Diisopropylethylamine → Ammonium Acetate

HRID 2068427Notes

Reaction equation

HRID 2068427 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:40]=[C:41]([C:47]3[CH:52]=[CH:51][C:50]([F:53])=[CH:49][CH:48]=3)[C:42]=2[C:43](=[O:46])[NH:44][CH3:45])[CH:25]=[CH:26][C:27]=1[C:28]1[C:29]([CH3:39])=[N:30][C:31]([O:37][CH3:38])=[C:32]([CH:36]=1)[C:33]([OH:35])=[O:34].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[C:33]([O-:35])(=[O:34])[CH3:32].[NH4+:11].[F:21][C:22]1[C:23]2[N:24]([N:40]=[C:41]([C:47]3[CH:48]=[CH:49][C:50]([F:53])=[CH:51][CH:52]=3)[C:42]=2[C:43]([NH:44][CH3:45])=[O:46])[CH:25]=[CH:26][C:27]=1[C:28]1[C:29]([CH3:39])=[N:30][C:31]([O:37][CH3:38])=[C:32]([C:33](=[O:34])[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:36]=1

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 59411416HCID 59411416, compound

Product 2

HCID 517165Ammonium AcetateHCID 46842510HCID 46842510, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution containing 1-phenylcyclopropanamine hydrochloride (0.0067 g, 0.040 mmol), diisopropylethylamine (0.14 mL, 0.79 mmol), 5-(4-fluoro-2-(4-fluorophenyl)-3-(methylcarbamoyl)pyrazolo[1,5-a]pyridin-5-yl)-2-methoxy-6-methylnicotinic acid (0.018 g, 0.040 mmol) and DMF (0.27 mL) was added HATU (0.030 g, 0.080 mmol) in one portion. The solution was maintained at room temperature for 1 h and concentrated. Purification of the resultant residue 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-(6-methoxy-2-methyl-5-(1-phenylcyclopropylcarbamoyl)pyridin-3-yl)-N-methylpyrazolo[1,5-a]pyridine-3-carboxamide as a white solid. Preparative HPLC retention time: 13.94 min. 1H NMR (400 MHz, MeOD) δ ppm 8.54 (1H, d, J=7.03 Hz), 8.16 (1H, s), 7.84-7.95 (2H, m), 7.29 (4H, d, J=4.27 Hz), 7.14-7.26 (3H, m), 6.93 (1H, t, J=6.90 Hz), 4.18 (3H, s), 2.85-2.96 (3H, m), 2.48 (3H, s), 1.37 (4H, d, J=6.27 Hz). LCMS: retention time: 1.847 min. LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a Phenomenex-Luna, 10 u, C18, 3.0×50 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 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 568 (MH+).

Workup

  1. concentrationconcentrated
  2. customPurification of the resultant residue

Sources & evidence

ORD record
ord-ce22a431fdda43679b4ecc2023409c71
Source dataset
uspto-grants-2012_10
Patent number
US08293909B2

Reaction notes

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