(3S)-3-aminopyrrolidin-2-one → (S)-5-(2,4-difluorophenoxy)-1-(2-fluoro-2-methylpropyl)-N-(2-oxopyrrolidin-3-yl)-1H-indazole-6-carboxamide

HRID 912466

Reaktionsgleichung

Reaktionsgleichung von HRID 912466
O=C1CCC(=O)N1[C:8]1[C:16]2[C:11](=[CH:12][C:13]([C:26]([O-:28])=O)=[C:14]([O:17][C:18]3[CH:23]=[CH:22][C:21]([F:24])=[CH:20][C:19]=3[F:25])[CH:15]=2)[N:10]([CH2:29][C:30]([F:33])([CH3:32])[CH3:31])[N:9]=1.[NH2:34][C@H:35]1[CH2:39][CH2:38][NH:37][C:36]1=[O:40]>ClCCl.C(OCC)(=O)C>[F:25][C:19]1[CH:20]=[C:21]([F:24])[CH:22]=[CH:23][C:18]=1[O:17][C:14]1[CH:15]=[C:16]2[C:11](=[CH:12][C:13]=1[C:26]([NH:34][C@H:35]1[CH2:39][CH2:38][NH:37][C:36]1=[O:40])=[O:28])[N:10]([CH2:29][C:30]([F:33])([CH3:32])[CH3:31])[N:9]=[CH:8]2

Komponenten

5

Edukt 2

HCID 12430456(3S)-3-aminopyrrolidin-2-oneHCID 866310522,5-dioxopyrrolidin-1-yl-5-(2,4-difluorophenoxy)-1-(2-fluoro-2-methylpropyl)-1H-indazole-6-carboxylate

Produkt 1

HCID 24865103(S)-5-(2,4-difluorophenoxy)-1-(2-fluoro-2-methylpropyl)-N-(2-oxopyrrolidin-3-yl)-1H-indazole-6-carboxamideAusbeute 1.032,3 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6344DichloromethaneLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

To a solution of 2,5-dioxopyrrolidin-1-yl-5-(2,4-difluorophenoxy)-1-(2-fluoro-2-methylpropyl)-1H-indazole-6-carboxylate (prepared according to Example 26; 100 mg, 0.217 mmol) in dichloromethane (1 mL) was added (S)-3-aminopyrrolidin-2-one (4a) 521 mg, 4.56 mmol), and the reaction mixture was allowed to stir overnight at ambient temperature. The reaction mixture was diluted with ethyl acetate and washed with 1M hydrochloric acid, 1M sodium hydroxide, saturated sodium bicarbonate, and saturated sodium chloride. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was purified by column chromatography on a silica gel column, eluting with 50% acetone/hexanes to yield (S)-5-(2,4-difluorophenoxy)-1-(2-fluoro-2-methylpropyl)-N-(2-oxopyrrolidin-3-yl)-1H-indazole-6-carboxamide (Ik) (1.00 g, 99%). Mass spec: 447 (M+1). 1H NMR (CDCl3) δ 8.42 (s, 1H), 8.21 (br, 1H), 7.15 (m, 1H), 7.03 (s, 1H), 7.01 (m, 1H), 6.91 (m, 1H), 6.59 (br, 1H), 4.58 (m, 1H), 4.55 (d, 2H), 3.43 (m, 2H), 2.84 (m, 1H), 2.06 (m, 1H), 1.40 (d, 3H), 1.39 (d, 3H).

Aufarbeitung

  1. washwashed with 1M hydrochloric acid, 1M sodium hydroxide, saturated sodium bicarbonate, and saturated sodium chloride
  2. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue was purified by column chromatography on a silica gel column
  6. washeluting with 50% acetone/hexanes

Quellen und Nachweise

ORD-Eintrag
ord-63863af0cc644b8ca06c3d955ebe43e7
Quelldatensatz
uspto-grants-2011_09
Patentnummer
US08026233B2

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