Dimethylformamide → N-Acetyl-D-thioproline alpha-methyl-L-tyrosine methyl ester

HRID 2289419Notes

Reaction equation

HRID 2289419 reaction equation
CCN=C=NCCCN(C)C.Cl.[C:13]([N:16]1[CH2:23][S:22][CH2:21][C@@H:17]1[C:18]([OH:20])=[O:19])(=[O:15])[CH3:14].[CH:24]1[CH:25]=[CH:26][C:27]2N(O)N=[N:30][C:28]=2[CH:29]=1.CN1CC[O:38][CH2:37]C1.CN([CH:44]=[O:45])C>>[C:13]([N:16]1[CH2:23][S:22][CH2:21][C@@H:17]1[C:18]([OH:20])=[O:19])(=[O:15])[CH3:14].[CH3:37][O:38][C:44](=[O:45])[C@:28]([CH3:27])([CH2:29][C:24]1[CH:21]=[CH:17][C:18]([OH:20])=[CH:26][CH:25]=1)[NH2:30]

Participants

6

Reactant 5

HCID 6228DimethylformamideHCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 749158(4S)-3-acetyl-1,3-thiazolidine-4-carboxylic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride

Product 1

HCID 131721908N-Acetyl-D-thioproline alpha-methyl-L-tyrosine methyl esterYield 52%

Procedure

EDC.HCl (760 mg, 3.96 mmol) was added to a solution of N-acetyl-D-thioproline (630 mg, 3.6 mmol), Intermediate 5 (880 mg, 3.6 mmol), HOBT (535 mg, 3.96 mmol) and NMM (834 μl, 7.6 mmol) in DMF (20 ml). The mixture was stirred at room temperature overnight. The DMF was evaporated in vacuo and the residue dissolved in ethyl acetate (150 ml) and water (50 ml). The organic phase was washed with 10% citric acid (50 ml), saturated aqueous NaHCO3 (50 ml) and water (50 ml), dried (Na2SO4) and evaporated in vacuo. The residue was purified by column chromatography (SiO2, methanol/DCM, 7:93) to give the title compound as a colourless gum (680 mg, 52%); δH (DMSO-d6, 400K) 7.40 (1H, br s, CONH), 6.93 (2H, d, J 8.6 Hz, ArH), 6.68 (2H, d, J 8.3 Hz, ArH), 4.84 (1H, dd, J 3.8, 7.4 Hz, CHαthiopro), 4.78 (1H, d, J 9.2 Hz, NCHAHBS), 4.40 (1H, d, J 9.2 Hz, NCHAHBS), 3.63 (3H, S, CO2CH3), 3.30 (1H, dd, J 7.4, 11.5 Hz, CHCHAHBS), 3.16 (1H, dd, J 3.8, 11.5 Hz, CHCHAHBS), 3.13 (1H, d, J 13.7 Hz, CHAHBAr), 3.03 (1H, d, J 13.7 Hz, CHAHBAr), 2.02 (3H, s, CH3CO) and 1.38 (3H, s, CCH3); m/z (ES, 15V) 367 (M+ +1).

Workup

  1. customThe DMF was evaporated in vacuo
  2. dissolutionthe residue dissolved in ethyl acetate (150 ml)
  3. washThe organic phase was washed with 10% citric acid (50 ml), saturated aqueous NaHCO3 (50 ml) and water (50 ml)
  4. dry with materialdried (Na2SO4)
  5. customevaporated in vacuo
  6. customThe residue was purified by column chromatography (SiO2, methanol/DCM, 7:93)

Sources & evidence

ORD record
ord-706f00abdfc542abb1006cc2f374a294
Source dataset
uspto-grants-2000_07
Patent number
US06093696

Reaction notes

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