Triethylamine → HCID 9872856, compound

HRID 1837382Notes

Reaction equation

HRID 1837382 reaction equation
[ClH:1].Cl.[CH:3]([N:6]1[CH2:11][CH2:10][N:9]([CH2:12][C:13]2[C:14]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)=[N:15][C:16]3[C:21]([C:22]=2[C:23](O)=[O:24])=[CH:20][CH:19]=[CH:18][CH:17]=3)[CH2:8][CH2:7]1)([CH3:5])[CH3:4].C(N(CC)CC)C.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.[CH:63]1([C@@H:69]([NH2:71])[CH3:70])[CH2:68][CH2:67][CH2:66][CH2:65][CH2:64]1>C(Cl)Cl.CC#N.C(Cl)Cl>[ClH:1].[ClH:1].[CH:63]1([C@@H:69]([NH:71][C:23]([C:22]2[C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[N:15]=[C:14]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[C:13]=2[CH2:12][N:9]2[CH2:8][CH2:7][N:6]([CH:3]([CH3:5])[CH3:4])[CH2:11][CH2:10]2)=[O:24])[CH3:70])[CH2:68][CH2:67][CH2:66][CH2:65][CH2:64]1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 5325951(S)-(+)-1-CyclohexylethylamineHCID 69547045HCID 69547045, compound

Product 1

HCID 9872856HCID 9872856, compoundYield 63%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 21877088Acetonitrile methylene chlorideSolvent

Conditions

Temperature
0 °C

Procedure

2.3 g (5.0 mmol) of crude 3-(4-isopropyl-piperazin-1-ylmethyl)-2-phenyl-quinoline-4-carboxylic acid dihydrochloride (compound of Description 6) were dissolved in 200 ml of a 1:1 mixture of CH2Cl2/CH3CN; 2.0 ml (15 mmol) of triethylamine (TEA) and 2.5 g (6.5 mmol) of O-benzotriazol-1-yl-N,N,N′,N′-tetramethyluroniumhexafluorophosphate (HBTU) were added and the reaction mixture was cooled at 0° C. 0.74 ml (5 mmol) of (S)-1-cyclohexyl-ethylamine, dissolved in 10 ml of dry CH2Cl2, were added dropwise and the reaction mixture was stirred at room temperature for 24 h. The solvent was evaporated in vacuo to dryness and the residue was taken up with EtOAc and washed with H2O, 1 N NaOH and brine, dried over Na2SO4 and evaporated to dryness to yield a crude material which was purified by flash column chromatography on 230-400 mesh silica gel, utilising a mixture of CH2Cl2/MeOH 95:5 containing 0.5% NH4OH (28%). The residue was dissolved in acetone and acidified with HCl/Et2O; the precipitate so formed was recovered by suction filtration to yield 0.9 g of the title compound as a yellow solid.

Workup

  1. additionwere added dropwise
  2. customThe solvent was evaporated in vacuo to dryness
  3. washwashed with H2O, 1 N NaOH and brine
  4. dry with materialdried over Na2SO4
  5. customevaporated to dryness
  6. customto yield a crude material which
  7. customwas purified by flash column chromatography on 230-400 mesh silica gel, utilising
  8. additiona mixture of CH2Cl2/MeOH 95:5 containing 0.5% NH4OH (28%)
  9. dissolutionThe residue was dissolved in acetone
  10. customthe precipitate so formed
  11. filtrationwas recovered by suction filtration

Sources & evidence

ORD record
ord-c851451043ec47aeb9a2471dce89b474
Source dataset
uspto-grants-2004_08
Patent number
US06780875B2

Reaction notes

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