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Hydrochloric Acid → 2-[4-(2-Chloro-phenylamino)-6-oxo-6h-pyridazin-1-yl]-4-methyl-pentanoic acid [1-((r)-2,3-dihydroxy-propyl)-1h-pyrazol-3-yl]-amide

HRID 2381546
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 2381546
CC1(C)[O:6][C@H:5]([CH2:7][N:8]2[CH:12]=[CH:11][C:10]([NH:13][C:14](=[O:35])[CH:15]([N:20]3[C:25](=[O:26])[CH:24]=[C:23]([NH:27][C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=4[Cl:34])[CH:22]=[N:21]3)[CH2:16][CH:17]([CH3:19])[CH3:18])=[N:9]2)[CH2:4][O:3]1.Cl>O1CCCC1>[OH:6][C@@H:5]([CH2:4][OH:3])[CH2:7][N:8]1[CH:12]=[CH:11][C:10]([NH:13][C:14](=[O:35])[CH:15]([N:20]2[C:25](=[O:26])[CH:24]=[C:23]([NH:27][C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=3[Cl:34])[CH:22]=[N:21]2)[CH2:16][CH:17]([CH3:19])[CH3:18])=[N:9]1
KomponentenReaktionsbedingungenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion

Komponenten

4

Edukt 2

HCID 313Hydrochloric AcidHCID 668931232-[4-(2-chloro-phenylamino)-6-oxo-6H-pyridazin-1-yl]-4-methyl-pentanoic acid [1-((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)-1H-pyrazol-3-yl]-amide

Produkt 1

HCID 579192422-[4-(2-Chloro-phenylamino)-6-oxo-6h-pyridazin-1-yl]-4-methyl-pentanoic acid [1-((r)-2,3-dihydroxy-propyl)-1h-pyrazol-3-yl]-amideAusbeute 78 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028
Tetrahydrofuran
Lösungsmittel

Reaktionsbedingungen

Temperatur
25 °C

Versuchsvorschrift

A solution of 2-[4-(2-chloro-phenylamino)-6-oxo-6H-pyridazin-1-yl]-4-methyl-pentanoic acid [1-((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)-1H-pyrazol-3-yl]-amide (41.2 mg, 0.08 mmol) in tetrahydrofuran (2 mL) was treated with a 1 M aqueous hydrochloric acid solution (2 mL), and the reaction stirred at 25° C. overnight. At this point, the reaction was dried under nitrogen and suspended in ethyl acetate (20 mL), then washed with a 1:1 aqueous sodium bicarbonate/water solution (20 mL total) and a saturated aqueous sodium chloride solution (10 mL). The organics were dried over sodium sulfate, concentrated in vacuo, and dried from methylene chloride, ethanol, and diethyl ether, and in a vacuum oven at 50° C. for 3 h to afford 2-[4-(2-chloro-phenylamino)-6-oxo-6H-pyridazin-1-yl]-4-methyl-pentanoic acid [1-((R)-2,3-dihydroxy-propyl)-1H-pyrazol-3-yl]-amide as a light yellow solid (29.6 mg, 78%); ES+-HRMS m/e calcd for C22H27N6O4Cl [M+H+] 475.1855 found 475.1855. 1H NMR (300 MHz, DMSO-d6) δ ppm 0.86 (d, J=6.6 Hz, 3H), 0.88 (d, J=6.6 Hz, 3H), 1.44 (br. s., 1H), 1.62-1.81 (m, 1H), 2.00-2.22 (m, 1H), 3.20-3.32 (m, 2H), 3.70-3.92 (m, 2H), 4.08 (dd, J=13.4, 3.8 Hz, 1H), 4.71 (t, J=5.6 Hz, 1H), 4.94 (dd, J=5.1, 1.8 Hz, 1H), 5.49 (dd, J=11.0, 4.1 Hz, 1H), 5.54 (d, J=2.7 Hz, 1H), 6.35 (d, J=2.1 Hz, 1H), 7.28 (td, J=7.8, 1.2 Hz, 1H), 7.40 (td, J=7.8, 1.2 Hz, 1H), 7.47 (dd, J=7.8, 1.2 Hz, 1H), 7.52 (d, J=2.1 Hz, 1H), 7.60 (dd, J=7.8, 1.2 Hz, 1H), 7.86 (d, J=2.7 Hz, 1H), 8.94 (s, 1H), 10.65 (s, 1H).

Aufarbeitung

  1. customAt this point, the reaction was dried under nitrogen
  2. washwashed with a 1:1 aqueous sodium bicarbonate/water solution (20 mL total)
  3. dry with materialThe organics were dried over sodium sulfate
  4. concentrationconcentrated in vacuo
  5. dry with materialdried from methylene chloride, ethanol, and diethyl ether

Quellen und Nachweise

ORD-Eintrag
ord-b8216088208a49d7a309d9b44b54e098
Quelldatensatz
uspto-grants-2012_09
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US08258134B2

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