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

HRID 1685961Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1685961
[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]

Komponenten

5

Edukt 3

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

Produkt 1

HCID 578147564-Acetylamino-N-[4-(2-amino-2-methyl-propoxy)-3-(4-bromo-2-methyl-2H-pyrazol-3-yl)-phenyl]-benzamideAusbeute 22,4 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel2×

Versuchsvorschrift

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, 3 H), 1.18 (s, 3 H), 2.08 (s, 3 H), 3.67 (s, 3 H), 3.82 (d, J=9.60 Hz, 1 H), 3.98 (d, J=9.85 Hz, 1 H), 7.27 (d, J=9.09 Hz, 1 H), 7.67 (s, 1 H), 7.69 (d, J=2.78 Hz, 1 H), 7.71 (d, J=8.84 Hz, 2 H), 7.85-7.91 (m, 3 H), 7.91 (d, J=8.84 Hz, 2 H), 7.95 (dd, J=8.97, 2.65 Hz, 1 H), 10.22 (s, 1 H), 10.23 (s, 1 H).

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-eedc63c9513848178bb1dfcbeab74dc5
Quelldatensatz
uspto-grants-2012_04
Patentnummer
US08148417B2

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