1,2-Dichloroethane → Trifluoroacetic acid

HRID 58096

Reaction equation

HRID 58096 reaction equation
[F:1][C:2]([F:22])([F:21])[C:3]1[CH:11]=[C:10]2[C:6]([CH:7]=[N:8][NH:9]2)=[C:5]([C:12]2[CH:17]=[CH:16][N:15]=[C:14]([C:18]([OH:20])=O)[CH:13]=2)[CH:4]=1.[Cl-].[NH4+].C1C=CC2N([OH:34])N=[N:31]C=2C=1.C(Cl)CCl.C(N(C(C)C)C(C)C)C.CN([CH:51]=[O:52])C>>[C:51]([OH:52])([C:2]([F:22])([F:21])[F:1])=[O:34].[F:21][C:2]([F:1])([F:22])[C:3]1[CH:11]=[C:10]2[C:6]([CH:7]=[N:8][NH:9]2)=[C:5]([C:12]2[CH:17]=[CH:16][N:15]=[C:14]([C:18]([NH2:31])=[O:20])[CH:13]=2)[CH:4]=1

Participants

8

Reactant 6

HCID 111,2-DichloroethaneHCID 6228DimethylformamideHCID 25517Ammonium ChlorideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 897828414-(6-(trifluoromethyl)-1H-indazol-4-yl)picolinic acid

Product 2

HCID 6422Trifluoroacetic acidHCID 897829074-(6-(trifluoromethyl)-1H-indazol-4-yl)picolinamide

Procedure

To a mixture of 4-(6-(trifluoromethyl)-1H-indazol-4-yl)picolinic acid (0.028 g, 0.091 mmol) in DMF (3 mL) were added ammonium chloride (0.024 g, 0.456 mmol), HOBt (0.018 g, 0.137 mmol), and EDC (0.028 g, 0.146 mmol), followed by N-ethyl-N-isopropylpropan-2-amine (0.079 mL, 0.456 mmol). The reaction mixture was stirred for 18 hours at room temperature. The crude reaction mixture was subsequently purified by preparative HPLC, eluting with a gradient of 30-35% acetonitrile (containing 0.035% TFA) in H2O (containing 0.05% TFA) over a period of 6.5 minutes. The product-containing fractions were combined and the solvent removed in vacuo to give a TFA salt of the title compound as an off white solid (0.012 g, 43%). 1H NMR (400 MHz, DMSO-d6) δ ppm 7.68 (s, 1H), 7.80 (br s, 1H), 7.95-8.15 (m, 2H), 8.27 (br s, 1H), 8.32-8.47 (m, 2H), 8.81 (d, J=5.05 Hz, 1H), 13.89 (br s, 1H); ESI-MS m/z [M+H]+ calc'd for C14H9F3N4O, 307.1. found 307.11.

Workup

  1. customThe crude reaction mixture
  2. customwas subsequently purified by preparative HPLC
  3. washeluting with a gradient of 30-35% acetonitrile (containing 0.035% TFA) in H2O (containing 0.05% TFA) over a period of 6.5 minutes
  4. customthe solvent removed in vacuo

Sources & evidence

ORD record
ord-768d7102f4d84836a4deb09f4e519dc5
Source dataset
uspto-grants-2016_09
Patent number
US09434743B2

Linked notes

Loading…