Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([OH:24])(=[O:23])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH3:22].O.[N+]([O-])([O-])=O.[Ag+:30]>C1C=CC=CC=1>[C:1]([O-:24])(=[O:23])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH3:22].[Ag+:30]
Reactant: CCCCCCCCCCCCCCCCCCCCCC(=O)O
Agent: [Ag+]
Agent: O=[N+]([O-])[O-]
Solvent: O
Solvent: c1ccccc1
Product: CCCCCCCCCCCCCCCCCCCCCC(=O)[O-]

Procedure:
3.4 g of behenic acid was dissolved in 100 ml of benzene at 60° C., and the temperature of this solution was adjusted to 60° C. 100 ml of water was added to the above solution with stirring to form an emulsion. 100 ml of an aqueous solution of silver ammonium complex, which was prepared by adding aqueous to about 80 ml of an aqueous solution containing 1.7 g of silver nitrate, and then adding water to the aqueous solution to make the total volume one liter, was then added to the above emulsion. Crystallites of silver behenate were obtained.
Reaction SMILES: [H-].[Al+3].[Li+].[H-].[H-].[H-].[Cl:7][C:8]1[CH:13]=[CH:12][C:11]([NH:14][CH:15]2[CH2:19][CH2:18][CH2:17][CH:16]2[C:20](OCC)=[O:21])=[CH:10][CH:9]=1.C(OCC)(=O)C.[OH-].[Na+]>C1COCC1>[Cl:7][C:8]1[CH:9]=[CH:10][C:11]([NH:14][CH:15]2[CH2:19][CH2:18][CH2:17][CH:16]2[CH2:20][OH:21])=[CH:12][CH:13]=1
Reactant: CCOC(=O)C1CCCC1Nc1ccc(Cl)cc1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: OCC1CCCC1Nc1ccc(Cl)cc1
Temperature: 25 °C
Reaction time: 14 h

Procedure:
Lithium aluminum hydride (1.60 g) was suspended in THF (70 ml) under ice cooling and thereto a solution of ethyl 2-(4-chlorophenylamino)-1-cyclopentanecarboxylate in THF (about 16 ml) was added gradually, and the mixture was stirred at room temperature for 14 hours. Ethyl acetate and a small amount of 1N aqueous sodium hydroxide solution were added to the reaction mixture to decompose the excess reducing agent. The mixture was filtered and concentrated under reduced pressure to give the oily desired product (3.24 g).
Reaction SMILES: Br[CH:2]1[C:11]2[C:6](=[CH:7][C:8]([O:13][CH3:14])=[C:9]([OH:12])[CH:10]=2)[C:4](=O)[O:3]1.OC1C=C2C(=CC=1OC)C(=O)OC2.BrN1C(=O)CCC1=O.O.[NH2:37][NH2:38]>C(Cl)(Cl)Cl.C(O)(=O)C>[OH:12][C:9]1[CH:10]=[C:11]2[C:6](=[CH:7][C:8]=1[O:13][CH3:14])[C:4](=[O:3])[NH:38][N:37]=[CH:2]2
Reactant: NN
Reactant: COc1cc2c(cc1O)C(Br)OC2=O
Agent: COc1cc2c(cc1O)COC2=O
Agent: O=C1CCC(=O)N1Br
Solvent: O
Solvent: CC(=O)O
Solvent: ClC(Cl)Cl
Product: COc1cc2c(=O)[nH]ncc2cc1O

Procedure:
3-Bromo-5-hydroxy-6-methoxyphthalide may be prepared by treating 5-hydroxy-6-methoxyphthalide with N-bromosuccinimide in chloroform. Treatment of 3-bromo-5-hydroxy-6-methoxyphthalide with hydrazine hydrate in boiling aqueous acetic acid gives 6-hydroxy-7-methoxy-1(2H)-phthalazinone, which may be converted into the sulphate of the title compound by the general procedure of Example 1.
Reaction SMILES: [CH:1](=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.NC1C(C)=CC=CN=1.N[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.C(O)(=O)C1C=CC=CC=1.C=CCCCC.C1(C)C=CC=CC=1.[PH3:46]>>[C:1]([C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)(=[O:8])[CH2:22][CH2:23][CH2:18][CH2:19][CH2:20][CH3:21].[PH3:46]
Reactant: Nc1ccccc1
Reactant: O=Cc1ccccc1
Agent: Cc1cccnc1N
Agent: O=C(O)c1ccccc1
Agent: P
Solvent: C=CCCCC
Solvent: Cc1ccccc1
Product: CCCCCCC(=O)c1ccccc1
Temperature: 130 °C
Reaction time: 0.04 h

Procedure:
Under the same reaction procedure and conditions as in Example 1 (benzaldehyde 0.5 mmol, 2-amino-3-picoline 0.1 mmol, aniline 0.3 mmol, bezoic acid 0.03 mmol, 1-hexene 2.5 mmol, toluene 0.87 mmol), the mixture in a 500 ml pressure reactor was stirred at normal temperature for 2-3 minutes and then [Rh(C8H14)2Cl]2 0.01 mmol and various phosphine ligands 0.025 mmol as shown in the following table 7 were introduced into each reactor. While the reactor was stopped with a stopper, the reactants were heated at 130° C. for 1 hour with stirring. After completion of the reaction, gas chromatography was conducted to determine the yields of heptanophenone, products from various phosphine ligands. The results are given in Table 7, below.
Reaction SMILES: [CH3:1][O:2][C:3]([CH2:5][CH2:6][CH:7]=[CH:8][C:9]1[CH2:16][C@H:15]2[C@H:11]([CH2:12][C@@H:13]([O:27][CH:28]3[CH2:33][CH2:32][CH2:31][CH2:30][O:29]3)[C@H:14]2/[CH:17]=[CH:18]/[C:19](=[O:26])[CH:20]([F:25])[CH2:21][CH2:22][CH2:23][CH3:24])[CH:10]=1)=[O:4]>C(OCC)(=O)C.[Pd]>[CH3:1][O:2][C:3]([CH2:5][CH2:6][CH2:7][CH2:8][C:9]1[CH2:16][C@H:15]2[C@H:11]([CH2:12][C@@H:13]([O:27][CH:28]3[CH2:33][CH2:32][CH2:31][CH2:30][O:29]3)[C@@H:14]2[CH2:17][CH2:18][C:19](=[O:26])[CH:20]([F:25])[CH2:21][CH2:22][CH2:23][CH3:24])[CH:10]=1)=[O:4]
Reactant: CCCCC(F)C(=O)/C=C/[C@H]1[C@H]2CC(C=CCCC(=O)OC)=C[C@H]2C[C@H]1OC1CCCCO1
Agent: [Pd]
Solvent: CCOC(C)=O
Product: CCCCC(F)C(=O)CC[C@@H]1[C@H]2CC(CCCCC(=O)OC)=C[C@H]2C[C@H]1OC1CCCCO1

Procedure:
(1S,5S,6S,7R)-3-[4-Methoxycarbonyl-1(EZ)-butenyl]-6-[4(RS)-fluoro-3-oxo-(E )-1-octenyl]-7-tetrahydropyranyloxybicyclo[3.3.0]oct-2-ene (5) (0.094 g) was dissolved in ethyl acetate. Into the solution, palladium(5 wt %)/carbon (0.0094 g) was added and the mixture was stirred under reaction mixture was filtered, and the filtrate was evaporated under reduced pressure. Obtained crude product was chromatographed using a silica gel treated with silver nitrate (15 wt %) (hexane/ethyl acetate=12/1-9/1) to give (1S,5S,6R,7R)-3-(4-methoxycarbonyl)-6-[4(RS)-fluoro-3-oxooctyl]- 7-tetrahydropyranyloxybicyclo[3.3.0]oct-2-ene (6) as a pale yellow oily product. Yield: 0.042 g (44%)
Reaction SMILES: [OH-].[Na+].[Cl:3][C:4]1[CH:9]=[C:8]([O:10][CH3:11])[CH:7]=[CH:6][C:5]=1[OH:12].[Br:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19]Br>C(O)C>[Cl:3][C:4]1[CH:9]=[C:8]([O:10][CH3:11])[CH:7]=[CH:6][C:5]=1[O:12][CH2:19][CH2:18][CH2:17][CH2:16][CH2:15][CH2:14][Br:13]
Reactant: COc1ccc(O)c(Cl)c1
Reactant: BrCCCCCCBr
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: COc1ccc(OCCCCCCBr)c(Cl)c1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
A solution of 29.6 g. (0.74 mole) sodium hydroxide pellets in 400 ml. absolute ethanol was prepared with stirring at room temperature and a solution of 108.0 g. (0.68 mole) 2-chloro-4-methoxyphenol in 200 ml. absolute ethanol was added in a fine stream. The solution was stirred at room temperature for 15 minutes, then warmed gently in a steam bath for one-half hour. The reaction mixture was chilled to about 5° C. in an ice bath and 500 g. (2.05 moles) 1,6-dibromohexane was added. The reaction was stirred and allowed to warm to room temperature, then stirred for 6 hours at room temperature and boiled overnight at reflux.
Reaction SMILES: [CH:1](=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:9]([O:11][CH:12]([O:15][CH2:16][CH3:17])[CH2:13][NH2:14])[CH3:10].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)(O)[O-].[Na+]>ClC(Cl)C.C(OCC)(=O)C.C(O)(=O)C>[CH2:9]([O:11][CH:12]([O:15][CH2:16][CH3:17])[CH2:13][NH:14][CH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)[CH3:10]
Reactant: CCOC(CN)OCC
Reactant: O=Cc1ccccc1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CC(=O)O
Solvent: CCOC(C)=O
Solvent: CC(Cl)Cl
Product: CCOC(CNCc1ccccc1)OCC

Procedure:
A solution of benzaldehyde (3.0 mL, 0.0295 mol) and 2-aminoacetaldehyde diethyl acetal (4.3 mL, 0.0295 mol) in dichloroethane (60 mL) was brought to pH 7 by the addition of acetic acid. Sodium triacetoxyborohydride (8.1 g, 0.038 mol) was added and the reaction stirred until complete. Saturated sodium bicarbonate was added and the reaction stirred for 30 min. Ethyl acetate was added and the organic phase washed with saturated sodium chloride, then dried over magnesium sulfate. The crude product was chromatographed on silica gel with 30% ethyl acetate in hexane. The title compound was obtained as a pale yellow oil (2.93 g). NMR (CDCl3, 300 MHz) δ 7.31 (5H, m), 4.62 (1H, t, J=5 Hz), 3.81 (2H, s), 3.68 (2H, m), 3.54 (2H, m), 2.75 (2H d, J=5 Hz), 1.20 (6H, t, J=7 Hz).
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([O:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)=[C:4]([N+:15]([O-:17])=[O:16])[CH:3]=1.O(C1C=CC([B:33]2[O:37][C:36]([CH3:39])([CH3:38])[C:35]([CH3:41])([CH3:40])[O:34]2)=CC=1C#N)C1C=CC=CC=1.CO[C@@H]1[C@@H](C(OC)=O)[C@@H]2[C@@H](CN3[C@H](C2)C2NC4C=C(OC)C=CC=4C=2CC3)C[C@H]1OC(C1C=C(OC)C(OC)=C(OC)C=1)=O>C(#N)C>[C:9]1([O:8][C:5]2[CH:6]=[CH:7][C:2]([B:33]3[O:37][C:36]([CH3:39])([CH3:38])[C:35]([CH3:41])([CH3:40])[O:34]3)=[CH:3][C:4]=2[N+:15]([O-:17])=[O:16])[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1
Reactant: O=[N+]([O-])c1cc(Br)ccc1Oc1ccccc1
Reactant: CC1(C)OB(c2ccc(Oc3ccccc3)c(C#N)c2)OC1(C)C
Agent: COC(=O)[C@H]1[C@H]2C[C@@H]3c4[nH]c5cc(OC)ccc5c4CCN3C[C@H]2C[C@@H](OC(=O)c2cc(OC)c(OC)c(OC)c2)[C@@H]1OC
Solvent: CC#N
Product: CC1(C)OB(c2ccc(Oc3ccccc3)c([N+](=O)[O-])c2)OC1(C)C

Procedure:
The title compound was prepared in a 56% from 4-bromo-2-nitro-1-phenoxybenzene in a similar manner to that described for the preparation 2-phenoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolane-2-yl)benzonitrile: 1H NMR (DMSO-d6, 400 MHz) δ 8.19(d, 1H), 7.91(d, 1H), 7.46(t, 2H), 7.27(t, 1H), 7.14(d, 2H), 7.06(d, 1H), 1.31(s, 12H); RP-HPLC (Hypersil HS, 5 μm, 100 A 4.6×250 mm; 25%-100% acetonitrile—0.05 M ammonium acetate over 10 min, 1 ml/min) tr 14.02 min.
Reaction SMILES: [OH:1][CH:2]([C:23]1[CH:28]=[CH:27][C:26]([O:29][C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)=[CH:25][CH:24]=1)[CH:3]([CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([O:16][C:17]([F:22])([F:21])[CH:18]([F:20])[F:19])[CH:11]=1)[C:4]([O:6]CC)=[O:5].[OH-].[Na+].Cl>CO>[OH:1][CH:2]([C:23]1[CH:24]=[CH:25][C:26]([O:29][C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)=[CH:27][CH:28]=1)[CH:3]([CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([O:16][C:17]([F:22])([F:21])[CH:18]([F:20])[F:19])[CH:11]=1)[C:4]([OH:6])=[O:5]
Reactant: CCOC(=O)C(Cc1cccc(OC(F)(F)C(F)F)c1)C(O)c1ccc(Oc2ccccc2)cc1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: O=C(O)C(Cc1cccc(OC(F)(F)C(F)F)c1)C(O)c1ccc(Oc2ccccc2)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 77.7 %

Procedure:
To a solution of ethyl(2RS,3RS)-3-hydroxy-3-(4-(phenyloxy)phenyl)-2-((3-((1,1,2,2-tetrafluoroethyl)oxy)phenyl)methyl)propionate (6.14 g, 12.5 mmol) in methanol (30 ml) was added 2N aqueous sodium hydroxide solution (12.5 ml, 25.0 mmol), and the mixture was stirred overnight at room temperature. The reaction solution was acidified with 1N hydrochloric acid and extracted with ethyl acetate (200 ml×2). The extract was washed with water and saturated brine, dried over anhydrous magnesium sulfate and evaporated under reduced pressure. Recrystallization of the residue from ethyl acetate-hexane gave (2RS,3RS)-3-hydroxy-3-(4-(phenyloxy)phenyl)-2-((3-((1,1,2,2-tetrafluoroethyl)oxy)phenyl)methyl)propionic acid (4.51 g, 89%).
Reaction SMILES: [F:1][C:2]1[CH:23]=[C:22]([F:24])[CH:21]=[CH:20][C:3]=1[O:4][C:5]1[CH:15]=[C:14](C(=S)CC)[CH:13]=[CH:12][C:6]=1[NH:7][S:8]([CH3:11])(=[O:10])=[O:9].ClC1C=CC=[C:28]([C:32]([O:34]O)=O)C=1>ClCCl>[F:1][C:2]1[CH:23]=[C:22]([F:24])[CH:21]=[CH:20][C:3]=1[O:4][C:5]1[CH:15]=[C:14]([C:32](=[O:34])[CH2:28][S:8]([CH3:11])(=[O:10])=[O:9])[CH:13]=[CH:12][C:6]=1[NH:7][S:8]([CH3:11])(=[O:9])=[O:10]
Reactant: CCC(=S)c1ccc(NS(C)(=O)=O)c(Oc2ccc(F)cc2F)c1
Reactant: O=C(OO)c1cccc(Cl)c1
Solvent: ClCCl
Product: CS(=O)(=O)CC(=O)c1ccc(NS(C)(=O)=O)c(Oc2ccc(F)cc2F)c1
Temperature: 25 °C
Reaction time: 1 h
Yield: 83.5 %

Procedure:
A mixture of 2'-(2,4-difluorophenoxy)-4'-(methylthioacetyl)methanesulfonanilide (1.4 g) and m-chloroperbenzoic acid (1.4 g) in dichloromethane (15 ml) was stirred for 1 hour at room temperature. The mixture was washed with an aqueous solution of sodium bicarbonate and water, dried, and concentrated. The residue was recrystallized from ethyl acetate to give colorless crystals of 2'-(2,4-difluorophenoxy)-4'-(methylsulfonylacetyl)methanesulfonanilide (0.66 g), mp 162° to 163° C.
Reaction SMILES: [F:1][C:2]([F:33])([C:18]1[N:22]2[CH:23]=[C:24]([C:27]3[CH:28]=[N:29][N:30]([CH3:32])[CH:31]=3)[CH:25]=[CH:26][C:21]2=[N:20][N:19]=1)[C:3]1[CH:4]=[CH:5][C:6]2[N:7]([CH:9]=[C:10]([NH:12]C(C3CC3)=O)[N:11]=2)[N:8]=1.CO.O>Cl>[F:33][C:2]([F:1])([C:18]1[N:22]2[CH:23]=[C:24]([C:27]3[CH:28]=[N:29][N:30]([CH3:32])[CH:31]=3)[CH:25]=[CH:26][C:21]2=[N:20][N:19]=1)[C:3]1[CH:4]=[CH:5][C:6]2[N:7]([CH:9]=[C:10]([NH2:12])[N:11]=2)[N:8]=1
Reactant: Cn1cc(-c2ccc3nnc(C(F)(F)c4ccc5nc(NC(=O)C6CC6)cn5n4)n3c2)cn1
Agent: Cl
Solvent: CO
Solvent: O
Product: Cn1cc(-c2ccc3nnc(C(F)(F)c4ccc5nc(N)cn5n4)n3c2)cn1
Yield: 35.4 %

Procedure:
A solution of 45 (100 mg) in 3N HCl:50% MeOH:water was heated at 50° C. for 3 hrs. The reaction was concentrated and purified by preparative LCMS to provide the title compound, 6-(difluoro(6-(1-methyl-1H-pyrazol-4-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)methyl)imidazo[1,2-b]pyridazin-2-amine (30 mg) as the TFA salt. 1H NMR (400 MHz, DMSO-d6) δ ppm 3.89 (s, 3 H) 7.46 (br. s., 1 H) 7.51-7.58 (m, 1 H) 7.90 (dd, J=9.47, 1.39 Hz, 1 H) 7.93-7.99 (m, 1 H) 8.04 (d, J=9.60 Hz, 1 H) 8.08 (s, 1 H) 8.39-8.43 (m, 2 H) 8.67 (s, 1 H). ESI-MS:m/z 382.2 (M+H)+.
Reaction SMILES: C(O[C:6]([NH:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][C:16]([NH:18][C:19]1[S:20][C:21]2[CH:27]=[C:26]([O:28][S:29]([C:32]3[CH:37]=[CH:36][C:35]([F:38])=[CH:34][CH:33]=3)(=[O:31])=[O:30])[CH:25]=[CH:24][C:22]=2[N:23]=1)=[O:17])=[O:7])(C)(C)C.NC1SC2C=C(OS(C3C=CC(F)=CC=3)(=O)=O)C=CC=2N=1.C(C(CCCCCCN)C(O)=O)([O:62][C:63]([CH3:66])([CH3:65])[CH3:64])=O>>[C:63]([O:62][CH:9]([N:8]=[C:6]=[O:7])[CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][C:16]([NH:18][C:19]1[S:20][C:21]2[CH:27]=[C:26]([O:28][S:29]([C:32]3[CH:33]=[CH:34][C:35]([F:38])=[CH:36][CH:37]=3)(=[O:30])=[O:31])[CH:25]=[CH:24][C:22]=2[N:23]=1)=[O:17])([CH3:66])([CH3:65])[CH3:64]
Reactant: CC(C)(C)OC(=O)NCCCCCCCC(=O)Nc1nc2ccc(OS(=O)(=O)c3ccc(F)cc3)cc2s1
Reactant: CC(C)(C)OC(=O)C(CCCCCCN)C(=O)O
Agent: Nc1nc2ccc(OS(=O)(=O)c3ccc(F)cc3)cc2s1
Product: CC(C)(C)OC(CCCCCCC(=O)Nc1nc2ccc(OS(=O)(=O)c3ccc(F)cc3)cc2s1)N=C=O

Procedure:
According to the method of intermediate 17, 4-fluorobenzenesulfonic acid 2-(8-tert-butoxycarbonylaminooctanoylamino)benzothiazol-6-yl ester is pre-pared by combining 4-fluorobenzenesulfonic acid 2-aminobenzothiazol-6-yl ester (intermediate 16) with Boc-8-aminocaprylic acid.
Reaction SMILES: [CH:1]([C:4]1[CH:9]=[CH:8][C:7]([CH:10]2[C:14]3[C:15]([CH3:20])=[CH:16][CH:17]=[C:18]([CH3:19])[C:13]=3[O:12][C:11]2=[O:21])=[CH:6][CH:5]=1)([CH3:3])[CH3:2]>CCCCCC.C(OCC)(=O)C>[OH:21][CH2:11][CH:10]([C:14]1[C:15]([CH3:20])=[CH:16][CH:17]=[C:18]([CH3:19])[C:13]=1[OH:12])[C:7]1[CH:6]=[CH:5][C:4]([CH:1]([CH3:3])[CH3:2])=[CH:9][CH:8]=1
Reactant: Cc1ccc(C)c2c1OC(=O)C2c1ccc(C(C)C)cc1
Solvent: CCCCCC
Solvent: CCOC(C)=O
Product: Cc1ccc(C)c(C(CO)c2ccc(C(C)C)cc2)c1O
Yield: 88 %

Procedure:
Using 3-(4-isopropylphenyl)-4,7-dimethyl-1-benzofuran-2 (3H)-one synthesized in Reference Example 230, the title compound was synthesized in the same manner as in Reference Example 8. Yield 88%. Melting point: 88-89° C. (hexane-ethyl acetate).
Reaction SMILES: [C:1]([C:4]1[CH:13]=[CH:12][C:7]([C:8]([O:10][CH3:11])=[O:9])=[CH:6][CH:5]=1)(=[O:3])[NH2:2].[F:14][C:15]([F:31])([F:30])[C:16]1[CH:17]=[C:18]([CH:23]=[C:24]([C:26]([F:29])([F:28])[F:27])[CH:25]=1)[C:19](=O)[CH2:20]Br>>[F:14][C:15]([F:30])([F:31])[C:16]1[CH:17]=[C:18]([C:19]2[N:2]=[C:1]([C:4]3[CH:13]=[CH:12][C:7]([C:8]([O:10][CH3:11])=[O:9])=[CH:6][CH:5]=3)[O:3][CH:20]=2)[CH:23]=[C:24]([C:26]([F:27])([F:28])[F:29])[CH:25]=1
Reactant: COC(=O)c1ccc(C(N)=O)cc1
Reactant: O=C(CBr)c1cc(C(F)(F)F)cc(C(F)(F)F)c1
Product: COC(=O)c1ccc(-c2nc(-c3cc(C(F)(F)F)cc(C(F)(F)F)c3)co2)cc1
Yield: 24 %

Procedure:
In the same manner as in Example 1, methyl 4-carbamoylbenzoate was reacted with 3,5-bis(trifluoromethyl)phenacyl bromide to obtain methyl 4-[4-[3,5-bis(trifluoromethyl)phenyl]-2-oxazolyl]benzoate. The product was. recrystallized from ethanol., Yield: 24%. Pale yellow prisms. Melting Point: 180 to 181° C.
Reaction SMILES: Cl[C:2]1[CH:11]=[C:10]([Cl:12])[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]=1.[OH:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1B(O)O.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>[Cl:12][C:10]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]=[C:2]([C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][C:14]=2[OH:13])[CH:11]=1
Reactant: Clc1cc(Cl)c2ccccc2n1
Reactant: OB(O)c1ccccc1O
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: O
Solvent: Cc1ccccc1
Product: Oc1ccccc1-c1cc(Cl)c2ccccc2n1
Yield: 52.4 %

Procedure:
2,4-Dichloroquinoline (0.500 g, 2.525 mmol), 2-hydroxyphenylboronic acid (0.332 g, 2.405 mmol), sodium carbonate (0.510 g, 4.810 mmol) and Pd(PPh3)4 (0.139 g, 120 mmol) were added to a degassed mixture of toluene (5 mL) and water (2 mL), and the mixture was heated for 15 hours. After cooling, water (100 mL) was added and the aqueous layer was extracted with ethyl acetate (2×100 mL). The organic layers were combined, washed with brine (50 mL), dried (MgSO4), and concentrated. The crude product was purified by silica gel chromatography (dichloromethane) to give the title compound (0.322 g, 50%).
Reaction SMILES: [CH2:1]([NH:8][C:9]([NH:11][C:12]1[CH:17]=[C:16]([C:18]#[N:19])[CH:15]=[CH:14][C:13]=1[NH:20][CH2:21][CH3:22])=[S:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl[CH2:24][C:25](OCC)=[O:26].C1CCN2C(=NCCC2)CC1>C(O)C>[CH2:1]([N:8]1[C:25](=[O:26])[CH2:24][S:10][C:9]1=[N:11][C:12]1[CH:17]=[C:16]([CH:15]=[CH:14][C:13]=1[NH:20][CH2:21][CH3:22])[C:18]#[N:19])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CCOC(=O)CCl
Reactant: CCNc1ccc(C#N)cc1NC(=S)NCc1ccccc1
Solvent: CCO
Solvent: C1CCC2=NCCCN2CC1
Product: CCNc1ccc(C#N)cc1N=C1SCC(=O)N1Cc1ccccc1
Temperature: 80 °C
Yield: 87.4 %

Procedure:
To a solution of 1-benzyl-3-(5-cyano-2-ethylaminophenyl)thiourea (1.0 g, 3.2 mmol) in ethanol (40 mL, anhyd) was added ethyl chloroacetate (0.39 g, 3.2 mmol) and then DBU (0.58 g, 3.8 mmol). The reaction mixture was heated at 80° C. with stirring. After 1 h the reaction mixture was cooled, concentrated under reduced pressure, and chromatographed (silica gel, 1:1 EtOAc/Hex) to afford the title product (0.98 g, 87%). 1H-NMR (CDCl3): δ 7.38 (6H, m), 7.11 (1H, d), 6.50 (1H, d), 5.05 (2H, s), 3.96 (2H, s), 3.01 (2K, m), 1.03 (3H, t).
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]([CH:8]([C:10]2[CH:15]=[CH:14][C:13]([CH3:16])=[CH:12][N:11]=2)[OH:9])[O:5][C:6]=1[CH3:7]>C(Cl)(Cl)Cl.[O-2].[O-2].[Mn+4]>[CH3:1][C:2]1[CH:3]=[C:4]([C:8]([C:10]2[CH:15]=[CH:14][C:13]([CH3:16])=[CH:12][N:11]=2)=[O:9])[O:5][C:6]=1[CH3:7]
Reactant: Cc1ccc(C(O)c2cc(C)c(C)o2)nc1
Agent: [Mn+4]
Agent: [O-2]
Solvent: ClC(Cl)Cl
Product: Cc1ccc(C(=O)c2cc(C)c(C)o2)nc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 93.6 %

Procedure:
(4,5-Dimethylfuran-2-yl)-(5-methyl-pyridin-2-yl)methanol (850 mg) was dissolved in chloroform (40 ml) to prepare a solution. Manganese dioxide (3.4 g) was added to the solution, and the mixture was stirred at room temperature overnight. The reaction solution was filtered through Celite. The solvent was removed from the filtrate by distillation under the reduced pressure, and the residue was purified by column chromatography using hexane-ethyl acetate to give (4,5-dimethylfuran-2-yl)-(5-methyl-pyridin-2-yl)-methanone (788 mg, yield 93%).
Reaction SMILES: I[C:2]1[N:6]2[CH:7]=[CH:8][CH:9]=[C:10]([C:11]#[N:12])[C:5]2=[N:4][CH:3]=1.[CH:13]([O:16][C:17]1[CH:18]=[C:19]([NH:32][C:33]([NH:35][CH2:36][C:37]([F:40])([F:39])[F:38])=[O:34])[CH:20]=[C:21](B2OC(C)(C)C(C)(C)O2)[CH:22]=1)([CH3:15])[CH3:14].C([O-])([O-])=O.[Na+].[Na+].CCOC(C)=O>O1CCOCC1.[Cl-].[Na+].O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl>[C:11]([C:10]1[C:5]2[N:6]([C:2]([C:21]3[CH:20]=[C:19]([NH:32][C:33]([NH:35][CH2:36][C:37]([F:38])([F:39])[F:40])=[O:34])[CH:18]=[C:17]([O:16][CH:13]([CH3:15])[CH3:14])[CH:22]=3)=[CH:3][N:4]=2)[CH:7]=[CH:8][CH:9]=1)#[N:12]
Reactant: CC(C)Oc1cc(NC(=O)NCC(F)(F)F)cc(B2OC(C)(C)C(C)(C)O2)c1
Reactant: N#Cc1cccn2c(I)cnc12
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: O=C([O-])[O-]
Solvent: CCOC(C)=O
Solvent: O
Solvent: ClCCl
Product: CC(C)Oc1cc(NC(=O)NCC(F)(F)F)cc(-c2cnc3c(C#N)cccn23)c1
Temperature: 110 °C
Yield: 32.1 %

Procedure:
To a mixture of 3-iodoimidazo[1,2-a]pyridine-8-carbonitrile (100 mg, 373 μmol), 1-(3-isopropoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-3-(2,2,2-trifluoroethyl)urea (90 mg, 224 μmol), PdCl2(dppf)-CH2Cl2 Adduct (30.5 mg, 37.3 μmol) in Dioxane (3 ml), was added 2M Na2CO3 (0.559 ml, 1119 μmol). The vial was degassed for 5 minutes then capped and heated to 110° C. for 30 minutes in microwave. After cooling to ambient temperature reaction was partioned between EtOAc and brine, separated and organics washed with brinex2. Combined organics were dried directly on to silica and purified via flash chromatography (0-100% Hex/EtOAc; 12 g column). Recovered the title compound (30 mg, 71.9 μmol, 32.1% yield) as a brown solid. MS (ES+) C20H18F3N5O2 requires: 417. found: 418 [M+H]+.
Reaction SMILES: CC(C[AlH]CC(C)C)C.[Cl:10][C:11]1[S:23][C:14]2[NH:15][C:16](=[O:22])[C:17]([C:20]#[N:21])=[C:18]([OH:19])[C:13]=2[C:12]=1[C:24]1[CH:33]=[CH:32][C:27]([C:28](OC)=[O:29])=[CH:26][CH:25]=1>C1COCC1>[Cl:10][C:11]1[S:23][C:14]2[NH:15][C:16](=[O:22])[C:17]([C:20]#[N:21])=[C:18]([OH:19])[C:13]=2[C:12]=1[C:24]1[CH:33]=[CH:32][C:27]([CH2:28][OH:29])=[CH:26][CH:25]=1
Reactant: COC(=O)c1ccc(-c2c(Cl)sc3[nH]c(=O)c(C#N)c(O)c23)cc1
Agent: CC(C)C[AlH]CC(C)C
Solvent: C1CCOC1
Product: N#Cc1c(O)c2c(-c3ccc(CO)cc3)c(Cl)sc2[nH]c1=O
Temperature: 25 °C
Reaction time: 8 h

Procedure:
1M DIBAL-H (10 mL, 10 mmol) was slowly added to a solution of methyl 4-(2-chloro-5-cyano-4-hydroxy-6-oxo-6,7-dihydrothieno[2,3-b]pyridin-3-yl)benzoate (0.3 g, 0.832 mmol) in anhydrous THF (80 mL) held at −78° C. The solution was then allowed to warm to rt and stirred overnight. The reaction was quenched with MeOH (2 mL) and 1N HCl (5 mL), filtered through silica gel, concentrated and purified on a RP-HPLC system. MS (ESI) m/e 330.9 (M−H)+; 1H NMR (400 MHz, DMSO-d6): δ ppm 7.35 (d, J=8.28, 2H), 7.29 (d, J=7.98, 2H), 4.60 (br s, 1H), 4.55 (s, 2H).
Reaction SMILES: [C:1]1([C:7]#[C:8][CH3:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH2:10]([SiH:12]([CH2:15][CH3:16])[CH2:13][CH3:14])[CH3:11].C([Si](CC)(CC)/C(/C)=C\C1C=CC=CC=1)C>>[CH2:10]([Si:12]([CH2:15][CH3:16])([CH2:13][CH3:14])/[C:7](/[C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1)=[CH:8]\[CH3:9])[CH3:11]
Reactant: CC#Cc1ccccc1
Reactant: CC[SiH](CC)CC
Agent: CC[Si](CC)(CC)/C(C)=C\c1ccccc1
Product: C/C=C(/c1ccccc1)[Si](CC)(CC)CC
Temperature: 100 °C
Yield: 86 %

Procedure:
A mixture of 0.125 ml (1.0 mmol) of 1-phenylpropyne, 0.192 ml (1.2 mmol) of triethylsilane, and 8.3 mg (0.01 mmol) of bis(triphenylphosphine)iminium μ-hydridebis(pentacarbonylchromium) was heated in a sealed tube at 100° C. for 16 hours while being stirred. GLC analysis of the reaction mixture revealed that (Z)-β-triethylsilyl-β-methylstyrene and (Z)-α-triethylsilyl-β-methylstyrene were produced in a yield of 86% and 4%, respectively.
Reaction SMILES: C([Li])CCC.[C:6]1([S:12]([C@H:15]([CH3:21])[C@H:16]([CH3:20])[CH2:17][CH2:18][OH:19])(=[O:14])=[O:13])[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1>C1COCC1>[C:6]1([S:12]([C@@H:15]([CH3:21])[C@H:16]([CH3:20])[CH2:17][CH2:18][OH:19])(=[O:13])=[O:14])[CH:7]=[CH:8][CH:9]=[CH:10][CH:11]=1
Reactant: C[C@H](CCO)[C@@H](C)S(=O)(=O)c1ccccc1
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: C[C@H](CCO)[C@H](C)S(=O)(=O)c1ccccc1
Temperature: 0 °C

Procedure:
n-Butyllithium in hexanes (0.165 ml, 0.25 mmol) was added dropwise to a stirred solution of (3R*,4R*)-4-benzenesulfonyl-3-methylpentan-1-ol (286 mg, 1.2 mmol) in THF (5 ml) at −78° C. The mixture was warmed to 0° C. over 30 min. and quenched with satd. aqueous NH4Cl and extracted with dichloromethane. The combined organic extracts were dried (Na2SO4) and concentrated to give a mixture syn:anti diastereoisomeric sulfones in a 6:1 ratio respectively.