Dicyclohexylamine → HCID 118022562, compound

HRID 1498863Notes

Reaction equation

HRID 1498863 reaction equation
C1(NC2CCCCC2)CCCCC1.[Li]CCCC.[F:19][C:20]1[CH:25]=[CH:24][C:23]([CH2:26][C:27]([O:29][CH3:30])=[O:28])=[CH:22][CH:21]=1.Br[C:32]1[CH:33]=[N:34][C:35]([N:38]2[CH2:43][CH2:42][N:41]([C:44]([O:46][C:47]([CH3:50])([CH3:49])[CH3:48])=[O:45])[CH2:40][CH2:39]2)=[N:36][CH:37]=1.P(C(C)(C)C)(C(C)(C)C)C(C)(C)C>C1COCC1.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]>[F:19][C:20]1[CH:21]=[CH:22][C:23]([CH:26]([C:32]2[CH:37]=[N:36][C:35]([N:38]3[CH2:39][CH2:40][N:41]([C:44]([O:46][C:47]([CH3:50])([CH3:49])[CH3:48])=[O:45])[CH2:42][CH2:43]3)=[N:34][CH:33]=2)[C:27]([O:29][CH3:30])=[O:28])=[CH:24][CH:25]=1

Participants

9

Reactant 5

HCID 7582DicyclohexylamineHCID 83681Tris(1,1-dimethylethyl)phosphineHCID 2733233Methyl 2-(4-fluorophenyl)acetateHCID 21914476tert-Butyl 4-(5-bromopyrimidin-2-yl)piperazine-1-carboxylateHCID 178418339Butyllithium

Product 1

HCID 118022562HCID 118022562, compoundYield 8%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of dicyclohexylamine (3.43 g, 18.94 mmol) in THF (60 mL) at −78° C. was added n-BuLi (2.5 M, 7.9 mL, 18.94 mmol) dropwise. The mixture was stirred at RT for 10 min, followed by the addition of methyl 2-(4-fluorophenyl)acetate (2.69 g, 16.02 mmol) in toluene (60 mL). After stirred at RT for another 10 min, tert-butyl 4-(5-bromopyrimidin-2-yl)piperazine-1-carboxylate (5.0 g, 14.57 mmol), Pd2(dba)3 (667 mg, 0.728 mmol) and P(t-Bu)3 (10%, 1.47 g, 0.728 mmol) were added sequentially. The reaction mixture was stirred at RT for 15 h, quenched by water (150 mL) and extracted with EA. The combined organic layers were washed with water and brine, dried over Na2SO4, filtered and concentrated. The residue was passed a column (silica gel, PE:EA=6:1) to afford the title compound (0.5 g, 8%) as an orange solid. MS (ES+) C22H27FN4O4 requires: 430. found: 431 [M+H]+.

Workup

  1. stirringAfter stirred at RT for another 10 min
  2. stirringThe reaction mixture was stirred at RT for 15 h
  3. customquenched by water (150 mL)
  4. extractionextracted with EA
  5. washThe combined organic layers were washed with water and brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-fa28f794e29446d189063fa082e2c65b
Source dataset
uspto-grants-2015_12
Patent number
US09200002B2

Reaction notes

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