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

HRID 1622513Notes

Reaction equation

HRID 1622513 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.C(N(CC)C(C)C)(C)C>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 24386Thionyl ChlorideHCID 81531DiisopropylethylamineHCID 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 58%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 8028TetrahydrofuranSolvent

Procedure

3-Iodo-4-methylbenzoyl chloride (0.48 g, 1.7 mmol), prepared from the reaction of 3-iodo-4-methylbenzoic acid and SOCl2 (as previously described), was added to a solution of 4-((4-methylpiperazin-1-yl)methyl)-3-(trifluoromethyl)aniline (0.47 g, 1.7 mmol), N,N-diisopropylethylamine (0.26 g, 2.0 mmol), and a catalytic amount of DMAP in THF (10 mL). After stirring at rt for 2 h, 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 (eluted with 5% MeOH/DCM, MeOH was pre-saturated with ammonia gas), to provide 0.51 g of product as an off-white solid.

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 (eluted with 5% MeOH/DCM, MeOH was pre-saturated with ammonia gas)

Sources & evidence

ORD record
ord-e03efaf87e554884af35a656e4a3aaec
Source dataset
uspto-grants-2014_07
Patent number
US08778942B2

Reaction notes

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