Nitrogen → Isopropyl 4-(3-bromopyrazolo[1,5-a]pyrimidin-5-yl)piperazine-1-carboxylate

HRID 1478265Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1478265
N#N.[Br:3][C:4]1[CH:5]=[N:6][N:7]2[CH:12]=[CH:11][C:10]([N:13]3[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]3)=[N:9][C:8]=12.CCN(C(C)C)C(C)C.Cl[C:29]([O:31][CH:32]([CH3:34])[CH3:33])=[O:30]>C(OCC)(=O)C.C1(C)C=CC=CC=1>[CH:32]([O:31][C:29]([N:16]1[CH2:17][CH2:18][N:13]([C:10]2[CH:11]=[CH:12][N:7]3[N:6]=[CH:5][C:4]([Br:3])=[C:8]3[N:9]=2)[CH2:14][CH2:15]1)=[O:30])([CH3:34])[CH3:33]

Komponenten

7

Edukt 4

HCID 947NitrogenHCID 7917Isopropyl chloroformateHCID 81531DiisopropylethylamineHCID 866974343-Bromo-5-(piperazin-1-yl)pyrazolo[1,5-a]pyrimidine

Produkt 1

HCID 86697433Isopropyl 4-(3-bromopyrazolo[1,5-a]pyrimidin-5-yl)piperazine-1-carboxylate

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 1140TolueneLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

To a rapidly stirred, 0° C., N2 blanketed, solution of 3-bromo-5-piperazin-1-yl-pyrazolo[1,5-a]pyrimidine (15.8 g, 56.0 mmol) and Hunig's base [7087-68-5] (20.0 mL, 114.8 mmol) in ethyl acetate (280 mL) was steadily added a 1.0M solution of isopropyl chloroformate in toluene (67.0 mL) over the course of 10 minutes. The reaction was allowed to stir and warm to ambient temperature over night at which time it was washed with brine, dried (MgSO4), preloaded onto silica gel, chromatographed (Silica gel, eluted with 100% ethyl acetate) and crystallized from ethyl acetate/heptane to afford 13.2 g of white powder, mp. 78-79° C. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.22 (d, J=6.32 Hz, 6 H) 3.44-3.54 (m, 4 H) 3.67-3.79 (m, 4 H) 4.82 (spt, J=6.23 Hz, 1 H) 6.77 (d, J=7.83 Hz, 1 H) 7.97 (s, 1 H) 8.69 (d, J=7.83 Hz, 1 H). 13C NMR (100 MHz, DMSO-d6) δ ppm 21.94, 42.80, 43.87, 68.17, 77.32, 97.66, 136.47, 143.87, 144.40, 154.29, 155.64. LRMS (ESI) m/z 368.0/370.0 [(M+H)]+, calc'd for C14H18BrN5O2: 368.24.

Aufarbeitung

  1. stirringto stir
  2. temperaturewarm to ambient temperature over night at which time it
  3. washwas washed with brine
  4. dry with materialdried (MgSO4)
  5. customchromatographed
  6. wash(Silica gel, eluted with 100% ethyl acetate)
  7. customcrystallized from ethyl acetate/heptane

Quellen und Nachweise

ORD-Eintrag
ord-ba3012f927ce44469c851b2c43f0dbdf
Quelldatensatz
uspto-grants-2016_08
Patentnummer
US09403832B2

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