Pyridine → N-(5-methylpyrazin-2-yl)-3-[(phenylmethyl)oxy]-5-[(3S)-tetrahydrofuran-3-yloxy]benzamide

HRID 548719Notes

Reaction equation

HRID 548719 reaction equation
C(Cl)(=O)C(Cl)=O.[C:7]1([CH2:13][O:14][C:15]2[CH:16]=[C:17]([CH:21]=[C:22]([O:24][C@H:25]3[CH2:29][CH2:28][O:27][CH2:26]3)[CH:23]=2)[C:18]([OH:20])=O)[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.[NH2:30][C:31]1[CH:36]=[N:35][C:34]([CH3:37])=[CH:33][N:32]=1.N1C=CC=CC=1>CN(C=O)C.C(Cl)Cl>[CH3:37][C:34]1[N:35]=[CH:36][C:31]([NH:30][C:18](=[O:20])[C:17]2[CH:21]=[C:22]([O:24][C@H:25]3[CH2:29][CH2:28][O:27][CH2:26]3)[CH:23]=[C:15]([O:14][CH2:13][C:7]3[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=3)[CH:16]=2)=[N:32][CH:33]=1

Participants

7

Reactant 4

HCID 1049PyridineHCID 65578Oxalyl chlorideHCID 3132155-Methylpyrazin-2-amineHCID 576631583-[(phenylmethyl)oxy]-5-[(3S)-tetrahydrofuran-3-yloxy]benzoic acid

Product 1

HCID 57663209N-(5-methylpyrazin-2-yl)-3-[(phenylmethyl)oxy]-5-[(3S)-tetrahydrofuran-3-yloxy]benzamideYield 68%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent2×

Procedure

Oxalyl chloride (1.9 mL, 22.2 mmol) and DMF (1 drop) were added to a solution of 3-[(phenylmethyl)oxy]-5-[(3S)-tetrahydrofuran-3-yloxy]benzoic acid (5.8 g, 18.5 mmol) in DCM (100 mL) and the mixture stirred at RT for 16 hours. The mixture was evaporated in vacuo to a residue which was redissolved in DCM (25 mL) and added to a stirred mixture of 2-amino-5-methylpyrazine (2.22 g, 20.35 mmol) and pyridine (1.81 mL, 22.2 mmol) in DCM (100 mL) at 5° C.-10° C. The mixture was stirred at RT for 18 hours, the DCM evaporated in vacuo to give a residue which was partitioned between water (50 mL) and ethyl acetate (125 mL). The organic layer was washed with brine, dried (MgSO4) and evaporated to a residue which was chromatographed on silica, eluting with 60% ethyl acetate in isohexane, to give the desired material (5.1 g). 1H NMR δ (CDCl3): 2.1-2.2 (m, 2H), 2.5 (s, 3H), 3.8-3.95 (m, 4H), 4.9 (m, 1H), 5.0 (s, 2H), 6.6 (s, 1H), 6.95 (s, 1H), 7.05 (s, 1H), 7.35 (m, 5H), 8.05 (s, 1H), 8.3 (s, 1H), 9.5 (s, 1H); m/z 406 (M+H)+.

Workup

  1. customThe mixture was evaporated in vacuo to a residue which
  2. dissolutionwas redissolved in DCM (25 mL)
  3. stirringThe mixture was stirred at RT for 18 hours
  4. customthe DCM evaporated in vacuo
  5. customto give a residue which
  6. customwas partitioned between water (50 mL) and ethyl acetate (125 mL)
  7. washThe organic layer was washed with brine
  8. dry with materialdried (MgSO4)
  9. customevaporated to a residue which
  10. customwas chromatographed on silica
  11. washeluting with 60% ethyl acetate in isohexane

Sources & evidence

ORD record
ord-b5e11a45ead644c9ae5297b4bcb52f61
Source dataset
uspto-grants-2011_05
Patent number
US07943607B2

Reaction notes

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