1,2-Dichloroethane → HCID 89783109, compound

HRID 58109Notes

Reaction equation

HRID 58109 reaction equation
[CH3:1][O:2][C:3]1[N:8]=[C:7]([C:9](O)=[O:10])[CH:6]=[CH:5][C:4]=1[C:12]1[CH:20]=[C:19]([C:21]([F:24])([F:23])[F:22])[CH:18]=[C:17]2[C:13]=1[CH:14]=[N:15][NH:16]2.[Cl-].[NH4+].C1C=CC2N([OH:36])N=[N:33]C=2C=1.C(Cl)CCl.C(N(C(C)C)C(C)C)C.CN([CH:53]=[O:54])C>>[C:53]([OH:54])([C:21]([F:24])([F:23])[F:22])=[O:36].[CH3:1][O:2][C:3]1[N:8]=[C:7]([C:9]([NH2:33])=[O:10])[CH:6]=[CH:5][C:4]=1[C:12]1[CH:20]=[C:19]([C:21]([F:22])([F:23])[F:24])[CH:18]=[C:17]2[C:13]=1[CH:14]=[N:15][NH:16]2

Participants

8

Reactant 6

HCID 111,2-DichloroethaneHCID 6228DimethylformamideHCID 25517Ammonium ChlorideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 89783129HCID 89783129, compound

Product 2

HCID 6422Trifluoroacetic acidHCID 89783109HCID 89783109, compoundYield 60%

Procedure

To 6-methoxy-5-(6-(trifluoromethyl)-1H-indazol-4-yl)picolinic acid (0.020 g, 0.059 mmol) in DMF (3 mL) were added ammonium chloride (0.016 g, 0.297 mmol), HOBt (0.011 g, 0.083 mmol), and EDC (0.017 g, 0.089 mmol), followed by N-ethyl-N-isopropylpropan-2-amine (0.052 mL, 0.297 mmol). The reaction mixture was stirred for 1 hour at room temperature. The crude reaction mixture was purified by preparative HPLC, eluting with a gradient of 30-40% acetonitrile (containing 0.035% TFA) in H2O (containing 0.05% TFA) over a period of 7 minutes. The product-containing fractions were combined and the volatiles removed in vacuo to give a TFA salt of the title compound as white solid (0.012 g, 60%). 1H NMR (400 MHz, DMSO-d6) δ ppm 3.99 (s, 3H), 7.45-7.51 (m, 1H), 7.70-7.83 (m, 1H), 7.98 (s, 1H), 8.03-8.12 (m, 2H), 8.13 (s, 1H); ESI-MS m/z [M+H]+ calc'd for C15H11F3N4O2, 337.1. found 337.15.

Workup

  1. customThe crude reaction mixture
  2. customwas purified by preparative HPLC
  3. washeluting with a gradient of 30-40% acetonitrile (containing 0.035% TFA) in H2O (containing 0.05% TFA) over a period of 7 minutes
  4. customthe volatiles removed in vacuo

Sources & evidence

ORD record
ord-6ab224ae60dc4e67a243795afcfb48bc
Source dataset
uspto-grants-2016_09
Patent number
US09434743B2

Reaction notes

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