Pyridine → HCID 178425946, compound

HRID 1434842Notes

Reaction equation

HRID 1434842 reaction equation
C(Cl)(=O)C(Cl)=O.[C:7]([O:11][C:12]([NH:14][C@@H:15]1[CH2:20][CH2:19][C@H:18]([O:21][C:22]2[CH:30]=[C:29]([CH3:31])[CH:28]=[CH:27][C:23]=2[C:24](O)=[S:25])[CH2:17][CH2:16]1)=[O:13])([CH3:10])([CH3:9])[CH3:8].N1C=CC=CC=1.[NH2:38][C:39]1[C:40]([C:45]([NH:47][C:48]2[CH:53]=[CH:52][C:51]([Cl:54])=[CH:50][N:49]=2)=[O:46])=[N:41][CH:42]=[CH:43][CH:44]=1>CN(C=O)C.C(Cl)Cl>[C:7]([O:11][C:12]([NH:14][C@@H:15]1[CH2:16][CH2:17][C@H:18]([O:21][C:22]2[CH:30]=[C:29]([CH3:31])[CH:28]=[CH:27][C:23]=2[C:24]([NH:38][C:39]2[C:40]([C:45]([NH:47][C:48]3[CH:53]=[CH:52][C:51]([Cl:54])=[CH:50][N:49]=3)=[O:46])=[N:41][CH:42]=[CH:43][CH:44]=2)=[S:25])[CH2:19][CH2:20]1)=[O:13])([CH3:8])([CH3:9])[CH3:10]

Participants

7

Reactant 4

HCID 1049Pyridine2×HCID 65578Oxalyl chlorideHCID 115578513-amino-N-(5-chloropyridin-2-yl)pyridine-2-carboxamideHCID 178425921HCID 178425921, compound

Product 1

HCID 178425946HCID 178425946, compoundYield 83.7%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent3×

Procedure

A solution of oxalyl chloride (1.6 mL, 18 mmol) and CH2Cl2 (12 mL) was added over 7 min to a solution of 2-(cis-4-tert-butoxycarbonylaminocyclohexyloxy)-4-methylthiobenzoic acid (7.00 g, 18.3 mmol), DMF (71 μL, 0.92 mmol), pyridine (1.5 mL, 18.9 mmol) and CH2Cl2 (62 mL) cooled in an ice bath. The bath was removed after the addition was complete. After 1 h the resulting yellow solution was added dropwise over 35 min to a slurry of 3-amino-N-(5-chloropyridin-2-yl)-pyridine-2-carboxamide (4.48 g, 18.0 mmol), pyridine (2.2 mL, 28 mmol), and CH2Cl2 (52 mL) cooled in an ice bath. At the end of the addition the bath was removed, and the mixture became homogeneous over 10-12 min, but became opaque again within 2 h. After 4 h the mixture was poured into satd citric acid (100 mL) and water (50 mL). The organic layer was extracted with a 1:1.5 solution of satd citric acid/water (125 mL), and the combined aqueous layers were back-extracted with CH2Cl2 (50 mL). The combined organic layers were rinsed with 25% NaCl (50 mL), heated to reflux on a steam bath to dissolve residual solids, dried (Na2SO4) and concentrated to a bright yellow solid (12.30 g) which was purified by flash chromatography (5% EtOAc/CH2Cl2, followed by 10% EtOAc/CH2Cl2) to provide 8.98 g (80%) of white foam.

Workup

  1. temperaturecooled in an ice bath
  2. customThe bath was removed
  3. additionafter the addition
  4. temperaturecooled in an ice bath
  5. additionAt the end of the addition the bath
  6. customwas removed
  7. customagain within 2 h
  8. additionAfter 4 h the mixture was poured into satd citric acid (100 mL) and water (50 mL)
  9. extractionThe organic layer was extracted with a 1:1.5 solution of satd citric acid/water (125 mL)
  10. extractionthe combined aqueous layers were back-extracted with CH2Cl2 (50 mL)
  11. washThe combined organic layers were rinsed with 25% NaCl (50 mL)
  12. temperatureheated
  13. temperatureto reflux on a steam bath
  14. dissolutionto dissolve residual solids
  15. dry with materialdried (Na2SO4)
  16. concentrationconcentrated to a bright yellow solid (12.30 g) which
  17. customwas purified by flash chromatography (5% EtOAc/CH2Cl2, followed by 10% EtOAc/CH2Cl2)

Sources & evidence

ORD record
ord-492c003ad9ac4f56a337633944d015b9
Source dataset
uspto-grants-2009_11
Patent number
US07615568B2

Reaction notes

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