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Potassium Acetate → ethyl 3-((6-chloro-2-cyclopropyl-7-fluoro-1-(1-propyl-1H-pyrazol-4-yl)-1H-indol-3-yl)thio)-2-fluorobenzoate

HRID 522763
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 522763
Br[C:2]1[N:3]([C:26]2[CH:27]=[N:28][N:29]([CH2:31][CH2:32][CH3:33])[CH:30]=2)[C:4]2[C:9]([C:10]=1[S:11][C:12]1[C:13]([F:23])=[C:14]([CH:20]=[CH:21][CH:22]=1)[C:15]([O:17][CH2:18][CH3:19])=[O:16])=[CH:8][CH:7]=[C:6]([Cl:24])[C:5]=2[F:25].[CH:34]1(B(O)O)[CH2:36][CH2:35]1.CC([O-])=O.[K+]>COCCOC.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[Cl:24][C:6]1[C:5]([F:25])=[C:4]2[C:9]([C:10]([S:11][C:12]3[C:13]([F:23])=[C:14]([CH:20]=[CH:21][CH:22]=3)[C:15]([O:17][CH2:18][CH3:19])=[O:16])=[C:2]([CH:34]3[CH2:36][CH2:35]3)[N:3]2[C:26]2[CH:27]=[N:28][N:29]([CH2:31][CH2:32][CH3:33])[CH:30]=2)=[CH:8][CH:7]=1
KomponentenReaktionsbedingungenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion

Komponenten

7

Edukt 3

HCID 517044Potassium AcetateHCID 2760897Cyclopropylboronic acidHCID 118094312ethyl 3-((2-bromo-6-chloro-7-fluoro-1-(1-propyl-1H-pyrazol-4-yl)-1H-indol-3-yl)thio)-2-fluorobenzoate

Produkt 1

HCID 118094215ethyl 3-((6-chloro-2-cyclopropyl-7-fluoro-1-(1-propyl-1H-pyrazol-4-yl)-1H-indol-3-yl)thio)-2-fluorobenzoateAusbeute 28,9 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 44119782
Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)
Katalysator
HCID 962WaterLösungsmittel
HCID 80711,2-DimethoxyethaneLösungsmittel

Reaktionsbedingungen

Temperatur
90 °C

Versuchsvorschrift

To a stirred solution of compound 3 (260 mg, 0.47 mmol) in DME (5 mL) under inert atmosphere were added cyclopropylboronic acid (40.4 mg, 0.47 mmol), Pd(dppf)2Cl2 (69 mg, 0.09 mmol), KOAc (138 mg, 1.41 mmol) at RT; heated to 90° C. and stirred for 16 h. The reaction was monitored by TLC; after completion of the reaction, the reaction mixture was diluted with water (20 mL) and extracted with EtOAc (2×25 mL). The combined organic extracts were washed with brine (20 mL), dried over Na2SO4, filtered and concentrated under reduced pressure to obtain the crude. This was purified by silica gel column chromatography using 7-9% EtOAc/Hexanes to afford 70 mg of compound 4 which was further purified by preparative HPLC to afford pure compound 4 (20 mg, 9%) as a yellow syrup. 1H NMR (400 MHz, CDCl3): δ 7.67 (s, 1H), 7.64-7.60 (m, 2H), 7.18 (d, J=8.8 Hz, 1H), 7.10-7.06 (m, 1H), 6.95-6.91 (m, 1H), 6.79-6.75 (m, 1H), 4.41 (q, J=7.2 Hz, 2H), 4.18 (t, J=7.2 Hz, 2H), 2.00-1.93 (m, 2H), 1.74-1.67 (m, 1H), 1.41 (t, J=7.2 Hz, 3H), 1.08-1.06 (m, 2H), 0.99 (t, J=7.2 Hz, 3H), 0.87-0.84 (m, 2H); LC-MS (ESI): 99.9%; m/z 516.5 (M+H+); (column: X Select CSH C-18, 50×3.0 mm, 3.5 μm); RT 5.00 min; 5 mM NH4OAc: ACN; 0.8 mL/min).

Aufarbeitung

  1. customafter completion of the reaction
  2. extractionextracted with EtOAc (2×25 mL)
  3. washThe combined organic extracts were washed with brine (20 mL)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customto obtain the crude
  8. customThis was purified by silica gel column chromatography

Quellen und Nachweise

ORD-Eintrag
ord-cccd9455ab4946c1b252354a4d2e7bf7
Quelldatensatz
uspto-grants-2016_05
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US09334261B2

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