Diisopropylethylamine → N-(3-(4-chloro-1-methyl-1H-pyrazol-5-yl)-4-hydroxyphenyl)-2-fluoro-4-methoxybenzamide

HRID 1183895노트

반응식

HRID 1183895 반응식
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[C:4]([C:9]2[N:13]([CH3:14])[N:12]=[CH:11][C:10]=2[Cl:15])[CH:3]=1.[F:16][C:17]1[CH:25]=[C:24]([O:26][CH3:27])[CH:23]=[CH:22][C:18]=1[C:19](O)=[O:20].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C(Cl)Cl.CN(C=O)C>[Cl:15][C:10]1[CH:11]=[N:12][N:13]([CH3:14])[C:9]=1[C:4]1[CH:3]=[C:2]([NH:1][C:19](=[O:20])[C:18]2[CH:22]=[CH:23][C:24]([O:26][CH3:27])=[CH:25][C:17]=2[F:16])[CH:7]=[CH:6][C:5]=1[OH:8]

참가 물질

7

반응물 4

HCID 81531DiisopropylethylamineHCID 27745422-Fluoro-4-methoxybenzoic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 1363880184-Amino-2-(4-chloro-1-methyl-1H-pyrazol-5-yl)phenol

생성물 1

HCID 136388017N-(3-(4-chloro-1-methyl-1H-pyrazol-5-yl)-4-hydroxyphenyl)-2-fluoro-4-methoxybenzamide수율 85.7%

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 6344Dichloromethane용매

실험 절차

4-Amino-2-(4-chloro-1-methyl-1H-pyrazol-5-yl)phenol (2.0 g, 8.94 mmol) was suspended in anhydrous CH2Cl2 (75 mL). The suspension was made to dissolve by the adding anhydrous DMF (5 mL) and briefly heating the solution using a heat gun (˜50° C.). 2-Fluoro-4-methoxybenzoic acid (1.52 g, 8.94 mmol), DIEA (2.34 mL, 13.4 mmol) and HATU (4.08 g, 10.7 mmol) were added to the solution. The reaction was stirred at room temperature for 2 hours. After this time, the reaction was extracted (120 mL, each of H2O/CH2Cl2). The aqueous layer was extracted once more with CH2Cl2 (120 mL). The combined organic layer was dried over MgSO4, filtered, and concentrated. The product was purified by column chromatography (0, 20, 40, 50, 70% EtOAc/Hexanes) to yield N-(3-(4-chloro-1-methyl-1H-pyrazol-5-yl)-4-hydroxyphenyl)-2-fluoro-4-methoxybenzamide (2.88 g, 7.66 mmol, 77.1%) as a colorless oil that turned solid upon standing. LCMS m/z 376.1 (M+H); 1H NMR (400 MHz, MeOH-d4) δ ppm 3.76 (s, 3 H), 3.90 (s, 3 H), 6.87 (dd, j=33.09, 2.53 Hz, 1 H), 6.87 (dd, J=11.49, 2.40 Hz, 1H), 7.00 (d, J=8.59 Hz, 1 H), 7.54 (s, 1 H), 7.55 (d, J=2.53 Hz, 1 H), 7.66 (dd, J=8.84, 2.53 Hz, 1 H), 7.76 (t, J=8.72 Hz, 1 H).

후처리

  1. temperaturebriefly heating the solution
  2. customa heat gun (˜50° C.)
  3. extractionAfter this time, the reaction was extracted (120 mL
  4. extractionThe aqueous layer was extracted once more with CH2Cl2 (120 mL)
  5. dry with materialThe combined organic layer was dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe product was purified by column chromatography (0, 20, 40, 50, 70% EtOAc/Hexanes)

출처 및 근거

ORD 기록
ord-6d5ecc9f381043b388f2462309cb2124
출처 데이터셋
uspto-grants-2014_03
특허 번호
US08664258B2

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