Dimethyl Sulfoxide → (7aR)-2-Chloro-3-methyl-4-(7a-methyl-3,7-dioxotetrahydropyrrolo[1,2-c]imidazol-2-yl)benzonitrile

HRID 501610Notes

Reaction equation

HRID 501610 reaction equation
C(Cl)(=O)C(Cl)=O.CS(C)=O.[Cl:11][C:12]1[C:19]([CH3:20])=[C:18]([N:21]2[CH2:25][C@:24]3([CH3:30])[C@H:26]([OH:29])[CH2:27][CH2:28][N:23]3[C:22]2=[O:31])[CH:17]=[CH:16][C:13]=1[C:14]#[N:15].C(N(CC)CC)C>C(Cl)Cl>[Cl:11][C:12]1[C:19]([CH3:20])=[C:18]([N:21]2[CH2:25][C@:24]3([CH3:30])[C:26](=[O:29])[CH2:27][CH2:28][N:23]3[C:22]2=[O:31])[CH:17]=[CH:16][C:13]=1[C:14]#[N:15]

Participants

6

Reactant 4

HCID 679Dimethyl SulfoxideHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 59754258(7R,7aR)-2-chloro-4-(7-hydroxy-7a-methyl-3-oxotetrahydropyrrolo[1,2-c]imidazol-2-yl)-3-methylbenzonitrile

Product 1

HCID 59754291(7aR)-2-Chloro-3-methyl-4-(7a-methyl-3,7-dioxotetrahydropyrrolo[1,2-c]imidazol-2-yl)benzonitrileYield 34.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

To a 2 M CH2Cl2 solution of oxalyl chloride (68 □L, 0.13 mmol) in CH2Cl2 (2 mL) at −78° C. was added DMSO (17 □L, 0.25 mmol). After 20 min, a solution of (7R,7aR)-2-chloro-4-(7-hydroxy-7a-methyl-3-oxotetrahydropyrrolo[1,2-c]imidazol-2-yl)-3-methylbenzonitrile (58F) (17 mg, 0.06 mmol) in CH2Cl2 (1 mL) was added. After an additional 20 min at −78° C., triethylamine (62 □L, 0.47 mmol) was added, the cold bath was removed, and the reaction mixture was stirred for 20 min. Water was added and the layers were separated. The organic layer was washed with brine then dried (MgSO4), filtered and concentrated. The resulting residue was purified via preparative HPLC (YMC ODS C-18, 100×20 mm, eluting with 30-80% solvent B (A=90% H2O-10% CH3CN-0.1% TFA and B=10% H2O-90% CH3CN-0.1% TFA) over 15 min; Flow rate at 20 mL/min; UV detection at 220 nm) to provide the title compound (6.3 mg) as a white solid. LC/MS m/z 629 [2M+23]+.

Workup

  1. waitAfter an additional 20 min at −78° C.
  2. customthe cold bath was removed
  3. additionWater was added
  4. customthe layers were separated
  5. washThe organic layer was washed with brine
  6. dry with materialthen dried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe resulting residue was purified via preparative HPLC (YMC ODS C-18, 100×20 mm
  10. washeluting with 30-80% solvent B (A=90% H2O-10% CH3CN-0.1% TFA and B=10% H2O-90% CH3CN-0.1% TFA) over 15 min

Sources & evidence

ORD record
ord-43e02fa1b1a24a41916a4657c49148ff
Source dataset
uspto-grants-2010_08
Patent number
US07772267B2

Reaction notes

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