1,2-Dichloroethane → HCID 86660286, compound

HRID 1631046Notes

Reaction equation

HRID 1631046 reaction equation
[Si:1]([O:8][C@H:9]1[CH2:13][N:12]([C:14]2[C:19]([Cl:20])=[CH:18][C:17]([C:21](=[N:23][OH:24])[NH2:22])=[CH:16][N:15]=2)[C@H:11]([C:25]([O:27][CH3:28])=[O:26])[CH2:10]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].Br[C:30]1[CH:39]=[CH:38][C:33]([C:34]([O:36][CH3:37])=O)=[CH:32][C:31]=1[CH2:40]OC.[CH2:43](Cl)[CH2:44]Cl>CC#N.N1C=CC=CC=1>[Cl:20][C:19]1[C:14]([N:12]2[CH2:13][C@H:9]([O:8][Si:1]([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2])[CH2:10][C@H:11]2[C:25]([O:27][CH3:28])=[O:26])=[N:15][CH:16]=[C:17]([C:21]2[N:22]=[C:40]([C:31]3[CH:30]=[CH:39][C:38]([C:25]4[CH:11]=[CH:10][CH:9]=[CH:13][C:43]=4[CH3:44])=[C:33]([CH2:34][O:36][CH3:37])[CH:32]=3)[O:24][N:23]=2)[CH:18]=1

Participants

6

Reactant 3

HCID 111,2-DichloroethaneHCID 58554220Methyl 4-bromo-3-(methoxymethyl)benzoateHCID 86660285HCID 86660285, compound

Product 1

HCID 86660286HCID 86660286, compound

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6342AcetonitrileSolvent

Procedure

To a solution of methyl (2S,4R)-4-(tert-butyldimethylsilyloxy)-1-(3-chloro-5-(N′-hydroxycarbamimidoyl)pyridin-2-yl)pyrrolidine-2-carboxylate (0.320 g; 0.75 mmol) and Intermediate A1 (0.210 g; 0.82 mmol) in MeCN (3 mL) was added EDC (0.157 g; 0.82 mmol). The reaction mixture was stirred at ambient temperature for 18 h. The reaction mixture was diluted with pyridine (2 mL) and heated at 150° C. in the microwave for 30 minutes. The solvent was removed in vacuo and the residue dissolved in DCM. The mixture was washed with water and the organic phase passed through a hydrophobic frit. The solvent was evaporated in vacuo. The residue was purified by flash chromatography on silica, eluting with iso-hexane/EtOAc (6:1) to afford the title product. 1H NMR (CDCl3, 400 MHz) δ 8.69 (1H, d, J=2 Hz), 8.30 (1H, d, J=1.6 Hz), 8.15 (1H, d, J=1.6 Hz), 8.06-8.03 (1H, m), 7.24-7.16 (4H, m), 7.04 (1H, d, J=7.2 Hz), 4.82 (1H, m), 4.50 (1H, m), 4.22-4.18 (1H, m), 4.13-4.12 (2H, m), 3.76 (1H, m), 3.64 (3H, s), 3.23 (3H, s), 2.20 (1H, m), 1.99-1.98 (4H, m), 0.79 (9H, s), 0.00 (3H, s), −0.02 (3H, s).

Workup

  1. temperatureheated at 150° C. in the microwave for 30 minutes
  2. customThe solvent was removed in vacuo
  3. dissolutionthe residue dissolved in DCM
  4. washThe mixture was washed with water
  5. customThe solvent was evaporated in vacuo
  6. customThe residue was purified by flash chromatography on silica
  7. washeluting with iso-hexane/EtOAc (6:1)

Sources & evidence

ORD record
ord-0f6e8a4392a5475c86a68e2b8b540e34
Source dataset
uspto-grants-2014_07
Patent number
US08791142B2

Reaction notes

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