Diisopropylethylamine → Ammonium Acetate

HRID 44045Notes

Reaction equation

HRID 44045 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][C:23]1[CH:24]=[C:25]([CH:29]=[C:30]([C:33]2[CH:38]=[CH:37][N:36]3[N:39]=[C:40]([C:46]4[CH:51]=[CH:50][C:49]([F:52])=[CH:48][CH:47]=4)[C:41]([C:42](=[O:45])[NH:43][CH3:44])=[C:35]3[C:34]=2[F:53])[C:31]=1[CH3:32])[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+:3].[F:53][C:34]1[C:35]2[N:36]([N:39]=[C:40]([C:46]3[CH:47]=[CH:48][C:49]([F:52])=[CH:50][CH:51]=3)[C:41]=2[C:42]([NH:43][CH3:44])=[O:45])[CH:37]=[CH:38][C:33]=1[C:30]1[CH:29]=[C:25]([C:26](=[O:27])[NH:12][C:9]2([C:4]3[CH:5]=[CH:6][CH:7]=[CH:8][N:3]=3)[CH2:11][CH2:10]2)[CH:24]=[C:23]([F:22])[C:31]=1[CH3:32]

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 672172243-Fluoro-5-(4-fluoro-2-(4-fluorophenyl)-3-(methylcarbamoyl)pyrazolo[1,5-a]pyridin-5-yl)-4-methylbenzoic acid

Product 2

HCID 517165Ammonium AcetateHCID 592337204-fluoro-5-(3-fluoro-2-methyl-5-(1-(pyridin-2-yl)cyclopropylcarbamoyl)phenyl)-2-(4-fluorophenyl)-N-methylpyrazolo[1,5-a]pyridine-3-carboxamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution containing 1-(pyridin-2-yl)cyclopropanamine dihydrochloride (0.070 g, 0.033 mmol), diisopropylethylamine (0.04 mL, 0.22 mmol), 3-fluoro-5-(4-fluoro-2-(4-fluorophenyl)-3-(methylcarbamoyl)pyrazolo[1,5-a]pyridin-5-yl)-4-methylbenzoic acid (0.012 g, 0.027 mmol) and DMF (0.19 mL) was added HATU (0.021 g, 0.055 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), 20 min. gradient) afforded 4-fluoro-5-(3-fluoro-2-methyl-5-(1-(pyridin-2-yl)cyclopropylcarbamoyl)phenyl)-2-(4-fluorophenyl)-N-methylpyrazolo[1,5-a]pyridine-3-carboxamide as a white solid. Preparative HPLC retention time: 11.0 min. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 8.44-8.53 (m, 1H), 8.38 (d, J=7.03 Hz, 1H), 7.80-7.90 (m, 2H), 7.55-7.67 (m, 3H), 7.36 (d, J=8.03 Hz, 1H), 7.31 (s, 1H), 7.14-7.22 (m, 2H), 7.10 (ddd, J=7.47, 4.96, 1.13 Hz, 1H), 6.74 (t, J=6.78 Hz, 1H), 5.87 (d, J=4.77 Hz, 1H), 2.97 (d, J=4.77 Hz, 3H), 2.25 (s, 3H), 1.66-1.73 (m, 2H), 1.38-1.46 (m, 2H). LCMS retention time: 1.828 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 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 556 (MH+).

Workup

  1. concentrationconcentrated
  2. customThe resultant residue was purified

Sources & evidence

ORD record
ord-ee5f4a7b420541f693300a65eb39c077
Source dataset
uspto-grants-2013_09
Patent number
US08536338B2

Reaction notes

Loading…