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Hydrochloric Acid → (R)-1-(1-(2-Hydroxy-3-(pyrrolidin-1-yl)propyl)-1H-indazol-5-yl)-4-(4-(trifluoromethyl)phenyl)pyridin-2(1H)-one hydrochloride

HRID 2390450
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 2390450
[O:1]1[CH2:3][C@@H:2]1[CH2:4][N:5]1[C:13]2[C:8](=[CH:9][C:10]([N:14]3[CH:19]=[CH:18][C:17]([C:20]4[CH:25]=[CH:24][C:23]([C:26]([F:29])([F:28])[F:27])=[CH:22][CH:21]=4)=[CH:16][C:15]3=[O:30])=[CH:11][CH:12]=2)[CH:7]=[N:6]1.[NH:31]1[CH2:35][CH2:34][CH2:33][CH2:32]1.[ClH:36]>O1CCCC1.ClCCl>[ClH:36].[OH:1][C@H:2]([CH2:3][N:31]1[CH2:35][CH2:34][CH2:33][CH2:32]1)[CH2:4][N:5]1[C:13]2[C:8](=[CH:9][C:10]([N:14]3[CH:19]=[CH:18][C:17]([C:20]4[CH:25]=[CH:24][C:23]([C:26]([F:27])([F:28])[F:29])=[CH:22][CH:21]=4)=[CH:16][C:15]3=[O:30])=[CH:11][CH:12]=2)[CH:7]=[N:6]1
KomponentenReaktionsbedingungenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion

Komponenten

6

Edukt 3

HCID 313Hydrochloric AcidHCID 31268PyrrolidineHCID 57625522(S)-1-(1-(oxiran-2-ylmethyl)-1H-indazol-5-yl)-4-(4-(trifluoromethyl)phenyl)-pyridin-2(1H)-one

Produkt 1

HCID 66719416(R)-1-(1-(2-Hydroxy-3-(pyrrolidin-1-yl)propyl)-1H-indazol-5-yl)-4-(4-(trifluoromethyl)phenyl)pyridin-2(1H)-one hydrochlorideAusbeute 83,1 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6344
Dichloromethane
Lösungsmittel
2×
HCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
45 °C

Versuchsvorschrift

To (S)-1-(1-(oxiran-2-ylmethyl)-1H-indazol-5-yl)-4-(4-(trifluoromethyl)phenyl)-pyridin-2(1H)-one (200 mg, 0.48 mmol) in tetrahydrofuran (5 mL) was added LiClO4 (775 mg, 7.28 mmol) followed by pyrrolidine (0.41 mL, 4.9 mmol). The reaction mixture was heated in a 45° C. oil bath for 4.5 h. The reaction mixture was cooled to ambient temperature, diluted with dichloromethane (50 ml), washed with water (25 mL) and brine (25 mL), dried (Na2SO4), and concentrated under reduced pressure. The material was purified by column chromatography (silica gel, 9:1 CH2Cl2/MeOH to 90:9:1 CH2Cl2/MeOH/conc. NH4OH). The dried residue (197 mg, 0.41 mmol) was dissolved in dichloromethane (10 mL) and HCl (1.25 M solution in methanol, 0.36 mL, 0.45 mmol) was added. The mixture was concentrated under reduced pressure and dried to afford the title compound (194 mg, 78%) as a yellow solid: mp 116-119° C.; 1H NMR (500 MHz, DMSO-d6) δ 9.65 (br s, 1H), 8.21 (s, 1H), 8.02-8.00 (m, 2H), 7.89-7.82 (m, 5H), 7.47 (dd, J=9.0, 2.0 Hz, 1H), 6.89 (d, J=2.0 Hz, 1H), 6.74 (dd, J=7.0, 2.0 Hz, 1H), 5.75 (br s, 1H), 4.57-4.47 (m, 2H), 4.33 (br s, 1H), 3.56-2.90 (br m, 6H), 1.89 (br s, 4H); ESI MS m/z 483 [M+H]+; HPLC (Method B)>99% (AUC), tR=14.5 min; [α]23D +10.8° (c 0.11, Methanol).

Aufarbeitung

  1. temperatureThe reaction mixture was cooled to ambient temperature
  2. washwashed with water (25 mL) and brine (25 mL)
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated under reduced pressure
  5. customThe material was purified by column chromatography (silica gel, 9:1 CH2Cl2/MeOH to 90:9:1 CH2Cl2/MeOH/conc. NH4OH)
  6. concentrationThe mixture was concentrated under reduced pressure
  7. customdried

Quellen und Nachweise

ORD-Eintrag
ord-a44e21d6ee5d4f9da6790b44b3ef8890
Quelldatensatz
uspto-grants-2012_09
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US08273770B2

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