1-Methylimidazole → HCID 66688127, compound

HRID 1425684Notes

Reaction equation

HRID 1425684 reaction equation
[OH:1][C@H:2]1[C@@:6]2([O:9][CH2:8][CH2:7]2)[C@H:5]([N:10]2[CH:15]=[CH:14][C:13](=[O:16])[NH:12][C:11]2=[O:17])[O:4][C@@H:3]1[CH2:18][OH:19].CN1C=CN=C1.Cl[C:27]1[CH:43]=[CH:42][CH:41]=[CH:40][C:28]=1[O:29][P:30](=[N:32][C:33]([CH3:39])([CH3:38])[C:34]([O:36][CH3:37])=[O:35])=[O:31]>C1COCC1>[O:17]=[C:11]1[NH:12][C:13](=[O:16])[CH:14]=[CH:15][N:10]1[C@@H:5]1[O:4][C@H:3]([CH2:18][O:19][C:40]2[CH:41]=[CH:42][CH:43]=[CH:27][C:28]=2[O:29][P:30](=[N:32][C:33]([CH3:39])([CH3:38])[C:34]([O:36][CH3:37])=[O:35])=[O:31])[C@@H:2]([OH:1])[C@:6]21[O:9][CH2:8][CH2:7]2

Participants

5

Reactant 3

HCID 13901-MethylimidazoleHCID 66678676HCID 66678676, compoundHCID 66687284HCID 66687284, compound

Product 1

HCID 66688127HCID 66688127, compoundYield 16.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 10 (1.0 eq., 0.28 mmol, 75 mg) in dry THF (3 mL) was added 1-methylimidazole (NMI; 12.0 eq., 3.33 mmol, 0.27 mL) at room temperature. A solution of intermediate 11 (1.4 eq., 0.39 mmol, 0.43 mL) was added dropwise and the mixture was stirred at room temperature for 1 hour. The reaction mixture was washed three times with 0.5 M HCl. The organic layer was dried over MgSO4 and concentrated in vacuo. The residue was purified by column chromatography on silica gel (0-10% methanol in CH2Cl2) to give compound 12e (24 mg, yield=15%, purity=95%) as a mixture of diastereomers. HPLC Condition A; Rt: 1.49 min, m/z=526 (M+H)+. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.33 (s, 3H), 1.37 (s, 3H), 2.42-2.43 (m, 2H), 3.56 (s, 3H), 3.70-3.79 (m, 1H), 3.80-3.88 (m, 0.4; H), 3.88-3.96 (m, 0.6; H), 4.09-4.20 (m, 1H), 4.26-4.48 (m, 3H), 5.50-5.56 (m, 1H), 5.61-5.69 (m, 1H), 5.88-5.97 (m, 1H), 5.97-6.04 (m, 1H), 7.12-7.24 (m, 3H), 7.31-7.41 (m, 2H), 7.44 (d, J=8.22 Hz, 0.4; H), 7.52 (d, J=8.02 Hz, 0.6; H), 11.49 (br. s., 1H).

Workup

  1. washThe reaction mixture was washed three times with 0.5 M HCl
  2. dry with materialThe organic layer was dried over MgSO4
  3. concentrationconcentrated in vacuo
  4. customThe residue was purified by column chromatography on silica gel (0-10% methanol in CH2Cl2)

Sources & evidence

ORD record
ord-06a13bbebbbc487696d2d10d7c67d6ab
Source dataset
uspto-grants-2015_01
Patent number
US08933052B2

Reaction notes

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