Methanesulfonamide → ((1S,3R)-1-biphenyl-4-ylmethyl-4-methanesuIfonylamino-3-methyl-4-oxo-butyl)-carbamic acid tert-butyl ester

HRID 2384119Notes

Reaction equation

HRID 2384119 reaction equation
[C:1]1([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH:6]=[CH:5][C:4]([CH2:7][C@@H:8]([NH:15][C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:9][C@@H:10]([CH3:14])[C:11](O)=[O:12])=[CH:3][CH:2]=1.[CH3:29][S:30]([NH2:33])(=[O:32])=[O:31].CCN=C=NCCCN(C)C.Cl.ON1C2N=CC=CC=2N=N1.CCN(C(C)C)C(C)C>CN(C=O)C>[C:19]([O:18][C:16](=[O:17])[NH:15][C@H:8]([CH2:7][C:4]1[CH:5]=[CH:6][C:1]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)=[CH:2][CH:3]=1)[CH2:9][C@@H:10]([CH3:14])[C:11]([NH:33][S:30]([CH3:29])(=[O:32])=[O:31])=[O:12])([CH3:22])([CH3:21])[CH3:20]

Participants

7

Reactant 5

HCID 72879MethanesulfonamideHCID 81531DiisopropylethylamineHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 46193546(2R,4S)-2-methyl-4-((2-methylpropan-2-yl)oxycarbonylamino)-5-(4-phenylphenyl)pentanoic acid

Product 1

HCID 59608279((1S,3R)-1-biphenyl-4-ylmethyl-4-methanesuIfonylamino-3-methyl-4-oxo-butyl)-carbamic acid tert-butyl esterYield 55.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of (2R,4S)-5-biphenyl-4-yl-4-tert-butoxycarbonylamino-2-methyl-pentanoic acid (500 mg, 1.304 mmol) in DMF (10 ml) at room temperature is added methyl sulfonamide (223 mg, 2.347 mmol), EDC.HCl (450 mg, 2.347 mmol), 1-hydroxy-7-azabenzotriazole (284 mg, 2.086 mmol) and DIPEA (0.501 ml, 2.87 mmol). The reaction mixture is stirred at room temperature over night. The reaction is quenched by brine and is extracted with EtOAc. The combined organic layer is washed with brine and is dried over anhydrous sodium sulfate, filtered and concentrated. Reverse phase HPLC [15 to 60% ACN—H2O (0.1% NH4OH) over 10 min by X-bridge phenyl column] provides ((1S,3R)-1-Biphenyl-4-ylmethyl-4-methanesulfonylamino-3-methyl-4-oxo-butyl)-carbamic acid tert-butyl ester (333 mg, 55%). HPLC retention time=1.03 minutes (condition D), MS (m−1)=495.5, MS (m−55)=405.3, MS (m−99)=361.3.

Workup

  1. customThe reaction is quenched by brine
  2. extractionis extracted with EtOAc
  3. washThe combined organic layer is washed with brine
  4. dry with materialis dried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-bcc6316340c4411b9283069860d89cac
Source dataset
uspto-grants-2012_09
Patent number
US08263629B2

Reaction notes

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