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Dichloromethane → N-(1-(6-(4-Cyanophenyl)-4,5-dimethylpyridazin-3-yl)piperidin-4-yl)-N-methyl-4-(trifluoromethyl)nicotinamide hydrochloride

HRID 1890774
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HRID 1890774 반응식
[CH3:1][C:2]1[C:7]([CH3:8])=[C:6]([N:9]2[CH2:14][CH2:13][CH:12]([NH:15][CH3:16])[CH2:11][CH2:10]2)[N:5]=[N:4][C:3]=1[C:17]1[CH:24]=[CH:23][C:20]([C:21]#[N:22])=[CH:19][CH:18]=1.[F:25][C:26]([F:37])([F:36])[C:27]1[C:32]([C:33]([OH:35])=O)=[CH:31][N:30]=[CH:29][CH:28]=1.C(N(CC)CC)C.CCN=C=NCCCN(C)C.C(Cl)[Cl:57]>O>[ClH:57].[C:21]([C:20]1[CH:23]=[CH:24][C:17]([C:3]2[N:4]=[N:5][C:6]([N:9]3[CH2:14][CH2:13][CH:12]([N:15]([CH3:16])[C:33](=[O:35])[C:32]4[C:27]([C:26]([F:25])([F:37])[F:36])=[CH:28][CH:29]=[N:30][CH:31]=4)[CH2:11][CH2:10]3)=[C:7]([CH3:8])[C:2]=2[CH3:1])=[CH:18][CH:19]=1)#[N:22]
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참가 물질

7

반응물 5

HCID 6344DichloromethaneHCID 8471TriethylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 27775493-Pyridinecarboxylic acid, 4-(trifluoromethyl)-HCID 67370777HCID 67370777, 화합물

생성물 1

HCID 46203697
N-(1-(6-(4-Cyanophenyl)-4,5-dimethylpyridazin-3-yl)piperidin-4-yl)-N-methyl-4-(trifluoromethyl)nicotinamide hydrochloride
수율 49%

시약·촉매·용매 1

HCID 962Water용매

실험 절차

Treat a solution of 4-(4,5-dimethyl-6-(4-(methylamino)piperidin-1-yl)pyridazin-3-yl)benzonitrile (102 mg, 0.32 mmol), 4-(trifluoromethyl)nicotinic acid (81 mg, 0.42 mmol), triethylamine (0.07 mL, 0.5 mmol) in CH2Cl2 (4 mL) with EDCI (99 mg, 0.52 mmol) and stir for 3 d. Pour the reaction mixture into H2O and extract with EtOAc. Wash the organic layer with H2O, dry over Na2SO4, filter, and concentrate under reduced pressure. Purify by flash silica gel chromatography (gradient of 0 to 10% MeOH in CH2Cl2). Dissolve the free base in MeOH (2 mL) and add 1 M HCl in Et2O (0.5 mL). Concentrate to provide the title compound (82 mg, 49%). ES/MS m/z 495.2 (M+1).

후처리

  1. extractionextract with EtOAc
  2. washWash the organic layer with H2O
  3. dry with materialdry over Na2SO4
  4. filtrationfilter
  5. concentrationconcentrate under reduced pressure
  6. customPurify by flash silica gel chromatography (gradient of 0 to 10% MeOH in CH2Cl2)
  7. dissolutionDissolve the free base in MeOH (2 mL)
  8. additionadd 1 M HCl in Et2O (0.5 mL)
  9. concentrationConcentrate

출처 및 근거

ORD 기록
ord-9ed8c64485e54a3a85d5aaa44840e3a1
출처 데이터셋
uspto-grants-2013_08
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08507490B2

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