Trifluoroacetic acid → 6-(2-(1H-indazol-5-yl)ethyl)-N-(4-(difluoromethoxy)phenyl)pyridazin-3-amine

HRID 77494Notes

Reaction equation

HRID 77494 reaction equation
[F:1][CH:2]([F:34])[O:3][C:4]1[CH:9]=[CH:8][C:7]([NH:10][C:11]2[N:12]=[N:13][C:14]([CH2:17][CH2:18][C:19]3[CH:20]=[C:21]4[C:25](=[CH:26][CH:27]=3)[N:24](C3CCCCO3)[N:23]=[CH:22]4)=[CH:15][CH:16]=2)=[CH:6][CH:5]=1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[NH:24]1[C:25]2[C:21](=[CH:20][C:19]([CH2:18][CH2:17][C:14]3[N:13]=[N:12][C:11]([NH:10][C:7]4[CH:8]=[CH:9][C:4]([O:3][CH:2]([F:34])[F:1])=[CH:5][CH:6]=4)=[CH:16][CH:15]=3)=[CH:27][CH:26]=2)[CH:22]=[N:23]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86679787N-(4-(difluoromethoxy)phenyl)-6-(2-(1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-5-yl)ethyl)pyridazin-3-amine

Product 1

HCID 715373366-(2-(1H-indazol-5-yl)ethyl)-N-(4-(difluoromethoxy)phenyl)pyridazin-3-amine

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of N-(4-(difluoromethoxy)phenyl)-6-(2-(1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-5-yl)ethyl)pyridazin-3-amine (0.12 g, 0.258 mmol) in DCM (10 mL) was added TFA (1 mL, 12.98 mmol) and the reaction mixture was stirred at room temperature for 3 h. The reaction mixture was concentrated and washed with diethyl ether. The crude product was purified by preparative LCMS on a Waters Xbridge C18 column (19×150 mm, 5 μm) using 0-100% mobile phase B (95:5 Methanol:water with 10 mM NH4OAc) in mobile phase A (5:95 Methanol:water with 10 mM NH4OAc) to give 6-(2-(1H-indazol-5-yl)ethyl)-N-(4-(difluoromethoxy)phenyl)pyridazin-3-amine. 1H-NMR (300 MHz, DMSO-d6) δ ppm 3.07-3.14 (m, 4H) 6.28 (s, 1H) 7.00-7.37 (m, 6H) 7.46 (s, 1H) 7.56 (s, 1H) 7.78 (s, 3H) 7.97 (s, 1H) 9.19 (s, 1H) 12.93 (br. s., 1H).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. washwashed with diethyl ether
  3. customThe crude product was purified by preparative LCMS on a Waters Xbridge C18 column (19×150 mm, 5 μm)

Sources & evidence

ORD record
ord-a48a5b4efdc94709bcf38c38d83198ab
Source dataset
uspto-grants-2014_09
Patent number
US08841301B2

Reaction notes

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