Trifluoroacetic acid → Ammonium Acetate

HRID 2188978Notes

Reaction equation

HRID 2188978 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:16]([C:17]([N:19](C)[C:20](=O)OC(C)(C)C)=[O:18])=[C:15]3[N:10]([N:11]=[CH:12][C:13]([C:28]4[CH:33]=[C:32]([C:34](=[O:45])[NH:35][C:36]5([C:39]6[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=6)[CH2:38][CH2:37]5)[CH:31]=[CH:30][C:29]=4[CH3:46])=[CH:14]3)[N:9]=2)=[CH:4][CH:3]=1.[C:47]([OH:53])([C:49](F)(F)F)=[O:48]>ClCCl>[C:47]([O-:53])(=[O:48])[CH3:49].[NH4+:9].[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:16]([C:17]([NH:19][CH3:20])=[O:18])=[C:15]3[N:10]([N:11]=[CH:12][C:13]([C:28]4[CH:33]=[C:32]([C:34](=[O:45])[NH:35][C:36]5([C:39]6[CH:40]=[CH:41][CH:42]=[CH:43][CH:44]=6)[CH2:38][CH2:37]5)[CH:31]=[CH:30][C:29]=4[CH3:46])=[CH:14]3)[N:9]=2)=[CH:4][CH:3]=1

Participants

5

Reactant 2

HCID 6422Trifluoroacetic acidHCID 66763708Tert-butyl 2-(4-fluorophenyl)-5-(2-methyl-5-(1-phenylcyclopropylcarbamoyl)phenyl)pyrazolo[1,5-b]pyridazine-3-carbonyl(methyl)carbamate

Product 2

HCID 517165Ammonium AcetateHCID 533788042-(4-fluorophenyl)-N-methyl-5-(2-methyl-5-(1-phenylcyclopropylcarbamoyl)phenyl)pyrazolo[1,5-b]pyridazine-3-carboxamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution containing tert-butyl 2-(4-fluorophenyl)-5-(2-methyl-5-(1-phenylcyclopropylcarbamoyl)phenyl)pyrazolo[1,5-b]pyridazine-3-carbonyl(methyl)carbamate (0.044 g, 0.065 mmol) and dichloromethane (4 mL) was added TFA (0.41 mL, 5.3 mmol) at room temperature. The solution was maintained for 15 min and concentrated. The resultant residue was purified using preparative HPLC (Waters-Xbridge, 50×100 mm, 5 micron, C18 column; 0.1M ammonium acetate, 0-100% B (B=5% H2O/CH3CN)/A (A=95% H2O/CH3CN), 15 min. gradient) to afford 2-(4-fluorophenyl)-N-methyl-5-(2-methyl-5-(1-phenylcyclopropylcarbamoyl)phenyl)pyrazolo[1,5-b]pyridazine-3-carboxamide as a white solid. Preparative HPLC: retention time: 12.6 min. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 8.68 (d, J=2.51 Hz, 1 H), 8.43 (d, J=2.26 Hz, 1 H), 7.85 (dd, J=7.91, 1.88 Hz, 1 H), 7.72-7.81 (m, 3 H), 7.45 (d, J=8.03 Hz, 1 H), 7.28-7.36 (m, 5 H), 7.16-7.27 (m, 3 H), 5.90 (d, J=4.52 Hz, 1 H), 2.90 (d, J=5.02 Hz, 3 H), 2.43 (s, 3 H), 1.42 (s, 2 H), 1.35-1.41 (m, 2 H). LCMS retention time: 2.310 min. LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a Phenomenex-Luna, 10 micron, C18, 3.0×50 mm column using a SPD-10AV UV-V is detector at a detector wave length of 220 nM. The elution conditions employed a flow rate of 4 mL/min, a gradient of 100% solvent A/0% solvent B to 0% solvent A/100% solvent B, a gradient time of 3 min, a hold time of 1 min, and an analysis time of 4 min where solvent A was 10% methanol/90% H2O/10 mM TFA and solvent B was 10% H2O/90% methanol/10 mM TFA. MS data was determined using a Micromass Platform for LC in electrospray mode. m/z 520 (MH+).

Workup

  1. temperatureThe solution was maintained for 15 min
  2. concentrationconcentrated
  3. customThe resultant residue was purified

Sources & evidence

ORD record
ord-a3aa02d1a66348d0a444314facaa4e93
Source dataset
uspto-grants-2012_12
Patent number
US08324212B2

Reaction notes

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