StartseiteMCPWorkbenchSkills
StartseiteWorkbenchBenachrichtigungenMein Bereich
llms.txt · MCP-AnleitungDatenschutz · Nutzungsbedingungen · Supportv1.8.0
  1. Startseite
  2. /Reaktion

Sodium Carbonate → 2-((3S,4S)-3-Amino-4-hydroxypyrrolidin-1-yl)-N-(4-(chlorodifluoromethoxy)phenyl)-5'-fluoro-[3,3'-bipyridine]-5-carboxamide

HRID 924131
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 924131
Cl[C:2]1[C:7]([C:8]2[CH:9]=[N:10][CH:11]=[C:12]([F:14])[CH:13]=2)=[CH:6][C:5]([C:15]([NH:17][C:18]2[CH:23]=[CH:22][C:21]([O:24][C:25]([Cl:28])([F:27])[F:26])=[CH:20][CH:19]=2)=[O:16])=[CH:4][N:3]=1.CCN(C(C)C)C(C)C.[NH2:38][C@H:39]1[CH2:43][NH:42][CH2:41][C@@H:40]1[OH:44].C([O-])([O-])=O.[Na+].[Na+]>CC(O)C>[NH2:38][C@@H:39]1[C@@H:40]([OH:44])[CH2:41][N:42]([C:2]2[C:7]([C:8]3[CH:9]=[N:10][CH:11]=[C:12]([F:14])[CH:13]=3)=[CH:6][C:5]([C:15]([NH:17][C:18]3[CH:19]=[CH:20][C:21]([O:24][C:25]([Cl:28])([F:26])[F:27])=[CH:22][CH:23]=3)=[O:16])=[CH:4][N:3]=2)[CH2:43]1
KomponentenReaktionsbedingungenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion

Komponenten

6

Edukt 4

HCID 10340Sodium CarbonateHCID 81531DiisopropylethylamineHCID 10559158(3S,4S)-4-Aminopyrrolidin-3-olHCID 722015872-Chloro-N-(4-(chlorodifluoromethoxy)phenyl)-5'-fluoro-[3,3'-bipyridine]-5-carboxamide

Produkt 1

HCID 1181953932-((3S,4S)-3-Amino-4-hydroxypyrrolidin-1-yl)-N-(4-(chlorodifluoromethoxy)phenyl)-5'-fluoro-[3,3'-bipyridine]-5-carboxamide

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 3776IsopropanolLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

2-Chloro-N-(4-(chlorodifluoromethoxy)phenyl)-5′-fluoro-[3,3′-bipyridine]-5-carboxamide (Stage 266.1, 70 mg, 0.160 mmol) and DIPEA (0.196 mL, 1.121 mmol) were added to a vial containing iPrOH (2 mL). (3S,4S)-4-Aminopyrrolidin-3-ol (30 mg, 0.168 mmol) was added. The mixture was stirred at 80° C. for 44 h. The RM was treated with sat. aq. Na2CO3 (20 mL) and extracted with EtOAc. The combined extracts were washed with brine (10 mL), dried over Na2SO4, filtered and evaporated to dryness under reduced to give the crude product which was purified by flash chromatography (Silica gel column, 4 g, DCM/MeOH, from 95:5 to 8:2) to afford the title product as a beige solid. HPLC (Condition 10) tR=5.83 min, UPLC-MS (Condition 3) tR=0.81 min, m/z=494.2/496.2 [M+H]+; 1H-NMR (400 MHz, DMSO-d6) δ ppm 2.91 (dd, J=11.53, 2.93 Hz, 1H) 3.22-3.28 (m, 1H) 3.36-3.46 (m, 2H) 3.59-3.66 (m, 1H) 4.02-4.08 (m, 1H) 5.48 (d, J=3.91 Hz, 1H) 7.35 (d, J=8.60 Hz, 2H) 7.87 (m, J=9.00 Hz, 3H) 8.13 (d, J=2.35 Hz, 1H) 8.55 (s, 1H) 8.64 (d, J=2.74 Hz, 1H) 8.79-8.83 (m, 1H) 10.22 (s, 1H).

Aufarbeitung

  1. extractionextracted with EtOAc
  2. washThe combined extracts were washed with brine (10 mL)
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. customevaporated to dryness
  6. customto give the crude product which
  7. customwas purified by flash chromatography (Silica gel column, 4 g, DCM/MeOH, from 95:5 to 8:2)

Quellen und Nachweise

ORD-Eintrag
ord-64fcad3b72f143a0936ffff85d153a8b
Quelldatensatz
uspto-grants-2016_03
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US09278981B2

Notizen zur Reaktion

Wird geladen…

Auf dieser SeiteKomponentenReaktionsbedingungenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion