Sodium Bicarbonate → tert-butyl (1-(2-(4-((cyclopropylamino)carbonyl)-7-methoxy-2-oxoquinolin-1-(2H)-yl)ethyl)piperidin-4-yl)(2,3-dihydro-1,4-benzodioxin-6-ylmethyl)carbamate

HRID 2193189Notes

Reaction equation

HRID 2193189 reaction equation
[CH:1]1([NH:4][C:5]([C:7]2[C:16]3[C:11](=[CH:12][C:13]([O:17][CH3:18])=[CH:14][CH:15]=3)[N:10]([CH2:19][CH:20]=O)[C:9](=[O:22])[CH:8]=2)=[O:6])[CH2:3][CH2:2]1.[C:23]([O:27][C:28](=[O:47])[N:29]([CH2:36][C:37]1[CH:46]=[CH:45][C:40]2[O:41][CH2:42][CH2:43][O:44][C:39]=2[CH:38]=1)[CH:30]1[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]1)([CH3:26])([CH3:25])[CH3:24].C([BH3-])#N.[Na+].C(=O)([O-])O.[Na+]>C(Cl)(Cl)Cl.CO.C(O)(=O)C>[C:23]([O:27][C:28](=[O:47])[N:29]([CH:30]1[CH2:35][CH2:34][N:33]([CH2:20][CH2:19][N:10]2[C:11]3[C:16](=[CH:15][CH:14]=[C:13]([O:17][CH3:18])[CH:12]=3)[C:7]([C:5]([NH:4][CH:1]3[CH2:3][CH2:2]3)=[O:6])=[CH:8][C:9]2=[O:22])[CH2:32][CH2:31]1)[CH2:36][C:37]1[CH:46]=[CH:45][C:40]2[O:41][CH2:42][CH2:43][O:44][C:39]=2[CH:38]=1)([CH3:26])([CH3:24])[CH3:25]

Participants

8

Reactant 4

HCID 516892Sodium BicarbonateHCID 5003444Sodium cyanoborohydride2×HCID 57815320Tert-butyl (2,3-dihydro-1,4-benzodioxin-6-ylmethyl)(piperidin-4-yl)carbamateHCID 59397881N-cyclopropyl-7-methoxy-2-oxo-1-(2-oxoethyl)-1,2-dihydroquinoline-4-carboxamide

Product 1

HCID 59398416tert-butyl (1-(2-(4-((cyclopropylamino)carbonyl)-7-methoxy-2-oxoquinolin-1-(2H)-yl)ethyl)piperidin-4-yl)(2,3-dihydro-1,4-benzodioxin-6-ylmethyl)carbamateYield 47.5%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolvent2×HCID 887MethanolSolvent2×HCID 6212ChloroformSolvent

Procedure

To 1.0 mL of methanol solution containing 0.13 g of N-cyclopropyl-7-methoxy-2-oxo-1-(2-oxoethyl)-1,2-dihydroquinoline-4-carboxamide, 0.16 g of tert-butyl(2,3-dihydro-1,4-benzodioxin-6-ylmethyl)(piperidin-4-yl)carbamate and 25 μL of acetic acid were added at room temperature and stirred at the same temperature for 1.5 hours. To the reaction mixture, 42 mg of sodium cyanoborohydride was added and stirred at the same temperature for 2 hours. Further, 42 mg of sodium cyanoborohydride was added and stirred at the same temperature for 2 hours and 15 min. 76 μL of acetic acid was added and stirred at the same temperature for 2 hours. To the mixture, aqueous saturated sodium hydrogen carbonate solution was added under ice-cooling to be adjusted to pH 8.7, 5.0 mL of methanol and 15 mL of chloroform were added, the organic layer was separated, and the aqueous layer was extracted with chloroform. The organic layer and extracts were combined, washed with aqueous saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. The residue thus obtained was purified by flash silica gel column chromatography [gradient elution of chloroform:methanol=100:0-70:30], to give 0.13 g of tert-butyl(1-(2-(4-((cyclopropylamino)carbonyl)-7-methoxy-2-oxoquinolin-1-(2H)-yl)ethyl)piperidin-4-yl)(2,3-dihydro-1,4-benzodioxin-6-ylmethyl)carbamate as a white foam.

Workup

  1. additionwere added at room temperature
  2. stirringstirred at the same temperature for 2 hours
  3. stirringstirred at the same temperature for 2 hours and 15 min
  4. stirringstirred at the same temperature for 2 hours
  5. temperaturecooling
  6. additionwere added
  7. customthe organic layer was separated
  8. extractionthe aqueous layer was extracted with chloroform
  9. washwashed with aqueous saturated sodium chloride solution
  10. dry with materialdried over anhydrous magnesium sulfate
  11. customthe solvent was removed under reduced pressure
  12. customThe residue thus obtained
  13. customwas purified by flash silica gel column chromatography [gradient elution of chloroform:methanol=100:0-70:30]

Sources & evidence

ORD record
ord-bc3b2b198a9a4f0f9f987dc58c48f08f
Source dataset
uspto-grants-2012_12
Patent number
US08329694B2

Reaction notes

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