Triethylamine → HCID 15952350, compound

HRID 1642247Notes

Reaction equation

HRID 1642247 reaction equation
[Cl:1][C:2]1[CH:23]=[C:22]([Cl:24])[CH:21]=[CH:20][C:3]=1[O:4][C:5]1[CH:19]=[CH:18][CH:17]=[CH:16][C:6]=1[C:7]([NH:9][CH:10]1[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]1)=[O:8].C(N(CC)CC)C.[C:32](Cl)(=[O:37])[CH2:33][CH:34]([CH3:36])[CH3:35]>C(Cl)Cl>[Cl:1][C:2]1[CH:23]=[C:22]([Cl:24])[CH:21]=[CH:20][C:3]=1[O:4][C:5]1[CH:19]=[CH:18][CH:17]=[CH:16][C:6]=1[C:7]([NH:9][CH:10]1[CH2:15][CH2:14][N:13]([C:32](=[O:37])[CH2:33][CH:34]([CH3:36])[CH3:35])[CH2:12][CH2:11]1)=[O:8]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 66054Isovaleryl chlorideHCID 575503182-(2,4-Dichlorophenoxy)-N-(piperidin-4-yl)benzamide

Product 1

HCID 15952350HCID 15952350, compoundYield 79%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To an ice cooled solution of 4-[2-(2,4-dichlorophenoxy)-N-piperidin-4-ylbenzamide (AMR01077, 100 mg, 0.274 mmol) in dry DCM (5 mL) were added triethylamine (0.2 mL, 1.37 mmol) and isovaleryl chloride (0.04 mL, 0.33 mmol). The reaction mixture was stirred at room temperature until completion by TLC (1.5 h), and quenched with saturated NaHCO3. The organic solution was evaporated to dryness and the oil obtained was purified by column chromatography using DCM/MeOH 95:5 as eluent. Further purification was carried out by treating a DCM solution of the obtained compound with trisamine scavenger (100 mg) for 2 h. The scavenger was filtered off, and the solvent evaporated to give 2-(2,4-dichlorophenoxy)-N-[1-(3-methylbutyryl)piperidin-4-yl]benzamide (97 mg, 79%) as a colorless oil. Rf: 0.15 (hexane/AcOEt 4:6) LC/MS (APCI) tr=4.44 min, m/z 451.43 (68), 449.42 (M++H, 100). HPLC tr=3.17 min (98.27%) 1H NMR (270 MHz, CDCl3) δ 0.95 (6H, d, J=6.7 Hz, 2CH3), 1.33 (3H, m, CH2+½CH2), 2.19 (2H, d, J=6.7 Hz, CH2CO), 2.83 (1H, m, ½CH2), 3.15 (1H, m, ½CH2), 3.76 (1H, m, ½CH2), 4.16 (1H, m, CH), 4.44 (1H, m, ½CH2), 6.79 (1H, dd, J=8.2, 1.0 Hz, ArH), 6.86 (1H, d, J=8.6 Hz, ArH), 7.20 (1H, dd, J=8.7, 2.5 Hz, ArH), 7.25 (1H, m, ArH), 7.29 (1H, br s, NH), 7.41 (1H, m, ArH), 7.49 (1H, d, J=2.5 Hz, ArH) and 8.16 (1H, dd, J=7.7, 1.7 Hz, ArH).

Workup

  1. customquenched with saturated NaHCO3
  2. customThe organic solution was evaporated to dryness
  3. customthe oil obtained
  4. customwas purified by column chromatography
  5. customFurther purification
  6. additionby treating a DCM solution of the obtained compound with trisamine scavenger (100 mg) for 2 h
  7. filtrationThe scavenger was filtered off
  8. customthe solvent evaporated

Sources & evidence

ORD record
ord-e4817ef46e104ae596890e4ed72c086c
Source dataset
uspto-grants-2012_02
Patent number
US08119627B2

Reaction notes

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