Dichloromethane → N-(2-benzo[1,3]dioxol-5-yl-ethyl)-2-(3-imidazol-1-yl-[1,2,4]thiadiazol-5-yl)-succinamic acid ethyl ester

HRID 1170503Notes

Reaction equation

HRID 1170503 reaction equation
C1N(P(Cl)(N2C(=O)OCC2)=O)C(=O)OC1.[CH2:16]([O:18][C:19](=[O:35])[CH:20]([C:25]1[S:29][N:28]=[C:27]([N:30]2[CH:34]=[CH:33][N:32]=[CH:31]2)[N:26]=1)[CH2:21][C:22]([OH:24])=O)[CH3:17].C(Cl)Cl.[O:39]1[C:43]2[CH:44]=[CH:45][C:46]([CH2:48][CH2:49][NH2:50])=[CH:47][C:42]=2[O:41][CH2:40]1>CCOC(C)=O>[CH2:16]([O:18][C:19](=[O:35])[CH:20]([C:25]1[S:29][N:28]=[C:27]([N:30]2[CH:34]=[CH:33][N:32]=[CH:31]2)[N:26]=1)[CH2:21][C:22]([NH:50][CH2:49][CH2:48][C:46]1[CH:45]=[CH:44][C:43]2[O:39][CH2:40][O:41][C:42]=2[CH:47]=1)=[O:24])[CH3:17]

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 738741,3-Benzodioxole-5-ethanamineHCID 152842Bis(2-oxo-3-oxazolidinyl)phosphinic chlorideHCID 586544532-(3-Imidazol-1-yl-[1,2,4]thiadiazol-5-yl)-succinic acid 1-ethyl ester

Product 1

HCID 11517884N-(2-benzo[1,3]dioxol-5-yl-ethyl)-2-(3-imidazol-1-yl-[1,2,4]thiadiazol-5-yl)-succinamic acid ethyl esterYield 3%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

BOP-Cl (784 mg, 3.08 mmol) was added all at once to a solution 2-(3-imidazol-1-yl-[1,2,4]thiadiazol-5-yl)-succinic acid 1-ethyl ester (389 mg, 1.54 mmol) and DCM (10 mL) and stirred at room temperature for 30 min prior to addition of 2-benzo[1,3]dioxol-5-yl-ethylamine (620 mg, 3.08 mmol) and TEA (859 μL, 6.16 mmol). The reaction mixture stirred at r.t. for an additional 20 h. The solvent was evaporated to afford a white slurry oil, diluted with EtOAc (50 mL), washed with sat. NaHCO3 (50 mL), brine (50 mL), dried over Na2SO4, filtered and concentrated to a white solid. Purification was achieved using column chromatography (CH2Cl2 to 4:1 CH2Cl2/MeOH) to afford 17 mg (3%) of N-(2-benzo[1,3]dioxol-5-yl-ethyl)-2-(3-imidazol-1-yl-[1,2,4]thiadiazol-5-yl)-succinamic acid ethyl ester as a white solid. [M+H]+ 443.90; 1H NMR (400 MHz, CDCl3) δ 8.50 (s, 1H), 7.74 (s, 1H), 7.15 (s, 1H), 6.66-6.52 (m, 3H), 6.04 (br s, 1H), 5.86 (s, 2H), 4.31 (q, 2H), 3.78 (t, 1H), 3.63 (t, 2H), 3.16 (t, 2H), 2.83 (d, 2H), 1.32 (t, 3H).

Workup

  1. stirringThe reaction mixture stirred at r.t. for an additional 20 h
  2. customThe solvent was evaporated
  3. customto afford a white slurry oil
  4. washwashed with sat. NaHCO3 (50 mL), brine (50 mL)
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated to a white solid
  8. customPurification

Sources & evidence

ORD record
ord-86fa5c4785e44fe59f864bc2715c91c0
Source dataset
uspto-grants-2010_11
Patent number
US07825256B2

Reaction notes

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