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 458473노트

반응식

HRID 458473 반응식
[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

참가 물질

7

반응물 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

생성물 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-carboxylate수율 83%

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-685c38834a8f433eb235f50b576b2af6
출처 데이터셋
uspto-grants-2007_03
특허 번호
US07189851B2

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