Methylamine hydrochloride → Ammonium Acetate

HRID 2068348Notes

Reaction equation

[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:43]([C:44]([OH:46])=[O:45])=[C:11]3[CH:12]=[C:13]([C:25]4[CH:30]=[CH:29][CH:28]=[C:27]([C:31](=[O:42])[NH:32][C:33]([C:36]5[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=5)([CH3:35])[CH3:34])[CH:26]=4)[C:14]([N:16]([CH2:21][CH2:22][O:23][CH3:24])[S:17]([CH3:20])(=[O:19])=[O:18])=[CH:15][N:10]3[N:9]=2)=[CH:4][CH:3]=1.Cl.[CH3:48][NH2:49]>>[C:44]([O-:46])(=[O:45])[CH3:43].[NH4+:9].[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[C:43]([C:44]([NH:49][CH3:48])=[O:46])=[C:11]3[CH:12]=[C:13]([C:25]4[CH:30]=[CH:29][CH:28]=[C:27]([C:31](=[O:42])[NH:32][C:33]([C:36]5[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=5)([CH3:34])[CH3:35])[CH:26]=4)[C:14]([N:16]([CH2:21][CH2:22][O:23][CH3:24])[S:17]([CH3:20])(=[O:19])=[O:18])=[CH:15][N:10]3[N:9]=2)=[CH:6][CH:7]=1

Participants

Reactant 2

HCID 6364545Methylamine hydrochloride

HCID 674186172-(4-fluorophenyl)-6-(N-(2-methoxyethyl)methylsulfonamido)-5-(3-(2-phenylpropan-2-ylcarbamoyl)phenyl)pyrazolo[1,5-a]pyridine-3-carboxylic acid

Product 2

HCID 517165Ammonium Acetate

HCID 59233797HCID 59233797, compound

Procedure

2-(4-fluorophenyl)-6-(N-(2-methoxyethyl)methylsulfonamido)-N-methyl-5-(3-(2-phenylpropan-2-ylcarbamoyl) phenyl)pyrazolo[1,5-a]pyridine-3-carboxamide was prepared from 2-(4-fluorophenyl)-6-(N-(2-methoxyethyl)methylsulfonamido)-5-(3-(2-phenylpropan-2-ylcarbamoyl)phenyl)pyrazolo[1,5-a]pyridine-3-carboxylic acid (0.032 g, 0.049 mmol) and methylamine hydrochloride (0.014 g, 0.19 mmol). 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), 10 min. gradient) to afford 2-(4-fluorophenyl)-6-(N-(2-methoxyethyl)methylsulfonamido)-N-methyl-5-(3-(2-phenylpropan-2-ylcarbamoyl)phenyl)pyrazolo[1,5-a]pyridine-3-carboxamide as a white solid. Preparative HPLC retention time: 8 min. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 8.58 (s, 1H), 8.38 (s, 1H), 8.25 (s, 1H), 7.92-7.98 (m, 1H), 7.73 (ddd, J=11.80, 5.14, 2.89 Hz, 2H), 7.61-7.66 (m, 1H), 7.52-7.58 (m, 1H), 7.47 (dd, J=8.41, 1.13 Hz, 2H), 7.24-7.34 (m, 10H), 7.18-7.23 (m, 1H), 5.61 (d, J=4.52 Hz, 1H), 3.76-3.87 (m, 1H), 3.26-3.34 (m, 7H), 3.18-3.26 (m, 3H), 2.88 (d, J=5.02 Hz, 3H), 2.61 (d, J=15.56 Hz, 1H), 1.82 (s, 6H). LCMS retention time: 2.232 min. LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a Sunfire C18, 5 u, C18, 4.6×50 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% CH3CN/90% H2O/10 mM TFA and solvent B was 10% H2O/90% CH3CN/10 mM TFA. MS data was determined using a Micromass Platform for LC in electrospray mode. m/z 657.7 (MNa+).

Workup

customThe resultant residue was purified

Sources & evidence

ORD record: ord-46e338e78716407fb3d530e9f6c028f8
Source dataset: uspto-grants-2012_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08293909B2

Reaction notes

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