Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br[CH2:2][C:3]([C:5]1[CH:10]=[CH:9][C:8]([Cl:11])=[CH:7][CH:6]=1)=[O:4].[CH3:12][S-:13].[Na+]>O1CCCC1.C(OCC)C>[Cl:11][C:8]1[CH:9]=[CH:10][C:5]([C:3](=[O:4])[CH2:2][S:13][CH3:12])=[CH:6][CH:7]=1
Reactant: O=C(CBr)c1ccc(Cl)cc1
Reactant: C[S-]
Agent: [Na+]
Solvent: CCOCC
Solvent: C1CCOC1
Product: CSCC(=O)c1ccc(Cl)cc1
Reaction time: 1 h
Yield: 86.9 %

Procedure:
To a suspension of 2-bromo-1-(4-chlorophenyl)ethanone (1, 20 g, 86 mmol) in tetrahydrofuran (250 ml) was added sodium methanethiolate (7.2 g, 103 mmol) in tetrahydrofuran (250 ml) at −40° C. and the mixture was stirred for 1 hour. The mixture was diluted with diethyl ether and filtered off, and the filtrate was washed with brine. The solvent was evaporated off under the reduced pressure, and the residue was subjected to silica gel column chromatography (Biotage) to obtain 15 g of the title compound.
Reaction SMILES: [N+:1]([C:4]1[CH:13]=[C:8]([C:9]([O:11][CH3:12])=[O:10])[C:7]([OH:14])=[CH:6][CH:5]=1)([O-:3])=[O:2].N1C=CN=C1.[C:20]([Si:24](Cl)([CH3:26])[CH3:25])([CH3:23])([CH3:22])[CH3:21].O>CN(C=O)C>[CH3:12][O:11][C:9](=[O:10])[C:8]1[CH:13]=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=[CH:6][C:7]=1[O:14][Si:24]([C:20]([CH3:23])([CH3:22])[CH3:21])([CH3:26])[CH3:25]
Reactant: CC(C)(C)[Si](C)(C)Cl
Reactant: COC(=O)c1cc([N+](=O)[O-])ccc1O
Agent: c1c[nH]cn1
Solvent: O
Solvent: CN(C)C=O
Product: COC(=O)c1cc([N+](=O)[O-])ccc1O[Si](C)(C)C(C)(C)C
Temperature: 25 °C
Reaction time: 16 h
Yield: 31 %

Procedure:
A solution of methyl 5-nitrosalicylate (10.0 g, 50.7 mmol) and imidazole (3.8 g, 55.8 mol) in DMF (50 mL) at 0° C. was treated with t-butyl-chloro-dimethyl-silane and stirred 16 h at room temperature. The reaction mixture was poured into water (100 mL) and extracted with ether (3×50 mL). The combined extracts were washed with water (4×100 mL) and brine (50 mL), dried over magnesium sulfate, and concentrated. The crude residue was purified by flash chromatography (silica gel, 4×15 cm, eluted with 95/5 hexanes/EtOAc) to yield 2-(tert-butyl-dimethyl-silanyloxy)-5-nitro-benzoic acid methyl ester as a white solid (4.9 g, 31%).
Reaction SMILES: [N:1]([CH:4]([CH3:10])[C:5]([O:7]CC)=O)=[C:2]=[O:3].[NH2:11][CH2:12][CH2:13][NH:14][C:15]1[N:20]=[C:19]([C:21]2[S:22][C:23]([C:26]3[S:27][CH:28]=[CH:29][CH:30]=3)=[CH:24][CH:25]=2)[CH:18]=[CH:17][N:16]=1>ClCCl>[CH3:10][CH:4]1[NH:1][C:2](=[O:3])[N:11]([CH2:12][CH2:13][NH:14][C:15]2[N:20]=[C:19]([C:21]3[S:22][C:23]([C:26]4[S:27][CH:28]=[CH:29][CH:30]=4)=[CH:24][CH:25]=3)[CH:18]=[CH:17][N:16]=2)[C:5]1=[O:7]
Reactant: CCOC(=O)C(C)N=C=O
Reactant: NCCNc1nccc(-c2ccc(-c3cccs3)s2)n1
Solvent: ClCCl
Product: CC1NC(=O)N(CCNc2nccc(-c3ccc(-c4cccs4)s3)n2)C1=O
Temperature: 25 °C
Reaction time: 8 h
Yield: 68.3 %

Procedure:
Ethyl 2-isocyanatopropanoate (104 mg, 0.73 mmol) was added to a suspension of N-(2-aminoethyl)-4-(5-(thiophen-2-yl)thiophen-2-yl)pyrimidin-2-amine (200 mg, 0.66 mmol) in dichloromethane (10 mL) at rt and stirred for 8 h. The solid was filtered off and added to 15 mL of hydrochloric acid (5 M). After refluxing for 6 h, the mixture was cooled to rt and the precipitate was filtered off, washed with water and then dissolved in 10 mL of methanol. 50 mg of potassium carbonate was added and the mixture was stirred for 10 min. 20 mL of dichloromethane was added and the mixture was filtered through Celite. The filtrate was concentrated to give the title compound (180 mg, 68%). MS (M+H)+ 400.
Reaction SMILES: [N+]([C@@H:4]1[CH2:9][CH2:8][C:7](=[O:10])[NH:6][C@H:5]1[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)([O-])=O.ClCCl.CC(C)([O-:23])C.[K+].CSC>CO>[O:10]=[C:7]1[CH2:8][CH2:9][C:4](=[O:23])[CH:5]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[NH:6]1
Reactant: CC(C)(C)[O-]
Reactant: O=C1CC[C@@H]([N+](=O)[O-])[C@H](c2ccccc2)N1
Agent: [K+]
Solvent: CO
Solvent: CSC
Solvent: ClCCl
Product: O=C1CCC(=O)C(c2ccccc2)N1
Temperature: 0 °C
Reaction time: 0.25 h
Yield: 78.4 %

Procedure:
trans-3 -Nitro-6-oxo-2-phenylpiperidine (80 g, 0.364 mol) was suspended in methanol:dichloromethane (Example 1a, 1:1, 500 ml) under nitrogen. The suspension was cooled to 0° C. and potassium t-butoxide (44.8 g, 0.4 mol) was added in portions over 30 mins. The cooling bath was then removed and the solution stirred for a further 15 mins to afford a clear yellow solution. The solution was then cooled to -78° C. and ozone bubbled through the reaction mixture for 4.5 hrs, the flow of ozone was then stopped and the mixture purged with a stream of nitrogen. Anhydrous dimethyl sulphide (53 ml, 0.73 mol) was then added dropwise and the reaction mixture allowed to warm to room temperature. The solvent was then removed at reduced pressure and the residual orange solid dissolved in dichloromethane (800 ml), washed with water (2×200 ml), dried (MgSO4), the solvent was then removed at reduced pressure. The residue was suspended in ether, filtered, and the pale yellow crystalline solid washed with ether (3×100ml) and dried under vacuum to afford 2,5-dioxo-6-phenylpiperidine (54 g, 78%): m.p. 160°-164° C.; 1H NMR (360 MHz, DMSO-d6) δ2.55-2.58 (2H, m, CH2), 2.63-2.70 (2H, m, CH2), 2.5-2.9 (4H, m, CH2CH2), 4.96 (1H, d, J=2.4 Hz, PhCH), 7.4-7.7 (5H, m, Ar), 8.2 (1H, brs, NH); m/z (CI+) 207 (M+NH4 +), 190 (M+H); Calculated for C11H11NO2C; 69.83; H, 5.86; N, 7.40%. Found C, 70.04; H, 5.77; N, 7.60%.
Reaction SMILES: [NH:1]([C:5]1[S:6][CH:7]=[C:8]([CH2:10][S:11][CH2:12][CH2:13][C:14]#[N:15])[N:9]=1)[C:2]([NH2:4])=[NH:3].Cl.[CH3:17][OH:18]>C(Cl)(Cl)Cl>[NH:1]([C:5]1[S:6][CH:7]=[C:8]([CH2:10][S:11][CH2:12][CH2:13][C:14](=[NH:15])[O:18][CH3:17])[N:9]=1)[C:2]([NH2:4])=[NH:3]
Reactant: N#CCCSCc1csc(NC(=N)N)n1
Reactant: CO
Agent: Cl
Solvent: ClC(Cl)Cl
Product: COC(=N)CCSCc1csc(NC(=N)N)n1
Temperature: 2 °C
Reaction time: 20 h

Procedure:
3-(2-Guanidino-4-thiazolylmethylthio)propionitrile (12.82 g) was dissolved in a mixture of dry methanol (75 ml) and dry chloroform (150 ml) and the stirred solution was cooled (under nitrogen) in an ice-salt bath to 2° C. Hydrogen chloride gas (dried) was passed through the solution for three hours, keeping the temperature at 0°-10° C. The solution was then allowed to stand in a stoppered flask at ca 0° C. for 20 hours. The solvents were removed at reduced pressure and the oily residue added to ice-water (200 ml) containing potassium carbonate (30 g). The mixture was extracted with chloroform containing 20% methanol (4×150 ml) and the combined organic extracts were dried (MgSO4). The solvent was removed to give methyl 3-(2-guanidino-4thiazolylmethylthio)propionimidate (13.60 g) as a tacky light-brown oil.
Reaction SMILES: [I:1][C:2]1[C:10]([I:11])=[C:9]([I:12])[CH:8]=[C:7]2[C:3]=1[C:4]([CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][C:20]([OH:22])=[O:21])([CH3:14])[C:5]([CH3:13])=[N:6]2.[CH2:23]1[CH2:29][S:26](=[O:28])(=[O:27])[O:25][CH2:24]1>>[C:20]([CH2:19][CH2:18][CH2:17][CH2:16][CH2:15][C:4]1([CH3:14])[C:3]2[C:7](=[CH:8][C:9]([I:12])=[C:10]([I:11])[C:2]=2[I:1])[N+:6]([CH2:24][CH2:23][CH2:29][S:26]([O-:28])(=[O:27])=[O:25])=[C:5]1[CH3:13])([OH:22])=[O:21]
Reactant: O=S1(=O)CCCO1
Reactant: CC1=Nc2cc(I)c(I)c(I)c2C1(C)CCCCCC(=O)O
Product: CC1=[N+](CCCS(=O)(=O)[O-])c2cc(I)c(I)c(I)c2C1(C)CCCCCC(=O)O
Yield: 42 %

Procedure:
600 mg (0.94 mmol) of 6-(4,5,6-triiodo-2,3-dimethyl-3H-3-indolyl)hexanoic acid was heated with 600 mg (4.7 mmol) of 1,3-propane sultone at 100° C. for 40 minutes. The raw product was column purified (Silica gel 60, 0-40% methanol-chloroform) to give 300 mg of 3-[3-(5-carboxypentyl)-4,5,6-triiodo-2,3-dimethyl-3H-1-indoliumyl]-1-propanesulfonate: 7.39 (1H, s, arom.), 4.31 (2H, m, NCH2), 3.27 (3H, s, CH3), 2.34-2.02 (2H, m, CH2), 2.19 (2H, t, CH2CO), 1.98-1.65 (4H, m, CH2), 1.31 (3H, s, CH3), 1.43-1.00 (4H, m, (CH2)3), 0.62-0.35 (2H, m, CH2).
Reaction SMILES: [CH3:1][O:2][C:3]1[N:8]=[C:7]([C:9]([O:11]C)=[O:10])[CH:6]=[C:5]([CH3:13])[N:4]=1.[OH-].[Na+]>CO.O>[CH3:1][O:2][C:3]1[N:8]=[C:7]([C:9]([OH:11])=[O:10])[CH:6]=[C:5]([CH3:13])[N:4]=1
Reactant: COC(=O)c1cc(C)nc(OC)n1
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: O
Product: COc1nc(C)cc(C(=O)O)n1
Yield: 46.1 %

Procedure:
15.5 g of methyl 2-methoxy-6-methylpyrimidine-4-carboxylate are added to a stirred solution of 3.6 g of sodium hydroxide in 100 ml of methanol and 10 ml of water. Stirring is continued at room temperature until the starting material disappears (TLC checking; 3 h). The methanol is distilled off under reduced pressure, the residue is taken up in water and the mixture is extracted once with ethyl acetate. The aqueous phase is acidified to pH 2 with conc. hydrochloric acid and then stirred for 1 h, and the product is filtered off with suction. 6.6 g of 2-methoxy-6-methylpyrimidine-4-carboxylic acid of melting point 161°-163° C. are obtained in this way. Concentration and extraction of the mother liquor using dichloromethane additionally gives 3.1 g of product of melting point 159°-161° C.
Reaction SMILES: [CH3:1][S:2]([C:5]1[CH:10]=[C:9]([N+:11]([O-])=O)[CH:8]=[CH:7][C:6]=1[CH3:14])(=[O:4])=[O:3].O.C(=O)([O-])[O-].[Na+].[Na+].C(OCC)(=O)C>C(O)C>[CH3:1][S:2]([C:5]1[CH:10]=[C:9]([CH:8]=[CH:7][C:6]=1[CH3:14])[NH2:11])(=[O:3])=[O:4]
Reactant: Cc1ccc([N+](=O)[O-])cc1S(C)(=O)=O
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O
Solvent: CCO
Solvent: CCOC(C)=O
Product: Cc1ccc(N)cc1S(C)(=O)=O
Temperature: 75 °C
Reaction time: 4 h
Yield: 84.5 %

Procedure:
2-Methylsulfonyl-1-methyl-4-nitrobenzene (500 mg, 2.3 mmol) was dissolved in absolute ethanol (15 mL). Stannous chloride (2.6 g, 11.6 mmol) was added and the reaction mixture was stirred at 75° C. for 4 hours. The mixture was poured into water (50 mL), pH was adjusted with a saturated solution of sodium carbonate to basic reaction, followed by addition of ethyl acetate (150 mL). The organic phase was extracted with water (2×50 mL), dried (MgSO4) and concentrated in vacuo to give 0.36 g of 3-methylsulfonyl-4-methylaniline as an oil.
Reaction SMILES: C(SCC(CC1C=CC=CC=1)C(NC1C=C(C=CC=1)C(O)=O)=O)(=O)C1C=CC=CC=1.C([S:34][CH2:35][CH:36]([CH2:49][C:50]1[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=1)[C:37]([NH:39][C:40]1[CH:48]=[CH:47][C:43]([C:44]([NH2:46])=[O:45])=[CH:42][CH:41]=1)=[O:38])(=O)C>>[SH:34][CH2:35][CH:36]([CH2:49][C:50]1[CH:51]=[CH:52][CH:53]=[CH:54][CH:55]=1)[C:37]([NH:39][C:40]1[CH:48]=[CH:47][C:43]([C:44]([NH2:46])=[O:45])=[CH:42][CH:41]=1)=[O:38]
Reactant: CC(=O)SCC(Cc1ccccc1)C(=O)Nc1ccc(C(N)=O)cc1
Agent: O=C(O)c1cccc(NC(=O)C(CSC(=O)c2ccccc2)Cc2ccccc2)c1
Product: NC(=O)c1ccc(NC(=O)C(CS)Cc2ccccc2)cc1

Procedure:
Using the procedure of Example 3, replace the product of Example 1 with the product of Example 12 to give the title compound as a white solid, m.p.=195°-197° C., mass spec M+=314.
Reaction SMILES: [Cl:1][C:2]1[N:3]=[C:4](Cl)[C:5]2[NH:10][CH:9]=[CH:8][C:6]=2[N:7]=1.C(=O)([O-])O.[Na+]>C(O)C.[Pd]>[Cl:1][C:2]1[N:3]=[CH:4][C:5]2[NH:10][CH:9]=[CH:8][C:6]=2[N:7]=1
Reactant: Clc1nc(Cl)c2[nH]ccc2n1
Agent: [Pd]
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCO
Product: Clc1ncc2[nH]ccc2n1
Temperature: 25 °C
Reaction time: 3 h
Yield: 60.9 %

Procedure:
To a solution of 2,4-dichloro-5H-pyrrolo[3,2-d]pyrimidine (6.6 g, 35.3 mmol) in ethanol (200 mL) was added sodium hydrogen carbonate (2.96 g) and Palladium on carbon (10%, 0.66 g). The mixture was stirred under an atmosphere of hydrogen at room temperature for 3 h. The mixture was filtered then filtrate absorbed onto silica gel. Flash chromatography, eluting with chloroform/methanol 4/1, afforded 2-chloro-5H-pyrrolo[3,2-d]pyrimidine (3.3 g, 61%). Also recovered from the column was 5H-pyrrolo[3,2-d]pyrimidine (1.5 g)
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]2[CH2:16][CH2:15][CH:14]([CH2:17][C:18](O)=[O:19])[N:6]3[C:7](=[O:13])[C:8](=[O:12])[NH:9][C:10]([CH:11]=1)=[C:5]23.[CH3:21][O:22][C:23]([CH2:25][C:26]1[CH:32]=[CH:31][CH:30]=[CH:29][C:27]=1[NH2:28])=[O:24]>>[Br:1][C:2]1[CH:3]=[C:4]2[CH2:16][CH2:15][CH:14]([CH2:17][C:18](=[O:19])[NH:28][C:27]3[CH:29]=[CH:30][CH:31]=[CH:32][C:26]=3[CH2:25][C:23]([O:22][CH3:21])=[O:24])[N:6]3[C:7](=[O:13])[C:8](=[O:12])[NH:9][C:10]([CH:11]=1)=[C:5]23
Reactant: COC(=O)Cc1ccccc1N
Reactant: O=C(O)CC1CCc2cc(Br)cc3[nH]c(=O)c(=O)n1c23
Product: COC(=O)Cc1ccccc1NC(=O)CC1CCc2cc(Br)cc3[nH]c(=O)c(=O)n1c23
Yield: 69.9 %

Procedure:
A procedure similar to that described in Example 52 was carried out with 9-bromo-5-carboxymethyl-6,7-dihydro-1H, 5 H-pyrido[1,2,3-de]quinoxaline-2,3-dione (340 mg, 1 mmol) and o-methoxycarbonylmethylaniline (180 mg, 1 mmol) to give 340 mg of the title compound (70%): mp 206°~207° C. (dec); 1H NMR (270 MHz, DMSO-d6) δ12.06 (bs, 1H), 9.51 (s, 1H), 7.36 (bd, 1H, J=8.6 Hz), 7.26~7.29 (m, 3H), 7.16~7.19 (m, 2H), 5.16~5.25 (m, 1H), 3.70 (s, 2H), 3.59 (s, 3H), 3.07 (ddd, 1H, J=17.1, 13.5, 4.5 Hz), 2.83 (dm, 1H, J=17.1 Hz), 2.60 (d, 2H, J=7.6 Hz), 2.11 (dm, 1H, J=13.5 Hz), 1.80~1.96 (m, 1H).
Reaction SMILES: [F:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6][OH:7])=[CH:4][CH:3]=1.[H-].[Na+].Cl[C:13]1[N:14]=[N:15][CH:16]=[C:17]2[C:21]([CH3:22])=[C:20]([CH3:23])[N:19]([CH2:24][C@H:25]3[CH2:27][C@@H:26]3[CH3:28])[C:18]=12>O1CCCC1>[F:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6][O:7][C:13]2[N:14]=[N:15][CH:16]=[C:17]3[C:21]([CH3:22])=[C:20]([CH3:23])[N:19]([CH2:24][C@H:25]4[CH2:27][C@@H:26]4[CH3:28])[C:18]=23)=[CH:4][CH:3]=1
Reactant: OCc1ccc(F)cc1
Reactant: Cc1c(C)n(C[C@H]2C[C@@H]2C)c2c(Cl)nncc12
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: Cc1c(C)n(C[C@H]2C[C@@H]2C)c2c(OCc3ccc(F)cc3)nncc12
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 66.3 %

Procedure:
A solution of p-fluorobenzyl alcohol (1.45 g, 11.5 mmol) in tetrahydrofuran (2 ml) was added dropwise to a solution of sodium hydride (0.26 g, 10.8 mmol) in tetrahydrofuran (6 ml) and the mixture was stirred at room temperature for 30 minutes. A solution of 7-chloro-2,3-dimethyl-1-[(1S,2S)-2-methylcyclopropylmethyl]pyrrolo[2,3-d]pyridazine (2.50 g, 10.0 mmol) in tetrahydrofuran (13 ml) was added dropwise to the reaction mixture at room temperature and the mixture was heated under reflux for 3 hours. After the reaction was completed, the reaction mixture was poured into ice-water and extracted with ethyl acetate. The extract was washed with a saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate and then concentrated in vacuo. Hexane was added to the concentrated solution, and the precipitate was collected by filtration and then recrystallized from a mixture of ethyl acetate and hexane to afford the title compound (2.25 g, 66.4%) as pale brown crystals.
Reaction SMILES: [CH3:1][N:2]1[N:6]=[N:5][C:4]([C@H:7]2[CH2:12][C@@H:11]([C:13]3[O:17][NH:16][C:15](=[O:18])[CH:14]=3)[CH2:10][CH2:9][N:8]2C(OCC2C=CC=CC=2)=O)=[N:3]1.Br>>[CH3:1][N:2]1[N:6]=[N:5][C:4]([C@H:7]2[CH2:12][C@@H:11]([C:13]3[O:17][NH:16][C:15](=[O:18])[CH:14]=3)[CH2:10][CH2:9][NH:8]2)=[N:3]1
Reactant: Cn1nnc([C@H]2C[C@@H](c3cc(=O)[nH]o3)CCN2C(=O)OCc2ccccc2)n1
Agent: Br
Product: Cn1nnc([C@H]2C[C@@H](c3cc(=O)[nH]o3)CCN2)n1
Yield: 73.3 %

Procedure:
(2R,4S)-Benzyl 2-(2-methyl-2H-tetrazol-5-yl)-4-(3-oxo-2,3-dihydroisoxazol-5-yl)piperidine-1-carboxylate (301 mg, 0.78 mmol) was dissolved in hydrogen bromide (33% in AcOH) (4.1 mL, 23.49 mmol) and reacted for 1 h. The mixture was evaporated and the residue was partitioned between water and EtOAc. The aqueous phase was purified by preparative HPLC on a Kromasil C8 column (10 μm 250×50 ID mm) using a gradient of 0-15% Acetonitrile in H2O/MeCN/NH3 95/5/0.2 buffer over 20 minutes with a flow of 100 mL/min. 5-((2R,4S)-2-(2-Methyl-2H-tetrazol-5-yl)piperidin-4-yl)isoxazol-3(2H)-one (143 mg, 73%) was isolated. 1H NMR (400 MHz, cdcl3) δ 1.70 (qd, 1H), 1.85 (q, 1H), 2.04-2.12 (m, 1H), 2.43-2.50 (m, 1H), 2.91-3.02 (m, 2H), 3.33-3.41 (m, 1H), 4.18 (dd, 1H), 4.32 (s, 3H), 5.68 (s, 1H). HRMS Calcd for [C10H14N6O2+H]+: 251.1256. Found: 251.1233.
Reaction SMILES: C(OC([N:8]1[CH2:11][CH:10]([CH2:12][N:13]2[CH:17]=[CH:16][CH:15]=[N:14]2)[CH2:9]1)=O)(C)(C)C.[C:18]([OH:24])([C:20]([F:23])([F:22])[F:21])=[O:19]>C(Cl)Cl>[NH:8]1[CH2:11][CH:10]([CH2:12][N:13]2[CH:17]=[CH:16][CH:15]=[N:14]2)[CH2:9]1.[C:18]([OH:24])([C:20]([F:23])([F:22])[F:21])=[O:19]
Reactant: CC(C)(C)OC(=O)N1CC(Cn2cccn2)C1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: c1cnn(CC2CNC2)c1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To 41.5 mg (0.17 mmol) 3-pyrazol-1-ylmethyl-azetidine-1-carboxylic acid tert-butyl ester was added 2 mL of 25% TFA in DCM and the reaction was stirred at room temperature for 1 hour. The solvent was evaporated to give the desired product as a TFA salt, which was used in the next step without further purification.
Reaction SMILES: [CH3:1][C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]=1[OH:12].ClC[CH:15]([O:18]C(CCl)CCl)CCl>ClCCl>[OH:12][C:3]1[C:4]2[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=2)[C:10]([CH:15]=[O:18])=[CH:11][C:2]=1[CH3:1]
Reactant: ClCC(CCl)OC(CCl)CCl
Reactant: Cc1ccc2ccccc2c1O
Solvent: ClCCl
Product: Cc1cc(C=O)c2ccccc2c1O
Reaction time: 0.75 h

Procedure:
2-Methyl-1-naphthol (7.0 g, 44.2 mmole) and 1,1-dichloromethyl-methyl ether (7.12 g, 61.9 mmol) were dissolved in dry dichloromethane (150 ml). To the stirred solution stannic chloride (20.72 g, 79.6 mmole) was added dropwise at -58°, the mixture stirred for 45 minutes, and warmed to +10°. It was poured onto ice-water (200 ml) and extracted with ethyl acetate (2×100 ml). The extract was washed with aqueous saturated sodium chloride solution, dried and evaporated. The residue solidified on trituration under diethyl ether:n-pentane (1:10) mixture, was filtered off and chromatographed on silica gel using dichloromethane as eluant to give 4-hydroxy-3-methyl-1-napthaldehyde as a buff coloured crystalline solid, (5.3 g, 64.4%), m.p. 160°-61°.
Reaction SMILES: [Si]([O:8][CH2:9][C:10]1[CH:15]=[CH:14][N:13]2[N:16]=[CH:17][C:18]([C:19]([O:21][CH3:22])=[O:20])=[C:12]2[CH:11]=1)(C(C)(C)C)(C)C.CCCC[N+](CCCC)(CCCC)CCCC.[F-].C(OCC)(=O)C>C1COCC1>[OH:8][CH2:9][C:10]1[CH:15]=[CH:14][N:13]2[N:16]=[CH:17][C:18]([C:19]([O:21][CH3:22])=[O:20])=[C:12]2[CH:11]=1
Reactant: COC(=O)c1cnn2ccc(CO[Si](C)(C)C(C)(C)C)cc12
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: COC(=O)c1cnn2ccc(CO)cc12
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 101.3 %

Procedure:
To a solution of methyl 5-((tert-butyldimethylsilyloxy)methyl)pyrazolo[1,5-a]pyridine-3-carboxylate (Y-5) (2.9 g, 9.1 mmol) in anhydrous THF (20 mL) was added TBAF (3.5 g, 13.7 mmol). The reaction mixture was stirred at room temperature for 10 min, then treated with ethyl acetate (50 mL). The resulting mixture was washed with brine, dried over Na2SO4 and concentrated to afford the title compound (1.9 g).
Reaction SMILES: [C:1]([C:5]1[CH:20]=[CH:19][C:8]([C:9]([NH:11][C:12]2[C:13]([NH2:18])=[CH:14][CH:15]=[CH:16][CH:17]=2)=[O:10])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[N+:21]([C:24]1[CH:32]=[CH:31][C:27]([C:28](O)=[O:29])=[CH:26][CH:25]=1)([O-:23])=[O:22]>>[N+:21]([C:24]1[CH:25]=[CH:26][C:27]([C:28]([NH:18][C:13]2[C:12]([NH:11][C:9](=[O:10])[C:8]3[CH:19]=[CH:20][C:5]([C:1]([CH3:4])([CH3:2])[CH3:3])=[CH:6][CH:7]=3)=[CH:17][CH:16]=[CH:15][CH:14]=2)=[O:29])=[CH:31][CH:32]=1)([O-:23])=[O:22]
Reactant: CC(C)(C)c1ccc(C(=O)Nc2ccccc2N)cc1
Reactant: O=C(O)c1ccc([N+](=O)[O-])cc1
Product: CC(C)(C)c1ccc(C(=O)Nc2ccccc2NC(=O)c2ccc([N+](=O)[O-])cc2)cc1

Procedure:
Using the procedure described in Example 102, Part A, N1-(4-tert-butylbenzoyl)-1,2-benzenediamine (3.1 mmol) and 4-nitrobenzoic acid (3.0 mmol) yielded the title product, which was used directly in the next step without additional purification.
Reaction SMILES: FC(F)(F)S(O[C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([CH2:13][CH:14]2[CH2:18][CH2:17][CH:16]=[C:15]2[C:19]2[O:20][C:21]([C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)=[C:22]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[N:23]=2)[CH:8]=1)(=O)=O.[CH3:38][O:39][C:40]([C:42]1[CH:43]=[C:44](B(O)O)[CH:45]=[CH:46][CH:47]=1)=[O:41].C(N(CC)CC)C>CN(C=O)C.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>[C:24]1([C:22]2[N:23]=[C:19]([C:15]3[CH:14]([CH2:13][C:9]4[CH:10]=[C:11]([C:44]5[CH:45]=[CH:46][CH:47]=[C:42]([C:40]([O:39][CH3:38])=[O:41])[CH:43]=5)[CH:12]=[CH:7][CH:8]=4)[CH2:18][CH2:17][CH:16]=3)[O:20][C:21]=2[C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1
Reactant: COC(=O)c1cccc(B(O)O)c1
Reactant: O=S(=O)(Oc1cccc(CC2CCC=C2c2nc(-c3ccccc3)c(-c3ccccc3)o2)c1)C(F)(F)F
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: COC(=O)c1cccc(-c2cccc(CC3CCC=C3c3nc(-c4ccccc4)c(-c4ccccc4)o3)c2)c1
Temperature: 100 °C
Reaction time: 3.5 h
Yield: 68 %

Procedure:
A mixture of 3-{[2-(4,5-diphenyloxazol-2-yl)-2-cyclopenten-1-yl]methyl}phenyl trifluoromethanesulfonate (400 mg), 3-methoxycarbonylphenylboronic acid (177 mg), triethylamine (0.318 ml), and tetrakis(triphenylphosphine)palladium(0) (64 mg) in DMF (8 ml) was stirred at 100° C. for 3.5 hours. After cooling to room temperature, the reaction mixture was diluted with EtOAc, washed with water, 1N HCl, water, saturated sodium hydrogen carbonate, water, and brine, dried over magnesium sulfate, evaporated in vacuo. The residue was purified by silica gel column chromatography (hexane-EtOAc 10:1) to give methyl 3′-{[2-(4,5-diphenyloxazol-2-yl)-2-cyclopenten-1-yl]-methyl}biphenyl-3-carboxylate (264.6 mg) as an oil.