Diisopropyl Ether → (S)-N-(a-ethylbenzyl)-3-[2-(4-pyridylacetyl)aminoethoxy]-2-phenylquinoline-4-carboxamide

HRID 651071Notes

Reaction equation

HRID 651071 reaction equation
Cl.[N:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([OH:11])=O)=[CH:4][CH:3]=1.C1C=CC2N(O)N=NC=2C=1.[CH2:22]([C@H:24]([NH:31][C:32]([C:34]1[C:43]2[C:38](=[CH:39][CH:40]=[CH:41][CH:42]=2)[N:37]=[C:36]([C:44]2[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=2)[C:35]=1[O:50][CH2:51][CH2:52][NH2:53])=[O:33])[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)[CH3:23].C1CCC(N=C=NC2CCCCC2)CC1.O(C(C)C)C(C)C>C(Cl)Cl>[CH2:22]([C@H:24]([NH:31][C:32]([C:34]1[C:43]2[C:38](=[CH:39][CH:40]=[CH:41][CH:42]=2)[N:37]=[C:36]([C:44]2[CH:45]=[CH:46][CH:47]=[CH:48][CH:49]=2)[C:35]=1[O:50][CH2:51][CH2:52][NH:53][C:9](=[O:11])[CH2:8][C:5]1[CH:4]=[CH:3][N:2]=[CH:7][CH:6]=1)=[O:33])[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)[CH3:23]

Participants

7

Reactant 5

HCID 7914Diisopropyl EtherHCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 810974-Pyridineacetic acid hydrochlorideHCID 10764865HCID 10764865, compound

Product 1

HCID 70248586(S)-N-(a-ethylbenzyl)-3-[2-(4-pyridylacetyl)aminoethoxy]-2-phenylquinoline-4-carboxamideYield 65%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

0.41 g (2.4 mmol) of 4-pyridylacetic acid hydrochloride were suspended in 80 ml of CH2Cl2; the suspension was cooled to 0° C. and 0.33 ml (2.4 mmol) of TEA, 0.64 g (4.7 mmol) of HOBT and 1.0 g (2.4 mmol) of (S)-N-(α-ethylbenzyl)-3-(2-aminoethoxy)-2-phenylquinoline-4-carboxamide (compound of Description 4) were added. 0.58 g (2.8 mmol) of DCC, dissolved in 10 ml of CH2Cl2, were added dropwise and the reaction mixture was stirred at 0° C. for 1 h and at room temperature overnight. The precipitated dicyclohexylurea was filtered off and the filtrate was washed with 20% citric acid, sat. sol. NaCl and brine, dried over Na2SO4 and evaporated in vacuo to dryness. The crude product was purified by flash column chromatography on 230-400 mesh silica gel, eluting with a mixture of CH2Cl2/MeOH 95:5 containing 0.5% NH4OH (28%), to yield, after trituration with i-Pr2O, 0.85 g of the title compound.

Workup

  1. additionwere added dropwise
  2. filtrationThe precipitated dicyclohexylurea was filtered off
  3. washthe filtrate was washed with 20% citric acid, sat. sol. NaCl and brine
  4. dry with materialdried over Na2SO4
  5. customevaporated in vacuo to dryness
  6. customThe crude product was purified by flash column chromatography on 230-400 mesh silica gel
  7. washeluting with a mixture of CH2Cl2/MeOH 95:5 containing 0.5% NH4OH (28%)
  8. customto yield

Sources & evidence

ORD record
ord-612e4f2bb57249e3a3dc0a1627f71d23
Source dataset
uspto-grants-2001_08
Patent number
US06277862B1

Reaction notes

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