Methyl vinyl sulfone → HCID 52938542, compound

HRID 1807585Notes

Reaction equation

Cl.[NH2:2][C@@H:3]1[CH2:12][CH2:11][CH2:10][C:9]2[C:8]([C:13]3[N:17]=[C:16]([C:18]4[CH:19]=[CH:20][C:21]([O:26][CH:27]([CH3:29])[CH3:28])=[C:22]([CH:25]=4)[C:23]#[N:24])[O:15][N:14]=3)=[CH:7][CH:6]=[CH:5][C:4]1=2.[CH3:30][S:31]([CH:34]=[CH2:35])(=[O:33])=[O:32]>CC(N(C)C)=O>[CH:27]([O:26][C:21]1[CH:20]=[CH:19][C:18]([C:16]2[O:15][N:14]=[C:13]([C:8]3[C:9]4[CH2:10][CH2:11][CH2:12][C@@H:3]([NH:2][CH2:35][CH2:34][S:31]([CH3:30])(=[O:33])=[O:32])[C:4]=4[CH:5]=[CH:6][CH:7]=3)[N:17]=2)=[CH:25][C:22]=1[C:23]#[N:24])([CH3:29])[CH3:28]

Participants

Conditions

Temperature: 80 °C

Procedure

To a solution of (R)-5-(3-(5-amino-5,6,7,8-tetrahydronaphthalen-1-yl)-1,2,4-oxadiazol-5-yl)-2-isopropoxybenzonitrile hydrochloride 3 (20 mg, 0.05 mmol) in DMA (0.5 mL) was added TEA (136 μL, 0.97 mmol) and methylvinylsulfone (52 mg, 0.5 mmol). The reaction was heated to 80° C. for 24 h. The crude reaction mixture was purified by preparative HPLC to give (R)-2-isopropoxy-5-(3-(5-((2-(methylsulfonyl)ethyl)amino)-5,6,7,8-tetrahydronaphthalen-1-yl)-1,2,4-oxadiazol-5-yl)benzonitrile 48. LCMS-ESI (m/z) calculated for C25H28N4O4S: 480.6; found 481.2 [M+H]+, tR=2.58 min. 1H NMR (400 MHz, CDCl3) δ 8.37 (t, J=9.1 Hz, 1H), 8.31 (dd, J=8.9, 2.2 Hz, 1H), 8.08 (d, J=7.1 Hz, 1H), 7.60 (d, J=7.6 Hz, 1H), 7.42 (t, J=7.7 Hz, 1H), 7.12 (d, J=9.1 Hz, 1H), 4.85-4.73 (m, 1H), 4.53 (t, J=5.0 Hz, 1H), 3.63 (dd, J=15.3, 4.0 Hz, 2H), 3.61-3.50 (m, 2H), 3.33-3.17 (m, 1H), 3.18-3.04 (m, 1H), 3.04 (d, J=8.6 Hz, 3H), 2.16 (ddd, J=29.6, 18.8, 12.2 Hz, 2H), 2.00 (dd, J=36.4, 18.4 Hz, 2H), 1.47 (d, J=6.1 Hz, 6H).

Workup

customThe crude reaction mixture
customwas purified by preparative HPLC

Sources & evidence

ORD record: ord-94f994f5eb91493b849f562acf8a4afe
Source dataset: uspto-grants-2013_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08357706B2

Reaction notes

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