Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([CH:3]([CH:8]([C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)[CH3:9])[C:4]([O:6][CH3:7])=[O:5])#[N:2].Br[CH:17]([CH2:22][CH2:23][Br:24])[C:18]([O:20][CH3:21])=[O:19].C(=O)([O-])[O-].[K+].[K+].Cl>CS(C)=O>[C:10]1([CH:8]([C:3]([C:1]#[N:2])([C:4]([O:6][CH3:7])=[O:5])[CH:17]([C:18]([O:20][CH3:21])=[O:19])[CH2:22][CH2:23][Br:24])[CH3:9])[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1
Reactant: COC(=O)C(Br)CCBr
Reactant: COC(=O)C(C#N)C(C)c1ccccc1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CS(C)=O
Product: COC(=O)C(CCBr)C(C#N)(C(=O)OC)C(C)c1ccccc1
Temperature: 0 °C
Reaction time: 4 h

Procedure:
A mixture of methyl 2-cyano-3-phenylbutyrate (78 g, 0.37 mole), methyl 2,4-dibromobutyrate (122 g, 0.47 mole), potassium carbonate (65 g, 0.47 mole) and DMSO (50 ml) was stirred on a ball mill apparatus. The reaction was completed in four hours. Ice water was added and the mixture was neutralized by adding cold hydrochloric acid. The aqueous solution was extracted several times with ether. The combined organic solution was washed sequentially with cold aqueous sodium bicarbonate and brine, then dried over magnesium sulfate. After removal of the solvent, the residue was purified by Kugelrohr distillation (100° C., 30 microns) to remove low boiling materials. The remaining oily residue (118 g., 84%) was found to be mainly the title bromide condensation product (ν<95% GC purity). MS m/e (% relative intensity) 383(M+., 3) 381 (3), 202 (33), 182 (7), 180 (7), 105 (100).
Reaction SMILES: C(OC([NH:11][CH:12]1[CH:17]([NH:18][C:19]([O:21][CH2:22][CH2:23][Si:24]([CH3:27])([CH3:26])[CH3:25])=[O:20])[CH2:16][CH2:15][CH:14]([C:28]([O:30][CH2:31][CH3:32])=[O:29])[CH2:13]1)=O)C1C=CC=CC=1.[H][H]>[Pd].C(O)(C)C>[NH2:11][CH:12]1[CH:17]([NH:18][C:19]([O:21][CH2:22][CH2:23][Si:24]([CH3:27])([CH3:25])[CH3:26])=[O:20])[CH2:16][CH2:15][CH:14]([C:28]([O:30][CH2:31][CH3:32])=[O:29])[CH2:13]1
Reactant: CCOC(=O)C1CCC(NC(=O)OCC[Si](C)(C)C)C(NC(=O)OCc2ccccc2)C1
Reactant: [H][H]
Agent: [Pd]
Solvent: CC(C)O
Product: CCOC(=O)C1CCC(NC(=O)OCC[Si](C)(C)C)C(N)C1
Yield: 81.8 %

Procedure:
A mixture of Racemate-ethyl 3-(benzyloxycarbonylamino)-4-((2-(trimethylsilyl)ethoxy)carbonylamino)cyclohexanecarboxylate (1.7 g, 3.7 mmol) and 5% palladium on carbon (50% wet, 300 mg) in isopropanol (35 mL) was stirred under 1 atm hydrogen atmosphere at room temperature for 18 hours. The mixture was filtered through a pad of celite. The filtrate was concentrated and purified by silica gel chromatography (methanol/dichloromethane=1/30 to 1/10) to afford the title compound (1.0 g, 89%) as a yellow oil. MS (ES+) C15H30H2O4Si requires: 330, found: 331 [M+H]+.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH:15]=[CH:16][CH:17]=1)[CH2:5][O:6][CH2:7][C:8]1[N:13]=[C:12]([NH2:14])[CH:11]=[CH:10][CH:9]=1.[F:18][C:19]1[CH:24]=[C:23]([F:25])[CH:22]=[CH:21][C:20]=1[S:26](Cl)(=[O:28])=[O:27]>>[F:18][C:19]1[CH:24]=[C:23]([F:25])[CH:22]=[CH:21][C:20]=1[S:26]([NH:14][C:12]1[CH:11]=[CH:10][CH:9]=[C:8]([CH2:7][O:6][CH2:5][C:4]2[CH:15]=[CH:16][CH:17]=[C:2]([F:1])[CH:3]=2)[N:13]=1)(=[O:28])=[O:27]
Reactant: O=S(=O)(Cl)c1ccc(F)cc1F
Reactant: Nc1cccc(COCc2cccc(F)c2)n1
Product: O=S(=O)(Nc1cccc(COCc2cccc(F)c2)n1)c1ccc(F)cc1F

Procedure:
This material was prepared in analogy to example 1 from 6-(3-fluoro-benzyloxymethyl)-pyridin-2-ylamine (0.06 g) and 2,4-difluoro-benzenesulfonyl chloride (0.06 g) as a yellow solid(0.07 g). MS (ESI−): 407.2 ([M−H]−).
Reaction SMILES: [Cl:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6]Br)=[C:4]([O:10][CH3:11])[CH:3]=1.[C-:12]#[N:13].[Na+]>C1(C)C=CC=CC=1.O.CCCCCCCC[N+](CCCCCCCC)(CCCCCCCC)C.[Cl-]>[Cl:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6][C:12]#[N:13])=[C:4]([O:10][CH3:11])[CH:3]=1
Reactant: COc1cc(Cl)ccc1CBr
Reactant: [C-]#N
Agent: CCCCCCCC[N+](C)(CCCCCCCC)CCCCCCCC
Agent: [Cl-]
Agent: [Na+]
Solvent: O
Solvent: Cc1ccccc1
Product: COc1cc(Cl)ccc1CC#N
Yield: 68 %

Procedure:
269 g of 4-chloro-2-methoxybenzyl bromide in 214 ml of toluene are reacted with 68.2 g of sodium cyanide in 69 ml of water and 1.8 g of Aliquat 336. 141 g of colorless oil are obtained (b.p. 107° C./0.08 mbar).
Reaction SMILES: [CH3:1][C:2]1[C:18]([CH3:19])=[CH:17][C:5]2[NH:6][C:7]([CH:9]=[CH:10][C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=3)=[N:8][C:4]=2[CH:3]=1.F[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][N:22]=1.N1C=CC=CC=1N1C2C=CC=CC=2N=C1/C=C/C1C=CC=CC=1>>[CH3:19][C:18]1[C:2]([CH3:1])=[CH:3][C:4]2[N:8]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][N:22]=3)[C:7](/[CH:9]=[CH:10]/[C:11]3[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=3)=[N:6][C:5]=2[CH:17]=1
Reactant: Cc1cc2nc(C=Cc3ccccc3)[nH]c2cc1C
Reactant: Fc1ccccn1
Agent: C(=C/c1nc2ccccc2n1-c1ccccn1)\c1ccccc1
Product: Cc1cc2nc(/C=C/c3ccccc3)n(-c3ccccn3)c2cc1C

Procedure:
The titled compound was prepared from 5,6dimethyl-2-styryl-1H-benzimidazole and 2-fluoropyridine according to the preparation of (E)-1-(2-pyridyl)-2-styryl-1H-benzimidazole (Example 1, method B). MW: 325.42; mp: 135.8-137.0° C.; 1H-NMR (CDCl3) δ: 8.77 (1H, ddd, J=4.8, 1.8, 0.7 Hz), 7.98 (1H, ddd, J=7.7, 7.7, 1.8 Hz), 7.94 (1H, d, J=16.1 Hz), 7.59 (1H, s) 7.55-7.42 (4H, m), 7.38-7.26 (3H, m), 7.23 (1H, s), 7.12 (1H, d, J=16.1 Hz), 2.39 (3H, s), 2.35 (3H, s).
Reaction SMILES: [F:1][S:2]([OH:5])(=[O:4])=[O:3].[Cl:6][C:7]1[CH:12]=[CH:11][C:10]([N:13]2[CH:18]=[CH:17][C:16](=[N:19][NH2:20])[CH:15]=[CH:14]2)=[CH:9][CH:8]=1.O.[Cl:22][C:23]1[CH:30]=[CH:29][C:26]([CH:27]=O)=[CH:25][CH:24]=1>C(O)C>[F:1][S:2]([OH:5])(=[O:4])=[O:3].[Cl:6][C:7]1[CH:8]=[CH:9][C:10]([N:13]2[CH:14]=[CH:15][C:16](=[N:19][N:20]=[CH:27][C:26]3[CH:29]=[CH:30][C:23]([Cl:22])=[CH:24][CH:25]=3)[CH:17]=[CH:18]2)=[CH:11][CH:12]=1
Reactant: NN=c1ccn(-c2ccc(Cl)cc2)cc1
Reactant: O=Cc1ccc(Cl)cc1
Agent: O=S(=O)(O)F
Solvent: CCO
Solvent: O
Product: Clc1ccc(C=NN=c2ccn(-c3ccc(Cl)cc3)cc2)cc1

Procedure:
To a solution of 2.4 g. (7.5 mmole) of 1-(4-chlorophenyl)-4(1H)-pyridinone hydrazone fluorosulfonate, prepared by the process set forth in Example 2, in 35 ml. ethanol and 30 ml. water was added a solution of 1.27 g. (9 mmole) of p-chlorobenzaldehyde in 5 ml. ethanol. After heating the reaction mixture on the steam bath for 3 minutes, the mixture was concentrated to remove most of the ethanol, cooled and the product collected by filtration. Yield 3.1 g. (94%), recrystallized from EtOH-H2O, m.p. 252°-253° C. The elemental analyses for C, H, N and Cl were within ±0.4% of the theoretical values.
Reaction SMILES: [CH3:1][N:2]1[CH:6]=[CH:5][CH:4]=[C:3]1[CH2:7][C:8]([O:10][CH3:11])=[O:9].Cl[C:13]1[CH:18]=[CH:17][C:16]([N+:19]([O-:21])=[O:20])=[CH:15][CH:14]=1.[H-].[Na+]>CN(C=O)C>[CH3:1][N:2]1[CH:6]=[CH:5][CH:4]=[C:3]1[CH:7]([C:13]1[CH:18]=[CH:17][C:16]([N+:19]([O-:21])=[O:20])=[CH:15][CH:14]=1)[C:8]([O:10][CH3:11])=[O:9]
Reactant: O=[N+]([O-])c1ccc(Cl)cc1
Reactant: COC(=O)Cc1cccn1C
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: COC(=O)C(c1ccc([N+](=O)[O-])cc1)c1cccn1C
Temperature: 25 °C
Reaction time: 1 h
Yield: 47.1 %

Procedure:
Methyl 1-methylpyrrole-2-acetate (5.0 g, 32.0 mmol) and 4-chloronitrobenzene (10.3 g, 65.0 mmol) were dissolved in DMF (30 ml) and the mixture was cooled in an ice bath under argon. Sodium hydride, 50% in mineral oil, (3.1 g, 64.0 mmol) was added in portions. After stirring for 1 h at room temperature the reaction mixture was poured into 1M HCl/ice and the product was extracted into ethyl acetate. The organic extracts were washed with water, dried over sodium sulfate, and concentrated to dryness. Purification on a Florisil® column (methylene chloride) gave methyl 2-(1-methylpyrrol-2-yl)-2-(4-nitrophenyl)acetate (4.13 g, 46%) as a solid. ##STR39##
Reaction SMILES: [NH2:1][C:2]1([CH2:19][OH:20])[C:15]2[CH:14]=[C:13]([Cl:16])[N:12]=[C:11]([F:17])[C:10]=2[O:9][C:8]2[C:3]1=[CH:4][C:5]([Br:18])=[CH:6][CH:7]=2.CC(C)([O-])C.[Li+].Br[CH2:28][C:29]#[N:30]>C1COCC1>[NH2:1][C:2]1([CH2:19][O:20][CH2:28][C:29]#[N:30])[C:15]2[CH:14]=[C:13]([Cl:16])[N:12]=[C:11]([F:17])[C:10]=2[O:9][C:8]2[C:3]1=[CH:4][C:5]([Br:18])=[CH:6][CH:7]=2
Reactant: N#CCBr
Reactant: NC1(CO)c2cc(Br)ccc2Oc2c1cc(Cl)nc2F
Agent: CC(C)(C)[O-]
Agent: [Li+]
Solvent: C1CCOC1
Product: N#CCOCC1(N)c2cc(Br)ccc2Oc2c1cc(Cl)nc2F
Reaction time: 16 h
Yield: 78 %

Procedure:
A 3-neck RBF was charged with (5-amino-7-bromo-3-chloro-1-fluoro-5H-chromeno[2,3-c]pyridin-5-yl)methanol (20.7 g, 57.6 mmol) and THF (10 mL). The flask was equipped with two addition funnels which were charged with lithium tert-butoxide solution (1.0M in THF; 98 mL, 98 mmol) and a solution of bromoacetonitrile (6.82 mL, 98 mmol) in THF (10 mL), respectively. The two solutions were added simultaneously to the stirring solution at ambient temperature over a time period of 3 hours. Upon complete addition, the addition funnels were recharged with lithium tert-butoxide solution, 1.0 M in THF (98 mL, 98 mmol) and a solution of bromoacetonitrile (6.82 mL, 98 mmol) in THF (10 mL), respectively. The two solutions were added simultaneously to the stirring solution at ambient temperature over a time period of 3 hours. The reaction was quenched with saturated aqueous ammonium chloride solution and stirred for 16 hours. The reaction was diluted with water and EtOAc. The organic layer was separated and the aqueous layer was extracted twice with EtOAc. The combined organic layers were washed with brine and dried over sodium sulfate. The solution was concentrated under reduced pressure, and the resulting black solid was triturated with ether and filtered to afford a brown precipitate. The filtrate was further concentrated and purified by chromatography (50-100% EtOAc/hexanes). The solids obtained through trituration and purification by chromatography were combined to afford 2-((5-amino-7-bromo-3-chloro-1-fluoro-5H-chromeno[2,3-c]pyridin-5-yl)methoxy)acetonitrile (17.9 g, 44.9 mmol).
Reaction SMILES: [CH:1]([C:3]1[CH:20]=[CH:19][C:6]([O:7][CH2:8][C:9]2[N:10]([CH3:18])[C:11]3[C:16]([N:17]=2)=[CH:15][CH:14]=[CH:13][N:12]=3)=[CH:5][CH:4]=1)=O.[S:21]1[CH2:25][C:24](=[O:26])[NH:23][C:22]1=[O:27].N1CCCCC1>C(O)C>[CH3:18][N:10]1[C:11]2=[N:12][CH:13]=[CH:14][CH:15]=[C:16]2[N:17]=[C:9]1[CH2:8][O:7][C:6]1[CH:19]=[CH:20][C:3]([CH:1]=[C:25]2[S:21][C:22](=[O:27])[NH:23][C:24]2=[O:26])=[CH:4][CH:5]=1
Reactant: O=C1CSC(=O)N1
Reactant: Cn1c(COc2ccc(C=O)cc2)nc2cccnc21
Solvent: CCO
Solvent: C1CCNCC1
Product: Cn1c(COc2ccc(C=C3SC(=O)NC3=O)cc2)nc2cccnc21
Yield: 79.2 %

Procedure:
A mixture of 0.35 g of 2-(4-formylphenoxymethyl)-3-methylimidazo[5,4-b]pyridine (prepared as described in Preparation 112), 0.31 g of 2,4-thiazolidinedione, 0.26 ml of piperidine and 10 ml of ethanol was heated under reflux for 4 hours. At the end of this time, the solvent was removed by distillation under reduced pressure and the residue was crystallized by trituration with water. The crystals were collected by filtration and washed with water and then with ethyl acetate, to give 0.38 g of the title compound, melting at 279°-281° C.
Reaction SMILES: Br[C:2]1[C:7](=[O:8])[N:6]([CH2:9][C:10]([O:12]CC)=[O:11])[N:5]=[CH:4][C:3]=1[NH:15][C@@H:16]1[CH2:21][C@@H:20]2[CH2:22][C@@H:18]([C:19]2([CH3:24])[CH3:23])[C@H:17]1[CH3:25].[CH3:26][S-:27].[Na+].O1CCOCC1.[OH-].[Na+]>C1(C)C=CC=CC=1>[CH3:26][S:27][C:2]1[C:7](=[O:8])[N:6]([CH2:9][C:10]([OH:12])=[O:11])[N:5]=[CH:4][C:3]=1[NH:15][C@@H:16]1[CH2:21][C@@H:20]2[CH2:22][C@@H:18]([C:19]2([CH3:24])[CH3:23])[C@H:17]1[CH3:25]
Reactant: C[S-]
Reactant: CCOC(=O)Cn1ncc(N[C@@H]2C[C@@H]3C[C@H]([C@H]2C)C3(C)C)c(Br)c1=O
Agent: [Na+]
Agent: [OH-]
Solvent: Cc1ccccc1
Solvent: C1COCCO1
Product: CSc1c(N[C@@H]2C[C@@H]3C[C@H]([C@H]2C)C3(C)C)cnn(CC(=O)O)c1=O
Yield: 90.2 %

Procedure:
Ethyl 2-{5-bromo-6-oxo-4-[(1R,2R,3R,5S)-2,6,6-trimethylbicyclo[3.1.1]hept-3-ylamino]pyridazin-1(6H)-yl}acetate (220 mg, 0.533 mmol) and sodium thiomethoxide (112 mg, 1.60 mmol) in toluene (22 mL) were stirred at 80° C. for 3 hours. After cooling, the reaction solution was stirred with 1,4-dioxane (6 mL) and 1 M aqueous sodium hydroxide (1.59 mL) at room temperature for 4 hours. After completion of the reaction, the reaction solution was mixed with toluene and extracted with 1 M aqueous sodium hydroxide twice. The resulting aqueous layer was acidified to pH 1 with 1 M hydrochloric acid and extracted with ethyl acetate twice, and the extract was dried over anhydrous sodium sulfate and evaporated under reduced pressure to give the desired product (169 mg, 90% yield).
Reaction SMILES: CN1CCOCC1.C(OC(Cl)=O)C(C)C.[CH3:16][CH2:17][CH2:18][CH2:19][C:20]1[CH:21]=[CH:22][C:23]([C:26]([OH:28])=O)=[N:24][CH:25]=1.Cl.[CH3:30][O:31][NH:32][CH3:33]>C(Cl)Cl>[CH3:30][O:31][N:32]([CH3:33])[C:26]([C:23]1[CH:22]=[CH:21][C:20]([CH2:19][CH2:18][CH2:17][CH3:16])=[CH:25][N:24]=1)=[O:28]
Reactant: CCCCc1ccc(C(=O)O)nc1
Reactant: CNOC
Agent: CC(C)COC(=O)Cl
Agent: Cl
Solvent: CN1CCOCC1
Solvent: ClCCl
Product: CCCCc1ccc(C(=O)N(C)OC)nc1
Reaction time: 19 h
Yield: 129.7 %

Procedure:
Add N-methylmorpholine (1.22 mL, 11.1 mmol) and isobutylchloroformate (1.44 mL, 11.1 mmol) to a solution of fusaric acid (2.0 g, 11.1 mmol) in methylene chloride at 0° C. After 15 minutes add O,N-dimethylhydroxylamine hydrochloride (1.1 g, 11.1 mmol) and N-methylmorpholine (1.22 mL, 11.1 mmol). Stir the reaction for at 0° C. 15 minutes and then room temperature for 19 hours. Dilute the reaction with methylene chloride and wash with water (1×50 mL), 10% aqueous citric acid (1×50 mL), brine (1×50 mL), saturated aqueous sodium bicarbonate (1×50 mL), and brine (1×50 mL). Dry the organic solution with sodium sulfate, filter, and concentrate in vacuo to provide the title compound 3.2 g (100%) as a clear yellow oil.
Reaction SMILES: [CH3:1][N:2]1[C:6]([C:7]2[CH:8]=[C:9]([NH2:21])[CH:10]=[CH:11][C:12]=2[O:13][CH2:14][CH2:15][N:16]2[CH2:20][CH2:19][CH2:18][CH2:17]2)=[CH:5][CH:4]=[N:3]1.[F:22][C:23]([F:34])([F:33])[C:24]1[CH:32]=[CH:31][C:27]([C:28](O)=[O:29])=[CH:26][CH:25]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)CC)C>CN(C=O)C>[CH3:1][N:2]1[C:6]([C:7]2[CH:8]=[C:9]([NH:21][C:28](=[O:29])[C:27]3[CH:31]=[CH:32][C:24]([C:23]([F:22])([F:33])[F:34])=[CH:25][CH:26]=3)[CH:10]=[CH:11][C:12]=2[O:13][CH2:14][CH2:15][N:16]2[CH2:20][CH2:19][CH2:18][CH2:17]2)=[CH:5][CH:4]=[N:3]1
Reactant: Cn1nccc1-c1cc(N)ccc1OCCN1CCCC1
Reactant: O=C(O)c1ccc(C(F)(F)F)cc1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: Cn1nccc1-c1cc(NC(=O)c2ccc(C(F)(F)F)cc2)ccc1OCCN1CCCC1
Temperature: 100 °C
Yield: 70.9 %

Procedure:
A mixture of 3-(2-Methyl-2H-pyrazol-3-yl)-4-(2-pyrrolidin-1-yl-ethoxy)-phenylamine (57 mg, 0.2 mmol), 4-trifluoromethyl-benzoic acid (42 mg, 0.22 mmol), HATU (91 mg, 0.24 mmol) and triethylamine (0.3 mL) in DMF (2 mL) was heated in microwave at 100° C. for 15 min. The crude was purified by HPLC to give the title compound (65 mg, 71%) as a brown solid as TFA salt. 1H NMR (DMSO-d6, 400 MHz) δ 1.73-1.76 (m, 2H), 1.87-1.92 (m, 2H), 2.85-2.90 (m, 2H), 3.29-3.32 (m, 2H), 3.53-3.57 (m, 2H), 3.69 (s, 3H), 4.32 (t, J=4.80 Hz, 2H), 6.32 (d, J=2.02 Hz, 1H), 7.26 (d, J=8.59 Hz, 1H), 7.50 (d, J=1.78 Hz, 1H), 7.75 (d, J=2.53 Hz, 1H), 7.88-7.94 (m, 3H), 8.15 (d, J=8.84 Hz, 2H), 9.81 (s, 1H), 10.5 (s, 1H). Exact mass calculated for C24H25F3N4O2 458.2. found 459.4 (MH+).
Reaction SMILES: [Br:1][C:2]1[C:3](Cl)=[N:4][CH:5]=[C:6]([CH:21]=1)[C:7]([NH:9][C:10]1[CH:11]=[N:12][C:13]([S:16][C:17]([F:20])([F:19])[F:18])=[CH:14][CH:15]=1)=[O:8].[NH:23]1[CH2:27][CH2:26][C@@H:25]([OH:28])[CH2:24]1>>[Br:1][C:2]1[C:3]([N:23]2[CH2:27][CH2:26][C@@H:25]([OH:28])[CH2:24]2)=[N:4][CH:5]=[C:6]([CH:21]=1)[C:7]([NH:9][C:10]1[CH:11]=[N:12][C:13]([S:16][C:17]([F:20])([F:19])[F:18])=[CH:14][CH:15]=1)=[O:8]
Reactant: O[C@@H]1CCNC1
Reactant: O=C(Nc1ccc(SC(F)(F)F)nc1)c1cnc(Cl)c(Br)c1
Product: O=C(Nc1ccc(SC(F)(F)F)nc1)c1cnc(N2CC[C@@H](O)C2)c(Br)c1

Procedure:
The title compound was prepared in an analogous fashion to that described in Stage 171.1 using 5-bromo-6-chloro-N-(6-((trifluoromethyl)thio)pyridin-3-yl)nicotinamide (Stage 279.2) and (R)-pyrrolidin-3-ol to afford an off-white powder. HPLC (Condition 4) tR=5.53 min, UPLC-MS (Condition 3) tR=1.01 min, m/z=463.1 [M+H]+.