Triethylamine → HCID 86719475, compound

HRID 1772222Notes

Reaction equation

HRID 1772222 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]2[O:9][CH:8]([CH2:10][N:11]3[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]3)[CH2:7][C:6]=2[CH:17]=1.[N+](C1C=CC(NC2CC[CH:31]([O:34]CC(O)=O)[CH2:30]C2)=CC=1C(F)(F)F)([O-])=O.CCN=C=NCCCN(C)C.[ClH:54].C1C=CC2N(O)N=NC=2C=1.C(N(CC)CC)C>O.ClCCl>[Cl:54][CH2:30][C:31]([N:14]1[CH2:13][CH2:12][N:11]([CH2:10][CH:8]2[CH2:7][C:6]3[CH:17]=[C:2]([F:1])[CH:3]=[CH:4][C:5]=3[O:9]2)[CH2:16][CH2:15]1)=[O:34]

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 66365445HCID 66365445, compoundHCID 672837722-(4-(4-Nitro-3-(trifluoromethyl)phenylamino)cyclohexyloxy)acetic acid

Product 1

HCID 86719475HCID 86719475, compoundYield 114.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

Into a 50 ml round-bottomed flask containing 20 ml of dichloromethane was added 1-(5-fluoro-2,3-dihydro-benzofuran-2-ylmethyl)-piperazine (100 mg, 0.42 mmol), 2-[(4-[[4-nitro-3-(trifluoromethyl)phenyl]amino]cyclohexyl)oxy]acetic acid (230 mg, 0.63 mmol, 1.5 eq), EDAC.HCl (122 mg, 0.64 mmol, 1.5 eq), HOBt (86 mg, 0.64 mmol, 1.5 eq) and triethylamine (128 mg, 1.26 mmol, 3.0 eq). The solution was stirred at room temperature for 16 hours. The crude contents were diluted with water and then extracted with 3×50 ml of ethyl acetate. The organic fractions were combined, dried over magnesium sulfate, filtered, and then concentrated under vacuum. The crude material was then chromatographed on silica gel using methanol/dichloromethane to elute. The product-containing fractions were then combined and concentrated to provide 150 mg of the amide as a light yellow solid (57%). (ES, m/z): [M+H]+ 581.3; 1H NMR (300 MHz, CDCl3): δ 8.02 (d, J=9 Hz, 1H), 6.75-6.91 (m, 3H), 6.60-6.71 (m, 2H), 5.00 (broad s, 1H), 4.48 (d, J=7.5 Hz, 1H), 3.66 (s, 2H), 3.48-3.80 (broad m, 4H), 3.22-3.50 (broad m, 3H), 2.95 (m, 1H), 2.75-2.90 (m, 1H), 2.50-2.75 (broad m, 4H), 2.16 (d, J=8.7 Hz, 4H), 1.38-1.58 (dd, J=10.5, 22.5 Hz, 2H), 1.22-1.34 (dd, J=−10.9, 22.5 Hz, 2H).

Workup

  1. extractionextracted with 3×50 ml of ethyl acetate
  2. dry with materialdried over magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated under vacuum
  5. customThe crude material was then chromatographed on silica gel
  6. washto elute
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-351a77578d104fbe8c65f510de314c9b
Source dataset
uspto-grants-2016_02
Patent number
US09249102B2

Reaction notes

Loading…