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Morpholine → 2-(3-methoxyphenyl)-9-morpholino-7,8-dihydro-[1,4]diazepino[7,1-a]isoquinolin-5(4H)-one

HRID 926284
ノート
印刷プレビュー

反応式

HRID 926284 の反応式
I[C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH2:4][CH2:5][N:6]1[C:16](=[O:17])[CH2:15][N:14]=[C:13]([C:18]3[CH:23]=[CH:22][CH:21]=[C:20]([O:24][CH3:25])[CH:19]=3)[CH:12]=[C:7]12.[NH:26]1[CH2:31][CH2:30][O:29][CH2:28][CH2:27]1.C([O-])([O-])=O.[Cs+].[Cs+]>C1(C)C=CC=CC=1.CC([O-])=O.CC([O-])=O.[Pd+2].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>[CH3:25][O:24][C:20]1[CH:19]=[C:18]([C:13]2[CH:12]=[C:7]3[C:8]4[C:3]([CH2:4][CH2:5][N:6]3[C:16](=[O:17])[CH2:15][N:14]=2)=[C:2]([N:26]2[CH2:31][CH2:30][O:29][CH2:28][CH2:27]2)[CH:11]=[CH:10][CH:9]=4)[CH:23]=[CH:22][CH:21]=1
参加物実験手順後処理出典と根拠反応ノート

参加物

7

反応物 3

HCID 8083MorpholineHCID 10796Cesium carbonateHCID 867113559-iodo-2-(3-methoxyphenyl)-7,8-dihydro-[1,4]diazepino[7,1-a]isoquinolin-5(4H)-one

生成物 1

HCID 733353432-(3-methoxyphenyl)-9-morpholino-7,8-dihydro-[1,4]diazepino[7,1-a]isoquinolin-5(4H)-one収率 60.5%

試薬・触媒・溶媒 3

HCID 167845palladium(II) acetate
触媒
HCID 634876Binap, (A+-)-触媒
HCID 1140Toluene溶媒2 回

実験手順

A solution of Pd(OAc)2 (4.0 mg, 0.017 mmol), and BINAP (10.5 mg, 0.017 mmol) in toluene (5 mL) was stirred at RT under N2 for 10 min, and then transferred to a mixture of 9-iodo-2-(3-methoxyphenyl)-7,8-dihydro-[1,4]diazepino[7,1-a]isoquinolin-5(4H)-one (Example 30) (150 mg, 0.34 mmol), morpholine (35 μL, 0.41 mmol) and Cs2CO3 (550 mg, 1.69 mmol) in toluene (5 mL). The reaction was stirred at RT under N2 for 5 min, and then heated to reflux for 24 h. The mixture was allowed to cool to RT, and then filtered and concentrated in vacuo. The crude product was purified by flash chromatography (SiO2, hexane to hexane/AcOEt 1:1) and the brown solid obtained was recrystallized from hexane to give the title compound (83 mg) as a beige solid. UPLC-MS: MS 404.5 (M+H+); UPLC rt 1.09 min. 1H NMR (400 MHz, CHLOROFORM-d): δ ppm 2.84-3.03 (m, 6 H); 3.76-3.95 (m, 6 H); 3.87 (s, 3H); 4.51 (br. s., 2 H); 6.92 (s, 1 H); 7.00 (dd, J=8.21, 2.74 Hz, 1 H); 7.14 (d, J=7.82 Hz, 1 H); 7.28-7.51 (m, 5 H).

後処理

  1. temperatureheated
  2. temperatureto reflux for 24 h
  3. temperatureto cool to RT
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude product was purified by flash chromatography (SiO2, hexane to hexane/AcOEt 1:1)
  7. customthe brown solid obtained
  8. customwas recrystallized from hexane

出典と根拠

ORDレコード
ord-f114f164caa14b089f1b1df960b552a9
出典データセット
uspto-grants-2016_03
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09284331B2

反応ノート

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