Water → HCID 58367122, compound

HRID 1891468Notes

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.Br[CH2:30][CH2:31][O:32][Si:33]([C:36]([CH3:39])([CH3:38])[CH3:37])([CH3:35])[CH3:34].O>CN(C=O)C>[Si:33]([O:32][CH2:31][CH2:30][NH: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)([C:36]([CH3:39])([CH3:38])[CH3:37])([CH3:35])[CH3:34]

Participants

Conditions

Temperature: 95 °C

Procedure

Prepared using General Procedure 9. To a suspension of (R)-5-(5-(1-amino-2,3-dihydro-1H-inden-4-yl)-1,3,4-thiadiazol-2-yl)-2-isopropoxybenzonitrile hydrochloride 5 (50 mg, 0.12 mmol) in anhydrous DMF (5 mL) was added TEA (36.7 mg, 0.36 mmol) and (2-bromoethoxy)(tert-butyl)dimethylsilane (34.6 mg, 0.14 mmol). The solution was stirred at 95° C. After 16 h more (2-bromoethoxy)(tert-butyl)dimethylsilane (34.6 mg, 0.14 mmol) was added and heating continued for 12 h. Water (5 mL) was added and the reaction mixture was extracted with EA (2×5 mL). The organic layers were washed with brine, dried, and purified by column chromatography (EA/hexanes) to afford 10 mg (15%) of (R)-5-(5-(1-((2-((tert-butyldimethylsilyl)oxy)ethyl)amino)-2,3-dihydro-1H-inden-4-yl)-1,3,4-thiadiazol-2-yl)-2-isopropoxybenzonitrile. LCMS-ESI (m/z) calculated for: C29H38N4O2SSi: 534.3; found 535.3 [M+H]+, tR=3.08 min.

Workup

customPrepared
temperatureheating
extractionthe reaction mixture was extracted with EA (2×5 mL)
washThe organic layers were washed with brine
customdried
custompurified by column chromatography (EA/hexanes)

Sources & evidence

ORD record: ord-af33c13f20874edc841cf30527bff9a6
Source dataset: uspto-grants-2013_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08507538B2

Reaction notes

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