Thiazole → 1-(2-Fluorobenzyl)-4-(2-thiazolyl)-1H-pyrazolo[3,4-d]pyrimidine-6-amine

HRID 1865907

Reaktionsgleichung

Reaktionsgleichung von HRID 1865907
[S:1]1[CH:5]=[CH:4][N:3]=[CH:2]1.[Li]CCCC.Cl[C:12]1[N:17]=[C:16]([NH2:18])[N:15]=[C:14]2[N:19]([CH2:22][C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=3[F:29])[N:20]=[CH:21][C:13]=12>C1COCC1.[NH4+].[Cl-].[Cl-].[Cl-].[Zn+2].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>[F:29][C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][C:23]=1[CH2:22][N:19]1[C:14]2=[N:15][C:16]([NH2:18])=[N:17][C:12]([C:2]3[S:1][CH:5]=[CH:4][N:3]=3)=[C:13]2[CH:21]=[N:20]1

Komponenten

8

Edukt 3

HCID 9256ThiazoleHCID 220155054-chloro-1-(2-fluorobenzyl)-1H-pyrazolo[3,4-d]pyrimidine-6-amineHCID 178418339Butyllithium

Produkt 1

HCID 220155091-(2-Fluorobenzyl)-4-(2-thiazolyl)-1H-pyrazolo[3,4-d]pyrimidine-6-amineAusbeute 31 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 3007855ZincchlorideKatalysatorHCID 178418397HCID 178418397, VerbindungKatalysatorHCID 8028TetrahydrofuranLösungsmittelHCID 25517Ammonium ChlorideLösungsmittel

Versuchsvorschrift

A stirred solution of thiazole (0.14 mL, 2 mmol) in dry THF (10 mL) at −78° C., under argon was treated n-BuLi (1.6-M in hexanes, 1.25 mL, 2 mmol), stirred for 15 min, treated with ZnCl2 solution (1-M in Et2O, 2 mL, 2 mmol) then allowed to warm gradually to room temperature. The mixture was treated with 4-chloro-1-(2-fluorobenzyl)-1H-pyrazolo[3,4-d]pyrimidine-6-amine (278 mg, 1 mmol) and Pd(PPh3)4 (100 mg, 10 mol %) refluxed for 2 h, diluted with saturated NH4Cl solution, extracted with EtOAc, dried (MgSO4) and concentrated in vacuo. The resulting brown oil was purified by chromatography [SiO2; heptane:EtOAc (4:1) then (3:1)] to give the title compound (101 mg, 31%) as a cream solid.

Aufarbeitung

  1. temperaturerefluxed for 2 h
  2. extractionextracted with EtOAc
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated in vacuo
  5. customThe resulting brown oil was purified by chromatography [SiO2

Quellen und Nachweise

ORD-Eintrag
ord-5f2deb09fc504b55a16b839a6a780746
Quelldatensatz
uspto-grants-2009_12
Patentnummer
US07629349B2

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