Diisopropylethylamine → Ammonium Acetate

HRID 2068429Notes

Reaction equation

HRID 2068429 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][CH:22]([F:55])[O:23][C:24]1[N:32]=[C:31]([CH3:33])[C:30]([C:34]2[CH:39]=[CH:38][N:37]3[N:40]=[C:41]([C:47]4[CH:52]=[CH:51][C:50]([F:53])=[CH:49][CH:48]=4)[C:42]([C:43](=[O:46])[NH:44][CH3:45])=[C:36]3[C:35]=2[F:54])=[CH:29][C:25]=1[C:26]([OH:28])=[O:27].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[C:26]([O-:28])(=[O:27])[CH3:25].[NH4+:11].[F:55][CH:22]([F:21])[O:23][C:24]1[N:32]=[C:31]([CH3:33])[C:30]([C:34]2[CH:39]=[CH:38][N:37]3[N:40]=[C:41]([C:47]4[CH:52]=[CH:51][C:50]([F:53])=[CH:49][CH:48]=4)[C:42]([C:43]([NH:44][CH3:45])=[O:46])=[C:36]3[C:35]=2[F:54])=[CH:29][C:25]=1[C:26](=[O:27])[NH:11][C:8]1([C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[CH2:10][CH2:9]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 67420228HCID 67420228, compound

Product 2

HCID 517165Ammonium AcetateHCID 46842543HCID 46842543, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution containing 1-phenylcyclopropanamine hydrochloride (0.0067 g, 0.040 mmol), diisopropylethylamine (0.43 mL, 0.25 mmol), 2-(difluoromethoxy)-5-(4-fluoro-2-(4-fluorophenyl)-3-(methylcarbamoyl)pyrazolo[1,5-a]pyridin-5-yl)-6-methylnicotinic acid (0.015 g, 0.031 mmol) and DMF (0.21 mL) was added HATU (0.023 g, 0.061 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 5-(6-(difluoromethoxy)-2-methyl-5-(1-phenylcyclopropylcarbamoyl)pyridin-3-yl)-4-fluoro-2-(4-fluorophenyl)-N-methylpyrazolo[1,5-a]pyridine-3-carboxamide as a white solid. Preparative HPLC retention time: 11.1 min. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 8.46-8.49 (1H, m), 8.39 (1H, d, J=7.03 Hz), 7.98 (1H, s), 7.78-7.89 (2H, m), 7.73 (1H, s), 7.29-7.39 (5H, m), 7.14-7.25 (3H, m), 6.71 (1H, t, J=6.78 Hz), 5.80 (1H, d, J=4.52 Hz), 2.98 (3H, d, J=4.77 Hz), 2.49 (3H, d, J=1.25 Hz), 1.41 (4H, d, J=1.00 Hz). LCMS: retention time: 1.823 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-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 604 (MH+).

Workup

  1. concentrationconcentrated
  2. customPurification of the resultant residue

Sources & evidence

ORD record
ord-005d92f9e73d4f4e8b14e0e3278c2a2e
Source dataset
uspto-grants-2012_10
Patent number
US08293909B2

Reaction notes

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