Dimethyl Sulfoxide → 4-(5-(4-(3-Cyanopropyl)phenyl)-8-oxo-6-thioxo-5,7-diazaspiro[3,4]octan-7-yl)-2-(trifluoromethyl)benzonitrile

HRID 245039Notes

Reaction equation

HRID 245039 reaction equation
CS(C)=O.C(Cl)(=O)C(Cl)=O.[C:11]([C:13]1[CH:18]=[CH:17][C:16]([N:19]2[C:26](=[O:27])[C:22]3([CH2:25][CH2:24][CH2:23]3)[N:21]([C:28]3[CH:33]=[CH:32][C:31]([CH2:34][CH2:35][CH2:36][C:37]([NH2:39])=O)=[CH:30][CH:29]=3)[C:20]2=[S:40])=[CH:15][C:14]=1[C:41]([F:44])([F:43])[F:42])#[N:12]>ClCCl>[C:37]([CH2:36][CH2:35][CH2:34][C:31]1[CH:30]=[CH:29][C:28]([N:21]2[C:20](=[S:40])[N:19]([C:16]3[CH:17]=[CH:18][C:13]([C:11]#[N:12])=[C:14]([C:41]([F:44])([F:42])[F:43])[CH:15]=3)[C:26](=[O:27])[C:22]32[CH2:23][CH2:24][CH2:25]3)=[CH:33][CH:32]=1)#[N:39]

Participants

5

Reactant 3

HCID 679Dimethyl SulfoxideHCID 65578Oxalyl chlorideHCID 159515234-(4-(7-(4-Cyano-3-(trifluoromethyl)phenyl)-8-oxo-6-thioxo-5,7-diazaspiro[3,4]octan-5-yl)phenyl)butanamide

Product 1

HCID 159516274-(5-(4-(3-Cyanopropyl)phenyl)-8-oxo-6-thioxo-5,7-diazaspiro[3,4]octan-7-yl)-2-(trifluoromethyl)benzonitrile

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

A solution of DMSO (0.01 mL, 0.12 mmol) in dry dichloromethane (1 mL) was added to a stirred solution of oxalyl chloride (0.01 mL, 0.09 mmol) in dry dichloromethane (2 mL) at −78° C. After 15 min, a dichloromethane solution of 4-(4-(7-(4-Cyano-3-(trifluoromethyl)phenyl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-5-yl)phenyl)butanamide, RD130 (Formula 52) (35 mg, 0.07 mmol) was added to the reaction mixture. Stirring was continued for 20 min at −78° C., and then biethylamine (0.03 mL, 0.22 mmol) was added. After 30 min at −78° C., the reaction mixture was warmed to room temperature and then reaction was quenched with saturated aq. NH4Cl solution. The reaction mixture was diluted with dichloromethane, and extracted with dichloromethane. The organic layer was dried over MgSO4, concentrated and chromatographed (dichloromethane:acetone, 95:5) to yield 4-(5-(4-(3-Cyanopropyl)phenyl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-7-yl)-2-(trifluoromethyl)benzonitrile, RD170 (Formula 53) (29 mg, 87%) as a viscous oil. 1H NMR δ 7.98 (d, 1H, J=1.8 Hz), 7.98 (d, 1H, J=8.3 Hz), 7.86 (dd, 1H, J=8.3, 1.8 Hz), 7.43 (d, 2H, J=8.4 Hz), 7.27 (d, 2H, J=8.4 Hz), 2.90 (t, 2H, J=7.3 Hz), 2.63-2.73 (m, 2H), 2.52-2.62 (m, 2H), 2.42 (t, 2H, J=7.3 Hz), 2.18-2.30 (m, 1H), 2.07 (p, 2H, J=7.3 Hz), 1.63-1.73 (m, 1H).

Workup

  1. waitwas continued for 20 min at −78° C.
  2. additionwas added
  3. waitAfter 30 min at −78° C.
  4. customreaction
  5. customwas quenched with saturated aq. NH4Cl solution
  6. additionThe reaction mixture was diluted with dichloromethane
  7. extractionextracted with dichloromethane
  8. dry with materialThe organic layer was dried over MgSO4
  9. concentrationconcentrated
  10. customchromatographed (dichloromethane:acetone, 95:5)

Sources & evidence

ORD record
ord-4cc739d8855543b4824d94ed80a5144d
Source dataset
uspto-grants-2014_02
Patent number
US08658681B2

Reaction notes

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