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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
ノート
印刷プレビュー

反応式

HRID 1782569 の反応式
[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
参加物実験手順後処理出典と根拠反応ノート

参加物

8

反応物 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

生成物 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
収率 68.1%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 57417360Sodium chloride; water溶媒

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-009a55b55ebb41f9a3d31789259d28a7
出典データセット
uspto-grants-2009_03
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US07498346B2

反応ノート

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