Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C(O[C:4]([C:6]1[NH:10][C:9]2[CH:11]=[C:12]([C:14]3[CH:19]=[CH:18][C:17]([N+:20]([O-:22])=[O:21])=[CH:16][CH:15]=3)[O:13][C:8]=2[CH:7]=1)=[O:5])C.[NH2:23][NH2:24].Br[CH2:26][CH2:27][CH2:28][C:29]([O:31][CH2:32][CH3:33])=[O:30].C(N(CC)CC)C>CC(O)C>[CH2:32]([O:31][C:29](=[O:30])[CH2:28][CH2:27][CH2:26][NH:23][NH:24][C:4]([C:6]1[NH:10][C:9]2[CH:11]=[C:12]([C:14]3[CH:15]=[CH:16][C:17]([N+:20]([O-:22])=[O:21])=[CH:18][CH:19]=3)[O:13][C:8]=2[CH:7]=1)=[O:5])[CH3:33]
Reactant: NN
Reactant: CCOC(=O)CCCBr
Reactant: CCOC(=O)c1cc2oc(-c3ccc([N+](=O)[O-])cc3)cc2[nH]1
Solvent: CC(C)O
Solvent: CCN(CC)CC
Product: CCOC(=O)CCCNNC(=O)c1cc2oc(-c3ccc([N+](=O)[O-])cc3)cc2[nH]1
Temperature: 80 °C

Procedure:
As depicted in Scheme 31 below, 2-(4-nitro-phenyl)-4H-furo[3,2-b]pyrrole-5-carboxylic acid ethyl ester (0.1 mmol) is dissolved in 2-propanol (10 ml) and hydrazine (0.11 mmol) is added. The resulting mixture is heated at 80° C., while monitoring the reaction progress by TLC. Once the reaction is completed (the starting material is no longer detected), the solvents are evaporated under reduced pressure, dioxane (20 ml) is added to the crude mixture, followed by addition of ethyl 4-bromobutyrate (0.1 mmol) and triethylamine (0.1 mmol), and the resulting mixture is heated to reflux, while monitoring the reaction progress by TLC. Once the reaction is completed (the starting material is no longer detected), the solvent is evaporated, and a mixture of ethyl acetate and water is added. The phases are separated, and the aqueous phase is extracted with ethyl acetate. The combined organic phase is dried over Na2SO4, and the solvents are evaporated under reduced pressure to give crude 4-{N′-[2-(4-Nitro-phenyl)-4H-furo[3,2-b]pyrrole-5-carbonyl]-hydrazino}-butyric acid ethyl ester which is purified by column chromatography.
Reaction SMILES: [F:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][CH:6]=[N:7]2.[Cl:12][S:13](O)(=[O:15])=[O:14]>>[F:1][C:2]1[CH:11]=[CH:10][C:9]([S:13]([Cl:12])(=[O:15])=[O:14])=[C:8]2[C:3]=1[CH:4]=[CH:5][CH:6]=[N:7]2
Reactant: Fc1cccc2ncccc12
Reactant: O=S(=O)(O)Cl
Product: O=S(=O)(Cl)c1ccc(F)c2cccnc12
Temperature: 130 °C

Procedure:
5-fluoroquinoline (800 mg, 5.4 mmol) was added slowly to 10 mL of chlorosulfonic acid at 0° C. When the addition was complete, the reaction mixture was heated at 130° C. overnight. The solution was allowed to cool and was slowly poured over ice. The aqueous layer was extracted with ethyl acetate (3×50 mL). The combined organic extracts were dried and evaporated to give the crude product, which was purified by column chromatography (5% EtOAc/PE) to afford 400 mg of title compound. 1H NMR (CHLOROFORM-d) δ: 7.40 (t, J=8.46 Hz, 1 H), 7.74 (dd, J=8.60, 4.30 Hz, 1 H), 8.55-8.64 (m, 2 H), 9.32 (dd, J=4.30, 1.88 Hz, 1 H). LC-MS: m/z 4 246 (M+H)+
Reaction SMILES: [C:1]1([CH3:11])[CH:6]=[CH:5][CH:4]=[C:3]([S:7](Cl)(=[O:9])=[O:8])[CH:2]=1.[C:12]1([NH2:19])[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[NH2:18]>>[C:1]1([CH3:11])[CH:6]=[CH:5][CH:4]=[C:3]([S:7]([NH:18][C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=2[NH2:19])(=[O:9])=[O:8])[CH:2]=1
Reactant: Cc1cccc(S(=O)(=O)Cl)c1
Reactant: Nc1ccccc1N
Product: Cc1cccc(S(=O)(=O)Nc2ccccc2N)c1

Procedure:
The sulfonamide was synthesized from 3-tolylsulfonyl chloride (0.01 mol) and o-phenylene diamine (0.01 mol) by general Method C. It was purified by recrystallization from EtOH (0.73 g, 28%). EI-MS m/z 263 (M+H)+
Reaction SMILES: Cl[CH2:2][CH2:3][C@H:4]([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[O:5][C:6]1[CH:11]=[CH:10][N:9]=[C:8]2[CH:12]=[CH:13][S:14][C:7]=12.[Na+].[I-:22]>CC(C)=O>[I:22][CH2:2][CH2:3][C@H:4]([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[O:5][C:6]1[CH:11]=[CH:10][N:9]=[C:8]2[CH:12]=[CH:13][S:14][C:7]=12
Reactant: [I-]
Reactant: ClCC[C@@H](Oc1ccnc2ccsc12)c1ccccc1
Agent: [Na+]
Solvent: CC(C)=O
Product: ICC[C@@H](Oc1ccnc2ccsc12)c1ccccc1
Temperature: 55 °C
Reaction time: 18 h
Yield: 86.9 %

Procedure:
To a solution of 7-[(1R)-(3-Chloro-1-phenyl-propoxy)]-thieno[3,2-b]pyridine (703 mg, 2.3 mmol) in 15 mL of acetone was added NaI (3.5 g, 23 mmol). The resulting solution was allowed to stir at 55° C. for 18 h before removing the acetone in vacuo. The residue was taken up in CH2Cl2 and water. The layers were separated and the aqueous phase was further extracted 2 times with CH2Cl2. The combined organic phase was dried (MgSO4) and concentrated in vacuo. The residue was purified by flash chromatography eluting silica gel with hexane:ethyl acetate [100:0 to 1:1] to yield the title compound (0.79 g, 87%); mass spectrum (ion spray): m/z=395.98 (m+1).
Reaction SMILES: [CH:1]([C:3]1[S:7][C:6]([C:8]2[S:9][C:10]([C:13]3[S:14][CH:15]=[CH:16][CH:17]=3)=[CH:11][CH:12]=2)=[CH:5][CH:4]=1)=O.[C:18]([OH:23])(=[O:22])[C:19]([CH3:21])=[O:20].[OH-].[Na+].Cl>C(O)C.O>[C:18]([C:19](=[O:20])[CH:21]=[CH:1][C:3]1[S:7][C:6]([C:8]2[S:9][C:10]([C:13]3[S:14][CH:15]=[CH:16][CH:17]=3)=[CH:11][CH:12]=2)=[CH:5][CH:4]=1)([OH:23])=[O:22]
Reactant: O=Cc1ccc(-c2ccc(-c3cccs3)s2)s1
Reactant: CC(=O)C(=O)O
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CCO
Product: O=C(O)C(=O)C=Cc1ccc(-c2ccc(-c3cccs3)s2)s1
Reaction time: 0.17 h

Procedure:
0.5 g of 5-formyl-2,2':5',2"-terthiophene was dissolved in 40 ml of ethanol, followed by dropping in 3 ml of water containing 0.3 g of pyruvic acid salt and stirring for 10 minutes. 1 ml of 50% NaOH solution was dropped into the solution and stirred overnight. The reaction solution was acidified by diluted HCl and extracted with 100 ml of ethyl acetate. The extract was treated in situ and separated by column chromatography. Unreactive materials were eluted by ethyl acetate/n-hexane (1/9). The black solid product was eluted by ethyl acetate.
Reaction SMILES: [CH2:1]([C:5]([CH2:7][Br:8])=[O:6])[CH:2]([CH3:4])[CH3:3].[C:9]1([P:15]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1>>[Br-:8].[CH2:1]([C:5]([CH2:7][P+:15]([C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1)([C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[C:9]1[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=1)=[O:6])[CH:2]([CH3:4])[CH3:3]
Reactant: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Reactant: CC(C)CC(=O)CBr
Product: CC(C)CC(=O)C[P+](c1ccccc1)(c1ccccc1)c1ccccc1
Product: [Br-]
Yield: 84.6 %

Procedure:
53.6 g of bromomethyl isobutyl ketone is added to 78.5 g of triphenylphosphine and the cooled reaction mixture is recrystallized in methylene chloride/ether (1:2). 111.7 g of isobutylcarbonylmethyltriphenylphosphonium bromide with a melting point of 244°-245° C., is obtained.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]([C@@H:22]1[CH2:26][CH2:25][N:24]([CH:27]2[CH2:32][C:31]([CH3:34])([CH3:33])[NH:30][C:29]([CH3:36])([CH3:35])[CH2:28]2)[CH2:23]1)[C:9]1[N:14]=[CH:13][C:12](/[CH:15]=[CH:16]/[C:17]([O:19]CC)=O)=[CH:11][CH:10]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.[NH2:38][OH:39].C[O-].[K+].Cl>CO>[OH:39][NH:38][C:17](=[O:19])/[CH:16]=[CH:15]/[C:12]1[CH:11]=[CH:10][C:9]([N:8]([C@@H:22]2[CH2:26][CH2:25][N:24]([CH:27]3[CH2:28][C:29]([CH3:36])([CH3:35])[NH:30][C:31]([CH3:34])([CH3:33])[CH2:32]3)[CH2:23]2)[C:6](=[O:7])[O:5][C:1]([CH3:3])([CH3:4])[CH3:2])=[N:14][CH:13]=1
Reactant: NO
Reactant: CCOC(=O)/C=C/c1ccc(N(C(=O)OC(C)(C)C)[C@@H]2CCN(C3CC(C)(C)NC(C)(C)C3)C2)nc1
Agent: C[O-]
Agent: Cl
Agent: [K+]
Solvent: CO
Product: CC1(C)CC(N2CC[C@@H](N(C(=O)OC(C)(C)C)c3ccc(/C=C/C(=O)NO)cn3)C2)CC(C)(C)N1
Temperature: 25 °C
Reaction time: 3 h
Yield: 39.9 %

Procedure:
To a stirred solution of ethyl (2E)-3-(6-{(tert-butoxycarbonyl)[(3R)-1-(2,2,6,6-tetramethyl-4-piperidinyl)-3-pyrrolidinyl]amino}-3-pyridinyl)acrylate (265 mg, 0.529 mmol) in methanol (5 mL) was added hydroxylamine hydrochloride (184 mg, 2.65 mmol) at ambient temperature. To this mixture was added 1N potassium methoxide in methanol (5.29 mL, 5.29 mmol) dropwise in an ice bath and the resulting mixture was stirred at ambient temperature for three hours. To the mixture was added 1N hydrogen chloride to neutralize the solution. The solvent was removed in vacuo and the residue was desalted using ion-exchange resin. The crude product was purified by preparative high-pressure liquid chromatography to afford tert-butyl {5-[(1E)-3-(hydroxyamino)-3-oxo-1-propen-1-yl]-2-pyridinyl}[(3R)-1-(2,2,6,6-tetramethyl-4-piperidinyl)-3-pyrrolidinyl]carbamate (103 mg) as a colorless wax.
Reaction SMILES: [C:1]([C:4]1[C:5]([NH:13][C:14]2[C:19]([F:20])=[CH:18][C:17]([N:21]3[CH2:26][CH2:25][N:24]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:23][CH2:22]3)=[C:16]([F:34])[CH:15]=2)=[N:6][C:7]([S:11][CH3:12])=[N:8][C:9]=1Cl)(=[O:3])[NH2:2].O.[NH2:36][NH2:37]>O1CCOCC1>[C:1]([C:4]1[C:5]([NH:13][C:14]2[C:19]([F:20])=[CH:18][C:17]([N:21]3[CH2:26][CH2:25][N:24]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:23][CH2:22]3)=[C:16]([F:34])[CH:15]=2)=[N:6][C:7]([S:11][CH3:12])=[N:8][C:9]=1[NH:36][NH2:37])(=[O:3])[NH2:2]
Reactant: CSc1nc(Cl)c(C(N)=O)c(Nc2cc(F)c(N3CCN(C(=O)OC(C)(C)C)CC3)cc2F)n1
Reactant: NN
Solvent: C1COCCO1
Solvent: O
Product: CSc1nc(NN)c(C(N)=O)c(Nc2cc(F)c(N3CCN(C(=O)OC(C)(C)C)CC3)cc2F)n1
Temperature: 25 °C
Reaction time: 4 h

Procedure:
To a solution of the product of Example 15D (3.53 mg, 0.69 mmol) in 1,4-dioxane (5 mL) was added hydrazine hydrate (0.3 mL). After stirring at ambient temperature for 4 hours, the mixture was concentrated. The residue was washed with hexane and dried under vacuum to give the crude title compound, which was used in the next step without further purification (281 mg, 80%). MS: 511 (M+H+).
Reaction SMILES: [CH2:1]([N:8]1[CH2:13][CH2:12][CH2:11][CH:10]([CH2:14][N:15]2[CH2:20][CH2:19][N:18](C(OC(C)(C)C)=O)[CH2:17][C:16]2=[O:28])[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[ClH:29]>ClCCl.O1CCOCC1>[ClH:29].[ClH:29].[CH2:1]([N:8]1[CH2:13][CH2:12][CH2:11][CH:10]([CH2:14][N:15]2[CH2:20][CH2:19][NH:18][CH2:17][C:16]2=[O:28])[CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CC(C)(C)OC(=O)N1CCN(CC2CCCN(Cc3ccccc3)C2)C(=O)C1
Agent: Cl
Solvent: C1COCCO1
Solvent: ClCCl
Product: O=C1CNCCN1CC1CCCN(Cc2ccccc2)C1
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 100 %

Procedure:
To a solution of tert-butyl 4-[(1-benzylpiperidin-3-yl)methyl]-3-oxopiperazine-1-carboxylate (95 mg) in dichloromethane (1 mL) was added 4M hydrochloric acid in dioxane (1 mL). The mixture was stirred at room temperature for 15 minutes and then evaporated to give the title compound as a sticky white solid (89 mg, 100%).
Reaction SMILES: [N:1]1[N:5]2[CH:6]=[CH:7][C:8]([OH:10])=[N:9][C:4]2=[CH:3][CH:2]=1.[Br:11]N1C(=O)CCC1=O>ClCCl.CN(C=O)C>[Br:11][C:3]1[CH:2]=[N:1][N:5]2[CH:6]=[CH:7][C:8]([OH:10])=[N:9][C:4]=12
Reactant: Oc1ccn2nccc2n1
Reactant: O=C1CCC(=O)N1Br
Solvent: ClCCl
Solvent: CN(C)C=O
Product: Oc1ccn2ncc(Br)c2n1
Temperature: 25 °C
Reaction time: 17 h
Yield: 89.9 %

Procedure:
A mixture of pyrazolo[1,5-a]pyrimidin-5-ol (Example 1, Step 1, 28.3 g, 210 mmol) and N-bromosuccinimide (37.3 g, 210 mmol) in dichloromethane (200 mL) and DMF (300 mL) was stirred at ambient temperature for 17 hours. The reaction mixture was concentrated and the product was precipitated using Et2O. The solids were collected by filtration and dried to afford 3-bromopyrazolo[1,5-a]pyrimidin-5-ol (40.4 g, 90%). LCMS (APCI−) m/z 211, 213 [M−H]−.
Reaction SMILES: [H-].[Na+].CN(C)C=O.[CH2:8]([O:11][C:12]1[C:24]2[C:23]3[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=3)[NH:17][C:16]=2[CH:15]=[CH:14][CH:13]=1)[CH:9]=[CH2:10].Cl[CH2:26][C:27]1[CH:46]=[CH:45][C:30]([O:31][CH2:32][C:33]2[N:34]=[C:35]([C:39]3[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=3)[O:36][C:37]=2[CH3:38])=[C:29]([O:47][CH3:48])[CH:28]=1>C(OCC)(=O)C.CCCCCC>[CH3:38][C:37]1[O:36][C:35]([C:39]2[CH:40]=[CH:41][CH:42]=[CH:43][CH:44]=2)=[N:34][C:33]=1[CH2:32][O:31][C:30]1[CH:45]=[CH:46][C:27]([CH2:26][N:17]2[C:16]3[CH:15]=[CH:14][CH:13]=[C:12]([O:11][CH2:8][CH:9]=[CH2:10])[C:24]=3[C:23]3[C:18]2=[CH:19][CH:20]=[CH:21][CH:22]=3)=[CH:28][C:29]=1[O:47][CH3:48]
Reactant: COc1cc(CCl)ccc1OCc1nc(-c2ccccc2)oc1C
Reactant: C=CCOc1cccc2[nH]c3ccccc3c12
Agent: [H-]
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Solvent: CCCCCC
Product: C=CCOc1cccc2c1c1ccccc1n2Cc1ccc(OCc2nc(-c3ccccc3)oc2C)c(OC)c1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
6.05 g of sodium hydride (60%) was added to N,N-dimethylformamide (170 mL) solution of 35 g of 4-(allyloxy)-9H-carbazole while being cooled in an ice bath, and stirred at room temperature for 1 hour. Thereafter, 49.4 g of 4-((4-(chloromethyl)-2-methoxyphenoxy)methyl)-5-methyl-2-phenyloxazole was added thereto, and stirred for 1 hour. The reaction mixture was diluted with mixture of ethyl acetate:n-hexane=1:1 (340 mL), poured into ice water (680 mL), and stirred for 1 hour. The crystalline precipitate was isolated by filtration, and washed with mixture of ethyl acetate:n-hexane=1:1. The crystalline precipitate was dried under reduced pressure, and 55.4 g the subject compound was prepared as pale yellow crystal.
Reaction SMILES: [N:1]#[N:2].[CH3:3][O:4][C:5]1[CH:6]=[C:7]2[C:12](=[CH:13][C:14]=1[O:15][CH3:16])[CH:11]=[C:10]([S:17]([NH:20][C@H:21]([C:29]([OH:31])=O)[CH2:22][CH2:23][CH2:24][NH:25][C:26](=[NH:28])[NH2:27])(=[O:19])=[O:18])[CH:9]=[CH:8]2.P(Cl)(Cl)(Cl)(Cl)[Cl:33].CCOCC>O1CCCC1>[N:1]#[N:2].[ClH:33].[ClH:33].[CH3:3][O:4][C:5]1[CH:6]=[C:7]2[C:12](=[CH:13][C:14]=1[O:15][CH3:16])[CH:11]=[C:10]([S:17]([NH:20][C@H:21]([C:29]([Cl:33])=[O:31])[CH2:22][CH2:23][CH2:24][NH:25][C:26](=[NH:28])[NH2:27])(=[O:19])=[O:18])[CH:9]=[CH:8]2
Reactant: COc1cc2ccc(S(=O)(=O)N[C@@H](CCCNC(=N)N)C(=O)O)cc2cc1OC
Reactant: ClP(Cl)(Cl)(Cl)Cl
Agent: N#N
Solvent: CCOCC
Solvent: C1CCOC1
Product: COc1cc2ccc(S(=O)(=O)N[C@@H](CCCNC(=N)N)C(=O)Cl)cc2cc1OC
Product: Cl
Temperature: 0 °C
Reaction time: 1 h

Procedure:
To a suspension of 1.00 g (0.00236 mole) of N2 -(6,7-dimethoxy-2-naphthalenesulfonyl)-L-arginine in 20 ml of tetrahydrofuran was added little by little 0.98 g (0.0047 mole) of phosphorus pentachloride while cooling with ice water. The mixture was stirred for 1 hour at 0°-5° C, and then, for 2 hours at room temperature. To this reaction mixture was added 100 ml of dry ether, and the supernatant was removed by decantation. The residual oily product was washed with 50 ml of dry ether to give powdery N2 -(6,7-dimethoxy-2-naphthalenesulfonyl)-L-arginyl chloride dihydrochloride, which was added with stirring to a solution of 1.31 g (0.015 mole) of N-methyl-N-butylamine in 10 ml of chloroform. Thereafter, following the same procedures as described in Example 1, N2 -(6,7-dimethoxy-2-naphthalenesulfonyl)-N-methyl-N-butyl-L-argininamide monoacetae was obtained. Yield 0.76 g (58%).
Reaction SMILES: [CH2:1]([N:8]1[CH:12]=[C:11]([CH2:13][C:14]#N)[C:10]([O:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[N:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH-:24].[Na+].[O:26]1CC[CH2:28][CH2:27]1.Cl>C(O)C>[CH2:1]([N:8]1[CH:12]=[C:11]([CH2:13][C:14]([O:26][CH2:27][CH3:28])=[O:24])[C:10]([O:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[N:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: N#CCc1cn(Cc2ccccc2)nc1OCc1ccccc1
Reactant: C1CCOC1
Reactant: [OH-]
Agent: Cl
Agent: [Na+]
Solvent: CCO
Product: CCOC(=O)Cc1cn(Cc2ccccc2)nc1OCc1ccccc1
Temperature: 25 °C
Reaction time: 3 h
Yield: 99 %

Procedure:
A mixture of 1-benzyl-3-benzyloxy-1H-pyrazol-4-ylacetonitrile (13.0 g), 4N aqueous sodium hydroxide solution (100 ml), tetrahydrofuran (100 ml) and ethanol (100 ml) was refluxed for 3 days. After cooling, the mixture was neutralized with dilute hydrochloric acid, which was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated aqueous sodium chloride solution, dried (MgSO4) and concentrated. A mixture of the residue, ethyl iodide (5.2 ml), potassium carbonate (11.9 g) and N,N-dimethylformamide (100 ml) was stirred at room temperature for 3 hours. The reaction mixture was poured into water, which was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated aqueous sodium chloride solution, dried (MgSO4), and concentrated. The residue was subjected to silica gel column chromatography to obtain ethyl 1-benzyl-3-benzyloxy-1H-pyrazol-4-ylacetate (14.9 g, yield 99%) as a colorless oily substance from the fraction eluted with ethyl acetate-hexane (1:2, volume ratio).
Reaction SMILES: I[C:2]1[CH:7]=[CH:6][N:5]=[CH:4][CH:3]=1.[Li]CCCC.[F:13][C:14]1[CH:19]=[CH:18][C:17]([C:20]2[CH:24]=[C:23]([C:25](=O)[CH3:26])[O:22][N:21]=2)=[CH:16][CH:15]=1>C1COCC1>[F:13][C:14]1[CH:15]=[CH:16][C:17]([C:20]2[CH:24]=[C:23]([CH:25]([C:2]3[CH:7]=[CH:6][N:5]=[CH:4][CH:3]=3)[CH3:26])[O:22][N:21]=2)=[CH:18][CH:19]=1
Reactant: Ic1ccncc1
Reactant: CC(=O)c1cc(-c2ccc(F)cc2)no1
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: CC(c1ccncc1)c1cc(-c2ccc(F)cc2)no1
Reaction time: 0.17 h
Yield: 30.8 %

Procedure:
To a stirred solution of 4-iodopyridine (0.3 g, 1.463 mmol) in THF (10 mL) was added n-BuLi (0.6 mL, 0.96 mmol) at −78° C. and stirred for 10 min. A solution of 1-(3-(4-fluorophenyl)isoxazol-5-yl)ethanone (0.1 g, 0.484 mmol) in THF (5 mL) was added to the reaction and the mixture stirred at −78° C. for 2 h. The reaction was quenched with saturated ammonium chloride solution (10 mL) and diluted with ethyl acetate (50 mL). The organic layer was separated, washed with saturated ammonium chloride (3×150 mL) followed by brine solution (2×20 mL). The organic layer was dried over sodium sulfate, filtered and concentrated under reduced pressure to obtain crude product. The crude product was purified by column chromatography (100-200μ silica gel; 50% ethyl acetate in hexane) to obtain 3-(4-fluorophenyl)-5-(1-(pyridin-4-yl)ethyl)isoxazole as off-white solid (0.04 g, 29% yield). 1H NMR (400 MHz, DMSO-d6): δ 8.55 (d, 2H), 7.91 (dd, 2H), 7.46 (d, 2H), 7.32 (t, 2H), 6.81 (s, 1H), 7.04 (s, 1H), 1.86 (s, 3H); LC-MS m/z calculated for [M+H]+285.10. found 285.1.
Reaction SMILES: Br[C:2]1[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[C:9]([C:16]2[CH:21]=[CH:20][C:19]([C:22]3[O:23][C:24]4[CH:30]=[CH:29][CH:28]=[CH:27][C:25]=4[N:26]=3)=[CH:18][CH:17]=2)=[C:8]2[C:3]=1[CH:4]=[CH:5][CH:6]=[CH:7]2.[C:31]1([C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=2)[CH:36]=[CH:35][C:34](B(O)O)=[CH:33][CH:32]=1.C(=O)([O-])[O-].[Na+].[Na+].C1(C)C=CC=CC=1>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.O.C(O)C>[C:31]1([C:40]2[CH:41]=[CH:42][CH:43]=[CH:44][CH:45]=2)[CH:36]=[CH:35][C:34]([C:2]2[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[C:9]([C:16]3[CH:21]=[CH:20][C:19]([C:22]4[O:23][C:24]5[CH:30]=[CH:29][CH:28]=[CH:27][C:25]=5[N:26]=4)=[CH:18][CH:17]=3)=[C:8]3[C:3]=2[CH:4]=[CH:5][CH:6]=[CH:7]3)=[CH:33][CH:32]=1
Reactant: Brc1c2ccccc2c(-c2ccc(-c3nc4ccccc4o3)cc2)c2ccccc12
Reactant: OB(O)c1ccc(-c2ccccc2)cc1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CCO
Solvent: O
Solvent: Cc1ccccc1
Product: c1ccc(-c2ccc(-c3c4ccccc4c(-c4ccc(-c5nc6ccccc6o5)cc4)c4ccccc34)cc2)cc1
Temperature: 25 °C
Yield: 49.7 %

Procedure:
In a 100 mL three-neck flask, 0.91 g (2.0 mmol) of 2-[4-(10-bromo-9-anthryl)phenyl]benzoxazole, 0.44 g (2.2 mmol) of 4-biphenylboronic acid, 0.47 g (4.4 mmol) of sodium carbonate, 10 mL of toluene, 3 mL of ethanol, and 3 mL of water were placed. The mixture was degassed by being stirred under reduced pressure, and the air in the flask was replaced with nitrogen. To the mixture, 29 mg (0.025 mmol) of tetrakis(triphenylphosphine)palladium(0) was added, and the mixture was stirred under nitrogen stream at 80° C. for 13 hours. After a certain period, the mixture was cooled to room temperature, and the precipitated solid was obtained by suction filtration and washed with water. A toluene solution of the obtained solid was subjected to suction filtration through Celite (produced by Wako Pure Chemical Industries, Ltd., Catalog No. 531-16855) and alumina, and the filtrate was condensed to give a solid. The solid was recrystallized with toluene/hexane, giving 0.52 g of the target white powder. Further, an aqueous layer of the filtrate which was obtained through suction filtration after stirring was extracted with toluene. The obtained extracted solution was washed with a saturated aqueous solution of sodium hydrogen carbonate and saturated saline, and the organic layer was dried with magnesium sulfate. The mixture was gravity filtered, and the filtrate was condensed to give a solid. A toluene solution of the solid was subjected to suction filtration through Celite (produced by Wako Pure Chemical Industries, Ltd., Catalog No. 531-16855) and alumina, and the filtrate was condensed to give a solid. The solid was recrystallized with toluene/hexane, giving 0.47 g of the target white powder. In this manner, a total of 0.99 g of the target white solid was obtained in a yield of 93%.
Reaction SMILES: O[CH2:2][C:3]1([S:6]([NH:9][C:10](=[O:16])[O:11][C:12]([CH3:15])([CH3:14])[CH3:13])(=[O:8])=[O:7])[CH2:5][CH2:4]1.CCN(S(F)(F)[F:23])CC>C(Cl)Cl>[F:23][CH2:2][C:3]1([S:6]([NH:9][C:10](=[O:16])[O:11][C:12]([CH3:15])([CH3:14])[CH3:13])(=[O:8])=[O:7])[CH2:5][CH2:4]1
Reactant: CC(C)(C)OC(=O)NS(=O)(=O)C1(CO)CC1
Reactant: CCN(CC)S(F)(F)F
Solvent: ClCCl
Product: CC(C)(C)OC(=O)NS(=O)(=O)C1(CF)CC1
Reaction time: 0.5 h
Yield: 72.8 %

Procedure:
A solution of tert-butyl 1-hydroxymethylcyclopropylsulfonylcarbamate (26 g, 103 mmol) in DCM (300 mL) was cooled to −78° C. To this solution was added DAST (41 mL, 310 mmol) and the reaction mass was stirred at the same temperature for 30 min. The reaction mass was quenched with aqueous 1N NaOH solutions. The organic layer was separated and the aqueous layer was acidified to pH ˜2 by using 1.5 N HCl solutions. The aqueous solution was extracted with DCM (50 mL×4). The combined organic layer was dried over anhydrous sodium sulphate and evaporated to get desired compound (19 g, 72%) as gummy mass. 1H NMR (400 MHz, DMSO-d6): δ ppm 11.25 (sb, 1H), 4.75 (s, 1H), 4.63 (s, 1H), 1.44 (s, 9H), 1.28 (m, 2H), 1.07 (m, 2H). 19F NMR: −211.7 (1F).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]#[C:9][CH2:10][NH:11][C:12](=[O:18])[O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[CH:4][CH:3]=1.[CH2:19]([SnH:23]([CH2:28][CH2:29][CH2:30][CH3:31])[CH2:24][CH2:25][CH2:26][CH3:27])[CH2:20][CH2:21][CH3:22]>C1COCC1.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>[Cl:1][C:2]1[CH:3]=[CH:4][C:5](/[C:8](/[Sn:23]([CH2:24][CH2:25][CH2:26][CH3:27])([CH2:28][CH2:29][CH2:30][CH3:31])[CH2:19][CH2:20][CH2:21][CH3:22])=[CH:9]\[CH2:10][NH:11][C:12](=[O:18])[O:13][C:14]([CH3:15])([CH3:17])[CH3:16])=[CH:6][CH:7]=1
Reactant: CC(C)(C)OC(=O)NCC#Cc1ccc(Cl)cc1
Reactant: CCCC[SnH](CCCC)CCCC
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Solvent: C1CCOC1
Product: CCCC[Sn](CCCC)(CCCC)/C(=C/CNC(=O)OC(C)(C)C)c1ccc(Cl)cc1
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 89.4 %

Procedure:
To a solution of tert-butyl [3-(4-chlorophenyl)prop-2-yn-1-yl]carbamate (5.97 g, 22.5 mmol) in THF (240 mL) under an atmosphere of argon was added bis(triphenylphosphine)palladium(II) chloride (0.788 g, 1.12 mmol) and tri-n-butyltin hydride (9.55 mL, 35.5 mmol). The solution was stirred at room temperature for 90 minutes. The solvent was evaporated and the residue was purified using column chromatography on silica gel (220 g Analogix column, gradient hexane to 20% EA in hexane over 30 minutes) to give the product (11.2 g, 90%). LCMS: (AA) ES+ 556, 558. 1H NMR (400 MHz, d6-DMSO) δ: 7.37-7.31 (m, 2H), 6.96 (m, 2H), 5.83-5.60 (m, 1H), 3.60-3.37 (m, 2H), 1.44-1.36 (m, 6H), 1.34 (m, 9H), 1.26-1.15 (m, 6H), 0.89-0.77 (m, 15H).