4-Aminopyridine → {1-[2-Bromo-4-(pyridine-4-ylcarbamoyl)-phenyl]-ethyl}-carbamic acid tert-butyl ester

HRID 1403664Notes

Reaction equation

HRID 1403664 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[CH:11]([NH:13][C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH3:12])[C:5]([OH:7])=O.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.C1C=CC2N(O)N=NC=2C=1.[NH2:62][C:63]1[CH:68]=[CH:67][N:66]=[CH:65][CH:64]=1>CN(C=O)C.CCOC(C)=O>[C:17]([O:16][C:14](=[O:15])[NH:13][CH:11]([C:10]1[CH:9]=[CH:8][C:4]([C:5](=[O:7])[NH:62][C:63]2[CH:68]=[CH:67][N:66]=[CH:65][CH:64]=2)=[CH:3][C:2]=1[Br:1])[CH3:12])([CH3:20])([CH3:19])[CH3:18]

Participants

8

Reactant 5

HCID 17274-Aminopyridine2×HCID 757711-Hydroxybenzotriazole2×HCID 81531Diisopropylethylamine2×HCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate2×HCID 674090933-Bromo-4-(1-tert-butoxycarbonylamino-ethyl)-benzoic acid

Product 1

HCID 67408319{1-[2-Bromo-4-(pyridine-4-ylcarbamoyl)-phenyl]-ethyl}-carbamic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 3-bromo-4-(1-tert-butoxycarbonylamino-ethyl)-benzoic acid (7496 to 61011 μmol) in DMF (10 to 30 ml) were added DIEA (2 eq.), TBTU (1.3 eq.) and HOBt (0.3 eq.). The reaction mixture was stirred at RT for 5 minutes. 4-Aminopyridine (1.5 eq) was added and the reaction mixture was stirred at RT for 2.5 hours up to overnight. When there was still starting material observed, more DIEA (0.39 eq), TBTU (0.25 eq), HOBt (0.06 eq) and 4-aminopyridine (0.28 eq) were added and the reaction mixture was stirred at RT for another 2 hours. The reaction mixture was diluted with EtOAc, washed with 0.1 M HCl and saturated Na2CO3 or with saturated NaHCO3. The organic layer was dried over MgSO4 and the solvent was removed under reduced pressure. The compound was purified by column chromatography (silicagel, DCM/MeOH gradient).

Workup

  1. stirringthe reaction mixture was stirred at RT for 2.5 hours up to overnight
  2. stirringthe reaction mixture was stirred at RT for another 2 hours
  3. washwashed with 0.1 M HCl and saturated Na2CO3 or with saturated NaHCO3
  4. dry with materialThe organic layer was dried over MgSO4
  5. customthe solvent was removed under reduced pressure
  6. customThe compound was purified by column chromatography (silicagel, DCM/MeOH gradient)

Sources & evidence

ORD record
ord-985790e5b24f44f587ad170e0516170e
Source dataset
uspto-grants-2014_12
Patent number
US08912209B2

Reaction notes

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