Dimethylformamide → N-Trityl Losartan Carboxaldehyde

HRID 919327Notes

Reaction equation

HRID 919327 reaction equation
CN(C=O)C.Br[CH2:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[C:20]2[N:24]([C:25]([C:38]3[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=3)([C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)[C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[N:23]=[N:22][N:21]=2)=[CH:10][CH:9]=1.[CH2:44]([C:48]1[NH:52][C:51]([CH:53]=[O:54])=[C:50]([Cl:55])[N:49]=1)[CH2:45][CH2:46][CH3:47].C([O-])([O-])=O.[K+].[K+]>CCOC(C)=O>[CH2:44]([C:48]1[N:52]([CH2:7][C:8]2[CH:13]=[CH:12][C:11]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=3[C:20]3[N:24]([C:25]([C:38]4[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=4)([C:32]4[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=4)[C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=4)[N:23]=[N:22][N:21]=3)=[CH:10][CH:9]=2)[C:51]([CH:53]=[O:54])=[C:50]([Cl:55])[N:49]=1)[CH2:45][CH2:46][CH3:47]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 100534615-(4'-(Bromomethyl)(1,1'-biphenyl)-2-yl)-1-trityl-1H-tetraazoleHCID 178418251HCID 178418251, compound

Product 1

HCID 11657587N-Trityl Losartan Carboxaldehyde

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a DMF (150 mL) solution of 5-(4′-bromomethylbiphenyl-2-yl)-1-trityl-1H-tetrazole (30 g, 53.8 mmol) was added 2-butyl-5-chloro-3H-imidazole-4-carbaldehyde (10 g, 53.8 mmol) and K2CO3 (7.4 g, 53.8 mmol). The mixture was stirred at room temperature overnight. EtOAc (500 mL) was added and the organic was washed three times with a NaHCO3 solution (200 mL) followed by saturated aqueous NaCl (200 mL). Solvent was removed and purification was achieved by silica gel chromatography (50:50 EtOAc:hexanes) using an isocratic gradient to provide intermediate (11a) a white solid (41 g). MS m/z: [M+H+] calcd for C41H35ClN6O, 663.26. found 663.4. 1H-NMR (d4-MeOH): 0.83 (m, 3H), 1.26 (m, 2H), 1.53 (m, 2H), 2.53 (m, 2H), 5.56 (s, 2H), 6.87-6.96 (m, 8H), 7.05 (m, 2H), 7.25-7.43 (m, 10H), 7.53-7.58 (m, 2H), 7.84 (d, 1H), 9.73 (s, 1H).

Workup

  1. washthe organic was washed three times with a NaHCO3 solution (200 mL)
  2. customSolvent was removed
  3. custompurification

Sources & evidence

ORD record
ord-cf2aedc765854461a9c86855ac03f442
Source dataset
uspto-grants-2016_03
Patent number
US09273008B2

Reaction notes

Loading…