Triethylamine → 6-Quinolineacetamide, N-(1-cyclobutyl-1H-imidazol-4-yl)-

HRID 353914Notes

Reaction equation

HRID 353914 reaction equation
[CH:1]1([N:5]2[CH:9]=[C:8]([N+:10]([O-])=O)[N:7]=[CH:6]2)[CH2:4][CH2:3][CH2:2]1.C(OCC)(=O)C.CCN(CC)CC.[N:26]1[C:35]2[C:30](=[CH:31][C:32]([CH2:36][C:37](O)=[O:38])=[CH:33][CH:34]=2)[CH:29]=[CH:28][CH:27]=1>C(Cl)Cl.[Pd]>[CH:1]1([N:5]2[CH:9]=[C:8]([NH:10][C:37](=[O:38])[CH2:36][C:32]3[CH:31]=[C:30]4[C:35](=[CH:34][CH:33]=3)[N:26]=[CH:27][CH:28]=[CH:29]4)[N:7]=[CH:6]2)[CH2:4][CH2:3][CH2:2]1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 8857Ethyl AcetateHCID 11389611HCID 11389611, compoundHCID 117887092-(Quinolin-6-yl)acetic acid

Product 1

HCID 98395156-Quinolineacetamide, N-(1-cyclobutyl-1H-imidazol-4-yl)-Yield 47.1%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
-10 °C

Procedure

To a Parr hydrogenation bottle was added 1-cyclobutyl-4-nitro-1H-imidazole (Preparation 1, 150 mg, 0.9 mmol) and ethyl acetate (10 mL), followed by 10% Pd on carbon (250 mg). The reaction mixture was placed on a Parr hydrogenation apparatus and was reacted for 6 h under 50 psi H2 at 23° C. The contents of the bottle were filtered through a short pad of celite and were rinsed with dry methylene chloride (25 mL) into a flame-dried flask under nitrogen. Et3N (626 uL, 4.5 mmol) was added and the reaction solution was cooled to −10° C. 6-Quinolylacetic acid (168 mg, 0.9 mmol) and tripropylphosphonic anhydride (530 uL, 1.7 M solution in ethyl acetate) were then added and the mixture was stirred at −10° C. for 2 h. The solution was diluted with methylene chloride (50 mL) and washed with water (2×). The aqueous layer was extracted with methylene chloride (3×) and the organic layers were combined and washed with brine (1×). The solvent was removed in vacuo, the residue was adsorbed onto silica gel and chromatographed using the Biotage Flash 12 system with SIM attachment (40:1 methylene chloride—methanol) to afford 130 mg (47% yield) of N-(1-cyclobutyl-1H-imidazol-4-yl)-2-quinolin-6-yl-acetamide (the title compound); 1H NMR (300 MHz, CDCl3) δ9.48 (s, 1H), 8.87 (dd, J=1.6, 4.3 Hz, 1H), 8.11 (m, 2H), 7.76 (d, J=1.8 Hz, 1H), 7.67 (dd, J=2.0, 8.7 Hz, 1H), 7.44 (d, J=1.6 Hz, 1H), 7.38 (m, 1H), 7.25 (d, J=1.6 Hz, 1H), 4.5 (m, 1H), 3.90 (s, 2H), 2.4 (m, 2H), 2.3 (m, 2H), 1.85 (m, 2H); MS (AP/Cl): 307.1 (M+H)+.

Workup

  1. customwas reacted for 6 h under 50 psi H2 at 23° C
  2. filtrationThe contents of the bottle were filtered through a short pad of celite
  3. washwere rinsed with dry methylene chloride (25 mL) into a flame-dried flask under nitrogen
  4. washwashed with water (2×)
  5. extractionThe aqueous layer was extracted with methylene chloride (3×)
  6. washwashed with brine (1×)
  7. customThe solvent was removed in vacuo
  8. customchromatographed

Sources & evidence

ORD record
ord-45e2fa32b570439492d74c9b2c77a152
Source dataset
uspto-grants-2004_06
Patent number
US06756385B2

Reaction notes

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