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

HRID 1406371ノート

反応式

HRID 1406371 の反応式
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

参加物

8

反応物 6

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒2 回

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-1ee1921f4c5d4ceba5146adc6d53cc69
出典データセット
uspto-grants-2014_12
特許番号
US08916589B2

反応ノート

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