Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: I[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=1.[C:8]([O:14][CH2:15][CH3:16])(=[O:13])[CH2:9][CH2:10][C:11]#[CH:12]>C(N(CC)CC)C.[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>[N:3]1[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=1[C:12]#[C:11][CH2:10][CH2:9][C:8]([O:14][CH2:15][CH3:16])=[O:13]
Reactant: Ic1ccccn1
Reactant: C#CCCC(=O)OCC
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: I[Cu]I
Solvent: CCN(CC)CC
Product: CCOC(=O)CCC#Cc1ccccn1
Temperature: 25 °C
Reaction time: 20 h
Yield: 91.4 %

Procedure:
In a dry reaction tube containing in suspension copper iodide (60 mg, 0.315 mmol) and triethylamine (17.70 mL, 126 mmol), were added 2-iodopyridine (1.29 g, 6.30 mmol) and the Pd(PPh3)2Cl2 (202 mg, 0.315 mmol). A yellow suspension is obtained and after a few minutes of stirring at room temperature, was added ethyl pent-4-ynoate (790 mg, 6.30 mmol) in solution in 2 mL of triethylamine. Immediately the color of the reaction turns to black. The mixture was stirred at room temperature for 30 min and then at 80° C. for 20 h. Triethylamine was concentrated under reduce pressure and the residue was dissolved in DCM. The organic layer was washed with saturated NH4Cl, water and brine. The solvent was removed under reduced pressure and the crude product was purified by flash chromatography system (prepacked silicagel column 25 g, DCM/MeOH: 98/2 as eluent) to afford 1.17 g of ethyl 5-(pyridin-2-yl)pent-4-ynoate (Yield: 78%) as brownish oil.
Reaction SMILES: [CH:1]1([C:4]2[O:8][N:7]=[C:6]([C:9]3[C:14]([Cl:15])=[CH:13][CH:12]=[CH:11][C:10]=3[Cl:16])[C:5]=2[CH2:17][O:18][CH:19]2[CH2:25][CH2:24][CH2:23][NH:22][CH2:21][CH2:20]2)[CH2:3][CH2:2]1.I[C:27]1[CH:37]=[CH:36][C:30]([C:31]([O:33][CH2:34][CH3:35])=[O:32])=[CH:29][CH:28]=1.N1CCC[C@H]1C(O)=O.C(=O)([O-])[O-].[K+].[K+]>CS(C)=O.[Cu]I>[CH2:34]([O:33][C:31](=[O:32])[C:30]1[CH:36]=[CH:37][C:27]([N:22]2[CH2:23][CH2:24][CH2:25][CH:19]([O:18][CH2:17][C:5]3[C:6]([C:9]4[C:10]([Cl:16])=[CH:11][CH:12]=[CH:13][C:14]=4[Cl:15])=[N:7][O:8][C:4]=3[CH:1]3[CH2:2][CH2:3]3)[CH2:20][CH2:21]2)=[CH:28][CH:29]=1)[CH3:35]
Reactant: CCOC(=O)c1ccc(I)cc1
Reactant: Clc1cccc(Cl)c1-c1noc(C2CC2)c1COC1CCCNCC1
Agent: [Cu]I
Agent: O=C(O)[C@@H]1CCCN1
Agent: O=C([O-])[O-]
Solvent: CS(C)=O
Product: CCOC(=O)c1ccc(N2CCCC(OCc3c(-c4c(Cl)cccc4Cl)noc3C3CC3)CC2)cc1
Temperature: 100 °C
Reaction time: 14 h

Procedure:
To a solution of 16 g (42 mmol) of 4-[5-cyclopropyl-3-(2,6-dichloro-phenyl)-isoxazol-4-ylmethoxy]-azepane in 40 mL of dimethyl sulfoxide, is added ethyl 4-iodobenzoate (21 g, 67 mmol), proline (2 g, 16.7 mmol) and copper(I) iodide (3.2 g, 16.7 mmol.). The resulting mixture is degassed with nitrogen followed by addition of potassium carbonate (11.6 g, 84 mmol). The reaction mixture is stirred at 100° C. for 14 hours. The mixture is cooled to room temperature and quenched with water. The mixture is extracted with EtOAc, the organics are dried over MgSO4, filtered and concentrated to afford a crude which is purified on silica gel column chromatography (Eluting with Hexanes/EtOAc 8:2), to obtained 17 g of the title racemic compound.
Reaction SMILES: [Mg].[F:2][C:3]([F:13])([F:12])[O:4][C:5]1[CH:10]=[CH:9][C:8](Br)=[CH:7][CH:6]=1.[Br-].[CH3:15][O:16][C:17]1[CH:22]=[CH:21][C:20]([CH2:23][N:24]2[CH2:29][CH2:28][CH:27]([C:30]([O:32]CC)=O)[CH2:26][CH2:25]2)=[CH:19][CH:18]=1.[Cl-].[NH4+]>C(OCC)C>[CH3:15][O:16][C:17]1[CH:18]=[CH:19][C:20]([CH2:23][N:24]2[CH2:25][CH2:26][CH:27]([C:30]([C:8]3[CH:7]=[CH:6][C:5]([O:4][C:3]([F:2])([F:12])[F:13])=[CH:10][CH:9]=3)([C:8]3[CH:9]=[CH:10][C:5]([O:4][C:3]([F:13])([F:12])[F:2])=[CH:6][CH:7]=3)[OH:32])[CH2:28][CH2:29]2)=[CH:21][CH:22]=1
Reactant: FC(F)(F)Oc1ccc(Br)cc1
Reactant: CCOC(=O)C1CCN(Cc2ccc(OC)cc2)CC1
Agent: [Br-]
Agent: [Cl-]
Agent: [Mg]
Solvent: CCOCC
Product: COc1ccc(CN2CCC(C(O)(c3ccc(OC(F)(F)F)cc3)c3ccc(OC(F)(F)F)cc3)CC2)cc1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 67 %

Procedure:
To a stirred mixture of 1.1 grams (0.045 gram-atom) of magnesium turnings in 30 mL of diethyl ether was added dropwise 15 mL of a solution of 11.0 grams (0.045 mole) of 4-trifluoromethoxyphenyl bromide in 30 mL of diethyl ether. Once the reaction had started, the remaining 15 mL of the bromide solution was added portionwise during a 45 minute period. When the reaction subsided, a solution of 5.0 grams (0.018 mole) of ethyl N-(4-methoxyphenylmethyl)piperidin-4-ylcarboxylate in 20 mL of diethyl ether was added dropwise during a five minute period. Upon completion of the addition, the reaction mixture was heated to reflux, where it stirred for about 30 minutes. The reaction mixture was then allowed to cool to ambient temperature, where it stirred for about 18 hours. After this time an aqueous solution saturated with ammonium chloride was added dropwise to quench the reaction. The mixture was then partitioned between water and diethyl ether. The diethyl ether layer was separated and washed first with a solution saturated with sodium chloride and then with water. The organic layer was dried with magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure to a residual oil. The oil was subjected to column chromatography on silica gel, with 10% diethyl ether in hexane, 100% diethyl ether, and 10% methanol in diethyl ether as eluants. The product-containing fractions were combined and concentrated under reduced pressure, yielding 6.7 grams of N-(4-methoxyphenylmethyl)-4-[bis(4-trifluoromethoxyphenyl)hydroxymethyl]piperidine, mp 86-96° C. The NMR spectrum was consistent with the proposed structure.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:34])[NH:4][CH:5]([C:9]([N:11]1[CH:15]([C:16]2[NH:17][CH:18]=[C:19]([C:21]3[CH:26]=[CH:25][C:24](Br)=[CH:23][CH:22]=3)[N:20]=2)[CH2:14][N:13]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[CH2:12]1)=[O:10])[CH:6]([CH3:8])[CH3:7].[CH3:35][O:36][C:37](=[O:70])[NH:38][CH:39]([C:43]([N:45]1[CH2:49][CH2:48][CH2:47][CH:46]1[C:50]1[NH:51][CH:52]=[C:53]([C:55]2[CH:60]=[CH:59][C:58](B3OC(C)(C)C(C)(C)O3)=[CH:57][CH:56]=2)[N:54]=1)=[O:44])[CH:40]([CH3:42])[CH3:41].C(=O)([O-])[O-].[K+].[K+].COCCOC>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>[CH3:1][O:2][C:3](=[O:34])[NH:4][CH:5]([C:9]([N:11]1[CH:15]([C:16]2[NH:20][C:19]([C:21]3[CH:26]=[CH:25][C:24]([C:58]4[CH:59]=[CH:60][C:55]([C:53]5[NH:54][C:50]([CH:46]6[CH2:47][CH2:48][CH2:49][N:45]6[C:43](=[O:44])[CH:39]([NH:38][C:37]([O:36][CH3:35])=[O:70])[CH:40]([CH3:42])[CH3:41])=[N:51][CH:52]=5)=[CH:56][CH:57]=4)=[CH:23][CH:22]=3)=[CH:18][N:17]=2)[CH2:14][N:13]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[CH2:12]1)=[O:10])[CH:6]([CH3:8])[CH3:7]
Reactant: COC(=O)NC(C(=O)N1CN(c2ccccc2)CC1c1nc(-c2ccc(Br)cc2)c[nH]1)C(C)C
Reactant: COC(=O)NC(C(=O)N1CCCC1c1nc(-c2ccc(B3OC(C)(C)C(C)(C)O3)cc2)c[nH]1)C(C)C
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: [K+]
Solvent: COCCOC
Solvent: O
Product: COC(=O)NC(C(=O)N1CCCC1c1ncc(-c2ccc(-c3ccc(-c4cnc(C5CN(c6ccccc6)CN5C(=O)C(NC(=O)OC)C(C)C)[nH]4)cc3)cc2)[nH]1)C(C)C
Temperature: 120 °C
Yield: 8.7 %

Procedure:
{1-[4-(4-Bromo-phenyl)-1′-phenyl-1′,2′,4′,5′-tetrahydro-1H-[2,4′]biimidazolyl-3′-carbonyl]-2-methyl-propyl}-carbamic acid methyl ester (40 mg, 0.076 mmol) was combined with [2-Methyl-1-(2-{4-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-1H-imidazol-2-yl}-pyrrolidine-1-carbonyl)-propyl]-carbamic acid methyl ester (37.6 mg, 0.076 mmol) under an argon atmosphere. Potassium carbonate (20.9 mg, 0.152 mmol) and Pd(PPh3)4 (8.7 mg, 0.0076 mmol) were added, followed by DME (1.8 mL) and water (0.3 mL). The mixture was heated under microwave conditions for 20 minutes at 120° C. All volatiles were removed in vacuo and the crude material was dissolved in DMF and purified via RP-HPLC (eluent: water/MeCN w 0.1% TFA) to yield the product {1-[5-(4′-{2-[1-(2-Methoxycarbonylamino-3-methyl-butyryl)-pyrrolidin-2-yl]-3H-imidazol-4-yl}-biphenyl-4-yl)-1′-phenyl-1′,2′,4′,5′-tetrahydro-1H-[2,4′]biimidazolyl-3′-carbonyl]-2-methyl-propyl}-carbamic acid methyl ester (5.4 mg): LCMS-ESI+: calc'd for C45H53N9O6: 815.9 (M+). Found: 816.5 (M+H+); 1H-NMR: 300 MHz, (MeOH-d4) δ: 7.89-7.86 (m, 10H), 7.35 (m, 2H), 7.18 (m, 1H), 6.94 (m, 2H), 5.67 (m, 1H), 5.37 (m, 1H), 5.25 (m, 1H), 5.12 (m, 1H), 4.31-4.08 (m, 3H), 4.01-3.79 (m, 3H), 3.67 (s, 3H), 3.66 (s, 3H), 2.58 (m, 1H), 2.29-1.99 (m, 5H), 0.99-0.89 (m, 12H).
Reaction SMILES: Br[CH:2]([CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([Br:13])[CH:8]=1)[C:3](=O)[CH3:4].[NH2:14][C:15](=[S:21])[C:16]([O:18][CH2:19][CH3:20])=[O:17]>CCO>[Br:13][C:9]1[CH:8]=[C:7]([CH:12]=[CH:11][CH:10]=1)[CH2:6][C:2]1[S:21][C:15]([C:16]([O:18][CH2:19][CH3:20])=[O:17])=[N:14][C:3]=1[CH3:4]
Reactant: CC(=O)C(Br)Cc1cccc(Br)c1
Reactant: CCOC(=O)C(N)=S
Solvent: CCO
Product: CCOC(=O)c1nc(C)c(Cc2cccc(Br)c2)s1
Yield: 42 %

Procedure:
A mixture of 3-bromo-4-(3-bromophenyl)butan-2-one (1.8 g, 5.9 mmol) and ethyl 2-amino-2-thioxoacetate (745 mg, 5.6 mmol) in EtOH (20 mL) was refluxed overnight. The solvent was removed and the residue was purified by silica gel column chromatography (EtOAc:Petroleum ether=1:5) to afford ethyl 5-(3-bromobenzyl)-4-methylthiazole-2-carboxylate as a light yellow solid (800 mg, 42.1%). MS (ES+) C14H14BrNO2S requires: 339, 341 found: 340[M+H]+, 342 [M+2+H]+(1:1).
Reaction SMILES: Br[C:2]1[N:7]=[N:6][C:5]([NH2:8])=[N:4][C:3]=1[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.CC1(C)C(C)(C)OB([C:23]2[CH:24]=[C:25]([NH:29][S:30]([CH3:33])(=[O:32])=[O:31])[CH:26]=[CH:27][CH:28]=2)O1>>[NH2:8][C:5]1[N:6]=[N:7][C:2]([C:23]2[CH:24]=[C:25]([NH:29][S:30]([CH3:33])(=[O:31])=[O:32])[CH:26]=[CH:27][CH:28]=2)=[C:3]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[N:4]=1
Reactant: Nc1nnc(Br)c(-c2ccccc2)n1
Reactant: CC1(C)OB(c2cccc(NS(C)(=O)=O)c2)OC1(C)C
Product: CS(=O)(=O)Nc1cccc(-c2nnc(N)nc2-c2ccccc2)c1
Yield: 41.1 %

Procedure:
N-[3-(3-Amino-5-phenyl-1,2,4-triazin-6-yl)phenyl]methanesulfonamide (42 mg, 41%) was prepared from 6-bromo-5-phenyl-1,2,4-triazin-3-amine (75 mg, 0.299 mmol) and N-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)methanesulfonamide (102 mg, 0.344 mmol) according to the general procedure of Example 1.
Reaction SMILES: [C:1]([Si:5]([CH3:11])([CH3:10])[O:6][CH2:7][C:8]#[CH:9])([CH3:4])([CH3:3])[CH3:2].[Li+].CCC[CH2-].CON(C)[C:20](=[O:27])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.Cl>C1COCC1>[Si:5]([O:6][CH2:7][C:8]#[C:9][C:20]([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)=[O:27])([C:1]([CH3:3])([CH3:4])[CH3:2])([CH3:10])[CH3:11]
Reactant: C#CCO[Si](C)(C)C(C)(C)C
Reactant: CON(C)C(=O)c1ccccc1
Agent: Cl
Agent: [CH2-]CCC
Agent: [Li+]
Solvent: C1CCOC1
Product: CC(C)(C)[Si](C)(C)OCC#CC(=O)c1ccccc1
Temperature: -30 °C
Reaction time: 0.5 h
Yield: 99.1 %

Procedure:
To a solution of tert-Butyldimethyl(2-propynyloxy)silane 166 (7.99 mL, 39.4 mmol) in 80 mL of THF at −78° C. was added dropwise N-BUTYLLITHIUM (15.76 mL, 39.4 mmol). The resulting mixture was then warmed up slowly to −30° C. and stirred for 30 min. A solution of N-Methoxy-N-methylbenzamide 165 (5 mL, 32.8 mmol) in 5 mL of TIE was added dropwise and the solution was warmed slowly to room temperature and stirred 2 hours. Aqueous 5% HCl was added to quench the reaction and the product was extracted twice with ethyl acetate. The combined organic layers were washed with a saturated solution of bicarbonate and brine, dried over sodium sulfate and filtered. The solvents were removed in vacuo and the crude material was purified by ISCO (120 g column, 0-30% ethyl acetate in hexanes) to yield 99% of a yellow oil 167 (8.924 g)
Reaction SMILES: [C:1]([O:4][CH2:5][CH:6]([CH2:10][O:11][C:12](=[O:14])[CH3:13])[CH2:7][CH2:8]O)(=[O:3])[CH3:2].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(Br)(Br)(Br)[Br:35]>CN(C)C=O>[C:1]([O:4][CH2:5][CH:6]([CH2:10][O:11][C:12](=[O:14])[CH3:13])[CH2:7][CH2:8][Br:35])(=[O:3])[CH3:2]
Reactant: CC(=O)OCC(CCO)COC(C)=O
Reactant: BrC(Br)(Br)Br
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CN(C)C=O
Product: CC(=O)OCC(CCBr)COC(C)=O
Yield: 993.2 %

Procedure:
A mixture of 2-acetoxymethyl-4-hydroxy-but-1-yl acetate 10 g, 49 mmol), triphenylphosphine (19.25 g, 73 mmol) and carbon tetrabromide (24.4 g, 73 mmol) was stirred for 18 hours at 4° C. in dimethylformamide (150 ml). The solvent was then evaporated, and the residue purified by column chromatography on silica gel, eluting with ether-light petroleum 2:3 to afford 2-acetoxymethyl-4-bromobut-1-yl acetate as a pale oil (130 g, 99%). δH (CDCl3) 1.73-2.56 (3H, m, CHCH2CH2), 2.04 (6H, s, 2×OCOCH3), 3.44 (2H, t, CH2Br), 4.04 (4H, d, 2×CH2OCOCH3).
Reaction SMILES: [F:1][C:2]1[CH:3]=[CH:4][C:5]([O:14][CH3:15])=[C:6]([CH:8]2[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]2)[CH:7]=1.Cl[CH2:17][CH2:18][N:19]1[C:28](=[O:29])[CH2:27][C:22]2([CH2:26][CH2:25][CH2:24][CH2:23]2)[CH2:21][C:20]1=[O:30]>>[F:1][C:2]1[CH:3]=[CH:4][C:5]([O:14][CH3:15])=[C:6]([CH:8]2[CH2:13][CH2:12][N:11]([CH2:17][CH2:18][N:19]3[C:20](=[O:30])[CH2:21][C:22]4([CH2:26][CH2:25][CH2:24][CH2:23]4)[CH2:27][C:28]3=[O:29])[CH2:10][CH2:9]2)[CH:7]=1
Reactant: COc1ccc(F)cc1C1CCNCC1
Reactant: O=C1CC2(CCCC2)CC(=O)N1CCCl
Product: COc1ccc(F)cc1C1CCN(CCN2C(=O)CC3(CCCC3)CC2=O)CC1
Temperature: 165 °C
Reaction time: 1 h
Yield: 7.5 %

Procedure:
A mixture of 4-(5-fluoro-2-methoxyphenyl)piperidine (20 mg, 0.096 mmol) and 8-(2-chloroethyl)-8-azaspiro[4.5]decane-7,9-dione(20 mg, 0.087 mmol) was heated with stirring at 165° C. for 1 hour. The residue was purified by preparative HPLC (see Example 8 for conditions), giving (after removal of the solvent) the title compound as a pale yellow oil (2.6 mg, 0.0065 mmol, 7%): ESI-MS m/z 403 (MH+).
Reaction SMILES: C([O:3][C:4]([C:6]1[CH:38]=[CH:37][C:9]2[N:10]([CH:31]3[CH2:36][CH2:35][CH2:34][CH2:33][CH2:32]3)[C:11]([C:13]3[CH:14]=[C:15]4[C:20](=[CH:21][CH:22]=3)[N:19]=[C:18]([C:23](=[O:30])NC(C(=O)N)C)[CH:17]=[CH:16]4)=[N:12][C:8]=2[CH:7]=1)=[O:5])C.[NH2:39][C@H:40]([C:44]([NH2:46])=[O:45])[CH:41]([CH3:43])[CH3:42].C(C(NC(C1C=CC2C(=CC=C(C3N(C4CCCCC4)C4C=CC(C(O)=O)=CC=4N=3)C=2)N=1)=O)C)(=O)N>>[C:44]([CH:40]([NH:39][C:23]([C:18]1[CH:17]=[CH:16][C:15]2[C:20](=[CH:21][CH:22]=[C:13]([C:11]3[N:10]([CH:31]4[CH2:36][CH2:35][CH2:34][CH2:33][CH2:32]4)[C:9]4[CH:37]=[CH:38][C:6]([C:4]([OH:5])=[O:3])=[CH:7][C:8]=4[N:12]=3)[CH:14]=2)[N:19]=1)=[O:30])[CH:41]([CH3:43])[CH3:42])(=[O:45])[NH2:46]
Reactant: CCOC(=O)c1ccc2c(c1)nc(-c1ccc3nc(C(=O)NC(C)C(N)=O)ccc3c1)n2C1CCCCC1
Reactant: CC(C)[C@H](N)C(N)=O
Agent: CC(NC(=O)c1ccc2cc(-c3nc4cc(C(=O)O)ccc4n3C3CCCCC3)ccc2n1)C(N)=O
Product: CC(C)C(NC(=O)c1ccc2cc(-c3nc4cc(C(=O)O)ccc4n3C3CCCCC3)ccc2n1)C(N)=O

Procedure:
The title compound (5 mg yield) was prepared as described for Compound 497a using L-valinamide in place of L-alaninamide, and hydrolyzed as described for Compound 497.
Reaction SMILES: C([N-]C(C)C)(C)C.[Li+].O1CCCC1.CCCCCCC.C(C1C=CC=CC=1)C.[Br:29][C:30]1[CH:35]=[C:34]([Si:36]([CH2:41][CH3:42])([CH2:39][CH3:40])[CH2:37][CH3:38])[C:33]([F:43])=[CH:32][N:31]=1.[F:44][CH:45]([F:51])[C:46](OCC)=[O:47]>C1COCC1>[Br:29][C:30]1[N:31]=[C:32]([C:46](=[O:47])[CH:45]([F:51])[F:44])[C:33]([F:43])=[C:34]([Si:36]([CH2:41][CH3:42])([CH2:39][CH3:40])[CH2:37][CH3:38])[CH:35]=1
Reactant: CC[Si](CC)(CC)c1cc(Br)ncc1F
Reactant: CCOC(=O)C(F)F
Agent: CC(C)[N-]C(C)C
Agent: [Li+]
Solvent: C1CCOC1
Solvent: CCCCCCC
Solvent: CCc1ccccc1
Product: CC[Si](CC)(CC)c1cc(Br)nc(C(=O)C(F)F)c1F
Temperature: -78 °C
Reaction time: 3 h
Yield: 22.1 %

Procedure:
To 3-neck 250-mL round bottomed flask was added THF (15 mL). The mixture was cooled to −78° C. and lithium diisopropylamide, 2.0 m solution in tetrahydrofuran/heptane/ethylbenzene (5.73 ml, 11.45 mmol) was added over 1 min. To the solution was then added 2-bromo-5-fluoro-4-(triethylsilyl)pyridine (2.89 g, 9.96 mmol) in 16 mL THF over 5 min. The temperature was not allowed to go above −70° C. during the addition. After 3 h at −78° C., ethyl difluoroacetate (1.099 ml, 10.45 mmol) was added dropwise and the resulting reaction mixture was stirred at −78° C. for 2 h. The cold bath was removed and the solution was allowed to warm to −40° C. At that point the solution was quenched with a solution of saturated NH4Cl. The solution was extracted with EtOAc (2×100 mL) and the combined extracts were washed with brine, dried (Na2SO4) and concentrated. Purification by silica gel chromatography (0.0 to 20% EtOAc/hexane, 120 g Grace column) afforded 1-(6-bromo-3-fluoro-4-(triethylsilyl)pyridin-2-yl)-2,2-difluoroethanone (0.81 g, 2.2 mmol, 22.1% yield) as a dark orange oil. MS m/z=386, 388 M+18, Calculated for C13H17BrF3NOSi: 368.26.
Reaction SMILES: CSC.C([O:11][C@@H:12]1[C@H:17]([O:18]CC2C=CC=CC=2)[C@H:16]([O:26]CC2C=CC=CC=2)[CH:15]([C:34]2[C:43]3[C:38](=[CH:39][CH:40]=[CH:41][CH:42]=3)[CH:37]=[C:36]([CH2:44][C:45]3[S:49][C:48]4[CH:50]=[CH:51][C:52]([O:54][CH3:55])=[CH:53][C:47]=4[CH:46]=3)[CH:35]=2)[O:14][C@@H:13]1[CH2:56][O:57]CC1C=CC=CC=1)C1C=CC=CC=1.C(=O)([O-])O.[Na+]>C(Cl)Cl>[OH:57][CH2:56][C@@H:13]1[C@@H:12]([OH:11])[C@H:17]([OH:18])[C@@H:16]([OH:26])[C@H:15]([C:34]2[C:43]3[C:38](=[CH:39][CH:40]=[CH:41][CH:42]=3)[CH:37]=[C:36]([CH2:44][C:45]3[S:49][C:48]4[CH:50]=[CH:51][C:52]([O:54][CH3:55])=[CH:53][C:47]=4[CH:46]=3)[CH:35]=2)[O:14]1
Reactant: COc1ccc2sc(Cc3cc(C4O[C@H](COCc5ccccc5)[C@H](OCc5ccccc5)[C@H](OCc5ccccc5)[C@@H]4OCc4ccccc4)c4ccccc4c3)cc2c1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Solvent: CSC
Product: COc1ccc2sc(Cc3cc([C@@H]4O[C@H](CO)[C@@H](O)[C@H](O)[C@H]4O)c4ccccc4c3)cc2c1
Temperature: 25 °C
Reaction time: 72 h
Yield: 69.5 %

Procedure:
Under a nitrogen atmosphere, dimethylsulfide (0.66 ml) and a boron trifluoride-diethyl ether complex (0.33 ml, 2.62 mmol) were added to a solution of (2R,3S,4R,5R)-3,4,5-trisbenzyloxy-2-benzyloxymethyl-6-[3-(5-methoxybenzo-[b]thiophen-2-ylmethyl)-naphthalen-1-yl]tetrahydropyran (217 ml, 0.262 mmol) in methylene chloride (4 ml) under cooling with ice. The reaction mixture was stirred at room temperature for three days, and then a saturated sodium hydrogen carbonate aqueous solution was added under cooling with ice and the mixture was extracted with methylene chloride. The organic layer was washed with a saturated sodium chloride aqueous solution and dried with sodium sulfate, and then the solvent was distilled under reduced pressure and the obtained residue was purified by silica gel column chromatography [developing solution=methylene chloride:methanol (30:1)] to obtain the title compound (85 mg, 65%).
Reaction SMILES: [OH:1][CH2:2][C:3]1[O:4][CH:5]=[C:6]([O:10][CH2:11][C:12]2[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][CH:13]=2)[C:7](=[O:9])[CH:8]=1.C(N(CC)CC)C.S(=O)(=O)([OH:29])N.Cl([O-])=O.[Na+]>C(Cl)(Cl)Cl.CC(C)=O.O.CS(C)=O>[CH3:19][O:18][C:15]1[CH:14]=[CH:13][C:12]([CH2:11][O:10][C:6]2[C:7](=[O:9])[CH:8]=[C:3]([C:2]([OH:29])=[O:1])[O:4][CH:5]=2)=[CH:17][CH:16]=1
Reactant: NS(=O)(=O)O
Reactant: COc1ccc(COc2coc(CO)cc2=O)cc1
Agent: [Na+]
Agent: [O-][Cl+][O-]
Solvent: CS(C)=O
Solvent: CCN(CC)CC
Solvent: CC(C)=O
Product: COc1ccc(COc2coc(C(=O)O)cc2=O)cc1
Temperature: 0 °C
Reaction time: 20 h
Yield: 54.2 %

Procedure:
To a solution of 2-(hydroxymethyl)-5-((4-methoxybenzyl)oxy)-4H-pyran-4-one (2.57 g, 9.80 mmol) in chloroform (45 ml) was added dimethyl sulfoxide (12 ml) and triethylamine (8.20 ml, 58.8 mmol). The mixture was cooled to 0° C., and sulfur trioxide, pyridine salt (3.96 ml, 49.0 mmol) was added. The mixture was allowed to warm to room temperature and stirred for 20 h. The resulting precipitate was filtered and washed with water. The filtrate was washed with water and the phases were separated. The organic layer was concentrated and combined with the precipitate. Water (20.0 ml), acetone (20.0 ml) and sulfamic acid (1.431 g, 14.74 mmol) were added, followed by sodium chlorite (1.332 g, 14.73 mmol) and the mixture was allowed to stir at room temperature for 70 h. The resulting precipitate was filtered, washed with water and acetone, and dried to give, 5-((4-methoxybenzyl)oxy)-4-oxo-4H-pyran-2-carboxylic acid (1.466 g, 5.31 mmol, 54.2% yield) as white solid. LCMS: (M+Na)+: 299.0.
Reaction SMILES: [CH3:1][CH:2]1[C:8]2[CH:9]=[CH:10][C:11]([N+:13]([O-])=O)=[CH:12][C:7]=2[CH2:6][CH2:5][N:4]([CH3:16])[CH2:3]1.CC1C2C=C([N+]([O-])=O)C=CC=2CCN(C)C1>[Pd].CO>[CH3:1][CH:2]1[C:8]2[CH:9]=[CH:10][C:11]([NH2:13])=[CH:12][C:7]=2[CH2:6][CH2:5][N:4]([CH3:16])[CH2:3]1
Reactant: CC1CN(C)CCc2cc([N+](=O)[O-])ccc21
Agent: [Pd]
Agent: CC1CN(C)CCc2ccc([N+](=O)[O-])cc21
Solvent: CO
Product: CC1CN(C)CCc2cc(N)ccc21

Procedure:
1.4 g (6.3 mmol) of a mixture of 1,3-dimethyl-7-nitro-2,3,4,5-tetrahydro-1H-benzo[d]azepine and 1,3-dimethyl-8-nitro-2,3,4,5-tetrahydro-1H-benzo[d]azepine, 20 ml of methanol and 0.20 g 10% palladium on charcoal is hydrogenated for 5.5 h under a hydrogen atmosphere (50 psi). It is filtered, concentrated and the mixture is purified by chromatography with silica gel (eluant: dichloromethane:95% ethanol/5% ammonia 99:1 to 80:20). 0.45 g of 1,3-dimethyl-7-amino-2,3,4,5-tetrahydro-1H-benzo[d]azepine are obtained
Reaction SMILES: [O:1]=[Sb:2]([O:4][Sb:5](=[O:7])=[O:6])=[O:3].[N+]([O-])([O-])=[O:9].[In+3:12].[N+]([O-])([O-])=[O:14].[N+]([O-])([O-])=O.N>O>[OH-:1].[In+3:12].[OH-:9].[OH-:14].[O:1]=[Sb:2]([O:4][Sb:5](=[O:7])=[O:6])=[O:3]
Reactant: O=[N+]([O-])[O-]
Agent: N
Agent: O=[Sb](=O)O[Sb](=O)=O
Agent: [In+3]
Solvent: O
Product: [OH-]
Temperature: 25 °C

Procedure:
334 g of water was added to 600 g of the diantimony pentoxide sol (specific gravity: 1.198, Sb2O5 concentration: 18.4 wt %) prepared in Preparation Example 1 for dilution. Then, an aqueous indium nitrate solution having 230.1 g of indium nitrate (In(NO3)3.3H2O, In2O3 content: 39.1 wt %, guaranteed reagent, manufactured by Mitsuwa Kagaku Yakuhin K. K.) dissolved in 280 g of water, was added thereto with stirring at room temperature. Then, the mixture was heated to 90° C. and maintained at that temperature for 10 hours. Then, 219.0 g of 28% aqueous ammonia (guaranteed reagent) was added to adjust the pH of the slurry to 7.06, to obtain a mixed slurry of indium hydroxide and diantimony pentoxide. This slurry had an In2O3 concentration of 6.23 wt %, a Sb2O5 concentration of 7.64 wt % and an In2O3 /Sb2O5 molar ratio of 0.95. This slurry was subjected to filtration under suction and then washed with water using 9000 g of pure water, to obtain a wet cake. This wet cake was evaporated to dryness at 150° C. by a hot air drier to obtain 234.6 g of a dried product. This dried product was pulverized by a mortar to obtain a powder. The powder was put into an aluminum crucible and calcined in an electric furnace at 720° C. for 4 hours and further calcined at 740° C. for 10 hours to obtain 191.7 g of a powder. This powder was bluish gray and as a result of the X-ray diffraction, found to correspond to the diffraction peaks of indium antimonate (InSbO4) of ASTM. This powder was pulverized by a Jet.O.Mizer to obtain a fine powder having an average particle diameter of 0.9 μm as measured by a centrifugal sedimentation particle size distribution measurement. Further, this powder had a specific surface area of 33.5 m2 /g as measured by a BET method and a particle diameter of 26.0 nm as calculated from the specific surface area. Further, from the transmission electron microscopic observation, the powder was found to be a colloidal particle of substantially spherical shape with a primary particle diameter of from 15 to 50 nm. This powder was press-molded under a pressure of 100 kg/cm2, and the press-molded product showed an electro-conductivity with a specific resistance of 8.0 Ωcm.