Tetrahydrofuran → tert-butyl (2,3-dihydro-1,4-benzodioxin-6-ylmethyl)(1-(2-(7-methoxy-2-oxo-4-(((pyridin-3-ylmethyl)amino)carbonyl)quinolin-1(2H)-yl)ethyl)piperidin-4-yl)carbamate

HRID 2193191

Reaction equation

HRID 2193191 reaction equation
O1CCCC1.[C:6]([O:10][C:11]([N:13]([CH2:38][C:39]1[CH:48]=[CH:47][C:42]2[O:43][CH2:44][CH2:45][O:46][C:41]=2[CH:40]=1)[CH:14]1[CH2:19][CH2:18][N:17]([CH2:20][CH2:21][N:22]2[C:31]3[C:26](=[CH:27][CH:28]=[C:29]([O:32][CH3:33])[CH:30]=3)[C:25]([C:34]([OH:36])=O)=[CH:24][C:23]2=[O:37])[CH2:16][CH2:15]1)=[O:12])([CH3:9])([CH3:8])[CH3:7].C(Cl)(=O)OCC(C)C.[NH2:57][CH2:58][C:59]1[CH:60]=[N:61][CH:62]=[CH:63][CH:64]=1>O.C(OCC)(=O)C.C(N(CC)CC)C>[O:43]1[C:42]2[CH:47]=[CH:48][C:39]([CH2:38][N:13]([CH:14]3[CH2:19][CH2:18][N:17]([CH2:20][CH2:21][N:22]4[C:31]5[C:26](=[CH:27][CH:28]=[C:29]([O:32][CH3:33])[CH:30]=5)[C:25]([C:34]([NH:57][CH2:58][C:59]5[CH:60]=[N:61][CH:62]=[CH:63][CH:64]=5)=[O:36])=[CH:24][C:23]4=[O:37])[CH2:16][CH2:15]3)[C:11](=[O:12])[O:10][C:6]([CH3:8])([CH3:9])[CH3:7])=[CH:40][C:41]=2[O:46][CH2:45][CH2:44]1

Participants

8

Reactant 4

HCID 8028TetrahydrofuranHCID 310183-PyridinemethanamineHCID 62365Isobutyl chloroformateHCID 593981451-(2-(4-((Tert-butoxycarbonyl)(2,3-dihydro-1,4-benzodioxin-6-ylmethyl)amino)piperidin-1-yl)ethyl)-7-methoxy-2-oxo-1,2-dihydroquinoline-4-carboxylic acid

Product 1

HCID 59398013tert-butyl (2,3-dihydro-1,4-benzodioxin-6-ylmethyl)(1-(2-(7-methoxy-2-oxo-4-(((pyridin-3-ylmethyl)amino)carbonyl)quinolin-1(2H)-yl)ethyl)piperidin-4-yl)carbamate

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8471TriethylamineSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To 3.0 mL of tetrahydrofuran suspension containing 0.15 g of 1-(2-(4-((tert-butoxycarbonyl)(2,3-dihydro-1,4-benzodioxin-6-ylmethyl)amino)piperidin-1-yl)ethyl)-7-methoxy-2-oxo-1,2-dihydroquinoline-4-carboxylic acid, 39 μL of triethylamine was added at room temperature, 36 μL of isobutyl chlorocarbonate was added dropwise under ice-cooling. After the reaction mixture was stirred at the same temperature for 2 hours, 26 μL of 3-(aminomethyl)pyridine was added, further 39 μL of triethylamine was added and stirred at the same temperature for 3 hours. To the reaction mixture, ethyl acetate and water were added, the organic layer was separated, and the aqueous layer was extracted with ethyl acetate. The organic layer and extracts were combined, washed sequentially with water and 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=100:0-90:10], to give 0.12 g of tert-butyl (2,3-dihydro-1,4-benzodioxin-6-ylmethyl)(1-(2-(7-methoxy-2-oxo-4-(((pyridin-3-ylmethyl)amino)carbonyl)quinolin-1(2H)-yl)ethyl)piperidin-4-yl)carbamate as a white foam.

Workup

  1. additionwas added at room temperature
  2. temperaturecooling
  3. stirringstirred at the same temperature for 3 hours
  4. customthe organic layer was separated
  5. extractionthe aqueous layer was extracted with ethyl acetate
  6. washwashed sequentially with water and aqueous saturated sodium chloride solution
  7. dry with materialdried over anhydrous magnesium sulfate
  8. customthe solvent was removed under reduced pressure
  9. customThe residue thus obtained
  10. customwas purified by flash silica gel column chromatography [gradient elution of chloroform : methanol=100:0-90:10]

Sources & evidence

ORD record
ord-755f43caf1894f968992edf444c8babc
Source dataset
uspto-grants-2012_12
Patent number
US08329694B2

Linked notes

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