Acetic Acid → HCID 58365159, compound

HRID 60338Notes

Reaction equation

HRID 60338 reaction equation
[CH:1](=O)[CH3:2].[CH2:4]([O:11][C:12]([N:14]1[C:18]2[CH:19]=[N:20][CH:21]=[C:22]([O:23][CH:24]3[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]3)[C:17]=2[C:16]2[CH:30]=[C:31]([Br:34])[CH:32]=[N:33][C:15]1=2)=[O:13])[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(O)(=O)C>CO.ClCCl>[CH2:4]([O:11][C:12]([N:14]1[C:18]2[CH:19]=[N:20][CH:21]=[C:22]([O:23][CH:24]3[CH2:29][CH2:28][N:27]([CH2:1][CH3:2])[CH2:26][CH2:25]3)[C:17]=2[C:16]2[CH:30]=[C:31]([Br:34])[CH:32]=[N:33][C:15]1=2)=[O:13])[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 177AcetaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 58364993HCID 58364993, compound

Product 1

HCID 58365159HCID 58365159, compoundYield 61.3%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

Acetaldehyde (3M solution in dichloromethane, 0.16 mL, 0.48 mmol) was added to a mixture of 3-bromo-5-(piperidin-4-yloxy)-dipyrido[2,3-b;4′,3′-d]pyrrole-9-carboxylic acid benzyl ester (116 mg, 0.24 mmol), sodium triacetoxyborohydride (77 mg, 0.36 mmol) and acetic acid (17 OL, 0.29 mmol) in methanol (3 mL) and dichloromethane (1 mL) and the mixture stirred for 18 hours. The solvent was evaporated and the resultant residue diluted with saturated aqueous sodium hydrogen carbonate solution (20 mL) and extracted with dichloromethane (3×30 mL). The combined organic layer was dried (Na2SO4), filtered and evaporated to give a residue. The resultant residue was purified by flash chromatography (silica, 12 g cartridge, ISCO, 0-8% methanol in dichloromethane). The appropriate fractions were collected and evaporated to afford the title compound as a light yellow solid (75 mg, 61%). LCMS (Method B): RT=3.43 min, M+H+=509/511. 1H NMR (400 MHz, CDCl3): 9.23 (s, 1H), 8.77 (d, J=2.3 Hz, 1H), 8.62 (s, 1H), 8.31 (s, 1H), 7.60-7.60 (m, 2H), 7.40-7.40 (m, 3H), 5.63 (s, 2H), 4.85 (s, 1H), 2.91 (br s, 2H), 2.62 (br s, 2H), 2.33 (br s, 2H), 2.14 (br s, 2H), 1.59 (br s, 2H), 1.23 (br s, 3H).

Workup

  1. customThe solvent was evaporated
  2. additionthe resultant residue diluted with saturated aqueous sodium hydrogen carbonate solution (20 mL)
  3. extractionextracted with dichloromethane (3×30 mL)
  4. dry with materialThe combined organic layer was dried (Na2SO4)
  5. filtrationfiltered
  6. customevaporated
  7. customto give a residue
  8. customThe resultant residue was purified by flash chromatography (silica, 12 g cartridge, ISCO, 0-8% methanol in dichloromethane)
  9. customThe appropriate fractions were collected
  10. customevaporated

Sources & evidence

ORD record
ord-888dbba0544b41838d758a7819203196
Source dataset
uspto-grants-2016_09
Patent number
US09440976B2

Reaction notes

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