Trifluoroacetic acid → Ammonium Acetate

HRID 2068436Notes

Reaction equation

HRID 2068436 reaction equation
F[C:2]([F:7])(F)[C:3]([OH:5])=[O:4].[N:8]1[CH:13]=[CH:12][C:11]([C:14]2([NH2:17])[CH2:16][CH2:15]2)=[CH:10][N:9]=1.C(N(C(C)C)CC)(C)C.C(O[C:32]([N:34](C)[C:35]([C:37]1[C:38]([C:59]2[CH:64]=CC(F)=[CH:61][CH:60]=2)=[N:39][N:40]2[CH:45]=[CH:44][C:43]([C:46]3[C:47]([CH3:57])=[CH:48][C:49]([O:55][CH3:56])=[C:50]([CH:54]=3)[C:51](O)=[O:52])=[C:42]([F:58])[C:41]=12)=[O:36])=O)(C)(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.FC(F)(F)C(O)=O>ClCCl.CN(C=O)C>[C:3]([O-:5])(=[O:4])[CH3:2].[NH4+:8].[F:58][C:42]1[C:41]2[N:40]([N:39]=[C:38]([C:59]3[CH:60]=[CH:61][C:2]([F:7])=[CH:3][CH:64]=3)[C:37]=2[C:35]([NH:34][CH3:32])=[O:36])[CH:45]=[CH:44][C:43]=1[C:46]1[CH:54]=[C:50]([C:51](=[O:52])[NH:17][C:14]2([C:11]3[CH:12]=[CH:13][N:8]=[N:9][CH:10]=3)[CH2:16][CH2:15]2)[C:49]([O:55][CH3:56])=[CH:48][C:47]=1[CH3:57]

Participants

9

Reactant 5

HCID 6422Trifluoroacetic acidHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 67405354HCID 67405354, compoundHCID 67419172HCID 67419172, compound

Product 2

HCID 517165Ammonium AcetateHCID 46842574HCID 46842574, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution containing 1-(pyridazin-4-yl)cyclopropanamine trifluoroacetate. (0.018 g, 0.076 mmol), diisopropylethylamine (0.076 mL, 0.44 mmol), 5-(3-(tert-butoxycarbonyl(methyl)carbamoyl)-4-fluoro-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-5-yl)-2-methoxy-4-methylbenzoic acid (0.030 g, 0.054 mmol) and DMF (0.37 mL) was added HATU (0.041 g, 0.11 mmol) in one portion. The solution was maintained at room temperature for 15 minutes. Dichloromethane (0.36 mL) was then added followed by trifluoroacetic acid (0.11 mL, 1.4 mmol). The solution was maintained for an additional 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) afforded 4-fluoro-2-(4-fluorophenyl)-5-(4-methoxy-2-methyl-5-(1-(pyridazin-4-yl)cyclopropylcarbamoyl)phenyl)-N-methylpyrazolo[1,5-a]pyridine-3-carboxamide as a white solid. Preparative HPLC retention time: 9.7 min. 1H NMR (400 MHz, MeOD) δ ppm 9.05-9.15 (3H, m), 8.50 (1H, d, J=7.03 Hz), 7.83-7.92 (2H, m), 7.76-7.80 (1H, m), 7.56 (1H, dd, J=5.65, 2.64 Hz), 7.15-7.26 (3H, m), 6.88 (1H, t, J=6.78 Hz), 4.04-4.13 (3H, m), 2.88-2.92 (3H, m), 2.36 (3H, s), 1.63 (5H, s). LCMS: retention time: 1.798 min. LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a Phenomenex-Luna, 3 micron, C18, 2.0×30 mm column using a SPD-10AV UV-Vis 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 2 min, a hold time of 1 min, and an analysis time of 3 min where solvent A was 5% CH3OH/95% H2O/10 mM ammonium acetate and solvent B was 5% H2O/95% CH3OH/10 mM ammonium acetate. MS data was determined using a Micromass Platform for LC in electrospray mode. m/z 569 (MH+).

Workup

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

Sources & evidence

ORD record
ord-afd655acab54466aa39567275d1e86c2
Source dataset
uspto-grants-2012_10
Patent number
US08293909B2

Reaction notes

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