Triethylamine → HCID 9848238, compound

HRID 1455514Notes

Reaction equation

HRID 1455514 reaction equation
CN(C(ON1[N:17]=[N:16][C:15]2[C:10]1=[CH:11][CH:12]=[CH:13][CH:14]=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH3:25][CH:26]([N:28]1[CH2:33][CH2:32][N:31]([CH2:34][C:35]2[C:36]([C:48]3[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=3)=[N:37][C:38]3[C:43]([C:44]=2[C:45](O)=[O:46])=[CH:42][CH:41]=[CH:40][CH:39]=3)[CH2:30][CH2:29]1)[CH3:27].NN1CCCCCC1.CCN(CC)CC>C1COCC1.C(Cl)Cl>[N:16]1([NH:17][C:45]([C:44]2[C:43]3[C:38](=[CH:39][CH:40]=[CH:41][CH:42]=3)[N:37]=[C:36]([C:48]3[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=3)[C:35]=2[CH2:34][N:31]2[CH2:32][CH2:33][N:28]([CH:26]([CH3:25])[CH3:27])[CH2:29][CH2:30]2)=[O:46])[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10][CH2:15]1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 221981-AminohomopiperidineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 11280720HCID 11280720, compound

Product 1

HCID 9848238HCID 9848238, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

O-Benzotriazole-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HBTU) (156 mg, 0.41 mmol) was added to a stirred mixture of 3-(4-(1-methylethyl)-piperazin-1-ylmethyl)-2-phenyl-quinoline-4-carboxylic acid (100 mg, 0.26 mmol) [J. Med. Chem. 2001, 44, 1675-1689], 1-aminohomopiperidine (47 μL, 0.41 mmol) and Et3N (178 μL, 1.3 mmol) in THF (5 mL) and CH2Cl2 (1.5 mL), and the mixture was heated at reflux for 18 h under N2. The solvent was evaporated under reduced pressure, and the residue was dissolved in CH2Cl2 and washed with H2O, 0.5 N NaOH solution, and H2O. The organic phase was dried (MgSO4) and concentrated under reduced pressure. The residue was purified by reverse phase preparative HPLC affording, after basic work up, the desired hydrazide (28 mg, 17%). 1H NMR (CD3OD, 360 MHz), Major rotamer δ 8.05 (1H, d, J=8.3 Hz), 7.96 (1H, d, J=8.3 Hz), 7.83-7.75 (1H, m), 7.72-7.60 (1H, m), 7.55-7.43 (5H, m), 3.66 (2H, s), 3.24-3.17 (4H, m), 2.53 (1H, septet, J=6.5 Hz), 2.45-2.10 (8H, m), 1.86-1.72 (8H, m), 1.00 (6H, d, J=6.5 Hz). MS (ES+) C30H39N5O requires: 485, found: 486 (M+H+, 100%).

Workup

  1. temperaturethe mixture was heated
  2. temperatureat reflux for 18 h under N2
  3. customThe solvent was evaporated under reduced pressure
  4. dissolutionthe residue was dissolved in CH2Cl2
  5. washwashed with H2O, 0.5 N NaOH solution, and H2O
  6. dry with materialThe organic phase was dried (MgSO4)
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by reverse phase preparative HPLC
  9. customaffording

Sources & evidence

ORD record
ord-9f4cbe73575e46e998de0dbcab668905
Source dataset
uspto-grants-2009_01
Patent number
US07482457B2

Reaction notes

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