Cyclohexylamine → Reversine

HRID 1875464

반응식

HRID 1875464 반응식
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

참가 물질

8

반응물 5

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

생성물 1

HCID 210332Reversine

시약·촉매·용매 2

HCID 2631-Butanol용매HCID 702Ethanol용매

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온도
80 °C

실험 절차

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, 153.31; MALDI-FTMS for C21H28N7O (MH+): calcd 394.2350; found 394.2341.

후처리

  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

출처 및 근거

ORD 기록
ord-df7bdb7cfe35463fa056343aed27e59e
출처 데이터셋
uspto-grants-2012_11
특허 번호
US08309555B2

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