Reaction SMILES: [N:1]1([C:5]([C:7]2[N:8]=[CH:9][C:10]([O:13][C:14]3[CH:15]=[C:16]([CH:20]=[C:21]([O:23][C@@H:24]([CH3:28])[CH2:25][O:26][CH3:27])[CH:22]=3)[C:17]([OH:19])=O)=[N:11][CH:12]=2)=[O:6])[CH2:4][CH2:3][CH2:2]1.[CH3:29][C:30]1[N:31]=[CH:32][C:33]([NH2:36])=[N:34][CH:35]=1.CC1CCCO1.CN1CCOCC1.CCCP1(OP(CCC)(=O)OP(CCC)(=O)O1)=O>O>[N:1]1([C:5]([C:7]2[N:8]=[CH:9][C:10]([O:13][C:14]3[CH:15]=[C:16]([CH:20]=[C:21]([O:23][C@@H:24]([CH3:28])[CH2:25][O:26][CH3:27])[CH:22]=3)[C:17]([NH:36][C:33]3[CH:32]=[N:31][C:30]([CH3:29])=[CH:35][N:34]=3)=[O:19])=[N:11][CH:12]=2)=[O:6])[CH2:4][CH2:3][CH2:2]1
Reactant: COC[C@H](C)Oc1cc(Oc2cnc(C(=O)N3CCC3)cn2)cc(C(=O)O)c1
Reactant: Cc1cnc(N)cn1
Agent: CCCP1(=O)OP(=O)(CCC)OP(=O)(CCC)O1
Solvent: O
Solvent: CC1CCCO1
Solvent: CN1CCOCC1
Product: COC[C@H](C)Oc1cc(Oc2cnc(C(=O)N3CCC3)cn2)cc(C(=O)Nc2cnc(C)cn2)c1
Temperature: 5 °C
Reaction time: 0.5 h
Yield: 85 %

Procedure:
To a flask fitted with overhead stirrer, thermometer, condenser, and nitrogen line 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 (1.12 eq) and 2-methyltetrahydrofuran (4.4 vols) under a nitrogen atmosphere. The mixture was cooled to 5° C., and then N-methylmorpholine (5.0 eq) added drop-wise over at least 15 minutes maintaining the temperature at 5±5° C. 1-Propanephosphonic acid cyclic anhydride (T3P) (as 50% w/w solution in ethyl acetate) (2.5 eq) was added drop-wise over at least 15 minutes maintaining the temperature at 5±5° C. The mixture was heated to reflux for at least 16 hours then cooled to 22±5° C. Water (4.0 vols) was added to the reaction mixture, followed by 2-methyltetrahydrofuran (4.0 vols). After agitating for 30 minutes, the mixture was separated. The upper organic layer was retained and the aqueous layer treated with 2-methyltetrahydrofuran (4.0 vols). After agitating for 30 minutes, this mixture was separated. The organic layers were combined and further 2-methyltetrahydrofuran (6.0 vols) was then added. The mixture was agitated, and 1.0N hydrochloric acid (4.0 vols) was added. The mixture was agitated for at least 30 minutes at 22±5° C., and the layers were then separated. The organic layer was treated with 1.0N hydrochloric acid (4.0 vols) then the mixture was agitated for at least 30 minutes at 22±5° C., then the layers were separated. The organic layer was treated with 5% w/w sodium hydrogen carbonate (4.0 vols). The mixture was agitated for at least 30 minutes at 22±5° C., the layers were separated. The organic layer was treated again with 5% w/w sodium hydrogen carbonate (4.0 vols) following the same procedure, and then with water (4.0 vols) following the same procedure. The organic layer was then distilled at atmospheric pressure to a pot volume of 4.7 vols. Methyl iso-butylketone (10 vols) was added, and the batch distilled at atmospheric pressure to a pot volume of 4.68 vols. Methyl iso-butylketone (10 vols) was added, and the batch distilled at atmospheric pressure to a pot volume of 4.68 vols. The batch was cooled to 70° C., heptane (2.02 vols) was added slowly drop-wise over at least 30 minutes maintaining the reaction temperature at 70±5° C. The mixture was cooled to 60° C., and seeded with 3-{[5-(azetidin-1-ylcarbonyl)pyrazin-2-yl]oxy}-5-[(1S)-2-methoxy-1-methylethoxy]-N-(5-methylpyrazin-2-yl)benzamide Form 1, agitated at 60° C. for 1 hour, cooled to 50° C. at 0.1° C., agitated at 50° C. for 140 minutes, then cooled to 22° C. at 0.1° C./minute. The mixture was held at 22° C. for at least 12 hours. Heptane (5.06 vols) was then added—drop-wise over at least 120 minutes maintaining the batch temperature at a temperature at 22±5° C. The mixture was cooled to 0° C. at 0.1° C./minute then held at 0° C. for at least 12 hours and then filtered. The isolated solid was washed with a mixture of methyl iso-butylketone (1.0 vols) and heptane (3.0 vols) pre-chilled to 0° C. The solid was dried at 40° C. After drying in the vacuum oven at 40° C. overnight, the desired product was obtained as a solid (corrected yield 85%. 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), 7.56 (s, 1H), 7.46 (s, 1H), 7.12 (s, 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)