Imidazole → HCID 67006584, compound

HRID 470786Notes

Reaction equation

[C:1]([C:3]1[CH:32]=[CH:31][C:6]([C:7]([NH:9][NH:10][C:11](=[O:30])[C@H:12]([NH:16][C:17]2[CH:22]=[CH:21][C:20]([C:23]#[N:24])=[C:19]([C:25]([F:28])([F:27])[F:26])[C:18]=2[CH3:29])[C@H:13]([OH:15])[CH3:14])=[O:8])=[CH:5][CH:4]=1)#[N:2].[CH3:33][C:34]([Si:37](Cl)([CH3:39])[CH3:38])([CH3:36])[CH3:35].N1C=CN=C1>CN(C=O)C>[Si:37]([O:15][C@H:13]([CH3:14])[C@@H:12]([NH:16][C:17]1[CH:22]=[CH:21][C:20]([C:23]#[N:24])=[C:19]([C:25]([F:28])([F:27])[F:26])[C:18]=1[CH3:29])[C:11]([NH:10][NH:9][C:7](=[O:8])[C:6]1[CH:5]=[CH:4][C:3]([C:1]#[N:2])=[CH:32][CH:31]=1)=[O:30])([C:34]([CH3:36])([CH3:35])[CH3:33])([CH3:39])[CH3:38]

Participants

Conditions

Temperature: 0 °C

Procedure

The crude material 4-cyano-N′-((2R,3R)-2-(4-cyano-2-methyl-3-(trifluoromethyl)phenylamino)-3-hydroxybutanoyl)benzohydrazide (800 mg, 1.75 mmol) was added to DMF (40 mL), followed by addition of TBDMS-Cl (1.06 g, 7.00 mmol) and imidazole (954 mg, 14.01 mmol) at 0° C. The solution was allowed to stir at 0° C. for 30 min and then at room temperature for overnight. The reaction was quenched with the addition of 200 mL brine and extract with EtOAc. The resulting crude material was chromatographed to get the desired product (640 mg) 1H NMR (400 MHz, acetone-d6, δ in ppm): 9.62 (br s), 7.93 (d, J=9 Hz, 2H), 7.79 (d, J=9 Hz, 2H), 7.55 (d, J=9 Hz, 1H), 6.98 (d, J=9 Hz, 1H), 5.38 (d, J=9 Hz, 1H), 4.41 (m, 1H), 4.18 (or, 1H), 2.25 (m, 3H), 1.31 (d, J=6 Hz, 3H), 0.77 (s, 9H), 0.03 (s, 6H), 0.00 (s, 3 H).

Workup

waitat room temperature for overnight
customThe reaction was quenched with the addition of 200 mL brine
extractionextract with EtOAc
customThe resulting crude material was chromatographed

Sources & evidence

ORD record: ord-751f2dd8a0db48d1b22772fe7d83c179
Source dataset: uspto-grants-2014_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08629167B2

Reaction notes

Loading…