Thionyl Chloride → 3-Phenyl-propynoic acid (1-acetyl-2,3-dihydro-1H-indol-6-yl)-(1-benzyl-piperidin-4-yl)-amide

HRID 2250871Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2250871
[C:1]1([C:7]#[C:8][C:9]([OH:11])=O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.S(Cl)(Cl)=O.[CH2:16]([N:23]1[CH2:28][CH2:27][CH:26]([NH:29][C:30]2[CH:38]=[C:37]3[C:33]([CH2:34][CH2:35][N:36]3[C:39](=[O:41])[CH3:40])=[CH:32][CH:31]=2)[CH2:25][CH2:24]1)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1>C1(C)C=CC=CC=1>[C:39]([N:36]1[C:37]2[C:33](=[CH:32][CH:31]=[C:30]([N:29]([CH:26]3[CH2:25][CH2:24][N:23]([CH2:16][C:17]4[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=4)[CH2:28][CH2:27]3)[C:9](=[O:11])[C:8]#[C:7][C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)[CH:38]=2)[CH2:34][CH2:35]1)(=[O:41])[CH3:40]

Komponenten

5

Edukt 3

HCID 24386Thionyl ChlorideHCID 69475Phenylpropiolic AcidHCID 27611281-Acetyl-N-(1-benzylpiperidin-4-yl)-indolin-6-amine

Produkt 1

HCID 117519253-Phenyl-propynoic acid (1-acetyl-2,3-dihydro-1H-indol-6-yl)-(1-benzyl-piperidin-4-yl)-amideAusbeute 84,2 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 1140TolueneLösungsmittel

Versuchsvorschrift

A mixture of phenyl-propynoic acid (220 mg, 1.5 mmol) and thionyl chloride (3.0 mL) in toluene (3.0 mL) was heated at reflux for 4 h. The reaction mixture was cooled to rt and the excess thionyl chloride and toluene were removed under reduced pressure. The resulting crude acid chloride was dissolved in CH2Cl2 (5 mL) and treated with 1-[6-(1-benzyl-piperidin-4-ylamino)-2,3-dihydro-indol-1-yl]-ethanone (349 mg, 1.0 mmol) and TEA (0.28 mL, 2.0 mmol) at rt for 20 h. The reaction mixture was concentrated, and the residue was purified on silica gel (60-70% EtOAc/hexanes) to afford the title compound (402 mg, 84%). 1H NMR (500 MHz, CDCl3): 8.12 (s, 1H), 7.28-7.18 (m, 9H), 7.09 (d, J=7.8 Hz, 2H), 6.86 (dd, J=8.0, 1.7 Hz, 1H), 4.65-4.59 (m, 1H), 4.13 (t, J=8.5 Hz, 2H) 3.44 (s, 2H), 3.24 (t, J=8.5 Hz, 2H), 2.89 (d, J=10.7 Hz, 2H), 2.22 (s, 3H), 2.10 (t, J=10.8 Hz, 2H), 1.90-1.78 (m, 2H), 1.63-1.58 (m, 2H). MS: exact mass calculated for C31H31N3O2, 477.24; m/z found, 478.3 [M+H]+.

Aufarbeitung

  1. temperaturewas heated
  2. temperatureat reflux for 4 h
  3. customthe excess thionyl chloride and toluene were removed under reduced pressure
  4. dissolutionThe resulting crude acid chloride was dissolved in CH2Cl2 (5 mL)
  5. concentrationThe reaction mixture was concentrated
  6. customthe residue was purified on silica gel (60-70% EtOAc/hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-37a0521436ab438393144070d8f5125a
Quelldatensatz
uspto-grants-2008_01
Patentnummer
US07317025B2

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