Diisopropylethylamine → 5-(5-(1-Acetyl-piperidin-4-yl)-2-{[4-cyano-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazole-2-carbonyl]-amino}-phenyl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester

HRID 1714662Notes

Reaction equation

[C:1]([O:5][C:6]([N:8]1[CH2:13][C:12]([C:14]2[CH:19]=[C:18]([CH:20]3[CH2:25][CH2:24][N:23]([C:26](=[O:28])[CH3:27])[CH2:22][CH2:21]3)[CH:17]=[CH:16][C:15]=2[NH2:29])=[CH:11][CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C1CN([P+](Br)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.[C:54]([C:56]1[N:57]=[C:58]([C:69](O)=[O:70])[N:59]([CH2:61][O:62][CH2:63][CH2:64][Si:65]([CH3:68])([CH3:67])[CH3:66])[CH:60]=1)#[N:55].[K+].C(C1N=C(C([O-])=O)N(COCC[Si](C)(C)C)C=1)#N.CCN(C(C)C)C(C)C>C(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[CH2:13][C:12]([C:14]2[CH:19]=[C:18]([CH:20]3[CH2:21][CH2:22][N:23]([C:26](=[O:28])[CH3:27])[CH2:24][CH2:25]3)[CH:17]=[CH:16][C:15]=2[NH:29][C:69]([C:58]2[N:59]([CH2:61][O:62][CH2:63][CH2:64][Si:65]([CH3:68])([CH3:67])[CH3:66])[CH:60]=[C:56]([C:54]#[N:55])[N:57]=2)=[O:70])=[CH:11][CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

Conditions

Temperature: 0 °C

Procedure

A solution of 5-[5-(1-acetyl-piperidin-4-yl)-2-amino-phenyl]-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester (as prepared in the previous step, 0.25 g, 0.63 mmol) in CH2Cl2 was treated with PyBroP (0.44 g, 0.94 mmol) and 4-cyano-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazole-2-carboxylic acid, potassium salt (as prepared in Example 3, step (d), 0.21 g, 0.69 mmol). The resulting slurry was cooled to 0° C. and treated with DIEA (0.33 mL, 1.88 mmol). The ice bath was removed and the mixture stirred at room temperature for 18 h. The reaction was diluted with CH2Cl2 and washed with saturated aqueous NaHCO3. The organic layer was dried over MgSO4 and concentrated in vacuo. Silica gel chromatography (25-45% EtOAc in hexanes then 100% EtOAc) afforded the title compound (399 mg, 98%) as a white solid. LC-MS (ESI, m/z): Calcd. for C34H48N6O5Si 649.4 (M+H), found 649.9.

Workup

customThe ice bath was removed
additionThe reaction was diluted with CH2Cl2
washwashed with saturated aqueous NaHCO3
dry with materialThe organic layer was dried over MgSO4
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-54f3110825f94a048d25305f5c63f9e8
Source dataset: uspto-grants-2010_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07795279B2

Reaction notes

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