Trifluoroacetic acid → HCID 178439951, compound

HRID 1895508Notes

Reaction equation

HRID 1895508 reaction equation
[CH2:1]([C@@H:8]([NH:21][C:22]([C:24]1[CH:35]=[C:34]([CH3:36])[C:27]2[N:28]=[C:29]([CH2:31][CH2:32][CH3:33])[NH:30][C:26]=2[CH:25]=1)=[O:23])[CH2:9][C:10](=[O:20])[NH:11][O:12][CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].Br[CH2:40][C:41]1[CH:46]=[CH:45][C:44]([C:47]2[CH:52]=[CH:51][CH:50]=[CH:49][C:48]=2[C:53]2[N:57](C(C3C=CC=CC=3)(C3C=CC=CC=3)C3C=CC=CC=3)[N:56]=[N:55][N:54]=2)=[CH:43][CH:42]=1.C(O)(C(F)(F)F)=O>CN(C=O)C.C(Cl)Cl>[CH2:1]([C@@H:8]([NH:21][C:22]([C:24]1[CH:35]=[C:34]([CH3:36])[C:27]2[N:28]([CH2:40][C:41]3[CH:46]=[CH:45][C:44]([C:47]4[CH:52]=[CH:51][CH:50]=[CH:49][C:48]=4[C:53]4[NH:54][N:55]=[N:56][N:57]=4)=[CH:43][CH:42]=3)[C:29]([CH2:31][CH2:32][CH3:33])=[N:30][C:26]=2[CH:25]=1)=[O:23])[CH2:9][C:10](=[O:20])[NH:11][O:12][CH2:13][C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 24758Sodium hydrideHCID 100534615-(4'-(Bromomethyl)(1,1'-biphenyl)-2-yl)-1-trityl-1H-tetraazoleHCID 441584617-Methyl-2-propyl-3H-benzoimidazole-5-carboxylic acid ((R)-1-benzyl-2-benzyloxycarbamoylethyl)amide

Product 1

HCID 178439951HCID 178439951, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a cold solution of 7-methyl-2-propyl-3H-benzoimidazole-5-carboxylic acid ((R)-1-benzyl-2-benzyloxycarbamoylethyl)amide (800 mg, 825 μmol) in DMF (50 mL) in ice bath was added NaH (60% dispersion in oil; 99 mg, 2.5 mmol) in small portions. After stirring for 30 minutes at the same temperature, 5-(4′-bromomethylbiphenyl-2-yl)-1-trityl-1H-tetrazole (460 mg, 825 μmol) was added to the mixture, and the final mixture was stirred at room temperature for 12 hours, then at 70° C. for 6 hours. The mixture was concentrated in vacuo. The residue was dissolved in EtOAc (200 mL) and washed with saturated aqueous NaCl. The organic layer was dried over MgSO4, and evaporated in vacuo, affording a pale yellow oil. The oil was dissolved in DCM (10 mL), followed by the addition of TFA (10 mL). The final mixture was stirred at room temperature for 1 hour, and concentrated to dryness, yielding a pale yellow oil. The oil was rinsed with ether and dried. The crude material was found to contain two regioisomeric N-alkylation products, compound 5a (a major product) and compound 5b (a minor desired product). ESMS [M+H]+ calcd for C43H42N8O3, 719.35. found 719.3.

Workup

  1. additionwas added to the mixture
  2. concentrationThe mixture was concentrated in vacuo
  3. dissolutionThe residue was dissolved in EtOAc (200 mL)
  4. washwashed with saturated aqueous NaCl
  5. dry with materialThe organic layer was dried over MgSO4
  6. customevaporated in vacuo
  7. customaffording a pale yellow oil
  8. concentrationconcentrated to dryness
  9. customyielding a pale yellow oil
  10. washThe oil was rinsed with ether
  11. customdried

Sources & evidence

ORD record
ord-3bab99c5a6424d1d94419b9d3c13d736
Source dataset
uspto-grants-2013_08
Patent number
US08513432B2

Reaction notes

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