(S)-tert-butyl 1-(3,3-dimethyl-1-(methylamino)-1-oxobutan-2-ylcarbamoyl)-3-(2,4,5-trifluorophenyl)-6,7-dihydro-1H-pyrazolo[4,3-c]pyridine-5(4H)-carboxylate → (S)-N-(3,3-dimethyl-1-(methylamino)-1-oxobutan-2-yl)-5-methyl-3-(2,4,5-trifluorophenyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine-1-carboxamide

HRID 18471

Reaktionsgleichung

Reaktionsgleichung von HRID 18471
[CH3:1][C:2]([CH3:37])([CH3:36])[C@H:3]([NH:8][C:9]([N:11]1[C:19]2[CH2:18][CH2:17][N:16]([C:20](OC(C)(C)C)=O)[CH2:15][C:14]=2[C:13]([C:27]2[CH:32]=[C:31]([F:33])[C:30]([F:34])=[CH:29][C:28]=2[F:35])=[N:12]1)=[O:10])[C:4]([NH:6][CH3:7])=[O:5]>C(O)(C(F)(F)F)=O.C(Cl)Cl.C1(C)C=CC=CC=1>[CH3:1][C:2]([CH3:37])([CH3:36])[C@H:3]([NH:8][C:9]([N:11]1[C:19]2[CH2:18][CH2:17][N:16]([CH3:20])[CH2:15][C:14]=2[C:13]([C:27]2[CH:32]=[C:31]([F:33])[C:30]([F:34])=[CH:29][C:28]=2[F:35])=[N:12]1)=[O:10])[C:4]([NH:6][CH3:7])=[O:5]

Komponenten

4

Edukt 1

HCID 66997658(S)-tert-butyl 1-(3,3-dimethyl-1-(methylamino)-1-oxobutan-2-ylcarbamoyl)-3-(2,4,5-trifluorophenyl)-6,7-dihydro-1H-pyrazolo[4,3-c]pyridine-5(4H)-carboxylate

Produkt 1

HCID 46863441(S)-N-(3,3-dimethyl-1-(methylamino)-1-oxobutan-2-yl)-5-methyl-3-(2,4,5-trifluorophenyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine-1-carboxamideAusbeute 49 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 1140TolueneLösungsmittelHCID 21863450Trifluoroacetic acid methylene chlorideLösungsmittel

Versuchsvorschrift

A solution of (S)-tert-butyl 1-(3,3-dimethyl-1-(methylamino)-1-oxobutan-2-ylcarbamoyl)-3-(2,4,5-trifluorophenyl)-6,7-dihydro-1H-pyrazolo[4,3-c]pyridine-5(4H)-carboxylate (0.92 g, 1.76 mmol) in TFA/DCM (1:1) was stirred at room temperature for 30 min. The reaction mixture was diluted with toluene and evaporated under vacuum. The resulting residue was dissolved in THF, to which formaldehyde (37%, 0.65 mL) and sodium triacetoxyborohydride (424 mg) was added sequentially. After stifling at room temperature for 2 h, THF was evaporated under vacuum. The residue was extracted between EtOAc and saturated aqueous sodium bicarbonate. The organic phase was dried over sodium sulfate and evaporated to dryness. The crude mixture was purified by column with a gradient of from 10% to 40% ethanol in MeCN to give (S)—N-(3,3-dimethyl-1-(methylamino)-1-oxobutan-2-yl)-5-methyl-3-(2,4,5-trifluoro-phenyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine-1-carboxamide 37 as a solid (412 mg, 49% yield for two steps). 1H NMR (CDCl3) δ 7.86 (d, J=9.4 Hz, 1H), 7.47-7.54 (m, 1H), 6.98-7.04 (m, 1H), 5.85 (br, 1H), 4.11 (d, J=9.4 Hz, 1H), 3.39 (s, 2H), 3.16-3.20 (m, 2H), 2.84 (d, J=4.8 Hz, 3H), 2.73 (t, J=6.2 Hz, 2H), 2.47 (s, 3H), 1.05 (s, 9H). LCMS (+ESI) m/z=438 [M+H]+.

Aufarbeitung

  1. customevaporated under vacuum
  2. dissolutionThe resulting residue was dissolved in THF, to which formaldehyde (37%, 0.65 mL) and sodium triacetoxyborohydride (424 mg)
  3. additionwas added sequentially
  4. customTHF was evaporated under vacuum
  5. extractionThe residue was extracted between EtOAc and saturated aqueous sodium bicarbonate
  6. dry with materialThe organic phase was dried over sodium sulfate
  7. customevaporated to dryness
  8. customThe crude mixture was purified by column with a gradient of from 10% to 40% ethanol in MeCN

Quellen und Nachweise

ORD-Eintrag
ord-edfc1c69344448a2b3676106f79e6222
Quelldatensatz
uspto-grants-2010_06
Patentnummer
US07741350B1

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