1,2-Dichloroethane → HCID 59316740, compound

HRID 2189787Notes

Reaction equation

HRID 2189787 reaction equation
ONC(=N)C1C2C(C=CC=1)=NN(CCCC(OCC)=O)C=2.[OH:22][NH:23][C:24](=[NH:42])[C:25]1[CH:33]=[CH:32][CH:31]=[C:30]2[C:26]=1[CH:27]=[N:28][N:29]2[CH2:34][CH2:35][CH2:36][C:37]([O:39][CH2:40][CH3:41])=[O:38].[Cl:43][C:44]1[CH:45]=[C:46]([CH:50]=[CH:51][C:52]=1[O:53][CH:54]([CH3:56])[CH3:55])[C:47](O)=O.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1>CN(C)C=O.C(OCC)(=O)C.O>[Cl:43][C:44]1[CH:45]=[C:46]([C:47]2[O:22][N:23]=[C:24]([C:25]3[CH:33]=[CH:32][CH:31]=[C:30]4[C:26]=3[CH:27]=[N:28][N:29]4[CH2:34][CH2:35][CH2:36][C:37]([O:39][CH2:40][CH3:41])=[O:38])[N:42]=2)[CH:50]=[CH:51][C:52]=1[O:53][CH:54]([CH3:55])[CH3:56]

Participants

9

Reactant 5

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 225977283-Chloro-4-(propan-2-yloxy)benzoic acidHCID 178471587HCID 178471587, compoundHCID 178471593HCID 178471593, compound

Product 1

HCID 59316740HCID 59316740, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of ethyl 4-{4-[(hydroxyamino)(imino)methyl]-2H-indazol-2-yl}butanoate & ethyl 4-{4-[(hydroxyamino)(imino)methyl]-1H-indazol-1-yl}butanoate (D56) (0.27 g, 0.930 mmol) (a 3:2 mix of 1 and 2-isomers), 3-chloro-4-[(1-methylethyl)oxy]benzoic acid (D3) (0.200 g, 0.930 mmol), EDC (0.196 g, 1.023 mmol) and HOBT (0.157 g, 1.023 mmol) in N,N-dimethylformamide (5 ml) was stirred at 80° C. for 16 hrs then at 120° C. for 2 hours. The reaction was cooled, diluted with ethyl acetate (40 ml) and water (40 ml) and the organic washed with 3×15 ml of water, dried (magnesium sulphate) and evaporated. The crude material was purified by flash chromatography eluting with 3:7 ethyl acetate/hexane to give two products which were triturated with 1:1 ether/hexane to give 66 mgs of upper spot and 36 mgs of lower. The upper spot was the desired 1-substituted indazole. δH (CDCl3, 400 MHz): 1.24 (3H, t), 1.46 (6H, d), 2.31 (4H, m), 4.12 (2H, q), 4.55 (2H, t), 4.73 (1H, m), 7.08 (1H, d), 7.52 (1H, dd), 7.62 (1H, d), 8.07 (1H, dd), 8.11 (1H, dd), 8.29 (1H, d), 8.70 (1H, d).

Workup

  1. waitat 120° C. for 2 hours
  2. temperatureThe reaction was cooled
  3. washthe organic washed with 3×15 ml of water
  4. dry with materialdried (magnesium sulphate)
  5. customevaporated
  6. customThe crude material was purified by flash chromatography
  7. washeluting with 3:7 ethyl acetate/hexane
  8. customto give two products which
  9. customwere triturated with 1:1 ether/hexane
  10. customto give 66 mgs of upper spot and 36 mgs of lower

Sources & evidence

ORD record
ord-d70181e7f8c64d47bfa71744d8306cbf
Source dataset
uspto-grants-2012_12
Patent number
US08324254B2

Reaction notes

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