N-Methyl-4-pyridinemethanamine

Colorless liquid

(a) N-Methyl-N-(4-picolyl)amine. To 4-picolyl chloride, hydrochloride (10 g, 0.06 mol) was added methylamine (50 mL of 40% aqueous solution, 0.58 mol), and the resulting purple solution was stirred at rt for 30 min, then poured into H2 O. The mixture was extracted with CH2 Cl2 (6*), and the combined organic extracts were evaporated. The residue was filtered under reduced pressure through a silica gel column, eluding with a solvent gradient of 0-10% MeOH/CHCl3 to provide the title compound as a light yellow oil (4.8 g, 66%): 1 H NMR (CDCl3): delta8.50 (dd, 2H); 7.20 (dd, 2H); 3.70 (s, 2H); 2.40 (s, 3H); 1.70 (br, 1H).Example 62g Preparation of 2al This compound was prepared according to the procedure described above for example 2ai except product isolation was achieved by evaporation of DMF, stirring the residue with methanol (3 ml) and washing the resulting precipitate with 50% methanol/ether (5 ml) and ether (5 ml). From example 2ag (20 mg, 0.065 mmol) and 4-(N-methyl-aminomethyl)pyridine (12 mg, 0.098 mmol) was obtained 18 mg (67%) of the title compound as a light brown solid. MS: 411 (M+H)+.A solution of 4-phenoxycarbonylamino-benzoic acid ethyl ester (50 mg, 0.175 mmol), methyl-pyridin-4-ylmethyl-amine (23.5mg, 0.193 mmol) and Et3N (53.15 mg, 0.526 mmol) in 1, 4- dioxane (2 ml) was stirred at 90 C overnight. The mixture was concentrated and purified by prep[IPLC to give 4-(3-benzyl-3-methyl-ureido)-benzoic acid ethyl ester (14 mg. yield: 25.5%) as a white solid. 'HNMR(400 IVIHz, CD3OD): oe = 8.81 (brs, 2H), 8.01 (brs, 2H), 7.92 (d, J= 6.8 Hz, 2H), 7.58 (d, J= 6.8 Hz, 2H), 4.91 (s, 2H), 4.33 (q, J= 7.2 Hz, 2H), 3.23 (s, 3H), 1.37 (t, J= 7.2 Hz, 3H). MS:m/z 314.0 (M+H).To a solution of A2 (100 mg, 0.3 12 mmol) in DCM (5 mL) was added TEA (156 mg, 1.55 mmol) and HATU (177 mg, 0.468 mmol) at 25 C. After stirring at 25 C for 30 mins, N-methyl-1-(pyridin-4- yl)methylamine (57.1 mg, 0.468 mmol) was added. The mixture was stirred at 25 C for 1 h, quenchedwith water (20 mL) and extracted with DCM (2 x 20 mL). The organic layers were washed with brine (20 mL), dried over Na2 SO4, concentrated in vacuo to give a crude product, which was purified by flash silica gel chromatography (030% of EtOAc in PE) to give Compound 13 (81 mg, 61%) as a solid.1H NMR (400MHz, CDCl3) delta 8.59-8.54 (m, 2H), 7.15 (d, J 4.0 Hz, 1.4H), 7.07 (d, J 4.0 Hz, 0.6H), 5.00 (d, J 20Hz, 0.3H), 4.89 (d, J 16Hz, 0.7H), 4.37-4.26 (m, 1H), 3.03 (s, 2.2H), 2.96 (m, 0.8H), 2.81 (t, J= 12Hz 0.8H), 2.56 (t, J= 12Hz 0.2H) 2.34-2.26 (m, 1H), 1.81-1.74 (m, 4H), 1.72-1.61 (m, 3H), 1.52-1.21 (m, 16H), 1.13-1.11 (m, 3H), 0.79 (s, 3H)LCMS Rt = 1.491 min in 3.0 mm chromatography, 10-8OAB, purity 100%, MS ESI calcd. for C27H41 N202 [M+H] 425, found 425.General procedure: To a 100-mL, one-necked, round-bottomed flask, sequentially charged with compound A (2.25 mmol, 1 equiv.), CS2 (11.25 mmol, 5 equiv.), K3PO4 (2.25 mmol, 1 equiv.) and 30 mL ofacetone. The mixture was stirred for 0.5 h at r.t. and then 4-(bromomethyl)benzoic acid (2.25 mmol, 1 equiv.) was added. TLCanalysis was used to indicate the completed reaction. The reactionmixture was concentrated to provide crude compound B.

Molecular Weight:122.17
XLogP3:0.3
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:2
Exact Mass:122.084398327
Monoisotopic Mass:122.084398327
Topological Polar Surface Area:24.9
Heavy Atom Count:9
Complexity:67.3
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes