5-(3-chloro-benzylamino)-2-methyl-2H-pyrazole-3-carbaldehyde → [5-(3-chloro-benzylamino)-2-methyl-2H-pyrazol-3-yl]-(5-chloro-1-triisopropylsilanyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-methanol

HRID 1024322Notes

Reaction equation

HRID 1024322 reaction equation
[Cl: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]([Cl: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 576191725-(3-chloro-benzylamino)-2-methyl-2H-pyrazole-3-carbaldehydeHCID 580879285-chloro-3-iodo-1-(triisopropylsilyl)-1H-pyrrolo[2,3-b]pyridineHCID 178418918HCID 178418918, compound

Product 1

HCID 66971157[5-(3-chloro-benzylamino)-2-methyl-2H-pyrazol-3-yl]-(5-chloro-1-triisopropylsilanyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-methanolYield 30%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-20 °C

Procedure

5-Chloro-3-iodo-1-triisopropylsilanyl-1H-pyrrolo[2,3-b]pyridine (629, 0.19 g, 0.44 mmol) was dissolved in tetrahydrofuran (0.9 mL). The solution was cooled to −20° C. 2M isopropylmagnesium chloride in tetrahydrofuran (200 μL) was added dropwise to the mixture, then stirred to −5° C. After the reaction was cooled to −20° C., 5-(3-chloro-benzylamino)-2-methyl-2H-pyrazole-3-carbaldehyde (648, 0.050 g, 0.20 mmol) in 2 mL of tetrahydrofuran was added at once to the mixture. The reaction was stirred to 0° C. and then concentrated. Ethyl acetate was added and the mixture was washed with sodium bicarbonate saturated solution and brine. The organic portion was dried over anhydrous sodium sulfate and concentrated. Purification with silica gel column chromatography eluting with a gradient of ethyl acetate (5-80%) in hexane gave the desired compound (649, 0.033 g, 30%). (ESI) [M+H+]+=558.3, 560.9.

Workup

  1. temperatureAfter the reaction was cooled to −20° C.
  2. stirringThe reaction was stirred to 0° C.
  3. concentrationconcentrated
  4. additionEthyl acetate was added
  5. washthe mixture was washed with sodium bicarbonate saturated solution and brine
  6. dry with materialThe organic portion was dried over anhydrous sodium sulfate
  7. concentrationconcentrated
  8. customPurification with silica gel column chromatography
  9. washeluting with a gradient of ethyl acetate (5-80%) in hexane

Sources & evidence

ORD record
ord-8448ab8d6cc24ff68c35a3ea64585c16
Source dataset
uspto-grants-2014_05
Patent number
US08722702B2

Reaction notes

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