Diisopropylethylamine → 4-{4-[5-(3-Iodo-4-methyl-phenylcarbamoyl)-pyridin-2-yl]-piperazin-1-yl}-benzoic acid ethyl ester

HRID 2190585Notes

Reaction equation

HRID 2190585 reaction equation
Cl[C:2]1[CH:18]=[CH:17][C:5]([C:6]([NH:8][C:9]2[CH:14]=[CH:13][C:12]([CH3:15])=[C:11]([I:16])[CH:10]=2)=[O:7])=[CH:4][N:3]=1.C(N(C(C)C)CC)(C)C.[CH2:28]([O:30][C:31](=[O:44])[C:32]1[CH:37]=[CH:36][C:35]([N:38]2[CH2:43][CH2:42][NH:41][CH2:40][CH2:39]2)=[CH:34][CH:33]=1)[CH3:29]>CN(C1C=CN=CC=1)C.O1CCOCC1>[CH2:28]([O:30][C:31](=[O:44])[C:32]1[CH:33]=[CH:34][C:35]([N:38]2[CH2:39][CH2:40][N:41]([C:2]3[CH:18]=[CH:17][C:5]([C:6](=[O:7])[NH:8][C:9]4[CH:14]=[CH:13][C:12]([CH3:15])=[C:11]([I:16])[CH:10]=4)=[CH:4][N:3]=3)[CH2:42][CH2:43]2)=[CH:36][CH:37]=1)[CH3:29]

Participants

6

Reactant 3

HCID 81531Diisopropylethylamine2×HCID 2761178Ethyl 4-(piperazin-1-yl)benzoate2×HCID 79255626-chloro-N-(3-iodo-4-methyl-phenyl)-nicotinamide

Product 1

HCID 593180634-{4-[5-(3-Iodo-4-methyl-phenylcarbamoyl)-pyridin-2-yl]-piperazin-1-yl}-benzoic acid ethyl esterYield 65%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

A solution of 6-chloro-N-(3-iodo-4-methyl-phenyl)-nicotinamide (50 mg, 0.13 mmol), a catalytic amount of DMAP, diisopropylethyl amine (0.07 mL, 0.41 mmol), 4-(piperazin-1-yl)-benzoic acid ethyl ester (94 mg, 0.41 mmol) in 5 mL in dioxane was heated at 120° C. in a sealed tube for about 23 h. The reaction mixture was cooled, followed addition of another portion of 4-(piperazin-1-yl)-benzoic acid ethyl ester (94 mg, 0.41 mmol) and diisopropyl ethyl amine (0.07 mL, 0.41 mmol) and the mixture was re-heated at 120° C. for 3 more days. The reaction mixture was then cooled and partitioned between EtOAc and aq. saturated Na2CO3. The organic layer was then collected, dried over Na2SO4 filtered and concentrated. The residue was chromatographed with a silica gel column and 20-40% EtOAc in hexanes to afford the product (23 mg. Yield: 65%). HRMS m/z calcd for C26H27N4O3I [M+H]: 571.1201. Found: 571.1197.

Workup

  1. temperatureThe reaction mixture was cooled
  2. temperatureThe reaction mixture was then cooled
  3. custompartitioned between EtOAc and aq. saturated Na2CO3
  4. customThe organic layer was then collected
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was chromatographed with a silica gel column and 20-40% EtOAc in hexanes
  9. customto afford the product (23 mg. Yield: 65%)

Sources & evidence

ORD record
ord-9b31a804e60f4b138644f0276dd256fe
Source dataset
uspto-grants-2012_12
Patent number
US08324385B2

Reaction notes

Loading…