Imidazole → HCID 67006584, compound

HRID 1254684Notes

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 (m, 1H), 2.25 (m, 3H), 1.31 (d, J=6 Hz, 3H), 0.77 (s, 9H), 0.03 (s, 6H), 0.00 (s, 3H).

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-fc59ec0191964c169760aa11fe318e72
Source dataset: uspto-grants-2013_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08455525B2

Reaction notes

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