Ethanol → HCID 178473778, compound

HRID 2367814Notes

Reaction equation

HRID 2367814 reaction equation
C(OC([N:8]1[CH2:13][C:12]([C:14]2[CH:19]=[C:18]([CH:20]3[CH2:25][CH2:24][N:23]([C:26](=[O:28])[CH3:27])[CH2:22][CH2:21]3)[CH:17]=[CH:16][C:15]=2[NH:29][C:30]([C:32]2[N:33](COCC[Si](C)(C)C)[CH:34]=[C:35]([C:37]#[N:38])[N:36]=2)=[O:31])=[CH:11][CH2:10][CH2:9]1)=O)(C)(C)C.CCO.[C:50]([OH:56])([C:52]([F:55])([F:54])[F:53])=[O:51]>C(Cl)Cl>[C:50]([OH:56])([C:52]([F:55])([F:54])[F:53])=[O:51].[F:53][C:52]([F:55])([F:54])[C:50]([OH:56])=[O:51].[C:26]([N:23]1[CH2:22][CH2:21][CH:20]([C:18]2[CH:17]=[CH:16][C:15]([NH:29][C:30]([C:32]3[NH:33][CH:34]=[C:35]([C:37]#[N:38])[N:36]=3)=[O:31])=[C:14]([C:12]3[CH2:13][NH:8][CH2:9][CH2:10][CH:11]=3)[CH:19]=2)[CH2:25][CH2:24]1)(=[O:28])[CH3:27]

Participants

6

Reactant 3

HCID 702EthanolHCID 6422Trifluoroacetic acidHCID 591285915-(5-(1-Acetyl-piperidin-4-yl)-2-{[4-cyano-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazole-2-carbonyl]-amino}-phenyl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester

Product 2

HCID 6422Trifluoroacetic acidYield 0.1%HCID 178473778HCID 178473778, compoundYield 22%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 5-(5-(1-acetyl-piperidin-4-yl)-2-{[4-cyano-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazole-2-carbonyl]-amino}-phenyl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester (as prepared in the previous step, 0.40 g, 0.61 mmol) in CH2Cl2 (20 mL) and EtOH (0.4 mL) was treated with TFA (3 mL). The solution was stirred at room temperature for 0.5 h. The solvents were evaporated in vacuo, and the residue was immediately taken up in EtOH (25 mL) and stored at 5° C. for 11 h. The solution was concentrated in vacuo, and the residue was taken up in CH2Cl2 (20 mL) and EtOH (0.4 mL) then treated with TFA (6 mL). The reaction was stirred at room temperature for 2 h, and the solvents were evaporated in vacuo. Reverse phase HPLC (C-18 column) (10 to 80% acetonitrile in water with 0.1% TFA over 30 min) afforded the title compound (56.9 mg, 22%) as a white solid. 1H-NMR (CDCl3; 400 MHz): δ 8.06 (s, 1H), 7.81 (d, 1H, J=8.4 Hz), 7.32 (d, 1H, J=8.4 Hz), 7.22 (s, 1H), 6.10-6.03 (m, 1H), 4.74-4.64 (m, 2H), 4.11-4.02 (m, 1H), 3.95 (s, 2H), 3.50-3.37 (m, 2H), 3.29-3.20 (m, 1H), 2.93-2.82 (m, 1H), 2.80-2.69 (m, 1H), 2.62-2.53 (m, 2H), 2.16 (s, 3H), 1.98-1.84 (m, 2H), 1.78-1.54 (m, 2H). LC-MS (ESI, m/z): Calcd. for C23H26N6O2 419.2 (M+H). found 419.2.

Workup

  1. customThe solvents were evaporated in vacuo
  2. waitstored at 5° C. for 11 h
  3. concentrationThe solution was concentrated in vacuo
  4. additionEtOH (0.4 mL) then treated with TFA (6 mL)
  5. stirringThe reaction was stirred at room temperature for 2 h
  6. customthe solvents were evaporated in vacuo

Sources & evidence

ORD record
ord-29c38351906d4f0a9205ab3011be71ed
Source dataset
uspto-grants-2014_04
Patent number
US08697716B2

Reaction notes

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