Methyl iodide → tert-butyl 5-{[2-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl]carbonyl}hexahydropyrrolo[3,4-c]pyrrole-2(1H)-carboxylate

HRID 1524915Notes

Reaction equation

HRID 1524915 reaction equation
[H-].[Na+].[N:3]1[N:4]=[C:5]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=2[C:14]([N:16]2[CH2:20][CH:19]3[CH2:21][N:22]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:23][CH:18]3[CH2:17]2)=[O:15])[NH:6][CH:7]=1.[CH3:31]I>CN(C=O)C.O>[NH3:3].[CH3:31][N:4]1[C:5]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=2[C:14]([N:16]2[CH2:17][CH:18]3[CH2:23][N:22]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:21][CH:19]3[CH2:20]2)=[O:15])=[N:6][CH:7]=[N:3]1.[CH3:31][N:3]1[CH:7]=[N:6][C:5]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=2[C:14]([N:16]2[CH2:17][CH:18]3[CH2:23][N:22]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:21][CH:19]3[CH2:20]2)=[O:15])=[N:4]1

Participants

8

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 178451519HCID 178451519, compound

Product 3

HCID 222AmmoniaYield 8%HCID 68161719tert-butyl 5-{[2-(1-methyl-1H-1,2,4-triazol-5-yl)phenyl]carbonyl}hexahydropyrrolo[3,4-c]pyrrole-2(1H)-carboxylateYield 18%HCID 69938919tert-butyl 5-{[2-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl]carbonyl}hexahydropyrrolo[3,4-c]pyrrole-2(1H)-carboxylateYield 68%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Procedure

To a heterogeneous mixture of NaH (60% dispersion in mineral oil, 80 mg, 2 mmol) in DMF (4 mL) was added Intermediate 59 (641 mg, 1.67 mmol) in DMF (4 mL). 30 min after gas evolution had ceased methyliodide (0.115 mL, 1.84 mmol) was added dropwise. The mixture was diluted with H2O and extracted with EtOAc. The combined organic extracts were dried over Na2SO4, filtered and concentrated in vacuo. Chromatography (DCM to 8% 2 M NH3 in MeOH/DCM) afforded two products, tert-butyl 5-{[2-(1-methyl-1H-1,2,4-triazol-5-yl)phenyl]carbonyl}hexahydropyrrolo[3,4-c]pyrrole-2(1H)-carboxylate (120 mg, 18%) and tert-butyl 5-{[2-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl]carbonyl}hexahydropyrrolo[3,4-c]pyrrole-2(1H)-carboxylate (454 mg, 68%) due to the tautomeric nature of the 1,2,4-triazole moiety. MS (ESI): mass calculated for C21H27N5O3, 397.21, m/z found 398.2 [M+1]+. 1H NMR (500 MHz, CDCl3): 7.90 (s, 1H), 7.61-7.41 (m, 4H), 3.83 (s, 3H), 3.74-3.36 (m, 5H), 3.29-3.12 (m, 3H), 2.88-2.75 (m, 2H), 1.47 (s, 9H).

Workup

  1. custom30 min
  2. additionwas added dropwise
  3. extractionextracted with EtOAc
  4. dry with materialThe combined organic extracts were dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-e28c6c1ac3864ed49dddc0778ee5275a
Source dataset
uspto-grants-2015_07
Patent number
US09079911B2

Reaction notes

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