1H-Benzotriazole-1-methanol → HCID 59257892, compound

HRID 1094117Notes

Reaction equation

HRID 1094117 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]2[C:17](=[CH:18][CH:19]=1)[CH2:16][C:6]1([C:14]3[C:9](=[N:10][CH:11]=[CH:12][CH:13]=3)[NH:8][C:7]1=[O:15])[CH2:5]2.O[CH2:21]N1C2C=CC=CC=2N=N1.[BH4-].[Na+]>CCO.CN(C=O)C>[CH3:21][NH:1][C:2]1[CH:3]=[C:4]2[C:17](=[CH:18][CH:19]=1)[CH2:16][C:6]1([C:14]3[C:9](=[N:10][CH:11]=[CH:12][CH:13]=3)[NH:8][C:7]1=[O:15])[CH2:5]2

Participants

6

Reactant 3

HCID 2241691H-Benzotriazole-1-methanolHCID 4311764Sodium borohydrideHCID 591667225-amino-1,3-dihydrospiro[indene-2,3'-pyrrolo[2,3-b]pyridin]-2'(1'H)-one2×

Product 1

HCID 59257892HCID 59257892, compound

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of (−)-5-amino-1,3-dihydrospiro[indene-2,3′-pyrrolo[2,3-b]pyridin]-2′(1′H)-one (154 mg, 0.613 mmol, described in Intermediate 3) and 1-(hydroxymethyl)benzotriazole (93 mg, 0.625 mmol) in EtOH (2 mL) and DMF (0.2 mL) was heated at reflux for 4 h, then concentrated to dryness under reduced pressure. The residue was resuspended in THF (3 mL) and sodium borohydride (40 mg, 1.05 mmol) was added. The resulting mixture was heated to 70° C. for 6 h then quenched with H2O (50 mL) and extracted with EtOAc (50 mL). The organic extract was dried over Na2SO4, filtered, and concentrated in vacuo. The crude product was purified by silica gel chromatography, eluting with a gradient of CH2Cl2:MeOH—100:0 to 80:20, to give the title compound, which was of sufficient purity for use in the next step. MS: m/z=266 (M+1).

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 4 h
  3. concentrationconcentrated to dryness under reduced pressure
  4. customthen quenched with H2O (50 mL)
  5. extractionextracted with EtOAc (50 mL)
  6. extractionThe organic extract
  7. dry with materialwas dried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe crude product was purified by silica gel chromatography
  11. washeluting with a gradient of CH2Cl2

Sources & evidence

ORD record
ord-3dae26b40a6248d3b6e70672ea8f897d
Source dataset
uspto-grants-2012_03
Patent number
US08133891B2

Reaction notes

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