1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → 2-(4-(((2-(diethylamino)ethyl)(methyl)amino)methyl)benzamido)-5-(piperidin-1-yl)-N-(1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-yl)benzamide

HRID 2409855노트

반응식

HRID 2409855 반응식
[NH2:1][C:2]1[CH:25]=[CH:24][C:23]([N:26]2[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]2)=[CH:22][C:3]=1[C:4]([NH:6][C:7]1[CH:11]=[CH:10][N:9]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([C:18]([F:21])([F:20])[F:19])[CH:13]=2)[N:8]=1)=[O:5].[CH2:32]([N:34]([CH2:49][CH3:50])[CH2:35][CH2:36][N:37]([CH2:39][C:40]1[CH:48]=[CH:47][C:43]([C:44](O)=[O:45])=[CH:42][CH:41]=1)[CH3:38])[CH3:33].CCN=C=NCCCN(C)C.Cl>ClCCl.CN(C)C1C=CN=CC=1>[CH2:49]([N:34]([CH2:32][CH3:33])[CH2:35][CH2:36][N:37]([CH2:39][C:40]1[CH:41]=[CH:42][C:43]([C:44]([NH:1][C:2]2[CH:25]=[CH:24][C:23]([N:26]3[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]3)=[CH:22][C:3]=2[C:4]([NH:6][C:7]2[CH:11]=[CH:10][N:9]([C:12]3[CH:17]=[CH:16][CH:15]=[C:14]([C:18]([F:20])([F:21])[F:19])[CH:13]=3)[N:8]=2)=[O:5])=[O:45])=[CH:47][CH:48]=1)[CH3:38])[CH3:50]

참가 물질

6

반응물 3

HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 548860664-(((2-(Diethylamino)ethyl)(methyl)amino)methyl)benzoic acidHCID 665874172-amino-5-(piperidin-1-yl)-N-(1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-yl)benzamide

생성물 1

HCID 566445552-(4-(((2-(diethylamino)ethyl)(methyl)amino)methyl)benzamido)-5-(piperidin-1-yl)-N-(1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-yl)benzamide수율 37.2%

시약·촉매·용매 2

HCID 142844-(Dimethylamino)pyridine촉매HCID 6344Dichloromethane용매

반응 조건

온도
30 °C

실험 절차

Into a 5-mL vial, was placed a solution of 2-amino-5-(piperidin-1-yl)-N-(1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-yl)benzamide 8d (100 mg, 0.23 mmol, 1.00 equiv) in dichloromethane (5 mL), 4-(((2-(diethylamino)ethyl)(methyl)amino)methyl)benzoic acid (74 mg, 0.28 mmol, 1.20 equiv), EDC.HCl (90 mg, 0.47 mmol, 2.00 equiv), and 4-dimethylaminopyridine (43 mg, 0.35 mmol, 1.50 equiv). The resulting solution was stirred overnight at 30° C. in an oil bath. The reaction progress was monitored by LCMS. The resulting mixture was washed with 3×10 mL of water and 1×10 mL of brine. The mixture was dried over anhydrous sodium sulfate and concentrated under vacuum. The crude product (150 mg) was purified by reverse phase HPLC eluting with a water/CH3CN gradient containing 0.05% TFA. The product was obtained as 57.8 mg (31%) of a light yellow solid. 1H-NMR (300 MHz, CD3OD, ppm): δ 8.684 (d, J=9 Hz, 1H), 8.392-8.400 (m, 1H), 8.179 (s, 1H), 8.047-8.075 (m, 3H), 7.991-7.999 (m, 1H), 7.589-7.727 (m, 5H), 7.078-7.087 (m, 1H), 4.007 (s, 2H), 3.556-3.615 (m, 4H), 3.393-3.436 (m, 2H), 3.171-3.263 (m, 4H), 3.052-3.095 (m, 2H), 2.538-2.560 (m, 3H), 1.998 (m, 4H), 1.788-1.804 (m, 2H), 1.286-1.334 (m, 6H). MS (ES, m/z): 676 [M+H]+.

후처리

  1. washThe resulting mixture was washed with 3×10 mL of water and 1×10 mL of brine
  2. dry with materialThe mixture was dried over anhydrous sodium sulfate
  3. concentrationconcentrated under vacuum
  4. customThe crude product (150 mg) was purified by reverse phase HPLC
  5. washeluting with a water/CH3CN gradient
  6. additioncontaining 0.05% TFA

출처 및 근거

ORD 기록
ord-925fa7fa4807466bb70c52f04dcc3d9f
출처 데이터셋
uspto-grants-2014_08
특허 번호
US08815910B2

반응 노트

불러오는 중…