Oxalyl chloride → HCID 59507028, compound

HRID 1800610Notes

Reaction equation

HRID 1800610 reaction equation
[Cl:1][C:2]1[C:10]([C:11]([C:14]#[N:15])([CH3:13])[CH3:12])=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=O.C(Cl)(=O)C(Cl)=O.[NH2:22][C:23]1[C:24]([F:46])=[CH:25][C:26]([Cl:45])=[C:27]([CH:44]=1)[O:28][C:29]1[N:34]=[C:33]2[S:35][C:36]([NH:38][C:39]([CH:41]3[CH2:43][CH2:42]3)=[O:40])=[N:37][C:32]2=[CH:31][CH:30]=1.C(=O)([O-])O.[Na+]>O1CCCC1.CN(C)C=O>[Cl:1][C:2]1[C:10]([C:11]([C:14]#[N:15])([CH3:13])[CH3:12])=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([NH:22][C:23]1[CH:44]=[C:27]([O:28][C:29]2[N:34]=[C:33]3[S:35][C:36]([NH:38][C:39]([CH:41]4[CH2:42][CH2:43]4)=[O:40])=[N:37][C:32]3=[CH:31][CH:30]=2)[C:26]([Cl:45])=[CH:25][C:24]=1[F:46])=[O:6]

Participants

7

Reactant 4

HCID 65578Oxalyl chlorideHCID 516892Sodium BicarbonateHCID 668102752-Chloro-3-(1-cyano-1-methylethyl)benzoic acidHCID 86646044N-[5-(5-amino-2-chloro-4-fluorophenoxy)[1,3]thiazolo[5,4-b]pyridin-2-yl]cyclopropanecarboxamide

Product 1

HCID 59507028HCID 59507028, compoundYield 51.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

2-Chloro-3-(1-cyano-1-methylethyl)benzoic acid (71.6 mg, 0.320 mmol) produced in Example C61(v) was dissolved in tetrahydrofuran (2 mL)/N,N-dimethylformamide (40 μL), oxalyl chloride (36 μL, 0.420 mmol) was added, and the mixture was stirred at room temperature for 45 min. The reaction mixture was concentrated under reduced pressure, and the residue was dissolved in N,N-dimethylacetamide (2 mL). N-[5-(5-Amino-2-chloro-4-fluorophenoxy)[1,3]thiazolo[5,4-b]pyridin-2-yl]cyclopropanecarboxamide (79.8 mg, 0.211 mmol) was added, and the mixture was stirred at room temperature for 15 hr. To the reaction mixture was added aqueous sodium hydrogen carbonate solution (5 mL), and the mixture was extracted with ethyl acetate (5 mL×4). The organic layer was washed successively with water (5 mL) and saturated brine (5 mL), dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate=80/20→10/90), and crystallized from diisopropyl ether/ethyl acetate to give the title compound (63.4 mg, 51%) as white crystals.

Workup

  1. additionwas added
  2. concentrationThe reaction mixture was concentrated under reduced pressure
  3. dissolutionthe residue was dissolved in N,N-dimethylacetamide (2 mL)
  4. stirringthe mixture was stirred at room temperature for 15 hr
  5. extractionthe mixture was extracted with ethyl acetate (5 mL×4)
  6. washThe organic layer was washed successively with water (5 mL) and saturated brine (5 mL)
  7. dry with materialdried over anhydrous magnesium sulfate
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate=80/20→10/90)
  10. customcrystallized from diisopropyl ether/ethyl acetate

Sources & evidence

ORD record
ord-7be810847f684497a424f30321a1c442
Source dataset
uspto-grants-2013_01
Patent number
US08344135B2

Reaction notes

Loading…