Triethylamine → HCID 86719489, compound

HRID 1772255Notes

Reaction equation

HRID 1772255 reaction equation
[Li][N:2]([C:8]1[CH:17]=[CH:16][C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH:9]=1)[C:3]([C:5]([O-:7])=O)=[O:4].N[CH2:19][CH2:20][O:21][CH:22]1[CH2:27][CH2:26][CH:25]([NH:28][C:29]2[CH:34]=[CH:33][C:32]([N+:35]([O-:37])=[O:36])=[C:31]([C:38]([F:41])([F:40])[F:39])[CH:30]=2)[CH2:24][CH2:23]1.CC[N:44]=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1.C(N(CC)CC)C>CN(C)C=O.C(OCC)(=O)C>[CH:9]1[C:10]2[C:15](=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH:16]=[CH:17][C:8]=1[N:2]([CH2:19][CH2:20][O:21][CH:22]1[CH2:27][CH2:26][CH:25]([NH:28][C:29]2[CH:34]=[CH:33][C:32]([N+:35]([O-:37])=[O:36])=[C:31]([C:38]([F:39])([F:40])[F:41])[CH:30]=2)[CH2:24][CH2:23]1)[C:3](=[O:4])[C:5]([NH2:44])=[O:7]

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 86719488HCID 86719488, compoundHCID 178506928HCID 178506928, compound

Product 1

HCID 86719489HCID 86719489, compoundYield 17.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of lithio[(naphthalen-2-yl)carbamoyl]formate (172 mg, 0.78 mmol, 1.5 eq) in N,N-dimethylformamide (15 ml) was added N-[4-(2-aminoethoxy)cyclohexyl]-4-nitro-3-(trifluoromethyl) aniline (180 mg, 0.52 mmol), EDAC.HCl (149 mg, 0.78 mmol, 1.5 eq), HOBt (105 mg, 0.78 mmol, 1.5 eq) and triethylamine (157 mg, 1.55 mmol, 3 eq). The resulting solution was stirred for 24 hours at room temperature. The solution was diluted with ethyl acetate (200 ml), washed with water (3×100 ml), and then washed with saturated aqueous sodium chloride (100 ml). The organic layer was then dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum. The crude material was purified by silica gel chromatography using 1% methanol in dichloromethane to elute. The product-containing fractions were combined and concentrated under vacuum to afford N-(naphthalen-2-yl)-N-[2-[(4-[[4-nitro-3-(trifluoromethyl)phenyl]amino]cyclohexyl)oxy]ethyl]ethanediamide as a yellow solid (48.6 mg, 17%). (ES, m/z) [M+H]+ 545.25; 1H NMR (300 MHz, CDCl3): δ 9.45 (s, 1H), 8.33 (d, J=2.1 Hz, 1H), 8.02 (d, J=9.0 Hz, 1H), 7.80-7.98 (m, 4H), 7.60 (dd, J=2.1 Hz, 8.7 Hz, 1H), 7.40-7.55 (m, 2H), 6.85 (d, J=2.4 Hz, 1H), 6.63 (dd, J=2.4 Hz, 9.0 Hz, 1H), 4.47 (d, J=7.5 Hz, 1H), 3.55-3.70 (m, 4H), 3.30-3.45 (m, 2H), 2.08-2.22 (m, 4H), 1.40-1.53 (m, 2H), 1.20-1.37 (m, 2H).

Workup

  1. washwashed with water (3×100 ml)
  2. washwashed with saturated aqueous sodium chloride (100 ml)
  3. dry with materialThe organic layer was then dried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under vacuum
  6. customThe crude material was purified by silica gel chromatography
  7. washto elute
  8. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-b26d5b3fb9e44cc9aeff50919f82a27f
Source dataset
uspto-grants-2016_02
Patent number
US09249102B2

Reaction notes

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