Borane → HCID 178433849, compound

HRID 628423Notes

Reaction equation

HRID 628423 reaction equation
[CH3:1][C:2]1[N:6]2[C:7]3[CH:13]=[C:12]([C:14]4[CH:18]=[CH:17][NH:16][N:15]=4)[N:11]([CH2:19][C:20]4[CH:21]=[C:22]([CH:26]=[CH:27][CH:28]=4)[C:23](O)=[O:24])[C:8]=3[CH:9]=[CH:10][C:5]2=[N:4][N:3]=1.B>C1COCC1>[CH3:1][C:2]1[N:6]2[C:7]3[CH:13]=[C:12]([C:14]4[CH:18]=[CH:17][NH:16][N:15]=4)[N:11]([CH2:19][C:20]4[CH:21]=[C:22]([CH2:23][OH:24])[CH:26]=[CH:27][CH:28]=4)[C:8]=3[CH:9]=[CH:10][C:5]2=[N:4][N:3]=1

Participants

4

Reactant 2

HCID 6331Borane2×HCID 178433850HCID 178433850, compound

Product 1

HCID 178433849HCID 178433849, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

A mixture of 3-{[1-methyl-7-(1H-pyrazol-3-yl)-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyridin-6-yl]methyl}benzoic acid (0.40 g, from Step 5) in THF (40. mL) at 0° C. was treated with 1.0 M borane in THF (1.7 mL, 1.7 mmol, Aldrich) dropwise. The mixture was stirred for 1.5 hours, with warming to room temperature. Additional 1.0 M borane in THF (45 mL, 45 mmol) was added portionwise to the reaction mixture at room temperature over the course of 48 hours. The reaction mixture was cooled to 0° C. and cautiously quenched by the dropwise addition of water, followed by the addition of 1N HCl (55 mL). The mixture was then neutralized by the addition of solid NaHCO3, and the product was extracted with 10% iPrOH in CHCl3. Precipitate was dissolved in MeOH and combined with the organic extracts. The resulting solution was dried over sodium sulfate, filtered and concentrated. The product was purified by flash chromatography, eluting with a gradient from 0-10% MeOH in DCM. Yield: (0.12 g, 31%).

Workup

  1. temperatureThe reaction mixture was cooled to 0° C.
  2. customcautiously quenched by the dropwise addition of water
  3. additionfollowed by the addition of 1N HCl (55 mL)
  4. additionThe mixture was then neutralized by the addition of solid NaHCO3
  5. extractionthe product was extracted with 10% iPrOH in CHCl3
  6. dissolutionPrecipitate was dissolved in MeOH
  7. dry with materialThe resulting solution was dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe product was purified by flash chromatography
  11. washeluting with a gradient from 0-10% MeOH in DCM

Sources & evidence

ORD record
ord-302c711d63fb478e8ba802862b9a3a08
Source dataset
uspto-grants-2016_04
Patent number
US09309246B2

Reaction notes

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