Morpholine → HCID 23117179, compound

HRID 900693Notes

Reaction equation

HRID 900693 reaction equation
[NH:1]1[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1.Cl.[Cl:30][C:31]1[C:32]([N:59]2[CH2:64][CH2:63][CH:62]([C:65](O)=[O:66])[CH2:61][CH2:60]2)=[N:33][CH:34]=[C:35]([C:37](=[O:58])[NH:38][C:39]2[S:40][C:41]([CH2:50][N:51]([CH2:53][CH2:54][CH2:55][O:56][CH3:57])[CH3:52])=[C:42]([C:44]3[S:45][CH:46]=[C:47]([Cl:49])[CH:48]=3)[N:43]=2)[CH:36]=1>C(Cl)(Cl)Cl.C1COCC1.C(N(CC)CC)C>[ClH:30].[Cl:30][C:31]1[C:32]([N:59]2[CH2:60][CH2:61][CH:62]([C:65]([N:1]3[CH2:6][CH2:5][O:4][CH2:3][CH2:2]3)=[O:66])[CH2:63][CH2:64]2)=[N:33][CH:34]=[C:35]([CH:36]=1)[C:37]([NH:38][C:39]1[S:40][C:41]([CH2:50][N:51]([CH2:53][CH2:54][CH2:55][O:56][CH3:57])[CH3:52])=[C:42]([C:44]2[S:45][CH:46]=[C:47]([Cl:49])[CH:48]=2)[N:43]=1)=[O:58]

Participants

8

Reactant 4

HCID 8083MorpholineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 86607412HCID 86607412, compound

Product 1

HCID 23117179HCID 23117179, compound

Reagents, catalysts & solvents 3

HCID 6212ChloroformSolventHCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolvent

Procedure

30 μl of triethylamine, 30 μl of morpholine, 45 mg of WSC.HCl and 30 mg of HOBt were added to 2 ml of a THF solution of 52 mg of 1-{3-chloro-5-[(4-(4-chlorothiophen-2-yl)-5-{[(3-methoxypropyl)(methyl)amino]methyl}thiazol-2-yl)carbamoyl]-2-pyridyl}piperidine-4-carboxylic acid hydrochloride, and the mixture was stirred overnight at room temperature. Chloroform was added to the reaction solution. The organic layer was washed with a saturated sodium hydrogencarbonate aqueous solution, with water and with brine, and then dried over sodium sulfate. After the solvent was distilled off, the residue was purified by silica gel column chromatography (eluent: chloroform:MeOH=100:1 to 50:1, hexane:EtOAc=2:1, then chloroform:MeOH=20:1), and suspended in 2 ml of diethyl ether. 2 ml of 4M HCl-EtOAc was added, and the precipitate was collected by filtration to obtain 25 mg of 5-chloro-N-(4-(4-chlorothiophen-2-yl)-5-{[(3-methoxypropyl)(methyl)amino]methyl}thiazol-2-yl)-6-[4-(morpholinocarbonyl)piperidino]nicotinamide hydrochloride.

Workup

  1. washThe organic layer was washed with a saturated sodium hydrogencarbonate aqueous solution, with water and with brine
  2. dry with materialdried over sodium sulfate
  3. distillationAfter the solvent was distilled off
  4. customthe residue was purified by silica gel column chromatography (eluent
  5. addition2 ml of 4M HCl-EtOAc was added
  6. filtrationthe precipitate was collected by filtration

Sources & evidence

ORD record
ord-e81e770bd9ca4e8da646e9d9a53b70f4
Source dataset
uspto-grants-2008_04
Patent number
US07361658B2

Reaction notes

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