Chlorosuccinimide → methyl 6-((6-chloro-2-cyclopropyl-1-(1-ethyl-1H-pyrazol-4-yl)-7-fluoro-1H-indol-3-yl)thio)picolinate

HRID 2171303Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2171303
[SH:1][C:2]1[N:7]=[C:6]([C:8]([O:10][CH3:11])=[O:9])[CH:5]=[CH:4][CH:3]=1.C1C(=O)N(Cl)C(=O)C1.[Cl:20][C:21]1[C:29]([F:30])=[C:28]2[C:24]([CH:25]=[C:26]([CH:38]3[CH2:40][CH2:39]3)[N:27]2[C:31]2[CH:32]=[N:33][N:34]([CH2:36][CH3:37])[CH:35]=2)=[CH:23][CH:22]=1>C(Cl)Cl>[Cl:20][C:21]1[C:29]([F:30])=[C:28]2[C:24]([C:25]([S:1][C:2]3[N:7]=[C:6]([C:8]([O:10][CH3:11])=[O:9])[CH:5]=[CH:4][CH:3]=3)=[C:26]([CH:38]3[CH2:40][CH2:39]3)[N:27]2[C:31]2[CH:32]=[N:33][N:34]([CH2:36][CH3:37])[CH:35]=2)=[CH:23][CH:22]=1

Komponenten

5

Edukt 3

HCID 31398ChlorosuccinimideHCID 1181041966-chloro-2-cyclopropyl-1-(1-ethyl-1H-pyrazol-4-yl)-7-fluoro-1H-indoleHCID 178498017HCID 178498017, Verbindung

Produkt 1

HCID 118104201methyl 6-((6-chloro-2-cyclopropyl-1-(1-ethyl-1H-pyrazol-4-yl)-7-fluoro-1H-indol-3-yl)thio)picolinateAusbeute 32,2 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel3×

Versuchsvorschrift

To a stirred solution of methyl 6-mercaptopicolinate 6 (3.15 g, crude) in CH2Cl2 (50 mL) under inert atmosphere was added NCS (2.49 g, 18.63 mmol) at RT and stirred for 1 h. To this, indole 5 (5.6 g, 18.47 mmol) in CH2Cl2 (50 mL) was added at RT and stirred for 16 h. After completion of the reaction (TLC), the reaction mixture was diluted CH2Cl2 (100 mL) washed with water (3×100 mL). The organic extract was dried over Na2SO4, filtered and concentrated under reduced pressure to obtain the crude. The crude was purified (silica gel column chromatography; 10% EtOAc/hexanes) to afford 9 (2.8 g, 32%) as a pale brown solid. 1H NMR (500 MHz, DMSO-d6): δ 7.79 (d, J=7.5 Hz, 1H), 7.66 (d, J=10.5 Hz, 2H), 7.51 (t, J=7.5 Hz, 1H), 7.19 (d, J=8.5 Hz, 1H), 7.10-7.07 (m, 1H), 6.78 (d, J=8.0 Hz, 1H), 4.28 (q, 2H), 4.00 (s, 3H), 1.75-1.69 (m, 1H), 1.58 (t, J=7.0 Hz, 3H), 1.09-1.08 (m, 2H), 0.87-0.84 (m, 2H); LC-MS: 98.4%; m/z 471.4 (M+H+);(column; X-select CSH C-18, (50×3.0 mm, 3.5 μm); RT 4.25 min. 5.0 mM NH4OAc (Aq): ACN; 0.8 mL/min); HPLC: 98.1%; (column: Acquity BEH C-18 (50×2.1 mm, 1.7μ); RT 3.02 min. ACN: 0.025% TFA (aq); 0.5 mL/min).

Aufarbeitung

  1. stirringstirred for 16 h
  2. customAfter completion of the reaction (TLC)
  3. washwashed with water (3×100 mL)
  4. extractionThe organic extract
  5. dry with materialwas dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customto obtain the crude
  9. customThe crude was purified (silica gel column chromatography; 10% EtOAc/hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-14f01761c5f94071afae37f992f2c59b
Quelldatensatz
uspto-grants-2015_06
Patentnummer
US09051320B1

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