Morpholine → 4,8-Dichloro-2-(2-isopropyl-thiazol-4-yl)-7-(2-morpholin-4-yl-ethoxy)-quinoline

HRID 1422527Notes

Reaction equation

HRID 1422527 reaction equation
[Cl:1][C:2]1[C:11]2[C:6](=[C:7]([Cl:19])[C:8]([O:12][CH2:13][CH:14](OC)OC)=[CH:9][CH:10]=2)[N:5]=[C:4]([C:20]2[N:21]=[C:22]([CH:25]([CH3:27])[CH3:26])[S:23][CH:24]=2)[CH:3]=1.[NH:28]1[CH2:33][CH2:32][O:31][CH2:30][CH2:29]1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>CC(O)=O.Cl.CCOC(C)=O.C(Cl)Cl>[Cl:1][C:2]1[C:11]2[C:6](=[C:7]([Cl:19])[C:8]([O:12][CH2:13][CH2:14][N:28]3[CH2:33][CH2:32][O:31][CH2:30][CH2:29]3)=[CH:9][CH:10]=2)[N:5]=[C:4]([C:20]2[N:21]=[C:22]([CH:25]([CH3:26])[CH3:27])[S:23][CH:24]=2)[CH:3]=1

Participants

9

Reactant 3

HCID 8083MorpholineHCID 5049666Sodium triacetoxyborohydrideHCID 582896314,8-Dichloro-7-(2,2-dimethoxy-ethoxy)-2-(2-isopropyl-thiazol-4-yl)-quinoline

Product 1

HCID 582895734,8-Dichloro-2-(2-isopropyl-thiazol-4-yl)-7-(2-morpholin-4-yl-ethoxy)-quinolineYield 86%

Reagents, catalysts & solvents 5

HCID 176Acetic AcidCatalystHCID 176Acetic AcidSolventHCID 313Hydrochloric AcidSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

4,8-Dichloro-7-(2,2-dimethoxy-ethoxy)-2-(2-isopropyl-thiazol-4-yl)-quinoline (250 mg, 0.565 mmol) was dissolved in AcOH (5.0 mL) and 2N HCl(aq). The reaction mixture was placed in a 60° C. oil bath and stirred for 1 h. Remove solvent under reduced pressure. The crude material was taken up in EtOAc and washed with ½ sat NaHCO3(aq). Organics were dried over Na2SO4, filtered and was concentrated. The crude material was then taken up in CH2Cl2. Morpholine (77 μL, 0.88 mmol) was added to the reaction mixture and stirred for 15 min. NaBH(OAc)3 (161 mg, 0.761 mmol) and AcOH (1 drop) were added and the reaction was monitored by LC/MS. After 5 min the reaction was determined to be complete. The mixture was diluted with DCM and washed with ½ sat brine, dried with Na2SO4, filtered and was concentrated. 4,8-dichloro-2-(2-isopropyl-thiazol-4-yl)-7-(2-morpholin-4-yl-ethoxy)-quinoline (218 mg, 86%) was isolated by silica gel chromatography as a yellow solid.

Workup

  1. customwas placed in a 60° C.
  2. washwashed with ½
  3. dry with materialOrganics were dried over Na2SO4
  4. filtrationfiltered
  5. concentrationwas concentrated
  6. stirringstirred for 15 min
  7. waitAfter 5 min the reaction was determined
  8. washwashed with ½
  9. dry with materialdried with Na2SO4
  10. filtrationfiltered
  11. concentrationwas concentrated

Sources & evidence

ORD record
ord-d9c65f760be242fc838fe0803f9a3c99
Source dataset
uspto-grants-2015_01
Patent number
US08927484B2

Reaction notes

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