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To a flask was added 3-{[5-(azetidin-1-ylcarbonyl)pyrazin-2-yl]oxy}-5-[(1S)-2-methoxy-1-methylethoxy]benzoic acid (1.0 eq), 5-methylpyrazin-2-amine (1.0 eq) and 2-methyltetrahydrofuran (3.5 vols) under a nitrogen atmosphere. The mixture was cooled to 0° C. N-methylmorpholine (5.0 eq) was added at 0° C., then 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane 2,4,6-trioxide (supplied as 50% w/w in ethyl acetate) (2.5 eq) was added in one portion via addition funnel over 45 minutes maintaining the reaction temperature at 0-5° C. The addition funnel was washed with 2-methyltetrahydrofuran (0.5 vols), then the reaction mixture was boiled under reflux under nitrogen for at least 14 hours, before being cooled to 22° C. Water (4.0 vols) was added to the reaction mixture in one portion, followed by 2-methyltetrahydrofuran (4.0 vols). After agitating for 30 minutes, the layers were separated. The upper organic layer was retained and the aqueous layer returned to the flask. 2-Methyltetrahydrofuran (4.0 vols) was added to the flask, the mixture was agitated for 30 minutes, then the layers were separated. The organic layers were combined in the flask and further 2-methyltetrahydrofuran (6.0 vols) was then added. The mixture was agitated, and 1.0N hydrochloric acid (4.0 vols) was then added. The mixture was agitated for at least 30 minutes at 22±5° C., and the layers were then separated. 1.0N Hydrochloric acid (4.0 vols) was added to the organic layer. The mixture was agitated for at least 30 minutes at 22±5° C. the mixture was separated 5% w/w Sodium hydrogen carbonate (4.0 vols) solution was added the organic layer. The mixture was agitated for at least 30 minutes at 22±5° C. then the mixture was separated. This process was repeated. Water (4.0 vols) was added to the organic layer, the mixture was agitated for at least 30 minutes at 22±5° C. then the layers were separated. The organic layer was distilled under vacuum at 35° C. collecting 19 vols of distillates. 2-Methyltetrahydrofuran (4 vols) was added, and the distillation was continued under vacuum at 35° C. collecting 6 vols distillates. Further 2-methyltetrahydrofuran (4 vols) was added and the reaction mixture sampled for water content. Further 2-methyltetrahydrofuran (4 vols) was added, and the reaction mixture was filtered through a CUNO™ filter then distilled until the pot volume was approximately 7 vols, then methyl iso-butylketone (11 vols) was added and the mixture vacuum distilled at 35° C. to a pot volume of approximately 7 vols. Methyl iso-butylketone (11 vols) was added and the mixture vacuum distilled at 35° C. to a pot volume of approximately 6 vols. N-Heptane (0.5 vols) was added to the mixture, and the temperature adjusted to 60° C., the mixture was cooled to 46° C., seeded, then cooled to 22° C. and agitated for at least 12 hours. The mixture was filtered. The solid was washed with a mixture of methyl iso-butylketone (1.5 vols)/heptane (0.16 vols). The solid was washed with heptane (˜1.5 vols). The isolated solid was dried at 22° C. under vacuum to afford the title compound as an off white solid. Corrected yield was 62%. 1H NMR δ (400 MHz DMSO) 11.04 (s, 1H), 9.26 (s, 1H), 8.68 (s, 1H), 8.57 (s, 1H), 8.36 (s, 1H), 7.57 (bs, 1H), 7.47 (bs, 1H), 7.13 (bs, 1H), 4.81-4.77 (m, 1H), 4.58-4.54 (t, 2H), 4.11-4.07 (t, 2H), 3.55-3.47 (m, 2H), 3.3 (s, 3H), 2.48 (s, 3H), 2.34-2.26 (m, 2H), 1.26-1.25 (d, 3H)

1. temperaturemaintaining the reaction temperature at 0-5° C
2. washThe addition funnel was washed with 2-methyltetrahydrofuran (0.5 vols)
3. temperatureunder reflux under nitrogen for at least 14 hours
4. temperaturebefore being cooled to 22° C
5. additionWater (4.0 vols) was added to the reaction mixture in one portion
6. customthe layers were separated
7. addition2-Methyltetrahydrofuran (4.0 vols) was added to the flask
8. stirringthe mixture was agitated for 30 minutes
9. customthe layers were separated
10. additionwas then added
11. stirringThe mixture was agitated
12. addition1.0N hydrochloric acid (4.0 vols) was then added
13. stirringThe mixture was agitated for at least 30 minutes at 22±5° C.
14. customthe layers were then separated
15. addition1.0N Hydrochloric acid (4.0 vols) was added to the organic layer
16. stirringThe mixture was agitated for at least 30 minutes at 22±5° C. the mixture
17. customwas separated 5% w/w Sodium hydrogen carbonate (4.0 vols) solution
18. additionwas added the organic layer
19. stirringThe mixture was agitated for at least 30 minutes at 22±5° C.
20. customthe mixture was separated
21. additionWater (4.0 vols) was added to the organic layer
22. stirringthe mixture was agitated for at least 30 minutes at 22±5° C.
23. customthe layers were separated
24. distillationThe organic layer was distilled under vacuum at 35° C.
25. distillationcollecting 19 vols of distillates
26. addition2-Methyltetrahydrofuran (4 vols) was added
27. distillationthe distillation
28. customwas continued under vacuum at 35° C.
29. distillationcollecting 6 vols distillates
30. additionFurther 2-methyltetrahydrofuran (4 vols) was added
31. aliquotthe reaction mixture sampled for water content
32. additionFurther 2-methyltetrahydrofuran (4 vols) was added
33. filtrationthe reaction mixture was filtered through a CUNO™
34. filtrationfilter
35. distillationthen distilled until the pot volume
36. additionmethyl iso-butylketone (11 vols) was added
37. distillationthe mixture vacuum distilled at 35° C. to a pot volume of approximately 7 vols
38. additionMethyl iso-butylketone (11 vols) was added
39. distillationthe mixture vacuum distilled at 35° C. to a pot volume of approximately 6 vols
40. additionN-Heptane (0.5 vols) was added to the mixture
41. customadjusted to 60° C.
42. temperaturethe mixture was cooled to 46° C.
43. temperaturecooled to 22° C.
44. stirringagitated for at least 12 hours
45. filtrationThe mixture was filtered
46. washThe solid was washed with a mixture of methyl iso-butylketone (1.5 vols)/heptane (0.16 vols)
47. washThe solid was washed with heptane (˜1.5 vols)
48. customThe isolated solid was dried at 22° C. under vacuum