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

HRID 423541Notes

Reaction equation

HRID 423541 reaction equation
[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

Participants

6

Reactant 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, compound

Product 1

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

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-b10170b0f202473eacadf4e01d2dc900
Source dataset
uspto-grants-2012_01
Patent number
US08101634B2

Reaction notes

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