1-Methylpiperazine → HCID 25118518, compound

HRID 386459Notes

Reaction equation

HRID 386459 reaction equation
[CH:1]([C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:14]=[CH:13][C:12]([CH2:15][CH2:16][C:17]([C:19]3[O:20][C:21]([C:24]4[N:29]=[C:28]([C:30]([O:32][CH3:33])=[O:31])[CH:27]=[CH:26][CH:25]=4)=[CH:22][N:23]=3)=[O:18])=[CH:11][CH:10]=2)=[CH:5][CH:4]=1)=O.[CH3:34][N:35]1[CH2:40][CH2:39][NH:38][CH2:37][CH2:36]1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>ClC(Cl)C>[CH3:34][N:35]1[CH2:40][CH2:39][N:38]([CH2:1][C:3]2[CH:8]=[CH:7][C:6]([C:9]3[CH:10]=[CH:11][C:12]([CH2:15][CH2:16][C:17]([C:19]4[O:20][C:21]([C:24]5[N:29]=[C:28]([C:30]([O:32][CH3:33])=[O:31])[CH:27]=[CH:26][CH:25]=5)=[CH:22][N:23]=4)=[O:18])=[CH:13][CH:14]=3)=[CH:5][CH:4]=2)[CH2:37][CH2:36]1

Participants

5

Reactant 3

HCID 531671-MethylpiperazineHCID 5049666Sodium triacetoxyborohydrideHCID 86645815HCID 86645815, compound

Product 1

HCID 25118518HCID 25118518, compoundYield 58%

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent

Procedure

Methyl 6-(2-(3-(4′-formylbiphenyl-4-yl)propanoyl)oxazol-5-yl)pyridine-2-carboxylate (19 mg, 0.043 mmol) and 1-methyl piperazine (0.007 mL, 0.07 mmol) were dissolved in dichloroethane (2 mL) and NaBH(OAc)3 (18 mg, 0.086 mmol) was added. The reaction solution was stirred under an atmosphere of Ar at ambient temperature for 3.5 h and then quenched with saturated aqueous NaHCO3. The crude product was extracted with EtOAc and the solvent was removed in vacuo. The crude product was purified by flash chromatography (SiO2, 2.5% Et3N/EtOAc) to furnish methyl 6-(2-(3-(4′-((4-methylpiperazin-1-yl)methyl)biphenyl-4-yl)propanoyl)oxazol-5-yl)pyridine-2-carboxylate as a clear tan oil (13 mg, 58%): 1H NMR (CDCl3, 600 MHz) δ 8.11 (d, 1H, J=7.7 Hz), 8.02 (d, 2H, J=9.0 Hz), 7.96 (t, 1H, J=7.8 Hz), 7.51 (dd, 4H, J=8.2, 2.2 Hz), 7.36 (d, 2H, J=8.0 Hz), 7.33 (d, 2H, J=8.0 Hz), 4.03 (s, 3H), 3.54 (s, 2H), 3.51 (t, 2H, J=7.6 Hz), 3.15 (t, 2H, J=7.6 Hz), 2.50 (bs, 8H), 2.30 (s, 3H); 13C NMR (CDCl3, 150 MHz) δ 187.3, 165.1, 157.4, 152.4, 148.5, 146.5, 139.7, 139.3, 139.0, 138.3, 137.1, 129.6, 128.9, 128.0, 127.1, 126.8, 125.2, 123.3, 62.6, 55.1, 53.1, 53.0, 45.9, 40.6, 29.3; HR ESI-TOF m/z 525.2493 (M+H+, C31H32N4O4, requires 525.2496).

Workup

  1. customquenched with saturated aqueous NaHCO3
  2. extractionThe crude product was extracted with EtOAc
  3. customthe solvent was removed in vacuo
  4. customThe crude product was purified by flash chromatography (SiO2, 2.5% Et3N/EtOAc)

Sources & evidence

ORD record
ord-401ce18cb8844ae48178d2a9c74fc940
Source dataset
uspto-grants-2013_02
Patent number
US08372823B2

Reaction notes

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