Morpholine → HCID 59619237, compound

HRID 1367567Notes

Reaction equation

HRID 1367567 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].[NH:30]1[CH2:35][CH2:34][O:33][CH2:32][CH2:31]1.C(C1C=CC=C(C(C)(C)C)N=1)(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:30]4[CH2:35][CH2:34][O:33][CH2:32][CH2:31]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 8083Morpholine2×HCID 10340Sodium CarbonateHCID 685102,6-Di-tert-butylpyridineHCID 59619475(1S,2S,4S)-4-(4-Bromo-2-trifluoromethyl-benzenesulfonyl)-2-methoxy-cyclopentanecarboxylic acid (1-cyano-cyclopropyl)-amide

Product 1

HCID 59619237HCID 59619237, compoundYield 65.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
100 °C

Procedure

A solution 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), morpholine (22 μl, 0.252 mmol) and 2,6-di-tert-butylpyridine (45.4 μl, 0.202 mmol) in DMA (1 ml) was heated in a sealed tube at 100° C. overnight. Then additional morpholine (8.8 μl, 0.1009 mmol) was added and the solution was stirred another 2 h at 100° C. 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 light brown solid was purified by silica gel chromatography (DCM/EtOAc 4:1-1:1) to obtain the title compound (33 mg, 65%) as white foam. MS (EI): 502.2 (M+H)+.

Workup

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

Sources & evidence

ORD record
ord-edf8f4a87db340a2af2b49f0c554899e
Source dataset
uspto-grants-2011_02
Patent number
US07893099B2

Reaction notes

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