Triethylamine → [3,3''-Dichloro-5'-(8-indol-1-yl-octylcarbamoyl)-[1,1';3',1'']terphenyl-2'-yloxy]-ethanol

HRID 1884698Notes

Reaction equation

HRID 1884698 reaction equation
[N:1]1([CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][NH2:18])[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[CH:2]1.[Cl:19][C:20]1[CH:21]=[C:22]([C:26]2[CH:27]=[C:28]([CH:32]=[C:33]([C:39]3[CH:44]=[CH:43][CH:42]=[C:41]([Cl:45])[CH:40]=3)[C:34]=2[O:35][CH2:36][CH2:37]O)[C:29](O)=[O:30])[CH:23]=[CH:24][CH:25]=1.CCN(CC)CC.C1C=CC2N([OH:62])N=NC=2C=1.C1CCC(N=C=NC2CCCCC2)CC1>C(Cl)Cl>[Cl:45][C:41]1[CH:40]=[C:39]([C:33]2[CH:32]=[C:28]([C:29](=[O:30])[NH:18][CH2:17][CH2:16][CH2:15][CH2:14][CH2:13][CH2:12][CH2:11][CH2:10][N:1]3[C:9]4[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=4)[CH:3]=[CH:2]3)[CH:27]=[C:26]([C:22]3[CH:23]=[CH:24][CH:25]=[C:20]([Cl:19])[CH:21]=3)[C:34]=2[O:35][CH:36]([OH:62])[CH3:37])[CH:44]=[CH:43][CH:42]=1

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 222373953,5-Bis(3-chlorophenyl)-4-(2-hydroxyethoxy)benzoic acidHCID 222375078-Indol-1-yloctylamine

Product 1

HCID 86583659[3,3''-Dichloro-5'-(8-indol-1-yl-octylcarbamoyl)-[1,1';3',1'']terphenyl-2'-yloxy]-ethanolYield 87.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a flame dried round bottom flask with 8-indol-1-yloctylamine (0.227 g, 0.930 mmol, preparation similar to step 1 of Example 54) in CH2Cl2 (10 mL) at room temperature was added 3,5-bis-(m-chlorophenyl)-4-(2-hydroxyethoxy)-benzoic acid (0.250 g, 0.620 mmol, prepared in step 2 of Example 55) followed by Et3N (0.259 mL, 1.86 mmol), HOBt (0.092 g, 0.682 mmol), and finally DCC (0.153 g, 0.744 mmol). After 3 days at this temperature, it was concentrated and then diluted with EtOAc (200 mL). The white solid (DCU) that formed was filtered off and washed with excess EtOAc. The organic layer was washed with 1 N HCl (20 mL), sat. aq. NaHCO3 (20 mL), and brine (20 mL) and then dried (MgSO4). After concentration, the residue was purified by the Biotage Flash 40 apparatus (30 to 50% EtOAc/petroleum ether) to afford the product (0.341 g, 87%) as a solid; 1H NMR (CDCl3) δ 1.21-1.38 (m, 8H), 1.46-1.63 (m, 3H), 1.75-1.89 (m, 2H), 3.27-3.49 (m, 6H), 4.11 (t, J=8.1 Hz, 2H), 6.01-6.13 (m, 1H), 6.47 (d, J=2.2 Hz, 1H), 7.05-7.13 (m, 2H), 7.19 (t, J=8.8 Hz, 1H), 7.39-7.46 (m, 5H), 7.48-7.55 (m, 2H), 7.58-7.66 (m, 3H), 7.74 (s, 2H); mass spectrum [(+) ESI], m/z 629 (M)+.

Workup

  1. concentrationAfter 3 days at this temperature, it was concentrated
  2. additiondiluted with EtOAc (200 mL)
  3. customThe white solid (DCU) that formed
  4. filtrationwas filtered off
  5. washwashed with excess EtOAc
  6. washThe organic layer was washed with 1 N HCl (20 mL), sat. aq. NaHCO3 (20 mL), and brine (20 mL)
  7. dry with materialdried (MgSO4)
  8. concentrationAfter concentration
  9. customthe residue was purified by the Biotage Flash 40 apparatus (30 to 50% EtOAc/petroleum ether)

Sources & evidence

ORD record
ord-d51d5933805e4f729ee0f1c9659135a5
Source dataset
uspto-grants-2004_07
Patent number
US06765021B2

Reaction notes

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