Trifluoroacetic acid → Ammonium Acetate

HRID 44052ノート

反応式

HRID 44052 の反応式
[F:1][C:2]1[N:7]2[N:8]=[C:9]([C:22]3[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=3)[C:10]([C:11]([N:13](C)[C:14](=O)OC(C)(C)C)=[O:12])=[C:6]2[CH:5]=[C:4]([C:29]2[CH:34]=[C:33]([C:35](=[O:46])[NH:36][C:37]3([C:40]4[CH:45]=[CH:44][CH:43]=[CH:42][N:41]=4)[CH2:39][CH2:38]3)[CH:32]=[CH:31][C:30]=2[CH3:47])[CH:3]=1.[C:48]([OH:54])([C:50](F)(F)F)=[O:49]>ClCCl>[C:48]([O-:54])(=[O:49])[CH3:50].[NH4+:7].[F:1][C:2]1[N:7]2[N:8]=[C:9]([C:22]3[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=3)[C:10]([C:11]([NH:13][CH3:14])=[O:12])=[C:6]2[CH:5]=[C:4]([C:29]2[CH:34]=[C:33]([C:35](=[O:46])[NH:36][C:37]3([C:40]4[CH:45]=[CH:44][CH:43]=[CH:42][N:41]=4)[CH2:38][CH2:39]3)[CH:32]=[CH:31][C:30]=2[CH3:47])[CH:3]=1

参加物

5

反応物 2

HCID 6422Trifluoroacetic acidHCID 59233755Tert-butyl 7-fluoro-2-(4-fluorophenyl)-5-(2-methyl-5-(1-(pyridin-2-yl)cyclopropylcarbamoyl)phenyl)pyrazolo[1,5-a]pyridine-3-carbonyl(methyl)carbamate

生成物 2

HCID 517165Ammonium AcetateHCID 592338207-fluoro-2-(4-fluorophenyl)-N-methyl-5-(2-methyl-5-(1-(pyridin-2-yl)cyclopropylcarbamoyl)phenyl)pyrazolo[1,5-a]pyridine-3-carboxamide

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

To a solution containing tert-butyl 7-fluoro-2-(4-fluorophenyl)-5-(2-methyl-5-(1-(pyridin-2-yl)cyclopropylcarbamoyl)phenyl)pyrazolo[1,5-a]pyridine-3-carbonyl(methyl)carbamate (0.022 g, 0.035 mmol) and dichloromethane (3.0 mL) was added TFA (0.22 mL, 2.8 mmol) at room temperature. The solution was maintained for 15 min at room temperature and concentrated to dryness. The residue thus obtained 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 7-fluoro-2-(4-fluorophenyl)-N-methyl-5-(2-methyl-5-(1-(pyridin-2-yl)cyclopropylcarbamoyl)phenyl)pyrazolo[1,5-a]pyridine-3-carboxamide as a white solid. Preparative HPLC retention time: 9.0 min. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 8.44-8.54 (m, 1H), 8.18 (d, J=1.51 Hz, 1H), 7.79-7.85 (m, 2H), 7.72-7.78 (m, 2H), 7.61 (td, J=7.78, 1.76 Hz, 1H), 7.41 (dd, J=8.03, 3.26 Hz, 2H), 7.22-7.32 (m, 2H), 7.20 (s, 1H), 7.08 (ddd, J=7.40, 4.89, 1.25 Hz, 1H), 6.69 (dd, J=5.65, 1.63 Hz, 1H), 5.58 (d, J=4.52 Hz, 1H), 2.87 (d, J=5.02 Hz, 3H), 2.42 (s, 3H), 1.67-1.78 (m, 2H), 1.39-1.48 (m, 2H). LCMS retention time: 1.873 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 538 (MH+).

後処理

  1. concentrationconcentrated to dryness
  2. customThe residue thus obtained
  3. customwas purified

出典と根拠

ORDレコード
ord-e86277dcfc3547a9973ff7fcf1c3cc30
出典データセット
uspto-grants-2013_09
特許番号
US08536338B2

反応ノート

読み込み中…