HCID 58365196, compound → HCID 58364993, compound

HRID 60337Notes

Reaction equation

HRID 60337 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[C:15]2[CH:16]=[N:17][CH:18]=[C:19]([O:20][CH:21]3[CH2:26][CH2:25][N:24](C(OC(C)(C)C)=O)[CH2:23][CH2:22]3)[C:14]=2[C:13]2[CH:34]=[C:35]([Br:38])[CH:36]=[N:37][C:12]1=2)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1>FC(F)(F)C(O)=O.ClCCl>[CH2:1]([O:8][C:9]([N:11]1[C:15]2[CH:16]=[N:17][CH:18]=[C:19]([O:20][CH:21]3[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]3)[C:14]=2[C:13]2[CH:34]=[C:35]([Br:38])[CH:36]=[N:37][C:12]1=2)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

4

Reactant 1

HCID 58365196HCID 58365196, compound

Product 1

HCID 58364993HCID 58364993, compoundYield 42%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 6422Trifluoroacetic acidSolvent

Procedure

A solution of 3-bromo-5-(1-tert-butoxycarbonyl-piperidin-4-yloxy)dipyrido[2,3-b;4′,3′-d]pyrrole-9-carboxylic acid benzyl ester (0.34 g, 0.59 mmol) in triflouroacetic acid (2 mL) and dichloromethane (4 mL) was allowed to stir at ambient temperature for 15 minutes. The solvent was evaporated and the resultant residue was treated with saturated sodium hydrogen carbonate solution (20 mL) and extracted with dichloromethane (3×30 mL). The combined organic phase was dried (Na2SO4), filtered and evaporated to afford a residue. The resultant residue was purified by flash chromatography (silica, 12 g cartridge, ISCO, 0-10% methanol in dichloromethane then 10% 2M NH3 in methanol in dichloromethane). The appropriate fractions were combined and evaporated to afford the title compound as a yellow solid (118 mg, 42%). LCMS (Method B): RT=3.13 min, M+H+=481/483. 1H NMR (400 MHz, CDCl3): 9.22 (s, 1H), 8.77 (d, J=2.3 Hz, 1H), 8.62 (d, J=2.4 Hz, 1H), 8.31 (s, 1H), 7.60-7.59 (m, 2H), 7.40-7.40 (m, 3H), 5.63 (s, 2H), 4.86-4.82 (m, 1H), 3.26-3.25 (m, 2H), 2.95-2.94 (m, 2H), 2.29-2.25 (m, 2H), 1.99-1.97 (m, 2H).

Workup

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

Sources & evidence

ORD record
ord-9b9bb8b8d68f4491929891cbaeb8038c
Source dataset
uspto-grants-2016_09
Patent number
US09440976B2

Reaction notes

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