Triethylamine → N-{1-[4-(2-chloro-4-methoxy-phenoxy)-benzylcarbamoyl]-cyclopropyl}-5-trifluoromethyl-nicotinamide

HRID 1406371Notes

Reaction equation

HRID 1406371 reaction equation
C(N(CC)CC)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.C(OC(NC1(C(O)=O)CC1)=O)(C)(C)C.ClC1C=C(OC)C=CC=1OC1C=CC(CN)=CC=1.[F:62][C:63]([F:74])([F:73])[C:64]1[CH:65]=[N:66][CH:67]=[C:68]([CH:72]=1)[C:69]([OH:71])=O.[Cl:75][C:76]1[CH:96]=[C:95]([O:97][CH3:98])[CH:94]=[CH:93][C:77]=1[O:78][C:79]1[CH:92]=[CH:91][C:82]([CH2:83][NH:84][C:85]([C:87]2([NH2:90])[CH2:89][CH2:88]2)=[O:86])=[CH:81][CH:80]=1>CN(C=O)C>[Cl:75][C:76]1[CH:96]=[C:95]([O:97][CH3:98])[CH:94]=[CH:93][C:77]=1[O:78][C:79]1[CH:92]=[CH:91][C:82]([CH2:83][NH:84][C:85]([C:87]2([NH:90][C:69](=[O:71])[C:68]3[CH:72]=[C:64]([C:63]([F:62])([F:74])[F:73])[CH:65]=[N:66][CH:67]=3)[CH2:88][CH2:89]2)=[O:86])=[CH:81][CH:80]=1

Participants

8

Reactant 6

HCID 8471Triethylamine2×HCID 6883961-((tert-Butoxycarbonyl)amino)cyclopropanecarboxylic acidHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate2×HCID 109763055-(Trifluoromethyl)nicotinic acidHCID 584879264-(2-Chloro-4-methoxy-phenoxy)-benzylamineHCID 674453771-Amino-cyclopropanecarboxylic acid-4-(2-chloro-4-methoxy-phenoxy)-benzylamide

Product 1

HCID 25234014N-{1-[4-(2-chloro-4-methoxy-phenoxy)-benzylcarbamoyl]-cyclopropyl}-5-trifluoromethyl-nicotinamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

102 μL (0.73 mmol) of triethylamine and 117 mg (0.36 mmol) of TBTU were added to a solution of 73.7 mg (0.37 mmol) of 1-tert-butoxycarbonylamino-cyclopropanecarboxylic acid in 6 mL DMF and the mixture was stirred for 5 min at RT. Then 96.6 mg (0.37 mmol) of 4-(2-chloro-4-methoxy-phenoxy)-benzylamine was added and the mixture was stirred overnight at ambient temperature. The reaction mixture was filtered through Alox B, washed with DMF and the filtrate was evaporated down. 10 ml of dichloromethane/trifluoroacetic acid=1/1 were added to the residue and this was shaken for 1 h at RT. The reaction mixture was evaporated down and the residue was purified by chromatography (reversed phase). The corresponding fractions were freeze-dried. 35 mg (0.18 mmol) of 5-(trifluoromethyl)nicotinic acid was dissolved in 2 ml DMF and combined with 52 μL (0.37 mmol) of triethylamine and 59 mg (0.18 mmol) of TBTU and stirred for 10 min at RT. Then the freeze-dried 1-amino-cyclopropanecarboxylic acid-4-(2-chloro-4-methoxy-phenoxy)-benzylamide was added and the mixture was stirred overnight at RT. The reaction mixture was purified directly by chromatography (reversed phase).

Workup

  1. stirringthe mixture was stirred overnight at ambient temperature
  2. filtrationThe reaction mixture was filtered through Alox B
  3. washwashed with DMF
  4. customthe filtrate was evaporated down
  5. addition10 ml of dichloromethane/trifluoroacetic acid=1/1 were added to the residue
  6. stirringthis was shaken for 1 h at RT
  7. customThe reaction mixture was evaporated down
  8. customthe residue was purified by chromatography (reversed phase)
  9. customThe corresponding fractions were freeze-dried
  10. stirringstirred for 10 min at RT
  11. stirringthe mixture was stirred overnight at RT
  12. customThe reaction mixture was purified directly by chromatography (reversed phase)

Sources & evidence

ORD record
ord-1ee1921f4c5d4ceba5146adc6d53cc69
Source dataset
uspto-grants-2014_12
Patent number
US08916589B2

Reaction notes

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