Sodium Carbonate → HCID 86679634, compound

HRID 577692Notes

Reaction equation

HRID 577692 reaction equation
[Cl:1][C:2]1[N:3]=[C:4]([O:20][C:21]2[CH:26]=[CH:25][CH:24]=[C:23]([N+:27]([O-:29])=[O:28])[CH: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:30]1[CH:35]=[CH:34][CH:33]=[C:32](B(O)O)[CH:31]=1.O1CCOCC1.C([O-])([O-])=O.[Na+].[Na+]>C(OCC)(=O)C.O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[Cl:1][C:2]1[N:3]=[C:4]([O:20][C:21]2[CH:26]=[CH:25][CH:24]=[C:23]([N+:27]([O-:29])=[O:28])[CH:22]=2)[C:5]2[C:10]([C:32]3[CH:31]=[N:30][CH:35]=[CH:34][CH:33]=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

8

Reactant 4

HCID 10340Sodium CarbonateHCID 312751,4-DioxaneHCID 27343783-Pyridinylboronic acid2×HCID 86679635HCID 86679635, compound

Product 1

HCID 86679634HCID 86679634, compoundYield 88%

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a vial was added 2-chloro-5-iodo-4-(3-nitrophenoxy)-7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidine (333.7 mg, 0.61 mmol), pyridin-3-ylboronic acid (79 mg, 0.64 mmol, 1.05 mol eq), 1,4-dioxane (4 mL), water (1 mL), Na2CO3 (78 mg, 0.73 mmol, 1.2 mol eq) and Pd(PPh3)2Cl2 (21 mg, 0.05 mol eq). The reaction vial was capped, stirred at rt for 1 hr and was then heated to 60° C. (block temperature) for 2 days (note: the reaction progress was monitored by LCMS after couple hours and more pyridin-3-ylboronic acid was added as needed). The reaction was diluted with ethyl acetate (100 mL) and water (20 mL) and the organic layer was separated, washed with water (20 mL) and brine (20 mL), dried over Na2SO4 and evaporated to give crude product (TLC: Rf 0.3 in 50% ethyl acetate-50% heptane). The crude product was purified on silica gel to give the title compound as a light yellow solid (266 mg, 88% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 9.01 (d, J=2.01 Hz, 1H) 8.54 (dd, J=4.78, 1.51 Hz, 1H) 8.38 (t, J=2.14 Hz, 1H) 8.23 (dd, J=8.06, 2.01 Hz, 2H) 8.15 (s, 1H) 7.86-7.93 (m, 1H) 7.77-7.85 (m, 1H) 7.50 (dd, J=7.93, 4.66 Hz, 1H) 5.68 (s, 2H) 3.58-3.74 (m, 2H) 0.83-1.02 (m, 2H) 0.00 (s, 9H). m/z (APCI+) for C23H24ClN5O4Si 498.0 (M+H)+.

Workup

  1. customThe reaction vial was capped
  2. temperaturewas then heated to 60° C. (block temperature) for 2 days (note
  3. additionwas added
  4. customthe organic layer was separated
  5. washwashed with water (20 mL) and brine (20 mL)
  6. dry with materialdried over Na2SO4
  7. customevaporated
  8. customto give crude product (TLC: Rf 0.3 in 50% ethyl acetate-50% heptane)
  9. customThe crude product was purified on silica gel

Sources & evidence

ORD record
ord-b14f05ae000641a88b31bcfc9a8e9a32
Source dataset
uspto-grants-2015_05
Patent number
US09040547B2

Reaction notes

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