Diisopropylethylamine → Ammonium Acetate

HRID 219367Notes

Reaction equation

HRID 219367 reaction equation
F[C:2](F)(F)[C:3]([O-:5])=[O:4].[CH3:8][C:9]1[N:13]=[C:12]([C:14]2([NH3+:17])[CH2:16][CH2:15]2)[O:11][N:10]=1.C(N(C(C)C)CC)(C)C.[F:27][C:28]1[C:29]2[N:30]([N:46]=[C:47]([C:53]3[CH:58]=[CH:57][C:56]([F:59])=[CH:55][CH:54]=3)[C:48]=2[C:49](=[O:52])[NH:50][CH3:51])[CH:31]=[CH:32][C:33]=1[C:34]1[C:35]([CH3:45])=[CH:36][C:37]([O:43][CH3:44])=[C:38]([CH:42]=1)[C:39](O)=[O:40].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[C:3]([O-:5])(=[O:4])[CH3:2].[NH4+:10].[F:27][C:28]1[C:29]2[N:30]([N:46]=[C:47]([C:53]3[CH:54]=[CH:55][C:56]([F:59])=[CH:57][CH:58]=3)[C:48]=2[C:49]([NH:50][CH3:51])=[O:52])[CH:31]=[CH:32][C:33]=1[C:34]1[CH:42]=[C:38]([C:39](=[O:40])[NH:17][C:14]2([C:12]3[O:11][N:10]=[C:9]([CH3:8])[N:13]=3)[CH2:16][CH2:15]2)[C:37]([O:43][CH3:44])=[CH:36][C:35]=1[CH3:45]

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 672170615-(4-Fluoro-2-(4-fluorophenyl)-3-(methylcarbamoyl)pyrazolo[1,5-a]pyridin-5-yl)-2-methoxy-4-methylbenzoic acidHCID 866399541-(3-Methyl-1,2,4-oxadiazol-5-yl)cyclopropanaminium 2,2,2-trifluoroacetate

Product 2

HCID 517165Ammonium AcetateHCID 468425094-fluoro-2-(4-fluorophenyl)-5-(4-methoxy-2-methyl-5-(1-(3-methyl-1,2,4-oxadiazol-5-yl)cyclopropylcarbamoyl)phenyl)-N-methylpyrazolo[1,5-a]pyridine-3-carboxamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution containing 1-(3-methyl-1,2,4-oxadiazol-5-yl)cyclopropanaminium 2,2,2-trifluoroacetate (0.024 g, 0.095 mmol), diisopropylethylamine (0.10 mL, 0.56 mmol), 5-(4-fluoro-2-(4-fluorophenyl)-3-(methylcarbamoyl)pyrazolo[1,5-a]pyridin-5-yl)-2-methoxy-4-methylbenzoic acid (0.033 g, 0.073 mmol) and DMF (0.49 mL) was added HATU (0.056 g, 0.15 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, 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-(3-methyl-1,2,4-oxadiazol-5-yl)cyclopropylcarbamoyl)phenyl)-N-methylpyrazolo[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 8.57 (s, 1H), 8.34 (d, J=7.03 Hz, 1H), 8.13 (s, 1H), 7.79-7.92 (m, 2H), 7.10-7.21 (m, 2H), 6.97 (s, 1H), 6.73 (t, J=6.78 Hz, 1H), 5.89 (d, J=4.52 Hz, 1H), 4.07 (s, 3H), 2.97 (d, J=5.02 Hz, 3H), 2.34 (s, 6H), 1.77-1.88 (m, 2H), 1.50-1.63 (m, 2H). LCMS retention time: 2.533 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 0.4 min, a hold time of 1 min, and an analysis time of 5 min where solvent A was 10% CH3OH/90% H2O/10 mM TFA and solvent B was 10% H2O/90% CH3OH/10 mM TFA. MS data was determined using a Micromass Platform for LC in electrospray mode. m/z 573 (MH+).

Workup

  1. concentrationconcentrated
  2. customThe resultant residue was purified

Sources & evidence

ORD record
ord-355d2445a439468eb9433f8b5c7a8a0a
Source dataset
uspto-grants-2012_06
Patent number
US08198449B2

Reaction notes

Loading…