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 1503953ノート

反応式

HRID 1503953 の反応式
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

参加物

5

反応物 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

生成物 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]propanenitrile収率 86%

試薬・触媒・溶媒 2

HCID 142844-(Dimethylamino)pyridine触媒HCID 679Dimethyl Sulfoxide溶媒

反応条件

温度
80 °C

実験手順

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]+.

後処理

  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)

出典と根拠

ORDレコード
ord-3d323c40a8884305bce01434c31d6cdd
出典データセット
uspto-grants-2015_12
特許番号
US09212190B2

反応ノート

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