1-Phenylcyclopropylamine → Ammonium Acetate

HRID 44042Notes

Reaction equation

[F:1][C:2]1[C:3]([C:22]2[CH:23]=[C:24]([CH:28]=[CH:29][C:30]=2[CH3:31])[C:25]([OH:27])=[O:26])=[CH:4][C:5]2[N:6]([N:8]=[C:9]([C:15]3[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=3)[C:10]=2[C:11](=[O:14])[NH:12][CH3:13])[CH:7]=1.Cl.[C:33]1([C:39]2([NH2:42])[CH2:41][CH2:40]2)[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1>>[C:25]([O-:27])(=[O:26])[CH3:24].[NH4+:6].[F:1][C:2]1[C:3]([C:22]2[CH:23]=[C:24]([C:25](=[O:26])[NH:42][C:39]3([C:33]4[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=4)[CH2:41][CH2:40]3)[CH:28]=[CH:29][C:30]=2[CH3:31])=[CH:4][C:5]2[N:6]([N:8]=[C:9]([C:15]3[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=3)[C:10]=2[C:11]([NH:12][CH3:13])=[O:14])[CH:7]=1

Participants

Reactant 2

HCID 1945481-Phenylcyclopropylamine

HCID 674197473-(6-Fluoro-2-(4-fluorophenyl)-3-(methylcarbamoyl)pyrazolo[1,5-a]pyridin-5-yl)-4-methylbenzoic acid

Product 2

HCID 517165Ammonium Acetate

HCID 592337596-fluoro-2-(4-fluorophenyl)-N-methyl-5-(2-methyl-5-(1-phenylcyclopropylcarbamoyl)phenyl)pyrazolo[1,5-a]pyridine-3-carboxamide

Procedure

6-fluoro-2-(4-fluorophenyl)-N-methyl-5-(2-methyl-5-(1-phenylcyclopropyl carbamoyl)phenyl)pyrazolo[1,5-a]pyridine-3-carboxamide was prepared from 3-(6-fluoro-2-(4-fluorophenyl)-3-(methylcarbamoyl)pyrazolo[1,5-a]pyridin-5-yl)-4-methylbenzoic acid (0.024 g, 0.059 mmol) and 1-phenylcyclopropanamine hydrochloride (0.015 g, 0.089 mmol). The resultant residue was purified using preparative HPLC (Waters—Xbridge, 50×100 mm, 5 micron, C18 column; 0.1M ammonium acetate, 10-100% B (B=5% H2O/CH3CN)/A (A=95% H2O/CH3CN), 15 min. gradient) to afford 6-fluoro-2-(4-fluorophenyl)-N-methyl-5-(2-methyl-5-(1-phenylcyclopropylcarbamoyl)phenyl)pyrazolo[1,5-a]pyridine-3-carboxamide as a white solid. Preparative HPLC retention time: 10.5 min. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 8.49 (d, J=4.02 Hz, 1H), 8.31 (d, J=7.53 Hz, 1H), 7.84 (dd, J=8.03, 1.76 Hz, 1H), 7.66-7.74 (m, 3H), 7.40 (d, J=8.03 Hz, 1H), 7.29-7.37 (m, 4H), 7.24-7.27 (m, 1H), 7.20 (t, J=6.02 Hz, 1H), 6.89 (s, 1H), 5.56 (d, J=4.27 Hz, 1H), 2.86 (d, J=4.77 Hz, 3H), 2.32 (s, 3H), 1.40 (d, J=9.03 Hz, 4H). LCMS retention time: 2.535 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% methanol/90% water/10 mM TFA and solvent B was 10% water/90% methanol/10 mM TFA. MS data was determined using a Micromass Platform for LC in electrospray mode. m/z 537 (MH+).

Workup

customThe resultant residue was purified

Sources & evidence

ORD record: ord-365b009d8c654f05be8b6e33befcd66e
Source dataset: uspto-grants-2013_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08536338B2

Reaction notes

Loading…