Sodium Carbonate → HCID 59619365, compound

HRID 1367556Notes

Reaction equation

HRID 1367556 reaction equation
[C:1]([C:3]1([NH:6][C:7]([C@H:9]2[CH2:13][C@H:12]([S:14]([C:17]3[CH:22]=[CH:21][C:20](Br)=[CH:19][C:18]=3[C:24]([F:27])([F:26])[F:25])(=[O:16])=[O:15])[CH2:11][C@@H:10]2[O:28][CH3:29])=[O:8])[CH2:5][CH2:4]1)#[N:2].[CH3:30][N:31]1[CH2:36][CH2:35][NH:34][CH2:33][CH2:32]1.C(N(C(C)C)C(C)C)C.C([O-])([O-])=O.[Na+].[Na+]>CC(N(C)C)=O.O>[C:1]([C:3]1([NH:6][C:7]([C@H:9]2[CH2:13][C@H:12]([S:14]([C:17]3[CH:22]=[CH:21][C:20]([N:34]4[CH2:35][CH2:36][N:31]([CH3:30])[CH2:32][CH2:33]4)=[CH:19][C:18]=3[C:24]([F:27])([F:26])[F:25])(=[O:16])=[O:15])[CH2:11][C@@H:10]2[O:28][CH3:29])=[O:8])[CH2:5][CH2:4]1)#[N:2]

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 531671-Methylpiperazine2×HCID 81531DiisopropylethylamineHCID 59619475(1S,2S,4S)-4-(4-Bromo-2-trifluoromethyl-benzenesulfonyl)-2-methoxy-cyclopentanecarboxylic acid (1-cyano-cyclopropyl)-amide

Product 1

HCID 59619365HCID 59619365, compoundYield 67.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of (1R,2R,4R) and (1S,2S,4S)-4-(4-bromo-2-trifluoromethyl-benzenesulfonyl)-2-methoxy-cyclopentanecarboxylic acid (1-cyano-cyclopropyl)-amide (50 mg, 0.1009 mmol, example 58), 1-methylpiperazine (25 μl, 0.252 mmol) and N-ethyl-N,N-diisopropyl amine (36 μl, 0.202 mmol) in DMA (1 ml) was heated in a sealed tube to 100° C. for 5 h. Then additional 1-methylpiperazine (25 μl, 0.252 mmol) was added and heating to 100° C. was continued overnight. The mixture was then cooled to room temperature and diluted with water. The pH was adjusted to 10 by addition of saturated Na2CO3 solution and the mixture was extracted 3 times with EtOAc. The combined organic layers were washed two times with Na2CO3 solution (pH 10) and with brine, dried over Na2SO4 and evaporated. The remaining brown gum was purified by silica gel chromatography (DCM/MeOH 98:2-19:1) to obtain the title compound (35 mg, 67%) as white foam. MS (EI): 515.4 (M+H)+.

Workup

  1. temperatureheating to 100° C.
  2. temperatureThe mixture was then cooled to room temperature
  3. extractionthe mixture was extracted 3 times with EtOAc
  4. washThe combined organic layers were washed two times with Na2CO3 solution (pH 10)
  5. dry with materialwith brine, dried over Na2SO4
  6. customevaporated
  7. customThe remaining brown gum was purified by silica gel chromatography (DCM/MeOH 98:2-19:1)

Sources & evidence

ORD record
ord-3c07a0a2c2324191a3f48e612c7d1f17
Source dataset
uspto-grants-2011_02
Patent number
US07893099B2

Reaction notes

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