4-Methylmorpholine → (S)-N-((S)-6-Cyano-1,2,3,4-tetrahydroquinolin-3-yl)-2-hydroxy-2-phenylacetamide

HRID 2234246Notes

Reaction equation

HRID 2234246 reaction equation
Cl.Cl.[NH2:3][CH:4]1[CH2:13][C:12]2[C:7](=[CH:8][CH:9]=[C:10]([C:14]#[N:15])[CH:11]=2)[NH:6][CH2:5]1.[C:16](O)(=[O:25])[C@H:17]([C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[OH:18].CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.CN1CCOCC1>CN(C=O)C.CCOC(C)=O>[C:14]([C:10]1[CH:11]=[C:12]2[C:7](=[CH:8][CH:9]=1)[NH:6][CH2:5][C@@H:4]([NH:3][C:16](=[O:25])[C@@H:17]([OH:18])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[CH2:13]2)#[N:15]

Participants

8

Reactant 5

HCID 79724-MethylmorpholineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 439616(S)-mandelic acidHCID 1317281063-Amino-1,2,3,4-tetrahydroquinoline-6-carbonitrile, dihydrochloride

Product 1

HCID 66757271(S)-N-((S)-6-Cyano-1,2,3,4-tetrahydroquinolin-3-yl)-2-hydroxy-2-phenylacetamideYield 20%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 3-amino-1,2,3,4-tetrahydroquinoline-6-carbonitrile, dihydrochloride (10.03 g, 40.7 mmol), prepared as described in Example 1D, in DMF (100 mL) was added (S)-(+)-mandelic acid (7.45 g, 48.9 mmol), followed by EDAC (9.37 g, 48.9 mmol), HOBt (7.49 g, 48.9 mmol) and NMM (16.1 mL, 146.1 mmol). The reaction mixture was stirred at RT overnight, then diluted with EtOAc (200 mL), washed with water (50 mL×3), 1N aqueous HCl (50 mL), water (50 mL) and saturated aqueous NaCl, dried (Na2SO4) and concentrated. The residue was chromatographed (silica gel) eluting with EtOAc/hexanes (2:1 ratio), and the purified compound crystallized from acetone three times to give the title compound as the (S, S) diastereoisomer (2.54 g, 20% yield).

Workup

  1. washwashed with water (50 mL×3), 1N aqueous HCl (50 mL), water (50 mL) and saturated aqueous NaCl
  2. dry with materialdried (Na2SO4)
  3. concentrationconcentrated
  4. customThe residue was chromatographed (silica gel)
  5. washeluting with EtOAc/hexanes (2:1 ratio)
  6. customthe purified compound crystallized from acetone three times

Sources & evidence

ORD record
ord-a9cdcd927e9847e99be9f3ee2cb12dad
Source dataset
uspto-grants-2010_05
Patent number
US07709647B2

Reaction notes

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