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

HRID 20518
Notes
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Reaction equation

HRID 20518 reaction equation
[CH3:1][C@H:2]([O:6][C:7]1[CH:8]=[C:9]([CH:13]=[C:14]([O:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH:15]=1)[C:10]([OH:12])=O)[CH2:3][O:4][CH3:5].C(Cl)(=O)C(Cl)=O.[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>[CH3:1][C@H:2]([O:6][C:7]1[CH:8]=[C:9]([CH:13]=[C:14]([O:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH:15]=1)[C:10]([NH:30][C:31]1[CH:36]=[N:35][C:34]([CH3:37])=[CH:33][N:32]=1)=[O:12])[CH2:3][O:4][CH3:5]
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

7

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 98.2%

Reagents, catalysts & solvents

2
HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent2×

Procedure

DMF (2 drops) was added to a solution of 3-{[(1S)-1-methyl-2-(methyloxy)ethyl]oxy}-5-[(phenylmethyl)oxy]benzoic acid (6.0 g, 19.0 mmol) and oxalyl chloride (1.99 mL, 22.8 mmol) in DCM (40 mL) The mixture was stirred at ambient temperature for 2 hours and the DCM and excess oxalyl chloride evaporated in vacuo. The residual acid chloride was dissolved in DCM and added dropwise to 2-amino-5 methylpyrazine [Tett lett. 2002, 9287-90] (2.28 g, 19.8 mmol) and pyridine (2.56 mL, 38 mmol) in DCM (40 mL), at 0° C. Stirred at ambient temperature for 24 hours. The DCM was evaporated in vacuo, and the residue partitioned between ethyl acetate (100 mL) and 1N hydrochloric acid (50 mL). The ethyl acetate layer was washed sequentially with saturated aqueous sodium hydrogen carbonate (50 mL) and brine (50 mL), dried (MgSO4), and evaporated in vacuo. The residue was chromatographed on silica, eluting with a gradient of 30-100% ethyl acetate in isohexane, to give the desired compound (7.6 g)

Workup

  1. customthe DCM and excess oxalyl chloride evaporated in vacuo
  2. dissolutionThe residual acid chloride was dissolved in DCM
  3. stirringStirred at ambient temperature for 24 hours
  4. customThe DCM was evaporated in vacuo
  5. customthe residue partitioned between ethyl acetate (100 mL) and 1N hydrochloric acid (50 mL)
  6. washThe ethyl acetate layer was washed sequentially with saturated aqueous sodium hydrogen carbonate (50 mL) and brine (50 mL)
  7. dry with materialdried (MgSO4)
  8. customevaporated in vacuo
  9. customThe residue was chromatographed on silica
  10. washeluting with a gradient of 30-100% ethyl acetate in isohexane

Sources & evidence

ORD record
ord-845e1b07085443ca9b53bab487b5f22b
Source dataset
uspto-grants-2010_06
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US07745475B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes