Dimethylacetamide → {2-[(S)-2-(2-Benzyl-2H-tetrazol-5-yl)-pyrrolidin-1-yl]-1-cyclohexyl-2-oxo-ethyl}-carbamic acid tert-butyl ester

HRID 29075Notes

Reaction equation

HRID 29075 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH:13]1[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]1)[C:10]([OH:12])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].CN(C(ON1N=N[C:29]2[CH:30]=[CH:31][CH:32]=[CH:33][C:28]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C1C=CC2[N:51](O)[N:50]=[N:49][C:47]=2C=1.[CH:53]([N:56]([CH:59]([CH3:61])[CH3:60])CC)([CH3:55])C.CC([N:65](C)C)=O>C(Cl)Cl>[C:1]([O:5][C:6](=[O:7])[NH:8][CH:9]([CH:13]1[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]1)[C:10]([N:56]1[CH2:53][CH2:55][CH2:61][C@H:59]1[C:60]1[N:51]=[N:50][N:49]([CH2:47][C:28]2[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=2)[N:65]=1)=[O:12])([CH3:2])([CH3:3])[CH3:4]

Participants

7

Reactant 5

HCID 31374DimethylacetamideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 7004938N-(tert-Butoxycarbonyl)-L-cyclohexylglycine

Product 1

HCID 59787961{2-[(S)-2-(2-Benzyl-2H-tetrazol-5-yl)-pyrrolidin-1-yl]-1-cyclohexyl-2-oxo-ethyl}-carbamic acid tert-butyl esterYield 92%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (S)-tert-butoxycarbonylamino-cyclohexyl-acetic acid (123.8 mg, 0.48 mmol) in DMA (5 mL) is added HBTU (248.8 mg, 0.656 mmol), HOBt (88.6 mg, 0.656 mmol) and diisopropylethylamine (305 uL, 1.75 mmol). The mixture is stirred at room temperature for 5 minutes. A solution of compound D in DCM (5 mL) is added to the above mixture at 0° C. The reaction mixture is stirred at room temperature for 1 hour and concentrated under vacuum. The residue is diluted with EtOAc. The organic is washed with brine, citric acid(5%), brine, NaHCO3(Sat.) and brine. The organic layer is then dried and concentrated under vacuum. The residue is purified by flash column chromatography (Hexanes/EtOAc) to provide the title compound 190 mg (92%). M+H+=369.

Workup

  1. stirringThe reaction mixture is stirred at room temperature for 1 hour
  2. concentrationconcentrated under vacuum
  3. additionThe residue is diluted with EtOAc
  4. washThe organic is washed with brine, citric acid(5%), brine, NaHCO3(Sat.) and brine
  5. customThe organic layer is then dried
  6. concentrationconcentrated under vacuum
  7. customThe residue is purified by flash column chromatography (Hexanes/EtOAc)

Sources & evidence

ORD record
ord-0f75f65eb740449a990875befa20b6c4
Source dataset
uspto-grants-2008_09
Patent number
US07419975B2

Reaction notes

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