Sodium Carbonate → (4-Isopropyl-piperazin-1-yl)-(4-morpholin-4-ylmethyl-phenyl)-methanone

HRID 1192769Notes

Reaction equation

HRID 1192769 reaction equation
Cl.[N:2]1([CH2:8][C:9]2[CH:17]=[CH:16][C:12]([C:13]([OH:15])=O)=[CH:11][CH:10]=2)[CH2:7][CH2:6][O:5][CH2:4][CH2:3]1.O.ON1C2C=CC=CC=2N=N1.[CH:29]([N:32]1[CH2:37][CH2:36][NH:35][CH2:34][CH2:33]1)([CH3:31])[CH3:30].Cl.CN(C)CCCN=C=NCC.C(=O)([O-])[O-].[Na+].[Na+]>O.C(#N)C.C1(C)C=CC=CC=1>[CH:29]([N:32]1[CH2:37][CH2:36][N:35]([C:13]([C:12]2[CH:11]=[CH:10][C:9]([CH2:8][N:2]3[CH2:3][CH2:4][O:5][CH2:6][CH2:7]3)=[CH:17][CH:16]=2)=[O:15])[CH2:34][CH2:33]1)([CH3:31])[CH3:30]

Participants

9

Reactant 5

HCID 10340Sodium CarbonateHCID 780131-IsopropylpiperazineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27292554-[(Morpholin-4-yl)methyl]benzoic acid--hydrogen chloride (1/1)HCID 27960291-Hydroxybenzotriazole hydrate

Product 1

HCID 10042344(4-Isopropyl-piperazin-1-yl)-(4-morpholin-4-ylmethyl-phenyl)-methanone

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1140TolueneSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
22.5 °C

Procedure

A 1 L three-necked flask equipped with an air stirrer and thermocouple was charged with 4-(4-morpholinylmethyl)benzoic acid hydrochloride (50 g, 0.194 mol), toluene (400 mL), acetonitrile (100 mL) and 1-hydroxybenzotriazole monohydrate (17.8 g, 0.116 mol). After stirring the resulting off-white slurry at about 20-25° C. for 5 minutes, 1-isopropyl-piperazine (27.4 g, 0.213 mol) was added and the reaction mixture was stirred for 20 minutes. Next, N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (44.6 g, 0.233 mol) was added and the reaction mixture was stirred at about 20-25° C. overnight. Water (250 mL) and aqueous saturated sodium carbonate (150 mL) were then added to the stirring suspension and mixed well. The resulting biphasic mixture was allowed to settle. The aqueous phase was discarded and the organic phase was washed with a 50% brine solution (water (150 mL)/brine (150 m L)). The organic phase was dried over anhydrous sodium sulfate, filtered, washed with acetonitrile and concentrated to yield (4-isopropyl-piperazin-1-yl)-(4-morpholin-4-ylmethyl-phenyl)-methanone, as a free base, as a light yellow oil.

Workup

  1. customA 1 L three-necked flask equipped with an air stirrer
  2. stirringthe reaction mixture was stirred for 20 minutes
  3. stirringthe reaction mixture was stirred at about 20-25° C. overnight
  4. additionmixed well
  5. washthe organic phase was washed with a 50% brine solution (water (150 mL)/brine (150 m L))
  6. dry with materialThe organic phase was dried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. washwashed with acetonitrile
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-c7b80f20e91140179858f040cc0f2299
Source dataset
uspto-grants-2014_03
Patent number
US08680273B2

Reaction notes

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