1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → Ethyl (9aS)-4-{4-[(2,3-dihydro-1H-indol-1-ylamino)carbonyl]phenyl}-2-(4-fluorobenzyl)-5-oxo-7,8,9,9a-tetrahydro-5H-pyrido[2,3-a]pyrrolizine-3-carboxylate

HRID 458473ノート

反応式

HRID 458473 の反応式
[CH2:1]([O:3][C:4]([C:6]1[C:18]([CH2:19][C:20]2[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=2)=[N:17][C:9]2[C@H:10]3[N:14]([C:15](=[O:16])[C:8]=2[C:7]=1[C:27]1[CH:35]=[CH:34][C:30]([C:31](O)=[O:32])=[CH:29][CH:28]=1)[CH2:13][CH2:12][CH2:11]3)=[O:5])[CH3:2].[N:36]1([NH2:45])[C:44]2[C:39](=[CH:40][CH:41]=[CH:42][CH:43]=2)[CH2:38][CH2:37]1.CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.C([O-])(O)=O.[Na+]>C(Cl)Cl>[N:36]1([NH:45][C:31]([C:30]2[CH:29]=[CH:28][C:27]([C:7]3[C:8]4[C:15](=[O:16])[N:14]5[C@H:10]([C:9]=4[N:17]=[C:18]([CH2:19][C:20]4[CH:21]=[CH:22][C:23]([F:26])=[CH:24][CH:25]=4)[C:6]=3[C:4]([O:3][CH2:1][CH3:2])=[O:5])[CH2:11][CH2:12][CH2:13]5)=[CH:35][CH:34]=2)=[O:32])[C:44]2[C:39](=[CH:40][CH:41]=[CH:42][CH:43]=2)[CH2:38][CH2:37]1

参加物

7

反応物 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 516892Sodium BicarbonateHCID 27609322,3-dihydro-1H-indol-1-amineHCID 697432854-[(9aS)-3-(ethoxycarbonyl)-2-(4-fluorobenzyl)-5-oxo-7,8,9,9a-tetrahydro-5H-pyrido[2,3-a]pyrrolizin-4yl]benzoic acid

生成物 1

HCID 86598180Ethyl (9aS)-4-{4-[(2,3-dihydro-1H-indol-1-ylamino)carbonyl]phenyl}-2-(4-fluorobenzyl)-5-oxo-7,8,9,9a-tetrahydro-5H-pyrido[2,3-a]pyrrolizine-3-carboxylate収率 83%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

実験手順

A solution of 4-[(9aS)-3-(ethoxycarbonyl)-2-(4-fluorobenzyl)-5-oxo-7,8,9,9a-tetrahydro-5H-pyrido[2,3-α]pyrrolizin-4yl]benzoic acid (0.200 g, 0.42 mmol, 1 equiv) in CH2Cl2 (1.0 mL) was treated with the 1-indolinamine (ref. Wijngaarden, I. et al., J Med Chem, 1993, 36, 3693–99) (0.113 g, 0.84 mmol, 2 equiv), EDCI (0.113 g, 0.59 mmol, 1.4 equiv), and HOBt (0.080 g, 0.59 mmol, 1.4 equiv). After 12 h at ambient temperature, the diluted with CH2Cl2 (1.0 mL) and treated with saturated aqueous NaHCO3. The organic potion was the washed with 1N HCl (1 mL) followed by brine (1 mL). Concentration gave a brown oil the was chromatographed radially (SiO2, 2 mm plate, 50% hexanes-EtOAc) to provide the title compound as a white solid (0.206 g, 83%): 1H NMR (CDCl3, 400 MHz) δ 7.86 (d, J=8.2 Hz, 2H), 7.68 (s, 1H), 7.45 (d, J=8.0 Hz, 2H ), 7.25–7.21 (m, 2H), 7.15–7.10 (m, 2H), 6.94 (t, J=8.6 Hz, 2H), 6.86 (t, J=7.4 Hz, 1H), 6.71 (d, J=7.7 Hz, 1H), 4.74 (dd, J=10.4, 6.2 Hz, 1H), 4.35 (d, J=14.3 Hz, 1H), 4.29 (d, J=14.3 Hz, 1H), 3.90 (q, J=6.8 Hz, 2H), 3.69–3.61 (m, 3H), 3.36–3.31 (m, 1H), 3.09–3.05 (m, 2H), 2.53–2.47 (m, 1H), 2.35–2.27 (m, 2H), 1.45–1.34 (m, 1H), 0.84 (t, J=7.1 Hz, 3H).

後処理

  1. washwashed with 1N HCl (1 mL)
  2. concentrationConcentration
  3. customgave a brown oil the
  4. customwas chromatographed radially (SiO2, 2 mm plate, 50% hexanes-EtOAc)

出典と根拠

ORDレコード
ord-685c38834a8f433eb235f50b576b2af6
出典データセット
uspto-grants-2007_03
特許番号
US07189851B2

反応ノート

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