4-Methylmorpholine → HCID 178427121, compound

HRID 1641733Notes

Reaction equation

HRID 1641733 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[CH:9]([S:20]([C:23]1[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=1)(=[O:22])=[O:21])[C:10]1[C:11]([CH3:19])=[CH:12][C:13]([C:16](O)=[O:17])=[N:14][CH:15]=1.Cl.[NH2:31][C@H:32]1[CH2:37][CH2:36][C@H:35]([OH:38])[CH2:34][CH2:33]1.ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.CN1CCOCC1>C(Cl)Cl.C(OCC)(=O)C>[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[CH:9]([S:20]([C:23]1[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=1)(=[O:22])=[O:21])[C:10]1[C:11]([CH3:19])=[CH:12][C:13]([C:16]([NH:31][C@H:32]2[CH2:37][CH2:36][C@H:35]([OH:38])[CH2:34][CH2:33]2)=[O:17])=[N:14][CH:15]=1

Participants

8

Reactant 5

HCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 577364395-[(2,5-Difluorophenyl)[(4-fluorophenyl)sulfonyl]methyl]-4-methylpyridine-2-carboxylic acidHCID 178479278HCID 178479278, compound

Product 1

HCID 178427121HCID 178427121, compoundYield 92%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 5-[(2,5-difluorophenyl)[(4-fluorophenyl)sulfonyl]methyl]-4-methylpyridine-2-carboxylic acid (114 mg, 0.271 mmol) obtained in Example 12 in methylene chloride (3 ml), trans-4-aminocyclohexanol hydrochloride (49 mg, 0.325 mmol), 1-hydroxybenzotriazole (37 mg, 0.271 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (62 mg, 0.325 mmol) and 4-methylmorpholine (71 μl, 0.650 mmol) were added, and the mixture was stirred for 17 hours at room temperature. Ethyl acetate was added to the reaction solution, and the mixture was washed sequentially with saturated aqueous sodium hydrogencarbonate and saturated brine. The organic layer was dried over anhydrous sodium sulfate and filtered, and then the filtrate was concentrated under reduced pressure. The resulting concentration residue was subjected to silica gel column chromatography, and the fraction obtained from an elution with methanol:methylene chloride (=1:40) was concentrated under reduced pressure, to obtain the title compound (129 mg, 0.249 mmol, 92%) as an amorphous substance.

Workup

  1. washthe mixture was washed sequentially with saturated aqueous sodium hydrogencarbonate and saturated brine
  2. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  3. filtrationfiltered
  4. concentrationthe filtrate was concentrated under reduced pressure
  5. concentrationThe resulting concentration residue
  6. customthe fraction obtained from an elution with methanol
  7. concentrationmethylene chloride (=1:40) was concentrated under reduced pressure

Sources & evidence

ORD record
ord-5c4d3562201f43ab80a3ba7b0dafcfa2
Source dataset
uspto-grants-2012_02
Patent number
US08114886B2

Reaction notes

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