Water → HCID 90077545, compound

HRID 2203264Notes

Reaction equation

HRID 2203264 reaction equation
[H-].[Na+].[Cl:3][C:4]1[N:5]=[C:6]2[C:11](=[CH:12][CH:13]=1)[N:10]=[CH:9][C:8]([C:14]([NH:16][CH2:17][C:18]1[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][CH:19]=1)=[O:15])=[C:7]2[NH:26][C:27]1[CH:32]=[CH:31][C:30]([C:33]([C:36]#[N:37])([CH3:35])[CH3:34])=[CH:29][CH:28]=1.Cl[C:39](OCC)=[O:40].O>CN(C=O)C>[Cl:3][C:4]1[CH:13]=[CH:12][C:11]2[N:10]=[CH:9][C:8]3[C:14](=[O:15])[N:16]([CH2:17][C:18]4[CH:19]=[CH:20][C:21]([O:24][CH3:25])=[CH:22][CH:23]=4)[C:39](=[O:40])[N:26]([C:27]4[CH:28]=[CH:29][C:30]([C:33]([CH3:34])([CH3:35])[C:36]#[N:37])=[CH:31][CH:32]=4)[C:7]=3[C:6]=2[N:5]=1

Participants

6

Reactant 4

HCID 962WaterHCID 10928Ethyl chloroformateHCID 24758Sodium hydrideHCID 90077558HCID 90077558, compound

Product 1

HCID 90077545HCID 90077545, compoundYield 46.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
60 °C

Procedure

Sodium hydride (1.0 g, 25 mmol) was suspended in 25 mL DMF. To the resulting mixture was slowly added dropwise a solution of 6-chloro-4-((4-(2-cyanoprop-2-yl)phenyl)amino)-N-(4-methoxybenzyl)-1,5-naphthyridine-3-carboxamide (2.43 g, 5 mmol) in DMF (25 mL) at room temperature. After the completion of the dropwise addition, the resulting mixture was warmed up to 60° C. and reacted for 1 hr. To the reaction mixture was slowly added dropwise ethyl chloroformate (1.36 g, 12.5 mmol) under an ice bath. After the completion of the dropwise addition, the resulting mixture was warmed up to 60° C. and reacted for 16 hrs. The reaction was cooled to room temperature, then slowly poured into water, and extracted with ethyl acetate (3×150 mL). The organic phases were combined, washed with a saturated sodium chloride solution, dried over anhydrous sodium sulfate, and concentrated. The resulting crude product was separated by silicagel column chromatography (EtOAc/PE=0-1/5) to produce a pale yellow solid (1.2 g).

Workup

  1. additionAfter the completion of the dropwise addition
  2. customreacted for 1 hr
  3. additionAfter the completion of the dropwise addition
  4. temperaturethe resulting mixture was warmed up to 60° C.
  5. customreacted for 16 hrs
  6. temperatureThe reaction was cooled to room temperature
  7. extractionextracted with ethyl acetate (3×150 mL)
  8. washwashed with a saturated sodium chloride solution
  9. dry with materialdried over anhydrous sodium sulfate
  10. concentrationconcentrated
  11. customThe resulting crude product was separated by silicagel column chromatography (EtOAc/PE=0-1/5)

Sources & evidence

ORD record
ord-55ed3bb6f93a41cbbb14d35c085e4442
Source dataset
uspto-grants-2016_06
Patent number
US09365572B2

Reaction notes

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