Oxalyl chloride → HCID 86732140, compound

HRID 930313Notes

Reaction equation

HRID 930313 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]([CH3:12])[C:6]([C:9]([OH:11])=O)=[N:7][CH:8]=1)#[N:2].C(Cl)(=O)C(Cl)=O.[NH2:19][C:20]1[N:25]=[C:24]([C@:26]2([CH3:44])[CH2:31][C@@H:30]([C:32]([F:35])([F:34])[F:33])[O:29][C:28]([NH:36][C:37](=[O:43])[O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[N:27]2)[C:23]([F:45])=[CH:22][CH:21]=1.C(N(CC)C(C)C)(C)C.C(C1C=C(C)C(C(Cl)=O)=NC=1)#N>C(Cl)Cl.C([O-])(O)=O.[Na+].CN(C=O)C>[C:1]([C:3]1[CH:4]=[C:5]([CH3:12])[C:6]([C:9]([NH:19][C:20]2[N:25]=[C:24]([C@:26]3([CH3:44])[CH2:31][C@@H:30]([C:32]([F:35])([F:33])[F:34])[O:29][C:28]([NH:36][C:37](=[O:43])[O:38][C:39]([CH3:40])([CH3:42])[CH3:41])=[N:27]3)[C:23]([F:45])=[CH:22][CH:21]=2)=[O:11])=[N:7][CH:8]=1)#[N:2]

Participants

9

Reactant 5

HCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 666658465-Cyano-3-methylpyridine-2-carboxylic acid2×HCID 86732135HCID 86732135, compoundHCID 86732141HCID 86732141, compound

Product 1

HCID 86732140HCID 86732140, compoundYield 48%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×HCID 516892Sodium BicarbonateSolvent

Procedure

To a solution of 5-cyano-3-methylpicolinic acid (intermediate 16, 0.050 g, 0.308 mmol) in DCM (2.5 mL) was added oxalyl chloride (0.040 mL, 0.463 mmol) and a drop of DMF. The reaction mixture was stirred for 30 min at room temperature. The reaction mixture was concentrated under reduced pressure and the residue was dissolved in DCM (1 mL). A flask was charged with a solution of tert-butyl ((4S,6S)-4-(6-amino-3-fluoropyridin-2-yl)-4-methyl-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-yl)carbamate (7k, 0.080 g, 0.204 mmol) and N,N-diisopropylethylamine (0.142 mL, 0.816 mmol, Aldrich) in DCM (2 mL). The solution of 5-cyano-3-methylpicolinoyl chloride was added and the reaction mixture was stirred at room temperature for 30 min, diluted with aqueous saturated NaHCO3 solution and extracted with EtOAc. The organic extract was washed with brine and dried over Na2SO4. The solution was concentrated under reduced pressure. The crude material was purified by silica gel chromatography (gradient of 5-50% EtOAc in hexane) to afford the title compound as a white solid (52 mg, 48% yield). MS m/z=537 [M+H]+. Calculated for C24H24F4N6O4: 536.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. dissolutionthe residue was dissolved in DCM (1 mL)
  3. stirringthe reaction mixture was stirred at room temperature for 30 min
  4. extractionextracted with EtOAc
  5. extractionThe organic extract
  6. washwas washed with brine
  7. dry with materialdried over Na2SO4
  8. concentrationThe solution was concentrated under reduced pressure
  9. customThe crude material was purified by silica gel chromatography (gradient of 5-50% EtOAc in hexane)

Sources & evidence

ORD record
ord-103681221a1e403fb59450e37ac79cf4
Source dataset
uspto-grants-2016_03
Patent number
US09296734B2

Reaction notes

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