Diisopropylethylamine → (S)-4-(5-chloro-1-methyl-1H-pyrazolo[4,3-d]pyrimidin-7-yl)-3-methylmorpholine

HRID 72181

Reaktionsgleichung

Reaktionsgleichung von HRID 72181
[Cl:1][C:2]1[N:3]=[C:4](Cl)[C:5]2[N:10]([CH3:11])[N:9]=[CH:8][C:6]=2[N:7]=1.C(N(CC)C(C)C)(C)C.[CH3:22][C@H:23]1[CH2:28][O:27][CH2:26][CH2:25][NH:24]1>CN(C=O)C.CCOCC>[Cl:1][C:2]1[N:3]=[C:4]([N:24]2[CH2:25][CH2:26][O:27][CH2:28][C@@H:23]2[CH3:22])[C:5]2[N:10]([CH3:11])[N:9]=[CH:8][C:6]=2[N:7]=1

Komponenten

6

Edukt 3

HCID 81531DiisopropylethylamineHCID 12012220(3S)-3-methylmorpholineHCID 574158625,7-dichloro-1-methyl-1H-pyrazolo[4,3-d]pyrimidine

Produkt 1

HCID 58222518(S)-4-(5-chloro-1-methyl-1H-pyrazolo[4,3-d]pyrimidin-7-yl)-3-methylmorpholineAusbeute 93,5 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 3283Diethyl EtherLösungsmittelHCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

To a stirred solution of 5,7-dichloro-1-methyl-1H-pyrazolo[4,3-d]pyrimidine (200.0 mg, 0.98 mmol) in anhydrous DMF (2 mL) was added N,N-diisopropylethylamine (0.21 mL, 1.18 mmol, 1.2 eq.) followed by (S)-3-methylmorpholine (199.3 mg, 1.9 mmol, 2.0 eq.). The reaction mixture was stirred at RT under N2 for 4 h and diluted with ether (50 mL). The organic layer was washed with saturated aqueous solution of sodium bicarbonate, water and brine, dried over Na2SO4, filtered, and concentrated in vacuo. The resultant residue was purified by column chromotagraphy (Si-PPC, gradient 0 to 100% ethyl acetate in heptane) to afford the desired product (k-1) as a foam (245.4 mg, 93.0%). 1H NMR (CDCl3, 500 MHz) δ ppm 8.03 (s, 1H), 4.21 (broad d, J=6.2 Hz, 1H), 4.15 (s, 3H), 3.97 (d, J=10.7 Hz, 1H), 3.90 (d, J=9.8 Hz, 1H), 3.81 to 3.65 (m, 3H), 3.56 (d, J=12.4 Hz, 1H), 1.38 (d, J=6.6 Hz, 3H); LC-MS m/z (method A)=268 [M+H]+, RT=1.71 min.

Aufarbeitung

  1. washThe organic layer was washed with saturated aqueous solution of sodium bicarbonate, water and brine
  2. dry with materialdried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe resultant residue was purified by column chromotagraphy (Si-PPC, gradient 0 to 100% ethyl acetate in heptane)

Quellen und Nachweise

ORD-Eintrag
ord-6509c6b03059425bb28feba1c042a567
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08828990B2

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