2-Methyl-2-butene → 6-chloro-5-[2-(morpholin-4-yl)pyrimidin-5-yl]-1H-indole-3-carboxylic acid

HRID 338407Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 338407
[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([CH:11]=[O:12])=[CH:7][NH:8]2)=[CH:4][C:3]=1[C:13]1[CH:14]=[N:15][C:16]([N:19]2[CH2:24][CH2:23][O:22][CH2:21][CH2:20]2)=[N:17][CH:18]=1.CC(=CC)C.Cl([O-])=[O:31].[Na+].O.O.OP([O-])(O)=O.[Na+]>C(#N)C.O.C(O)(C)(C)C>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11]([OH:31])=[O:12])=[CH:7][NH:8]2)=[CH:4][C:3]=1[C:13]1[CH:14]=[N:15][C:16]([N:19]2[CH2:24][CH2:23][O:22][CH2:21][CH2:20]2)=[N:17][CH:18]=1

Komponenten

8

Edukt 4

HCID 105532-Methyl-2-buteneHCID 23668197Sodium ChloriteHCID 23673460Sodium Phosphate, Monobasic, DihydrateHCID 866987436-chloro-5-[2-(morpholin-4-yl)pyrimidin-5-yl]-1H-indole-3-carbaldehyde

Produkt 1

HCID 866987446-chloro-5-[2-(morpholin-4-yl)pyrimidin-5-yl]-1H-indole-3-carboxylic acidAusbeute 40,6 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 962WaterLösungsmittelHCID 6342AcetonitrileLösungsmittelHCID 6386tert-ButanolLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

6-chloro-5-[2-(morpholin-4-yl)pyrimidin-5-yl]-1H-indole-3-carbaldehyde (159 mg, 0.464 mmol) was dissolved in acetonitrile (6 mL) and warm tert-butanol (6 mL) and treated with 2-methyl-2-butene. The reaction mixture was cooled to 0° C. and treated with a solution of sodium chlorite (630 mg, 9.27 mmol) and sodium phosphate monobasic dihydrate (1.45 g, 9.30 mmol) in water (5 mL) via addition funnel. The mixture was stirred at room temperature overnight. The reaction mixture was then concentrated in vacuo to remove the organics and extracted with EtOAc (3×20 mL). The combined organics were washed with brine (20 mL), dried and concentrated in vacuo to give a crude, which was purified by prep-HPLC to give 6-chloro-5-[2-(morpholin-4-yl)pyrimidin-5-yl]-1H-indole-3-carboxylic acid (67.6 mg, 40.60% yield) as a white solid. MS (ES+) 359.1 (M+H)+. 1H NMR (400 MHz, DMSO-d6) δ 12.22 (s, 1H), 12.03 (s, 1H), 8.49 (m, 2H), 8.12 (m, 1H), 7.97 (s, 1H), 7.69 (s, 1H), 3.78 (m, 4H), 3.70 (m, 4H).

Aufarbeitung

  1. concentrationThe reaction mixture was then concentrated in vacuo
  2. customto remove the organics and
  3. extractionextracted with EtOAc (3×20 mL)
  4. washThe combined organics were washed with brine (20 mL)
  5. customdried
  6. concentrationconcentrated in vacuo
  7. customto give a crude, which
  8. customwas purified by prep-HPLC

Quellen und Nachweise

ORD-Eintrag
ord-d7ce4c07515c44d08cf5a784840cc923
Quelldatensatz
uspto-grants-2014_11
Patentnummer
US08889730B2

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