1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 6-(adamantan-1-ylmethoxy)-5-cyclopropyl-N-((2-methoxyethyl)-sulfonyl)nicotinamide

HRID 1849695Notes

Reaction equation

HRID 1849695 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(N=C=NCCCN(C)C)C.[CH3:36][O:37][CH2:38][CH2:39][S:40]([NH2:43])(=[O:42])=[O:41]>CN(C)C1C=CN=CC=1.ClCCl.C(OCC)(=O)C>[C:1]12([CH2:11][O:12][C:13]3[C:21]([CH:22]4[CH2:23][CH2:24]4)=[CH:20][C:16]([C:17]([NH:43][S:40]([CH2:39][CH2:38][O:37][CH3:36])(=[O:42])=[O:41])=[O:19])=[CH:15][N:14]=3)[CH2:10][CH:5]3[CH2:4][CH:3]([CH2:9][CH:7]([CH2:6]3)[CH2:8]1)[CH2:2]2

Participants

7

Reactant 3

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 189515062-Methoxyethane-1-sulfonamideHCID 867029246-(Adamantan-1-ylmethoxy)-5-cyclopropylnicotinic acid

Product 1

HCID 867035666-(adamantan-1-ylmethoxy)-5-cyclopropyl-N-((2-methoxyethyl)-sulfonyl)nicotinamideYield 76.3%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 6-(adamantan-1-ylmethoxy)-5-cyclopropylnicotinic acid (0.24 g, 0.73 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (0.35 g, 1.83 mmol), 4-dimethylaminopyridine (0.22 g, 1.83 mmol), and 2-methoxyethanesulfonamide (0.13 g, 0.95 mmol) in dichloromethane (10 mL) was stirred at ambient temperature for 3 days. The reaction mixture was diluted with ethyl acetate (50 mL), washed with 1 M aqueous hydrochloric acid solution (2×30 mL), brine (30 mL); dried over anhydrous sodium sulfate; filtered and concentrated in vacuo. The residue was purified by silica gel column chromatography (3:1 hexanes:ethyl acetate (+0.2% acetic acid v/v)) to provide the title compound (0.25 g, 76%): 1H NMR (300 MHz, DMSO-d6) δ 11.97 (br s, 1H), 8.45 (d, J=2.3 Hz, 1H), 7.70 (d, J=2.3 Hz, 1H), 3.93 (s, 2H), 3.75-3.65 (m, 4H), 3.14 (s, 3H), 2.07-1.98 (m, 1H), 1.98-1.91 (m, 3H), 1.73-1.58 (m, 12H) 0.99-0.91 (m, 2H), 0.76-0.70 (m, 2H); MS (ES+) m/z 449.2 (M+1).

Workup

  1. washwashed with 1 M aqueous hydrochloric acid solution (2×30 mL), brine (30 mL)
  2. dry with materialdried over anhydrous sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by silica gel column chromatography (3:1 hexanes

Sources & evidence

ORD record
ord-5dfc90599eca4e2a8ee5db0b1df9b71b
Source dataset
uspto-grants-2015_02
Patent number
US08952169B2

Reaction notes

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