Diisopropylethylamine → Ammonium Acetate

HRID 2068430Notes

Reaction equation

HRID 2068430 reaction equation
Cl.Cl.[N:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]1([NH2:12])[CH2:11][CH2:10]1.C(N(C(C)C)CC)(C)C.[F:22][CH:23]([F:56])[O:24][C:25]1[N:33]=[C:32]([CH3:34])[C:31]([C:35]2[CH:40]=[CH:39][N:38]3[N:41]=[C:42]([C:48]4[CH:53]=[CH:52][C:51]([F:54])=[CH:50][CH:49]=4)[C:43]([C:44](=[O:47])[NH:45][CH3:46])=[C:37]3[C:36]=2[F:55])=[CH:30][C:26]=1[C:27]([OH:29])=[O:28].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[C:27]([O-:29])(=[O:28])[CH3:26].[NH4+:3].[F:56][CH:23]([F:22])[O:24][C:25]1[N:33]=[C:32]([CH3:34])[C:31]([C:35]2[CH:40]=[CH:39][N:38]3[N:41]=[C:42]([C:48]4[CH:53]=[CH:52][C:51]([F:54])=[CH:50][CH:49]=4)[C:43]([C:44]([NH:45][CH3:46])=[O:47])=[C:37]3[C:36]=2[F:55])=[CH:30][C:26]=1[C:27](=[O:28])[NH:12][C:9]1([C:4]2[CH:5]=[CH:6][CH:7]=[CH:8][N:3]=2)[CH2:11][CH2:10]1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 533931811-(2-Pyridyl)cyclopropylamine DihydrochlorideHCID 67420228HCID 67420228, compound

Product 2

HCID 517165Ammonium AcetateHCID 46842545HCID 46842545, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution containing 1-(pyridin-2-yl)cyclopropanamine dihydrochloride (0.0082 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-(pyridin-2-yl)cyclopropylcarbamoyl)pyridin-3-yl)-4-fluoro-2-(4-fluorophenyl)-N-methylpyrazolo[1,5-a]pyridine-3-carboxamide as a white solid. Preparative HPLC retention time: 10.2 min. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 8.47-8.56 (2H, m), 8.40 (1H, d, J=7.03 Hz), 8.09 (1H, br. s.), 7.80-7.90 (2H, m), 7.75 (1H, s), 7.57 (1H, s), 7.42 (1H, d, J=8.03 Hz), 7.09-7.22 (3H, m), 6.73 (1H, t, J=6.78 Hz), 5.80 (1H, d, J=4.52 Hz), 2.98 (3H, d, J=5.02 Hz), 2.51 (3H, d, J=1.25 Hz), 1.77-1.86 (2H, m), 1.39-1.50 (2H, m). LCMS: retention time: 2.288 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 3 min, a hold time of 1 min, and an analysis time of 4 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 605 (MH+).

Workup

  1. concentrationconcentrated
  2. customPurification of the resultant residue

Sources & evidence

ORD record
ord-e3173eaa7b4a457c8d13b0e17daa3b8f
Source dataset
uspto-grants-2012_10
Patent number
US08293909B2

Reaction notes

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