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

HRID 2409864
ノート
印刷プレビュー

反応式

HRID 2409864 の反応式
[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:41]=[C:42]([CH:46]=[CH:47][CH:48]=1)[C:43](O)=[O:44])[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]=[C:42]([CH:46]=[CH:47][CH:48]=1)[C:43]([NH: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:20])([F:21])[F:19])[CH:13]=2)[N:8]=1)=[O:5])=[O:44])[CH3:38])[CH3:50]
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

6

反応物 3

HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 665868393-(((2-(Diethylamino)ethyl)(methyl)amino)methyl)benzoic acidHCID 665874172-amino-5-(piperidin-1-yl)-N-(1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-yl)benzamide

生成物 1

HCID 566439302-(3-(((2-(diethylamino)ethyl)(methyl)amino)methyl)benzamido)-5-(piperidin-1-yl)-N-(1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-yl)benzamide収率 37.6%

試薬・触媒・溶媒 2

HCID 142844-(Dimethylamino)pyridine触媒HCID 6344Dichloromethane溶媒

反応条件

温度
30 °C

実験手順

Into a 50-mL round bottom flask, 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), 3-(((2-(diethylamino)ethyl)(methyl)amino)methyl)benzoic acid (74 mg, 0.28 mmol, 1.20 equiv), EDC.HCl (90 mg, 0.47 mmol, 2.01 equiv), and 4-dimethylaminopyridine (43 mg, 0.35 mmol, 1.51 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 sodium sulfate. The solids were filtered out. The resulting mixture was 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 58.5 mg (32%) of a yellow solid. 1H-NMR (300 MHz, CD3OD, ppm): δ 8.502-8.532 (d, J=9.0 Hz, 1H), 8.277-8.286 (m, 1H), 8.060 (s, 1H), 7.851-7.966 (m, 4H), 7.475-7.610 (m, 5H), 6.949-6.958 (m, 1H), 3.922 (s, 2H), 3.450-3.485 (m, 4H), 3.273-3.316 (m, 2H), 3.035-3.108 (m, 4H), 2.957-2.998 (m, 2H), 2.449-2.475 (m, 3H), 1.857-1.872 (m, 4H), 1.666-1.683 (m, 2H), 1.139-1.200 (m, 6H). MS (ES, m/z): 676 [M+H]+.

後処理

  1. customInto a 50-mL round bottom flask, was placed
  2. washThe resulting mixture was washed with 3×10 mL of water and 1×10 mL of brine
  3. dry with materialThe mixture was dried over sodium sulfate
  4. filtrationThe solids were filtered out
  5. concentrationThe resulting mixture was concentrated under vacuum
  6. customThe crude product (150 mg) was purified by reverse phase HPLC
  7. washeluting with a water/CH3CN gradient
  8. additioncontaining 0.05% TFA

出典と根拠

ORDレコード
ord-79a496db15624eaaabe33e0d103a0bc7
出典データセット
uspto-grants-2014_08
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08815910B2

反応ノート

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