Pyridine → HCID 10203446, compound

HRID 890524Notes

Reaction equation

HRID 890524 reaction equation
CN(C)C=O.C(Cl)(=O)C(Cl)=O.[CH3:12][O:13][C:14]1[CH:19]=[CH:18][C:17]([N:20]2[C:24]3[C:25](=[O:42])[N:26]([C:29]4[CH:34]=[CH:33][C:32]([N:35]5[CH:40]=[CH:39][CH:38]=[CH:37][C:36]5=[O:41])=[CH:31][CH:30]=4)[CH2:27][CH2:28][C:23]=3[C:22]([C:43]([NH2:45])=O)=[N:21]2)=[CH:16][CH:15]=1.N1C=CC=CC=1>CC#N>[CH3:12][O:13][C:14]1[CH:19]=[CH:18][C:17]([N:20]2[C:24]3[C:25](=[O:42])[N:26]([C:29]4[CH:34]=[CH:33][C:32]([N:35]5[CH:40]=[CH:39][CH:38]=[CH:37][C:36]5=[O:41])=[CH:31][CH:30]=4)[CH2:27][CH2:28][C:23]=3[C:22]([C:43]#[N:45])=[N:21]2)=[CH:16][CH:15]=1

Participants

6

Reactant 4

HCID 1049PyridineHCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 10226178HCID 10226178, compound

Product 1

HCID 10203446HCID 10203446, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To dimethylformamide (0.2 mL, 2.6 mmol) in CH3CN (20 mL) at 0° C. was added oxalyl chloride (0.23 mL, 2.6 mmol) and the reaction was stirred 0.5 h. The amide from Example 27 was added and the reaction was stirred cold 0.5 h. Pyridine (0.37 mL, 4.6 mmol) was added and the reaction was allowed to warm to rt and stirred for 24 h. The solvent was stripped, the residue was partitioned between CH2Cl2 and 1N HCl, and the layers separated. The aqueous layer was basified with 1N NaOH and extracted with EtOAc. The organic layers were combined and dried (MgSO4). Purification by chromatography on silica gel using 3% MeOH in CH2Cl2 and recrystallization from CH2Cl2/hexanes afforded 117 mg (89%); 1H NMR (CDCl3) δ 7.50 (d,j=8.8 Hz, 2H), 7.44 (m, 5H), 7.31 (m, 1H), 6.97 (d,j=9.2 Hz, 2H), 6.71 (d,j=9.5 Hz, 2H), 6.28 (m, 1H), 4.24 (t,j=6.6 Hz, 2H), 3.85 (s, 3H), 3.24 (t,j=6.6 Hz, 2H) ppm; LRMS (M+H)+ 438.4.

Workup

  1. stirringthe reaction was stirred cold 0.5 h
  2. stirringstirred for 24 h
  3. customthe residue was partitioned between CH2Cl2 and 1N HCl
  4. customthe layers separated
  5. extractionextracted with EtOAc
  6. dry with materialdried (MgSO4)
  7. customPurification by chromatography
  8. customon silica gel using 3% MeOH in CH2Cl2 and recrystallization from CH2Cl2/hexanes
  9. customafforded 117 mg (89%)

Sources & evidence

ORD record
ord-5ee4a19832de4a528cee71b1da9f38fe
Source dataset
uspto-grants-2006_02
Patent number
US06995172B2

Reaction notes

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