1-(2-{[tert-butyl(dimethyl)silyl]oxy}-1,1-dimethylethyl)-3-iodo-1H-pyrrolo[3,2-c]pyridine → [1-(2-{[tert-butyl(methyl)silyl]oxyl}-1,1-dimethylethyl)-1H-pyrrolo[3,2-c]pyridin-3-yl](4-chloropyridin-2-yl)methanone

HRID 1753054Notes

Reaction equation

HRID 1753054 reaction equation
[Si:1]([O:8][CH2:9][C:10]([N:13]1[C:21]2[CH:20]=[CH:19][N:18]=[CH:17][C:16]=2[C:15](I)=[CH:14]1)([CH3:12])[CH3:11])([C:4]([CH3:7])([CH3:6])[CH3:5])(C)[CH3:2].C([Mg]Cl)(C)C.[Cl:28][C:29]1[CH:34]=[CH:33][N:32]=[C:31]([C:35](NOC)=[O:36])[C:30]=1C>C1COCC1>[C:4]([SiH:1]([CH3:2])[O:8][CH2:9][C:10]([N:13]1[C:21]2[CH:20]=[CH:19][N:18]=[CH:17][C:16]=2[C:15]([C:35]([C:31]2[CH:30]=[C:29]([Cl:28])[CH:34]=[CH:33][N:32]=2)=[O:36])=[CH:14]1)([CH3:11])[CH3:12])([CH3:5])([CH3:6])[CH3:7]

Participants

5

Reactant 3

HCID 900934361-(2-{[tert-butyl(dimethyl)silyl]oxy}-1,1-dimethylethyl)-3-iodo-1H-pyrrolo[3,2-c]pyridineHCID 900937914-chloro-N-methoxy-M-methylpicolinamideHCID 178418918HCID 178418918, compound

Product 1

HCID 137331321[1-(2-{[tert-butyl(methyl)silyl]oxyl}-1,1-dimethylethyl)-1H-pyrrolo[3,2-c]pyridin-3-yl](4-chloropyridin-2-yl)methanoneYield 60.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-5 °C

Procedure

1-(2-{[tert-butyl(dimethyl)silyl]oxy}-1,1-dimethylethyl)-3-iodo-1H-pyrrolo[3,2-c]pyridine (Preparation 65, 3.99 g, 9.06 mmol) was dissolved in THF (75 mL) and the solution was degassed and cooled to −5° C. 2M iPrMgCl in THF (5.44 mL, 10.9 mmol) was added dropwise and the resulting yellow solution stirred at this temperature for 45 minutes. A solution of 4-chloro-N-methoxy-M-methylpicolinamide (2.18 g, 10.9 mmol) in THF (20 mL) was added dropwise and the reaction allowed to warm to room temperature for 4.5 hours. The reaction was partitioned between saturated aqueous ammonium chloride solution (30 mL) and EtOAc (50 mL), the organic layer was collected, dried and concentrated in vacuo. The residue was purified using silica gel column chromatography eluting with 0-90% EtOAc in DCM to afford the title compound as an orange oil (2.37 g, 59%). Taken on to the next step directly.

Workup

  1. customthe solution was degassed
  2. temperatureto warm to room temperature for 4.5 hours
  3. customThe reaction was partitioned between saturated aqueous ammonium chloride solution (30 mL) and EtOAc (50 mL)
  4. customthe organic layer was collected
  5. customdried
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified
  8. washeluting with 0-90% EtOAc in DCM

Sources & evidence

ORD record
ord-b20284d6cfa7497f97132974f2aeadcc
Source dataset
uspto-grants-2015_10
Patent number
US09163021B2

Reaction notes

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