4,5-Pyrimidinediamine,6-chloro-2-methyl-

Preparation 2. 6-Chloro-4, 5-diamino-2-methylpyrimidine. A 200 mL stainless steel Parr vessel was loaded with 5-amino-4, 6-dichloro-2-methylpyrimidine (7.2 g, 40 mmol) and 2 M ammonia in isopropanol (100 mL), and then was sealed and heated at 150° C. for 16 h. HPLC analysis indicated complete conversion. The mixture was concentrated in vacuo, and the residue was suspended in a mixture of HPreparation 19; 6-Chloro-2-methyl-pyrimidine-4, 5-diamine; 2-methyl-4, 6-dichloro-5-aminopyrinnidine (2. g , 11.235 mmol) was suspended in 20 ml of 37percent aqueous ammonia. The mixture was shared between 4 high pressure vials and they were heated at 100°C for 10 min. The temperature was then reduced to 7ODichloropyrimidine (compound 9, Scheme 1E) was subjected to nucleophilic displacement with 4-methoxy-N-methylaniline and a catalytic amount of concentrated HC1 in the presence of i-PrOH to afford compound 2, Section E. Compound 2, section E., was hydrogenated under Pd/C at 50 psi for 3 hours (h) to afford compound 3, Section E. The synthesis of compounds 4 and 5, Section E., used trialkylaluminium in the presence of Pd catalyst and THF under reflux conditions. Compound 7, Section E., was obtained from 2 using aqueous hydriodic acid at 0 °C-rt. Compound 7 was then heated at 120 °C in the presence of DMF and copper cyanide to yield compound 8, Section E. One of the chloro groups of compound 9, Section E, was substituted with the amino group under SNAr conditions with ethanolic ammonia to produce compound 10, Section E., which was then subjected to nucleophilic displacement with 4-methoxy-N-methylaniline and a catalytic amount of concentrated HC1 in the presence of butanol to afford compound 6, Section E.Preparation 2. 6-Chloro-4, 5-diamino-2-methylpyrimidine. A 200 mL stainless steel Parr vessel was loaded with 5-amino-4, 6-dichloro-2-methylpyrimidine (7.2 g, 40 mmol) and 2 M ammonia in isopropanol (100 mL), and then was sealed and heated at 150° C. for 16 h. HPLC analysis indicated complete conversion. The mixture was concentrated in vacuo, and the residue was suspended in a mixture of HPreparation 19; 6-Chloro-2-methyl-pyrimidine-4, 5-diamine; 2-methyl-4, 6-dichloro-5-aminopyrinnidine (2. g , 11.235 mmol) was suspended in 20 ml of 37percent aqueous ammonia. The mixture was shared between 4 high pressure vials and they were heated at 100°C for 10 min. The temperature was then reduced to 7ODichloropyrimidine (compound 9, Scheme 1E) was subjected to nucleophilic displacement with 4-methoxy-N-methylaniline and a catalytic amount of concentrated HC1 in the presence of i-PrOH to afford compound 2, Section E. Compound 2, section E., was hydrogenated under Pd/C at 50 psi for 3 hours (h) to afford compound 3, Section E. The synthesis of compounds 4 and 5, Section E., used trialkylaluminium in the presence of Pd catalyst and THF under reflux conditions. Compound 7, Section E., was obtained from 2 using aqueous hydriodic acid at 0 °C-rt. Compound 7 was then heated at 120 °C in the presence of DMF and copper cyanide to yield compound 8, Section E. One of the chloro groups of compound 9, Section E, was substituted with the amino group under SNAr conditions with ethanolic ammonia to produce compound 10, Section E., which was then subjected to nucleophilic displacement with 4-methoxy-N-methylaniline and a catalytic amount of concentrated HC1 in the presence of butanol to afford compound 6, Section E.

6-Chloro-2-methylpyrimidine-4,5-diamine is an intermediate in the synthesis of selective inhibitors of Class I Phosphatidylinositol 3-Kinases.

Molecular Weight:158.59
XLogP3:0.5
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:4
Exact Mass:158.0359239
Monoisotopic Mass:158.0359239
Topological Polar Surface Area:77.8
Heavy Atom Count:10
Complexity:120
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes