1-Methylimidazole → HCID 86652494, compound

HRID 1971133Notes

Reaction equation

HRID 1971133 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][N:5]([CH:8]2[O:14][CH:13]([CH2:15][OH:16])[CH:12]([OH:17])[C:9]32[CH2:11][CH2:10]3)[C:4](=[O:18])[N:3]=1.Cl[C:20]1[CH:41]=[CH:40][CH:39]=[CH:38][C:21]=1[O:22][P:23](=[N:25][C@@H:26]([CH3:37])[C:27]([O:29][CH2:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)=[O:28])=[O:24].CN1C=CN=C1>C1COCC1.N1C=CC=CC=1>[NH2:1][C:2]1[CH:7]=[CH:6][N:5]([C@@H:8]2[O:14][C@H:13]([CH2:15][O:16][C:38]3[CH:39]=[CH:40][CH:41]=[CH:20][C:21]=3[O:22][P:23](=[N:25][C@@H:26]([CH3:37])[C:27]([O:29][CH2:30][C:31]3[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=3)=[O:28])=[O:24])[C@@H:12]([OH:17])[C:9]32[CH2:11][CH2:10]3)[C:4](=[O:18])[N:3]=1

Participants

5

Reactant 3

HCID 13901-MethylimidazoleHCID 67088393HCID 67088393, compoundHCID 86652495HCID 86652495, compound

Product 1

HCID 86652494HCID 86652494, compoundYield 35.6%

Reagents, catalysts & solvents 1

HCID 16069498Pyridine tetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

Compound 1 (100 mg) was dissolved in dry THF/pyridine together with (2S)-benzyl 2-(chloro(phenoxy)phosphorylamino)propanoate (279 mg, 2.0 eq). The mixture was cooled to −78° C. N-methylimidazole (NMI) (259 mg, 8 eq) was added and this mixture was stirred for 15 minutes at −78° C. and then stirred at RT overnight. The resulting mixture was evaporated to dryness. 10 mL CH2Cl2 added and the residue washed with 10 mL 0.5N HCl. The organic layer was separated and washed with 10 mL water, dried on Na2SO4, filtered and evaporated. The compound was purified by silica gel chromatography using CH2Cl2 to CH2Cl2/MeOH 9-1 as the eluent. (Rf=0.2 in this eluent). A yellow solid was obtained, which was repurified using column chromatography using EtOAc to EtOAc/MeOH 8-2 as the eluent. After evaporation and drying overnight in vacuo, 80 mg (33.4%) of 2a was obtained (mixture of diastereomers). LC-MS: Rt: 3.37 min m/z: 569 (M−H)−. 1H NMR (400 MHz, DMSO-d6) δ ppm 0.31-0.41 (m, 1H), 0.43-0.58 (m, 2H), 0.95-1.06 (m, 1H), 1.20-1.31 (m, 3H), 3.82-4.01 (m, 3H), 4.09-4.23 (m, 1H), 4.23-4.36 (m, 1H), 4.98-5.15 (m, 2H), 5.29-5.39 (m, 1H), 5.70 (d, J=7.43 Hz, 1H), 6.07 (s, 1H), 6.13 (dd, J=12.81, 10.47 Hz, 1H), 7.08-7.25 (m, 6H), 7.29-7.39 (m, 6H), 7.54 (d, 1H).

Workup

  1. stirringstirred at RT overnight
  2. customThe resulting mixture was evaporated to dryness
  3. addition10 mL CH2Cl2 added
  4. washthe residue washed with 10 mL 0.5N HCl
  5. customThe organic layer was separated
  6. washwashed with 10 mL water
  7. customdried on Na2SO4
  8. filtrationfiltered
  9. customevaporated
  10. customThe compound was purified by silica gel chromatography
  11. customA yellow solid was obtained
  12. customwhich was repurified
  13. customAfter evaporation
  14. customdrying overnight in vacuo

Sources & evidence

ORD record
ord-998ba6a2ba144e85b44688c0236dccc5
Source dataset
uspto-grants-2013_04
Patent number
US08431588B2

Reaction notes

Loading…