Dimethyl Sulfate → HCID 77263952, compound

HRID 1807171Notes

Reaction equation

HRID 1807171 reaction equation
[NH:1]1[C:5]([C:6]2[CH:11]=[CH:10][C:9]([NH:12][C:13]([CH:15]3[CH:19]([C:20]4[CH:25]=[CH:24][CH:23]=[C:22]([Cl:26])[C:21]=4[CH3:27])[C:18]([C:30]4[CH:35]=[CH:34][C:33]([Cl:36])=[CH:32][C:31]=4[F:37])([C:28]#[N:29])[CH:17]([CH2:38][C:39]([CH3:42])([CH3:41])[CH3:40])[NH:16]3)=[O:14])=[CH:8][CH:7]=2)=[N:4][N:3]=[N:2]1.[C:43](=O)(O)[O-].[Na+].S(OC)(OC)(=O)=O>CC(C)=O>[CH3:43][N:4]1[C:5]([C:6]2[CH:7]=[CH:8][C:9]([NH:12][C:13]([CH:15]3[CH:19]([C:20]4[CH:25]=[CH:24][CH:23]=[C:22]([Cl:26])[C:21]=4[CH3:27])[C:18]([C:30]4[CH:35]=[CH:34][C:33]([Cl:36])=[CH:32][C:31]=4[F:37])([C:28]#[N:29])[CH:17]([CH2:38][C:39]([CH3:42])([CH3:41])[CH3:40])[NH:16]3)=[O:14])=[CH:10][CH:11]=2)=[N:1][N:2]=[N:3]1

Participants

5

Reactant 3

HCID 6497Dimethyl SulfateHCID 516892Sodium BicarbonateHCID 178427901HCID 178427901, compound

Product 1

HCID 77263952HCID 77263952, compoundYield 9.2%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

To a stirred solution of rac (2R,3R,4R,5S)-4-(4-Chloro-2-fluoro-phenyl)-3-(3-chloro-2-methyl-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carboxylic acid [4-(1H-tetrazol-5-yl)-phenyl]-amide (32 mg, 0.0524 mmol) in acetone (5 mL), sodium bicarbonate (45 mg, 0.6 mmol) and dimethyl sulfate (0.11 mmol) was added and the mixture was stirred at rt for 5 hrs. The solvent was removed and the residue was suspended in 3 mL of methylene chloride. The mixture was filtered and the filtrate was loaded on a silica gel column. Eluting with 35-70% EtOAc/Hexanes on an ISCO machine gave the desired product (3 mg) and the other regioisomer (18 mg).

Workup

  1. customThe solvent was removed
  2. filtrationThe mixture was filtered
  3. washEluting with 35-70% EtOAc/Hexanes on an ISCO machine

Sources & evidence

ORD record
ord-e65a1036f2214320a4220f96164d41ae
Source dataset
uspto-grants-2013_01
Patent number
US08354444B2

Reaction notes

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