4-Methylmorpholine → HCID 178452358, compound

HRID 489951Notes

Reaction equation

HRID 489951 reaction equation
O.[F:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[NH:13][N:12]=[C:11]([C:14](O)=[O:15])[C:10]=2[C:17]2[CH:22]=[CH:21][N:20]=[CH:19][CH:18]=2)=[CH:5][CH:4]=1.O.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.[C:46]([O:50][C:51]([N:53]1[CH2:58][CH2:57][NH:56][CH2:55][CH2:54]1)=[O:52])([CH3:49])([CH3:48])[CH3:47].CN1CCOCC1>CN(C)C=O.C(OCC)(=O)C.C([O-])(O)=O.[Na+].C(O)(C)C.C1(C)C=CC=CC=1>[F:2][C:3]1[CH:4]=[CH:5][C:6]([C:9]2[NH:13][N:12]=[C:11]([C:14]([N:56]3[CH2:57][CH2:58][N:53]([C:51]([O:50][C:46]([CH3:49])([CH3:47])[CH3:48])=[O:52])[CH2:54][CH2:55]3)=[O:15])[C:10]=2[C:17]2[CH:18]=[CH:19][N:20]=[CH:21][CH:22]=2)=[CH:7][CH:8]=1

Participants

10

Reactant 5

HCID 79724-MethylmorpholineHCID 143452tert-Butyl piperazine-1-carboxylateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 178526953HCID 178526953, compound

Product 1

HCID 178452358HCID 178452358, compoundYield 78.4%

Reagents, catalysts & solvents 4

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolventHCID 516892Sodium BicarbonateSolventHCID 21881414Toluene isopropyl alcoholSolvent

Conditions

Temperature
0 °C

Procedure

In a solution of 5-(4-fluorophenyl)-4-(4-pyridinyl)-1H-pyrazole-3-carboxylic acid, monohydrate (0.9905 g, 3.5 mmol) from step 1 and 1-hydroxybenzotriazole hydrate (0.4824 g, 3.57 mmol) in dimethylformamide (20 mL) at 0° C. under N2, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.6983 g, 3.57 mmol) was added. The solution was stirred at 0° C. under N2 for 1 hour, then was added 1-tert.-butoxycarbonylpiperazine (0.6585 g, 3.5 mmol) followed by N-methyl morpholine (0.40 mL, 3.6 mmol). The reaction was stirred from 0° C. to room temperature overnight. The reaction mixture was diluted with ethyl acetate and saturated NaHCO3 solution, extracted. The organic layer was washed with water and brine, and dried over MgSO4. After filtration, the solvent was removed under reduced pressure, and crude product was obtained (1.7595 g). The desired product 1,1-dimethylethyl 4-[[5-(4-fluorophenyl)-4-(4-pyridinyl)-1H-pyrazol-3-yl)carbonyl]-1-piperazinecarboxylate (1.2375 g, 78.4%) was isolated by chromatography (silica gel, 10:90 isopropyl alcohol/toluene). Anal. Calc'd for C24H26N5FO3: C, 63.85; H, 5.80; N, 15.51; Found: C, 63.75; H, 5.71; N, 15.16. MS (MH−): 452 (base peak).

Workup

  1. stirringThe reaction was stirred from 0° C. to room temperature overnight
  2. extractionextracted
  3. washThe organic layer was washed with water and brine
  4. dry with materialdried over MgSO4
  5. filtrationAfter filtration
  6. customthe solvent was removed under reduced pressure
  7. customcrude product was obtained (1.7595 g)

Sources & evidence

ORD record
ord-8039fe63f57f4e8da9ffbc30821d6087
Source dataset
uspto-grants-2005_12
Patent number
US06979686B1

Reaction notes

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