Ethylene Glycol → [1-(6-Chloropyridin-3-yl)-pyrrolidin-3-yl]-(2,4-dichlorobenzyl)-amine

HRID 252104Notes

Reaction equation

[Cl:1][C:2]1[CH:7]=[CH:6][C:5](I)=[CH:4][N:3]=1.C(=O)([O-])[O-].[K+].[K+].[Cl:15][C:16]1[CH:28]=[C:27]([Cl:29])[CH:26]=[CH:25][C:17]=1[CH2:18][NH:19][C@H:20]1[CH2:24][CH2:23][NH:22][CH2:21]1.C(O)CO>C(O)(C)C.[Cu](I)I>[Cl:1][C:2]1[N:3]=[CH:4][C:5]([N:22]2[CH2:23][CH2:24][CH:20]([NH:19][CH2:18][C:17]3[CH:25]=[CH:26][C:27]([Cl:29])=[CH:28][C:16]=3[Cl:15])[CH2:21]2)=[CH:6][CH:7]=1

Participants

Conditions

Temperature: 80 °C

Procedure

Add 2-chloro-5-iodopyridine (193 mg, 0.84 mmol) to a mixture of potassium carbonate (344 mg, 1.61 mmol) and copper iodide (7 mg, 5% mol) and purge with nitrogen for 10 min. Add a solution of (S)-(2,4-dichlorobenzyl)-pyrrolidin-3-ylamine (238 mg, 0.97 mmol) in ethylene glycol (0.09 mL, 1.61 mmol) and isopropanol (1 mL). Stir at 80° C. for 4 days. Add water (2 mL) and extract with ethyl acetate, wash with saturated aqueous sodium chloride, dry (magnesium sulfate), concentrate and chromatograph using preparative mass guided chromatography to give the title compound. Form the hydrochloride by essentially the procedure in Example 1 to give 1H NMR (400 MHz, MeOH-d4) δ 7.79 (1H, d, J=2.69 Hz), 7.63-7.70 (2H, m), 7.49 (1H, dd, J=8.31, 1.96 Hz), 7.34 (1H, d, J=8.80 Hz), 7.21 (1H, dd, J=8.80, 2.93 Hz), 4.48 (2H, s), 4.17-4.24 (1H, m), 3.72-3.79 (1H, m), 3.61-3.68 (2H, m), 3.38-3.44 (1H, m), 2.59-2.69 (1H, m), 2.32-2.33 (1H, m), 2.32-2.40 (1H, m), MS (ES): m/z=356 [M+].

Workup

custompurge with nitrogen for 10 min
extractionAdd water (2 mL) and extract with ethyl acetate
washwash with saturated aqueous sodium chloride
dry with materialdry (magnesium sulfate)
concentrationconcentrate

Sources & evidence

ORD record: ord-38731da8b6a548eea4a0c5ede23b8de4
Source dataset: uspto-grants-2011_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07868014B2

Reaction notes

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