Pyrrolidine → 1-Methylethyl 4-[({6-[4-(1-pyrrolidinylcarbonyl)phenyl]-3-pyridinyl}oxy)methyl]-1-piperidinecarboxylate

HRID 423541ノート

反応式

HRID 423541 の反応式
[CH3:1][CH:2]([O:4][C:5]([N:7]1[CH2:12][CH2:11][CH:10]([CH2:13][O:14][C:15]2[CH:16]=[CH:17][C:18]([C:21]3[CH:29]=[CH:28][C:24]([C:25]([OH:27])=O)=[CH:23][CH:22]=3)=[N:19][CH:20]=2)[CH2:9][CH2:8]1)=[O:6])[CH3:3].[NH:30]1[CH2:34][CH2:33][CH2:32][CH2:31]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C>CN(C=O)C>[N:30]1([C:25]([C:24]2[CH:28]=[CH:29][C:21]([C:18]3[N:19]=[CH:20][C:15]([O:14][CH2:13][CH:10]4[CH2:9][CH2:8][N:7]([C:5]([O:4][CH:2]([CH3:3])[CH3:1])=[O:6])[CH2:12][CH2:11]4)=[CH:16][CH:17]=3)=[CH:22][CH:23]=2)=[O:27])[CH2:34][CH2:33][CH2:32][CH2:31]1

参加物

6

反応物 4

HCID 31268PyrrolidineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 66673118HCID 66673118、化合物

生成物 1

HCID 249965531-Methylethyl 4-[({6-[4-(1-pyrrolidinylcarbonyl)phenyl]-3-pyridinyl}oxy)methyl]-1-piperidinecarboxylate収率 25.6%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

4-(5-{[(1-{[(1-Methylethyl)oxy]carbonyl}-4-piperidinyl)methyl]oxy}-2-pyridinyl)benzoic acid (0.05 g, 0.13 mmol) was added to a solution of pyrrolidine (0.01 g, 0.13 mmol) in DMF (2 mL), followed by addition of HATU (0.05 g, 0.13 mmol), and diisopropylethylamine (0.02 g, 0.13 mmol). The reaction mixture was stirred at room temperature for 10 minutes. The reaction was then purified by reverse-phase preparative HPLC using CH3CN:H2O gradient (0:100 to 90:10) with 0.05% TFA as a modifier. The resultant lyophilized material was converted to its free base by dissolving the solid in CH2Cl2, washing with saturated aqueous NaHCO3 and concentrating in vacuo to give the title compound (15 mg, 25%) as a white solid. 1H NMR (400 MHz, CDCl3): δ 8.44 (d, 1H, J=2.9 Hz), 7.93 (d, 2H, J=8.4 Hz), 7.65 (d, 1H, J=8.6 Hz), 7.68 (d, 2H, J=8.4 Hz), 7.27-7.20 (m, 1H), 4.95-4.85 (m, 1H), 4.29-4.12 (m, 2H), 3.87 (d, 2H, J=6.4 Hz), 3.68-3.59 (m, 2H), 3.47-3.41 (m, 2 H), 2.78-2.72 (m, 2H), 2.04-1.78 (m, 7H), 1.34-1.28 (m, 2H), 1.22 (d, 6H, J=6.2 Hz); LRMS (ESI), m/z 452 (M+H).

後処理

  1. customThe reaction was then purified by reverse-phase preparative HPLC
  2. dissolutionby dissolving the solid in CH2Cl2
  3. washwashing with saturated aqueous NaHCO3
  4. concentrationconcentrating in vacuo

出典と根拠

ORDレコード
ord-b10170b0f202473eacadf4e01d2dc900
出典データセット
uspto-grants-2012_01
特許番号
US08101634B2

反応ノート

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