Morpholine → HCID 22641424, compound

HRID 2415490Notes

Reaction equation

HRID 2415490 reaction equation
Cl.[Cl:2][C:3]1[N:8]=[CH:7][C:6]([CH2:9][O:10][C:11]2[CH:20]=[C:19]3[C:14]([C:15]([N:22]4[CH2:26][CH2:25][CH2:24][CH2:23]4)=[CH:16][C:17]([CH3:21])=[N:18]3)=[CH:13][CH:12]=2)=[CH:5][CH:4]=1.[NH:27]1[CH2:32][CH2:31][O:30][CH2:29][CH2:28]1>>[ClH:2].[CH3:21][C:17]1[CH:16]=[C:15]([N:22]2[CH2:26][CH2:25][CH2:24][CH2:23]2)[C:14]2[C:19](=[CH:20][C:11]([O:10][CH2:9][C:6]3[CH:7]=[N:8][C:3]([N:27]4[CH2:32][CH2:31][O:30][CH2:29][CH2:28]4)=[CH:4][CH:5]=3)=[CH:12][CH:13]=2)[N:18]=1

Participants

3

Reactant 2

HCID 8083MorpholineHCID 22641487HCID 22641487, compound

Product 1

HCID 22641424HCID 22641424, compoundYield 20.9%

Procedure

A suspension of 98.5 mg (0.25 mmol) of 7-(6-chloro-pyridin-3-ylmethoxy)-2-methyl-4-pyrrolidin-1-yl-quinoline hydrochloride, product of example 56, in 0.44 ml (5 mmol) of morpholine was heated under nitrogen at 60° C. (oil bath temperature) for 23 h and further 72 h at 100° C. The mixture was cooled to RT and partitioned between EtOAc and water. The organic layer was separated, washed with water, dried over magnesium acetate and concentrated in vacuo. The residue was taken up in ether (20 ml), insoluble material was removed by filtration and the filtrate treated with 0.1 ml of 3 N HCl in MeOH. The solid that precipitated was collected, triturated with ether (5 ml), filtered off by suction, dried in a high vacuum and then applied to a to silica gel column with CH2Cl2/MeOH/NH4OH (19:1:0.05) as eluent. The purified fractions were combined and concentrated in vacuo to a small volume then acidified by adding a few drops of 3 N HCl in MeOH. The solvent was taken off in vacuo to give 23 mg (18%) of the desired 2-methyl-7-(6-morpholin-4-yl-pyridin-3-ylmethoxy)-4-pyrrolidin-1-yl-quinoline hydrochloride as a light yellow solid. ISP mass spectrum, m/e: 405.5 (M+1 calculated for C24H28N4O2: 405).

Workup

  1. customfurther 72 h
  2. customat 100° C
  3. custompartitioned between EtOAc and water
  4. customThe organic layer was separated
  5. washwashed with water
  6. dry with materialdried over magnesium acetate
  7. concentrationconcentrated in vacuo
  8. custominsoluble material was removed by filtration
  9. additionthe filtrate treated with 0.1 ml of 3 N HCl in MeOH
  10. customThe solid that precipitated
  11. customwas collected
  12. customtriturated with ether (5 ml)
  13. filtrationfiltered off by suction
  14. customdried in a high vacuum
  15. concentrationconcentrated in vacuo to a small volume
  16. additionby adding a few drops of 3 N HCl in MeOH

Sources & evidence

ORD record
ord-fa9ed13fd6df45c89ab7481fe24f26e5
Source dataset
uspto-grants-2004_11
Patent number
US06818767B2

Reaction notes

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