Diisopropylethylamine → tert-butyl (2,3-dihydro-1,4-benzodioxin-6-ylmethyl)(1-(2-(7-methoxy-5-((methylamino)carbonyl)-2-oxoquinolin-1(2H)-yl)ethyl)piperidin-4-yl)carbamate

HRID 2193237Notes

Reaction equation

HRID 2193237 reaction equation
[C:1]([O:5][C:6]([N:8]([CH2:33][C:34]1[CH:43]=[CH:42][C:37]2[O:38][CH2:39][CH2:40][O:41][C:36]=2[CH:35]=1)[CH:9]1[CH2:14][CH2:13][N:12]([CH2:15][CH2:16][N:17]2[C:26]3[CH:25]=[C:24]([O:27][CH3:28])[CH:23]=[C:22]([C:29]([OH:31])=O)[C:21]=3[CH:20]=[CH:19][C:18]2=[O:32])[CH2:11][CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.CN.F[P-](F)(F)(F)(F)F.[N:54]1(O[P+](N2CCCC2)(N2CCCC2)N2CCCC2)[C:58]2C=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C>CN(C)C=O.O>[O:38]1[C:37]2[CH:42]=[CH:43][C:34]([CH2:33][N:8]([CH:9]3[CH2:14][CH2:13][N:12]([CH2:15][CH2:16][N:17]4[C:26]5[C:21](=[C:22]([C:29]([NH:54][CH3:58])=[O:31])[CH:23]=[C:24]([O:27][CH3:28])[CH:25]=5)[CH:20]=[CH:19][C:18]4=[O:32])[CH2:11][CH2:10]3)[C:6](=[O:7])[O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[CH:35][C:36]=2[O:41][CH2:40][CH2:39]1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 6364545Methylamine hydrochlorideHCID 593980221-(2-(4-((Tert-butoxycarbonyl) (2,3-dihydro-1,4-benzodioxin-6-ylmethyl)amino)piperidin-1-yl)ethyl)-7-methoxy-2-oxo-1,2-dihydroquinoline-5-carboxylic acid

Product 1

HCID 59398105tert-butyl (2,3-dihydro-1,4-benzodioxin-6-ylmethyl)(1-(2-(7-methoxy-5-((methylamino)carbonyl)-2-oxoquinolin-1(2H)-yl)ethyl)piperidin-4-yl)carbamateYield 84.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

463 mg 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-5-carboxylic acid and 144 mg of methylamine hydrochloride were dissolved in 10 mL of N,N-dimethylformamide. To the mixture, 706 mg of (benzotriazol-1-yloxy)tripyrrolidinophosphonium hexafluorophosphate and 0.47 mL of N,N-diisopropylethylamine were added and stirred at room temperature overnight. The reaction mixture was poured into water, and extracted with a mixture of ethyl acetate:toluene=5:1. The organic layer was 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 silica gel column chromatography [Silica Gel; Kanto Chemical Co., Inc., Silica Gel 60, eluent; chloroform:methanol=20:1], to give 401 mg of tert-butyl (2,3-dihydro-1,4-benzodioxin-6-ylmethyl)(1-(2-(7-methoxy-5-((methylamino)carbonyl)-2-oxoquinolin-1(2H)-yl)ethyl)piperidin-4-yl)carbamate as a pale brown foam.

Workup

  1. extractionextracted with a mixture of ethyl acetate
  2. washThe organic layer was washed sequentially with water and aqueous saturated sodium chloride solution
  3. dry with materialdried over anhydrous magnesium sulfate
  4. customthe solvent was removed under reduced pressure
  5. customThe residue thus obtained
  6. customwas purified by silica gel column chromatography [Silica Gel; Kanto Chemical Co., Inc., Silica Gel 60, eluent; chloroform:methanol=20:1]

Sources & evidence

ORD record
ord-d63add37ac8a42869282948033480903
Source dataset
uspto-grants-2012_12
Patent number
US08329694B2

Reaction notes

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