Formaldehyde → [(S)-7-Cyano-4-((2R,3R)-3-hydroxy-1-methyl-pyrrolidin-2-ylmethyl)-1,2,3,4-tetrahydro-cyclopenta[b]indol-2-yl]-carbamic acid isopropyl ester

HRID 449843Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 449843
Cl.[CH:2]([O:5][C:6](=[O:29])[NH:7][C@@H:8]1[CH2:28][C:11]2[N:12]([CH2:21][C@@H:22]3[C@H:26]([OH:27])[CH2:25][CH2:24][NH:23]3)[C:13]3[CH:14]=[CH:15][C:16]([C:19]#[N:20])=[CH:17][C:18]=3[C:10]=2[CH2:9]1)([CH3:4])[CH3:3].C=O.[C:32](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)(O)[O-].[Na+]>C(#N)C.C(OCC)(=O)C.CO>[CH:2]([O:5][C:6](=[O:29])[NH:7][C@@H:8]1[CH2:28][C:11]2[N:12]([CH2:21][C@@H:22]3[C@H:26]([OH:27])[CH2:25][CH2:24][N:23]3[CH3:32])[C:13]3[CH:14]=[CH:15][C:16]([C:19]#[N:20])=[CH:17][C:18]=3[C:10]=2[CH2:9]1)([CH3:4])[CH3:3]

Komponenten

8

Edukt 4

HCID 712FormaldehydeHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 66933117[(S)-7-Cyano-4-((2R,3R)-3-hydroxy-pyrrolidin-2-ylmethyl)-1,2,3,4-tetrahydro-cyclopenta[b]indol-2-yl]-carbamic acid isopropyl ester hydrochloride

Produkt 1

HCID 66933305[(S)-7-Cyano-4-((2R,3R)-3-hydroxy-1-methyl-pyrrolidin-2-ylmethyl)-1,2,3,4-tetrahydro-cyclopenta[b]indol-2-yl]-carbamic acid isopropyl esterAusbeute 61 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 887MethanolLösungsmittelHCID 6342AcetonitrileLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

A solution of [(S)-7-cyano-4-((2R,3R)-3-hydroxy-pyrrolidin-2-ylmethyl)-1,2,3,4-tetrahydro-cyclopenta[b]indol-2-yl]-carbamic acid isopropyl ester hydrochloride salt (380 mg, 907.1 μmol) in acetonitrile (50 mL) is treated with methanol (5 mL) until most of the solid is dissolved and then treated with formaldehyde (136.3 μL, 1.81 mmol) and sodium triacetoxyborohydride (400.5 mg, 1.81 mmol). The reaction is stirred at room temperature overnight. Saturated aqueous sodium bicarbonate solution (50 mL) is added and stirred for 30 min. The mixture is diluted with ethyl acetate (120 mL) and the resulting suspension is washed with water (3×100 mL) and brine. The organic portion is dried over sodium sulfate, filtered, and concentrated to dryness. The residue is purified by medium pressure liquid chromatography, eluting with methanol:chloroform (5:95). Fractions containing pure product are combined and concentrated to afford 0.2 g (61%) of the title compound. LC-ES/MS m/z 397.2 [M+H]+, TR=1.87 min.

Aufarbeitung

  1. dissolutionis dissolved
  2. stirringstirred for 30 min
  3. washthe resulting suspension is washed with water (3×100 mL) and brine
  4. dry with materialThe organic portion is dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated to dryness
  7. customThe residue is purified by medium pressure liquid chromatography
  8. washeluting with methanol:chloroform (5:95)
  9. additionFractions containing pure product
  10. concentrationconcentrated

Quellen und Nachweise

ORD-Eintrag
ord-522ee113492d4d8597265a4f04041d8d
Quelldatensatz
uspto-grants-2013_07
Patentnummer
US08486943B2

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