5-Fluoro-3-iodo-1-triisopropylsilanyl-1H-pyrrolo[2,3-b]pyridine → [5-(3-chloro-benzylamino)-2-methyl-2H-pyrazol-3-yl]-(5-fluoro-1-triisopropylsilanyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-methanol

HRID 509992Notes

Reaction equation

HRID 509992 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:10](I)=[CH:9][N:8]([Si:12]([CH:19]([CH3:21])[CH3:20])([CH:16]([CH3:18])[CH3:17])[CH:13]([CH3:15])[CH3:14])[C:5]2=[N:6][CH:7]=1.C([Mg]Cl)(C)C.[Cl:27][C:28]1[CH:29]=[C:30]([CH:41]=[CH:42][CH:43]=1)[CH2:31][NH:32][C:33]1[CH:34]=[C:35]([CH:39]=[O:40])[N:36]([CH3:38])[N:37]=1>O1CCCC1>[Cl:27][C:28]1[CH:29]=[C:30]([CH:41]=[CH:42][CH:43]=1)[CH2:31][NH:32][C:33]1[CH:34]=[C:35]([CH:39]([C:10]2[C:4]3[C:5](=[N:6][CH:7]=[C:2]([F:1])[CH:3]=3)[N:8]([Si:12]([CH:19]([CH3:21])[CH3:20])([CH:16]([CH3:18])[CH3:17])[CH:13]([CH3:15])[CH3:14])[CH:9]=2)[OH:40])[N:36]([CH3:38])[N:37]=1

Participants

5

Reactant 3

HCID 242292305-Fluoro-3-iodo-1-triisopropylsilanyl-1H-pyrrolo[2,3-b]pyridineHCID 576191725-(3-chloro-benzylamino)-2-methyl-2H-pyrazole-3-carbaldehydeHCID 178418918HCID 178418918, compound

Product 1

HCID 58259270[5-(3-chloro-benzylamino)-2-methyl-2H-pyrazol-3-yl]-(5-fluoro-1-triisopropylsilanyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-methanol

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-20 °C

Procedure

5-Fluoro-3-iodo-1-triisopropylsilanyl-1H-pyrrolo[2,3-b]pyridine (146, 0.33 g, 0.79 mmol) and 1.5 mL of tetrahydrofuran were combined in a round bottom flask and cooled to −20° C. Isopropylmagnesium chloride (400 μL, 2.0 M in tetrahydrofuran, 0.8 mmol) was added dropwise and the reaction stirred and brought to −5° C. The reaction was cooled to −20° C. and 5-(3-chloro-benzylamino)-2-methyl-2H-pyrazole-3-carbaldehyde (145, 0.090 g, 0.36 mmol) in tetrahydrofuran was added and the reaction stirred and brought to 0° C. The reaction was concentrated under vacuum, diluted with ethyl acetate and washed with saturated aqueous sodium bicarbonate, then brine. The organic layer was separated and dried over sodium sulfate, filtered and the filtrate purified by silica gel flash column chromatography eluting with a gradient of 5-80% ethyl acetate in hexane. Appropriate fractions were combined and concentrated under vacuum to provide the desired compound. MS (ESI) [M+H+]+=542.7, 543.95.

Workup

  1. custombrought to −5° C
  2. temperatureThe reaction was cooled to −20° C.
  3. stirringthe reaction stirred
  4. custombrought to 0° C
  5. concentrationThe reaction was concentrated under vacuum
  6. additiondiluted with ethyl acetate
  7. washwashed with saturated aqueous sodium bicarbonate
  8. customThe organic layer was separated
  9. dry with materialdried over sodium sulfate
  10. filtrationfiltered
  11. customthe filtrate purified by silica gel flash column chromatography
  12. washeluting with a gradient of 5-80% ethyl acetate in hexane
  13. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-76d31f5bef634ee982e54297870b4cf8
Source dataset
uspto-grants-2015_08
Patent number
US09096593B2

Reaction notes

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