tert-Butyl piperazine-1-carboxylate → Tert-butyl 4-(4-(pyrrolidin-1-yl)quinazolin-7-yl)piperazine-1-carboxylate

HRID 2090812Notes

Reaction equation

HRID 2090812 reaction equation
CC(C)([O-])C.[K+].C1(P(C2CCCCC2)C2(C(C)C)CC(C(C)C)=CC(C(C)C)=C2C2C=CC=CC=2)CCCCC1.Cl[C:42]1[CH:51]=[C:50]2[C:45]([C:46]([N:52]3[CH2:56][CH2:55][CH2:54][CH2:53]3)=[N:47][CH:48]=[N:49]2)=[CH:44][CH:43]=1.[N:57]1([C:63]([O:65][C:66]([CH3:69])([CH3:68])[CH3:67])=[O:64])[CH2:62][CH2:61][NH:60][CH2:59][CH2:58]1>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].C(OCC)(=O)C.O>[N:52]1([C:46]2[C:45]3[C:50](=[CH:51][C:42]([N:60]4[CH2:59][CH2:58][N:57]([C:63]([O:65][C:66]([CH3:69])([CH3:68])[CH3:67])=[O:64])[CH2:62][CH2:61]4)=[CH:43][CH:44]=3)[N:49]=[CH:48][N:47]=2)[CH2:56][CH2:55][CH2:54][CH2:53]1

Participants

9

Reactant 4

HCID 143452tert-Butyl piperazine-1-carboxylateHCID 17479737HCID 17479737, compoundHCID 23665647Potassium tert-butoxideHCID 672859322-Dicyclohexylphosphino-2,4,6-triisopropylbiphenyl

Product 1

HCID 59746514Tert-butyl 4-(4-(pyrrolidin-1-yl)quinazolin-7-yl)piperazine-1-carboxylate

Reagents, catalysts & solvents 4

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

Potassium tert-butoxide (998 mg, 8.99 mmol), 2-dicyclohexylphosphino-2,4,6-triisopropyl-biphenyl (X-Phos) (79 mg, 0.18 mmol) and tris-(dibenzylideneacetone)-dipalladium [Pd2(dba)3] (36 mg, 0.036 mmol) were added, under nitrogen, to a mixture of 7-chloro-4-(pyrrolidin-1-yl)quinazoline (A) (840 mg, 3.59 mmol) and tert-butyl piperazine-1-carboxylate (1.0 g, 5.39 mmol) in toluene (49 ml). The reaction mixture was then heated for 15 h at 100° C. The reaction mixture was cooled to room temperature, and water (25 ml) and ethyl acetate (25 ml) were added. The aqueous phase was extracted with ethyl acetate (2×25 ml), and the combined organic phases were washed with saturated sodium chloride solution (20 ml). The organic phase was then dried (MgSO4) and concentrated in vacuo. The crude product was purified by column chromatography (silica gel) using ethyl acetate/-dichloromethane/ammonia solution (25% aq.) (50:10:0.5) and ethyl acetate/dichloro-methane/methyl tert-butyl ether/ammonia solution (25% aq.) (50:10:10:0.7).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. extractionThe aqueous phase was extracted with ethyl acetate (2×25 ml)
  3. washthe combined organic phases were washed with saturated sodium chloride solution (20 ml)
  4. dry with materialThe organic phase was then dried (MgSO4)
  5. concentrationconcentrated in vacuo
  6. customThe crude product was purified by column chromatography (silica gel)

Sources & evidence

ORD record
ord-21ec4c1f22c14a65a569bc67b5d27e3f
Source dataset
uspto-grants-2013_05
Patent number
US08435978B2

Reaction notes

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