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

Participants

Role	Name	HCID	Charge
Reactant	Methanesulfonamide	HCID 72879	—
Reactant	Diisopropylethylamine	HCID 81531	—
Reactant	HOAt	HCID 181649	—
Reactant	1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride	HCID 2723939	—
Reactant	(2R,4S)-2-methyl-4-((2-methylpropan-2-yl)oxycarbonylamino)-5-(4-phenylphenyl)pentanoic acid	HCID 46193546	—
Solvent	Dimethylformamide	HCID 6228	—
Product	((1S,3R)-1-biphenyl-4-ylmethyl-4-methanesuIfonylamino-3-methyl-4-oxo-butyl)-carbamic acid tert-butyl ester	HCID 59608279	55.4%

Reaction Steps

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.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US09006249B2
Source dataset	uspto-grants-2015_04
ORD ID	ord-8f240d3a0faa43eba1f2b87e2c3c8034
Source note	uspto-grants-2015_04