Triethylamine → tert-butyl(2S,3S)-3-methyl-2-(2-oxo-3-{[2-(2-pyridinyl)-1,3-thiazol-4-yl]methyl}-1-imidazolidinyl)pentanoate

HRID 1174119Notes

Reaction equation

HRID 1174119 reaction equation
[NH2:1][CH2:2][CH2:3][NH:4][C@@H:5]([C@@H:13]([CH3:16])[CH2:14][CH3:15])[C:6]([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7].[N:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1[C:23]1[S:24][CH:25]=[C:26]([CH:28]=O)[N:27]=1.[BH4-].[Na+].[C:32](=O)(OC1C=CC([N+]([O-])=O)=CC=1)[O:33]C1C=CC([N+]([O-])=O)=CC=1.C(N(CC)CC)C>C1C=CC=CC=1.C(O)C.ClCCCl>[CH3:16][C@@H:13]([CH2:14][CH3:15])[C@H:5]([N:4]1[CH2:3][CH2:2][N:1]([CH2:28][C:26]2[N:27]=[C:23]([C:18]3[CH:19]=[CH:20][CH:21]=[CH:22][N:17]=3)[S:24][CH:25]=2)[C:32]1=[O:33])[C:6]([O:8][C:9]([CH3:10])([CH3:11])[CH3:12])=[O:7]

Participants

9

Reactant 5

HCID 8471TriethylamineHCID 78756Bis(4-nitrophenyl) carbonateHCID 21253372-(Pyridin-2-yl)-1,3-thiazole-4-carbaldehydeHCID 4311764Sodium borohydrideHCID 86598803tert-butyl(2S,3S)-2-[(2-aminoethyl)amino]-3-methylpentanoate

Product 1

HCID 67405680tert-butyl(2S,3S)-3-methyl-2-(2-oxo-3-{[2-(2-pyridinyl)-1,3-thiazol-4-yl]methyl}-1-imidazolidinyl)pentanoateYield 38.2%

Reagents, catalysts & solvents 3

HCID 111,2-DichloroethaneSolventHCID 241BenzeneSolventHCID 702EthanolSolvent

Conditions

Temperature
70 °C

Procedure

A solution containing the product of Example 3G (0.30 g, 1.30 mmol) in a mixture of benzene (3 mL) and ethanol (3 mL) was treated with the product of Example 3J (0.25 g, 1.31 mmol), heated at 70° C. for 16 hours, cooled to 25° C., treated with sodium borohydride (0.15 g, 3.97 mmol), stirred at 25° C. for 3 hours, quenched with sodium bicarbonate solution and partitioned between ethyl acetate and water. The organic phase was washed with brine, dried over MgSO4, filtered and concentrated. A solution of the residue (1.3 mmol) in 1,2-dichloroethane (50 mL) was treated with bis(4-nitrophenyl) carbonate (0.425 g, 1.40 mmol) and triethylamine (0.225 ml, 1.83 mmol), heated at 70° C. for 16 hours, and partitioned between ethyl acetate and saturated NaHCO3. The organic phase was washed with brine, dried over MgSO4, filtered and concentrated. The residue was chromatographed on silica gel eluting with 0-35% ethyl acetate in dichloromethane to give the title compound (0.214 g, 38% yield).

Workup

  1. temperaturecooled to 25° C.
  2. customquenched with sodium bicarbonate solution
  3. custompartitioned between ethyl acetate and water
  4. washThe organic phase was washed with brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. temperatureheated at 70° C. for 16 hours
  9. custompartitioned between ethyl acetate and saturated NaHCO3
  10. washThe organic phase was washed with brine
  11. dry with materialdried over MgSO4
  12. filtrationfiltered
  13. concentrationconcentrated
  14. customThe residue was chromatographed on silica gel eluting with 0-35% ethyl acetate in dichloromethane

Sources & evidence

ORD record
ord-05be62d3a8e54c83b4c99d5eafbdaa3d
Source dataset
uspto-grants-2010_11
Patent number
US07834043B2

Reaction notes

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