Kaye, Irving Allan published the artcileReductive alkylation of 2-aminopyridine and 2-aminopyrimidine, Safety of N-(4-Methoxybenzyl)pyridin-2-amine, the publication is Recueil des Travaux Chimiques des Pays-Bas et de la Belgique (1952), 309-17, database is CAplus.
Reductive alkylation of amines with aldehydes and HCO2H gives better yields of purer products than alkylation with the corresponding bromides and condensing agent. Method A: procedure of Tschitschibabin and Knunianz, C.A. 26, 1932, without significant modification. Method B: 2-C5H4NNH2 (I) or 2-aminopyrimidine (II) (0.5 mol.) and 0.5 mol. aldehyde (III) in 125 ml. 85-90% HCO2H, were refluxed 20 hrs., poured onto ice, treated with H2O containing 125 g. NaOH, the mixture was extracted with CHCl3, and the extract dried over K2CO3, concentrated, and distilled in vacuo (the b.ps. listed may be too high because rapid distillation was necessary to prevent crystallization in the side arm of the flask). The products could be used directly, but more conveniently after crystallization from Me2CHOH (IV) or C6H6–hexane (V). Method C: To I or II and III (1 mol. each) in 125 ml. cumene, refluxed (about 2 hrs.) until the volume of H2O distilled was constant, was added 108 g. 85-90% HCO2H (CO2 was evolved), the solution refluxed 12-24 hrs., concentrated in vacuo, and the residue distilled The following intermediate imine N-derivatives of 2-aminopyridine were isolated (after refluxing with cumene alone) by vacuum distillation: 89% p-chlorobenzylidene (VI), b0.5 122.5-5°; 89% p-methoxybenzylidene (VII), b0.6 147-8°, m. 55-7.5° (from MeOH); 95% 3,4-dimethoxybenzylidene (VIII), b0.2 148-53°; 71% 2-thienylidene, b0.03 110-12°; 76% furfurylidene (IX), b0.05 109-13°, m. 52-5° (from (Me2CH)2O) (crystallization from Me2CHOAc converted IX to 2,2′-(furfurylidenediimino)bipyridine, m. 82.5-4°); 93% 3,4-methylenedioxybenzylidene (X), b0.5 152-3°, m. 99.5-100° (from heptane); 81% 2,3-dimethoxybenzylidene, b0.09 130-9°; and 73% benzylidene, b22 174-85° (yellow liquid from which, even when it was kept in a glass-stoppered bottle, precipitated 2,2′-(benzylidenediimino)bi-pyridine, m. 103-5°). To 95.1 g. II and 106.1 g. BzH refluxed 3 hrs. in 200 ml. cumene was added 200 ml. IV and the solution cooled and filtered to give 86% 2,2′-(benzylidenediimino)bipyrimidine (XI), m. 213-15°. The N-benzylidene derivative of II was prepared in poor yield when Ph2CH2 was the solvent, or when XI was heated above its m.p. Method D: To 94.1 g. I in 900 ml. refluxing absolute C6H6 was added (3 hrs.) 23 g. LiNH2, then (dropwise) 161 g. p-ClC6H4CH2Cl in 100 ml. C6H6, and the mixture refluxed 16 hrs., cooled, washed, concentrated, and distilled, giving 62% 2-(p-chlorobenzylamino)pyridine (XII), b0.08 133-40° (crystallization from V gave 52% solid, m. 96-8.5°). The following amines, RNHCH2R’, were prepared [m.p. (from IV unless otherwise specified), procedures used, length of reflux (hrs.), b.p. (°/mm.), and yield (%), resp., given]: When R = 2-pyridyl and R’ = Ph: 97-8°; A, 8, -, 52; A, 94, -, 58; B, 168, 181-2°/12, 68; C, 20, 133-4°/0.12, 88. p-ClC6H4: 103-4° (from V); C, -, 136-8°/0.02, 79. p-MeOC6H4 (XIII): 124-5°; B, 20, 153°/0.1, 54; C, 20, 143-6°/0.06, 87. 2,3-(MeO)2C6H3: 83.5-4.5°; A, 94, -, 67; B, 168, 142-6°/0.1, 73; C, 24, 156-7°/0.1, 81. 3,4-(MeO)2C6H3 (XIV): 104.5°; B, 20, 156°/0.08, 62; C, 20, 173-6°/0.08, 83. 3,4-CH2O2C6H3: 97-8°; B, 20, 148°/0.12, 53; C, 24, 158-9°/0.08, 92. 2-Thienyl: 80-1°; C, 15, 120-5°/0.02, 61. When R = 2-pyrimidyl and R’ = Ph: 82.5-3°: A, 94, -, 40; B, 168, 179-84°/13, 51; B, 17, 105°/0.08, 53. p-MeOC6H4: 108.5-9.5° (from MeOH); B, 20, 150°/0.3, 45; B, 71, 148°/0.3, 29; C, 12, 150-2°/0.2, 42. 2,3-(MeO)2C6H3: 94-5°; A, 94, -, 55; B, 168, 208-16°/19, 43; B, 17, 136°/ 0.12, 72; C, 12, 162-3°/0.4, 63. 3,4-(MeO)2C6H3 (XV): 123.5-4.5° (from MeOH); A, 20, -, 37; B, 19, 176-87°/0.5, 39; C, 12, 155-63°/0.16, 45 [HCl salt, m. 159-60° (from EtOH)]. 3,4-CH2O2C6H3: 118-18.5°; A, 16.5, -, 39; A, 20, -, 42; B, 19, 156-63°/0.1, 41; C, 20, 168-70°/0.5, 47 [HCl salt, m. 172.5-3.5° (from EtOH)]. No evidence of ability to retard the growth of sarcoma 180 in rats was shown by VI, VII, VIII, IX, X, XII, XIII, XIV, or XV.
Recueil des Travaux Chimiques des Pays-Bas et de la Belgique published new progress about 52818-63-0. 52818-63-0 belongs to ethers-buliding-blocks, auxiliary class Pyridine,Amine,Benzene,Ether, name is N-(4-Methoxybenzyl)pyridin-2-amine, and the molecular formula is C13H14N2O, Safety of N-(4-Methoxybenzyl)pyridin-2-amine.
Referemce:
https://en.wikipedia.org/wiki/Ether,
Ether | (C2H5)2O – PubChem