Pyridine → HCID 117642556, compound

HRID 1507730Notes

Reaction equation

HRID 1507730 reaction equation
C(Cl)([C:3](Cl)=[O:4])=O.[CH2:7]([O:14][C:15]1[C:19]([O:20][CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)=[C:18]([C:28](=[O:32])[N:29](C)[CH3:30])[N:17]([C:33]2[CH:38]=[CH:37][C:36]([O:39][CH3:40])=[CH:35][CH:34]=2)[C:16]=1[C:41]([O-])=[O:42])[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.[CH2:44]([NH+:46](CC)[CH2:47]C)C.N1C=CC=CC=1>C(Cl)Cl.CN(C=O)C.O>[CH2:21]([O:20][C:19]1[C:15]([O:14][CH2:7][C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)=[C:16]([C:41]([N:46]([CH3:47])[CH3:44])=[O:42])[N:17]([C:33]2[CH:34]=[CH:35][C:36]([O:39][CH3:40])=[CH:37][CH:38]=2)[C:18]=1[C:28]([N:29]([O:4][CH3:3])[CH3:30])=[O:32])[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1

Participants

7

Reactant 3

HCID 1049PyridineHCID 65578Oxalyl chlorideHCID 89610615HCID 89610615, compound

Product 1

HCID 117642556HCID 117642556, compoundYield 29%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Procedure

(COCl)2 (560 μL, 6.39 mmol) was added dropwise to a stirred solution of 3,4-bis(benzyloxy)-5-(dimethylcarbamoyl)-1-(4-methoxyphenyl)-1H-pyrrole-2-carboxylic acid (7) (1.6 g, 3.20 mmol) in DCM (20 mL) at 0° C., followed by 2 drops of DMF. The reaction mixture was stirred at RT for 5 h, concentrated in vacuo and the resulting residue was dissolved in DCM (15 mL). N,O-dimethylhydroxylamine was added (215 mg, 3.52 mmol) followed by pyridine (620 μL, 7.67 mmol), and the reaction allowed to stir at RT for 18 h. The mixture was diluted with DCM (25 mL) and water (50 mL), the organic layer was separated and washed with water (2×25 mL), brine (25 mL), dried (MgSO4), filtered and concentrated in vacuo. The product was purified by silica gel chromatography (40 g, 0-80% EtOAc in isohexane) to afford 3,4-bis(benzyloxy)-N2-methoxy-1-(4-methoxyphenyl)-N2,N5,N5-trimethyl-1H-pyrrole-2,5-dicarboxamide (33) (505 mg, 22%) as a colourless oil. m/z 544 (M+H)+ (ES+).

Workup

  1. concentrationconcentrated in vacuo
  2. dissolutionthe resulting residue was dissolved in DCM (15 mL)
  3. additionN,O-dimethylhydroxylamine was added (215 mg, 3.52 mmol)
  4. stirringto stir at RT for 18 h
  5. customthe organic layer was separated
  6. washwashed with water (2×25 mL), brine (25 mL)
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe product was purified by silica gel chromatography (40 g, 0-80% EtOAc in isohexane)

Sources & evidence

ORD record
ord-6795b49bb9d349daa4b75417eb06291c
Source dataset
uspto-grants-2015_12
Patent number
US09221756B2

Reaction notes

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