1,1'-Carbonyldiimidazole → (S)-N-(5-((R)-2-(3-chloro-5-fluorophenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidin-3-yl)-3-hydroxypyrrolidine-1-carboxamide

HRID 537787

Reaktionsgleichung

Reaktionsgleichung von HRID 537787
[Cl:1][C:2]1[CH:3]=[C:4]([C@H:9]2[CH2:13][CH2:12][CH2:11][N:10]2[C:14]2[CH:19]=[CH:18][N:17]3[N:20]=[CH:21][C:22]([NH2:23])=[C:16]3[N:15]=2)[CH:5]=[C:6]([F:8])[CH:7]=1.C1N=CN([C:29]([N:31]2[CH:35]=N[CH:33]=[CH:32]2)=[O:30])C=1.N1CC[C@H:38]([OH:41])C1>C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[C:4]([C@H:9]2[CH2:13][CH2:12][CH2:11][N:10]2[C:14]2[CH:19]=[CH:18][N:17]3[N:20]=[CH:21][C:22]([NH:23][C:29]([N:31]4[CH2:32][CH2:33][C@H:38]([OH:41])[CH2:35]4)=[O:30])=[C:16]3[N:15]=2)[CH:5]=[C:6]([F:8])[CH:7]=1

Komponenten

5

Edukt 3

HCID 682631,1'-CarbonyldiimidazoleHCID 2733874(3S)-pyrrolidin-3-olHCID 67330213(R)-5-(2-(3-chloro-5-fluorophenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidin-3-amine

Produkt 1

HCID 58386251(S)-N-(5-((R)-2-(3-chloro-5-fluorophenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidin-3-yl)-3-hydroxypyrrolidine-1-carboxamideAusbeute 187,3 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

To a DCM (0.6 mL) solution of (R)-5-(2-(3-chloro-5-fluorophenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidin-3-amine (Example 11, Step A; 20 mg, 0.06 mmol), was added CDI (20 mg, 0.12 mmol) at ambient temperature in one portion. After stirring two hours, (S)-pyrrolidin-3-ol (16 mg, 0.18 mmol) was added in one portion. The reaction was stirred overnight before it was concentrated and directly purified by reverse-phase column chromatography, eluting with 0 to 60% acetonitrile/water to yield the final product as a solid (50 mg, 83% yield). MS (apci) m/z=445.2 (M+H).

Aufarbeitung

  1. stirringThe reaction was stirred overnight before it
  2. concentrationwas concentrated
  3. customdirectly purified by reverse-phase column chromatography
  4. washeluting with 0 to 60% acetonitrile/water

Quellen und Nachweise

ORD-Eintrag
ord-3cf0a8e1e9a04fabbab7d9e8446470b0
Quelldatensatz
uspto-grants-2014_10
Patentnummer
US08865698B2

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