Acetic Acid → 1-(4-{2-[(Pyrimidin-2-yl)sulfanyl]anilino}piperidin-1-yl)ethan-1-one

HRID 1642264Notes

Reaction equation

HRID 1642264 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[N:3][C:2]=1[S:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[NH2:14].[C:15]([N:18]1[CH2:23][CH2:22][CH2:21][CH2:20][C:19]1=O)(=[O:17])[CH3:16].C(O)(=O)C.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>ClCCCl.C(Cl)Cl>[N:1]1[CH:6]=[CH:5][CH:4]=[N:3][C:2]=1[S:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[NH:14][CH:21]1[CH2:22][CH2:23][N:18]([C:15](=[O:17])[CH3:16])[CH2:19][CH2:20]1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 5049666Sodium triacetoxyborohydrideHCID 118159051-Acetylpiperidin-2-oneHCID 14531193HCID 14531193, compound

Product 1

HCID 159517751-(4-{2-[(Pyrimidin-2-yl)sulfanyl]anilino}piperidin-1-yl)ethan-1-oneYield 22.3%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
100 °C

Procedure

A solution of 2-(pyrimidin-2-ylsulfanyl)-phenylamine (AMR01106, 100 mg, 0.492 mmol), 1-acetylpiperidone (69.5 mg, 0.492 mmol) and acetic acid (0.15 mL, 2.46 mmol) in DCE (2 mL) was treated with NaBH(OAc)3 (261 mg, 1.23 mmol) and stirred under microwave irradiation for 15 min at 100° C. The reaction mixture was diluted with DCM (10 mL) and quenched with saturated NaHCO3 solution. The aqueous layer was washed with DCM (2×20 mL), and the combined organic layers were dried (MgSO4), filtered and evaporated to dryness. Column chromatography on silica gel of the crude product using AcOEt/MeOH 98:2 as eluent gave 1-{4-[2-(pyrimidin-2-ylsulfanyl)-phenylamino]-piperidin-1-yl}-ethanone 36 mg, 22%) as a colorless oil. 1H NMR (270 MHz, CDCl3) δ 1.20-1.40 (2H, m, CH2), 1.90-2.10 (2H, m, CH2), 2.05 (3H, s, CH3), 2.89 (1H, m, ½CH2), 3.18 (1H, m, ½CH2), 3.54-3.74 (2H, m, CH2), 4.26 (1H, m, CH), 4.75 (1H, br s, NH), 6.69-6.75 (2H, m, ArH), 6.97 (1H, t, J=4.7 Hz, Pyrimidine-H), 7.33 (1H, m, ArH), 7.49 (1H, dd, J=7.4, 1.7 Hz, ArH) and 8.47 (2H, d, J=4.7 Hz, Pyrimidine-H), 13C NMR (270 MHz, CDCl3) δ 21.57 (CH3), 31.74, 32.56, 40.14, 45.00 (CH2), 49.63 (CH), 111.45, 111.57, 117.35, 132.12, 138.13, 148.49, 157.88 (ArC and Pyridine-C), and 171.77 (C═O).

Workup

  1. customquenched with saturated NaHCO3 solution
  2. washThe aqueous layer was washed with DCM (2×20 mL)
  3. dry with materialthe combined organic layers were dried (MgSO4)
  4. filtrationfiltered
  5. customevaporated to dryness

Sources & evidence

ORD record
ord-e256f9281a1d4de0ad551ac907b67272
Source dataset
uspto-grants-2012_02
Patent number
US08119627B2

Reaction notes

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