Sodium Carbonate → 1-Benzylindol-3-yl-n-[6-(1-methylpiperidin-4-ylcarbonyl)-pyridin-2-yl]-carboxamide

HRID 404232

반응식

HRID 404232 반응식
C(Cl)(=O)C(Cl)=O.[CH2:7]([N:14]1[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[C:16]([C:23]([OH:25])=O)=[CH:15]1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.[NH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[C:29]([C:33]([CH:35]2[CH2:40][CH2:39][N:38]([CH3:41])[CH2:37][CH2:36]2)=[O:34])[N:28]=1.C([O-])([O-])=O.[Na+].[Na+]>N1C=CC=CC=1.CC#N.C(Cl)(Cl)Cl>[CH2:7]([N:14]1[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[C:16]([C:23]([NH:26][C:27]2[CH:32]=[CH:31][CH:30]=[C:29]([C:33]([CH:35]3[CH2:40][CH2:39][N:38]([CH3:41])[CH2:37][CH2:36]3)=[O:34])[N:28]=2)=[O:25])=[CH:15]1)[C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1

참가 물질

8

반응물 4

HCID 10340Sodium CarbonateHCID 336711-benzyl-1H-indole-3-carboxylic acidHCID 65578Oxalyl chlorideHCID 11401723(6-Aminopyridin-2-yl)(1-methylpiperidin-4-yl)methanone

생성물 1

HCID 597893621-Benzylindol-3-yl-n-[6-(1-methylpiperidin-4-ylcarbonyl)-pyridin-2-yl]-carboxamide수율 51.2%

시약·촉매·용매 3

HCID 1049Pyridine용매2회HCID 6212Chloroform용매HCID 6342Acetonitrile용매2회

실험 절차

Add oxalyl chloride (0.18 mL, 2.1 mmol) dropwise to a solution of 1-benzylindol-3-carboxylic acid (0.48 g, 1.9 mmol) in pyridine and CH3CN (5 mL each) cooled in an ice bath. Stir the reaction mixture for 2.25 hr. and then add a suspension of 2-amino-6-(1-methylpiperidin-4-ylcarbonyl)pyridine (0.56 g, 1.9 mmol) in CH3CN (5 mL) and pyridine (12 mL). Warm the reaction mixture to room temperature overnight. Quench the reaction with cold H2O (20 mL) and dilute with CHCl3. Adjust the pH to 11 with Na2CO3 and separate the layers. Extract the aqueous layer with CHCl3 (2×30 mL). Combine the organic fractions and dry with anhydrous MgSO4, filter and concentrate the mixture in vacuo. Purify the product by chromatography on a silica gel column, eluting with methanol/CH2Cl2 (5:95) followed by methanol/CH2Cl2 (10:90) to afford the sub-title compound (0.44 g, 51%). 1H NMR (CD3OD) 8.45 (d, J=8 Hz, 1H), 8.32 (s, 1H), 8.26 (m, 1H), 7.95 (t, J=8 Hz, 1H), 7.72 (d, J=8 Hz, 1H), 7.45 (m, 1H), 7.22-7.37 (m, 7H), 5.51 (s, 2H), 3.90 (m, 1H), 2.93-3.01 (m, 2H), 2.33 (s, 3H), 2.21-2.31 (m, 2H), 1.92-1.99 (m, 2H), 1.71-1.84 (m, 2H); CIMS (Methane) m/z 453 [C28H28N4O2+H]+.

후처리

  1. temperaturecooled in an ice bath
  2. additionand then add
  3. customQuench
  4. customthe reaction with cold H2O (20 mL)
  5. customseparate the layers
  6. extractionExtract the aqueous layer with CHCl3 (2×30 mL)
  7. dry with materialCombine the organic fractions and dry with anhydrous MgSO4
  8. filtrationfilter
  9. concentrationconcentrate the mixture in vacuo
  10. customPurify the product by chromatography on a silica gel column
  11. washeluting with methanol/CH2Cl2 (5:95)

출처 및 근거

ORD 기록
ord-f72ab836894148299e348a18037649a0
출처 데이터셋
uspto-grants-2014_06
특허 번호
US08748459B2

연결된 노트

불러오는 중…