Diisopropylethylamine → tert-butyl (3S,5R)-3-[({4-[(3-methoxypropyl)amino]-6-(1-methylethyl)pyridin-3-yl}carbonyl)(2-methylpropyl)amino]-5-(morpholin-4-ylcarbonyl)piperidine-1-carboxylate

HRID 2192881Notes

Reaction equation

HRID 2192881 reaction equation
[CH3:1][O:2][CH2:3][CH2:4][CH2:5][NH:6][C:7]1[CH:12]=[C:11]([CH:13]([CH3:15])[CH3:14])[N:10]=[CH:9][C:8]=1[C:16]([OH:18])=O.[CH3:19][CH:20]([CH3:44])[CH2:21][NH:22][C@H:23]1[CH2:28][C@@H:27]([C:29]([N:31]2[CH2:36][CH2:35][O:34][CH2:33][CH2:32]2)=[O:30])[CH2:26][N:25]([C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])[CH2:24]1.C(N(C(C)C)CC)(C)C.F[P-](F)(F)(F)(F)F.ClC(N(C)C)=[N+](C)C.C(=O)([O-])O.[Na+]>C(Cl)Cl>[CH3:1][O:2][CH2:3][CH2:4][CH2:5][NH:6][C:7]1[CH:12]=[C:11]([CH:13]([CH3:14])[CH3:15])[N:10]=[CH:9][C:8]=1[C:16]([N:22]([CH2:21][CH:20]([CH3:44])[CH3:19])[C@H:23]1[CH2:28][C@@H:27]([C:29]([N:31]2[CH2:36][CH2:35][O:34][CH2:33][CH2:32]2)=[O:30])[CH2:26][N:25]([C:37]([O:39][C:40]([CH3:41])([CH3:42])[CH3:43])=[O:38])[CH2:24]1)=[O:18]

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 10989639Chloro-N,N,N',N'-tetramethylformamidinium HexafluorophosphateHCID 59356577tert-Butyl (3S,5R)-3-(isobutylamino)-5-(morpholine-4-carbonyl)piperidine-1-carboxylateHCID 596256684-[(3-Methoxypropyl)amino]-6-(1-methylethyl)pyridine-3-carboxylic acid

Product 1

HCID 59625537tert-butyl (3S,5R)-3-[({4-[(3-methoxypropyl)amino]-6-(1-methylethyl)pyridin-3-yl}carbonyl)(2-methylpropyl)amino]-5-(morpholin-4-ylcarbonyl)piperidine-1-carboxylateYield 88.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

4-[(3-Methoxypropyl)amino]-6-(1-methylethyl)pyridine-3-carboxylic acid (160 mg), tert-butyl (3S,5R)-3-[(2-methylpropyl)amino]-5-(morpholin-4-ylcarbonyl)piperidine-1-carboxylate (185 mg) and diisopropylethylamine (431 μl) were dissolved in methylene chloride (10 ml), chloro-N,N,N′,N′-tetramethylformamidinium hexafluorophosphate (168 mg) was added and the mixture was stirred at room temperature for 15 hr. Aqueous sodium hydrogen carbonate was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The residue was subjected to basic silica gel column chromatography, and the fraction eluted with ethyl acetate-hexane (7:3) was concentrated under reduced pressure to give the object compound (268 mg).

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe extract was washed with saturated brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. customThe solvent was evaporated under reduced pressure
  5. washthe fraction eluted with ethyl acetate-hexane (7:3)
  6. concentrationwas concentrated under reduced pressure

Sources & evidence

ORD record
ord-db11cfafe89d49538f30e2fccd2771ca
Source dataset
uspto-grants-2012_12
Patent number
US08329691B2

Reaction notes

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