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

HRID 2189797Notes

Reaction equation

HRID 2189797 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[O:11][CH:12]([CH3:14])[CH3:13])[C:5]([OH:7])=O.O[NH:16][C:17](=[NH:36])[C:18]1[CH:26]=[CH:25][CH:24]=[C:23]2[C:19]=1[CH:20]=[N:21][N:22]2[CH2:27][C:28]([CH3:35])([CH3:34])[C:29]([O:31][CH2:32][CH3:33])=[O:30].C(N(C(C)C)C(C)C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([C:5]2[O:7][N:16]=[C:17]([C:18]3[CH:26]=[CH:25][CH:24]=[C:23]4[C:19]=3[CH:20]=[N:21][N:22]4[CH2:27][C:28]([CH3:34])([CH3:35])[C:29]([O:31][CH2:32][CH3:33])=[O:30])[N:36]=2)[CH:8]=[CH:9][C:10]=1[O:11][CH:12]([CH3:14])[CH3:13]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 225977283-Chloro-4-(propan-2-yloxy)benzoic acidHCID 178471466HCID 178471466, compound

Product 1

HCID 59316762Ethyl 3-[4-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1H-indazol-1-yl]-2,2-dimethylpropanoateYield 42.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 3-chloro-4-[(1-methylethyl)oxy]benzoic acid (D3) (245 mg, 1.143 mmol), ethyl 3-{4-[(hydroxyamino)(imino)methyl]-1H-indazol-1-yl}-2,2-dimethylpropanoate (D103) (348 mg, 1.143 mmol), in DMF (5 ml) at room temperature was treated with N-ethyl-N-(1-methylethyl)-2-propanamine (0.240 ml, 1.372 mmol) followed by HATU (522 mg, 1.372 mmol). The resulting mixture was stirred at room temperature for 1 hour and at 80° C. overnight and then for a further 4 hours, then cooled to room temperature and concentrated in vacuo. The residue was dissolved in EtOAc and the organic phase was washed twice with H2O then brine, dried and concentrated in vacuo. Purification of the residue by flash chromatography on silica gel [gradient ethyl acetate/cyclohexane] gave the title compound (233 mg, 39%) as a cream solid. MS (ES) C25H27ClN4O4 requires 482, found 483 [M+H]+

Workup

  1. waitfor a further 4 hours
  2. temperaturecooled to room temperature
  3. concentrationconcentrated in vacuo
  4. dissolutionThe residue was dissolved in EtOAc
  5. washthe organic phase was washed twice with H2O
  6. dry with materialbrine, dried
  7. concentrationconcentrated in vacuo
  8. customPurification of the residue by flash chromatography on silica gel [gradient ethyl acetate/cyclohexane]

Sources & evidence

ORD record
ord-0c9e03968a0b4f16b2c732c480a700a5
Source dataset
uspto-grants-2012_12
Patent number
US08324254B2

Reaction notes

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