Formaldehyde → 1-[1-(4-fluorophenyl)-6,7-dihydro-5H-pyrazolo[4,3-b]pyridin-4-yl]-3-hydroxy-2-[5-methyl-3-(trifluoromethyl)pyrazol-1-yl]propan-1-one

HRID 710664Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 710664
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:16]3[CH2:15][CH2:14][CH2:13][N:12]([C:17](=[O:29])[CH2:18][N:19]4[C:23]([CH3:24])=[CH:22][C:21]([C:25]([F:28])([F:27])[F:26])=[N:20]4)[C:11]=3[CH:10]=[N:9]2)=[CH:4][CH:3]=1.[Li+].CC([N-]C(C)C)C.[CH2:38]=[O:39].[NH4+].[Cl-]>C1COCC1>[F:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[C:16]3[CH2:15][CH2:14][CH2:13][N:12]([C:17](=[O:29])[CH:18]([N:19]4[C:23]([CH3:24])=[CH:22][C:21]([C:25]([F:27])([F:26])[F:28])=[N:20]4)[CH2:38][OH:39])[C:11]=3[CH:10]=[N:9]2)=[CH:6][CH:7]=1

Komponenten

6

Edukt 4

HCID 712FormaldehydeHCID 25517Ammonium ChlorideHCID 2724682Lithium diisopropylamideHCID 733351261-[1-(4-fluorophenyl)-6,7-dihydro-5H-pyrazolo[4,3-b]pyridin-4-yl]-2-[5-methyl-3-(trifluoromethyl)pyrazol-1-yl]ethanone

Produkt 1

HCID 733359171-[1-(4-fluorophenyl)-6,7-dihydro-5H-pyrazolo[4,3-b]pyridin-4-yl]-3-hydroxy-2-[5-methyl-3-(trifluoromethyl)pyrazol-1-yl]propan-1-oneAusbeute 55 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
-78 °C

Versuchsvorschrift

To a mixture of 1-[1-(4-fluorophenyl)-6,7-dihydro-5H-pyrazolo[4,3-b]pyridin-4-yl]-2-[5-methyl-3-(trifluoromethyl)pyrazol-1-yl]ethanone (0.100 g, 0.25 mmol) in THF (3 mL) at −78° C. was added LDA (0.15 mL, 0.3 mmol, 2 M in THF). After stirring for 10 min at −78° C., dry paraformaldehyde (0.025 g, 0.82 mmol, suspended in THF) was added. The mixture was then warmed to rt for 8 min, followed by the addition of sat. NH4Cl. The mixture was partitioned between EtOAc (50 mL) and brine (30 mL). The organic layer was separated, dried over Na2SO4, concentrated in vacuo, and purified by reverse phase HPLC to yield the desired product (0.056 g, 55%). 1H NMR (400 MHz, CDCl3) δ 8.50 (s, 1H), 7.42 (m, 2H), 7.18 (dd, J=8.4, 8.4 Hz, 2H), 6.36 (s, 1H), 5.41 (t, J=5.6 Hz, 1H), 4.36 (m, 1H), 4.20 (m, 1H), 3.69 (m, 1H), 3.26 (m, 1H), 2.76 (m, 2H), 2.31 (s, 3H), 1.92 (m, 2H); MS: (ES) m/z calculated for C20H19F4N5O2 [M+H]+ 438.1, found 438.1.

Aufarbeitung

  1. temperatureThe mixture was then warmed to rt for 8 min
  2. customThe mixture was partitioned between EtOAc (50 mL) and brine (30 mL)
  3. customThe organic layer was separated
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. custompurified by reverse phase HPLC

Quellen und Nachweise

ORD-Eintrag
ord-0d7cd4dde4d04e4d9e27e9d6e86a8b4e
Quelldatensatz
uspto-grants-2015_11
Patentnummer
US09181241B2

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