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 1503953Notes

Reaction equation

HRID 1503953 reaction equation
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

Participants

5

Reactant 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

Product 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]propanenitrileYield 86%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
80 °C

Procedure

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]+.

Workup

  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)

Sources & evidence

ORD record
ord-3d323c40a8884305bce01434c31d6cdd
Source dataset
uspto-grants-2015_12
Patent number
US09212190B2

Reaction notes

Loading…