Quinaldic Acid → HCID 58355425, compound

HRID 1509539Notes

Reaction equation

HRID 1509539 reaction equation
[CH3:1][CH:2]([CH3:26])[CH2:3][NH:4][C@H:5]1[CH2:10][C@@H:9]([C:11]([N:13]2[CH2:18][CH2:17][O:16][CH2:15][CH2:14]2)=[O:12])[CH2:8][N:7](C(OC(C)(C)C)=O)[CH2:6]1.[N:27]1[C:36]2[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=2)[CH:30]=[CH:29][C:28]=1[C:37](O)=[O:38].F[P-](F)(F)(F)(F)F.ClC(N(C)C)=[N+](C)C.C(N(CC)C(C)C)(C)C.C(=O)([O-])O.[Na+]>CN(C=O)C>[CH3:26][CH:2]([CH3:1])[CH2:3][N:4]([C@H:5]1[CH2:10][C@@H:9]([C:11]([N:13]2[CH2:14][CH2:15][O:16][CH2:17][CH2:18]2)=[O:12])[CH2:8][NH:7][CH2:6]1)[C:37]([C:28]1[CH:29]=[CH:30][C:31]2[C:36](=[CH:35][CH:34]=[CH:33][CH:32]=2)[N:27]=1)=[O:38]

Participants

7

Reactant 5

HCID 7124Quinaldic AcidHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 10989639Chloro-N,N,N',N'-tetramethylformamidinium HexafluorophosphateHCID 59356577tert-Butyl (3S,5R)-3-(isobutylamino)-5-(morpholine-4-carbonyl)piperidine-1-carboxylate

Product 1

HCID 58355425HCID 58355425, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A 0.08M solution (1000 μL, 80 μmol) of tert-butyl (3S,5R)-3-[(2-methylpropyl)amino]-5-(morpholin-4-ylcarbonyl)piperidine-1-carboxylate in DMF and quinoline-2-carboxylic acid (15.2 mg, 88 μmol) were mixed, a 0.32M solution (500 μL, 160 μmol) of chloro-N,N,N′,N′-tetramethylformamidinium hexafluorophosphate and N,N-diisopropylethylamine in DMF was added at room temperature and the mixture was stirred for 16 hr. After completion of the reaction, 2% aqueous sodium hydrogen carbonate solution (1.0 ml) was added, and extracted with ethyl acetate (3.5 ml). The organic layer was separated by upper layer Phase Septube (manufactured by Wako Pure Chemical Industries, Ltd.). The solvent was evaporated under reduced pressure, and the residue was dissolved in DMSO-methanol (1:1) (1 ml), purified by preparative HPLC, and the object fraction was concentrated to give a protected title compound. 1M MSA acetonitrile solution (3 ml) was added to the obtained protected compound, and the mixture was stirred at room temperature for 16 hr. After completion of the reaction, 1M DIEA acetonitrile solution (3.5 ml) was added, and the reaction mixture was directly developed by preparative HPLC to give the object product (12.3 mg).

Workup

  1. additionwas added
  2. extractionextracted with ethyl acetate (3.5 ml)
  3. customThe organic layer was separated by upper layer Phase Septube (manufactured by Wako Pure Chemical Industries, Ltd.)
  4. customThe solvent was evaporated under reduced pressure
  5. dissolutionthe residue was dissolved in DMSO-methanol (1:1) (1 ml)
  6. custompurified by preparative HPLC
  7. concentrationthe object fraction was concentrated

Sources & evidence

ORD record
ord-fb938932ff914a328f80e8a739470e1c
Source dataset
uspto-grants-2015_12
Patent number
US09221836B2

Reaction notes

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