Diisopropylethylamine → Ammonium Acetate

HRID 2068433Notes

Reaction equation

HRID 2068433 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]([C:8]2([NH2:11])[CH2:10][CH2:9]2)[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+:5].[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:4]3[CH:3]=[C:2]([F:1])[CH:7]=[CH:6][N:5]=3)[CH2:9][CH2:10]2)[CH:36]=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 59411416HCID 59411416, compoundHCID 67406299HCID 67406299, compound

Product 2

HCID 517165Ammonium AcetateHCID 46842571HCID 46842571, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution containing 1-(4-fluoropyridin-2-yl)cyclopropanamine (0.011 g, 0.044 mmol), diisopropylethylamine (0.62 mL, 0.35 mmol), 5-(4-fluoro-2-(4-fluorophenyl)-3-(methylcarbamoyl)pyrazolo[1,5-a]pyridin-5-yl)-2-methoxy-6-methylnicotinic acid (0.020 g, 0.044 mmol) and DMF (0.30 mL) was added HATU (0.034 g, 0.088 mmol) in one portion. The solution was maintained at room temperature for 15 minutes 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-(5-(1-(4-fluoropyridin-2-yl)cyclopropylcarbamoyl)-6-methoxy-2-methylpyridin-3-yl)-N-methylpyrazolo[1,5-a]pyridine-3-carboxamide as a white solid. Preparative HPLC retention time: 11.0 min. 1H NMR (400 MHz, MeOD) δ ppm 8.55 (1H, d, J=7.03 Hz), 8.44 (1H, dd, J=8.66, 5.65 Hz), 8.17 (1H, s), 7.83-7.93 (2H, m), 7.19-7.31 (3H, m), 6.91-7.01 (2H, m), 4.20 (3H, s), 2.91 (3H, s), 2.49 (3H, d, J=1.00 Hz), 1.69-1.77 (2H, m), 1.38-1.46 (2H, m). LCMS: retention time: 2.018 min. LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a Phenomenex-Luna, 3 micron, C18, 2.0×30 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 587 (MH+).

Workup

  1. concentrationconcentrated
  2. customPurification of the resultant residue

Sources & evidence

ORD record
ord-8750a480a1344a3298e2f31cf51fafec
Source dataset
uspto-grants-2012_10
Patent number
US08293909B2

Reaction notes

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