Cyclohexylamine → Reversine

HRID 523352

Reaktionsgleichung

Reaktionsgleichung von HRID 523352
FC1N=C2C(NC=N2)=C(Cl)N=1.C1(N)CCCCC1.C(N(C(C)C)CC)(C)C.F[C:29]1[N:37]=[C:36]2[C:32]([NH:33][CH:34]=[N:35]2)=[C:31]([NH:38][CH:39]2[CH2:44][CH2:43][CH2:42][CH2:41][CH2:40]2)[N:30]=1.[O:45]1[CH2:50][CH2:49][N:48]([C:51]2[CH:57]=[CH:56][C:54]([NH2:55])=[CH:53][CH:52]=2)[CH2:47][CH2:46]1>C(O)CCC.C(O)C>[O:45]1[CH2:46][CH2:47][N:48]([C:51]2[CH:57]=[CH:56][C:54]([NH:55][C:29]3[N:37]=[C:36]4[C:32]([NH:33][CH:34]=[N:35]4)=[C:31]([NH:38][CH:39]4[CH2:44][CH2:43][CH2:42][CH2:41][CH2:40]4)[N:30]=3)=[CH:53][CH:52]=2)[CH2:49][CH2:50]1

Komponenten

8

Edukt 5

HCID 7965CyclohexylamineHCID 75655Benzenamine, 4-(4-morpholinyl)-HCID 81531DiisopropylethylamineHCID 52879146-Chloro-2-fluoropurineHCID 236319592-Fluoro-6-cyclohexylaminopurine

Produkt 1

HCID 210332Reversine

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 2631-ButanolLösungsmittelHCID 702EthanolLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

2-(4-Morpholinoanilino)-6-cyclohexylamino-purine (i.e., reversine or Compound A) was synthesized using the methods similar to those previously described in Ding et al., J. Am. Chem. Soc. 124:1594 (2002). To a solution of 2-fluoro-6-chloropurine (87 mg, 0.5 mmol) in n-butanol (5 mL) was added cyclohexylamine (58 μL, 0.5 mmol) and diisopropylethylamine (100 μL, 0.6 mmol). The mixture was heated to 80° C. with vigorous stirring for 12 hours. The solvent was then removed under reduced pressure and the crude was used directly in the next step reaction without further purification. The crude 2-fluoro-6-cyclohexylamino-purine (0.5 mmol) was dissolved in ethanol (1 mL), followed by addition of 4-morpholinoaniline (178 mg, 1.0 mmol). The mixture was heated to 75° C. in a sealed tube with vigorous stirring for 24 hours. The solvent was then removed under reduced pressure and the crude material was directly purified by flash chromatography to afford 2-(4-morpholinoanilino)-6-cyclohexylamino-purine as a pale white solid (130 mg, overall 67% yield). 1H NMR (500 MHz, DMSO-d6) δ 1.14-1.24 (m, 1H), 1.26-1.39 (m, 4H), 1.59-1.67 (m, 1H), 1.73-1.81 (m, 2H), 1.94-1.99 (m, 2H), 3.07 (dd, J=4.8, 4.7 Hz, 4H), 3.74 (dd, J=4.8, 4.7 Hz, 4H), 3.90-4.06 (m, 2H), 6.93 (d, J=9.1 Hz, 2H), 7.51 (d, J=8.8 Hz, 2H), 8.31 (s, 1H), 8.38 (br. s, 1H), 9.68 (br. s, 1H); 13C NMR (125 MHz, CD3OD) δ 26.1, 26.5, 33.4, 40.4, 52.1, 67.4, 116.5, 118.6, 124.9, 133.2, 141.8, 147.9, 148.6, 152.9, 153.3; MALDI-FTMS for C21H28N7O (MH+): calcd 394.2350. found 394.2341.

Aufarbeitung

  1. custom2-(4-Morpholinoanilino)-6-cyclohexylamino-purine (i.e., reversine or Compound A) was synthesized
  2. customThe solvent was then removed under reduced pressure
  3. customthe crude was used directly in the next step reaction without further purification
  4. temperatureThe mixture was heated to 75° C. in a sealed tube
  5. stirringwith vigorous stirring for 24 hours
  6. customThe solvent was then removed under reduced pressure
  7. customthe crude material was directly purified by flash chromatography

Quellen und Nachweise

ORD-Eintrag
ord-cfaead1f7c0b45dc8eef7dc35b4f0b17
Quelldatensatz
uspto-grants-2016_05
Patentnummer
US09334481B2

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