Tetrahydrofuran → HCID 24758023, compound

HRID 1711305Notes

Reaction equation

HRID 1711305 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 178418689HCID 178418689, 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 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 SPE column 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 SPE column
  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-5c0900a0edbb41c182fc50781c2f78c8
Source dataset
uspto-grants-2010_09
Patent number
US07790724B2

Reaction notes

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