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

HRID 423541노트

반응식

HRID 423541 반응식
[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

참가 물질

6

반응물 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, 화합물

생성물 1

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

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-b10170b0f202473eacadf4e01d2dc900
출처 데이터셋
uspto-grants-2012_01
특허 번호
US08101634B2

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