Water → [2-fluoro-6-(6-methoxy-pyridin-3-ylamino)-pyridin-3-yl]-(5-methyl-1-triisopropylsilanyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-methanol

HRID 1396164Notes

Reaction equation

HRID 1396164 reaction equation
I[C:2]1[C:10]2[C:5](=[N:6][CH:7]=[C:8]([CH3:11])[CH:9]=2)[N:4]([Si:12]([CH:19]([CH3:21])[CH3:20])([CH:16]([CH3:18])[CH3:17])[CH:13]([CH3:15])[CH3:14])[CH:3]=1.C([Mg]Cl)(C)C.[F:27][C:28]1[C:33]([CH:34]=[O:35])=[CH:32][CH:31]=[C:30]([NH:36][C:37]2[CH:38]=[N:39][C:40]([O:43][CH3:44])=[CH:41][CH:42]=2)[N:29]=1.O>O1CCCC1>[F:27][C:28]1[C:33]([CH:34]([C:2]2[C:10]3[C:5](=[N:6][CH:7]=[C:8]([CH3:11])[CH:9]=3)[N:4]([Si:12]([CH:19]([CH3:21])[CH3:20])([CH:16]([CH3:18])[CH3:17])[CH:13]([CH3:15])[CH3:14])[CH:3]=2)[OH:35])=[CH:32][CH:31]=[C:30]([NH:36][C:37]2[CH:38]=[N:39][C:40]([O:43][CH3:44])=[CH:41][CH:42]=2)[N:29]=1

Participants

6

Reactant 4

HCID 962WaterHCID 582588923-iodo-5-methyl-1-triisopropylsilanyl-1H-pyrrolo[2,3-b]pyridineHCID 584857752-Fluoro-6-(6-methoxy-pyridin-3-ylamino)-pyridine-3-carbaldehydeHCID 178418918HCID 178418918, compound

Product 1

HCID 67447101[2-fluoro-6-(6-methoxy-pyridin-3-ylamino)-pyridin-3-yl]-(5-methyl-1-triisopropylsilanyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-methanolYield 92.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
5 °C

Procedure

To a solution of 3-iodo-5-methyl-1-triisopropylsilanyl-1H-pyrrolo[2,3-b]pyridine (8, 1.02 g, 2.461 mmol) in 6.0 mL of tetrahydrofuran at −50° C. under nitrogen, isopropylmagnesium chloride (1.23 mL, 2.00 M in tetrahydrofuran, 2.46 mmol) is added slowly. The reaction is allowed to warm to 5° C. over 70 minutes, then cooled to −45° C., followed by addition of 2-fluoro-6-(6-methoxy-pyridin-3-ylamino)-pyridine-3-carbaldehyde (56, 0.165 g, 0.667 mmol) in 2.0 mL of tetrahydrofuran. The reaction is allowed to warm to room temperature over an hour, then poured into water and extracted with ethyl acetate. The organic layer is dried over sodium sulfate, filtered and the filtrate concentrated under vacuum. The resulting material is purified by silica gel column chromatography eluting with 20-100% ethyl acetate in hexane. Appropriate fractions are combined and concentrated under vacuum to provide the desired compound (68, 330 mg). MS (ESI) [M+H+]+=536.2.

Workup

  1. temperaturecooled to −45° C.
  2. temperatureto warm to room temperature over an hour
  3. extractionextracted with ethyl acetate
  4. dry with materialThe organic layer is dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationthe filtrate concentrated under vacuum
  7. customThe resulting material is purified by silica gel column chromatography
  8. washeluting with 20-100% ethyl acetate in hexane
  9. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-e4670b88107244e2abc5bc0f8d0a2b3e
Source dataset
uspto-grants-2014_12
Patent number
US08901118B2

Reaction notes

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