Diisopropylethylamine → 4-Acetylamino-N-[4-(2-amino-2-methyl-propoxy)-3-(4-bromo-2-methyl-2H-pyrazol-3-yl)-phenyl]-benzamide

HRID 521645

반응식

HRID 521645 반응식
[C:1]([NH:4][C:5]1[CH:13]=[CH:12][C:8]([C:9](Cl)=[O:10])=[CH:7][CH:6]=1)(=[O:3])[CH3:2].[Br:14][C:15]1[CH:19]=[N:18][N:17]([CH3:20])[C:16]=1[C:21]1[CH:22]=[C:23]([CH:25]=[CH:26][C:27]=1[O:28][CH2:29][C:30]([CH3:35])([N+:32]([O-])=O)[CH3:31])[NH2:24].C(N(CC)C(C)C)(C)C>ClCCl>[C:1]([NH:4][C:5]1[CH:13]=[CH:12][C:8]([C:9]([NH:24][C:23]2[CH:25]=[CH:26][C:27]([O:28][CH2:29][C:30]([NH2:32])([CH3:35])[CH3:31])=[C:21]([C:16]3[N:17]([CH3:20])[N:18]=[CH:19][C:15]=3[Br:14])[CH:22]=2)=[O:10])=[CH:7][CH:6]=1)(=[O:3])[CH3:2]

참가 물질

5

반응물 3

HCID 81531DiisopropylethylamineHCID 70103414-Acetamidobenzoyl chlorideHCID 672655183-(4-bromo-2-methyl-2H-pyrazol-3-yl)-4-(2-methyl-2-nitropropoxy)aniline

생성물 1

HCID 578147564-Acetylamino-N-[4-(2-amino-2-methyl-propoxy)-3-(4-bromo-2-methyl-2H-pyrazol-3-yl)-phenyl]-benzamide수율 22.4%

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

실험 절차

4-Acetamidobenzoyl chloride (11 mg, 0.06 mmol) was added to a solution of 3-(4-bromo-2-methyl-2H-pyrazol-3-yl)-4-(2-methyl-2-nitropropoxy)aniline (18 mg, 0.05 mmol) and N,N-diisopropylethylamine (10 μl, 0.06 mmol) in dichloromethane (0.5 mL) and the mixture was stirred at room temperature. After 1 h, the solution was diluted with dichloromethane, washed with 1M hydrochloric acid and saturated sodium bicarbonate, dried with sodium sulfate, filtered, and evaporated to dryness. The residue was dissolved in methanol (0.5 mL). Acetic acid (0.1 mL) was added followed by zinc dust (33 mg) and the mixture was stirred at room temperature. After 4 h, the suspension was made basic with ammonium hydroxide and extracted twice with ethyl acetate. The combined extracts were evaporated to dryness, purified by preparative LCMS and lyophilized to give the product (5.6 mg, 22%) as a TFA-salt. LCMS m/z (%)=502.3 (M+H 81Br 42.9%), 500.4 (M+H 79Br 52.1%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.16 (s, 3H), 1.18 (s, 3H), 2.08 (s, 3H), 3.67 (s, 3H), 3.82 (d, J=9.60 Hz, 1H), 3.98 (d, J=9.85 Hz, 1H), 7.27 (d, J=9.09 Hz, 1H), 7.67 (s, 1H), 7.69 (d, J=2.78 Hz, 1H), 7.71 (d, J=8.84 Hz, 2H), 7.85-7.91 (m, 3H), 7.91 (d, J=8.84 Hz, 2H), 7.95 (dd, J=8.97, 2.65 Hz, 1H), 10.22 (s, 1H), 10.23 (s, 1H).

후처리

  1. washwashed with 1M hydrochloric acid and saturated sodium bicarbonate
  2. dry with materialdried with sodium sulfate
  3. filtrationfiltered
  4. customevaporated to dryness
  5. dissolutionThe residue was dissolved in methanol (0.5 mL)
  6. additionAcetic acid (0.1 mL) was added
  7. stirringthe mixture was stirred at room temperature
  8. waitAfter 4 h
  9. extractionextracted twice with ethyl acetate
  10. customThe combined extracts were evaporated to dryness
  11. custompurified by preparative LCMS

출처 및 근거

ORD 기록
ord-6f2293d93d1f4f7581efa037065b20d9
출처 데이터셋
uspto-grants-2016_05
특허 번호
US09328107B2

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