1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 67025190, compound

HRID 1512734Notes

Reaction equation

HRID 1512734 reaction equation
CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.[C:22]([C:24]1[CH:25]=[C:26]([CH:30]=[CH:31][C:32]=1[O:33][CH:34]([CH3:36])[CH3:35])[C:27]([OH:29])=O)#[N:23].O[NH:38][C:39](=[NH:58])[C:40]1[CH:48]=[C:47]2[C:43]([C:44]([CH2:49][CH2:50][C:51]([O:53][C:54]([CH3:57])([CH3:56])[CH3:55])=[O:52])=[CH:45][NH:46]2)=[CH:42][CH:41]=1>CN(C=O)C>[C:22]([C:24]1[CH:25]=[C:26]([C:27]2[O:29][N:38]=[C:39]([C:40]3[CH:48]=[C:47]4[C:43]([C:44]([CH2:49][CH2:50][C:51]([O:53][C:54]([CH3:57])([CH3:56])[CH3:55])=[O:52])=[CH:45][NH:46]4)=[CH:42][CH:41]=3)[N:58]=2)[CH:30]=[CH:31][C:32]=1[O:33][CH:34]([CH3:36])[CH3:35])#[N:23]

Participants

6

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 21956832RP-101124HCID 178450933HCID 178450933, compound

Product 1

HCID 67025190HCID 67025190, compoundYield 33.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

EDCI (151 mg) and HOBT (121 mg) were added to a solution of 3-cyano-4-[(1-methylethyl)oxy]benzoic acid (can be prepared as described in WO2005/58848, 135 mg) in DMF (5 mL) at RT. The resulting solution was stirred for 45 min. 1,1-dimethylethyl 3-{6-[(hydroxyamino)(imino)methyl]-1H-indol-3-yl}propanoate (D16) (199 mg) was added and the reaction mixture was stirred at RT for 3 hours. The reaction mixture was heated to 80° C. and stirred at that temperature for 5 hours. DMF was evaporated. EtOAc (100 mL) was added and the organic solution was washed with saturated aqueous sodium bicarbonate solution (75 mL) and water (75 mL). The organic fraction was dried over anhydrous magnesium sulfate. The dried solution was concentrated. The residue was purified by Biotage (25→33% EtOAc in hexane) to afford 1,1-dimethylethyl 3-[6-(5-{3-cyano-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1H-indol-3-yl]propanoate (D19) (105 mg) as a white solid. δH (DMSO-d6, 400 MHz): 1.38 (9H, s), 1.39 (6H, d), 2.60 (2H, t), 2.96 (2H, t), 4.98 (1H, m), 7.35 (1H, d), 7.55 (1H, d), 7.72 (2H, m), 8.12 (1H, d), 8.42 (1H, dd), 8.51 (1H, d), 11.21 (1H, s). MS (ES): C27H28N4O4 requires 472; found 473.0 (M+H+).

Workup

  1. stirringthe reaction mixture was stirred at RT for 3 hours
  2. stirringstirred at that temperature for 5 hours
  3. customDMF was evaporated
  4. additionEtOAc (100 mL) was added
  5. washthe organic solution was washed with saturated aqueous sodium bicarbonate solution (75 mL) and water (75 mL)
  6. dry with materialThe organic fraction was dried over anhydrous magnesium sulfate
  7. concentrationThe dried solution was concentrated
  8. customThe residue was purified by Biotage (25→33% EtOAc in hexane)

Sources & evidence

ORD record
ord-d772084cf801483dba4576617f8db2fb
Source dataset
uspto-grants-2012_07
Patent number
US08217028B2

Reaction notes

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