Imidazole → HCID 67006538, compound

HRID 563255Notes

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,3S)-2-(4-cyano-2-methyl-3-(trifluoromethyl)phenylamino)-3-hydroxybutanoyl)benzohydrazide (507 mg, 1.14 mmol) was added to DMF (30 mL), followed by addition of TBDMS-Cl (686 mg, 4.55 mmol) and imidazole (619 mg, 9.10 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 extracted with EtOAc. The resulting crude material was chromatographed to give the desired product (390 mg) 1H NMR (400 MHz, acetone-d6, δ in ppm): 9.6 (br s), 7.92 (d, J=9 Hz, 2H), 7.8 (d, J=9 Hz, 2H), 7.56 (d, J=9 Hz, 1H), 6.92 (d, J=9 Hz, 1H), 5.55 (d, J=9 Hz, 1H), 4.51 (m, 1H), 4.16 (m, 1H), 2.25 (m, 3H), 1.24 (d, J=6 Hz, 3H), 0.82 (s, 9H), 0.05 (s, 6H), 0.00 (s, 3H).

Workup

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

Sources & evidence

ORD record: ord-c5077ff6c4394610819657af75322e9c
Source dataset: uspto-grants-2011_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08067448B2

Reaction notes

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