Triethylamine → 3-iodo-4-methyl-N-(4-((4-methylpiperazin-1-yl)methyl)-3-(trifluoromethyl)phenyl)benzamide

HRID 535836Notes

Reaction equation

HRID 535836 reaction equation
[I:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[CH3:11])[C:5](Cl)=[O:6].IC1C=C(C=CC=1C)C(O)=O.O=S(Cl)Cl.[CH3:27][N:28]1[CH2:33][CH2:32][N:31]([CH2:34][C:35]2[CH:41]=[CH:40][C:38]([NH2:39])=[CH:37][C:36]=2[C:42]([F:45])([F:44])[F:43])[CH2:30][CH2:29]1.CCN(CC)CC>CN(C1C=CN=CC=1)C.C1COCC1>[I:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[CH3:11])[C:5]([NH:39][C:38]1[CH:40]=[CH:41][C:35]([CH2:34][N:31]2[CH2:30][CH2:29][N:28]([CH3:27])[CH2:33][CH2:32]2)=[C:36]([C:42]([F:45])([F:44])[F:43])[CH:37]=1)=[O:6]

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 24386Thionyl ChlorideHCID 6216403-Iodo-4-methylbenzoic acidHCID 177521573-Iodo-4-methylbenzoyl chlorideHCID 46838908AP-24592

Product 1

HCID 468389103-iodo-4-methyl-N-(4-((4-methylpiperazin-1-yl)methyl)-3-(trifluoromethyl)phenyl)benzamideYield 67.2%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 8028TetrahydrofuranSolvent

Procedure

3-Iodo-4-methylbenzoyl chloride (1.06 g, 3.8 mmol), prepared from the reaction of 3-iodo-4-methylbenzoic acid and SOCl2, was added to a solution of 4-((4-methylpiperazin-1-yl)methyl)-3-(trifluoromethyl)aniline (1.00 g, 3.6 mmol), Et3N (0.36 g 3.6 mmol), and a catalytic amount of DMAP in THF (20 mL). After stirring at rt for 2 hrs, the reaction was quenched with water. EtOAc was added and the layers separated. The combined organic layers were concentrated to dryness and purified by silica gel chromatography (eluent: 5% MeOH in CH2Cl2, MeOH was added 0.5% Et3N) to provide the desired product as an off-white solid (67.2%, 1.25 g). 1H NMR (300 MHz, CDCl3) δ: 8.29 (1H, s), 8.00 (1H, s), 7.85 ((1H, m), 7.73-7.76 ((2H, m), 7.31-7.34 ((1H, d, J=9.0 Hz), 3.64 (2H, s), 2.53 (8H, brs), 2.49 (3H, s), 2.33 (3H, s).

Workup

  1. customthe reaction was quenched with water
  2. additionEtOAc was added
  3. customthe layers separated
  4. concentrationThe combined organic layers were concentrated to dryness
  5. custompurified by silica gel chromatography (eluent: 5% MeOH in CH2Cl2, MeOH was added 0.5% Et3N)

Sources & evidence

ORD record
ord-48fa6a024c4d424eb41c866372abfdf4
Source dataset
uspto-grants-2014_10
Patent number
US08859553B2

Reaction notes

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