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

HRID 2250871ノート

反応式

HRID 2250871 の反応式
[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]

参加物

5

反応物 3

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

生成物 1

HCID 117519253-Phenyl-propynoic acid (1-acetyl-2,3-dihydro-1H-indol-6-yl)-(1-benzyl-piperidin-4-yl)-amide収率 84.2%

試薬・触媒・溶媒 1

HCID 1140Toluene溶媒

実験手順

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]+.

後処理

  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)

出典と根拠

ORDレコード
ord-37a0521436ab438393144070d8f5125a
出典データセット
uspto-grants-2008_01
特許番号
US07317025B2

反応ノート

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