Triethylamine → HCID 20765558, compound

HRID 1815521Notes

Reaction equation

HRID 1815521 reaction equation
C([O:3][C:4]([CH:6]1[CH2:11][CH2:10][N:9]([C:12]2[CH:13]=[C:14]([S:18][C:19]3[CH:24]=[CH:23][C:22](/[CH:25]=[CH:26]/[C:27](O)=[O:28])=[C:21]([Cl:30])[C:20]=3[Cl:31])[CH:15]=[CH:16][CH:17]=2)[CH2:8][CH2:7]1)=[O:5])C.[OH:32][CH:33]1[CH2:38][CH2:37][NH:36][CH2:35][CH2:34]1.CN(C)CCCN=C=NCC.C1C=CC2N(O)N=NC=2C=1.C(N(CC)CC)C.O.[OH-].[Li+]>CN(C=O)C.O.C(OCC)(=O)C>[C:4]([CH:6]1[CH2:11][CH2:10][N:9]([C:12]2[CH:13]=[C:14]([S:18][C:19]3[CH:24]=[CH:23][C:22](/[CH:25]=[CH:26]/[C:27]([N:36]4[CH2:37][CH2:38][CH:33]([OH:32])[CH2:34][CH2:35]4)=[O:28])=[C:21]([Cl:30])[C:20]=3[Cl:31])[CH:15]=[CH:16][CH:17]=2)[CH2:8][CH2:7]1)([OH:3])=[O:5]

Participants

10

Reactant 6

HCID 8471TriethylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 79341Piperidin-4-olHCID 168937Lithium hydroxide, monohydrateHCID 20765610HCID 20765610, compound

Product 1

HCID 20765558HCID 20765558, compoundYield 79.5%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a suspension of Example 412C (150 mg, 0.31 mmol) in DMF (3 mL) was added 4-hydroxypiperidine (63 mg, 0.62 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodimide (120 mg, 0.62 mmol), HOBt (84 mg, 0.62 mmol) and triethylamine (87 μL, 0.62 mmol) at room temperature. The mixture was stirred at the same temperature for 15 hours. Ethyl acetate was added, the mixture was washed with brine, water, and was concentrated. The residual oil was dissolved in THF (3 mL), and was added lithium hydroxide monohydrate (26 mg, 0.62 mmol) in water (1.5 mL). After stirring for 15 hours, the solution was separated by HPLC (Zorbax C-18) to give the title compound (132 mg, 55%). 1H NMR (300 MHz, DMSO-d6) δ 1.32 (m, 2H), 1.65 (m, 2H), 1.75 (m, 2H), 1.92 (m, 2H), 2.43 (m, 1H), 2.86 (t, J =10.6 Hz, 2H), 3.15 (m, 1H), 3.32 (m, 1H), 3.71 (m, 3H), 3.95 (m, 2H), 6.73 (d, J=8.5 Hz, 1H), 6.94 (d, J=7.2 Hz, 1H), 7.13 (d, J=7.8 Hz, 1H), 7.13 (s, 1H), 7.24 (d, J=15.2 Hz, 1H), 7.37 (t, J=8.1 Hz, 1H), 7.72 (d, J=15.2 Hz, 1H), 7.85 (d, J=8.5 Hz, 1H); MS (ESI+) m/z 535, 537 (M+H)+. Anal. calcd for C26H28N2Cl2SO4 0.25 TFA: C, 56.43; H, 5.05; N, 4.97. Found: C, 56.37; H, 5.00; N, 4.91.

Workup

  1. washthe mixture was washed with brine, water
  2. concentrationwas concentrated
  3. dissolutionThe residual oil was dissolved in THF (3 mL)
  4. stirringAfter stirring for 15 hours
  5. customthe solution was separated by HPLC (Zorbax C-18)

Sources & evidence

ORD record
ord-67167db308c04521a9dbaac69d0e46dc
Source dataset
uspto-grants-2005_04
Patent number
US06878700B1

Reaction notes

Loading…