Iodo benzene diacetate → HCID 71005110, compound

HRID 338857Notes

Reaction equation

HRID 338857 reaction equation
[CH:1]1([CH2:4][O:5][C:6]2[CH:7]=[CH:8][CH:9]=[C:10]3[C:15]=2[N:14]=[C:13]([CH:16]=O)[CH:12]=[CH:11]3)[CH2:3][CH2:2]1.[CH3:18][N:19]([C@H:27]1[CH2:31][CH2:30][N:29]([CH:32]([C:37]2[CH:38]=[N:39][C:40]([NH:43][NH2:44])=[CH:41][CH:42]=2)[C:33]([F:36])([F:35])[F:34])[CH2:28]1)C(=O)OC(C)(C)C.C(O)(=O)C.C(O)(=O)C.IC1C=CC=CC=1>C(O)C.CC#N>[CH:1]1([CH2:4][O:5][C:6]2[CH:7]=[CH:8][CH:9]=[C:10]3[C:15]=2[N:14]=[C:13]([C:16]2[N:39]4[CH:38]=[C:37]([CH:32]([N:29]5[CH2:30][CH2:31][C@H:27]([NH:19][CH3:18])[CH2:28]5)[C:33]([F:34])([F:36])[F:35])[CH:42]=[CH:41][C:40]4=[N:43][N:44]=2)[CH:12]=[CH:11]3)[CH2:3][CH2:2]1

Participants

6

Reactant 3

HCID 12217721Iodo benzene diacetateHCID 86707408HCID 86707408, compoundHCID 86707419HCID 86707419, compound

Product 1

HCID 71005110HCID 71005110, compoundYield 50.9%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 6342AcetonitrileSolvent

Procedure

A solution of 8-(cyclopropylmethoxy)quinoline-2-carbaldehyde (0.14 g, 0.62 mmol) and tert-butyl methyl((3S)-1-(2,2,2-trifluoro-1-(6-hydrazinylpyridin-3-yl)ethyl)pyrrolidin-3-yl)carbamate (0.20 g, 0.51 mmol) in ethanol (10 mL) was stirred at ambient temperature for 16 hours. The solvent was removed under reduced pressure. The residue was dissolved in dichloromethane (10 mL) and treated with iodobenzene diacetate (0.20 g, 0.62 mmol) and stirred at ambient temperature for 4 hours. The mixture was partitioned between ethyl acetate (20 mL) and saturated sodium bicarbonate solution (10 mL). The organic layer was separated, washed with brine, dried (MgSO4, filtered and concentrated under reduced pressure. The residue was purified by reverse phase chromatography (Biotage SP4, C-18 25M; 10-90% CH3CN/water gradient). The residue was dissolved in dichloromethane (1 mL), treated with TFA (4 mL) and stirred at ambient temperature for 1 hour. The solution was concentrated under reduced pressure and the residue was purified by reverse phase chromatography (Biotage SP4, C-18 25M; 10-70% CH3CN/water gradient). The TFA salt was dissolved in methanol (0.50 mL) and treated with 2N HCl in diethyl ether (4 mL) and stirred for 10 minutes. The solvent was removed under reduced pressure and the solid obtained suspended in MeCN (5 mL) and stirred for 10 minutes. The solid was collected by filtration to afford (3S)-1-(1-(3-(8-(cyclopropylmethoxy)quinolin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yl)-2,2,2-trifluoroethyl)-N-methylpyrrolidin-3-amine (0.129 g, 44%). LCMS APCI (+) m/z 497 (M+H).

Workup

  1. customThe solvent was removed under reduced pressure
  2. dissolutionThe residue was dissolved in dichloromethane (10 mL)
  3. customThe mixture was partitioned between ethyl acetate (20 mL) and saturated sodium bicarbonate solution (10 mL)
  4. customThe organic layer was separated
  5. washwashed with brine
  6. dry with materialdried (MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by reverse phase chromatography (Biotage SP4
  10. dissolutionThe residue was dissolved in dichloromethane (1 mL)
  11. additiontreated with TFA (4 mL)
  12. stirringstirred at ambient temperature for 1 hour
  13. concentrationThe solution was concentrated under reduced pressure
  14. customthe residue was purified by reverse phase chromatography (Biotage SP4
  15. dissolutionThe TFA salt was dissolved in methanol (0.50 mL)
  16. additiontreated with 2N HCl in diethyl ether (4 mL)
  17. stirringstirred for 10 minutes
  18. customThe solvent was removed under reduced pressure
  19. customthe solid obtained
  20. stirringstirred for 10 minutes
  21. filtrationThe solid was collected by filtration

Sources & evidence

ORD record
ord-acd4c47d80ed4d8fab1aee879662465e
Source dataset
uspto-grants-2014_11
Patent number
US08889704B2

Reaction notes

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