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 926878ノート

反応式

HRID 926878 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: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]

参加物

6

反応物 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

生成物 1

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

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 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]+.

後処理

  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

出典と根拠

ORDレコード
ord-2c31696509cc4356959330df3aa66cf9
出典データセット
uspto-grants-2016_03
特許番号
US09289430B2

反応ノート

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