1,1'-Carbonyldiimidazole → (R)-N-(5-(4,4-difluoro-2-(3-fluorophenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidin-3-yl)-3-hydroxyazetidine-1-carboxamide

HRID 1893772

Reaktionsgleichung

Reaktionsgleichung von HRID 1893772
[F:1][C:2]1([F:24])[CH2:6][N:5]([C:7]2[CH:12]=[CH:11][N:10]3[N:13]=[CH:14][C:15]([NH2:16])=[C:9]3[N:8]=2)[C@@H:4]([C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([F:23])[CH:18]=2)[CH2:3]1.C1N=CN([C:30]([N:32]2[CH:36]=N[CH:34]=[CH:33]2)=[O:31])C=1.Cl.N1CC([OH:42])C1.CCN(C(C)C)C(C)C>C(Cl)Cl>[F:24][C:2]1([F:1])[CH2:6][N:5]([C:7]2[CH:12]=[CH:11][N:10]3[N:13]=[CH:14][C:15]([NH:16][C:30]([N:32]4[CH2:33][CH:34]([OH:42])[CH2:36]4)=[O:31])=[C:9]3[N:8]=2)[C@@H:4]([C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([F:23])[CH:18]=2)[CH2:3]1

Komponenten

6

Edukt 4

HCID 682631,1'-CarbonyldiimidazoleHCID 81531DiisopropylethylamineHCID 27592903-Hydroxyazetidine hydrochlorideHCID 67329839(R)-5-(4,4-difluoro-2-(3-fluorophenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidin-3-amine

Produkt 1

HCID 58386337(R)-N-(5-(4,4-difluoro-2-(3-fluorophenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidin-3-yl)-3-hydroxyazetidine-1-carboxamideAusbeute 48 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

To a DCM (0.7 mL) solution of (R)-5-(4,4-difluoro-2-(3-fluorophenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidin-3-amine (25 mg, 0.074 mmol), was added CDI (18 mg, 0.11 mmol) at ambient temperature in one portion. After stirring two hours, azetidin-3-ol hydrochloride (16 mg, 0.15 mmol) was added in one portion, followed by addition of DIEA (0.039 mL, 0.22 mmol). The reaction was stirred overnight, then concentrated, and the residue was directly purified by reverse-phase column chromatography, eluting with 0 to 45% acetonitrile/water to yield the final product as a yellowish oil (15 mg, 48% yield). MS (apci) m/z=433.1 (M+H).

Aufarbeitung

  1. stirringThe reaction was stirred overnight
  2. concentrationconcentrated
  3. customthe residue was directly purified by reverse-phase column chromatography
  4. washeluting with 0 to 45% acetonitrile/water

Quellen und Nachweise

ORD-Eintrag
ord-762b1ae7025c40e295157516426146a1
Quelldatensatz
uspto-grants-2013_08
Patentnummer
US08513263B2

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