Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: FC(F)(F)C(O)=O.[Cl:8][C:9]1[CH:14]=[CH:13][C:12]([C@H:15](O)[C@@H:16]([C:20]2[CH:35]=[CH:34][C:23]([C:24]([NH:26][CH2:27][CH2:28][C:29]([O:31][CH2:32][CH3:33])=[O:30])=[O:25])=[CH:22][CH:21]=2)[CH2:17][CH2:18][CH3:19])=[CH:11][CH:10]=1.[CH3:37][O:38][C:39]1[CH:48]=[CH:47][C:46]2[C:41](=[CH:42][CH:43]=[CH:44][CH:45]=2)[CH:40]=1>>[Cl:8][C:9]1[CH:14]=[CH:13][C:12]([CH:15]([C:44]2[CH:43]=[CH:42][C:41]3[C:46](=[CH:47][CH:48]=[C:39]([O:38][CH3:37])[CH:40]=3)[CH:45]=2)[C@@H:16]([C:20]2[CH:35]=[CH:34][C:23]([C:24]([NH:26][CH2:27][CH2:28][C:29]([O:31][CH2:32][CH3:33])=[O:30])=[O:25])=[CH:22][CH:21]=2)[CH2:17][CH2:18][CH3:19])=[CH:11][CH:10]=1
Reactant: CCC[C@H](c1ccc(C(=O)NCCC(=O)OCC)cc1)[C@@H](O)c1ccc(Cl)cc1
Reactant: COc1ccc2ccccc2c1
Solvent: O=C(O)C(F)(F)F
Product: CCC[C@H](c1ccc(C(=O)NCCC(=O)OCC)cc1)C(c1ccc(Cl)cc1)c1ccc2cc(OC)ccc2c1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
Trifluoroacetic acid (5 mL) was added to ethyl N-(4-{(1R)-1-[(R)-(4-chlorophenyl)(hydroxy)methyl]butyl}benzoyl)-β-alaninate (EXAMPLE 1, Step A, 600 mg, 1.436 mmol) and 2-methoxynaphthalene (341 mg, 2.15 mmol). The solution was stirred overnight at RT, then the solvent was evaporated and the residue was purified by PTLC to afford the major diastereomer of the title compound. LC2 2.85 min. [M+H]+ 558.
Reaction SMILES: [Si]([C@@:8]1([OH:42])[C@@H:12]([CH2:13][O:14][Si](C(C)(C)C)(C)C)[O:11][C@@H:10]([N:22]2[CH:29]=[C:28]([CH2:30][O:31][CH2:32][C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=3[CH:39]([CH3:41])[CH3:40])[C:26](=[O:27])[NH:25][C:23]2=[O:24])[CH2:9]1)(C(C)(C)C)(C)C.O.O.O.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>C1COCC1>[CH:39]([C:34]1[CH:35]=[CH:36][CH:37]=[CH:38][C:33]=1[CH2:32][O:31][CH2:30][C:28]1[C:26](=[O:27])[NH:25][C:23](=[O:24])[N:22]([CH:29]=1)[C@@H:10]1[O:11][C@H:12]([CH2:13][OH:14])[C@@H:8]([OH:42])[CH2:9]1)([CH3:41])[CH3:40]
Reactant: CC(C)c1ccccc1COCc1cn([C@H]2C[C@@](O)([Si](C)(C)C(C)(C)C)[C@@H](CO[Si](C)(C)C(C)(C)C)O2)c(=O)[nH]c1=O
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: C1CCOC1
Solvent: O
Product: CC(C)c1ccccc1COCc1cn([C@H]2C[C@H](O)[C@@H](CO)O2)c(=O)[nH]c1=O
Temperature: 25 °C
Reaction time: 1 h

Procedure:
Compounds 3′,5′-O-bis-(tert-butyldimethylsilyl)-5-(2-isopropylbenzyl-oxy)methyl-2′-deoxyuridine (134 mg, 0.22 mmol) and (3′ or 5′)-O-(tert-butyldimethylsilyl)-5-(2-isopropylbenzyloxy)methyl-2′-deoxyuridine (98 mg, 0.19 mmol) were dissolved in THF (5 mL), and a solution of tetra-n-butylammonium fluoride trihydrate (323 mg, 1.05 mmol) in THF (2 mL) was added. The mixture was stirred at room temperature for one hour, then concentrated in vacuo and purified by silica gel column chromatography to give 5-(2-isopropylbenzyloxy)methyl-2′-deoxyuridine dU.n6 (108 mg, 67%).
Reaction SMILES: [CH3:1][C:2]1[NH:13][C:12]2[C:7](=[CH:8][C:9]([O:14][CH3:15])=[CH:10][CH:11]=2)[C:3]=1[CH2:4][CH2:5][NH2:6].[CH:16]1([C:19](Cl)=[O:20])[CH2:18][CH2:17]1.CC1NC2C=CC(OC)=CC=2C=1CCNC(C)=O>C1COCC1>[CH3:1][C:2]1[NH:13][C:12]2[C:7](=[CH:8][C:9]([O:14][CH3:15])=[CH:10][CH:11]=2)[C:3]=1[CH2:4][CH2:5][NH:6][C:19]([CH:16]1[CH2:18][CH2:17]1)=[O:20]
Reactant: O=C(Cl)C1CC1
Reactant: COc1ccc2[nH]c(C)c(CCN)c2c1
Agent: COc1ccc2[nH]c(C)c(CCNC(C)=O)c2c1
Solvent: C1CCOC1
Product: COc1ccc2[nH]c(C)c(CCNC(=O)C3CC3)c2c1

Procedure:
A solution of the crude 2-methyl-5-methoxytryptamine (from 5 mmol of 3a), in THF (15 mL) and TEA (0.7 mL) was acylated with cyclopropanecarbonyl chloride (0.45 mL) at room temperature for 1.5 h using the procedure described for 4a. The desired product 4e was obtained as white solid (0.615 g, 45% overall yield), mp 102°-103° C. IR νmax : 3460, 3300, 1650. 1H NMR: 0.70(m, 2H, CH2cyclopropyl), 0.97(m, 2H, CH2 cyclopropyl), 1.24(m, 1H, cyclopropyl-CH), 2.36(s, 3H, 2-CH3), 2.90(t, 2H, β -CH2), 3.51(q, 2H, α-CH2), 3.85(s, 3H, OCH3), 5.75(br s, 1H, NH), 6.75-7.25 (m, 3Harom), 8.00(br s, 1H, NHindole).
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([CH:10]=[O:11])=[CH:2]1.[S:12](Cl)([C:15]1[CH:21]=[CH:20][C:18]([CH3:19])=[CH:17][CH:16]=1)(=[O:14])=[O:13].C(N(C(C)C)CC)(C)C.C(=O)([O-])O.[Na+]>C(Cl)Cl>[S:12]([N:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([CH:10]=[O:11])=[CH:2]1)([C:15]1[CH:21]=[CH:20][C:18]([CH3:19])=[CH:17][CH:16]=1)(=[O:14])=[O:13]
Reactant: O=Cc1c[nH]c2ccccc12
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: Cc1ccc(S(=O)(=O)n2cc(C=O)c3ccccc32)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 78.8 %

Procedure:
A solution of 1H-indole-3-carboxaldehyde (7.26 g, 50.0 mmol) in methylene chloride (100 mL) was added with tosyl chloride (11.4 g, 60.0 mmol) and diisopropylethylamine (7.75 g, 60.0 mmol), and the mixture was stirred overnight at room temperature. The reaction mixture was added with saturated aqueous sodium hydrogencarbonate to terminate the reaction, and then extracted three times with methylene chloride, and the organic layer was dried over anhydrous magnesium sulfate. The solvent was evaporated, and the resulting residue was purified by silica gel column chromatography (hexane/ethyl acetate) to obtain 1-tosyl-1H-indole-3-carboxaldehyde (11.8 g, 78%).
Reaction SMILES: N#N.[CH3:3][O:4][C:5]1[CH:6]=[C:7]([C:15]2[C:16]([C:21]([OH:23])=O)=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH:8]=[C:9]([O:13][CH3:14])[C:10]=1[O:11][CH3:12].C(Cl)(=O)C([Cl:27])=O>C(Cl)Cl.CN(C=O)C>[CH3:3][O:4][C:5]1[CH:6]=[C:7]([C:15]2[C:16]([C:21]([Cl:27])=[O:23])=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH:8]=[C:9]([O:13][CH3:14])[C:10]=1[O:11][CH3:12]
Reactant: COc1cc(-c2ccccc2C(=O)O)cc(OC)c1OC
Reactant: O=C(Cl)C(=O)Cl
Agent: N#N
Solvent: CN(C)C=O
Solvent: ClCCl
Product: COc1cc(-c2ccccc2C(=O)Cl)cc(OC)c1OC
Reaction time: 2 h

Procedure:
(The following reaction is done in an anhydrous N2 atmosphere.) Dissolve 3′,4′,5′-Trimethoxy-biphenyl-2-carboxylic acid (56) (54 mg, 0.18 mmol) in anhydrous DCM (1.3 mL) and add anhydrous DMF (1 drop, cat. amount). Then add slowly oxalyl chloride (21 μL, 0.24 mmol) by keeping temperature at ca. 20° C. with a water bath and stir the turbid mixture for additional 2 h at it Remove solvent and dry in vacuum to obtain crude 3′,4′,5′-Trimethoxy-biphenyl-2-carbonyl chloride (57) as a yellow solid. No further purification.
Reaction SMILES: [CH2:1]([N:8]1[CH2:12][CH2:11][N:10]([C:13]2[S:14][C:15]([C:19]([OH:21])=O)=[C:16]([CH3:18])[N:17]=2)[C:9]1=[O:22])[C:2]1[CH:7]=[CH:6][CH:5]=CC=1.C1(CCN2CCN(C3SC(C(O)=O)=C(C)N=3)C2=O)CC1.[CH2:43]([NH2:50])[C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1>>[CH2:43]([NH:50][C:19]([C:15]1[S:14][C:13]([N:10]2[CH2:11][CH2:12][N:8]([CH2:1][CH2:2][CH:7]3[CH2:6][CH2:5]3)[C:9]2=[O:22])=[N:17][C:16]=1[CH3:18])=[O:21])[C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1
Reactant: Cc1nc(N2CCN(Cc3ccccc3)C2=O)sc1C(=O)O
Reactant: NCc1ccccc1
Agent: Cc1nc(N2CCN(CCC3CC3)C2=O)sc1C(=O)O
Product: Cc1nc(N2CCN(CCC3CC3)C2=O)sc1C(=O)NCc1ccccc1
Yield: 15 %

Procedure:
Following the procedure as describe in Example 9, making variations as required to replace 2-(3-benzyl-2-oxoimidazolidin-1-yl)-4-methylthiazole-5-carboxylic acid with 2-(3-(2-cyclopropylethyl)-2-oxoimidazolidin-1-yl)-4-methylthiazole-5-carboxylic acid to react with benzylamine, the title compound was obtained as a white powder in 15% yield: mp 137-138° C.: 1H NMR (300 MHz, CDCl3) δ 7.36-7.25 (m, 5H), 5.88 (s, 1H), 4.54 (d, J=5.7 Hz, 2H), 4.09 (t, J=7.8 Hz, 2H), 3.58 (t, J=8.7 Hz, 2H), 3.37 (t, J=7.8 Hz, 2H), 2.60 (s, 3H), 1.46 (m, 2H), 0.70-0.58 (m, 1H), 0.46-0.37 (m, 2H), 0.13-0.03 (m, 2H); 13C NMR (75 MHz, CDCl3) δ 162.4, 155.3, 153.0, 137.9, 128.7, 127.8, 127.6, 44.8, 44.0, 42.5, 42.0, 32.4, 17.1, 8.4, 4.3: MS (ES+) m/z 385.2 (M+1).
Reaction SMILES: CS[C:3]1[S:4][CH2:5][C:6](=[O:8])[N:7]=1.[NH:9]1[CH2:14][CH2:13][CH:12]([C:15]([OH:17])=[O:16])[CH2:11][CH2:10]1>CO>[O:8]=[C:6]1[CH2:5][S:4][C:3]([N:9]2[CH2:14][CH2:13][CH:12]([C:15]([OH:17])=[O:16])[CH2:11][CH2:10]2)=[N:7]1
Reactant: CSC1=NC(=O)CS1
Reactant: O=C(O)C1CCNCC1
Solvent: CO
Product: O=C1CSC(N2CCC(C(=O)O)CC2)=N1
Temperature: 25 °C
Reaction time: 16 h

Procedure:
To a solution of 2-methylsulfanyl-thiazol-4-one (4.4 g, 30 mmol) in MeOH (60 mL) was added piperidine-4-carboxylic acid (3.9 g, 30 mmol). The mixture was stirred at room temperature for 16 hours. The resulting solid was collected by filtration, washed with fresh MeOH and dried to give the title compound.
Reaction SMILES: [OH:1][C:2]([CH3:7])([CH3:6])[C:3](O)=[O:4].ClC(N(C)C)=C(C)C.Cl.[NH2:17][CH2:18][C:19]1[CH:20]=[C:21]([CH2:25][N:26]2[C:34]3[C:29](=[C:30]([O:35][CH3:36])[CH:31]=[CH:32][CH:33]=3)[C:28]([NH:37][S:38]([C:41]3[S:42][C:43]([Cl:46])=[CH:44][CH:45]=3)(=[O:40])=[O:39])=[N:27]2)[CH:22]=[CH:23][CH:24]=1.CCN(C(C)C)C(C)C>C1COCC1>[Cl:46][C:43]1[S:42][C:41]([S:38]([NH:37][C:28]2[C:29]3[C:34](=[CH:33][CH:32]=[CH:31][C:30]=3[O:35][CH3:36])[N:26]([CH2:25][C:21]3[CH:20]=[C:19]([CH2:18][NH:17][C:3](=[O:4])[C:2]([OH:1])([CH3:7])[CH3:6])[CH:24]=[CH:23][CH:22]=3)[N:27]=2)(=[O:39])=[O:40])=[CH:45][CH:44]=1
Reactant: CC(C)(O)C(=O)O
Reactant: COc1cccc2c1c(NS(=O)(=O)c1ccc(Cl)s1)nn2Cc1cccc(CN)c1
Agent: CC(C)=C(Cl)N(C)C
Agent: Cl
Solvent: C1CCOC1
Solvent: CCN(C(C)C)C(C)C
Product: COc1cccc2c1c(NS(=O)(=O)c1ccc(Cl)s1)nn2Cc1cccc(CNC(=O)C(C)(C)O)c1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 88 %

Procedure:
To a solution of 2-hydroxy-2-methylpropanoic acid (Aldrich) (20.84 mg, 0.200 mmol) in THF (2 mL) was added dropwise at room temperature 1-chloro-N,N,2-trimethyl-1-propen-1-amine (0.026 mL, 0.200 mmol). The resulting mixture was stirred at room temperature for 30 min. To this were successively added N-[1-{[3-(aminomethyl)phenyl]methyl}-4-(methyloxy)-1H-indazol-3-yl]-5-chloro-2-thiophenesulfonamide hydrochloride (for a preparation see Intermediate 4) (50 mg, 0.100 mmol) and DIPEA (0.052 mL, 0.300 mmol). After 1 hour of stirring at room temperature LCMS showed product as the major peak. The reaction mixture was concentrated under a stream of nitrogen in the Radleys blowdown apparatus, the residue was dissolved in 1:1 MeOH:DMSO (1 mL) and purified by MDAP on Sunfire C18 column using Acetonitrile Water with a Formic acid modifier. The solvent was removed under a stream of nitrogen in the Radleys blowdown apparatus to give the title compound (48.5 mg, 88%). LCMS (System A) RT=1.05 min, ES+ve m/z 549/551 (M+H)+.
Reaction SMILES: C[Sn](C)(C)[C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH2:13][CH:12]([CH2:14][N:15]3[CH:19]=[CH:18][N:17]=[N:16]3)[O:11][N:10]=2)=[CH:5][CH:4]=1.[F:22][C:23]1[CH:24]=[C:25]([N:30]2[CH2:34][C@H:33]([CH2:35][NH:36][C:37](=[O:39])[CH3:38])[O:32][C:31]2=[O:40])[CH:26]=[CH:27][C:28]=1I.O1C=CC=C1P(C1OC=CC=1)C1OC=CC=1>O1CCOCC1>[F:22][C:23]1[CH:24]=[C:25]([N:30]2[CH2:34][C@H:33]([CH2:35][NH:36][C:37](=[O:39])[CH3:38])[O:32][C:31]2=[O:40])[CH:26]=[CH:27][C:28]=1[C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH2:13][CH:12]([CH2:14][N:15]3[CH:19]=[CH:18][N:17]=[N:16]3)[O:11][N:10]=2)=[CH:5][CH:4]=1
Reactant: C[Sn](C)(C)c1ccc(C2=NOC(Cn3ccnn3)C2)cc1
Reactant: CC(=O)NC[C@H]1CN(c2ccc(I)c(F)c2)C(=O)O1
Agent: c1coc(P(c2ccco2)c2ccco2)c1
Solvent: C1COCCO1
Product: CC(=O)NC[C@H]1CN(c2ccc(-c3ccc(C4=NOC(Cn5ccnn5)C4)cc3)c(F)c2)C(=O)O1
Temperature: 90 °C
Yield: 31.7 %

Procedure:
1-({3-[4-(Trimethylstannyl)phenyl]-4,5-dihydroisoxazol-5-yl}methyl)-1H-1,2,3-triazole (0.62 g, 1.58 mmol), N-{[(5S)-3-(3-fluoro-4-iodophenyl)-2-oxo-1,3-oxazolidin-5-yl]methyl}acetamide (0.5 g, 1.32 mmol) and tri-2-furylphosphine (0.08 g, 0.34 mmol) were dissolved in 1,4-dioxane (6 ml) and degassed three times. Tris(dibenzylideneacetone)palladium (0) (0.16 g, 0.18 mmol) was added and the solution was degassed three times. The solution was stirred and heated to 90° C. for 18 hours. The mixture was concentrated in vacuo and then purified by silica flash chromatography with 5-10% methanol in dichloromethane as eluent giving 0.20 g desired product.
Reaction SMILES: [CH:1]([C:3]1[C:4]([OH:13])=[C:5]([CH:10]=[CH:11][CH:12]=1)[C:6]([O:8][CH3:9])=[O:7])=O.[N+:14]([CH2:17][CH3:18])([O-:16])=[O:15].N1CCCCC1>C1(C)C=CC=CC=1>[OH:13][C:4]1[C:3]([CH:1]=[C:17]([N+:14]([O-:16])=[O:15])[CH3:18])=[CH:12][CH:11]=[CH:10][C:5]=1[C:6]([O:8][CH3:9])=[O:7]
Reactant: CC[N+](=O)[O-]
Reactant: COC(=O)c1cccc(C=O)c1O
Solvent: Cc1ccccc1
Solvent: C1CCNCC1
Product: COC(=O)c1cccc(C=C(C)[N+](=O)[O-])c1O
Yield: 81.9 %

Procedure:
A mixture of 1.90 g of methyl 3-formyl-2-hydroxybenzoate, 3.0 g of nitroethane, 0.15 ml of piperidine and 30 ml of toluene is refluxed overnight while removing water. The reaction mixture is poured into ice-water and the aqueous mixture is extracted with ethyl acetate. The extract is washed successively with 10% hydrochloric acid and an aqueous saturated sodium chloride solution, dried and evaporated to remove solvent. The residue is recrystallized from methanol to give 2.05 g of methyl 2-hydroxy-3-(2-nitro-1-propenyl)benzoate.
Reaction SMILES: [O:1]=[C:2]1[C:7]([CH2:8][C:9]2[CH:14]=[CH:13][C:12]([C:15]3[C:16]([C:21]#[N:22])=[CH:17][CH:18]=[CH:19][CH:20]=3)=[CH:11][CH:10]=2)=[C:6]([CH2:23][CH2:24][CH3:25])[N:5]2[N:26]=[CH:27][CH:28]=[C:4]2[N:3]1[C@H:29]1[CH2:34][CH2:33][C@H:32]([O:35][CH2:36][C:37](=[O:39])[CH3:38])[CH2:31][CH2:30]1.[CH:40]1([Mg]Br)[CH2:42][CH2:41]1.C(OCC)(=O)C>O1CCCC1>[CH:40]1([C:37]([OH:39])([CH3:38])[CH2:36][O:35][C@H:32]2[CH2:31][CH2:30][C@H:29]([N:3]3[C:2](=[O:1])[C:7]([CH2:8][C:9]4[CH:14]=[CH:13][C:12]([C:15]5[C:16]([C:21]#[N:22])=[CH:17][CH:18]=[CH:19][CH:20]=5)=[CH:11][CH:10]=4)=[C:6]([CH2:23][CH2:24][CH3:25])[N:5]4[N:26]=[CH:27][CH:28]=[C:4]34)[CH2:34][CH2:33]2)[CH2:42][CH2:41]1
Reactant: CCCc1c(Cc2ccc(-c3ccccc3C#N)cc2)c(=O)n([C@H]2CC[C@H](OCC(C)=O)CC2)c2ccnn12
Reactant: Br[Mg]C1CC1
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: CCCc1c(Cc2ccc(-c3ccccc3C#N)cc2)c(=O)n([C@H]2CC[C@H](OCC(C)(O)C3CC3)CC2)c2ccnn12
Reaction time: 2 h

Procedure:
To a solution of 4′-({5-oxo-4-[trans-4-(2-oxopropoxy)cyclohexyl]-7-propyl-4,5-dihydropyrazolo[1,5-a]pyrimidin-6-yl}methyl)biphenyl-2-carbonitrile (0.30 g) in tetrahydrofuran (3 mL) was added dropwise cyclopropylmagnesium bromide (0.5M tetrahydrofuran solution, 2.3 mL) at 0° C., and the mixture was stirred for 2 hr. To the reaction mixture were added ethyl acetate and then saturated aqueous ammonium chloride solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated. The residue was purified by silica gel column chromatography to give the title compound as a pale-yellow amorphous solid (0.22 g, 68%).
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]([CH2:8][C:9]([OH:11])=[O:10])[CH:5]=[CH:6][CH:7]=1.[Br:12]N1C(=O)CCC1=O>ClC(Cl)(Cl)Cl.N(C(C)(C)C#N)=NC(C)(C)C#N>[Br:12][CH2:1][C:2]1[CH:3]=[C:4]([CH2:8][C:9]([OH:11])=[O:10])[CH:5]=[CH:6][CH:7]=1
Reactant: O=C1CCC(=O)N1Br
Reactant: Cc1cccc(CC(=O)O)c1
Agent: CC(C)(C#N)N=NC(C)(C)C#N
Solvent: ClC(Cl)(Cl)Cl
Product: O=C(O)Cc1cccc(CBr)c1
Yield: 31 %

Procedure:
To a solution of 3-methylphenylacetic acid (125 g) in tetrachloro methane (1660 ml), N-bromosuccinimide (148 g) and 2,2′-azobisisobutyronitrile (AIBN; 1.37 g) were added. The mixture was refluxed with heating. After termination of reaction, the solution was cooled with ice. The white precipitate was filtered by glass-filter. The filtrate was washed by tetrachloro methane. The filtrate together with washing liquid was concentrated. The obtained residue was dissolved into ethyl acetate. Thereto, hexane was added. The mixture was crystallized to obtain the title compound (59 g).
Reaction SMILES: [Cl:1][C:2]1[C:7](I)=[CH:6][C:5]([NH:9][CH2:10][C:11]([O:13]C)=[O:12])=[C:4]([O:15][CH3:16])[CH:3]=1.[Cl:17][C:18]1[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][C:19]=1B(O)O.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.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>[Cl:17][C:18]1[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][C:19]=1[C:7]1[C:2]([Cl:1])=[CH:3][C:4]([O:15][CH3:16])=[C:5]([NH:9][CH2:10][C:11]([OH:13])=[O:12])[CH:6]=1
Reactant: OB(O)c1cc(Cl)ccc1Cl
Reactant: COC(=O)CNc1cc(I)c(Cl)cc1OC
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: C1COCCO1
Solvent: O
Product: COc1cc(Cl)c(-c2cc(Cl)ccc2Cl)cc1NCC(=O)O
Temperature: 25 °C
Yield: 59.1 %

Procedure:
A mixture of methyl 2-(4-chloro-5-iodo-2-methoxyphenylamino)acetate (5.0 g, 14.08 mmol), 2,5-dichlorophenylboronic acid (4.03 g, 21.12 mmol), Pd(PPh3)4 (1.626 g, 1.04 mmol), Na2CO3 (4.477 g, 42.24 mmol) in 1,4-dioxane (100 mL) and water (20 mL) was stirred at reflux under argon for 6 h. Then reaction mixture was allowed to cool to room temperature, quenched with water and acidified with HCl (10% in water) to adjust the pH to 3-4. The mixture was extracted with ethyl acetate, washed with brine, dried over Na2SO4 and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel (50% petroleum ether/ethyl acetate) to afford the desired product (3 g, 59% yield) as an off-white solid. ESI-MS m/z: 360.2 [M−H]−.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:16]=[CH:15][CH:14]=[C:13]3[C:9]=2[CH2:10][C:11](=[O:17])[NH:12]3)=[CH:4][CH:3]=1.[CH2:18]([N:20]([CH2:36][CH3:37])[CH2:21][CH2:22][CH2:23][NH:24][C:25]([C:27]1[C:31]([CH3:32])=[C:30]([CH:33]=O)[NH:29][C:28]=1[CH3:35])=[O:26])[CH3:19]>C(O)C.N1CCCCC1>[CH2:36]([N:20]([CH2:18][CH3:19])[CH2:21][CH2:22][CH2:23][NH:24][C:25]([C:27]1[C:31]([CH3:32])=[C:30]([CH:33]=[C:10]2[C:9]3[C:13](=[CH:14][CH:15]=[CH:16][C:8]=3[C:5]3[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=3)[NH:12][C:11]2=[O:17])[NH:29][C:28]=1[CH3:35])=[O:26])[CH3:37]
Reactant: O=C1Cc2c(cccc2-c2ccc(F)cc2)N1
Reactant: CCN(CC)CCCNC(=O)c1c(C)[nH]c(C=O)c1C
Solvent: C1CCNCC1
Solvent: CCO
Product: CCN(CC)CCCNC(=O)c1c(C)[nH]c(C=C2C(=O)Nc3cccc(-c4ccc(F)cc4)c32)c1C
Temperature: 25 °C
Reaction time: 72 h
Yield: 60.9 %

Procedure:
To a solution of 4-(4-fluoro-phenyl)-1,3-dihydro-indol-2-one (56.8 mg, 0.25 mmol) and 5-formyl-2,4-dimethyl-1H-pyrrole-3-carboxylic acid (3-diethylamino-propyl)-amide (69.8 mg, 0.26 mmol) in ethanol (2 mL) was added piperidine (3 drops). The reaction mixture was stirred at room temperature for three days. A yellow solid product was precipitated out, filtered, washed by ethanol for three times, and dried under high vacuum to provide pure product 5-[4-(4-fluoro-phenyl)-2-oxo-1,2-dihydro-indol-3-ylidenemethyl]-2,4-dimethyl-1H-pyrrole-3 carboxylic acid (3-diethylamino-propyl)-amide as a yellow solid (74.4 mg, 61%).
Reaction SMILES: [CH:1]([C:3]1[O:7][CH:6]=[C:5](B2OC(C)(C)C(C)(C)O2)[CH:4]=1)=[O:2].P(OCC)(OCC)(O[CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)=O.C(C1OC(C=O)=CC=1)C1C=CC=CC=1>CC#N.C(O)(C)C.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH2:20]([C:5]1[CH:4]=[C:3]([CH:1]=[O:2])[O:7][CH:6]=1)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1
Reactant: CCOP(=O)(OCC)OCc1ccccc1
Reactant: CC1(C)OB(c2coc(C=O)c2)OC1(C)C
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: O=Cc1ccc(Cc2ccccc2)o1
Solvent: CC(C)O
Solvent: CC#N
Product: O=Cc1cc(Cc2ccccc2)co1
Yield: 40.8 %

Procedure:
The title compound was synthesized from 5-formylfuran-3-boronic acid pinacol ester (878 mg, 3.95 mmol), and benzyl diethyl phosphate (1.25 g, 5.14 mmol) using the same conditions used to synthesize 5-benzyl-furan-2-carbaldehyde, with the exception that TPP and Pd(OAc)2 were dissolved in 2:1 CH3CN/isopropyl alcohol. Purification by flash chromatography yielded 4-benzyl-furan-2-carbaldehyde as a white solid (300 mg, 41%). 1H NMR (400 MHz, CDCl3) δ ppm 9.56 (s, 1 H) 7.29-7.38 (m, 3 H) 7.24-7.28 (m, 2 H) 7.17 (d, J=3.5 Hz, 1 H) 6.19 (d, J=3.6 Hz, 1 H) 4.07 (s, 2 H).
Reaction SMILES: [C:1]([C:5]1[C:10]2[O:11][CH2:12][C:13]([CH3:15])([CH3:14])[C:9]=2[CH:8]=[C:7]([C:16](=[N:18][OH:19])[NH2:17])[CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[C:20](Cl)(=O)[CH3:21]>N1C=CC=CC=1>[C:1]([C:5]1[C:10]2[O:11][CH2:12][C:13]([CH3:14])([CH3:15])[C:9]=2[CH:8]=[C:7]([C:16]2[N:17]=[C:20]([CH3:21])[O:19][N:18]=2)[CH:6]=1)([CH3:2])([CH3:3])[CH3:4]
Reactant: CC(=O)Cl
Reactant: CC(C)(C)c1cc(C(N)=NO)cc2c1OCC2(C)C
Solvent: c1ccncc1
Product: Cc1nc(-c2cc(C(C)(C)C)c3c(c2)C(C)(C)CO3)no1
Temperature: 95 °C
Yield: 52.4 %

Procedure:
To a solution of 7-tert-butyl-2,3-dihydro-3,3-dimethyl-5-benzo-[b]furancarboxamide oxime (1.05 g, 4.0 mmol) in 20 mL of pyridine is added acetyl chloride (0.43 mL, 6.0 mmol). The reaction mixture is heated at 95° C. for 22 h and cooled to room temperature. Pyridine is removed in vacuo at 50° C.; the residue is partitioned between water and ethyl acetate. The organic layer is washed with water and with brine, dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo to give 1.33 g of the crude product. Purification by flash column chromatography on silica gel (10% ethyl acetate-hexane) produces about 0.60 g (52%) of the title compound as a colorless solid: mp 81-82° C.
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[N:10]([CH2:11][C:12]2[CH:17]=[CH:16][C:15]([Cl:18])=[C:14]([Cl:19])[CH:13]=2)[C:9]2[CH:20]=[C:21](Br)[S:22][C:8]=2[CH:7]=1)=[O:5])[CH3:2].[S:24]1[CH:28]=[CH:27][CH:26]=[C:25]1B(O)O.Cl>C(O)C.C1(C)C=CC=CC=1.C(=O)([O-])[O-].[K+].[K+]>[Cl:19][C:14]1[CH:13]=[C:12]([CH:17]=[CH:16][C:15]=1[Cl:18])[CH2:11][N:10]1[C:6]([C:4]([O:3][CH2:1][CH3:2])=[O:5])=[CH:7][C:8]2[S:22][C:21]([C:25]3[S:24][CH:28]=[CH:27][CH:26]=3)=[CH:20][C:9]1=2
Reactant: CCOC(=O)c1cc2sc(Br)cc2n1Cc1ccc(Cl)c(Cl)c1
Reactant: OB(O)c1cccs1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: Cc1ccccc1
Solvent: CCO
Product: CCOC(=O)c1cc2sc(-c3cccs3)cc2n1Cc1ccc(Cl)c(Cl)c1
Temperature: 80 °C
Reaction time: 6 h
Yield: 76.4 %

Procedure:
Tetrakis-(triphenylphosphine)palladium (0) (20 mg) was added to a degassed solution of ethyl4-(3,4-dichlorobenzyl)-2-bromothieno[3,2-b]pyrrole-5-carboxylate (0.1 g) and thiophene-2-boronic acid (34 mg) in ethanol (1 ml), toluene (1 ml) and aqueous potassium carbonate (2N, 1 ml), and the reaction stirred at 80° C. under an argon atmosphere for 6 hours. The reaction was cooled, poured into 2N HCl and extracted with ether. Combined organic extracts were cried (MgSO4), concentrated in vacuo and the residue purified by column chromatography using isohexane to isohexane-25% ethyl acetate as eluent to give the product as a pale yellow crystalline solid (77 mg, 77%), M/z (+) 435 (MH+), 276, 204, 159, 127.
Reaction SMILES: S1[CH2:6][CH2:5][C:4](=[O:7])[CH2:3][CH2:2]1.O[O:9][S:10]([O-:12])=O.[K+].C([O-])(O)=O.[Na+]>CC#N.O>[O:9]=[S:10]1(=[O:12])[CH2:6][CH2:5][C:4](=[O:7])[CH2:3][CH2:2]1
Reactant: O=C1CCSCC1
Reactant: O=S([O-])OO
Agent: O=C([O-])O
Agent: [K+]
Agent: [Na+]
Solvent: CC#N
Solvent: O
Product: O=C1CCS(=O)(=O)CC1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To tetrahydrothiopyran-4-one in CH3CN (50 mL) and H2O (35 mL) at 0° C. was added in portions over 1 hour a mixture of oxone (70.5 g, 115 mmol) and NaHCO3 (29.9 g, 356 mmol). The reaction mixture was then stirred at room temperature for 1 h, diluted in CH3CN (250 mL) and filtered. The filtrate was concentrated, suspended in acetone and filtered. 1,1-Dioxo-tetrahydrothiopyran-4-one (6.3 g, quantitative yield) was obtained as a white solid.
Reaction SMILES: CC([SiH:12]([CH2:23]CCCCCCCCC)[CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH3:22])=CCCCCCCCC.[CH3:33][CH:34]([SiH](CCCCCCCCCC)CCCCCCCCCC)[CH:35]=CCCCCCCC>C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Cl-].[Rh]>[CH3:23][SiH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:33][CH2:34][CH3:35]
Reactant: CCCCCCCC=CC(C)[SiH](CCCCCCCCCC)CCCCCCCCCC
Reactant: CCCCCCCCC=C(C)[SiH](CCCCCCCCCC)CCCCCCCCCC
Agent: [Rh]
Agent: [Cl-]
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Product: CCCCCCCCCCCCC[SiH2]C
Yield: 85 %

Procedure:
The test of Example 20 was repeated using 0.005 gram of chlorotris(triphenylphosphine)rhodium(I). The reaction was over in one hour at 50° C., and produced an 85 percent yield of methyltridecylsilane and 15 percent of methyldidecylsilyl-1-decene and methyldidecylsilyl-2-decene.