A PROCESS FOR THE PREPARATION OF N-(BIS(4-METHOXYPHENYL)METHYL)-6-OXO-2-(PYRIDAZIN-3-YL)-1,6-DIHYDROPYRIMIDINE-5-CARBOXAMIDE

1 . A process of making a compound of Formula I

comprising

a) reacting a compound of Formula BMPN

with formamide and formic acid to produce a compound of Formula BMPF

b) hydrolyzing the compound of Formula BMPF with acid to yield a compound of Formula BMMA

and

c) reacting the compound of Formula BMMA with a compound of Formula DHP

to yield the compound of Formula I.

2 . A process of making a compound of Formula I

comprising

a) reducing a compound of Formula BMMI

with a reducing agent to yield a compound of Formula BMMA free base

b) reacting the compound of Formula BMMA free base with a compound of Formula DHP

to yield the compound of Formula I.

3 . A process of making a compound of Formula I

comprising

a) reacting pyridazine with between about 1.0 equivalent and about 1.5 equivalent of each of trimethylsilyl cyanide and toluenesulfonyl chloride to yield a compound of the Formula TPN

b) washing the compound of the Formula TPN with sodium bicarbonate to yield a compound of Formula PYN

c) reacting the compound of Formula PYN with sodium in methanol at ambient temperature and then adding ammonium chloride to yield a compound of Formula PYA

d) reacting the compound of Formula PYA with diethyl ethoxymethylenemalonate and sodium carbonate to yield a compound of Formula DHP

and

e) reacting the compound of Formula DHP with a compound of Formula BMMA

or a free base thereof to yield the compound of Formula I.

4 . A process of making a compound of Formula BMMA

comprising

a) reacting a compound of Formula BMPN

with formamide and formic acid to produce a compound of Formula BMPF

and

b) hydrolyzing the compound of Formula BMPF with an acid to yield the salt of the compound of Formula BMMA.

5 . The process of claim 4 , wherein the acid is selected from sulfuric acid, hydrobromic acid, phosphoric acid or hydrochloric acid.

6 . A process of making a compound of Formula BMMA free base

comprising

a) reducing a compound of Formula BMMI

with a reducing agent to yield the compound of Formula BMMA free base.

7 . The process of claim 6 , wherein the reducing agent is sodium borohydride, a borane complexes, LiAlH4) or catalytic hydrogenation with a Rhodium (Rh) or Iridium (Ir) catalyst.

8 . A process of making a compound of Formula PYN

comprising

a) reacting pyridazine with between about 1.0 equivalent and about 1.5 equivalent of each of trimethylsilyl cyanide and toluenesulfonyl chloride

to yield a compound of the Formula TPN

and

b) washing the compound of the Formula TPN with sodium bicarbonate

to yield the compound of Formula PYN.

9 . The process of claim 8 , wherein the equivalents of each of trimethylsilyl cyanide and toluenesulfonyl chloride are about 1.2 equivalents.

10 . The process of claim 8 , wherein the process is conducted in a solvent of between about 8 to 15 volumes.

11 . The process of claim 10 , wherein the solvent is 2-methyltetrahydrofuran.

12 . The process of claim 8 , wherein the process of step a) further comprises adding aluminum trichloride in two, three or four portions.

13 . A process of making a compound of Formula PYA

comprising

a) reacting a compound of Formula PYN with sodium in methanol at ambient temperature without reflux; and

b) adding ammonium chloride

to yield the compound of Formula PYA.

14 . A process of making a compound of Formula DHP

comprising reacting a compound of Formula PYA with diethyl ethoxymethylenemalonate and sodium carbonate to yield the compound of Formula DHP.

15 . The process of claim 14 , wherein the pH of the process is reduced to below about 3.5, preferably to 1.0.

16 . The process of claim 9 , wherein the process is conducted in a solvent of between about 8 to 15 volumes.

17 . The process of claim 9 , wherein the process of step a) further comprises adding aluminum trichloride in two, three or four portions.

18 . The process of claim 10 , wherein the process of step a) further comprises adding aluminum trichloride in two, three or four portions.

19 . The process of claim 11 , wherein the process of step a) further comprises adding aluminum trichloride in two, three or four portions.