Methanol → HCID 178424461, compound

HRID 536982Notes

Reaction equation

HRID 536982 reaction equation
[CH3:1][C:2]1([CH3:35])[CH2:7][CH2:6][C:5]([C:8]2[CH:13]=[C:12]([C:14]3(O)[CH2:20][C:19]4([CH3:22])[O:21][C:16]([CH3:23])([CH2:17][CH2:18]4)[CH2:15]3)[CH:11]=[CH:10][C:9]=2[NH:25][C:26]([C:28]2[NH:29][CH:30]=[C:31]([C:33]#[N:34])[N:32]=2)=[O:27])=[CH:4][CH2:3]1.[Si]([C:40]#[N:41])(C)(C)C.Cl[Sn](Cl)(Cl)Cl.CO>C(Cl)Cl.C(Cl)(Cl)Cl.O>[C:40]([C:14]1([C:12]2[CH:11]=[CH:10][C:9]([NH:25][C:26]([C:28]3[NH:29][CH:30]=[C:31]([C:33]#[N:34])[N:32]=3)=[O:27])=[C:8]([C:5]3[CH2:6][CH2:7][C:2]([CH3:35])([CH3:1])[CH2:3][CH:4]=3)[CH:13]=2)[CH2:20][C:19]2([CH3:22])[O:21][C:16]([CH3:23])([CH2:17][CH2:18]2)[CH2:15]1)#[N:41]

Participants

8

Reactant 4

HCID 887MethanolHCID 24287Tin tetrachloride2×HCID 82115Trimethylsilyl cyanide2×HCID 178424472HCID 178424472, compound

Product 1

HCID 178424461HCID 178424461, compoundYield 28.2%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6212ChloroformSolventHCID 6344DichloromethaneSolvent3×

Procedure

To a slurry of 4-cyano-1H-imidazole-2-carboxylic acid [2-(4,4-dimethyl-cyclohex-1-enyl)-4-(3-hydroxy-1,5-dimethyl-8-oxa-bicyclo[3.2.1]oct-3-yl)-phenyl]-amide (21 mg, 0.044 mmol, as prepared in Example 93) in 1 mL of DCM at 0° C. was added TMSCN (25 μL, 0.19 mmol) followed by SnCl4 (4 mg, 0.01 mmol) dissolved in 0.08 mL of DCM. The reaction was warmed to room temperature and again treated with 25 μL of TMSCN and then SnCl4 (8 mg, 0.02 mmol) in 0.2 mL of DCM. After the reaction became homogeneous 1 mL of MeOH was added followed by 2 mL of water. The mixture was stirred for 5 min, CHCl3 (5 mL) was added and the layers were separated. The organic layer was dried (Na2SO4) and concentrated in vacuo. Purification of the residue twice by preparative TLC (5% MeOH—CHCl3, then 50% EtOAc-hexanes) afforded the title compound (6 mg, 28%). 1H-NMR (CD3OD; 400 MHz): δ 8.09 (d, 1H, J=8.3 Hz), 7.70 (s, 1H), 7.27-7.23 (m, 1H), 7.16-7.12 (m, 1H), 5.66-5.64 (m, 1H), 2.80-2.56 (m, 4H), 2.22-2.14 (m, 2H), 2.02-1.97 (m, 2H), 1.81-1.77 (m, 4H), 1.51-1.46 (m, 2H), 1.25 (s, 3H), 1.25 (s, 1H), 0.98 (s, 6H). Mass spectrum (ESI, m/z): Calcd. for C29H33N5O2 484.2 (M+1). found 484.0.

Workup

  1. additionwas added
  2. customthe layers were separated
  3. dry with materialThe organic layer was dried (Na2SO4)
  4. concentrationconcentrated in vacuo
  5. customPurification of the residue twice by preparative TLC (5% MeOH—CHCl3

Sources & evidence

ORD record
ord-4fb6a74a769a45cba5f57b0df54a5292
Source dataset
uspto-grants-2014_10
Patent number
US08859602B2

Reaction notes

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