Methanesulfonyl chloride → 4-(6-Azidomethyl-4-methyl-2-propylbenzoimidazol-1-ylmethyl)-2-fluorobenzoic acid methyl ester

HRID 476299Notes

Reaction equation

HRID 476299 reaction equation
[CH3:1][O:2][C:3](=[O:27])[C:4]1[CH:9]=[CH:8][C:7]([CH2:10][N:11]2[C:15]3[CH:16]=[C:17]([CH2:21]O)[CH:18]=[C:19]([CH3:20])[C:14]=3[N:13]=[C:12]2[CH2:23][CH2:24][CH3:25])=[CH:6][C:5]=1[F:26].CCN(C(C)C)C(C)C.CS(Cl)(=O)=O.[N-:42]=[N+:43]=[N-:44].[Na+]>CN(C)C1C=CN=CC=1.C(Cl)Cl>[CH3:1][O:2][C:3](=[O:27])[C:4]1[CH:9]=[CH:8][C:7]([CH2:10][N:11]2[C:15]3[CH:16]=[C:17]([CH2:21][N:42]=[N+:43]=[N-:44])[CH:18]=[C:19]([CH3:20])[C:14]=3[N:13]=[C:12]2[CH2:23][CH2:24][CH3:25])=[CH:6][C:5]=1[F:26]

Participants

7

Reactant 4

HCID 31297Methanesulfonyl chlorideHCID 33557Sodium AzideHCID 81531DiisopropylethylamineHCID 687231872-Fluoro-4-(6-hydroxymethyl-4-methyl-2-propyl-benzoimidazol-1-ylmethyl)-benzoic acid methyl ester

Product 1

HCID 866257634-(6-Azidomethyl-4-methyl-2-propylbenzoimidazol-1-ylmethyl)-2-fluorobenzoic acid methyl esterYield 81.7%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

Intermediate (8a) (2.4 g, 6.5 mmol) was added to 125 mL of DCM followed by DIPEA (4.6 mL, 26.1 mmol) and 4-dimethylaminopyridine (80 mg, 653 μmol). Methanesulfonyl chloride (1.0 mL, 13.1 mmol) was then added at 0° C. and the mixture was warmed to room temperature. After 3 hours, the mixture was concentrated and the material redissolved in 40 mL DMF. Sodium azide (467 mg, 7.2 mmol) was added and the mixture was heated at 80° C. for 1 hour. The mixture was then cooled to room temperature. The solution was partitioned between EtOAc (100 mL) and 50 mL 10% LiCl (aqueous). The organic layer was concentrated and flash chromatographed 20-70% EtOAc:hexanes to yield Intermediate (8b) as a yellow oil (2.1 g). MS m/z: [M+H+] calcd for C21H22FN5O2, 396.2. found 396.0.

Workup

  1. concentrationthe mixture was concentrated
  2. dissolutionthe material redissolved in 40 mL DMF
  3. temperaturethe mixture was heated at 80° C. for 1 hour
  4. temperatureThe mixture was then cooled to room temperature
  5. customThe solution was partitioned between EtOAc (100 mL) and 50 mL 10% LiCl (aqueous)
  6. concentrationThe organic layer was concentrated
  7. customflash chromatographed 20-70% EtOAc

Sources & evidence

ORD record
ord-46825a98e2e44690be27eeec19120f3c
Source dataset
uspto-grants-2014_01
Patent number
US08637676B2

Reaction notes

Loading…