Tetrabutylammonium Fluoride → 1-(benzo[d][1,3]dioxol-5-yl)-N-(5-((2-chlorophenyl)((S)-3-hydroxypyrrolidin-1-yl)methyl)-4-methylthiazol-2-yl)cyclopropanecarboxamide

HRID 2043241Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2043241
[O:1]1[C:5]2[CH:6]=[CH:7][C:8]([C:10]3([C:13]([NH:15][C:16]4[S:17][C:18]([CH:22]([N:30]5[CH2:34][CH2:33][C@H:32]([O:35][Si](C(C)(C)C)(C)C)[CH2:31]5)[C:23]5[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=5[Cl:29])=[C:19]([CH3:21])[N:20]=4)=[O:14])[CH2:12][CH2:11]3)=[CH:9][C:4]=2[O:3][CH2:2]1.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>>[O:1]1[C:5]2[CH:6]=[CH:7][C:8]([C:10]3([C:13]([NH:15][C:16]4[S:17][C:18]([CH:22]([C:23]5[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=5[Cl:29])[N:30]5[CH2:34][CH2:33][C@H:32]([OH:35])[CH2:31]5)=[C:19]([CH3:21])[N:20]=4)=[O:14])[CH2:12][CH2:11]3)=[CH:9][C:4]=2[O:3][CH2:2]1

Komponenten

3

Edukt 2

HCID 2724141Tetrabutylammonium FluorideHCID 86621216HCID 86621216, Verbindung

Produkt 1

HCID 866212171-(benzo[d][1,3]dioxol-5-yl)-N-(5-((2-chlorophenyl)((S)-3-hydroxypyrrolidin-1-yl)methyl)-4-methylthiazol-2-yl)cyclopropanecarboxamide

Versuchsvorschrift

A mixture of 1-(benzo[d][1,3]dioxol-5-yl)-N-(5-(((S)-3-(tert-butyldimethylsilyloxy)pyrrolidin-1-yl)(2-chlorophenyl)methyl)-4-methylthiazol-2-yl)cyclopropanecarboxamide (Isomer A) (400 mg, 0.64 mmol) and TBAF (1M in THF, 3.84 mL, 3.84 mmol) was stirred at room temperature for 5 h. The reaction was partitioned between H2O and EtOAc. The combined organic layers were washed with brine, dried over MgSO4 and concentrated. The residue was adsorbed onto silica gel and purified by column chromatography (25-75% EtOAc/hexanes) to afford 1-(benzo[d][1,3]dioxol-5-yl)-N-(5-((2-chlorophenyl)((S)-3-hydroxypyrrolidin-1-yl)methyl)-4-methylthiazol-2-yl)cyclopropanecarboxamide (Isomer A) as a pale yellow solid (245 mg, 75%, >99% de). 1H NMR (400 MHz, CDCl3) δ 8.41 (s, 1H), 7.85 (dd, J=8.1, 1.7 Hz, 1H), 7.29-7.26 (m, 2H), 7.14 (m, 1H), 6.88-6.84 (m, 2H), 6.79 (d, J=7.9 Hz, 1H), 6.00 (s, 2H), 5.07 (s, 1H), 4.30 (m, 1H), 2.79 (td, J=8.6, 5.8 Hz, 1H), 2.63-2.56 (m, 2H), 2.36 (s, 3H), 2.29 (td, J=9.0, 5.9 Hz, 1H), 2.15 (m, 1H), 1.85 (d, J=7.9 Hz, 1H), 1.78-1.65 (m, 3H), 1.18 (m, 2H); HPLC ret. time 2.70 min, 10-99% CH3CN, 5 min run; ESI-MS 512.5 m/z (MH+).

Aufarbeitung

  1. customThe reaction was partitioned between H2O and EtOAc
  2. washThe combined organic layers were washed with brine
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated
  5. custompurified by column chromatography (25-75% EtOAc/hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-4fec2983df9249bc8243560c31fe6f9c
Quelldatensatz
uspto-grants-2013_11
Patentnummer
US08586615B2

Notizen zur Reaktion

Wird geladen…