Trifluoroacetic acid → Ammonium Acetate

HRID 2068434노트

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HRID 2068434 반응식
F[C:2]([F:7])(F)[C:3]([OH:5])=[O:4].[N:8]1[CH:13]=[CH:12][N:11]=[CH:10][C:9]=1[C:14]1([NH2:17])[CH2:16][CH2:15]1.C(N(C(C)C)CC)(C)C.C(O[C:32]([N:34](C)[C:35]([C:37]1[C:38]([C:59]2[CH:64]=CC(F)=[CH:61][CH:60]=2)=[N:39][N:40]2[CH:45]=[CH:44][C:43]([C:46]3[C:47]([CH3:57])=[CH:48][C:49]([O:55][CH3:56])=[C:50]([CH:54]=3)[C:51](O)=[O:52])=[C:42]([F:58])[C:41]=12)=[O:36])=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:3]([O-:5])(=[O:4])[CH3:2].[NH4+:8].[F:58][C:42]1[C:41]2[N:40]([N:39]=[C:38]([C:59]3[CH:60]=[CH:61][C:2]([F:7])=[CH:3][CH:64]=3)[C:37]=2[C:35]([NH:34][CH3:32])=[O:36])[CH:45]=[CH:44][C:43]=1[C:46]1[CH:54]=[C:50]([C:51](=[O:52])[NH:17][C:14]2([C:9]3[CH:10]=[N:11][CH:12]=[CH:13][N:8]=3)[CH2:16][CH2:15]2)[C:49]([O:55][CH3:56])=[CH:48][C:47]=1[CH3:57]

참가 물질

9

반응물 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 67404879HCID 67404879, 화합물HCID 67419172HCID 67419172, 화합물

생성물 2

HCID 517165Ammonium AcetateHCID 46842607HCID 46842607, 화합물

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 6344Dichloromethane용매

실험 절차

To a solution containing 1-(pyrazin-2-yl)cyclopropanamine 2,2,2-trifluoroacetate (0.014 g, 0.058 mmol), diisopropylethylamine (0.050 mL, 0.30 mmol), 5-(3-(tert-butoxycarbonyl(methyl)carbamoyl)-4-fluoro-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-5-yl)-2-methoxy-4-methylbenzoic acid (0.020 g, 0.036 mmol) and DMF (0.24 mL) was added HATU (0.027 g, 0.073 mmol) in one portion. The solution was maintained at room temperature for 15 minutes. Dichloromethane (0.25 mL) was then added followed by trifluoroacetic acid (0.078 mL, 1.0 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-(4-methoxy-2-methyl-5-(1-(pyrazin-2-yl)cyclopropylcarbamoyl)phenyl)-N-methylpyrazolo[1,5-a]pyridine-3-carboxamide as a white solid. Preparative HPLC retention time: 10.6 min. 1H NMR (400 MHz, MeOD) δ ppm 8.70 (1H, d, J=1.51 Hz), 8.51 (1H, s), 8.50 (1H, dd, J=3.51, 1.76 Hz), 8.35 (1H, d, J=2.51 Hz), 7.84-7.90 (2H, m), 7.79 (1H, s), 7.17-7.26 (3H, m), 6.89 (1H, t, J=6.90 Hz), 4.09 (3H, s), 2.90 (3H, s), 2.36 (3H, s), 1.69-1.75 (2H, m), 1.41-1.46 (2H, m). LCMS: retention time: 1.942 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 569 (MH+).

후처리

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

출처 및 근거

ORD 기록
ord-23d75cd5ff094a08a57fda81eea3c6ac
출처 데이터셋
uspto-grants-2012_10
특허 번호
US08293909B2

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