Hydrochloric Acid → HCID 66749253, compound

HRID 2402037Notes

Reaction equation

HRID 2402037 reaction equation
[CH2:1]([NH:4][C:5]([C:7]1[S:11][C:10]([C:12]2[CH:17]=[CH:16][N:15]=[CH:14][CH:13]=2)=[N:9][C:8]=1[CH2:18][C:19]1[CH:24]=[CH:23][C:22]([Cl:25])=[CH:21][CH:20]=1)=O)[CH:2]=[CH2:3].P(Cl)(Cl)(Cl)(Cl)Cl.Cl.O1CCOCC1.CO[CH:41](OC)[CH2:42][NH2:43]>C(Cl)Cl>[CH2:1]([N:4]1[CH:41]=[CH:42][N:43]=[C:5]1[C:7]1[S:11][C:10]([C:12]2[CH:17]=[CH:16][N:15]=[CH:14][CH:13]=2)=[N:9][C:8]=1[CH2:18][C:19]1[CH:24]=[CH:23][C:22]([Cl:25])=[CH:21][CH:20]=1)[CH:2]=[CH2:3]

Participants

7

Reactant 5

HCID 313Hydrochloric Acid2×HCID 24819Phosphorus pentachlorideHCID 312751,4-Dioxane2×HCID 89728Aminoacetaldehyde dimethyl acetalHCID 66748238HCID 66748238, compound

Product 1

HCID 66749253HCID 66749253, compoundYield 62.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
60 °C

Procedure

To a solution of N-allyl-4-(4-chlorobenzyl)-2-(pyridin-4-yl)thiazole-5-carboxamide (150 mg, 0.406 mmol) in DCM (2.64 mL) was added phosphorus pentachloride (101 mg, 0.485 mmol) and 4 M hydrochloric acid in 1,4-dioxane (0.0154 mL, 0.0614 mmol) and the mixture was heated to 60° C. for 1.5 h. The reaction was cooled to room temperature and aminoacetaldehyde dimethyl acetal (0.486 mL, 4.46 mmol) was added. The resulting mixture was heated at 60° C. for 2 h. The mixture was cooled to room temperature, diluted with DCM (10 mL), washed with water (2×2 mL) and brine (2 mL), dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was taken up in DCM (3.0 mL) and 4 M hydrochloric acid in 1,4-dioxane (0.608 mL, 2.43 mmol) was added and the mixture was stirred at 60° C. overnight. The reaction was cooled and concentrated in vacuo. The residue was taken up in ethyl acetate (20 mL) and saturated sodium bicarbonate (5 mL). The layers were separated and the aqueous layer was extracted with ethyl acetate (5 mL). The combined organic layers were dried over MgSO4, filtered, and concentrated in vacuo. The residue was purified by silica gel chromatography (methanol/DCM=0/100→5/95) to give 99 mg of the title compound (62% yield). LC/MS (FA) ES+ 393. 1H NMR (300 MHz, CDCl3) δ: 8.72-8.70 (m, 2H), 7.80-7.72 (m, 2H), 7.26 (m, 1H), 7.22-7.14 (m, 4H), 7.06 (m, 1H), 5.84-5.71 (m, 1H), 5.23-5.19 (m, 1H), 5.01-4.96 (m, 1H), 4.38-4.34 (m, 2H), 4.20 (s, 2H).

Workup

  1. temperatureThe reaction was cooled to room temperature
  2. temperatureThe resulting mixture was heated at 60° C. for 2 h
  3. temperatureThe mixture was cooled to room temperature
  4. washwashed with water (2×2 mL) and brine (2 mL)
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. temperatureThe reaction was cooled
  9. concentrationconcentrated in vacuo
  10. customThe layers were separated
  11. extractionthe aqueous layer was extracted with ethyl acetate (5 mL)
  12. dry with materialThe combined organic layers were dried over MgSO4
  13. filtrationfiltered
  14. concentrationconcentrated in vacuo
  15. customThe residue was purified by silica gel chromatography (methanol/DCM=0/100→5/95)

Sources & evidence

ORD record
ord-19ba7e419cf34efd914dc54306c8755b
Source dataset
uspto-grants-2014_08
Patent number
US08796271B2

Reaction notes

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