Pyridine → 3-{[(1S)-1-methyl-2-(methyloxy)ethyl]oxy}-N-(5-methylpyrazin-2-yl)-5-[(phenylmethyl)oxy]benzamide

HRID 1990217Notes

Reaction equation

HRID 1990217 reaction equation
C(Cl)(=O)C(Cl)=O.[CH3:7][O:8][CH2:9][C@@H:10]([O:12][C:13]1[CH:14]=[C:15]([CH:19]=[C:20]([O:22][CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH:21]=1)[C:16]([OH:18])=O)[CH3:11].[NH2:30][C:31]1[CH:36]=[N:35][C:34]([CH3:37])=[CH:33][N:32]=1.N1C=CC=CC=1>C(Cl)Cl>[CH3:11][C@H:10]([O:12][C:13]1[CH:14]=[C:15]([CH:19]=[C:20]([O:22][CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH:21]=1)[C:16]([NH:30][C:31]1[CH:36]=[N:35][C:34]([CH3:37])=[CH:33][N:32]=1)=[O:18])[CH2:9][O:8][CH3:7]

Participants

6

Reactant 4

HCID 1049PyridineHCID 65578Oxalyl chlorideHCID 3132155-Methylpyrazin-2-amineHCID 59127150Benzoic acid, 3-[(1S)-2-methoxy-1-methylethoxy]-5-(phenylmethoxy)-

Product 1

HCID 536296643-{[(1S)-1-methyl-2-(methyloxy)ethyl]oxy}-N-(5-methylpyrazin-2-yl)-5-[(phenylmethyl)oxy]benzamideYield 85.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Oxalyl chloride (2.1 mL, 24.0 mmol) was added to a solution of 3-[(1S)-2-methoxy-(1-methylethyl)oxy]-5-{[phenylmethyl]oxy}benzoic acid (6.32 g, 20.0 mmol) in DCM (100 mL) and the mixture stirred at RT for 4 hours. The mixture was evaporated in vacuo to a residue, which was taken up in DCM (25 mL) and added to a stirred mixture of 2-amino-5-methylpyrazine (2.29 g, 21.0 mmol) and pyridine (1.94 mL, 24.0 mmol) in DCM (100 mL) at 5° C.-10° C. The mixture was stirred at RT for 18 hours, the DCM evaporated in vacuo. The residue was partitioned between water (50 mL) and ethyl acetate (150 mL), the organic layer washed with brine, dried (MgSO4) and evaporated to a residue, which was chromatographed on silica, eluting with 50% ethyl acetate in isohexane, to give the desired compound (7.0 g). 1H NMR δ (CDCl3): 1.3 (d, 3H), 2.5 (s, 3H), 3.3 (s, 3H), 3.4-3.5 (m, 2H), 4.5 (m, 1H), 5.0 (s, 2H), 6.7 (s, 1H), 7.0 (s, 1H), 7.05 (s, 1H), 7.35 (m, 5H), 8.05 (s, 1H), 8.3 (s, 1H) and 9.5 (s, 1H). m/z 408 (M+H)+.

Workup

  1. customThe mixture was evaporated in vacuo to a residue, which
  2. stirringThe mixture was stirred at RT for 18 hours
  3. customthe DCM evaporated in vacuo
  4. customThe residue was partitioned between water (50 mL) and ethyl acetate (150 mL)
  5. washthe organic layer washed with brine
  6. dry with materialdried (MgSO4)
  7. customevaporated to a residue, which
  8. customwas chromatographed on silica
  9. washeluting with 50% ethyl acetate in isohexane

Sources & evidence

ORD record
ord-cceba8e28cc44e1b8ac8e857928c0928
Source dataset
uspto-grants-2010_01
Patent number
US07642259B2

Reaction notes

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