4-Bromobenzoic acid → HCID 68407948, compound

HRID 888018Notes

Reaction equation

HRID 888018 reaction equation
[Br:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=O)=[CH:4][CH:3]=1.F[P-](F)(F)(F)(F)F.N1C2C=CC=C(O[P+](N3CCCC3)(N3CCCC3)N3CCCC3)C=2N=N1.[NH2:44][C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][C:46]=1[NH:51][C:52](=[O:65])[C:53]1[CH:58]=[CH:57][C:56]([CH:59]2[CH2:64][CH2:63][NH:62][CH2:61][CH2:60]2)=[CH:55][CH:54]=1>CN(C=O)C>[NH2:44][C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][C:46]=1[NH:51][C:52](=[O:65])[C:53]1[CH:58]=[CH:57][C:56]([CH:59]2[CH2:64][CH2:63][N:62]([C:6](=[O:8])[C:5]3[CH:4]=[CH:3][C:2]([Br:1])=[CH:10][CH:9]=3)[CH2:61][CH2:60]2)=[CH:55][CH:54]=1

Participants

5

Reactant 3

HCID 114644-Bromobenzoic acidHCID 16225584N-(2-Aminophenyl)-4-piperidin-4-ylbenzamideHCID 178506432HCID 178506432, compound

Product 1

HCID 68407948HCID 68407948, compoundYield 35.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 4-bromobenzoic acid (1.0 g, 3.3 mmol) in DMF (5 ml) was added benzotriazolyloxytripyrollidinophosphonium hexafluorophosphate (99 mg, 0.19 mmol) and the mixture stirred at ambient temperature for 30 minutes. N-(2-aminophenyl)-4-piperidin-4-ylbenzamide (Example 5, 50 mg, 0.17 mmol) was added and the mixture stirred for a further 24 hours. The resulting solution was absorbed onto an SCX-2 column, washed with methanol (2 column volumes) and eluted with a 2M solution of ammonia in methanol (2 column volumes) to afford the product. This was purified by flash chromatography (eluting with 0-20% methanol/dichloromethane) to afford the title compound as a colourless solid (29 mg, 18%); NMR Spectrum: (DMSO-d6) 1.70 (m, 4H), 2.60 (m, 1H), 2.91 (m, 2H), 3.31 (m, 2H), 4.89 (s, 2H), 6.60 (t, 1H), 6.78 (d, 1H), 6.97 (t, 1H), 7.16 (d, 1H), 7.43 (d, 4H), 7.67 (d, 2H), 7.93 (d, 2H), 9.60 (s, 1H); Mass Spectrum: M+H+ 478.

Workup

  1. stirringthe mixture stirred for a further 24 hours
  2. customThe resulting solution was absorbed onto an SCX-2 column
  3. washwashed with methanol (2 column volumes)
  4. washeluted with a 2M solution of ammonia in methanol (2 column volumes)
  5. customto afford the product
  6. customThis was purified by flash chromatography (eluting with 0-20% methanol/dichloromethane)

Sources & evidence

ORD record
ord-b099877386c2436db1e4d0bfb5f855ff
Source dataset
uspto-grants-2012_08
Patent number
US08247562B2

Reaction notes

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