Reaction SMILES: [F:1][C:2]1[C:7]2[C:8]([C:18](=[O:21])[NH:19][CH3:20])=[C:9]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=3)[O:10][C:6]=2[CH:5]=[CH:4][C:3]=1[C:22]1[C:23]([CH3:33])=[CH:24][C:25]([O:31][CH3:32])=[C:26]([CH:30]=1)[C:27](O)=[O:28].[N:34]1[CH:39]=[CH:38][CH:37]=[N:36][C:35]=1[C:40]1([NH2:43])[CH2:42][CH2:41]1.C(O)(C(F)(F)F)=O.C(N(CC)C(C)C)(C)C>CN(C=O)C.CO>[F:1][C:2]1[C:7]2[C:8]([C:18]([NH:19][CH3:20])=[O:21])=[C:9]([C:11]3[CH:12]=[CH:13][C:14]([F:17])=[CH:15][CH:16]=3)[O:10][C:6]=2[CH:5]=[CH:4][C:3]=1[C:22]1[CH:30]=[C:26]([C:27](=[O:28])[NH:43][C:40]2([C:35]3[N:36]=[CH:37][CH:38]=[CH:39][N:34]=3)[CH2:42][CH2:41]2)[C:25]([O:31][CH3:32])=[CH:24][C:23]=1[CH3:33]
Reactant: NC1(c2ncccn2)CC1
Reactant: CNC(=O)c1c(-c2ccc(F)cc2)oc2ccc(-c3cc(C(=O)O)c(OC)cc3C)c(F)c12
Solvent: O=C(O)C(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: CNC(=O)c1c(-c2ccc(F)cc2)oc2ccc(-c3cc(C(=O)NC4(c5ncccn5)CC4)c(OC)cc3C)c(F)c12
Temperature: 25 °C
Reaction time: 20 h

Procedure:
To a mixture of 5-(4-fluoro-2-(4-fluorophenyl)-3-(methylcarbamoyl)benzofuran-5-yl)-2-methoxy-4-methylbenzoic acid (30 mg, 0.066 mmol), 1-(pyrimidin-2-yl)cyclopropanamine, TFA (33.1 mg, about 75% pure, assumed 0.133 mmol,) and 2-(1H-benzo[d][1,2,3]triazol-1-yl)-1,1,3,3-tetramethylisouronium tetrafluoroborate (64.0 mg, 0.199 mmol) in DMF (1 mL) at r.t. under N2 was added N,N-diisopropylethyl amine (0.058 mL, 0.332 mmol). The mixture was stirred at r.t. for 20 hours. The mixture was diluted with MeOH and purified by Shimadzu-VP preparative reverse phase HPLC using the separation method: Solvent A=10% MeOH-90% H20-0.1% TFA, Solvent B=90% MeOH-10% H20-0.1% TFA, Start % B=50, Final % B=100, Gradient time=10 min, Stop time=12 min, Flow Rate=25 mL/min, Column: Waters-Sunfire 19×100 mm S5, UV detection at 220 nm, Fraction Collection: 7.25-7.73 min. The residue after evaporation of the combined fractions was further purified by preparative TLC (two of 500 um×20×20 cm plates, 5% MeOH/CH2Cl2) to give 4-fluoro-2-(4-fluorophenyl)-5-(4-methoxy-2-methyl-5-(1-(pyrimidin-2-yl)cyclopropylcarbamoyl)phenyl)-N-methylbenzofuran-3-carboxamide as a white solid. Analytical TLC Rf=0.32 (5% MeOH/CH2Cl2). 1H NMR (500 MHz, CD3OD) δ 8.65 (d, J=4.88, 2H), 7.95 (m, 2H), 7.89 (s, 1H), 7.50 (d, J=8.55, 1H), 7.28 (t, J=8.70, 2H), 7.28-7.25 (m overlapping with t, 1H), 7.23 (t, J=4.88, 1H), 7.17 (s, 1H), 4.09 (s, 3H), 2.95 (s, 3H), 2.30 (s, 3H), 1.79 (m, 2H), 1.51 (m, 2H). 19F NMR (470.45 MHz, CD3OD) δ −112.81, −123.16. LC/MS were performed by using Shimadzu-VP instrument with UV detection at 220 nm and Waters Micromass. HPLC method: Solvent A=10% MeOH-90% H2O-0.1% TFA, Solvent B=90% MeOH-10% H2O-0.1% TFA, Start % B=0, Final % B=100, Gradient time=2 min, Stop time=3 min, Flow Rate=5 ml/min, Column: Phenomenex-Luna, 3.0×50 mm, S10; (ES+) m/z (M+H)+=569.38, HPLC Rt=1.660 min. Analytical HPLC were performed by using Shimadzu-VP instrument with UV detection at 220 nm and 254 nm. Analytical HPLC method: Solvent A=5% MeCN-95% H2O-0.1% TFA, Solvent B=95% MeCN-5% H2O-0.1% TFA, Start % B=50, Final % B=100, Gradient time=15 min, Stop time=18 min, Flow Rate=1 ml/min, Column: Sunfire C18, 3.5 um, 4.6×150 mm, Rt=6.29 min; Column: Xbridge Phenyl 3.5 um, 4.6×150 mm, Rt=5.18 min. Analytical HPLC method: Solvent A=5% MeOH-95% H2O-10 mM NH4HCO3, Solvent B=95% MeOH-5% H2O-10 mM NH4HCO3, Start % B=50, Final % B=100, Gradient time=15 min, Stop time=18 min, Flow Rate=1 ml/min, Column: Xbridge Phenyl 3.5 um, 4.6×150 mm, Rt=9.39 min.