Ethyl Acetate → HCID 178474042, compound

HRID 2402082Notes

Reaction equation

HRID 2402082 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([OH:44])([CH:37]2[CH2:42][CH2:41][N:40]([CH3:43])[CH2:39][CH2:38]2)[C:9]2[CH:10]=[C:11]([C:27]3[CH:32]=[CH:31][N:30]=[C:29]([NH:33][C:34](=[O:36])[CH3:35])[CH:28]=3)[S:12][C:13]=2[C:14]2[N:18]=[CH:17][N:16](COCC[Si](C)(C)C)[N:15]=2)=[CH:4][CH:3]=1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC.C([O-])(O)=O.[Na+].CCOC(C)=O>O1CCCC1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]([OH:44])([CH:37]2[CH2:42][CH2:41][N:40]([CH3:43])[CH2:39][CH2:38]2)[C:9]2[CH:10]=[C:11]([C:27]3[CH:32]=[CH:31][N:30]=[C:29]([NH:33][C:34](=[O:36])[CH3:35])[CH:28]=3)[S:12][C:13]=2[C:14]2[NH:18][CH:17]=[N:16][N:15]=2)=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 516892Sodium BicarbonateHCID 2724141Tetrabutylammonium FluorideHCID 66749527HCID 66749527, compound

Product 1

HCID 178474042HCID 178474042, compoundYield 25%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
80 °C

Procedure

A 5 mL microwave tube was charged with N-(4-{4-[(4-chlorophenyl)(hydroxy)(1-methylpiperidin-4-yl)methyl]-5-(1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-1,2,4-triazol-3-yl)-2-thienyl}pyridin-2-yl)acetamide (10.0 mg, 0.0153 mmol) and tetrahydrofuran (0.500 mL, 6.16 mmol). To the solution was added 1.00 M of tetra-n-butylammonium fluoride in tetrahydrofuran (61.2 uL). The tube was sealed and heated to 80° C. in an oil bath for 4 hrs. The resulting mixture was cooled to rt and distributed between NaHCO3(aq) saturated solution and EtOAc. The aqueous layer was extracted with EtOAc (×2). The combined org layer was dried and concentrated. Purification on HPLC (reverse phase, AA) provided N-(4-{4-[(4-chlorophenyl)(hydroxy)(1-methylpiperidin-4-yl)methyl]-5-(4H-1,2,4-triazol-3-yl)-2-thienyl}pyridin-2-yl)acetamide as a white solid. (2.0 mg, 25% yield) LCMS (AA) ES+ 523, 525; 1H NMR (400 MHz, MeOD) δ 8.50-8.42 (s, 1H), 8.41-8.36 (s, 1H), 8.36-8.29 (d, J=5.3 Hz, 1H), 7.92-7.83 (s, 1H), 7.50-7.43 (m, 1H), 7.43-7.34 (d, J=8.6 Hz, 2H), 7.25-7.14 (d, J=8.6 Hz, 2H), 2.91-2.76 (m, 1H), 2.65-2.55 (m, 4H), 2.26-2.15 (s, 3H), 2.11-2.01 (m, 2H), 1.88-1.72 (m, 2H), 1.70-1.57 (s, 1H), 1.47-1.35 (dd, J=15.0, 7.4 Hz, 1H), 1.31-1.20 (m, 2H).

Workup

  1. customThe tube was sealed
  2. temperatureThe resulting mixture was cooled to rt
  3. extractionThe aqueous layer was extracted with EtOAc (×2)
  4. customThe combined org layer was dried
  5. concentrationconcentrated
  6. customPurification on HPLC (reverse phase, AA)

Sources & evidence

ORD record
ord-b42182d441014cdd85e0162390bd720b
Source dataset
uspto-grants-2014_08
Patent number
US08796271B2

Reaction notes

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