1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → tert-butyl [(3R)-1-(4-benzoylbenzyl)-3-pyrrolidinyl](5-{(1E)-3-oxo-3-[(tetrahydro-2H-pyran-2-yloxy)amino]-1-propen-1-yl}-2-pyridyl)carbamate

HRID 2376016Notes

Reaction equation

HRID 2376016 reaction equation
Cl.Cl.[C:3]([C:11]1[CH:41]=[CH:40][C:14]([CH2:15][N:16]2[CH2:20][CH2:19][C@@H:18]([N:21]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[C:22]3[N:27]=[CH:26][C:25](/[CH:28]=[CH:29]/[C:30](O)=[O:31])=[CH:24][CH:23]=3)[CH2:17]2)=[CH:13][CH:12]=1)(=[O:10])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[O:42]1[CH2:47][CH2:46][CH2:45][CH2:44][CH:43]1[O:48][NH2:49].ON1C2C=CC=CC=2N=N1.CN(C)CCCN=C=NCC.C([O-])(O)=O.[Na+]>CN(C)C=O.O>[C:3]([C:11]1[CH:12]=[CH:13][C:14]([CH2:15][N:16]2[CH2:20][CH2:19][C@@H:18]([N:21]([C:22]3[CH:23]=[CH:24][C:25](/[CH:28]=[CH:29]/[C:30](=[O:31])[NH:49][O:48][CH:43]4[CH2:44][CH2:45][CH2:46][CH2:47][O:42]4)=[CH:26][N:27]=3)[C:33](=[O:34])[O:35][C:36]([CH3:39])([CH3:38])[CH3:37])[CH2:17]2)=[CH:40][CH:41]=1)(=[O:10])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1

Participants

8

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 516892Sodium BicarbonateHCID 5142091O-(Tetrahydropyran-2-yl)hydroxylamineHCID 68964974(2E)-3-{6-[[(3R)-1-(4-benzoylbenzyl)-3-pyrrolidinyl](tert-butoxycarbonyl)amino]-3-pyridyl}acrylic acid dihydrochloride

Product 1

HCID 86603642tert-butyl [(3R)-1-(4-benzoylbenzyl)-3-pyrrolidinyl](5-{(1E)-3-oxo-3-[(tetrahydro-2H-pyran-2-yloxy)amino]-1-propen-1-yl}-2-pyridyl)carbamateYield 36.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a mixture of (2E)-3-{6- [[(3R)-1-(4-benzoylbenzyl)-3-pyrrolidinyl](tert-butoxycarbonyl)amino]-3-pyridyl}acrylic acid dihydrochloride (93 mg), O-tetrahydro-2H-pyran-2-ylhydroxylamine (27 mg.), and 1-hydroxybenzotriazole (31 mg) in N,N-dimethylformamide (1.6 mL) was added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (36 mg) at 4° C. The mixture was warmed to ambient temperature and stirred for 8 hours. The reaction mixture was added saturated NaHCO3 (2 mL) and water (8 mL), and extracted with ethyl acetate. The organic layer was washed with water and brine, dried over MgSO4, filtered, and evaporated in vacuo. The residue was purified by column chromatography on silica gel to give tert-butyl [(3R)-1-(4-benzoylbenzyl)-3-pyrrolidinyl](5-{(1E)-3-oxo-3-[(tetrahydro-2H-pyran-2-yloxy)amino]-1-propen-1-yl}-2-pyridyl)carbamate (35 mg)

Workup

  1. extractionextracted with ethyl acetate
  2. washThe organic layer was washed with water and brine
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. customevaporated in vacuo
  6. customThe residue was purified by column chromatography on silica gel

Sources & evidence

ORD record
ord-8e1c1262d1884af7ba8afdcc576c8e2e
Source dataset
uspto-grants-2008_12
Patent number
US07465731B2

Reaction notes

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