1-Acetylpiperazine → HCID 68717175, compound

HRID 506393Notes

Reaction equation

HRID 506393 reaction equation
[CH2:1]([O:3][C:4]([N:6]1[C:15]2[C:10](=[N:11][C:12]([O:16][CH3:17])=[CH:13][CH:14]=2)[C@@H:9]([NH:18][CH:19]([C:32]2[N:37]=[CH:36][C:35](Br)=[CH:34][N:33]=2)[C:20]2[CH:25]=[C:24]([C:26]([F:29])([F:28])[F:27])[CH:23]=[C:22]([C:30]#[N:31])[CH:21]=2)[CH2:8][C@H:7]1[CH2:39][CH3:40])=[O:5])[CH3:2].CC(C)([O-])C.[Na+].C(P(C(C)(C)C)C1C=CC=CC=1C1C=CC=CC=1)(C)(C)C.[C:68]([N:71]1[CH2:76][CH2:75][NH:74][CH2:73][CH2:72]1)(=[O:70])[CH3:69]>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH2:1]([O:3][C:4]([N:6]1[C:15]2[C:10](=[N:11][C:12]([O:16][CH3:17])=[CH:13][CH:14]=2)[C@@H:9]([NH:18][CH:19]([C:32]2[N:37]=[CH:36][C:35]([N:74]3[CH2:75][CH2:76][N:71]([C:68](=[O:70])[CH3:69])[CH2:72][CH2:73]3)=[CH:34][N:33]=2)[C:20]2[CH:25]=[C:24]([C:26]([F:29])([F:28])[F:27])[CH:23]=[C:22]([C:30]#[N:31])[CH:21]=2)[CH2:8][C@H:7]1[CH2:39][CH3:40])=[O:5])[CH3:2]

Participants

7

Reactant 4

HCID 837951-AcetylpiperazineHCID 27342152-(Di-tert-butylphosphino)biphenylHCID 23676156Sodium t-butoxideHCID 68718040HCID 68718040, compound

Product 1

HCID 68717175HCID 68717175, compoundYield 54.8%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Procedure

(2R,4S)-4-[(5-Bromopyrimidin-2-yl)-(3-cyano-5-trifluoromethyl-benzyl)]amino-2-ethyl-6-methoxy-3,4-dihydro-2H-[1,5]naphthyridine-1-carboxylic acid ethyl ester (300 mg) is dissolved in toluene (4 ml), and thereto are added tris(dibenzylideneacetone)dipalladium (44 mg), sodium tert-butoxide (70 mg), 2-(di-tert-butylphosphino)biphenyl (58 mg) and acetyl piperazine (93 mg). The mixture is stirred at room temperature for 1 hour under nitrogen flow, then heated at 50° C. and stirred for 5.5 hours, and partitioned by adding a saturated aqueous sodium hydrogen carbonate solution and ethyl acetate. The organic layer is washed with saturated brine and dried over magnesium sulfate, then concentrated under reduced pressure. The resulting residue is purified by column chromatography (silica gel; hexane:ethyl acetate=1:1→0:1) to give (2R,4S)-4-{[5-(4-acetylpiperazin-1-yl)pyrimidin-2-yl]-(3-cyano-5-trifluoromethyl-benzyl)}amino-2-ethyl-6-methoxy-3,4-dihydro-2H-[1,5]naphthyridine-1-carboxylic acid ethyl ester (177 mg). MS (m/z): 667 [M+H]+.

Workup

  1. temperatureheated at 50° C.
  2. stirringstirred for 5.5 hours
  3. custompartitioned
  4. additionby adding a saturated aqueous sodium hydrogen carbonate solution and ethyl acetate
  5. washThe organic layer is washed with saturated brine
  6. dry with materialdried over magnesium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customThe resulting residue is purified by column chromatography (silica gel; hexane:ethyl acetate=1:1→0:1)

Sources & evidence

ORD record
ord-e23c329b5bd545aab7aa4ecee155c169
Source dataset
uspto-grants-2010_08
Patent number
US07781443B2

Reaction notes

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