1,2-Dichloroethane → Ethyl 3-[4-(5-{5-chloro-6-[(1-methylethyl)oxy]-3-pyridinyl}-1,2,4-oxadiazol-3-yl)-1H-indazol-1-yl]-2,2-dimethylpropanoate

HRID 2189798Notes

Reaction equation

HRID 2189798 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:12]([OH:14])=O)[CH:5]=[N:6][C:7]=1[O:8][CH:9]([CH3:11])[CH3:10].C(N(CC)CC)C.C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl.O[NH:37][C:38](=[NH:57])[C:39]1[CH:47]=[CH:46][CH:45]=[C:44]2[C:40]=1[CH:41]=[N:42][N:43]2[CH2:48][C:49]([CH3:56])([CH3:55])[C:50]([O:52][CH2:53][CH3:54])=[O:51]>CN(C)C=O.CCOC(C)=O>[Cl:1][C:2]1[CH:3]=[C:4]([C:12]2[O:14][N:37]=[C:38]([C:39]3[CH:47]=[CH:46][CH:45]=[C:44]4[C:40]=3[CH:41]=[N:42][N:43]4[CH2:48][C:49]([CH3:55])([CH3:56])[C:50]([O:52][CH2:53][CH3:54])=[O:51])[N:57]=2)[CH:5]=[N:6][C:7]=1[O:8][CH:9]([CH3:10])[CH3:11]

Participants

8

Reactant 5

HCID 111,2-DichloroethaneHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 180705825-Chloro-6-isopropoxynicotinic acidHCID 178471466HCID 178471466, compound

Product 1

HCID 59316746Ethyl 3-[4-(5-{5-chloro-6-[(1-methylethyl)oxy]-3-pyridinyl}-1,2,4-oxadiazol-3-yl)-1H-indazol-1-yl]-2,2-dimethylpropanoateYield 18.8%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

5-chloro-6-[(1-methylethyl)oxy]-3-pyridinecarboxylic acid (D31) (70.9 mg, 0.329 mmol), triethylamine (0.092 ml, 0.657 mmol), HOBT (60.4 mg, 0.394 mmol) then EDC (76 mg, 0.394 mmol) followed by ethyl 3-{4-[(hydroxyamino)(imino)methyl]-1H-indazol-1-yl}-2,2-dimethylpropanoate (D103) (100 mg, 0.329 mmol) were dissolved in N,N-Dimethylformamide (DMF) (5 ml). The resulting mixture was stirred at 50° C. overnight then cooled to room temperature and diluted in EtOAc. The organic phase was washed with H2O, dried and concentrated in vacuo. Purification of the residue by flash chromatography on silica gel [15-40% EtOAc/cyclohexane] gave the title compound (30 mg, 17%) as a light yellow solid. MS (ES) C24H26ClN5O4 requires 483, found 484 [M+H]+

Workup

  1. temperaturethen cooled to room temperature
  2. washThe organic phase was washed with H2O
  3. customdried
  4. concentrationconcentrated in vacuo
  5. customPurification of the residue by flash chromatography on silica gel [15-40% EtOAc/cyclohexane]

Sources & evidence

ORD record
ord-f79a2f1ae36740c3961d032dc9f62980
Source dataset
uspto-grants-2012_12
Patent number
US08324254B2

Reaction notes

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