1,2-Dichloroethane → 2-(4-(6-(trifluoromethyl)-1H-indazol-4-yl)-1H-pyrazol-1-yl)acetamide

HRID 58091Notes

Reaction equation

HRID 58091 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:13]=[N:14][N:15]([CH2:17][C:18]([OH:20])=O)[CH:16]=2)[CH:4]=1.C1C=CC2N(O)N=[N:29]C=2C=1.C(Cl)CCl.[Cl-].[NH4+].C(N(C(C)C)C(C)C)C>CN(C=O)C>[F:1][C:2]([F:21])([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:13]=[N:14][N:15]([CH2:17][C:18]([NH2:29])=[O:20])[CH:16]=2)[CH:4]=1

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 25517Ammonium ChlorideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 897830682-(4-(6-(trifluoromethyl)-1H-indazol-4-yl)-1H-pyrazol-1-yl)acetic acid

Product 1

HCID 897829792-(4-(6-(trifluoromethyl)-1H-indazol-4-yl)-1H-pyrazol-1-yl)acetamideYield 31%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To 2-(4-(6-(trifluoromethyl)-1H-indazol-4-yl)-1H-pyrazol-1-yl)acetic acid (0.052 g, 0.168 mmol) in DMF (3 mL) were added HOBt (0.029 g, 0.218 mmol), EDC (0.045 g, 0.235 mmol), ammonium chloride (0.045 g, 0.838 mmol), followed by N-ethyl-N-isopropylpropan-2-amine (0.146 mL, 0.838 mmol). The reaction mixture was stirred for 18 hours at room temperature. The crude mixture was subsequently purified by preparative HPLC (Waters SunFire C18, 5 μm, 30 mm ID×75 mm column) eluting with a gradient of 20-30% ACN (containing 0.035% TFA) in water (containing 0.05% TFA) to give the title compound as white solid (0.016 g, 31%). 1H NMR (400 MHz, DMSO-d6) δ ppm 4.84 (s, 2H), 7.33 (br s, 1 H), 7.51-7.68 (m, 2H), 7.75 (s, 1H), 8.23 (d, J=0.76 Hz, 1H), 8.56 (d, J=4.29 Hz, 2H), 13.62 (s, 1H); ESI-MS m/z [M+H]+ calc'd for C13H10F3N5O, 310.1. found 310.

Workup

  1. customThe crude mixture was subsequently purified by preparative HPLC (Waters SunFire C18, 5 μm, 30 mm ID×75 mm column)
  2. washeluting with a gradient of 20-30% ACN (containing 0.035% TFA) in water (containing 0.05% TFA)

Sources & evidence

ORD record
ord-58d423bc481a4f31bba1e25ff11a0c76
Source dataset
uspto-grants-2016_09
Patent number
US09434743B2

Reaction notes

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