StartseiteMCPWorkbenchSkills
StartseiteWorkbenchBenachrichtigungenMein Bereich
llms.txt · MCP-AnleitungDatenschutz · Nutzungsbedingungen · Supportv1.8.0
  1. Startseite
  2. /Reaktion

Dichloromethane → 8-fluoro-9-(3-hydroxy-3-methylbut-1-yn-1-yl)-3-((1-methyl-1H-pyrazol-5-yl)methyl)-3,4,5,6-tetrahydro-4,6-methanobenzo[3,4]cyclohepta[1,2-d]imidazole-2-carboxamide

HRID 575440
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 575440
[F:1][C:2]1[C:26](I)=[CH:25][C:5]2[C:6]3[N:10]=[C:9]([C:11]([NH2:13])=[O:12])[N:8]([CH2:14][C:15]4[N:19]([CH3:20])[N:18]=[CH:17][CH:16]=4)[C:7]=3[CH:21]3[CH2:24][CH:23]([C:4]=2[CH:3]=1)[CH2:22]3.[CH3:28][C:29]([OH:33])([C:31]#[CH:32])[CH3:30].ClCCl>N1CCCCC1.CO.[Cu]I.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>[NH3:8].[F:1][C:2]1[C:26]([C:32]#[C:31][C:29]([OH:33])([CH3:30])[CH3:28])=[CH:25][C:5]2[C:6]3[N:10]=[C:9]([C:11]([NH2:13])=[O:12])[N:8]([CH2:14][C:15]4[N:19]([CH3:20])[N:18]=[CH:17][CH:16]=4)[C:7]=3[CH:21]3[CH2:24][CH:23]([C:4]=2[CH:3]=1)[CH2:22]3
KomponentenReaktionsbedingungenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion

Komponenten

9

Edukt 3

HCID 6344DichloromethaneHCID 82582-Methyl-3-butyn-2-olHCID 866934978-fluoro-9-iodo-3((1-methyl-1H-pyrazol-5-yl)methyl)-3,4,5,6-tetrahydro-4,6-methanobenzo[3,4]cyclohepta[1,2-d]imidazole-2-carboxamide

Produkt 2

HCID 222AmmoniaHCID 866934988-fluoro-9-(3-hydroxy-3-methylbut-1-yn-1-yl)-3-((1-methyl-1H-pyrazol-5-yl)methyl)-3,4,5,6-tetrahydro-4,6-methanobenzo[3,4]cyclohepta[1,2-d]imidazole-2-carboxamide
Ausbeute 157,1 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)KatalysatorHCID 178418397HCID 178418397, VerbindungKatalysatorHCID 887MethanolLösungsmittelHCID 8082PiperidineLösungsmittel

Reaktionsbedingungen

Temperatur
50 °C

Versuchsvorschrift

To a solution of 8-fluoro-9-iodo-3-((1-methyl-1H-pyrazol-5-yl)methyl)-3,4,5,6-tetrahydro-4,6-methanobenzo[3,4]cyclohepta[1,2-d]imidazole-2-carboxamide (67 mg, 0.14 mmol) in piperidine (2 mL) was introduced 2-methyl-3-butyn-2-ol (68 mg, 0.81 mmol) and copper(I) iodide (2 mg, 0.01 mmol). The solution was de-oxygenated by nitrogen bubbling for five minutes, then tetrakis(triphenylphosphine)palladium(0) (9 mg, 0.01 mmol) added and bubbling continued for a further two minutes. The pressure tube was closed under an atmosphere of nitrogen and the reaction mixture warmed to 50° C. for 4 hr. After evaporation of the reaction mixture in vacuo, the residue was suspended in ethyl acetate (30 mL) and washed with saturated aqueous sodium bicarbonate (2×10 mL), water (2×10 mL) and brine (10 mL). The organic extract was dried over sodium sulfate, filtered and the filtrate adsorbed onto silica gel in vacuo. Purification of the dry-loaded material by silica gel flash column chromatography (eluent: dichloromethane containing a 0-4% gradient of 7M ammonia in methanol) furnished the title compound (47 mg, 0.11 mmol, 78%) as off-white fine crystals: 1H NMR (500 MHz, CDCl3) δ 1.64-1.72 (m, 8H), 2.43 (br. s., 1H), 2.90 (qd, J=7.93, 3.00 Hz, 2H), 3.31-3.40 (m, 1H), 3.54-3.61 (m, 1H), 3.92 (br. s., 3H), 5.49 (br. s., 1H), 5.87 (s, 2H), 6.83 (d, J=10.09 Hz, 1H), 7.42 (br. s., 1H), 8.42 (d, J=7.57 Hz, 1H); M+1=434.

Aufarbeitung

  1. custombubbling
  2. waitcontinued for a further two minutes
  3. customThe pressure tube was closed under an atmosphere of nitrogen
  4. customAfter evaporation of the reaction mixture in vacuo
  5. washwashed with saturated aqueous sodium bicarbonate (2×10 mL), water (2×10 mL) and brine (10 mL)
  6. extractionThe organic extract
  7. dry with materialwas dried over sodium sulfate
  8. filtrationfiltered
  9. customPurification of the dry-loaded material by silica gel flash column chromatography (eluent

Quellen und Nachweise

ORD-Eintrag
ord-eb6943eac78f40e5a0e57a5a74f265dd
Quelldatensatz
uspto-grants-2015_05
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US09034866B2

Notizen zur Reaktion

Wird geladen…

Auf dieser SeiteKomponentenReaktionsbedingungenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion