Tetrahydrofuran → HCID 24758023, compound

HRID 1508132Notes

Reaction equation

HRID 1508132 reaction equation
[C:1]([C:4]1[N:9]=[C:8]([C:10]2[CH2:15][CH2:14]C(C)(C)[CH2:12][CH:11]=2)[C:7]([NH:18][C:19]([C:21]2[NH:22][C:23]([C:26]#[N:27])=[CH:24][N:25]=2)=[O:20])=[CH:6][CH:5]=1)(=[O:3])[CH3:2].[CH3:28][Mg]Br.[CH2:31]1[CH2:35]OC[CH2:32]1>>[CH3:32][CH:31]1[CH2:35][CH2:14][CH2:15][C:10]([C:8]2[C:7]([NH:18][C:19]([C:21]3[NH:22][C:23]([C:26]#[N:27])=[CH:24][N:25]=3)=[O:20])=[CH:6][CH:5]=[C:4]([C:1]([OH:3])([CH3:28])[CH3:2])[N:9]=2)=[C:11]1[CH3:12]

Participants

4

Reactant 3

HCID 8028TetrahydrofuranHCID 59457538HCID 59457538, compoundHCID 178418573HCID 178418573, compound2×

Product 1

HCID 24758023HCID 24758023, compoundYield 43%

Procedure

To a solution of 5-cyano-1H-imidazole-2-carboxylic acid [6-acetyl-2-(4,4-dimethyl-cyclohex-1-enyl)-pyridin-3-yl]-amide (as prepared in the previous step, 6 mg, 0.016 mmol) in THF (1 mL) was added methylmagnesium bromide (MeMgBr) (3 M in THF, 41 μL, 0.072 mmol). After 20 min another 2.5 equivalents of MeMgBr was added and the reaction was allowed to warm to room temperature and quenched with saturated aqueous NaHCO3 (2 mL). The slurry was filtered through a 5-g Sep-Pak and concentrated in vacuo. The crude product was purified by silica gel chromatography (250-mg, 3-mL Supelco Si-tube, gradient CHCl3-2% CHCl3-MeOH) to afford 2.6 mg (43%) of the title compound as a white solid. 1H-NMR (CD3OD; 400 MHz): δ 8.44 (d, 1H, J=8.5 Hz), 7.90 (s, 1H), 7.42 (d, 1H, J=8.5 Hz), 5.86 (s, 1H), 2.39-2.37 (m, 2H), 1.99-1.94 (m, 2H), 1.51 (t, 1H, J=6.3 Hz), 1.43 (s, 6H), 0.99 (s, 6H). Mass spectrum (ESI, m/z): Calcd. for C21H25N5O2, 380.2 (M+H). found 380.1.

Workup

  1. customquenched with saturated aqueous NaHCO3 (2 mL)
  2. filtrationThe slurry was filtered through a 5-g Sep-Pak
  3. concentrationconcentrated in vacuo
  4. customThe crude product was purified by silica gel chromatography (250-mg, 3-mL Supelco Si-tube, gradient CHCl3-2% CHCl3-MeOH)

Sources & evidence

ORD record
ord-d8c886244eeb40d99acd4ea4fc9b50e5
Source dataset
uspto-grants-2015_12
Patent number
US09221797B2

Reaction notes

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