Diisopropylethylamine → HCID 178486791, Verbindung

HRID 2064611Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2064611
N1C=CC=C(CNC(C2C=CC3NC(C4C(C(=O)NC(C)C)=CNN=4)=NC=3C=2)=O)C=1.[Cl:31][C:32]1[C:33]([O:47][CH3:48])=[CH:34][C:35]2[N:39]=[C:38]([C:40]3[C:44]([NH2:45])=[CH:43][NH:42][N:41]=3)[NH:37][C:36]=2[CH:46]=1.C(N(C(C)C)CC)(C)C.[N:58]1([C:64](Cl)=[O:65])[CH2:63][CH2:62][CH2:61][CH2:60][CH2:59]1>O1CCCC1>[Cl:31][C:32]1[C:33]([O:47][CH3:48])=[CH:34][C:35]2[N:39]=[C:38]([C:40]3[C:44]([NH:45][C:64]([N:58]4[CH2:63][CH2:62][CH2:61][CH2:60][CH2:59]4)=[O:65])=[CH:43][NH:42][N:41]=3)[NH:37][C:36]=2[CH:46]=1

Komponenten

6

Edukt 4

HCID 81531DiisopropylethylamineHCID 2420851-Piperidinecarbonyl chlorideHCID 178457736HCID 178457736, VerbindungHCID 178486793HCID 178486793, Verbindung

Produkt 1

HCID 178486791HCID 178486791, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

By proceeding in a manner similar to Example 248(a) above but (i) treating a solution of 3-(6-chloro-5-methoxy-1H-benzoimidazol-2-yl)-1H-pyrazol-4-ylamine [0.2 g, Example 233(e)] and diisopropylethylamine (392 mg, 4 eq) in tetrahydrofuran (25 mL) with piperidinecarbonyl chloride (450 mg, 4 eq), stirring overnight at ambient temperature, and evaporating the reaction mixture, (ii) triturating the reaction product with water (30 mL) and ethyl acetate (50 mL) and extracting with aqueous layer with ethyl acetate, (iii) combining the organic phases, drying over magnesium sulfate, then evaporating (iv) chromatographing the residue on silica gel (ethyl acetate), (v) triturating the partially purified material with ethyl acetate (15 mL) for 1.5 hours and filtering, and (vi) evaporating the filtrate and chromatographing the residue on silica gel (ethyl acetate/heptane gradient of 20-0%) there was prepared piperidine-1-carboxylic acid[3-(6-chloro-5-methoxy-1H-benzoimidazol-2-yl)-1H-pyrazol-4-yl]-amide (50 mg) as a yellow solid, mp>310° C. LC-MS (Method E) RT=3.25 minutes, 374 (M+H)+.

Aufarbeitung

  1. customevaporating the reaction mixture, (ii)
  2. customtriturating the reaction product with water (30 mL) and ethyl acetate (50 mL)
  3. extractionextracting with aqueous layer with ethyl acetate, (iii)
  4. dry with materialdrying over magnesium sulfate
  5. customevaporating (iv) chromatographing the residue on silica gel (ethyl acetate), (v)
  6. customtriturating the partially purified material with ethyl acetate (15 mL) for 1.5 hours
  7. filtrationfiltering
  8. custom(vi) evaporating the filtrate and chromatographing the residue on silica gel (ethyl acetate/heptane gradient of 20-0%) there
  9. customwas prepared piperidine-1-carboxylic acid[3-(6-chloro-5-methoxy-1H-benzoimidazol-2-yl)-1H-pyrazol-4-yl]-amide (50 mg) as a yellow solid, mp>310° C

Quellen und Nachweise

ORD-Eintrag
ord-f6b86ef24e9c48ab826992e5d1fbfc41
Quelldatensatz
uspto-grants-2012_10
Patentnummer
US08288425B2

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