Triethylamine → HCID 178467494, compound

HRID 541332Notes

Reaction equation

HRID 541332 reaction equation
[CH2:1]([O:3][C:4]1[NH:5][C:6]([C:9]2[C:10]([CH2:34][CH3:35])=[CH:11][C:12]([CH2:32][CH3:33])=[C:13]([CH:31]=2)[C:14]([N:16]2[CH2:21][CH2:20][CH:19]([C:22]3[CH:30]=[CH:29][C:25]([C:26]([NH2:28])=O)=[CH:24][CH:23]=3)[CH2:18][CH2:17]2)=[O:15])=[N:7][N:8]=1)[CH3:2].C(N(CC)CC)C.O(C(C(F)(F)F)=O)C(C(F)(F)F)=O>ClCCl.C(OCC)(=O)C>[CH2:1]([O:3][C:4]1[NH:5][C:6]([C:9]2[C:10]([CH2:34][CH3:35])=[CH:11][C:12]([CH2:32][CH3:33])=[C:13]([CH:31]=2)[C:14]([N:16]2[CH2:21][CH2:20][CH:19]([C:22]3[CH:23]=[CH:24][C:25]([C:26]#[N:28])=[CH:29][CH:30]=3)[CH2:18][CH2:17]2)=[O:15])=[N:7][N:8]=1)[CH3:2]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 9845Trifluoroacetic anhydrideHCID 178467497HCID 178467497, compound2×

Product 1

HCID 178467494HCID 178467494, compoundYield 64.3%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a round-bottom flask was added a solution of 4-(1-(5-(5-ethoxy-4H-1,2,4-triazol-3-yl)-2,4-diethylbenzoyl)piperidin-4-yl)benzamide (compound 204.9, 100 mg, 0.170 mmol, 1.00 equiv) in dichloromethane (10 mL). Triethylamine (170 mg, 1.68 mmol, 8.00 equiv) was added to the reaction at room temperature, followed by dropwise addition of a solution of (CF3CO)2O (160 mg, 0.760 mmol, 4.50 equiv) in dichloromethane (0.5 mL) at 0 to 5° C. The resulting solution was stirred at room temperature for another 2 hours. The mixture was diluted with 60 mL of ethyl acetate, then washed with 3×20 mL of brine. The organic layer was dried over anhydrous sodium sulfate, and concentrated in vacuo. The residue was purified by prep-HPLC (SunFire Prep C18, 19*150 mm 5 um, water with 0.05% TFA and CH3CN (53.0% CH3CN up to 65.0% in 8 min, up to 100.0% in 2 min, down to 53.0% in 1 min). The fractions containing pure compound were combined and lyophilized to yield 50 mg (50%) of the title compound as a white solid. m/z (ES+) 458 (M+H)+. 1H NMR (300 MHz, CD3OD): δ 7.63 (d, 2H), 7.45-7.30 (m, 4H), 4.89-4.80 (m, 1H, overlapped), 4.36 (q, 2H), 3.60-3.57 (m, 1H), 3.29-3.23 (m, 1H), 3.19-2.85 (m, 4H), 2.74-2.56 (m, 2H), 2.00-1.82 (m, 1H), 1.77-1.66 (m, 3H), 1.40 (t, 3H), 1.30-1.21 (m, 3H), 1.11 (t, 3H).

Workup

  1. washwashed with 3×20 mL of brine
  2. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  3. concentrationconcentrated in vacuo
  4. customThe residue was purified by prep-HPLC (SunFire Prep C18, 19*150 mm 5 um, water with 0.05% TFA and CH3CN (53.0% CH3CN up to 65.0% in 8 min
  5. waitup to 100.0% in 2 min
  6. waitdown to 53.0% in 1 min)
  7. additionThe fractions containing pure compound

Sources & evidence

ORD record
ord-5ee75f1f62a04121afdc2e6e655b809d
Source dataset
uspto-grants-2014_10
Patent number
US08871790B2

Reaction notes

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