Sodium Cyanide → 3-[(3S)-12-[[4-(morpholin-4-yl)cyclohexyl]oxy]-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraen-3-yl]propanenitrile

HRID 1503953노트

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HRID 1503953 반응식
CS(O[CH2:6][CH2:7][C@H:8]1[CH2:19][CH2:18][C:17]2[S:16][C:15]3[N:14]=[CH:13][N:12]=[C:11]([O:20][CH:21]4[CH2:26][CH2:25][CH:24]([N:27]5[CH2:32][CH2:31][O:30][CH2:29][CH2:28]5)[CH2:23][CH2:22]4)[C:10]=3[C:9]1=2)(=O)=O.[C-:33]#[N:34].[Na+]>CS(C)=O.CN(C)C1C=CN=CC=1>[N:27]1([CH:24]2[CH2:23][CH2:22][CH:21]([O:20][C:11]3[C:10]4[C:9]5[C@@H:8]([CH2:7][CH2:6][C:33]#[N:34])[CH2:19][CH2:18][C:17]=5[S:16][C:15]=4[N:14]=[CH:13][N:12]=3)[CH2:26][CH2:25]2)[CH2:28][CH2:29][O:30][CH2:31][CH2:32]1

참가 물질

5

반응물 2

HCID 8929Sodium CyanideHCID 866951242-[(3R)-12-[[4-(morpholin-4-yl)cyclohexyl]oxy]-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraen-3-yl]ethyl methanesulfonate

생성물 1

HCID 866951253-[(3S)-12-[[4-(morpholin-4-yl)cyclohexyl]oxy]-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraen-3-yl]propanenitrile수율 86%

시약·촉매·용매 2

HCID 142844-(Dimethylamino)pyridine촉매HCID 679Dimethyl Sulfoxide용매

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온도
80 °C

실험 절차

Into a 50-mL round-bottom flask, purged and maintained with an inert atmosphere of nitrogen, was placed a solution of 2-[(3R)-12-[[4-(morpholin-4-yl)cyclohexyl]oxy]-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraen-3-yl]ethyl methanesulfonate (230 mg, 0.48 mmol, 1.00 equiv) in DMSO (5 mL) at room temperature. Then NaCN (141 mg, 2.88 mmol, 6.00 equiv) and 4-dimethylaminopyridine (5.86 mg, 0.05 mmol, 0.10 equiv) were added and the resulting solution was stirred for 2 h at 80° C. After cooling down to room temperature, the reaction was quenched with brine, extracted with DCM. The organic phase was dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was purified by column chromatography on silica gel with EtOAc/petroleum ether (1:10 to 1:2) to afford the desired 3-[(3S)-12-[[4-(morpholin-4-yl)cyclohexyl]oxy]-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraen-3-yl]propanenitrile (170 mg, 86%) as a white solid. LCMS (ES): m/z 413 [M+H]+.

후처리

  1. customInto a 50-mL round-bottom flask, purged
  2. temperaturemaintained with an inert atmosphere of nitrogen
  3. customat room temperature
  4. temperatureAfter cooling down to room temperature
  5. customthe reaction was quenched with brine
  6. extractionextracted with DCM
  7. dry with materialThe organic phase was dried over anhydrous sodium sulfate
  8. concentrationconcentrated under vacuum
  9. customThe residue was purified by column chromatography on silica gel with EtOAc/petroleum ether (1:10 to 1:2)

출처 및 근거

ORD 기록
ord-3d323c40a8884305bce01434c31d6cdd
출처 데이터셋
uspto-grants-2015_12
특허 번호
US09212190B2

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