Trifluoroacetic acid → Ammonium Acetate

HRID 2068435ノート

反応式

HRID 2068435 の反応式
Cl.[NH2:2][C:3]1([C:6]2[N:11]=[C:10]([OH:12])[CH:9]=[CH:8][N:7]=2)[CH2:5][CH2:4]1.C(N(C(C)C)CC)(C)C.C(O[C:27]([N:29](C)[C:30]([C:32]1[C:33]([C:54]2[CH:59]=[CH:58][C:57]([F:60])=[CH:56][CH:55]=2)=[N:34][N:35]2[CH:40]=[CH:39][C:38]([C:41]3[C:42]([CH3:52])=[CH:43][C:44]([O:50][CH3:51])=[C:45]([CH:49]=3)[C:46]([OH:48])=[O:47])=[C:37]([F:53])[C:36]=12)=[O:31])=O)(C)(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.FC(F)(F)C(O)=O>ClCCl.CN(C=O)C>[C:46]([O-:48])(=[O:47])[CH3:45].[NH4+:2].[F:53][C:37]1[C:36]2[N:35]([N:34]=[C:33]([C:54]3[CH:55]=[CH:56][C:57]([F:60])=[CH:58][CH:59]=3)[C:32]=2[C:30]([NH:29][CH3:27])=[O:31])[CH:40]=[CH:39][C:38]=1[C:41]1[CH:49]=[C:45]([C:46](=[O:47])[NH:2][C:3]2([C:6]3[N:11]=[C:10]([OH:12])[CH:9]=[CH:8][N:7]=3)[CH2:5][CH2:4]2)[C:44]([O:50][CH3:51])=[CH:43][C:42]=1[CH3:52]

参加物

9

反応物 5

HCID 6422Trifluoroacetic acidHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 67419172HCID 67419172、化合物HCID 178479017HCID 178479017、化合物

生成物 2

HCID 517165Ammonium AcetateHCID 178485241HCID 178485241、化合物

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 6344Dichloromethane溶媒

実験手順

To a solution containing 2-(1-aminocyclopropyl)pyrimidin-4-ol hydrochloride (0.025 g, 0.13 mmol), diisopropylethylamine (0.15 mL, 0.89 mmol), 5-(3-(tert-butoxycarbonyl(methyl)carbamyl)-4-fluoro-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-5-yl)-2-methoxy-4-methylbenzoic acid (0.070 g, 0.11 mmol) and DMF (0.74 mL) was added HATU (0.085 g, 0.22 mmol) in one portion. The solution was maintained at room temperature for 15 minutes. Dichloromethane (0.22 mL) was then added followed by trifluoroacetic acid (0.068 mL, 0.88 mmol). The solution was maintained for an additional 15 min 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), 15 min. gradient) afforded 4-fluoro-2-(4-fluorophenyl)-5-(5-(1-(4-hydroxypyrimidin-2-yl)cyclopropylcarbamoyl)-4-methoxy-2-methylphenyl)-N-methylpyrazolo[1,5-a]pyridine-3-carboxamide as a white solid. Preparative HPLC retention time: 9.4 min. 1H NMR (400 MHz, MeOD) δ ppm 8.50 (1H, d, J=7.03 Hz), 7.78-7.90 (4H, m), 7.17-7.29 (3H, m), 6.87 (1H, t, J=6.90 Hz), 6.22 (1H, br. s.), 4.10 (3H, s), 2.87-2.93 (3H, m), 2.30-2.39 (3H, m), 1.81 (2H, br. s.), 1.40-1.48 (2H, m). LCMS: retention time: 1.798 min. LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a Phenomenex-Luna, 3 micron, C18, 2.0×30 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 2 min, a hold time of 1 min, and an analysis time of 3 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 585 (MH+).

後処理

  1. temperatureThe solution was maintained for an additional 15 min
  2. concentrationconcentrated
  3. customThe resultant residue was purified

出典と根拠

ORDレコード
ord-9e4d3620c4264b428a9ded2f2d4c2c0d
出典データセット
uspto-grants-2012_10
特許番号
US08293909B2

反応ノート

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