as a yellow oil. 1H NMR (400 MHz, DMSO-d6) δ ppm −0.06 (s, 9 H) 0.82-0.91 (m, 2 H) 1.74 (dtd, J=12.74, 8.37, 8.37, 3.71 Hz, 2 H) 2.01-2.16 (m, 2 H) 3.50-3.63 (m, 4 H) 3.69-3.83 (m, 2 H) 5.50 (tt, J=7.91, 3.81 Hz, 1 H) 5.59 (s, 2 H) 7.72 (d, J=6.25 Hz, 2 H) 8.12 (s, 1 H) 8.60 (d, J=6.25 Hz, 2 H); MS (ESI) m/z 461.0 [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 product was purified by silica gel column chromatography (0-90%) ethyl acetate (with 10% 1N ammonia in methanol) in hexane)

Sources & evidence

ORD record
ord-30040f90986b47c7a6a9edaef5df5ded
Source dataset
uspto-grants-2016_05
Patent number
US09346812B2

Reaction notes

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