1-(Chloroacetyl)pyrrolidine → HCID 178521327, Verbindung

HRID 2369431Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2369431
[C:1]12[C:12]([NH:13][CH:14]3[CH2:19][CH2:18][CH:17]([NH2:20])[CH2:16][CH2:15]3)=[N:11][CH:10]=[N:9][C:8]=1[S:7][C:6]1[CH2:5][CH2:4][CH2:3][C:2]2=1.Cl[CH2:22][C:23]([N:25]1[CH2:29][CH2:28][CH2:27][CH2:26]1)=[O:24]>C(O)C>[N:25]1([C:23](=[O:24])[CH2:22][NH:20][C@H:17]2[CH2:18][CH2:19][C@H:14]([NH:13][C:12]3[C:1]4[C:2]5[CH2:3][CH2:4][CH2:5][C:6]=5[S:7][C:8]=4[N:9]=[CH:10][N:11]=3)[CH2:15][CH2:16]2)[CH2:29][CH2:28][CH2:27][CH2:26]1.[O:24]=[C:23]([N:25]1[CH2:29][CH2:28][CH2:27][CH2:26]1)[CH2:22][N:20]([C@H:17]1[CH2:18][CH2:19][C@H:14]([NH:13][C:12]2[C:1]3[C:2]4[CH2:3][CH2:4][CH2:5][C:6]=4[S:7][C:8]=3[N:9]=[CH:10][N:11]=2)[CH2:15][CH2:16]1)[CH2:22][C:23]([N:25]1[CH2:29][CH2:28][CH2:27][CH2:26]1)=[O:24]

Komponenten

5

Edukt 2

HCID 884401-(Chloroacetyl)pyrrolidineHCID 575201561-N-[7-thia-9,11-diazatricyclo[6.4.0.0^[2,6]]dodeca-1(8),2(6),9,11-tetraen-12-yl]cyclohexane-1,4-diamine

Produkt 2

HCID 178521327HCID 178521327, VerbindungHCID 178521332HCID 178521332, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 702EthanolLösungsmittel

Reaktionsbedingungen

Temperatur
90 °C

Versuchsvorschrift

Note: For the preparation of the starting material compound 1, see Example 147. Into a 50-mL round-bottom flask, was placed 1-N-[7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraen-12-yl]cyclohexane-1,4-diamine (170 mg, 0.59 mmol, 1.00 equiv), 2-chloro-1-(pyrrolidin-1-yl)ethan-1-one (89 mg, 0.60 mmol, 1.00 equiv), KI (10 mg, 1.00 equiv) and ethanol (20 mL) at room temperature under nitrogen. The resulting solution was stirred overnight at 90° C. in an oil bath. The solvent was removed under reduced pressure. The crude product (180 mg) was purified by Prep-HPLC with the following conditions (SHIMADZU): Column, SunFire Prep C18, 19*150 mm 5 um; mobile phase, water with 0.05% NH4HCO3 and CH3CN (6.0% CH3CN up to 50.0% in 21 min); Flow rate, 20 mL/min; UV detection at 254/220 nm. The product-containing fractions were collected and partially evaporated to remove water and CH3CN under reduced pressure. The residue was lyophilized overnight to give the desired trans-1-(pyrrolidin-1-yl)-2-[[4-([7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraen-12-yl]amino)cyclohexyl]amino]ethan-1-one (20.5 mg) as a white solid and trans-2-[[2-oxo-2-(pyrrolidin-1-yl)ethyl][4-([7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraen-12-yl]amino)cyclohexyl]amino]-1-(pyrrolidin-1-yl)ethan-1-one (26.7 mg) as a white solid, respectively.

Aufarbeitung

  1. customInto a 50-mL round-bottom flask, was placed
  2. customat room temperature
  3. customThe solvent was removed under reduced pressure
  4. customThe crude product (180 mg) was purified by Prep-HPLC with the following conditions (SHIMADZU)
  5. waitmobile phase, water with 0.05% NH4HCO3 and CH3CN (6.0% CH3CN up to 50.0% in 21 min)
  6. customThe product-containing fractions were collected
  7. custompartially evaporated
  8. customto remove water and CH3CN under reduced pressure
  9. waitThe residue was lyophilized overnight

Quellen und Nachweise

ORD-Eintrag
ord-8187a5a527de4fadafb159c50aa63a1f
Quelldatensatz
uspto-grants-2014_04
Patentnummer
US08703941B2

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