Lithium borohydride → HCID 9823354, compound

HRID 722009Notes

Reaction equation

HRID 722009 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([N:24]2[CH:28]=[CH:27][C:26]([C:29](OC)=[O:30])=[N:25]2)[CH:5]=[CH:6][C:7]=1[C:8]([N:10]1[C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][C:15]=2[CH2:14][N:13]2[CH:21]=[CH:22][CH:23]=[C:12]2[CH2:11]1)=[O:9].[BH4-].[Li+]>O1CCCC1>[Cl:1][C:2]1[CH:3]=[C:4]([N:24]2[CH:28]=[CH:27][C:26]([CH2:29][OH:30])=[N:25]2)[CH:5]=[CH:6][C:7]=1[C:8]([N:10]1[C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][C:15]=2[CH2:14][N:13]2[CH:21]=[CH:22][CH:23]=[C:12]2[CH2:11]1)=[O:9]

Participants

4

Reactant 2

HCID 4148881Lithium borohydrideHCID 21882345HCID 21882345, compound

Product 1

HCID 9823354HCID 9823354, compoundYield 37%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A stirred solution of methyl 1-[3-chloro-4-(5H-pyrrolo[2,1-c][1,4]benzodiazepin-10(11H)-ylcarbonyl)phenyl]-1H-pyrazole-3-carboxylate (0.14 g, 0.31 mmol) in tetrahydrofuran (5 mL) was heated at reflux and treated with a solution of 2.0 M lithium borohydride in tetrahydrofuran (3 mL, 6.0 mmol) in three 1 mL aliquots over 1.5 hours. After cooling to room temperature, the reaction was quenched with 2 N hydrochloric acid, and extracted with ethyl acetate (3×). The combined organic phase was washed with water, dried over anhydrous sodium sulfate, filtered, and evaporated in vacuo to a residue. Trituration of the residue with a mixture of methyl tert-butyl ether and hexane afforded a white amorphous powder which was purified by preparative normal phase high-performance liquid chromatography on a Primesphere® silica gel column (50 mm×250 mm), eluting with 100% methyl tert-butyl ether at a flow rate of 70 mL/min. to yield, after evaporation of the solvent, the title compound (0.05 g, 0.11 mmol, 37%) as a colorless amorphous solid, m.p. 85° C.;

Workup

  1. temperatureat reflux
  2. customthe reaction was quenched with 2 N hydrochloric acid
  3. extractionextracted with ethyl acetate (3×)
  4. washThe combined organic phase was washed with water
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. customevaporated in vacuo to a residue
  8. additionTrituration of the residue with a mixture of methyl tert-butyl ether and hexane
  9. customafforded a white amorphous powder which
  10. customwas purified by preparative normal phase high-performance liquid chromatography on a Primesphere® silica gel column (50 mm×250 mm)
  11. washeluting with 100% methyl tert-butyl ether at a flow rate of 70 mL/min.
  12. customto yield
  13. customafter evaporation of the solvent

Sources & evidence

ORD record
ord-0bfb164fbe024526b851be29837bbb6d
Source dataset
uspto-grants-2006_11
Patent number
US07138393B2

Reaction notes

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