Cyanoacetic acid → HCID 90427540, compound

HRID 2279053Notes

Reaction equation

HRID 2279053 reaction equation
[C:1]([CH2:3][C:4]([OH:6])=O)#[N:2].C(Cl)(=O)C(Cl)=O.[NH2:13][C:14]1[CH:19]=[C:18]([O:20][C:21]2[C:26]([Cl:27])=[CH:25][C:24]([NH:28][C:29]([N:31]3[CH2:35][CH2:34][N:33]([CH:36]4[CH2:41][CH2:40][O:39][CH2:38][CH2:37]4)[C:32]3=[O:42])=[O:30])=[C:23]([F:43])[CH:22]=2)[CH:17]=[CH:16][N:15]=1>C(Cl)Cl.CN(C=O)C.N1C=CC=CC=1>[Cl:27][C:26]1[C:21]([O:20][C:18]2[CH:17]=[CH:16][N:15]=[C:14]([NH:13][C:4](=[O:6])[CH2:3][C:1]#[N:2])[CH:19]=2)=[CH:22][C:23]([F:43])=[C:24]([NH:28][C:29]([N:31]2[CH2:35][CH2:34][N:33]([CH:36]3[CH2:41][CH2:40][O:39][CH2:38][CH2:37]3)[C:32]2=[O:42])=[O:30])[CH:25]=1

Participants

7

Reactant 3

HCID 9740Cyanoacetic acidHCID 65578Oxalyl chlorideHCID 90426712HCID 90426712, compound

Product 1

HCID 90427540HCID 90427540, compoundYield 49.7%

Reagents, catalysts & solvents 3

HCID 1049PyridineSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

A RT solution of cyanoacetic acid (0.500 g, 5.88 mmol) in DCM (20 mL) and DMF (0.1 mL) was treated drop-wise with oxalyl chloride (1.1 mL, 12.52 mmol), stirred at RT for 2.5 h, then concentrated to dryness. The residue was dissolved in DCM (5 mL), added drop-wise to a 0° C. solution of N-(4-((2-aminopyridin-4-yl)oxy)-5-chloro-2-fluorophenyl)-2-oxo-3-(tetrahydro-2H-pyran-4-yl)imidazolidine-1-carboxamide (0.210 g, 0.467 mmol) in pyridine (10 mL), stirred for 0.5 h, then concentrated to dryness. The residue was dissolved in DCM, washed with satd. NaHCO3 and the aqueous layer extracted with EtOAc (3×). The combined organics were dried over Na2SO4, concentrated to dryness and purified twice via silica gel chromatography (MeOH/DCM, then MeOH/EtOAc). The material was further purified via silica gel chromatography (MeOH/DCM) to afford N-(5-chloro-4-((2-(2-cyanoacetamido)pyridin-4-yl)oxy)-2-fluorophenyl)-2-oxo-3-(tetrahydro-2H-pyran-4-yl)imidazolidine-1-carboxamide (120 mg, 49%). MS (ESI) m/z: (M+H+): 516.8.

Workup

  1. concentrationconcentrated to dryness
  2. dissolutionThe residue was dissolved in DCM (5 mL)
  3. stirringstirred for 0.5 h
  4. concentrationconcentrated to dryness
  5. dissolutionThe residue was dissolved in DCM
  6. washwashed with satd
  7. extractionNaHCO3 and the aqueous layer extracted with EtOAc (3×)
  8. dry with materialThe combined organics were dried over Na2SO4
  9. concentrationconcentrated to dryness
  10. custompurified twice via silica gel chromatography (MeOH/DCM
  11. customThe material was further purified via silica gel chromatography (MeOH/DCM)

Sources & evidence

ORD record
ord-c4276d18f83647bfa56a9e448b286b38
Source dataset
uspto-grants-2015_09
Patent number
US09133183B2

Reaction notes

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