1,2-Ethanediamine, N1,N1-diethyl-N2-methyl- → N1-(2-(diethylamino)ethyl)-N1-methyl-N3-(4-(piperidin-1-yl)-2-(4-((3-(trifluoromethyl)benzyl)carbamoyl)pyridin-2-yl)phenyl)-isophthalamide

HRID 625234

반응식

HRID 625234 반응식
[F:1][C:2]([F:44])([F:43])[C:3]1[CH:4]=[C:5]([CH:40]=[CH:41][CH:42]=1)[CH2:6][NH:7][C:8]([C:10]1[CH:15]=[CH:14][N:13]=[C:12]([C:16]2[CH:21]=[C:20]([N:22]3[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]3)[CH:19]=[CH:18][C:17]=2[NH:28][C:29]([C:31]2[CH:32]=[C:33]([CH:37]=[CH:38][CH:39]=2)[C:34]([OH:36])=O)=[O:30])[CH:11]=1)=[O:9].CCN=C=NCCCN(C)C.Cl.[CH2:57]([N:59]([CH2:64][CH3:65])[CH2:60][CH2:61][NH:62][CH3:63])[CH3:58]>ClCCl.CN(C)C1C=CN=CC=1>[CH2:57]([N:59]([CH2:64][CH3:65])[CH2:60][CH2:61][N:62]([CH3:63])[C:34](=[O:36])[C:33]1[CH:37]=[CH:38][CH:39]=[C:31]([C:29]([NH:28][C:17]2[CH:18]=[CH:19][C:20]([N:22]3[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]3)=[CH:21][C:16]=2[C:12]2[CH:11]=[C:10]([C:8](=[O:9])[NH:7][CH2:6][C:5]3[CH:40]=[CH:41][CH:42]=[C:3]([C:2]([F:43])([F:1])[F:44])[CH:4]=3)[CH:15]=[CH:14][N:13]=2)=[O:30])[CH:32]=1)[CH3:58]

참가 물질

6

반응물 3

HCID 660341,2-Ethanediamine, N1,N1-diethyl-N2-methyl-HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 665867843-((2-(4-((3-(Trifluoromethyl)benzyl)carbamoyl)pyridin-2-yl)-4-(piperidin-1-yl)phenyl)carbamoyl)benzoic acid

생성물 1

HCID 66588039N1-(2-(diethylamino)ethyl)-N1-methyl-N3-(4-(piperidin-1-yl)-2-(4-((3-(trifluoromethyl)benzyl)carbamoyl)pyridin-2-yl)phenyl)-isophthalamide수율 39.3%

시약·촉매·용매 2

HCID 142844-(Dimethylamino)pyridine촉매HCID 6344Dichloromethane용매2회

반응 조건

온도
25 °C

실험 절차

Into a 10-mL round bottom flask, was placed a solution of 3-((2-(4-((3-(trifluoromethyl)benzyl)carbamoyl)pyridin-2-yl)-4-(piperidin-1-yl)phenyl)carbamoyl)-benzoic acid (100 mg, 0.17 mmol, 1.00 equiv) in dichloromethane (5 mL), EDC.HCl (63.75 mg, 0.33 mmol, 2.00 equiv), 4-dimethylaminopyridine (40.5 mg, 0.33 mmol, 2.00 equiv), N1,N1-diethyl-N2-methylethane-1,2-diamine (64.8 mg, 0.56 mmol, 3.00 equiv). The resulting solution was stirred overnight at 25° C. in an oil bath. The reaction progress was monitored by LCMS. The resulting solution was diluted with 50 mL of dichloromethane. The resulting mixture was washed with 3×70 mL of NH4Cl (aq). 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 47.8 mg (34%) of a yellow solid. 1H-NMR (300 MHz, DMSO-d6, ppm): δ 12.36 (s, 1H), 9.57 (t, 1H), 9.28 (s, 1H), 8.90 (d, J=5.1 Hz, 1H), 8.30 (m, 2H), 7.98 (d, J=7.2 Hz, 2H), 7.84 (d, J=4.8 Hz, 1H), 7.65 (m, 7H), 7.28 (d, J=8.4 Hz, 1H), 4.66 (d, J=6.0 Hz, 2H), 3.82 (m, 2H), 3.31 (m, 9H), 2.97 (s, 4H), 1.71 (m, 6H), 1.24 (m, 6H). MS (ES, m/z): 715 [M+H]+.

후처리

  1. customInto a 10-mL round bottom flask, was placed
  2. washThe resulting mixture was washed with 3×70 mL of NH4Cl (aq)
  3. dry with materialThe mixture was dried over anhydrous sodium sulfate
  4. concentrationconcentrated under vacuum
  5. customThe crude product (150 mg) was purified by reverse phase HPLC
  6. washeluting with a water/CH3CN gradient
  7. additioncontaining 0.05% TFA

출처 및 근거

ORD 기록
ord-f382842f4eb040cdb885018837e014b9
출처 데이터셋
uspto-grants-2016_04
특허 번호
US09301951B2

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