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1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 6-Fluoro-n-((r)-3-{4-[(4-methoxy-phenyl)-(4-methyl-pyridin-3-ylmethyl)-amino]-piperidin-1-yl}-butyl)-2,4-dimethyl-nicotinamide

HRID 1782569
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HRID 1782569 반응식
[NH2:1][CH2:2][CH2:3][C@H:4]([N:6]1[CH2:11][CH2:10][CH:9]([N:12]([C:21]2[CH:26]=[CH:25][C:24]([O:27][CH3:28])=[CH:23][CH:22]=2)[CH2:13][C:14]2[CH:15]=[N:16][CH:17]=[CH:18][C:19]=2[CH3:20])[CH2:8][CH2:7]1)[CH3:5].[F:29][C:30]1[CH:38]=[C:37]([CH3:39])[C:33]([C:34](O)=[O:35])=[C:32]([CH3:40])[N:31]=1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.CCN(C(C)C)C(C)C>CN(C=O)C.[Cl-].[Na+].O>[F:29][C:30]1[CH:38]=[C:37]([CH3:39])[C:33]([C:34]([NH:1][CH2:2][CH2:3][C@H:4]([N:6]2[CH2:7][CH2:8][CH:9]([N:12]([C:21]3[CH:26]=[CH:25][C:24]([O:27][CH3:28])=[CH:23][CH:22]=3)[CH2:13][C:14]3[CH:15]=[N:16][CH:17]=[CH:18][C:19]=3[CH3:20])[CH2:10][CH2:11]2)[CH3:5])=[O:35])=[C:32]([CH3:40])[N:31]=1
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참가 물질

8

반응물 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 57562991(R)-[1-(3-Amino-1-methyl-propyl)-piperidin-4-yl]-(4-methoxy-phenyl)-(4-methyl-pyridin-3-ylmethyl)-amineHCID 687753516-Fluoro-2,4-dimethyl-nicotinic acid

생성물 1

HCID 44511934
6-Fluoro-n-((r)-3-{4-[(4-methoxy-phenyl)-(4-methyl-pyridin-3-ylmethyl)-amino]-piperidin-1-yl}-butyl)-2,4-dimethyl-nicotinamide
수율 68.1%

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 57417360Sodium chloride; water용매

실험 절차

To a solution of [1-((R)-3-amino-1-methyl-propyl)-piperidin-4-yl]-(4-methoxy-phenyl)-(4-methyl-pyridin-3-ylmethyl)-amine (41 mg, 0.11 mmol) in DMF (0.5 mL) was added 6-fluoro-2,4-dimethyl-nicotinic acid (27 mg, 0.16 mmol), HOBT (20 mg, 0.15 mmol), EDCI (29 mg, 0.15 mmol) and DIPEA (55 μL, 0.32 mmol). After the mixture was stirred at room temperature overnight brine (5 mL) was added, and the mixture was extracted with CH2Cl2 (2×5 mL). The organic extracts were combined and dried (Na2SO4). After filtration the solvent was removed under vacuum, and the residue was purified by flash chromatography on a silica gel column (50:1:0.1, CH2Cl2/MeOH/NH4OH) to afford the title compound as a white solid (40 mg, 67%). 1H NMR (CDCl3) δ 0.99 (d, 3H, J=6.6 Hz), 1.00 (m, 1H), 1.19 (m, 1H), 1.54 (m, 1H), 1.72 (m, 1H), 1.82 (br d, 2H, J=12.6 Hz), 2.12 (t, 1H, J=10.5 Hz), 2.32 (s, 3H), 2.34 (s, 3H), 2.47 (s, 3H), 2.48 (t, 1H, J=12.6 Hz), 2.65-2.85 (m, 3H), 3.15-3.45 (m, 2H), 3.72 (s, 3H), 3.82 (m, 1H), 3.96 (s, 2H), 6.51 (s, 1H), 6.60-6.76 (m, 4H), 7.03 (d, 1H, J=4.8 Hz), 8.08 (br. S, 1H), 8.25 (s, 1H), 8.29 (d, 1H, J=4.8 Hz). 13C NMR (CDCl3) δ 13.81, 19.08, 19.50, 22.26, 30.09, 30.90, 31.82, 39.89, 44.46, 47.79, 52.05, 55.92, 59.16, 59.94, 107.62 (d, 1C, J=146 Hz), 114.75 (2C), 120.21 (2C), 125.48, 132.05, 133.47, 142.68, 145.64, 148.27, 149.45, 150.58 (d, 1C, J=32 Hz), 153.08 (d, 1C, J=48 Hz), 162.64 (d, 1C, J=949 Hz), 162.88, 167.92. ES-MS m/z 533 (M+H). Anal. Calcd. For C31H40N5FO2.0.2CH2Cl2: C, 68.05; H, 7.39; N, 12.72. Found: C, 68.26; H, 7.78; N, 13.08.

후처리

  1. additionwas added
  2. extractionthe mixture was extracted with CH2Cl2 (2×5 mL)
  3. dry with materialdried (Na2SO4)
  4. filtrationAfter filtration the solvent
  5. customwas removed under vacuum
  6. customthe residue was purified by flash chromatography on a silica gel column (50:1:0.1, CH2Cl2/MeOH/NH4OH)

출처 및 근거

ORD 기록
ord-009a55b55ebb41f9a3d31789259d28a7
출처 데이터셋
uspto-grants-2009_03
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07498346B2

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