Diisopropylethylamine → Ammonium Acetate

HRID 2068431Notes

Reaction equation

HRID 2068431 reaction equation
Cl.[N:2]1[CH:7]=[CH:6][CH:5]=[N:4][C:3]=1[C:8]1([NH2:11])[CH2:10][CH2:9]1.C(N(C(C)C)CC)(C)C.[F:21][C:22]1[C:23]2[N:24]([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:25]=[CH:26][C:27]=1[C:28]1[C:29]([CH3:45])=[N:30][C:31]([O:37][CH2:38][CH:39]2[CH2:44][CH2:43][O:42][CH2:41][CH2:40]2)=[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+:2].[F:21][C:22]1[C:23]2[N:24]([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]([NH:50][CH3:51])=[O:52])[CH:25]=[CH:26][C:27]=1[C:28]1[C:29]([CH3:45])=[N:30][C:31]([O:37][CH2:38][CH:39]2[CH2:40][CH2:41][O:42][CH2:43][CH2:44]2)=[C:32]([C:33](=[O:34])[NH:11][C:8]2([C:3]3[N:4]=[CH:5][CH:6]=[CH:7][N:2]=3)[CH2:10][CH2:9]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 569656581-(Pyrimidin-2-yl)cyclopropan-1-amine hydrochlorideHCID 674195645-(4-Fluoro-2-(4-fluorophenyl)-3-(methylcarbamoyl)pyrazolo[1,5-a]pyridin-5-yl)-6-methyl-2-((tetrahydro-2h-pyran-4-yl)methoxy)nicotinic acid

Product 2

HCID 517165Ammonium AcetateHCID 46842546HCID 46842546, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution containing 1-(pyrimidin-2-yl)cyclopropanamine hydrochloride (0.0058 g, 0.034 mmol), diisopropylethylamine (0.36 mL, 0.21 mmol), 5-(4-fluoro-2-(4-fluorophenyl)-3-(methylcarbamoyl)pyrazolo[1,5-a]pyridin-5-yl)-6-methyl-2-((tetrahydro-2H-pyran-4-yl)methoxy)nicotinic acid (0.014 g, 0.026 mmol) and DMF (0.17 mL) was added HATU (0.020 g, 0.052 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)-N-methyl-5-(2-methyl-5-(1-(pyrimidin-2-yl)cyclopropyl carbamoyl)-6-((tetrahydro-2H-pyran-4-yl)methoxy)pyridin-3-yl)pyrazolo[1,5-a]pyridine-3-carboxamide as a white solid. Preparative HPLC retention time: 10.6 min. 1H NMR (400 MHz, MeOD) δ ppm 8.65 (2H, d, J=5.02 Hz), 8.55 (1H, d, J=7.03 Hz), 8.25 (1H, s), 7.83-7.93 (2H, m), 7.18-7.28 (3H, m), 6.95 (1H, t, J=6.90 Hz), 4.52 (2H, d, J=6.27 Hz), 3.99 (2H, dd, J=11.29, 3.01 Hz), 3.48 (2H, td, J=11.80, 2.01 Hz), 2.88-2.94 (3H, m), 2.48 (3H, d, J=1.00 Hz), 2.17-2.29 (1H, m), 1.83 (1H, d, J=1.76 Hz), 1.75-1.82 (3H, m), 1.48-1.60 (4H, m). LCMS: retention time: 2.333 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 654 (MH+).

Workup

  1. concentrationconcentrated
  2. customPurification of the resultant residue

Sources & evidence

ORD record
ord-1e31d15cf4fa4846aeb183ca7392637f
Source dataset
uspto-grants-2012_10
Patent number
US08293909B2

Reaction notes

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