1,2-Dichloroethane → HCID 89782824, compound

HRID 58108Notes

Reaction equation

HRID 58108 reaction equation
[CH3:1][C:2]1[N:7]=[C:6]([C:8]([OH:10])=O)[CH:5]=[CH:4][C:3]=1[C:11]1[CH:19]=[C:18]([C:20]([F:23])([F:22])[F:21])[CH:17]=[C:16]2[C:12]=1[CH:13]=[N:14][NH:15]2.C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl.[NH2:38][CH2:39][CH2:40][OH:41].C(N(C(C)C)C(C)C)C>CN(C=O)C.CCOC(C)=O>[OH:41][CH2:40][CH2:39][NH:38][C:8](=[O:10])[C:6]1[CH:5]=[CH:4][C:3]([C:11]2[CH:19]=[C:18]([C:20]([F:23])([F:21])[F:22])[CH:17]=[C:16]3[C:12]=2[CH:13]=[N:14][NH:15]3)=[C:2]([CH3:1])[N:7]=1

Participants

8

Reactant 5

HCID 111,2-DichloroethaneHCID 700EthanolamineHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 897833556-methyl-5-(6-(trifluoromethyl)-1H-indazol-4-yl)picolinic acid

Product 1

HCID 89782824HCID 89782824, compoundYield 36.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To 6-methyl-5-(6-(trifluoromethyl)-1H-indazol-4-yl)picolinic acid (1.6 g, 4.98 mmol) in DMF (20 mL) were added HOBt (0.942 g, 6.97 mmol), EDC (1.432 g, 7.47 mmol), 2-aminoethanol (0.913 g, 14.94 mmol), followed by N-ethyl-N-isopropylpropan-2-amine (4.34 mL, 24.90 mmol). The reaction mixture was stirred for 16 hours at room temperature, was subsequently diluted with EtOAc and was washed with brine. Volatiles were evaporated from the organic phase and the residue was purified by CombiFlash® chromatography, eluting with a gradient of 0-20% MeOH in DCM. The product-containing fractions were combined and concentrated in vacuo to give the title compound as a white solid (0.658 g, 36.3%). 1H NMR (400 MHz, DMSO-d6) δ ppm 2.43 (s, 3H), 3.44 (q, J=5.98 Hz, 2H), 3.57 (t, J=5.94 Hz, 2H), 7.38-7.44 (m, 1H), 7.90-8.07 (m, 4H), 8.70 (t, J=5.81 Hz, 1H); ESI-MS m/z [M+H]+ calc'd for C17H15F3N4O2, 365.1. found 365.2.

Workup

  1. washwas washed with brine
  2. customVolatiles were evaporated from the organic phase
  3. customthe residue was purified by CombiFlash® chromatography
  4. washeluting with a gradient of 0-20% MeOH in DCM
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-d8e84ccb75fa4262a6068ee19592e58f
Source dataset
uspto-grants-2016_09
Patent number
US09434743B2

Reaction notes

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