Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [O:1]=[C:2]1[N:6]([C:7]2[CH:12]=[CH:11][C:10]([CH:13]3[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]3)=[C:9]([F:19])[CH:8]=2)[CH2:5][C@H:4]([CH2:20][NH:21][C:22](=[O:24])[CH3:23])[O:3]1.Cl.CN(C)CCCN=C=NCC.[CH:37](O)=[O:38]>O1CCCC1.C(Cl)Cl>[CH:37]([N:16]1[CH2:15][CH2:14][CH:13]([C:10]2[CH:11]=[CH:12][C:7]([N:6]3[CH2:5][C@H:4]([CH2:20][NH:21][C:22](=[O:24])[CH3:23])[O:3][C:2]3=[O:1])=[CH:8][C:9]=2[F:19])[CH2:18][CH2:17]1)=[O:38]
Reactant: O=CO
Reactant: CC(=O)NC[C@H]1CN(c2ccc(C3CCNCC3)c(F)c2)C(=O)O1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Solvent: ClCCl
Solvent: C1CCOC1
Product: CC(=O)NC[C@H]1CN(c2ccc(C3CCN(C=O)CC3)c(F)c2)C(=O)O1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
A mixture of (S)-(-)-3-[[2-oxo-3-[4-(4-piperidinyl)-3-fluorophenyl]-5-oxazolidinyl]methyl]acetamide (EXAMPLE 20, 150 mg), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (171 mg) and formic acid (34 μL) in dry tetrahydrofuran (6 mL) is stirred at ambient temperature for one hour, diluted with methylene chloride (10 mL), washed with water (10 mL) and saline (10 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure, and the residue is recrystallized from methylene chloride/diethyl ether to give the title compound, mp 186-187° C.
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([CH2:6][C:7](=[O:11])[NH:8]2)=[CH:4][CH:3]=1.[S:12]1[CH:16]=[CH:15][C:14]([CH:17]=O)=[CH:13]1.N1CCCCC1>CO>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5](/[C:6](=[CH:17]/[C:14]3[CH:15]=[CH:16][S:12][CH:13]=3)/[C:7](=[O:11])[NH:8]2)=[CH:4][CH:3]=1
Reactant: O=C1Cc2ccc(Cl)cc2N1
Reactant: O=Cc1ccsc1
Solvent: C1CCNCC1
Solvent: CO
Product: O=C1Nc2cc(Cl)ccc2/C1=C/c1ccsc1
Yield: 77.1 %

Procedure:
In a manner similar to the method described in Example 1, 6-chlorooxindole (2 g, 11.9 mmol) (Alfa) was reacted with 3-thiophenecarboxaldehyde (1.09 mL, 11.9 mmol) (Aldrich) and piperidine (1.18 mL, 11.9 mmol) in methanol to give E/Z-6-chloro-3-thiophen-3-ylmethylene-1,3-dihydro-indol-2-one as a yellow solid (Yield 2.4 g, 77%)
Reaction SMILES: [C:1]([CH:3]([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[NH:4][C:5](=[O:16])[CH2:6][C:7]1[CH:12]=[CH:11][C:10]([CH:13]([CH3:15])[CH3:14])=[CH:9][CH:8]=1)#[N:2].[NH4+].[Cl-].[N-:25]=[N+:26]=[N-:27].[Na+]>CN(C=O)C>[CH:13]([C:10]1[CH:11]=[CH:12][C:7]([CH2:6][C:5]([NH:4][CH:3]([C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=2)[C:1]2[NH:27][N:26]=[N:25][N:2]=2)=[O:16])=[CH:8][CH:9]=1)([CH3:15])[CH3:14]
Reactant: [N-]=[N+]=[N-]
Reactant: CC(C)c1ccc(CC(=O)NC(C#N)c2ccccc2)cc1
Agent: [Cl-]
Agent: [NH4+]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CC(C)c1ccc(CC(=O)NC(c2ccccc2)c2nnn[nH]2)cc1
Temperature: 110 °C
Reaction time: 16 h
Yield: 79.8 %

Procedure:
To a solution N-[cyano(phenyl)methyl]-2-(4-isopropylphenyl)acetamide (58.0 mg, 0.198 mmol) in 0.5 ml of anhydrous DMF was added NH4Cl (12.0 mg, 0.218 mmol) and NaN3 (14.00 mg, 0.218 mmol). The resulting solution was stirred at 110° C. for 16 hour. Filtered and the filtrate was purified by preparative HPLC (5-90% CH3CN/H2O over 30 min, 0.05% added TFA, C18 column) to afford 53.0 mg (80%) of the title compound. 1H NMR (CD3OD, 400 MHz) δ 7.326 (m, 5H), 7.169 (ABq, J=8.2 Hz, 4H), 6.460 (s, 1H), 3.583 (ABq, J=14.5 Hz, 2H), 2.856 (sept, J=7.0 Hz, 1H), 1.214 (d, J=7.0 Hz, 6H). ES-MS [M+1]+: 336.2.
Reaction SMILES: C([C:3]1[C:4](Cl)=[N:5][C:6]([Cl:9])=[N:7][CH:8]=1)C.[CH3:11][S-:12].[Na+]>O1CCCC1.C(OCC)(=O)C>[Cl:9][C:6]1[N:5]=[C:4]([S:12][CH3:11])[CH:3]=[CH:8][N:7]=1
Reactant: CCc1cnc(Cl)nc1Cl
Reactant: C[S-]
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: CSc1ccnc(Cl)n1
Temperature: 25 °C
Reaction time: 5 h
Yield: 53.6 %

Procedure:
To a solution of ethyl 2,4-dichloropyrimidine (20.0 g, 0.13 mol) in 150 mL of anhydrous tetrahydrofurane was added sodium thiomethoxide (49.30 mL, 0.15 mol) at −10° C. The reaction mixture was allowed to warm up to room temperature and then stirred for 5 hours with monitoring a reaction with LC-MS or thin layer chromatography (TLC). The reaction mixture was diluted with ethyl acetate and washed with brine (×2). The collected organic layer was dried over anhydrous sodium sulfate and then concentrated in vacuo. The resulting solid was slurrified with diethyl ether and then collected by filtration to afford the desired intermediate 10 as a white solid (11.2 g, 52%)
Reaction SMILES: [CH2:1]([O:3][CH2:4][C:5]1[N:6]([CH2:18][CH:19]([CH3:21])[CH3:20])[C:7]2[CH:12]=[C:11]([CH3:13])[N:10]3N=N[N:16]=[C:9]3[C:8]=2[N:17]=1)[CH3:2].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(C)C=CC=CC=1.[ClH:48]>CC(O)C.C(OCC)C>[ClH:48].[CH2:1]([O:3][CH2:4][C:5]1[N:6]([CH2:18][CH:19]([CH3:20])[CH3:21])[C:7]2[CH:12]=[C:11]([CH3:13])[N:10]=[C:9]([NH2:16])[C:8]=2[N:17]=1)[CH3:2]
Reactant: CCOCc1nc2c(cc(C)n3nnnc23)n1CC(C)C
Agent: Cl
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CC(C)O
Solvent: Cc1ccccc1
Solvent: CCOCC
Product: CCOCc1nc2c(N)nc(C)cc2n1CC(C)C
Reaction time: 72 h

Procedure:
A mixture of 8-(ethoxymethyl)-7-(2-methylpropyl)-5-methyl-7H-imidazo[4,5-c]tetraazolo[1,5-a]pyridine (6.5 g, 22.5 mmol), triphenylphosphine (6.5 g, 24.8 mmol), and toluene (130 mL) was stirred and heated at reflux under nitrogen for 24 hours. Additional triphenylphosphine (3.0 g, 11.4 mmol) was added to the cloudy mixture, and the reaction was continued for three days. The solvent was removed under reduced pressure, and the resulting brown oil was dissolved in methanol (100 mL). Following the addition of a 1.0 M solution of hydrochloric acid in diethyl ether (45 mL) to the methanol solution, the reaction was heated at reflux overnight. The solvents were removed under reduced pressure, and water (200 mL) was added to the resulting brown oil, forming a white precipitate that was removed by filtration. Solid sodium carbonate (6.5 g) was added to the aqueous solution, followed by extraction with dichloromethane (2×200 mL). The combined extracts were dried over magnesium sulfate, filtered, and concentrated under reduced pressure to provide a brown oil, which was dissolved in 2-propanol (45 mL). A 1.0 M solution of hydrochloric acid in diethyl ether (22.5 mL) was added to the solution of crude product, and a white solid formed. After one hour the solid was isolated by filtration, washed with cold 2-propanol and diethyl ether, and dried in a vacuum oven at 90° C. for two days to yield 4.3 g of 2-(ethoxymethyl)-1-(2-methylpropyl)-6-methyl-1H-imidazo[4,5-c]pyridin-4-amine hydrochloride as a white solid, m.p. 181–183° C.
Reaction SMILES: [I:1][CH2:2][I:3].[C:4]1([P:10]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1>C1(C)C=CC=CC=1>[I-:1].[I:3][CH:2]=[C:22]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]1[PH+:10]([C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1)[C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1
Reactant: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Reactant: ICI
Solvent: Cc1ccccc1
Product: IC=C1C=CC=CC1[PH+](c1ccccc1)c1ccccc1
Product: [I-]
Temperature: 50 °C
Yield: 47042.6 %

Procedure:
Diiodomethane (150 mL, 1.86 mmol) and triphenylphosphine (425 g, 1.62 mmol) was dissolved in toluene (500 mL) and the resulting solution heated to 50° C. for eighteen hours. The solution was allowed to cool to room temperature before being filtered. The precipitate was washed with toluene (2×500 mL) before being dried under vacuo to yield the title compound (404 g, 41% yield) as a white solid:
Reaction SMILES: [F:1][C:2]1[CH:24]=[CH:23][C:5]([C:6]([NH:8][CH:9]([C:18]2[S:19][CH:20]=[CH:21][CH:22]=2)[C:10](=[O:17])[CH2:11][C:12]([O:14][CH2:15][CH3:16])=[O:13])=O)=[CH:4][CH:3]=1.P(Cl)(Cl)(Cl)=O.O.C(=O)([O-])O.[Na+]>CN(C)C=O>[F:1][C:2]1[CH:24]=[CH:23][C:5]([C:6]2[O:17][C:10]([CH2:11][C:12]([O:14][CH2:15][CH3:16])=[O:13])=[C:9]([C:18]3[S:19][CH:20]=[CH:21][CH:22]=3)[N:8]=2)=[CH:4][CH:3]=1
Reactant: CCOC(=O)CC(=O)C(NC(=O)c1ccc(F)cc1)c1cccs1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O=P(Cl)(Cl)Cl
Solvent: CN(C)C=O
Solvent: O
Product: CCOC(=O)Cc1oc(-c2ccc(F)cc2)nc1-c1cccs1
Temperature: 25 °C
Reaction time: 2.5 h
Yield: 28.7 %

Procedure:
A mixture of ethyl 4-(4-fluorobenzoylamino)-4-(2-thienyl)-3-ketobutyrate (349 mg), and phosphorus oxychloride (0.12 ml) in N,N-dimethylformamide (5 ml) was stirred at room temperature for 2.5 hours. The reaction mixture was poured into water, neutralized with a saturated aqueous sodium hydrogen carbonate solution and extracted with ethyl acetate. The organic layer was washed with water and brine, dried over anhydrous sodium sulfate and the solvent was removed under reduced pressure. The resulting residue was purified by silica gel flush column chromatography (solvent: hexane:ethyl acetate=20:1) to obtain ethyl 2-(4-fluorophenyl)-4-(2-thienyl)oxazol-5-ylacetate (95 mg) as pale yellowish powder.
Reaction SMILES: [C:1]([O:10][CH3:11])(=[O:9])[C:2]1[C:3](=[CH:5][CH:6]=[CH:7][CH:8]=1)[OH:4].Br[CH2:13][CH2:14][CH2:15][CH2:16][CH2:17]Br.[H-].[Na+].[Na].[NH:22]1[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24][C:23]1=[O:29]>C1(C)C=CC=CC=1>[CH3:11][O:10][C:1]([C:2]1[CH:8]=[CH:7][CH:6]=[CH:5][C:3]=1[O:4][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][N:22]1[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24][C:23]1=[O:29])=[O:9]
Reactant: O=C1CCCCCN1
Reactant: BrCCCCCBr
Reactant: COC(=O)c1ccccc1O
Agent: [H-]
Agent: [Na+]
Agent: [Na]
Solvent: Cc1ccccc1
Product: COC(=O)c1ccccc1OCCCCCN1CCCCCC1=O
Temperature: 100 °C

Procedure:
3.04 g of methyl salicylate and 18.4 g of 1,5-dibromopentane were added to a solution of 1.06 g of 50% sodium hydride in toluene, heated to 100° C. for 3 hurs, washed with water, dried, freed from the solvent by distillation off at reduced pressure and then further distilled to obtain an oily substance. A mixture of the thus obtained oily substance and 2.70 g of sodium salt of azacycloheptane-2-one was heated to 100° C. in toluene solvent for 5 hours, washed with water, dried and freed from the solvent by distillation off at reduced pressure and then finally distilled to obtain 4.90 g of colorless 1-[5-(2-methoxycarbonylphenoxy) pentyl] azacycloheptane-2-one having the following appearance, column temperature and analysis:
Reaction SMILES: [CH3:1][C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8]C)=[O:7])=[CH:4][C:3]=1[C:12]1[CH:13]=[C:14]2[C:19](=[CH:20][CH:21]=1)[C:18]([C:22]1[CH:27]=[CH:26][C:25]([S:28]([C:31]([F:34])([F:33])[F:32])(=[O:30])=[O:29])=[CH:24][C:23]=1[CH3:35])=[N:17][N:16]=[CH:15]2.[OH-].[Na+].Cl>C1COCC1.CO>[CH3:1][C:2]1[CH:11]=[CH:10][C:5]([C:6]([OH:8])=[O:7])=[CH:4][C:3]=1[C:12]1[CH:13]=[C:14]2[C:19](=[CH:20][CH:21]=1)[C:18]([C:22]1[CH:27]=[CH:26][C:25]([S:28]([C:31]([F:33])([F:32])[F:34])(=[O:30])=[O:29])=[CH:24][C:23]=1[CH3:35])=[N:17][N:16]=[CH:15]2
Reactant: COC(=O)c1ccc(C)c(-c2ccc3c(-c4ccc(S(=O)(=O)C(F)(F)F)cc4C)nncc3c2)c1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CO
Product: Cc1ccc(C(=O)O)cc1-c1ccc2c(-c3ccc(S(=O)(=O)C(F)(F)F)cc3C)nncc2c1
Reaction time: 8 h
Yield: 70.2 %

Procedure:
To a solution of methyl 4-methyl-3-(1-(2-methyl-4-(trifluoromethylsulfonyl)phenyl)phthalazin-6-yl)benzoate (120 mg, 0.24 mmol) in 3 mL of 2/1 THF/MeOH was added NaOH (30 mg, 0.72 mmol) at RT. After 8 h, the mixture was acidified with 2M HCl and extracted with DCM (3×). The combined DCM layers were washed with brine, dried and concentrated to afford the 4-methyl-3-(1-(2-methyl-4-(trifluoromethylsulfonyl)phenyl)phthalazin-6-yl)benzoic acid (82 mg) as a tan solid. The crude acid was used in the next step. MS (ESI, pos. ion) m/z: 486.9 (M+1).
Reaction SMILES: O1CCOCC1.[NH2:7][CH:8]([CH3:20])[CH2:9][C:10]1[C:18]2[C:13](=[CH:14][CH:15]=[C:16]([OH:19])[CH:17]=2)[NH:12][N:11]=1.[CH:21]1[C:33]2[CH:32]([CH2:34][O:35][C:36](Cl)=[O:37])[C:31]3[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=3)[C:25]=2[CH:24]=[CH:23][CH:22]=1.C(=O)(O)[O-].[Na+]>O>[CH:21]1[C:33]2[CH:32]([CH2:34][O:35][C:36]([NH:7][CH:8]([CH3:20])[CH2:9][C:10]3[C:18]4[C:13](=[CH:14][CH:15]=[C:16]([OH:19])[CH:17]=4)[NH:12][N:11]=3)=[O:37])[C:31]3[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=3)[C:25]=2[CH:24]=[CH:23][CH:22]=1
Reactant: CC(N)Cc1n[nH]c2ccc(O)cc12
Reactant: O=C(Cl)OCC1c2ccccc2-c2ccccc21
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O
Solvent: C1COCCO1
Product: CC(Cc1n[nH]c2ccc(O)cc12)NC(=O)OCC1c2ccccc2-c2ccccc21

Procedure:
To a mixture of dioxane and water (4:1, 10 mL) was added 3-(2-aminopropyl)-1H-indazol-5-ol (0.10 g, 0.36 mmol), 9-fluorenylmethoxycarbonyl chloride (0.13 g, 0.54 mmol) and sodium bicarbonate (0.9 g, 0.54 mmol). The reaction mixture poured into dilute sodium bicarbonate and the resulting mixture extracted with ether. The combined organic extracts were dried (MgSO4) and concentrated to a residue that was purified by chromatography.
Reaction SMILES: COC1C=C(OC)C=CC=1C[N:6]([CH2:13][C:14]1[C:15]([CH2:24][CH3:25])=[N:16][O:17][C:18]=1[C:19](OCC)=[O:20])[CH2:7][C:8]([O:10][CH2:11][CH3:12])=[O:9].CC(C)([O-])C.[K+].S(Cl)(Cl)=O>C1COCC1.C(Cl)Cl>[CH2:11]([O:10][C:8]([C:7]1[N:6]=[CH:13][C:14]2[C:15]([CH2:24][CH3:25])=[N:16][O:17][C:18]=2[C:19]=1[OH:20])=[O:9])[CH3:12]
Reactant: CCOC(=O)CN(Cc1ccc(OC)cc1OC)Cc1c(CC)noc1C(=O)OCC
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: O=S(Cl)Cl
Solvent: ClCCl
Solvent: C1CCOC1
Product: CCOC(=O)c1ncc2c(CC)noc2c1O
Temperature: -78 °C
Reaction time: 14 h
Yield: 91.8 %

Procedure:
Ethyl 4-(((2,4-dimethoxybenzyl)(2-ethoxy-2-oxoethyl)amino)methyl)-3-ethyl-isoxazole-5-carboxylate (0.88 g, 2.03 mmol) was dissolved in 40 mL of THF and cooled to −78° C. Potassium tert-butoxide solution (4.1 mL, 4.1 mmol, 1M in THF) was added dropwise, and the mixture was stirred for 14 hours, the cold bath allowed to evaporate spontaneously. The reaction mixture was cooled in an ice bath and quenched with 50 mL of 1M HCl. The product was extracted with EtOAc and the organic layer was dried over MgSO4 and concentrated to give 0.8 g of crude oil. The crude intermediate was dissolved in 12 mL of CH2Cl2. Thionyl chloride (0.23 mL, 3.09 mmol) was added and the reaction mixture was stirred for 5 h at ambient temperature. The volatiles were evaporated and the residue was partitioned between CH2Cl2 (50 mL) and saturated sodium bicarbonate solution (50 mL). To the vigorously stirring biphasic mixture was added 4M hydrochloric acid until pH was 2. The aqueous layer was extracted with additional CH2Cl2 and the combined organic layer was dried over MgSO4 and concentrated. The crude residue was purified by chromatography (0-100% CH2Cl2/hexanes) to give 440 mg of the title compound. MS: (+) m/z 237.29 (M+1).
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([Cl:8])[CH:5]=[C:4]([Cl:9])[N:3]=1.[F:10][C:11]([F:21])([F:20])[O:12][C:13]1[CH:19]=[CH:18][C:16]([NH2:17])=[CH:15][CH:14]=1.C(N(CC)CC)C>C(Cl)(Cl)Cl.CCCCCC>[Cl:9][C:4]1[CH:5]=[C:6]([Cl:8])[N:7]=[C:2]([NH:17][C:16]2[CH:18]=[CH:19][C:13]([O:12][C:11]([F:10])([F:20])[F:21])=[CH:14][CH:15]=2)[N:3]=1
Reactant: Nc1ccc(OC(F)(F)F)cc1
Reactant: Clc1cc(Cl)nc(Cl)n1
Solvent: CCN(CC)CC
Solvent: ClC(Cl)Cl
Solvent: CCCCCC
Product: FC(F)(F)Oc1ccc(Nc2nc(Cl)cc(Cl)n2)cc1

Procedure:
The title compound was prepared by reacting 2,4,6-trichloro pyrimidine (2 g, 10 mmol) with 4-trifluoromethoxy aniline (1.94 g, 10 mmol) in presence of triethylamine (5.5 g, 50 mmol) in a solvent chloroform: hexane (1:1, 20 mL) at reflux temperature for 7 hours.
Reaction SMILES: [Cl:1][CH2:2][C:3]([C:5]1[CH:10]=[C:9]([CH3:11])[CH:8]=[CH:7][C:6]=1[CH3:12])=[O:4].[CH2:13](O)[CH2:14][OH:15].[Na+].[Cl-]>C1(C)C(C)=CC=CC=1.O>[Cl:1][CH2:2][C:3]1([C:5]2[CH:10]=[C:9]([CH3:11])[CH:8]=[CH:7][C:6]=2[CH3:12])[O:15][CH2:14][CH2:13][O:4]1
Reactant: OCCO
Reactant: Cc1ccc(C)c(C(=O)CCl)c1
Agent: [Cl-]
Agent: [Na+]
Solvent: Cc1ccccc1C
Solvent: O
Product: Cc1ccc(C)c(C2(CCl)OCCO2)c1
Reaction time: 3 h
Yield: 80.9 %

Procedure:
A mixture of 18.3 g [0.1 mol] of 2-chloro-1-(2,5-dimethylphenyl)ethanone, 12.6 g [0.2 mol] of ethylene glycol, 1.9 g [0.01 mol] of p-TsOH hydrate and 100 ml of xylene is heated to boiling with a water trap for about 3 hours. 40 ml of water and 20 ml of saturated aqueous NaCl solution are then added to the reaction mixture at room temperature. After addition of 20 ml of xylene, the organic phase is separated off and extracted with 20 ml each of water and saturated aqueous NaCl solution. The organic phase is dried over sodium sulfate and concentrated in vacuo. 18.35 g of oil result with, according to GC, 95.3% product (77.2% of theory).
Reaction SMILES: [NH2:1][C:2]1[N:7]2[N:8]=[C:9]([CH3:11])[CH:10]=[C:6]2[N:5]=[CH:4][C:3]=1[C:12]([O:14]C)=O.O.[NH2:17][NH2:18]>CCO>[NH2:1][C:2]1[N:7]2[N:8]=[C:9]([CH3:11])[CH:10]=[C:6]2[N:5]=[CH:4][C:3]=1[C:12]([NH:17][NH2:18])=[O:14]
Reactant: NN
Reactant: COC(=O)c1cnc2cc(C)nn2c1N
Solvent: CCO
Solvent: O
Product: Cc1cc2ncc(C(=O)NN)c(N)n2n1
Temperature: 25 °C

Procedure:
A 250 mL flask containing the Methyl 7-amino-2-methylpyrazolo[1,5-a]pyrimidine-6-carboxylate (2.1 g, 20 mmol), EtOH (55 mL), and hydrazine hydrate (20 mL) was heated to reflux for 6 hours. The mixture was allowed to cool to room temperature. The precipitated solid was filtered and washed with water (2×10 mL) to provide Compound (10-1) as a white solid.
Reaction SMILES: [OH:1][C:2]1[CH:10]=[C:9](I)[CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].[CH3:12][N:13]([CH3:30])[C:14]1[C:19]([CH:20]([CH3:22])[CH3:21])=[CH:18][C:17]([CH:23]([OH:26])[C:24]#[CH:25])=[CH:16][C:15]=1[CH:27]([CH3:29])[CH3:28]>[Cu](I)I.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>[CH3:30][N:13]([CH3:12])[C:14]1[C:19]([CH:20]([CH3:21])[CH3:22])=[CH:18][C:17]([CH:23]([OH:26])[C:24]#[C:25][C:9]2[CH:8]=[CH:7][C:3]([C:4]([OH:6])=[O:5])=[C:2]([OH:1])[CH:10]=2)=[CH:16][C:15]=1[CH:27]([CH3:29])[CH3:28]
Reactant: C#CC(O)c1cc(C(C)C)c(N(C)C)c(C(C)C)c1
Reactant: O=C(O)c1ccc(I)cc1O
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: I[Cu]I
Product: CC(C)c1cc(C(O)C#Cc2ccc(C(=O)O)c(O)c2)cc(C(C)C)c1N(C)C
Yield: 22.5 %

Procedure:
In a manner analogous to example 1 f, the process is carried out by a reaction of 360 mg (1.35 mmol) of 2-hydroxy-4-iodobenzoic acid with 500 mg (1.9 mmol) of 1-(4-dimethylamino-3,5-diisopropylphenyl)prop-2-yn-1-ol in the presence of 15 mg (0.08 mmol) of copper iodide and 27 mg (0.04 mmol) of bis(triphenylphosphine)-palladium chloride. 120 mg of 4-[3-(4-dimethylamino-3,5-diisopropylphenyl)-3-hydroxyprop-1-ynyl]-2-hydroxy-benzoic acid are obtained in the form of a yellowish solid (Mp: dec>250° C., yield=22%).
Reaction SMILES: C([Li])(C)(C)C.[C:6]([O:10][C:11]([N:13]1[C:21]2[C:16](=[CH:17][C:18]([S:22]([N:25]3[CH2:30][CH2:29][N:28]([C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[CH2:27][CH2:26]3)(=[O:24])=[O:23])=[CH:19][CH:20]=2)[CH:15]=[CH:14]1)=[O:12])([CH3:9])([CH3:8])[CH3:7].[B:38](OC)([O:41]C)[O:39]C.B(F)(F)F.CCOCC>CCCCC.C1COCC1>[C:6]([O:10][C:11]([N:13]1[C:21]2[C:16](=[CH:17][C:18]([S:22]([N:25]3[CH2:30][CH2:29][N:28]([C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[CH2:27][CH2:26]3)(=[O:24])=[O:23])=[CH:19][CH:20]=2)[CH:15]=[C:14]1[B:38]([OH:41])[OH:39])=[O:12])([CH3:9])([CH3:8])[CH3:7]
Reactant: CC(C)(C)OC(=O)N1CCN(S(=O)(=O)c2ccc3c(ccn3C(=O)OC(C)(C)C)c2)CC1
Reactant: COB(OC)OC
Agent: FB(F)F
Agent: [Li]C(C)(C)C
Solvent: CCCCC
Solvent: CCOCC
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)N1CCN(S(=O)(=O)c2ccc3c(c2)cc(B(O)O)n3C(=O)OC(C)(C)C)CC1
Temperature: 0 °C
Reaction time: 0.33 h

Procedure:
A solution of tert-butyllithium (1.7 M, 4.55 mL, 7.73 mmol, 2.00 equiv) in pentane was added to a solution of tert-butyl 5-{[4-(tert-butoxycarbonyl) piperazin-1-yl]sulfonyl}-1H-indole-1-carboxylate (2-2, 1.80 g, 3.87 mmol, 1 equiv) in THF (100 mL) at −78° C. The resulting orange-colored reaction mixture was stirred at −78° C. for 1.5 hour before trimethyl borate (1.10 mL, 9.66 mmol, 2.50 equiv) was added. The mixture was warmed to 0° C. and stirred for 20 minutes. Boron trifluoride diethyl etherate (1.20 mL, 9.66 mmol, 2.50 equiv) was then added, and the resulting mixture was partitioned between aqueous half-saturated ammonium chloride solution (200 mL) and EtOAc (2×200 mL). The organic layer was dried over sodium sulfate and concentrated to give 1-(tert-butoxycarbonyl)-5-{[4-(tert-butoxycarbonyl) piperazin-1-yl]sulfonyl}-1H-indol-2-ylboronic acid (2-3) as a tan solid. LCMS [M+H]+ observed=510.3; calculated=510.4.
Reaction SMILES: Br[C:2]1[C:3](=[O:30])[C:4]2[C:9]([C:10]=1[C:11]1[CH:16]=[C:15]([F:17])[CH:14]=[C:13]([F:18])[CH:12]=1)=[CH:8][CH:7]=[C:6]([O:19][CH2:20][CH2:21][N:22]1[CH2:27][CH2:26][S:25](=[O:29])(=[O:28])[CH2:24][CH2:23]1)[CH:5]=2.O1CCN(CCO[C:40]2[CH:48]=[C:47]3[C:43]([C:44](C4C=CC=CC=4)=C(Br)C3=O)=[CH:42][CH:41]=2)CC1.B(O)(O)C1C=CC(C)=CC=1>>[F:17][C:15]1[CH:16]=[C:11]([C:10]2[C:9]3[C:4](=[CH:5][C:6]([O:19][CH2:20][CH2:21][N:22]4[CH2:23][CH2:24][S:25](=[O:29])(=[O:28])[CH2:26][CH2:27]4)=[CH:7][CH:8]=3)[C:3](=[O:30])[C:2]=2[C:40]2[CH:48]=[CH:47][C:43]([CH3:44])=[CH:42][CH:41]=2)[CH:12]=[C:13]([F:18])[CH:14]=1
Reactant: O=C1C(Br)=C(c2cc(F)cc(F)c2)c2ccc(OCCN3CCS(=O)(=O)CC3)cc21
Reactant: O=C1C(Br)=C(c2ccccc2)c2ccc(OCCN3CCOCC3)cc21
Agent: Cc1ccc(B(O)O)cc1
Product: Cc1ccc(C2=C(c3cc(F)cc(F)c3)c3ccc(OCCN4CCS(=O)(=O)CC4)cc3C2=O)cc1
Yield: 71 %

Procedure:
The procedure of Step 7 of Example 1 was repeated except for using 2-bromo-3-(3,5-difluorophenyl)-6-[2-(1,1-dioxothiomorpholin-4-yl)ethoxy]-1H-inden-1-one obtained in Step 1 of Example 92 as a starting material instead of 6-(2-morpholinoethoxy)-2-bromo-3-phenyl-1H-inden-1-one, p-tolylboronic acid instead of 3-pyridinylboronic acid, and being purified by silica gel column chromatography (EtOAc/hexanes=1:1) to obtain the title compound (71%).
Reaction SMILES: [CH:1]1[C:6]([C:7](C2C=CC3C(OC(=O)C=3C=2)=O)=[O:8])=[CH:5][C:4]2[C:20](O[C:23](=O)[C:3]=2[CH:2]=1)=O.[Cl:25][C:26]1[CH:27]=[C:28]([CH3:33])[C:29]([CH3:32])=[CH:30][CH:31]=1.C(Cl)(=O)C([Cl:37])=O>>[Cl:25][C:26]1[CH:27]=[C:28]([CH3:33])[C:29]([CH3:32])=[CH:30][C:31]=1[C:7]([C:6]1[CH:5]=[C:4]([CH3:20])[C:3]([CH3:23])=[CH:2][C:1]=1[Cl:37])=[O:8]
Reactant: Cc1ccc(Cl)cc1C
Reactant: O=C(Cl)C(=O)Cl
Reactant: O=C(c1ccc2c(c1)C(=O)OC2=O)c1ccc2c(c1)C(=O)OC2=O
Product: Cc1cc(Cl)c(C(=O)c2cc(C)c(C)cc2Cl)cc1C

Procedure:
Specific benzophenonetetracarboxylic dianhydrides preferred in this invention are readily available from commercial sources or synthesis. For instance, 3,3',4,4'-benzophenonetetracarboxylic dianhydride (D1) is available from Aldrich Chemical Co., Inc. (1001 W. St. Paul Ave., Milwaukee, Wis. 53233). 2,2'-Dichloro-4,4',5,5'-benzophenone tetracarboxylic dianhydride (D2) is available from 4-chloro-o-xylene by Friedel-Crafts acylation with oxalyl chloride to give 2,2'dichloro-4,4',5,5',-tetramehtylbenzophenone, followed by oxidation with nitric acid and dehydration of the resulting tetracarboxylic acid as described by Falcigno, et al., J. Poly. Sci. 1992, 30, 1433.
Reaction SMILES: C([SiH](CC)CC)C.[Br:8][C:9]1[CH:10]=[C:11]([CH:18]([C:20]2[CH:25]=[CH:24][C:23]([CH2:26][CH3:27])=[CH:22][CH:21]=2)O)[CH:12]=[CH:13][C:14]=1[O:15][CH2:16][CH3:17].CO.O>C(Cl)Cl>[Br:8][C:9]1[CH:10]=[C:11]([CH2:18][C:20]2[CH:25]=[CH:24][C:23]([CH2:26][CH3:27])=[CH:22][CH:21]=2)[CH:12]=[CH:13][C:14]=1[O:15][CH2:16][CH3:17]
Reactant: CCOc1ccc(C(O)c2ccc(CC)cc2)cc1Br
Agent: CC[SiH](CC)CC
Solvent: ClCCl
Solvent: O
Solvent: CO
Product: CCOc1ccc(Cc2ccc(CC)cc2)cc1Br
Reaction time: 3 h
Yield: 99.8 %

Procedure:
Triethylsilane (2.7 mL, 16.9 mmol) and a boron trifluoride-diethyl ether complex (1.2 mL, 9.47 mmol) were added to a solution of (3-bromo-4-ethoxyphenyl)-(4-ethylphenyl)methanol (2.83 g, 8.44 mmol) in methylene chloride (20 mL) at 0° C. and the mixture was stirred for three hours. Methanol (50%)-water (4 mL) was added to the reaction mixture and the resulting mixture was extracted with methylene chloride. The extract was washed with a saturated sodium chloride aqueous solution, and then dried over magnesium sulfate. The residue obtained by distilling the solvent under reduced pressure was purified by silica gel column chromatography {developing solution=n-hexane to n-hexane-ethyl acetate [4% (v/v)]} to obtain the title compound (2.69 g, 100%).