1,2-Dichloroethane → Ethyl 3-[4-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1H-indazol-1-yl]propanoate

HRID 2189789Notes

Reaction equation

HRID 2189789 reaction equation
ONC(=N)C1C2C(C=CC=1)=NN(CCC(OCC)=O)C=2.[OH:21][NH:22][C:23](=[NH:40])[C:24]1[CH:32]=[CH:31][CH:30]=[C:29]2[C:25]=1[CH:26]=[N:27][N:28]2[CH2:33][CH2:34][C:35]([O:37][CH2:38][CH3:39])=[O:36].[Cl:41][C:42]1[CH:43]=[C:44]([CH:48]=[CH:49][C:50]=1[O:51][CH:52]([CH3:54])[CH3:53])[C:45](O)=O.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1>CN(C)C=O.C(OCC)(=O)C>[Cl:41][C:42]1[CH:43]=[C:44]([C:45]2[O:21][N:22]=[C:23]([C:24]3[CH:32]=[CH:31][CH:30]=[C:29]4[C:25]=3[CH:26]=[N:27][N:28]4[CH2:33][CH2:34][C:35]([O:37][CH2:38][CH3:39])=[O:36])[N:40]=2)[CH:48]=[CH:49][C:50]=1[O:51][CH:52]([CH3:53])[CH3:54]

Participants

8

Reactant 5

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 225977283-Chloro-4-(propan-2-yloxy)benzoic acidHCID 178471831HCID 178471831, compoundHCID 178471848HCID 178471848, compound

Product 1

HCID 59316710Ethyl 3-[4-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1H-indazol-1-yl]propanoateYield 65.8%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of ethyl 3-{4-[(hydroxyamino)(imino)methyl]-2H-indazol-2-yl}propanoate & ethyl 3-{4-[(hydroxyamino)(imino)methyl]-1H-indazol-1-yl}propanoate (D55) (700 mg, 1.27 mmol) (a 3:1 mix of 1 and 2-isomers), 3-chloro-4-[(1-methylethyl)oxy]benzoic acid (D3) (0.544 g, 2.53 mmol), EDC (0.534 g, 2.79 mmol) and HOBT (0.427 g, 2.79 mmol) in N,N-dimethylformamide (10 ml) was heated at 120° C. for 2 hrs, cooled, diluted with ethyl acetate (60 ml) and washed with water (3×20 ml). The organic layer was dried (MgSO4), evaporated and purified by flash chromatography eluting with EtOAc/hexane 1:4 to give the title compound (380 mg) as a white solid. δH (CDCl3, 400 MHz): 1.17 (3H, t), 1.46 (6H, d), 3.02 (2H, t), 4.10 (2H, q), 4.70-4.77 (3H, m), 7.08 (1H, d), 7.53 (1H, dd), 7.69 (1H, d), 8.05-8.12 (2H, m), 8.29 (1H, d), 8.71 (1H, d). MS (ES): C23H2335ClN4O4 requires 454; found (MH+) 455.

Workup

  1. temperaturecooled
  2. washwashed with water (3×20 ml)
  3. dry with materialThe organic layer was dried (MgSO4)
  4. customevaporated
  5. custompurified by flash chromatography
  6. washeluting with EtOAc/hexane 1:4

Sources & evidence

ORD record
ord-5541b79475924df890a966435eec43a6
Source dataset
uspto-grants-2012_12
Patent number
US08324254B2

Reaction notes

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