4-Cyanobenzoic acid → HCID 10432796, compound

HRID 222675Notes

Reaction equation

HRID 222675 reaction equation
[C:1]([C:3]1[CH:11]=[CH:10][C:6]([C:7]([OH:9])=O)=[CH:5][CH:4]=1)#[N:2].O.ON1C2C=CC=CC=2N=N1.[CH:23]1([N:27]2[CH2:33][CH2:32][C:31]3[CH:34]=[C:35]([O:38][CH:39]4[CH2:44][CH2:43][NH:42][CH2:41][CH2:40]4)[CH:36]=[CH:37][C:30]=3[CH2:29][CH2:28]2)[CH2:26][CH2:25][CH2:24]1>ClCCl>[CH:23]1([N:27]2[CH2:33][CH2:32][C:31]3[CH:34]=[C:35]([O:38][CH:39]4[CH2:44][CH2:43][N:42]([C:7]([C:6]5[CH:5]=[CH:4][C:3]([C:1]#[N:2])=[CH:11][CH:10]=5)=[O:9])[CH2:41][CH2:40]4)[CH:36]=[CH:37][C:30]=3[CH2:29][CH2:28]2)[CH2:24][CH2:25][CH2:26]1

Participants

5

Reactant 3

HCID 120874-Cyanobenzoic acidHCID 27960291-Hydroxybenzotriazole hydrateHCID 685061053-cyclobutyl-7-(piperidin-4-yloxy)-2,3,4,5-tetrahydro-1H-benzo[d]azepine

Product 1

HCID 10432796HCID 10432796, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

4-Cyanobenzoic acid (147 mg, 1 mmol), 1-hydroxy benzotriazole hydrate (154 mg, 1 mmol) and N-cyclohexylcarbodiimide N′-methyl polystyrene (1.8 mmol/g, 555 mg, 1 mmol) were stirred at room temperature in dichloromethane (5 ml) for 15 minutes. 3-cyclobutyl-7-(piperidin-4-yloxy)-2,3,4,5-tetrahydro-1H-benzo[d]azepine (E6) (150 mg, 0.5 mmol) was added and stirring continued for 16 hours. The reaction mixture was applied to a SCX ion exchange cartridge (Varian bond-elute, 5 g) and washed with methanol and then a mixture of 0.880 ammonia:methanol (1:9). The combined basic fractions were concentrated in vacuo and the resulting residue was purified by column chromatography eluting with dichloromethane then a mixture of 0.880 ammonia:ethanol:dichloromethate (1:9:90) to afford the title product (E13). MS (ES+) m/e 430 [M+H]+.

Workup

  1. washwashed with methanol
  2. additiona mixture of 0.880 ammonia:methanol (1:9)
  3. concentrationThe combined basic fractions were concentrated in vacuo
  4. customthe resulting residue was purified by column chromatography
  5. washeluting with dichloromethane
  6. additiona mixture of 0.880 ammonia

Sources & evidence

ORD record
ord-5c3894921d8d44a28f54e2efdb733043
Source dataset
uspto-grants-2012_06
Patent number
US08207331B2

Reaction notes

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