Sodium Bicarbonate → tert-butyl 4-(((9H-pyrido[3,4-b]indol-1-yl)methyl)(5,6,7,8-tetrahydroquinolin-8-yl)amino)butylcarbamate

HRID 628669노트

반응식

HRID 628669 반응식
[C:1]1([CH:14]=O)[C:6]2[NH:7][C:8]3[C:13]([C:5]=2[CH:4]=[CH:3][N:2]=1)=[CH:12][CH:11]=[CH:10][CH:9]=3.[N:16]1[C:25]2[CH:24]([NH:26][CH2:27][CH2:28][CH2:29][CH2:30][NH:31][C:32](=[O:38])[O:33][C:34]([CH3:37])([CH3:36])[CH3:35])[CH2:23][CH2:22][CH2:21][C:20]=2[CH:19]=[CH:18][CH:17]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)(O)[O-].[Na+]>ClCCCl.C(O)(=O)C>[C:1]1([CH2:14][N:26]([CH:24]2[C:25]3[N:16]=[CH:17][CH:18]=[CH:19][C:20]=3[CH2:21][CH2:22][CH2:23]2)[CH2:27][CH2:28][CH2:29][CH2:30][NH:31][C:32](=[O:38])[O:33][C:34]([CH3:37])([CH3:36])[CH3:35])[C:6]2[NH:7][C:8]3[C:13]([C:5]=2[CH:4]=[CH:3][N:2]=1)=[CH:12][CH:11]=[CH:10][CH:9]=3

참가 물질

7

반응물 4

HCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 53173759H-pyrido(3,4-b)indole-1-carbaldehydeHCID 42609132558446-23-4

생성물 1

HCID 59176352tert-butyl 4-(((9H-pyrido[3,4-b]indol-1-yl)methyl)(5,6,7,8-tetrahydroquinolin-8-yl)amino)butylcarbamate수율 24%

시약·촉매·용매 2

HCID 176Acetic Acid촉매HCID 111,2-Dichloroethane용매

실험 절차

A heavy-walled Pyrex tube was charged with a solution of 9H-pyrido[3,4-b]indole-1-carbaldehyde, 2, (0.20 g, 1.02 mmol) in 1,2-dichloroethane (5 mL). This solution was treated with tert-butyl 4-(5,6,7,8-tetrahydroquinolin-8-ylamino)butylcarbamate, 3, (0.36 g, 1.12 mmol), sodium triacetoxyborohydride (0.43 g, 2.04 mmol), 4 A molecular sieves and a catalytic amount of acetic acid (2 drops). The reaction mixture was exposed to microwave irradiation for 10 min at a temperature of 100° C. After the irradiation, the reaction mixture was cooled with high-pressure air until the temperature had fallen below 40° C. The crude reaction mixture was poured onto a saturated aqueous solution of sodium bicarbonate. The product was extracted with dichloromethane. The combined organic layers were washed with brine, dried over potassium carbonate, filtered and concentrated in vacuo. The crude product was purified by silica gel chromatography (0-5% methanol/CH2Cl2) to afford 0.12 g (24% yield) of desired product 4: 1H NMR (400 MHz, CDCl3) δ 13.43 (bs, 1H), 8.67 (d, J=3.6 Hz, 1H), 8.24 (d, J=5.6 Hz, 1H), 8.10 (d, J=7.6 Hz, 1H), 7.82 (d, J=5.2 Hz, 1H), 7.69 (d, J=8.4 Hz, 1H), 7.54 (dt, J=1.2, 7.4 Hz, 1H), 7.41 (d, J=7.2 Hz, 1H), 7.21 (dt, J=0.8, 7.2 Hz, 1H), 7.14 (dd, J=4.8, 7.6 Hz, 1H), 4.28-4.02 (m, 4H), 2.90-2.60 (m, 5H), 2.44-2.26 (m, 2H), 2.12-2.04 (m, 1H), 1.96-1.84 (m, 1H), 1.80-1.65 (m, 1H), 1.44-1.25 (m, 1H), 1.33 (s, 9H), 1.22-1.12 (m, 1H); ESI+ MS: m/z (rel intensity) 500.2 (100, [M+H]+).

후처리

  1. customirradiation for 10 min at a temperature of 100° C
  2. customAfter the irradiation
  3. temperaturethe reaction mixture was cooled with high-pressure air until the temperature
  4. customhad fallen below 40° C
  5. customThe crude reaction mixture
  6. extractionThe product was extracted with dichloromethane
  7. washThe combined organic layers were washed with brine
  8. dry with materialdried over potassium carbonate
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe crude product was purified by silica gel chromatography (0-5% methanol/CH2Cl2)

출처 및 근거

ORD 기록
ord-3aafe4747bea43afa5449748860307e2
출처 데이터셋
uspto-grants-2016_04
특허 번호
US09314468B2

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