Diisopropylethylamine → Ammonium Acetate

HRID 2068355Notes

Reaction equation

HRID 2068355 reaction equation
Cl.[C:2]1([C:8]2([NH2:11])[CH2:10][CH2:9]2)[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(C(C)C)CC)(C)C.[F:21][C:22]1[C:23]2[N:24]([N:38]=[C:39]([C:45]3[CH:50]=[CH:49][C:48]([F:51])=[CH:47][CH:46]=3)[C:40]=2[C:41](=[O:44])[NH:42][CH3:43])[CH:25]=[CH:26][C:27]=1[C:28]1[CH:29]=[C:30]([CH:34]=[CH:35][C:36]=1[CH3:37])[C:31]([OH:33])=[O:32].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[C:31]([O-:33])(=[O:32])[CH3:30].[NH4+:11].[F:21][C:22]1[C:23]2[N:24]([N:38]=[C:39]([C:45]3[CH:46]=[CH:47][C:48]([F:51])=[CH:49][CH:50]=3)[C:40]=2[C:41]([NH:42][CH3:43])=[O:44])[CH:25]=[CH:26][C:27]=1[C:28]1[CH:29]=[C:30]([C:31](=[O:32])[NH:11][C:8]2([C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)[CH2:10][CH2:9]2)[CH:34]=[CH:35][C:36]=1[CH3:37]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 1945481-PhenylcyclopropylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 592338113-(4-Fluoro-2-(4-fluorophenyl)-3-(methylcarbamoyl)pyrazolo[1,5-a]pyridin-5-yl)-4-methylbenzoic acid

Product 2

HCID 517165Ammonium AcetateHCID 461746964-fluoro-2-(4-fluorophenyl)-N-methyl-5-(2-methyl-5-(1-phenylcyclopropylcarbamoyl)phenyl)pyrazolo[1,5-a]pyridine-3-carboxamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution containing 1-phenylcyclopropanamine hydrochloride (0.030 g, 0.18 mmol), diisopropylethylamine (0.16 mL, 0.95 mmol), 3-(4-fluoro-2-(4-fluorophenyl)-3-(methylcarbamoyl)pyrazolo[1,5-a]pyridin-5-yl)-4-methylbenzoic acid (0.050 g, 0.12 mmol) and DMF (0.8 mL) was added HATU (0.09 g, 0.24 mmol) in one portion. The solution was maintained at room temperature for 1 h and concentrated. The resultant residue was purified using preparative HPLC (Waters-Xbridge, 50×100 mm, 5 micron, C18 column; 0.1M ammonium acetate, 10-100% B (B=5% H2O/CH3CN)/A (A=95% H2O/CH3CN), 15 min. gradient) to afford 4-fluoro-2-(4-fluorophenyl)-N-methyl-5-(2-methyl-5-(1-phenylcyclopropylcarbamoyl)phenyl)pyrazolo[1,5-a]pyridine-3-carboxamide as a white solid. Preparative HPLC retention time: 9.0 min. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 8.35 (d, J=6.78 Hz, 1H), 7.81-7.90 (m, 2H), 7.76 (d, J=7.78 Hz, 1H), 7.72 (s, 1H), 7.40 (d, J=8.03 Hz, 1H), 7.29-7.37 (m, 4H), 7.13-7.24 (m, 3H), 6.90 (s, 1H), 6.73 (t, J=6.65 Hz, 1H), 5.90 (d, J=4.52 Hz, 1H), 2.97 (d, J=4.77 Hz, 3H), 2.32 (s, 3H), 1.39 (br. s., 4H). LCMS retention time: 1.975 min. LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a Xbridge, 5 micron, C18, 4.6×50 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 3 min, a hold time of 1 min, and an analysis time of 4 min where solvent A was 5% CH3CN/95% H2O/10 mM ammonium acetate and solvent B was 5% H2O/95% CH3CN/10 mM ammonium acetate. MS data was determined using a Micromass Platform for LC in electrospray mode. m/z 537 (MH+).

Workup

  1. concentrationconcentrated
  2. customThe resultant residue was purified

Sources & evidence

ORD record
ord-ec02ef76947349abbcbf32fb854c17aa
Source dataset
uspto-grants-2012_10
Patent number
US08293909B2

Reaction notes

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