1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → N1-(4-(butyl(methyl)amino)-2-(4-(3-(trifluoromethyl)benzylcarbamoyl)pyridin-2-yl)phenyl)-N3-methyl-N3-(2-morpholinoethyl)isophthalamide

HRID 625433ノート

反応式

HRID 625433 の反応式
[F:1][C:2]([F:33])([F:32])[C:3]1[CH:4]=[C:5]([CH:29]=[CH:30][CH:31]=1)[CH2:6][NH:7][C:8](=[O:28])[C:9]1[CH:14]=[CH:13][N:12]=[C:11]([C:15]2[CH:20]=[C:19]([N:21]([CH2:23][CH2:24][CH2:25][CH3:26])[CH3:22])[CH:18]=[CH:17][C:16]=2[NH2:27])[CH:10]=1.[CH3:34][N:35]([CH2:47][CH2:48][N:49]1[CH2:54][CH2:53][O:52][CH2:51][CH2:50]1)[C:36]([C:38]1[CH:39]=[C:40]([CH:44]=[CH:45][CH:46]=1)[C:41](O)=[O:42])=[O:37].CCN=C=NCCCN(C)C.Cl>ClCCl.CN(C)C1C=CN=CC=1>[CH2:23]([N:21]([CH3:22])[C:19]1[CH:18]=[CH:17][C:16]([NH:27][C:41](=[O:42])[C:40]2[CH:44]=[CH:45][CH:46]=[C:38]([C:36]([N:35]([CH3:34])[CH2:47][CH2:48][N:49]3[CH2:50][CH2:51][O:52][CH2:53][CH2:54]3)=[O:37])[CH:39]=2)=[C:15]([C:11]2[CH:10]=[C:9]([C:8](=[O:28])[NH:7][CH2:6][C:5]3[CH:29]=[CH:30][CH:31]=[C:3]([C:2]([F:32])([F:1])[F:33])[CH:4]=3)[CH:14]=[CH:13][N:12]=2)[CH:20]=1)[CH2:24][CH2:25][CH3:26]

参加物

6

反応物 3

HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 66586752N-(3-(trifluoromethyl)benzyl)-2-(2-amino-5-(butyl(methyl)amino)phenyl)isonicotinamideHCID 665869413-(Methyl(2-morpholinoethyl)carbamoyl)benzoic acid

生成物 1

HCID 66588227N1-(4-(butyl(methyl)amino)-2-(4-(3-(trifluoromethyl)benzylcarbamoyl)pyridin-2-yl)phenyl)-N3-methyl-N3-(2-morpholinoethyl)isophthalamide

試薬・触媒・溶媒 2

HCID 142844-(Dimethylamino)pyridine触媒HCID 6344Dichloromethane溶媒2 回

実験手順

Into a 50-mL round-bottom flask, was placed a solution of N-(3-(trifluoromethyl)benzyl)-2-(2-amino-5-(butyl(methyl)amino)phenyl)isonicotinamide (250 mg, 0.55 mmol, 1.00 equiv) in dichloromethane (10 mL), 3-(methyl(2-morpholinoethyl)carbamoyl)benzoic acid (190 mg, 0.65 mmol, 1.19 equiv), 4-dimethylaminopyridine (133 mg, 1.09 mmol, 1.99 equiv), EDC.HCl (210 mg, 1.09 mmol, 2.00 equiv). The resulting solution was stirred overnight at room temperature. The reaction progress was monitored by LCMS. The resulting solution was diluted with 100 mL of dichloromethane. The resulting mixture was washed with 2×50 mL of NH4Cl aq. and 2×50 mL of brine. The mixture was dried over sodium sulfate and concentrated under vacuum. The crude product was purified by Prep-HPLC with the following conditions (1#-Waters 2767-3): Column, SunFire Prep C18, 5 um, 19*150 mm; mobile phase, water with 0.05% TFA and CH3CN (30% CH3CN up to 42% in 6 min); Detector, UV 220&254 nm. This resulted in 87.2 mg (15%) of N1-(4-(butyl(methyl)amino)-2-(4-(3-(trifluoromethyl)benzylcarbamoyl)pyridin-2-yl)phenyl)-N3-methyl-N3-(2-morpholinoethyl)isophthalamide as a yellow solid. LC-MS (ES, m/z): 731 [M+H]+ H-NMR (300 MHz, DMSO, ppm): 11.95 (s, 1H), 9.75 (s, 1H), 9.52 (s, 1H), 8.88 (d, J=5.1 Hz, 1H), 8.27 (s, 1H), 8.10 (d, J=9.3 Hz, 1H), 7.97-7.83 (m, 2H), 7.82 (d, J=5.1 Hz, 1H), 7.70-7.54 (m, 6H), 7.17 (s, 1H), 6.95 (d, J=7.5 Hz, 1H), 4.61 (d, J=5.7 Hz, 2H), 4.02 (s, 2H), 3.90 (s, 2H), 3.65 (s, 4H), 3.45-3.39 (m, 4H), 3.20 (s, 2H), 3.0 (d, J=12.3 Hz, 6H), 1.55-1.50 (m, 2H), 1.35-1.30 (m, 2H), 0.93-0.88 (m, 3H).

後処理

  1. customInto a 50-mL round-bottom flask, was placed
  2. washThe resulting mixture was washed with 2×50 mL of NH4Cl aq. and 2×50 mL of brine
  3. dry with materialThe mixture was dried over sodium sulfate
  4. concentrationconcentrated under vacuum
  5. customThe crude product was purified by Prep-HPLC with the following conditions (1#-Waters 2767-3)
  6. waitmobile phase, water with 0.05% TFA and CH3CN (30% CH3CN up to 42% in 6 min)
  7. customThis resulted in 87.2 mg (15%) of N1-(4-(butyl(methyl)amino)-2-(4-(3-(trifluoromethyl)benzylcarbamoyl)pyridin-2-yl)phenyl)-N3-methyl-N3-(2-morpholinoethyl)isophthalamide as a yellow solid

出典と根拠

ORDレコード
ord-2407f7ba244648129166b6e1f05bd85a
出典データセット
uspto-grants-2016_04
特許番号
US09301951B2

反応ノート

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