1,1'-Carbonyldiimidazole → 6-(adamantan-1-ylmethoxy)-5-cyclopropyl-N-(methylsulfonyl)-nicotinamide

HRID 1427902Notes

Reaction equation

HRID 1427902 reaction equation
[C:1]12([CH2:11][O:12][C:13]3[C:21]([CH:22]4[CH2:24][CH2:23]4)=[CH:20][C:16]([C:17]([OH:19])=O)=[CH:15][N:14]=3)[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH2:2]1)[CH2:8]2.C(N1C=CN=C1)(N1C=CN=C1)=O.N12CCCN=C1CCCCC2.[CH3:48][S:49]([NH2:52])(=[O:51])=[O:50]>O1CCCC1.C(OCC)(=O)C>[C:1]12([CH2:11][O:12][C:13]3[C:21]([CH:22]4[CH2:24][CH2:23]4)=[CH:20][C:16]([C:17]([NH:52][S:49]([CH3:48])(=[O:51])=[O:50])=[O:19])=[CH:15][N:14]=3)[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH2:2]1)[CH2:8]2

Participants

7

Reactant 4

HCID 682631,1'-CarbonyldiimidazoleHCID 72879MethanesulfonamideHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 867029246-(Adamantan-1-ylmethoxy)-5-cyclopropylnicotinic acid

Product 1

HCID 867029256-(adamantan-1-ylmethoxy)-5-cyclopropyl-N-(methylsulfonyl)-nicotinamideYield 58.5%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 6-(adamantan-1-ylmethoxy)-5-cyclopropylnicotinic acid (0.43 g, 1.31 mmol) and carbonyldiimidazole (0.42 g, 2.62 mmol) in anhydrous tetrahydrofuran (22 mL) was refluxed under nitrogen for 30 min. The reaction mixture was cooled to ambient temperature and treated with 1,8-Diazabicyclo[5.4.0]undec-7-ene (0.59 mL, 3.93 mmol) and methylsulfonamide (0.54 g, 3.93 mmol). The resulting mixture was stirred at ambient temperature for 2 h. The reaction mixture was diluted with ethyl acetate (60 mL), washed with 1 M aqueous hydrochloric acid (2×30 mL) and brine (50 mL); dried over anhydrous sodium sulfate; filtered and concentrated in vacuo. The residue was purified by flash chromatography eluting with 30% ethyl acetate (containing 0.2% acetic acid) in hexanes to afford the title compound as a white solid (0.31 g, 58%); 1H NMR (300 MHz, DMSO-d6) δ 12.01 (br s, 1H), 8.47 (d, J=2.5 Hz, 1H), 7.72 (d, J=2.5 Hz, 1H), 3.93 (s, 2H), 3.33 (s, 3H), 2.07-1.98 (m, 1H), 1.97-1.90 (m, 3H), 1.72-1.56 (m, 12H), 0.98-0.90 (m, 2H), 0.76-0.70 (m, 2H); MS (ES+) m/z: 405.2 (M+H).

Workup

  1. washwashed with 1 M aqueous hydrochloric acid (2×30 mL) and brine (50 mL)
  2. dry with materialdried over anhydrous sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by flash chromatography
  6. washeluting with 30% ethyl acetate (containing 0.2% acetic acid) in hexanes

Sources & evidence

ORD record
ord-cc3a451839624a6086e33d9e704db13e
Source dataset
uspto-grants-2015_01
Patent number
US08933236B2

Reaction notes

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