Dimethylformamide → N-Trityl Losartan Carboxaldehyde

HRID 907213Notes

Reaction equation

HRID 907213 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′-bromomethyl-biphenyl-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 (1a) 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-678b3c58d1f143f6ab4adcf88f608f85
Source dataset
uspto-grants-2011_09
Patent number
US08013005B2

Reaction notes

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