Triethylamine → HCID 178467492, compound

HRID 541376Notes

Reaction equation

HRID 541376 reaction equation
[CH:1]1([C:4]2[C:26]([C:27]3[NH:31][C:30]([O:32][CH2:33][CH3:34])=[N:29][N:28]=3)=[CH:25][C:7]([C:8]([N:10]3[CH2:15][CH2:14][CH:13]([C:16]4[CH:24]=[CH:23][C:19]([C:20]([NH2:22])=O)=[CH:18][CH:17]=4)[CH2:12][CH2:11]3)=[O:9])=[C:6]([CH2:35][CH3:36])[CH:5]=2)[CH2:3][CH2:2]1.FC(F)(F)C(OC(=O)C(F)(F)F)=O.C(N(CC)CC)C>ClCCl>[CH:1]1([C:4]2[C:26]([C:27]3[NH:31][C:30]([O:32][CH2:33][CH3:34])=[N:29][N:28]=3)=[CH:25][C:7]([C:8]([N:10]3[CH2:11][CH2:12][CH:13]([C:16]4[CH:24]=[CH:23][C:19]([C:20]#[N:22])=[CH:18][CH:17]=4)[CH2:14][CH2:15]3)=[O:9])=[C:6]([CH2:35][CH3:36])[CH:5]=2)[CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 9845Trifluoroacetic anhydrideHCID 178467495HCID 178467495, compound2×

Product 1

HCID 178467492HCID 178467492, compoundYield 20%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
25 °C

Procedure

To a round-bottom flask, which was purged and maintained with a nitrogen atmosphere, was added a solution of 4-(1-(4-cyclopropyl-5-(5-ethoxy-4H-1,2,4-triazol-3-yl)-2-ethylbenzoyl)piperidin-4-yl)benzamide (compound 228.4, 80.0 mg, 0.160 mmol, 1.00 equiv) in dichloromethane (10 mL). Trifluoroacetic anhydride (34.0 mg, 0.160 mmol, 1.00 equiv) and triethylamine (33.0 mg, 0.330 mmol, 2.00 equiv) were added dropwise to the stirred mixture. The resulting solution was stirred for 2 h at 25° C., then washed with 1×10 mL of brine. The aqueous layer was extracted with 2×20 mL of dichloromethane and the combined organic layers were dried over anhydrous sodium sulfate and concentrated in vacuo. The crude product (30 mg) was purified by Prep-HPLC with the following conditions (1#-Pre-HPLC-001(SHIMADZU)): Column, SunFire Prep C18, 19*150 mm 5 um; mobile phase, water with 0.05% TFA and CH3CN (42% CH3CN up to 57% in 8 min, up to 100% in 1.5 min, down to 42% in 1 min); Detector, Waters 2489 254&220 nm. The fractions containing pure compound were combined and lyophilized to yield 15 mg (20%) of the title compound as a an off-white solid. m/z (ES+) 470 (M+H)+. 1H-NMR (300 MHz, CD3OD, ppm): δ 7.64 (d, 2H), 7.46-7.28 (m, 3H), 7.02-7.01 (m, 1H), 4.89-4.80 (m, 1H), 4.40-4.33 (m, 2H), 3.58-3.56 (m, 1H), 3.27-3.25 (m, 1H), 3.04-2.90 (m, 2H), 2.73-2.58 (m, 2H), 2.31-2.29 (m, 1H), 1.94-1.96 (m, 1H), 1.82-1.78 (m, 3H), 1.45 (t, 3H), 1.32-1.12 (m, 3H), 0.98-0.88 (m, 2H), 0.71-0.68 (m, 2H).

Workup

  1. customTo a round-bottom flask, which was purged
  2. temperaturemaintained with a nitrogen atmosphere
  3. washwashed with 1×10 mL of brine
  4. extractionThe aqueous layer was extracted with 2×20 mL of dichloromethane
  5. dry with materialthe combined organic layers were dried over anhydrous sodium sulfate
  6. concentrationconcentrated in vacuo
  7. customThe crude product (30 mg) was purified by Prep-HPLC with the following conditions (1#-Pre-HPLC-001(SHIMADZU))
  8. waitmobile phase, water with 0.05% TFA and CH3CN (42% CH3CN up to 57% in 8 min
  9. waitup to 100% in 1.5 min
  10. waitdown to 42% in 1 min)
  11. additionThe fractions containing pure compound

Sources & evidence

ORD record
ord-dd9ae83752a844ac8c3be6a32cb4d6a5
Source dataset
uspto-grants-2014_10
Patent number
US08871790B2

Reaction notes

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