Triethylamine → HCID 15952251, compound

HRID 1642246Notes

Reaction equation

HRID 1642246 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:36])[CH:33]([CH3:35])[CH3:34]>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:36])[CH:33]([CH3:35])[CH3:34])[CH2:12][CH2:11]1)=[O:8]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 62325Isobutyryl chlorideHCID 575503182-(2,4-Dichlorophenoxy)-N-(piperidin-4-yl)benzamide

Product 1

HCID 15952251HCID 15952251, compoundYield 78%

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 isobutyryl chloride (0.035 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-isobutyrylpiperidin-4-yl)benzamide (93 mg, 77%) as a white solid. Rf: 0.15 (hexane/AcOEt 4:6), mp 51-54° C. LC/MS (APCI) tr=4.66 min, m/z 437.33 (66), 435.31 (M++H, 100). HPLC tr=2.39 min (97.97%) 1H NMR (270 MHz, CDCl3) δ 1.10 (6H, d, J=6.7 Hz, 2CH3), 1.36 (2H, m, CH2), 2.00 (2H, m, CH2), 2.78 (1H, hept, J=6.7 Hz, CHMe2), 2.80 (1H, m, ½CH2), 3.18 (1H, br t, ½CH2), 3.83 (1H, m, ½CH2), 4.19 (1H, m, CH), 4.44 (1H, m, ½CH2), 6.79 (1H, d, J=8.6 Hz, ArH), 6.87 (1H, d, J=8.7 Hz, ArH), 7.19-7.28 (2H, m, ArH), 7.35 (1H, br s, NH), 7.40 (1H, m, ArH), 7.50 (1H, d, J=2.5 Hz, ArH) and 8.17 (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-cd4f71ec81374fa0a2668c78f27cdcc3
Source dataset
uspto-grants-2012_02
Patent number
US08119627B2

Reaction notes

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