Tetrahydrofuran → 3-(6-Chloro-pyridin-3-ylmethyl)-1-triisopropylsilanyl-1H-pyrrolo[2,3-b]pyridine

HRID 1754630Notes

Reaction equation

HRID 1754630 reaction equation
I[C:2]1[CH:3]=[CH:4][C:5]([Cl:8])=[N:6][CH:7]=1.O1CCCC1.C([Mg]Cl)(C)C.C([Cu])#N.P(OC)(OC)OC.Cl[CH2:30][C:31]1[C:39]2[C:34](=[N:35][CH:36]=[CH:37][CH:38]=2)[N:33]([Si:40]([CH:47]([CH3:49])[CH3:48])([CH:44]([CH3:46])[CH3:45])[CH:41]([CH3:43])[CH3:42])[CH:32]=1>O.C1(C)C=CC=CC=1.CCCCCC.C(OCC)(=O)C>[Cl:8][C:5]1[N:6]=[CH:7][C:2]([CH2:30][C:31]2[C:39]3[C:34](=[N:35][CH:36]=[CH:37][CH:38]=3)[N:33]([Si:40]([CH:41]([CH3:43])[CH3:42])([CH:47]([CH3:49])[CH3:48])[CH:44]([CH3:46])[CH3:45])[CH:32]=2)=[CH:3][CH:4]=1

Participants

10

Reactant 6

HCID 8028Tetrahydrofuran3×HCID 8472Trimethyl phosphiteHCID 43971762-Chloro-5-iodopyridineHCID 497589211H-Pyrrolo[2,3-B]pyridine, 3-(chloromethyl)-1-[tris(1-methylethyl)silyl]-HCID 178418546HCID 178418546, compoundHCID 178418918HCID 178418918, compound

Product 1

HCID 575880773-(6-Chloro-pyridin-3-ylmethyl)-1-triisopropylsilanyl-1H-pyrrolo[2,3-b]pyridineYield 59%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1140TolueneSolventHCID 21226206Ethyl acetate hexaneSolvent

Conditions

Temperature
40 °C

Procedure

Into a round bottom flask was added 5-iodo-2-chloro-pyridine (315.0 mg, 1.32 mmol) and tetrahydrofuran (12.0 mL, 0.15 mol) at −40° C. under an atmosphere of nitrogen. Into the reaction 2.0 M of isopropylmagnesium chloride in tetrahydrofuran (0.72 mL, 1.44 mmol) was added. The reaction mixture was stirred for 40 minutes at 40° C. TLC (hexane/ethyl acetate 2:1) indicated no starting material. Into the reaction mixture 0.6 M of CuCN.2LiCl in tetrahydrofuran (2.4 mL, 1.44 mmol) was added. The reaction mixture was allowed to come to room temperature for 5 minutes and trimethyl phosphite (0.29 mL, 2.4 mmol) was added. After 10 minutes, this solution was added into a round bottom flask containing compound 5 (315.0 mg) and toluene (8.0 mL). The reaction was stirred at 20° C. for 40 hours. The reaction mixture was poured into water and the compound extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate, concentrated and purified with biotage (dichloromethane/methanol 1:10) to give compound 6 (230 mg, yield=59.0%) as a white solid. Compound 6a (3-(6-Bromo-pyridin-3-ylmethyl)-1-triisopropylsilanyl-1H-pyrrolo[2,3-b]pyridine) (MS (ESI) [M+H+]+=288.1, 290.1) was prepared substituting 5-iodo-2-chloro-pyridine with 5-iodo-2-bromo-pyridine in Step 4, with reaction conditions and work up procedure the same as that for the synthesis of compound 6.

Workup

  1. additionwas added
  2. waitto come to room temperature for 5 minutes
  3. waitAfter 10 minutes
  4. additionthis solution was added into a round bottom flask
  5. stirringThe reaction was stirred at 20° C. for 40 hours
  6. extractionthe compound extracted with ethyl acetate
  7. washThe organic layer was washed with brine
  8. dry with materialdried over sodium sulfate
  9. concentrationconcentrated
  10. custompurified with biotage (dichloromethane/methanol 1:10)

Sources & evidence

ORD record
ord-ae52015bfaf2415ea6a86c9d2e924957
Source dataset
uspto-grants-2015_10
Patent number
US09169250B2

Reaction notes

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