Pyridine → HCID 67289903, compound

HRID 1626402Notes

Reaction equation

HRID 1626402 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][C:14]1[CH:22]=[CH:21][C:17]([C:18](O)=[O:19])=[CH:16][C:15]=1[CH3:23])[O:9][CH2:8][CH2:7][CH:6]2[C:24]([O:26][CH3:27])=[O:25])#[N:2].C(Cl)(=O)C(Cl)=O.[F:34][C:35]([F:44])([F:43])[C:36]1[N:41]=[CH:40][C:39]([NH2:42])=[CH:38][CH:37]=1.N1C=CC=CC=1>C(Cl)Cl.CN(C1C=CN=CC=1)C.O.CN(C=O)C>[C:1]([C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][C:14]1[CH:22]=[CH:21][C:17]([C:18](=[O:19])[NH:42][C:39]3[CH:40]=[N:41][C:36]([C:35]([F:44])([F:34])[F:43])=[CH:37][CH:38]=3)=[CH:16][C:15]=1[CH3:23])[O:9][CH2:8][CH2:7][CH:6]2[C:24]([O:26][CH3:27])=[O:25])#[N:2]

Participants

9

Reactant 4

HCID 1049PyridineHCID 65578Oxalyl chlorideHCID 27377445-Amino-2-(trifluoromethyl)pyridineHCID 670807034-(6-Cyano-4-(methoxycarbonyl)chroman-7-yloxy)-3-methylbenzoic acid

Product 1

HCID 67289903HCID 67289903, compoundYield 68%

Reagents, catalysts & solvents 4

HCID 142844-(Dimethylamino)pyridineCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

4-(6-Cyano-4-(methoxycarbonyl)chroman-7-yloxy)-3-methylbenzoic acid (0.103 g, 0.280 mmol) was dissolved in 4 mL dry DCM at ambient temperature under nitrogen. Oxalyl chloride (0.0489 mL, 0.561 mmol) was added to the reaction followed by 10 μL DMF. The solution was stirred at ambient temperature for 1 hour. The solution was concentrated and the residue was taken up in 4 mL dry DCE. 6-(Trifluoromethyl)pyridin-3-amine (0.136 g, 0.841 mmol), pyridine (0.0567 mL, 0.701 mmol) and DMAP (0.0034 g, 0.0280 mmol) were added and the solution was stirred at ambient temperature overnight. The reaction was poured into water, extracted with ethyl acetate, dried over sodium sulfate, filtered and concentrated. The crude material was purified by silica gel column chromatography, eluting with 30-50% ethyl acetate/hexanes, followed by a second silica gel chromatography eluting with 30% acetone/hexanes to provide the desired product (0.097 g, 68%).

Workup

  1. concentrationThe solution was concentrated
  2. stirringthe solution was stirred at ambient temperature overnight
  3. extractionextracted with ethyl acetate
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude material was purified by silica gel column chromatography
  8. washeluting with 30-50% ethyl acetate/hexanes
  9. washeluting with 30% acetone/hexanes

Sources & evidence

ORD record
ord-95eeeea77e704ca6a5809695d3cfe328
Source dataset
uspto-grants-2014_07
Patent number
US08785445B2

Reaction notes

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