2,2'-(Naphthalene-2,6-diyl)bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolane) → HCID 178451934, Verbindung

HRID 625585Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 625585
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[NH:12][C:11]([C@@H:13]3[CH2:17][CH2:16][CH2:15][N:14]3[C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])=[N:10][C:9]=2[Cl:25])=[CH:4][CH:3]=1.[CH3:26][C:27]1([CH3:53])[C:31]([CH3:33])([CH3:32])[O:30][B:29]([C:34]2[CH:43]=[CH:42][C:41]3[C:36](=[CH:37][CH:38]=[C:39](B4OC(C)(C)C(C)(C)O4)[CH:40]=3)[CH:35]=2)[O:28]1>COCCOC.O.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>[Cl:25][C:9]1[N:10]=[C:11]([C@@H:13]2[CH2:17][CH2:16][CH2:15][N:14]2[C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[NH:12][C:8]=1[C:5]1[CH:6]=[CH:7][C:2]([C:39]2[CH:38]=[CH:37][C:36]3[C:41](=[CH:42][CH:43]=[C:34]([B:29]4[O:28][C:27]([CH3:53])([CH3:26])[C:31]([CH3:33])([CH3:32])[O:30]4)[CH:35]=3)[CH:40]=2)=[CH:3][CH:4]=1

Komponenten

6

Edukt 2

HCID 596108242,2'-(Naphthalene-2,6-diyl)bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolane)HCID 178451933HCID 178451933, Verbindung

Produkt 1

HCID 178451934HCID 178451934, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178418397HCID 178418397, VerbindungKatalysator2×HCID 962WaterLösungsmittelHCID 80711,2-DimethoxyethaneLösungsmittel

Versuchsvorschrift

A solution of (S)-tert-butyl 2-(5-(4-bromophenyl)-4-chloro-1H-imidazol-2-yl)pyrrolidine-1-carboxylate (1.04 g, 2.44 mmol) and 2,6-bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)naphthalene (0.926 g, 2.44 mmol) in DME (10 mL) and water (2 mL) was degassed under vacuum for 10 min. The mixture was heated at ca ˜80° C., Pd(Ph3P)4 (0.282 g, 0.244 mmol) was added under a stream of nitrogen and the reactor was sealed. The heating was pursued further to 130° C. for 8 h. Additional Pd(PPh3)4 (100 mg) was added and the heating was pursued overnight. The DME was removed in vacuo and the crude material was partitioned between EtOAc/H2O. The layers were separated and the aqueous layer was extracted several times with EtOAc. The combined organic extracts were dried over Na2SO4 and evaporated in vacuo. The residue was purified by flash column chromatography (BIOTAGE®), eluting with a gradient of 0 to 100% EtOAc/hexanes to afford the partially pure (S)-tert-butyl 2-(4-chloro-5-(4-(6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)naphthalen-2-yl)phenyl)-1H-imidazol-2-yl)pyrrolidine-1-carboxylate contaminated with triphenylphosphine (292 mg). A small aliquot was purified further by a reverse phase HPLC (water/acetonitrile/TFA) to afford the pure title material. The remaining material was used in subsequent step without further purification. LC-MS retention time 2.227 min; m/z 598.46 (MH−) LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a PHENOMENEX® Luna 10u C18 3.0×50 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 4 mL/min, a gradient of 100% Solvent A/0% Solvent B to 0% Solvent A/100% Solvent B, a gradient time of 2 min, a hold time of 1 min, and an analysis time of 3 min where Solvent A was 10% MeOH/90% H2O/10 mM ammonium acetate and Solvent B was 10% H2O/90% MeOH/10 mM ammonium acetate. MS data was determined using a MICROMASS® Platform for LC in electrospray mode. 1H NMR (500 MHz, MeOD, TFA salt, partial NMR) δ ppm 3.71 (br s, 2H), 3.55 (br s, 2H), 2.45 (br s, 1H), 2.07-2.17 (m, 2H), 1.97-2.06 (m, 1H), 1.50 (s, 3H), 1.43 (m, 6H), 1.31 (br s, 6H).

Aufarbeitung

  1. additionwas added under a stream of nitrogen
  2. customthe reactor was sealed
  3. waitthe heating was pursued overnight
  4. customThe DME was removed in vacuo
  5. customthe crude material was partitioned between EtOAc/H2O
  6. customThe layers were separated
  7. extractionthe aqueous layer was extracted several times with EtOAc
  8. dry with materialThe combined organic extracts were dried over Na2SO4
  9. customevaporated in vacuo
  10. customThe residue was purified by flash column chromatography (BIOTAGE®)
  11. washeluting with a gradient of 0 to 100% EtOAc/hexanes

Quellen und Nachweise

ORD-Eintrag
ord-ba06ec6d0e204f4a98885dffebce5778
Quelldatensatz
uspto-grants-2016_04
Patentnummer
US09303007B2

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