1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → [5-(5-{3-Chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1H-indol-2-yl]methanol

HRID 1512871Notes

Reaction equation

HRID 1512871 reaction equation
CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.[Cl:22][C:23]1[CH:24]=[C:25]([CH:29]=[CH:30][C:31]=1[O:32][CH:33]([CH3:35])[CH3:34])[C:26]([OH:28])=O.O[NH:37][C:38]([C:40]1[CH:41]=[C:42]2[C:46](=[CH:47][CH:48]=1)[NH:45][C:44]([CH2:49][OH:50])=[CH:43]2)=[NH:39]>CN(C=O)C.CCOC(C)=O>[Cl:22][C:23]1[CH:24]=[C:25]([C:26]2[O:28][N:39]=[C:38]([C:40]3[CH:41]=[C:42]4[C:46](=[CH:47][CH:48]=3)[NH:45][C:44]([CH2:49][OH:50])=[CH:43]4)[N:37]=2)[CH:29]=[CH:30][C:31]=1[O:32][CH:33]([CH3:35])[CH3:34]

Participants

7

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 225977283-Chloro-4-(propan-2-yloxy)benzoic acidHCID 178513239HCID 178513239, compound

Product 1

HCID 44547463[5-(5-{3-Chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1H-indol-2-yl]methanolYield 35.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

EDCI (144 mg) and HOBT (104 mg) were added to a solution of 3-chloro-4-[(1-methylethyl)oxy]benzoic acid (D32) (150 mg) in DMF (5 mL) at RT. The resulting solution was stirred for 10 min. N-Hydroxy-2-(hydroxymethyl)-1H-indole-5-carboximidamide (D25) (144 mg) was added and the reaction mixture was stirred at RT for 1 hour. The reaction mixture was heated to 80° C. and stirred at that temperature for 7 hours. EtOAc (50 mL) was added and the organic solution was washed with water (50 mL), saturated aqueous sodium bicarbonate solution (50 mL) and water (50 mL). The organic fraction was dried over anhydrous magnesium sulfate. The dried solution was concentrated. The residue was recrystallized from EtOAc/ether to afford [5-(5-{3-Chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1H-indol-2-yl]methanol (E11) (95 mg) as a light brown solid. δH (DMSO-d6, 400 MHz): 1.37 (6H, d), 4.65 (2H, d), 4.89 (1H, m), 5.36 (1H, t), 6.46 (1H, s), 7.47 (2H, m), 7.78 (1H, dd), 8.12 (1H, dd), 8.19 (1H, d), 8.27 (1H, s), 11.43 (1H, s). MS (ES): C20H18ClN3O3 requires 383; found 384.0 (M+H+).

Workup

  1. stirringthe reaction mixture was stirred at RT for 1 hour
  2. stirringstirred at that temperature for 7 hours
  3. washthe organic solution was washed with water (50 mL), saturated aqueous sodium bicarbonate solution (50 mL) and water (50 mL)
  4. dry with materialThe organic fraction was dried over anhydrous magnesium sulfate
  5. concentrationThe dried solution was concentrated
  6. customThe residue was recrystallized from EtOAc/ether

Sources & evidence

ORD record
ord-17edeed0666f43d3aedbf24d91577bde
Source dataset
uspto-grants-2012_07
Patent number
US08217028B2

Reaction notes

Loading…