Morpholine → HCID 59519519, compound

HRID 1622007Notes

Reaction equation

HRID 1622007 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([NH2:9])[C:5]([Cl:8])=[N:6][CH:7]=1.[NH:10]1[CH2:15][CH2:14][O:13][CH2:12][CH2:11]1.[S:16](Cl)(Cl)(=[O:18])=[O:17].CCOC(C)=O>N1C=CC=CC=1.CN(C)C1C=CN=CC=1>[Br:1][C:2]1[CH:3]=[C:4]([NH:9][S:16]([N:10]2[CH2:15][CH2:14][O:13][CH2:12][CH2:11]2)(=[O:18])=[O:17])[C:5]([Cl:8])=[N:6][CH:7]=1

Participants

7

Reactant 4

HCID 8083MorpholineHCID 8857Ethyl AcetateHCID 24648Sulfuryl chlorideHCID 218583543-Amino-5-bromo-2-chloropyridine

Product 1

HCID 59519519HCID 59519519, compoundYield 46.5%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 1049PyridineSolvent

Conditions

Temperature
-30 °C

Procedure

To a solution of 5-bromo-2-chloropyridin-3-amine (Small Molecules, Inc.) (1.000 g, 4.82 mmol) in pyridine (8 mL) was added 4-dimethylaminopyridine (Aldrich) (0.147 g, 1.205 mmol) and morpholine (Aldrich) (0.546 mL, 6.27 mmol). The reaction mixture was cooled to −30° C. and allowed the mixture to stir for 10 minutes. Then sulfuryl chloride (Aldrich) (0.586 mL, 7.23 mmol) was added dropwise into the reaction mixture. After the addition, the mixture was allowed to stir an additional 20 min. in the cooling bath then was allowed to warm to rt and continued to stir under N2 for 20 h. The reaction mixture was poured into the beaker which filled with EtOAc (50 mL) and hand stirred for 10 minutes. The organic layer was decanted into a round-bottom flask. The original mixture (black paste) was dissolved into DCM (3 ml) followed by adding EtOAc (20 mL) and hand stirred for 10 min and decanted to the same round-bottom flask that was mentioned earlier. The combined organic layers were concentrated in-vacuo. The crude product was purified by column chromatography (80 g, 10% to 20% acetone in hexanes) to obtain the desired product as light yellow solid (800 mg). MS (ESI pos. ion) m/z: 356.8. 1H NMR (300 MHz, CDCl3) δ ppm 3.15-3.41 (m, 4H) 3.60-3.83 (m, 4H) 6.79 (br. s., 1H) 8.08 (s, 1H) 8.23 (s, 1H).

Workup

  1. additionAfter the addition
  2. stirringto stir an additional 20 min. in the cooling bath
  3. temperatureto warm to rt
  4. stirringto stir under N2 for 20 h
  5. additionThe reaction mixture was poured into the beaker which
  6. stirringstirred for 10 minutes
  7. customThe organic layer was decanted into a round-bottom flask
  8. dissolutionThe original mixture (black paste) was dissolved into DCM (3 ml)
  9. additionby adding EtOAc (20 mL) and hand
  10. stirringstirred for 10 min
  11. customdecanted to the same round-bottom flask that
  12. concentrationThe combined organic layers were concentrated in-vacuo
  13. customThe crude product was purified by column chromatography (80 g, 10% to 20% acetone in hexanes)

Sources & evidence

ORD record
ord-61efc31fce544eb8b4d1ef253ab2612e
Source dataset
uspto-grants-2014_07
Patent number
US08772480B2

Reaction notes

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