Triethylamine → (1R,3S,5R)-tert-butyl 3-(5-((trimethylsilyl)ethynyl)-1H-imidazol-2-yl)-2-azabicyclo[3.1.0]hexane-2-carboxylate

HRID 1471166Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1471166
I[C:2]1[NH:6][C:5]([C@@H:7]2[CH2:12][C@@H:11]3[C@@H:9]([CH2:10]3)[N:8]2[C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])=[N:4][CH:3]=1.C(N(CC)CC)C.[C:27]([Si:29]([CH3:32])([CH3:31])[CH3:30])#[CH:28]>CN(C=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:30][Si:29]([C:27]#[C:28][C:2]1[NH:6][C:5]([C@@H:7]2[CH2:12][C@@H:11]3[C@@H:9]([CH2:10]3)[N:8]2[C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])=[N:4][CH:3]=1)([CH3:32])[CH3:31]

Komponenten

6

Edukt 3

HCID 8471TriethylamineHCID 66111TrimethylsilylacetyleneHCID 58498724(1R,3S,5R)-tert-butyl 3-(4-iodo-1H-imidazol-2-yl)-2-azabicyclo[3.1.0]hexane-2-carboxylate

Produkt 1

HCID 58498793(1R,3S,5R)-tert-butyl 3-(5-((trimethylsilyl)ethynyl)-1H-imidazol-2-yl)-2-azabicyclo[3.1.0]hexane-2-carboxylateAusbeute 64,5 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

Nitrogen was bubbled through a solution of (1R,3S,5R)-tert-butyl 3-(5-iodo-1H-imidazol-2-yl)-2-azabicyclo[3.1.0]hexane-2-carboxylate (1.65 g, 4.40 mmol) and Cu(I)I (168 mg, 0.880 mmol) in triethylamine (3.07 mL, 22.0 mmol) and DMF (40 mL) for 20 min. Then, ethynyltrimethylsilane (2.16 g, 22.0 mmol) and Pd(PPh3)4 (254 mg, 0.220 mmol) were added, the reaction was flushed with nitrogen, sealed and stirred at rt for 24 h. The reaction was concentrated to a brown oil, and purified by BIOTAGE® Horizon (160 g SiO2, 20-40% EtOAc/hexanes) to yield (1R,3S,5R)-tert-butyl 3-(5-((trimethylsilyl)ethynyl)-1H-imidazol-2-yl)-2-azabicyclo[3.1.0]hexane-2-carboxylate (980 mg) as a yellow solid. LC-MS retention time 3.230 min; m/z 346.17 (MH+). LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a PHENOMENEX® Luna 3u C18 2.0×50 mm column using a SPD-10AV UV-Vis detector at a detector wave length of 220 nM. The elution conditions employed a flow rate of 0.8 mL/min, a gradient of 100% Solvent A/0% Solvent B to 0% Solvent A/100% Solvent B, a gradient time of 4 min, a hold time of 1 min, and an analysis time of 5 min where Solvent A was 10% MeOH/90% H2O/0.1% trifluoroacetic acid and Solvent B was 10% H2O/90% MeOH/0.1% trifluoroacetic acid. MS data was determined using a MICROMASS® Platform for LC in electrospray mode. 1H NMR (400 MHz, chloroform-d) d ppm 7.18 (s, 1 H), 4.77 (dd, J=9.2, 5.1 Hz, 1 H), 3.20 (br. s., 1 H), 3.14-3.39 (m, 1 H), 2.33 (dd, J=13.2, 9.4 Hz, 1 H), 1.69-1.78 (m, 1 H), 1.34-1.56 (m, 1 H), 1.49 (s, 9 H), 0.85 (dt, J=8.5, 5.7 Hz, 1 H), 0.41-0.47 (m, 1 H), 0.22-0.24 (m, 9 H).

Aufarbeitung

  1. customthe reaction was flushed with nitrogen
  2. customsealed
  3. concentrationThe reaction was concentrated to a brown oil
  4. custompurified by BIOTAGE® Horizon (160 g SiO2, 20-40% EtOAc/hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-47604eeedf654417a4df975601d30c2a
Quelldatensatz
uspto-grants-2015_04
Patentnummer
US09006455B2

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