Methyl vinyl sulfone → (S)-2-isopropoxy-5-(5-(1-((2-(methylsulfonyl)ethyl)amino)-2,3-dihydro-1H-inden-4-yl)-1,3,4-thiadiazol-2-yl)benzonitrile

HRID 1891476Notes

Reaction equation

Cl.[NH2:2][C@@H:3]1[C:11]2[C:6](=[C:7]([C:12]3[S:16][C:15]([C:17]4[CH:18]=[CH:19][C:20]([O:25][CH:26]([CH3:28])[CH3:27])=[C:21]([CH:24]=4)[C:22]#[N:23])=[N:14][N:13]=3)[CH:8]=[CH:9][CH:10]=2)[CH2:5][CH2:4]1.CCN(C(C)C)C(C)C.[CH3:38][S:39]([CH:42]=[CH2:43])(=[O:41])=[O:40]>CC(N(C)C)=O>[CH:26]([O:25][C:20]1[CH:19]=[CH:18][C:17]([C:15]2[S:16][C:12]([C:7]3[CH:8]=[CH:9][CH:10]=[C:11]4[C:6]=3[CH2:5][CH2:4][C@@H:3]4[NH:2][CH2:43][CH2:42][S:39]([CH3:38])(=[O:41])=[O:40])=[N:13][N:14]=2)=[CH:24][C:21]=1[C:22]#[N:23])([CH3:28])[CH3:27]

Participants

Conditions

Temperature: 90 °C

Procedure

To a stirred solution of (S)-5-(5-(1-amino-2,3-dihydro-1H-inden-4-yl)-1,3,4-thiadiazol-2-yl)-2-isopropoxybenzonitrile hydrochloride 4 (25 mg, 0.06 mmol) and DIEA (32 mg, 0.24 mmol) in DMA (1 mL) was added (methylsulfonyl)ethene (20 mg, 0.18 mmol). The reaction mixture was heated at 90° C. for 24 h. The solvent was evaporated and the product purified by preparative HPLC to afford 9 mg (31%) of (S)-2-isopropoxy-5-(5-(1-((2-(methylsulfonyl)ethyl)amino)-2,3-dihydro-1H-inden-4-yl)-1,3,4-thiadiazol-2-yl)benzonitrile 31 as half-white solid. LCMS-ESI (m/z) calculated for. C24H26N4O3S2: 482.1; found 483.1 [M+H]+, tR=2.49 min.

Workup

customThe solvent was evaporated
customthe product purified by preparative HPLC

Sources & evidence

ORD record: ord-990f4cd548f24e9795bf3d31bb49683d
Source dataset: uspto-grants-2013_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08507538B2

Reaction notes

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