Di-tert-butyl dicarbonate → HCID 22317711, compound

HRID 498679Notes

Reaction equation

HRID 498679 reaction equation
C(O[C:6](=[O:23])[CH2:7][C:8]([C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([C:16]2[CH:17]=[N:18][C:19]([NH2:22])=[CH:20][CH:21]=2)[CH:11]=1)=O)(C)(C)C.CC(OC(OC(OC(C)(C)C)=O)=O)(C)C.C([O-])(O)=O.[Na+].C(OC(=O)[NH:50][C:51]1[CH:56]=[CH:55][C:54]([C:57]([F:60])([F:59])[F:58])=[CH:53][C:52]=1[NH2:61])(C)(C)C>CN(C1C=CN=CC=1)C.C1COCC1.C1(C)C=CC=CC=1>[NH2:22][C:19]1[N:18]=[CH:17][C:16]([C:12]2[CH:11]=[C:10]([C:8]3[CH2:7][C:6](=[O:23])[NH:61][C:52]4[CH:53]=[C:54]([C:57]([F:58])([F:59])[F:60])[CH:55]=[CH:56][C:51]=4[N:50]=3)[CH:15]=[CH:14][CH:13]=2)=[CH:21][CH:20]=1

Participants

8

Reactant 4

HCID 90495Di-tert-butyl dicarbonateHCID 516892Sodium BicarbonateHCID 24689211tert-butyl N-(2-amino-4-(trifluoromethyl)phenyl)carbamateHCID 69489751HCID 69489751, compound

Product 1

HCID 22317711HCID 22317711, compound

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
23 °C

Procedure

The title compound was prepared by the following sequence: 1.) To a solution of 3-[3-(6-Amino-pyridin-3-yl)-phenyl]-3-oxo-propionic acid tert-butyl ester (Example K25) (1.0 g, 3.2 mmol) and DMAP (8 mg, 0.064 mmol) in THF (6.4 mL) was added Boc2O (699 mg, 3.2 mmol) and mixture was stirred for 26.5 h at 23° C., poured onto sat. NaHCO3-solution (20 mL), extracted with EtOAc (twice 25 mL). The combined organic layers were washed with 0.5 M HCl (20 mL) and brine (20 mL), dried over Na2SO4. Removal of the solvent in vacuum left a light brown foam (1.273 g). 2.) Part of this material (206 mg, 0.5 mmol) and (2-amino-4-trifluoromethyl-phenyl)-carbamic acid tert-butyl ester (Example J3) (214 mg, 0.75 mmol) were refluxed in toluene (3 mL) for 8 h, then the reaction mixture was cooled to 23° C., the precipitate was filtered off and washed with Et2O (10 mL) to give a light brown solid (96.5 mg). 3.) Part of the obtained material (88.9 mg, 0.145 mmol) was converted into the title compound by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light brown solid (35.2 mg, 61%).

Workup

  1. extractionextracted with EtOAc (twice 25 mL)
  2. washThe combined organic layers were washed with 0.5 M HCl (20 mL) and brine (20 mL)
  3. dry with materialdried over Na2SO4
  4. customRemoval of the solvent in vacuum
  5. waitleft a light brown foam (1.273 g)
  6. temperaturethe reaction mixture was cooled to 23° C.
  7. filtrationthe precipitate was filtered off
  8. washwashed with Et2O (10 mL)

Sources & evidence

ORD record
ord-eeb8d22b3b2641dd9f09ca9f98de2c90
Source dataset
uspto-grants-2005_09
Patent number
US06949542B2

Reaction notes

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