Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C([N-]C(C)C)(C)C.[Li+].[O:9]=[C:10]1[NH:19][CH:18]([C:20]2[CH:27]=[CH:26][C:23]([C:24]#[N:25])=[CH:22][CH:21]=2)[C:17]2[C:16](=[O:28])[CH2:15][CH2:14][CH2:13][C:12]=2[N:11]1[C:29]1[CH:34]=[CH:33][CH:32]=[C:31]([C:35]([F:38])([F:37])[F:36])[CH:30]=1.[CH2:39](I)[CH2:40][CH2:41][CH3:42]>CN(C)C=O>[CH2:39]([N:19]1[CH:18]([C:20]2[CH:21]=[CH:22][C:23]([C:24]#[N:25])=[CH:26][CH:27]=2)[C:17]2[C:16](=[O:28])[CH2:15][CH2:14][CH2:13][C:12]=2[N:11]([C:29]2[CH:34]=[CH:33][CH:32]=[C:31]([C:35]([F:38])([F:36])[F:37])[CH:30]=2)[C:10]1=[O:9])[CH2:40][CH2:41][CH3:42]
Reactant: N#Cc1ccc(C2NC(=O)N(c3cccc(C(F)(F)F)c3)C3=C2C(=O)CCC3)cc1
Reactant: CCCCI
Agent: CC(C)[N-]C(C)C
Agent: [Li+]
Solvent: CN(C)C=O
Product: CCCCN1C(=O)N(c2cccc(C(F)(F)F)c2)C2=C(C(=O)CCC2)C1c1ccc(C#N)cc1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
Lithium diisopropylamide (2.0 M in tetrahydrofuran, 135 μL, 0.27 mmol) is added at 0° C. to a solution of 4-(2,5-dioxo-1-(3-(trifluoromethyl)phenyl)-1,2,3,4,5,6,7,8-octahydroquinazolin-4-yl)-benzonitrile (example 1, 100 mg, 0.243 mmol) in N,N-dimethylformamide (5 mL). n-Butyl iodide (30 μL, 0.264 mmol) is added, and the mixture is warmed to room temperature and stirred for 2 h. Another portion of n-Butyl iodide (15 μL, 0.132 mmol) is added and the mixture is stirred over night and purified by reversed phase HPLC (Waters Xbridge™-C18, gradient of acetonitrile in water, 0.1% TFA). Yield: 28 mg; ESI mass spectrum [M+H]+=468; Retention time HPLC: 1.47 min (V001—006).
Reaction SMILES: [NH2:1][CH:2]([C:9]1[C:14]([O:15][CH3:16])=[CH:13][CH:12]=[CH:11][C:10]=1[O:17][CH3:18])[CH2:3][CH2:4][C:5]([O:7]C)=O.[C:19]1([C:25]2[CH:26]=[C:27]([CH:30]=[CH:31][N:32]=2)[CH:28]=O)[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1>>[CH3:18][O:17][C:10]1[CH:11]=[CH:12][CH:13]=[C:14]([O:15][CH3:16])[C:9]=1[CH:2]1[N:1]([CH2:28][C:27]2[CH:30]=[CH:31][N:32]=[C:25]([C:19]3[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=3)[CH:26]=2)[C:5](=[O:7])[CH2:4][CH2:3]1
Reactant: O=Cc1ccnc(-c2ccccc2)c1
Reactant: COC(=O)CCC(N)c1c(OC)cccc1OC
Product: COc1cccc(OC)c1C1CCC(=O)N1Cc1ccnc(-c2ccccc2)c1

Procedure:
Prepared according to the described general procedure 2 (GP2) by reaction of methyl 4-amino-4-(2,6-dimethoxyphenyl)butanoate with 2-phenylisonicotinaldehyde. Subsequent purification by preparative HPLC afforded the target compound. LC-MS (conditions A): tR=0.61 min.; [M+H]+: 389.16 g/mol.
Reaction SMILES: [CH2:1]([C:3]1[C:8]2[C:9]([C:15]3[CH:20]=[CH:19][C:18]([CH2:21][CH3:22])=[CH:17][C:16]=3[CH2:23][CH3:24])=[N:10][CH2:11][C:12](=S)[NH:13][C:7]=2[CH:6]=[C:5]([CH2:25][CH3:26])[CH:4]=1)[CH3:2].[CH2:27]([O:29][CH2:30][C:31]([NH:33][NH2:34])=O)[CH3:28]>C(O)CCC>[CH2:1]([C:3]1[C:8]2[C:9]([C:15]3[CH:20]=[CH:19][C:18]([CH2:21][CH3:22])=[CH:17][C:16]=3[CH2:23][CH3:24])=[N:10][CH2:11][C:12]3[N:13]([C:31]([CH2:30][O:29][CH2:27][CH3:28])=[N:33][N:34]=3)[C:7]=2[CH:6]=[C:5]([CH2:25][CH3:26])[CH:4]=1)[CH3:2]
Reactant: CCOCC(=O)NN
Reactant: CCc1ccc(C2=NCC(=S)Nc3cc(CC)cc(CC)c32)c(CC)c1
Solvent: CCCCO
Product: CCOCc1nnc2n1-c1cc(CC)cc(CC)c1C(c1ccc(CC)cc1CC)=NC2

Procedure:
In the manner given in Example 1, a solution of 1,3-dihydro-6,8-diethyl-5-(2,4-diethylphenyl)-2H-1,4-benzodiazepine-2-thione in n-butyl alcohol was heated to reflux with ethoxyacetic acid hydrazide to give 7,9-diethyl-1-(ethoxymethyl)-6-(2,4-diethylphenyl)-4H-s-triazolo[4,3-a][1,4]benzodiazepine.
Reaction SMILES: [CH2:1]([O:3][C:4]1[N:8]=[C:7]([CH:9]2[CH2:14][CH:13]([C:15]3[CH:20]=[CH:19][C:18]([C:21]([F:24])([F:23])[F:22])=[CH:17][CH:16]=3)[CH2:12][N:11]([C:25]([N:27]3[CH2:32][CH2:31][S:30][CH2:29][CH2:28]3)=[O:26])[CH2:10]2)[O:6][N:5]=1)[CH3:2].ClC1C=CC=C(C(OO)=[O:41])C=1>>[CH2:1]([O:3][C:4]1[N:8]=[C:7]([CH:9]2[CH2:14][CH:13]([C:15]3[CH:20]=[CH:19][C:18]([C:21]([F:24])([F:22])[F:23])=[CH:17][CH:16]=3)[CH2:12][N:11]([C:25]([N:27]3[CH2:28][CH2:29][S:30](=[O:41])[CH2:31][CH2:32]3)=[O:26])[CH2:10]2)[O:6][N:5]=1)[CH3:2]
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: CCOc1noc(C2CC(c3ccc(C(F)(F)F)cc3)CN(C(=O)N3CCSCC3)C2)n1
Product: CCOc1noc(C2CC(c3ccc(C(F)(F)F)cc3)CN(C(=O)N3CCS(=O)CC3)C2)n1

Procedure:
65.0 mg (0.138 mmol) of the compound from Example 44 were reacted according to General Method 2 with 42.9 mg (0.124 mmol) of meta-chloroperbenzoic acid. Yield: 50.8 mg (72% of theory)
Reaction SMILES: [F:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=O)=[CH:4][CH:3]=1.[CH:10]([C:13]1[CH:19]=[CH:18][C:16]([NH2:17])=[CH:15][CH:14]=1)([CH3:12])[CH3:11]>>[F:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6][NH:17][C:16]2[CH:18]=[CH:19][C:13]([CH:10]([CH3:12])[CH3:11])=[CH:14][CH:15]=2)=[CH:4][CH:3]=1
Reactant: CC(C)c1ccc(N)cc1
Reactant: O=Cc1ccc(F)cc1
Product: CC(C)c1ccc(NCc2ccc(F)cc2)cc1
Yield: 93.5 %

Procedure:
By the reaction and treatment in the same manner as in Preparation Example 1 using 4-fluorobenzaldehyde (1.2 g) and 4-isopropylaniline (1.4 g) as starting materials, [(4-fluorophenyl)methyl](4-isopropylphenyl)amine (2.2 g) was obtained.
Reaction SMILES: [CH:1](=O)[CH:2]=[CH:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[C:11]([O:14]C(=O)C)(=[O:13])[CH3:12].C([O-])(=O)C.[K+].C([O-])(=O)C.[Na+]>C(O)(=O)C.C(OC(=O)C)(=O)C>[C:4]1([CH:3]=[CH:2][CH:1]=[CH:12][C:11]([OH:14])=[O:13])[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1
Reactant: O=CC=Cc1ccccc1
Reactant: CC(=O)OC(C)=O
Agent: CC(=O)[O-]
Agent: [K+]
Agent: [Na+]
Solvent: CC(=O)O
Product: O=C(O)C=CC=Cc1ccccc1
Temperature: 25 °C

Procedure:
Into a one liter round bottom flask equipped with a stirrer, condenser, thermometer and heating mantle, 198 grams (1.5 mols) of cinnamaldehyde, 230 grams (2.25 mols) of acetic anhydride, 25 grams (0.25 mols) potassium acetate, and 49 grams (0.60 mols) of sodium acetate were charged. The contents were brought up to 145° C. and maintained at 145°-150° C. for ninety minutes. Approximately 100 ml of acetic acid/acetic anhydride were stripped off leaving a red brown slurry. The resultant slurry was cooled to room temperature and the solids filtered off and rinsed with acetone. The dry filtercake (185 grams) was dissolved in two liters of 5% potassium carbonate solution at 65° C. Addition of 100 ml of 37.8% HCl to this solution yielded 5-phenyl-2,4-pentadienoic acid as a light yellow precipitate. The precipitate was filtered and dried. The dried acid was esterified with ethanol in the presence of sulfuric acid. The resultant ethyl 5-phenyl-2,4-pentadienoate was purified by vacuum distillation. The pure product was found to have a max of 309 nm, and an extinction coefficient of 35,500.
Reaction SMILES: C(N(CC)CC)C.[NH2:8][C:9]1[S:10][CH:11]=[C:12]([C:17]([CH3:20])([CH3:19])[CH3:18])[C:13]=1[C:14]([NH2:16])=[O:15].[C:21](Cl)(=[O:23])[CH3:22]>C1(C)C=CC=CC=1>[C:21]([NH:8][C:9]1[S:10][CH:11]=[C:12]([C:17]([CH3:20])([CH3:19])[CH3:18])[C:13]=1[C:14]([NH2:16])=[O:15])(=[O:23])[CH3:22]
Reactant: CC(C)(C)c1csc(N)c1C(N)=O
Reactant: CC(=O)Cl
Solvent: CCN(CC)CC
Solvent: Cc1ccccc1
Product: CC(=O)Nc1scc(C(C)(C)C)c1C(N)=O
Yield: 80.3 %

Procedure:
21.2 g (0.21 mole) of triethylamine were first added to a suspension of 39.6 g (0.2 mole) of 2-amino-3-aminocarbonyl-4-tert.-butyl-thiophene in 300 ml of toluene, and 16.5 g (0.21 mole) of acetyl chloride were then added dropwise. After the exothermic reaction had ended, the mixture was worked up by filtering off the solid product and washing it with water. 38.6 g of 2-acetylamino-3-aminocarbonyl-4-tert.-butyl-thiophene of melting point 251° C. were obtained in this manner.
Reaction SMILES: [CH3:1][O:2][C:3]1[C:4]([CH3:25])=[C:5]([C:16]([O:23][CH3:24])=[C:17]([O:21][CH3:22])[C:18]=1[O:19][CH3:20])[CH2:6][C:7]1[C:12]([CH:13]=[O:14])=[C:11]([OH:15])[CH:10]=[CH:9][CH:8]=1.C(=O)([O-])[O-].[Na+].[Na+].[CH2:32](Br)[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1>CC(C)=O>[CH3:1][O:2][C:3]1[C:4]([CH3:25])=[C:5]([C:16]([O:23][CH3:24])=[C:17]([O:21][CH3:22])[C:18]=1[O:19][CH3:20])[CH2:6][C:7]1[C:12]([CH:13]=[O:14])=[C:11]([O:15][CH2:32][C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[CH:10]=[CH:9][CH:8]=1
Reactant: COc1c(C)c(Cc2cccc(O)c2C=O)c(OC)c(OC)c1OC
Reactant: BrCc1ccccc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CC(C)=O
Product: COc1c(C)c(Cc2cccc(OCc3ccccc3)c2C=O)c(OC)c(OC)c1OC
Yield: 94.4 %

Procedure:
6-(3,4,5,6-Tetramethoxy-2-methylbenzyl)-2-hydroxybenzaldehyde (187 mg, 0.54 mmol) was dissolved in acetone (20 ml) and after adding thereto anhydrous sodium carbonate (149 mg, 1.08 mmol) and benzyl bromide (120 mg, 0.70 mmol), the solution was stirred at room temperature for 16 hours. The reaction solution was filtered, the filtrate was concentrated and the obtained residue was purified by silica gel column chromatography (hexand:ethyl acetate=3:1) to obtain the titled compound (221 mg, 0.51 mmol, 94%).
Reaction SMILES: [CH3:1][C:2]1[N:3]=[C:4]2[CH:12]=[CH:11][CH:10]=[C:9]3[N:5]2[C:6]=1[C:7]([S:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][N:19]1C(=O)C2=CC=CC=C2C1=O)=[N:8]3.O>C(O)C>[CH3:1][C:2]1[N:3]=[C:4]2[CH:12]=[CH:11][CH:10]=[C:9]3[N:5]2[C:6]=1[C:7]([S:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][NH2:19])=[N:8]3
Reactant: Cc1nc2cccc3nc(SCCCCCN4C(=O)c5ccccc5C4=O)c1n23
Solvent: O
Solvent: CCO
Product: Cc1nc2cccc3nc(SCCCCCN)c1n23
Yield: 70.4 %

Procedure:
To a suspension of 2.50 g (6.2 mmol) of 3-methyl-2-[5-(phthalimido)pentan-1-ylthio]-1,4,7b-triazacyclopent[cd]indene in 50 ml of ethanol was added 928 mg (18.5 mmol) of hydrazinemonohydrate. The mixture was heated for two hours under reflux. After cooling, the resulting precipitates were collected by filtration and washed with ethanol. The filtrate and washing were combined and concentrated to give the residue. Water was added, extracted with methylene chloride, dried over anhydrous magnesium sulfate. The solvent was distilled off to afford 1.197 g of the desired compound (70.6%, a greenish brown solid).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C@@H:9]([NH:27][C:28]([C@@H:30]2[CH2:39][C:38]3[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=3)[CH2:32][N:31]2C(OC(C)(C)C)=O)=[O:29])[C:10]([N:12]2[CH2:17][CH2:16][N:15]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=3[N+:24]([O-:26])=[O:25])[CH2:14][CH2:13]2)=[O:11])=[CH:4][CH:3]=1.Cl>CCOC(C)=O>[ClH:1].[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C@@H:9]([NH:27][C:28]([C@@H:30]2[CH2:39][C:38]3[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=3)[CH2:32][NH:31]2)=[O:29])[C:10]([N:12]2[CH2:17][CH2:16][N:15]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=3[N+:24]([O-:26])=[O:25])[CH2:14][CH2:13]2)=[O:11])=[CH:4][CH:3]=1
Reactant: CC(C)(C)OC(=O)N1Cc2ccccc2C[C@H]1C(=O)N[C@H](Cc1ccc(Cl)cc1)C(=O)N1CCN(c2ccccc2[N+](=O)[O-])CC1
Agent: Cl
Solvent: CCOC(C)=O
Product: O=C(N[C@H](Cc1ccc(Cl)cc1)C(=O)N1CCN(c2ccccc2[N+](=O)[O-])CC1)[C@@H]1Cc2ccccc2CN1
Yield: 123.6 %

Procedure:
The titled compound was prepared from tert-butyl 3-(N-{(1R)-1-[(4-chlorophenyl)methyl]-2-[4-(2-nitrophenyl)piperazinyl]-2-oxoethyl}carbamoyl)(3S)-1,2,3,4-tetrahydroisoquinoline-2-carboxylate (120 mg, 0.18 mmol, Preparation VIII) by treatment with 5 mL of a satd soln of HCl in EtOAc. This was purified by preparative HPLC (TFA buffer) to give the title compound as white solid (65 mg). MS (ESI, pos. ion) m/z: 548 (M+H). Calc'd for C29H30ClN5O4: 547.20.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[NH:18][C:17]([O:19][C@H:20]3[CH2:25][O:24][C@H:23]([CH2:26][OH:27])[C@@H:22]([OH:28])[CH2:21]3)=[N:16][C:5]2=[N:6][C:7]=1[C:8]1[CH:13]=[CH:12][C:11]([C:14]#[CH:15])=[CH:10][CH:9]=1.Br[C:30]1[N:31]=[N:32][N:33]([CH3:35])[N:34]=1.C(N(C(C)C)CC)(C)C>O1CCOCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Cu]I>[Cl:1][C:2]1[CH:3]=[C:4]2[NH:18][C:17]([O:19][C@H:20]3[CH2:25][O:24][C@H:23]([CH2:26][OH:27])[C@@H:22]([OH:28])[CH2:21]3)=[N:16][C:5]2=[N:6][C:7]=1[C:8]1[CH:13]=[CH:12][C:11]([C:14]#[C:15][C:30]2[N:31]=[N:32][N:33]([CH3:35])[N:34]=2)=[CH:10][CH:9]=1
Reactant: C#Cc1ccc(-c2nc3nc(O[C@H]4CO[C@H](CO)[C@@H](O)C4)[nH]c3cc2Cl)cc1
Reactant: Cn1nnc(Br)n1
Agent: [Cu]I
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: C1COCCO1
Solvent: CCN(C(C)C)C(C)C
Product: Cn1nnc(C#Cc2ccc(-c3nc4nc(O[C@H]5CO[C@H](CO)[C@@H](O)C5)[nH]c4cc3Cl)cc2)n1

Procedure:
A mixture of (2R,3 S,5R)-5-((6-chloro-5-(4-ethynylphenyl)-1H-imidazo[4,5-b]pyridin-2-yl)-oxy)-2-(hydroxymethyl)tetrahydro-2H-pyran-3-ol (60 mg, 0.150 mmol), Pd(Ph3P)4(17.34 mg, 0.015 mmol), copper(I) iodide (2.85 mg, 0.015 mmol), 5-bromo-2-methyl-2H-tetrazole (48.9 mg, 0.300 mmol) and diisopropylethylamine (0.210 ml, 0.450 mmol) in dioxane (2 ml) was charged in a reaction tube. The tube was sealed and N2 was bubbled through for 5 min. The reaction was heated at 80 C for 18 h, and then concentrated. The resulting residue was purified on reverse phase HPLC eluting with 10-70% CH3CN/H2O with TFA as an additive to give the title compound. LC-MS: m/e: 481.97.53 (M+H)+ (Rt 1.70/4 min); 1H NMR δ (ppm) (CD3OD): 7.84-7.75 (m, 4H), 5.11 (septet, 1H, J=5 Hz)), 4.38-4.31 (m, 1H), 4.24 (s, 3H), 3.89 (dd, 1H, J=12, 2 Hz), 3.69-3.59 (m, 2H), 3.37 (t, 1H, J=11 Hz), 3.20-3.15 (m, 1H), 2.79-2.72 (m, 1H), 1.70 (dd, 1H, J=23, 12 Hz),
Reaction SMILES: [NH:1]1[CH:5]=[CH:4][N:3]=[N:2]1.C(=O)([O-])[O-].[K+].[K+].F[C:13]1[CH:20]=[CH:19][C:16]([CH:17]=[O:18])=[CH:15][CH:14]=1>N1C=CC=CC=1>[N:1]1([C:13]2[CH:20]=[CH:19][C:16]([CH:17]=[O:18])=[CH:15][CH:14]=2)[CH:5]=[CH:4][N:3]=[N:2]1
Reactant: O=Cc1ccc(F)cc1
Reactant: c1c[nH]nn1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: c1ccncc1
Product: O=Cc1ccc(-n2ccnn2)cc1

Procedure:
A mixture of 1,2,3-triazole (3.4 ml, 58.7 mmol), potassium carbonate (9.03 g, 65.4 mmol), and 4-fluorobenzaldehyde (6.3 ml, 58.7 mmol) in pyridine (30 ml) is heated under nitrogen atmosphere at reflux overnight. After pyridine is distilled, the mixture is diluted with methylene chloride, filtered and washed with chloroform. The combined filtrate is washed with water, dried over magnesium sulfate, and concentrated in vacuo. The crude material is purified by column chromatography on silica with hexane/ethyl acetate (5:1) to give 4-(1,2,3-triazol-1-yl)-benzaldehyde and with hexane/ethyl acetate (1:2) to give 4-(1,2,3-triazol-1-yl)-benzaldehyde.
Reaction SMILES: [C:1](Cl)(Cl)=[S:2].[F:5][C:6]1[CH:12]=[C:11]([I:13])[CH:10]=[CH:9][C:7]=1[NH2:8]>C(Cl)(Cl)Cl.O>[F:5][C:6]1[CH:12]=[C:11]([I:13])[CH:10]=[CH:9][C:7]=1[N:8]=[C:1]=[S:2]
Reactant: S=C(Cl)Cl
Reactant: Nc1ccc(I)cc1F
Solvent: ClC(Cl)Cl
Solvent: O
Product: Fc1cc(I)ccc1N=C=S
Temperature: 25 °C
Reaction time: 16 h
Yield: 100.2 %

Procedure:
Thiophosgene (3.55 mL, 46.4 mmol) was added to a rapidly-stirred mixture of 2-fluoro-4-iodoaniline (10.0 g, 42.2 mmol) in CHCl3 (200 mL) and water (100 mL). The mixture was stirred at r.t. for 16 h. The organic phase was dried (Na2SO4) and concentrated in vacuo to give the title compound as an off-white crystalline solid (11.8 g, quant.). δH (DMSO-d6) 7.87 (1H, dd, J 1.8, 9.5 Hz), 7.63 (1H, ddd, J 1.0, 1.8, 8.4 Hz), 7.25 (1H, dd, J 8.2, 8.4 Hz).
Reaction SMILES: [Br:1][C:2]1[C:6]([Br:7])=[C:5]([Br:8])[NH:4][N:3]=1.C(=O)([O-])[O-].[K+].[K+].[C:15]([O:18][CH2:19][CH2:20]Br)(=[O:17])[CH3:16].C(OC(=O)C)(=O)C>CC(C)=O>[C:15]([O:18][CH2:19][CH2:20][N:3]1[C:2]([Br:1])=[C:6]([Br:7])[C:5]([Br:8])=[N:4]1)(=[O:17])[CH3:16]
Reactant: Brc1n[nH]c(Br)c1Br
Reactant: CC(=O)OCCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(=O)OC(C)=O
Solvent: CC(C)=O
Product: CC(=O)OCCn1nc(Br)c(Br)c1Br
Temperature: 0 °C
Reaction time: 0.17 h

Procedure:
A quantity (3.04 g., 0.01 mole) of 3,4,5-tribromopyrazole was dissolved in 70 ml. acetone and 2.76 g. (0.02 mole) solid anhydrous potassium carbonate was added. The mixture was heated at the reflux temperature with stirring for 10 minutes and after cooling, 1.85 g. (0.011 mole) of 2-bromoethyl acetate was added. This reaction mixture was heated at the reflux temperature for 12 hrs. cooled, filtered, and the acetone removed under reduced pressure. The resultant oil consisted of a mixture of the desired acetate and the corresponding alcohol. The mixture was dissolved in pyridine (15 ml.) and treated with acetic anhydride (3.06 g., 0.03 mole) at 0° C. This reaction mixture was kept at about 25° C. overnight, and then poured into 200 ml. of ice water. The precipitate that formed was collected on a filter, and washed with water. After drying and recrystallizing from hexane there was obtained 3,4,5-tribromopyrazole-1-ethanol acetate (ester) having a melting point at 64° to 67° C.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:19]=[CH:18][C:6]([O:7][C:8]2[CH:9]=[N+:10]([O-])[CH:11]=[CH:12][C:13]=2[N+:14]([O-])=O)=[CH:5][CH:4]=1.[H][H]>O=[Pt]=O.C(O)C>[CH3:1][O:2][C:3]1[CH:19]=[CH:18][C:6]([O:7][C:8]2[CH:9]=[N:10][CH:11]=[CH:12][C:13]=2[NH2:14])=[CH:5][CH:4]=1
Reactant: COc1ccc(Oc2c[n+]([O-])ccc2[N+](=O)[O-])cc1
Reactant: [H][H]
Agent: O=[Pt]=O
Solvent: CCO
Product: COc1ccc(Oc2cnccc2N)cc1

Procedure:
To 250 ml ethanol in a 500 ml Parr hydrogenation bottle, were added 3-(4-methoxyphenoxy)-4-nitropyridine-1-oxide (7.9 g) and 0.4 g PtO2. After shaking for two hours at fifty psi of hydrogen, the mixture was filtered and concentrated to 5.8 g of oil.
Reaction SMILES: [Br:1][C:2]1[C:3]([O:11][CH2:12][CH3:13])=[CH:4][C:5](F)=[C:6]([CH:9]=1)[C:7]#[N:8].[CH3:14][NH:15][CH3:16]>O1CCOCC1>[Br:1][C:2]1[C:3]([O:11][CH2:12][CH3:13])=[CH:4][C:5]([N:15]([CH3:16])[CH3:14])=[C:6]([CH:9]=1)[C:7]#[N:8]
Reactant: CNC
Reactant: CCOc1cc(F)c(C#N)cc1Br
Solvent: C1COCCO1
Product: CCOc1cc(N(C)C)c(C#N)cc1Br
Temperature: 80 °C
Reaction time: 8 h
Yield: 88.4 %

Procedure:
To a solution of 5-bromo-4-ethoxy-2-fluoro-benzonitrile (2 g, 8.2 mmol) in 16.5 mL of dioxane was added dimethylamine (16.5 mL, 33 mmol, 2.0 M in tetrahydrofuran). The reaction was stirred at 80° C. overnight. The reaction mixture was concentrated in vacuo. Purification of the crude residue by flash column chromatography (silica gel, eluting with a gradient of ethyl acetate in hexanes) gave 5-bromo-2-dimethylamino-4-ethoxy-benzonitrile (1.95 g, 88%). LC-MS: 269.2 [(M+H)+].
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[S:9][CH:10]=[CH:11][N:12]=1.[CH3:13][C:14]1[CH:19]=[CH:18][C:17]([Sn](C)(C)C)=[CH:16][CH:15]=1.O>CN(C)C=O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH3:13][C:14]1[CH:19]=[CH:18][C:17]([C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=2[C:8]2[S:9][CH:10]=[CH:11][N:12]=2)=[CH:16][CH:15]=1
Reactant: Cc1ccc([Sn](C)(C)C)cc1
Reactant: Brc1ccccc1-c1nccs1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Solvent: O
Solvent: CN(C)C=O
Product: Cc1ccc(-c2ccccc2-c2nccs2)cc1
Temperature: 150 °C
Yield: 30.8 %

Procedure:
A solution of 1.18 g (4.92 mmol) of 1-bromo-2-(thiazol-2-yl)benzene and 1.67 g (6.55 mmol) of 4-metylphenyltrimethylstannane in 20 mL of dimethylformamide was treated with 621 mg of bis(triphenylphosphine)palladium(II) chloride. The reaction mixture was heated at 150° C. for 6 hours, cooled and poured into 300 mL of water. The resultant mixture was extracted with ether (3×100 mL). The combined ether extracts were washed with water (4×), dried over magnesium sulfate and evaporated under vacuum. The residue was purified by chromatography on silica gel, eluting with hexane/ether (100:10) to give 381 mg of the product. EI-MS: calculated for C16H13NS 251; found 250. 1H NMR (200 MHz, CDCl3): 2.36 (s, 3H), 7.14 (s, 4H), 7.24 (d, 1H), 7.40 (m, 1H), 7.42 (m, 2H), 7.73 (d, 1H), 8.20 (dt, 1H).
Reaction SMILES: Br[C:2]1[C:3]2[N:4]([CH:8]=[C:9]([CH2:11][CH2:12][C:13]#[C:14][C:15]3[CH:20]=[CH:19][CH:18]=[C:17]([CH2:21][F:22])[N:16]=3)[N:10]=2)[CH:5]=[CH:6][CH:7]=1.[C:23]1(B(O)O)[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>COCCOC.CCOC(C)=O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:22][CH2:21][C:17]1[N:16]=[C:15]([C:14]#[C:13][CH2:12][CH2:11][C:9]2[N:10]=[C:3]3[C:2]([C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=4)=[CH:7][CH:6]=[CH:5][N:4]3[CH:8]=2)[CH:20]=[CH:19][CH:18]=1
Reactant: OB(O)c1ccccc1
Reactant: FCc1cccc(C#CCCc2cn3cccc(Br)c3n2)n1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=P([O-])([O-])[O-]
Agent: [K+]
Solvent: COCCOC
Solvent: CCOC(C)=O
Product: FCc1cccc(C#CCCc2cn3cccc(-c4ccccc4)c3n2)n1
Temperature: 25 °C
Reaction time: 0.08 h
Yield: 45.9 %

Procedure:
To a solution of 8-bromo-2-(4-(6-(fluoromethyl)pyridin-2-yl)but-3-ynyl)-imidazo[1,2-a]pyridine (compound 171(C), 301 mg, 0.84 mmol) and phenylboronic acid (50 mg, 1.3 mmol) in degazed DME (4.2 mL) was added 1.32 mL of a solution of K3PO4 2M (degazed before use). After stirring at room temperature for 5 min under N2, Pd(PPh3)4 (190 mg, 0.17 mmol) was added in one portion. The resulting mixture was heated at 80° C. for 4 h. The Mixture was cooled down to room temperature and diluted in AcOEt. The organic layer was washed twice with saturated NaCl, dried over magnesium sulfate, filtered and concentrated. The crude product was purified over silicagel chromatography (prepacked 25 g silicagel column, Cyclohexane/AcOEt: 60/40 as eluent) to afford 137 mg of 2-(4-(6-(fluoromethyl)pyridin-2-yl)but-3-ynyl)-8-phenyl-imidazo[1,2-a]pyridine (Yield: 46%) as a yellow oil.
Reaction SMILES: [Br:1][C:2]1[N:3]([CH3:11])[C:4]([C:7]([O:9]C)=[O:8])=[CH:5][N:6]=1.[OH-].[Li+]>O1CCCC1.O>[Br:1][C:2]1[N:3]([CH3:11])[C:4]([C:7]([OH:9])=[O:8])=[CH:5][N:6]=1
Reactant: COC(=O)c1cnc(Br)n1C
Agent: [Li+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: O
Product: Cn1c(C(=O)O)cnc1Br
Temperature: 25 °C
Reaction time: 2.5 h
Yield: 82 %

Procedure:
To a suspension of methyl 2-bromo-1-methyl-1H-imidazole-5-carboxylate (2.18 g, 10 mmol) in tetrahydrofuran (60 mL) and water (6 mL) was added lithium hydroxide (0.72 mg, 30 mmol) and the reaction mixture was allowed to stir at room temperature for 2.5 h. The solvent was removed under reduced pressure and water was added followed by formic acid, the resulting precipitate was filtered, washed with water and dried under vacuum overnight to afford the 2-bromo-1-methyl-1H-imidazole-5-carboxylic acid (82%). 1H-NMR (300 MHz, CDCl3): 7.79 (s, 1H), 3.91 (s, 3H). LCMS (ESI+) 205.0 (MH+). To a solution of the carboxylic acid (1.68 g, 8.2 mmol) in anhydrous tetrahydrofuran (24 mL) was added EDC (1.53 g, 9.9 mmol) followed by HOBt (1.22 g, 9.1 mmol) and the reaction mixture was allowed to stir for 1 h at room temperature. A solution of pyrrolidine (1.03 ml, 12.4 mmol) in tetrahydrofuran (8 mL) was added and the reaction mixture was allowed to stir overnight at room temperature. The solvent was removed under reduced pressure and residue partitioned between ethyl acetate and 1 M aqueous potassium carbonate. The organic layer was dried (Na2SO4) and solvent evaporated under reduced pressure. Purification by flash column chromatography (silica, EtOAc/MeOH 9:1) afforded the title compound (95%). 1H NMR (300 MHz, CDCl3): 7.79 (s, 1H), 3.92 (s, 3H), δ 3.35 (bs, 4H), δ 1.97 (bs, 4H). LCMS (ESI+) 257.0 (MH+).