Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[C:9]([Cl:10])=[CH:8][CH:7]=[CH:6][C:3]=1[CH2:4]Cl.[CH2:11]([N:18]1[C:26]2[C:21](=[CH:22][CH:23]=[C:24]([CH2:27][C:28]([OH:30])=[O:29])[CH:25]=2)[CH:20]=[CH:19]1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1>>[Cl:1][C:2]1[C:9]([Cl:10])=[CH:8][CH:7]=[CH:6][C:3]=1[CH2:4][N:18]1[C:26]2[C:21](=[CH:22][CH:23]=[C:24]([CH2:27][C:28]([OH:30])=[O:29])[CH:25]=2)[CH:20]=[CH:19]1.[CH2:11]([N:18]1[C:26]2[C:21](=[CH:22][CH:23]=[C:24]([CH2:27][C:28]([OH:30])=[O:29])[CH:25]=2)[CH:20]=[CH:19]1)[C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1
Reactant: ClCc1cccc(Cl)c1Cl
Agent: O=C(O)Cc1ccc2ccn(Cc3ccccc3)c2c1
Product: O=C(O)Cc1ccc2ccn(Cc3cccc(Cl)c3Cl)c2c1

Procedure:
The titled compound (13 mg) as a white solid was prepared from the compound [4-6] obtained in the process (6) of Example 4 (100 mg) and 2,3-dichlorobenzyl chloride according to the method of the process (7) of Example 4.
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][C:10](=[O:15])[CH2:11][C:12](=[O:14])[CH3:13])=[CH:4][CH:3]=1.B(OB=O)=O.[OH:21][C:22]1[CH:29]=[CH:28][C:25]([CH:26]=O)=[C:24]([O:30][CH3:31])[CH:23]=1.B(OCCCC)(OCCCC)OCCCC.C(N)CCC.Cl.C([O-])(O)=O.[Na+]>C(OCC)(=O)C.[Cl-].[Na+].O>[OH:21][C:22]1[CH:29]=[CH:28][C:25](/[CH:26]=[CH:13]/[C:12](=[O:14])[CH2:11][C:10](=[O:15])[CH2:9][CH2:8][C:5]2[CH:4]=[CH:3][C:2]([OH:1])=[CH:7][CH:6]=2)=[C:24]([O:30][CH3:31])[CH:23]=1
Reactant: CC(=O)CC(=O)CCc1ccc(O)cc1
Reactant: COc1cc(O)ccc1C=O
Agent: CCCCOB(OCCCC)OCCCC
Agent: Cl
Agent: O=BOB=O
Solvent: CCOC(C)=O
Solvent: CCCCN
Solvent: O
Product: COc1cc(O)ccc1/C=C/C(=O)CC(=O)CCc1ccc(O)cc1
Reaction time: 1 h
Yield: 43.7 %

Procedure:
6-(4-Hydroxyphenyl)hexane-2,4-dione (18 mg, 87 μmol) and boron trioxide (22 mg, 0.32 mmol) was placed in a 20 mL reaction vessel, and dissolved in 0.4 mL of ethyl acetate. To the stirring solution at 80° C. were added 4-hydroxy-2-methoxybenzaldehyde (12 mg, 78 μmol) and tri-n-butyl borate (50 μL, 0.19 mmol). After the reaction mixture was stirred for 2 h at the same temperature, n-butylamine (19 μL, 0.19 mmol) was added with additional stirring for 1 h. The reaction mixture was treated with a 1:1 solution (1 mL) of 1N HCl and brine, and was stirred at 50° C. for 5 min to 1 h (if necessary, the reaction mixture was neutralized by saturated NaHCO3 aqueous solution). The organic layer was purified directly by silica gel column chromatography (eluting with hexane/ethyl acetate or chloroform/methanol) to obtain the title compound as a solid (11.6 mg, 44%) having the following characteristics.
Reaction SMILES: I[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH2:8][S:9][CH3:10])[CH:3]=1.CC(C)([O-])C.[Na+].[NH:17]1[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]1>C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].C1(C)C=CC=CC=1>[CH3:10][S:9][CH2:8][C:4]1[CH:3]=[C:2]([N:17]2[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]2)[CH:7]=[CH:6][CH:5]=1
Reactant: C1CNCCN1
Reactant: CSCc1cccc(I)c1
Agent: [Fe+2]
Agent: CC(C)(C)[O-]
Agent: [Na+]
Solvent: Cc1ccccc1
Product: CSCc1cccc(N2CCNCC2)c1
Temperature: 900 °C
Yield: 31.8 %

Procedure:
A mixture of 2.5 g of 1-iodo-3-(methylsulphanylmethyl)benzene, 1.3 g of sodium tert-butoxide, 0.35 mg of [1,1′-bis(diphenylphosphino)ferrocenyl]palladium chloride, 0.79 g of 1,1′-bis(diphenylphosphino)ferrocene, 4 g of piperazine and 100 cm3 of toluene was heated at 900° C. under a nitrogen stream for 24 hours. The reaction mixture was cooled to room temperature and filtered through sintered glass. The filtrate was washed with 250 cm3 of dichloromethane and then concentrated to dryness under reduced pressure (2.7 kPa). The residue obtained was purified by silica gel column chromatography (particle size 0.04-0.06 mm, diameter 4 cm, height 20 cm) under a pressure of 0.5 bar of nitrogen with a mixture of dichloromethane and methanol (90/10 by volume) and then a mixture of dichloromethane and methanol (85/15 by volume) as eluents, 100-cm3 fractions were collected. Fractions 29 to 36 were combined and concentrated to dryness under reduced pressure (2.7 kPa). The oil obtained was distilled in a bulb oven (B.p.=160° C. approximately under a pressure of 0.1 mm of mercury). 0.67 g of 4-[3-(methylsulphanylmethyl)phenyl]piperazine was obtained in the form of a colorless oil.
Reaction SMILES: [N+](C1C=CC(COC(N2C[C@@H](S)C[C@H]2C(N2CCN(C(=O)COCCNC(OCC3C=CC([N+]([O-])=O)=CC=3)=O)CC2)=O)=O)=CC=1)([O-])=O.[CH2:48]([CH2:50][NH2:51])[OH:49].[C:52]1(=O)[O:57][C:55](=[O:56])[C:54]2=[CH:58][CH:59]=[CH:60][CH:61]=[C:53]12>C1(C)C=CC=CC=1>[C:52]1(=[O:57])[N:51]([CH2:50][CH2:48][OH:49])[C:55](=[O:56])[C:54]2=[CH:58][CH:59]=[CH:60][CH:61]=[C:53]12
Reactant: O=C1OC(=O)c2ccccc21
Reactant: NCCO
Agent: O=C(NCCOCC(=O)N1CCN(C(=O)[C@@H]2C[C@H](S)CN2C(=O)OCc2ccc([N+](=O)[O-])cc2)CC1)OCc1ccc([N+](=O)[O-])cc1
Solvent: Cc1ccccc1
Product: O=C1c2ccccc2C(=O)N1CCO

Procedure:
(2S, 4S )-1-(p-nitrobenzyloxycarbonyl)-2-(4-(2-(2-(p-nitrobenzyloxycarbonylamino) ethoxy)acetyl)piperazine-1-yl) carbonyl-4-mercaptopyrrolidine ##STR12## 1) A 6.11 g portion of ethanolamine and 14.81 g of phthalic anhydride were stirred in 100 ml of toluene for 3 hours with heating. After concentration of the reaction solution, a residue was crystallized from chloroform, collected by filtration and then dried to yield 17.2 g of white 2-phthalimidoethanol.
Reaction SMILES: Cl[C:2]1[CH:10]=[CH:9][C:5]([C:6]([NH2:8])=[O:7])=[CH:4][N:3]=1.[NH:11]1[CH2:14][CH:13]([OH:15])[CH2:12]1.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[OH:15][CH:13]1[CH2:14][N:11]([C:2]2[CH:10]=[CH:9][C:5]([C:6]([NH2:8])=[O:7])=[CH:4][N:3]=2)[CH2:12]1
Reactant: NC(=O)c1ccc(Cl)nc1
Reactant: OC1CNC1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: NC(=O)c1ccc(N2CC(O)C2)nc1
Temperature: 125 °C
Reaction time: 24 h
Yield: 25.9 %

Procedure:
To a solution of 6-chloronicotinamide (0.16 g, 1 mmol) and azetidin-3-ol (73 mg, 1 mmol) in DMF (5 ml) under nitrogen was added K2CO3 (0.41 g, 3 mmol). The resulting solution was stirred under nitrogen at 125° C. for 24 h. After all the starting materials were consumed, the reaction mixture was allowed to cool to ambient temperature. The reaction mixture was then filtered and the filter cake was washed with ethyl acetate. The combined filtrates were concentrated to afford the title compound (50 mg, 25%) as a yellow solid. [LCMS RtA=0.81 min, [M+H]+=194.1].
Reaction SMILES: Br[C:2]1[CH:24]=[N:23][C:5]2[N:6]([CH2:15][O:16][CH2:17][CH2:18][Si:19]([CH3:22])([CH3:21])[CH3:20])[C:7]3[CH:12]=[N:11][C:10]([C:13]#[N:14])=[CH:9][C:8]=3[C:4]=2[CH:3]=1.[CH3:25][C:26]([OH:30])([C:28]#[CH:29])[CH3:27]>O1CCOCC1.C(Cl)Cl.O.[Cu]I.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>[OH:30][C:26]([CH3:27])([CH3:25])[C:28]#[C:29][C:2]1[CH:24]=[N:23][C:5]2[N:6]([CH2:15][O:16][CH2:17][CH2:18][Si:19]([CH3:22])([CH3:21])[CH3:20])[C:7]3[CH:12]=[N:11][C:10]([C:13]#[N:14])=[CH:9][C:8]=3[C:4]=2[CH:3]=1
Reactant: C[Si](C)(C)CCOCn1c2cnc(C#N)cc2c2cc(Br)cnc21
Reactant: C#CC(C)(C)O
Agent: [Cu]I
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Solvent: C1COCCO1
Solvent: O
Product: CC(C)(O)C#Cc1cnc2c(c1)c1cc(C#N)ncc1n2COCC[Si](C)(C)C
Temperature: 105 °C
Yield: 124.2 %

Procedure:
In a flame dried flask, a mixture of 3-bromo-9-(2-trimethylsilanylethoxymethyl)-dipyrido[2,3-b;4′,3′-d]pyrrole-6-carbonitrile (203 mg, 0.503 mmol) and copper (I) iodide (9.58 mg, 50.3 μmol) in 1,4-dioxane (5.3 mL) was degassed and flushed with nitrogen. Tetrakis(triphenylphosphine)palladium(0) (58.1 mg, 50.3 μmol) and 2-methyl-3-butyn-2-ol (244 μL, 2.52 mmol) were added and the reaction mixture was degassed, purged with nitrogen, and heated at 105° C. for 70 min. The cooled reaction mixture was diluted with DCM and water, the layers separated, and the aqueous phase extracted into DCM. The combined organic phase was dried over sodium sulfate and concentrated in vacuo. The resultant residue was dissolved in EtOAc and absorbed onto silica gel for purification by flash chromatography (silica, 25 g column, Biotage, 1-100% EtOAc in heptane) to afford further title compound as a white-yellow solid (254 mg, 124%). The solid was used without further purification. 1H NMR (DMSO-D6, 400 MHz): 9.33 (s, 1H), 8.98 (s, 1H), 8.91 (d, J=1.9 Hz, 1H), 8.76 (d, J=1.9 Hz, 1H), 6.03 (s, 2H), 5.55 (s, 1H), 3.57 (t, J=7.9 Hz, 2H), 1.51 (s, 6H), 0.82 (t, J=8.0 Hz, 2H), −0.16 (s, 9H).
Reaction SMILES: [CH3:1][O:2][C:3](=[O:28])[CH2:4][O:5][C:6]1[CH:14]=[CH:13][CH:12]=[C:11]2[C:7]=1[C:8]([CH2:24][C:25]([NH2:27])=[O:26])=[C:9](CC)[N:10]2[CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.C(C1N(CC2C=CC=CC=2)C2C(C=1CC(N)=O)=C(O)C=CC=2)C.[H-].[Na+].BrCC(OC)=O>CN(C=O)C.O>[CH3:1][O:2][C:3](=[O:28])[CH2:4][O:5][C:6]1[CH:14]=[CH:13][CH:12]=[C:11]2[C:7]=1[C:8]([CH2:24][C:25]([NH2:27])=[O:26])=[CH:9][N:10]2[CH2:15][C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1
Reactant: CCc1c(CC(N)=O)c2c(OCC(=O)OC)cccc2n1Cc1ccccc1
Agent: CCc1c(CC(N)=O)c2c(O)cccc2n1Cc1ccccc1
Agent: COC(=O)CBr
Agent: [H-]
Solvent: O
Solvent: CN(C)C=O
Product: COC(=O)COc1cccc2c1c(CC(N)=O)cn2Cc1ccccc1
Reaction time: 1.5 h
Yield: 34 %

Procedure:
2-[[3-(2-Amino-2-oxoethyl)-2-ethyl-1-(phenylmethyl)-1H-indol-4-yl]oxy]acetic acid methyl ester. 2-Ethyl-4-hydroxy-1-(phenylmethyl)-1H-indole-3-acetamide (135 mg, 0.44 mmol) was added to 17.6 mg (0.44 mmol) of NaH/mineral oil (washed with hexanes) in 5 mL of DMF, stirred 1.5 hours, 0.04 mL (0.44 mmol) of methyl 2-bromoacetate added and stirring maintained for 3 hours. The mixture was diluted with water, extracted with ethyl acetate. The ethyl acetate was washed with brine, dried (MgSO4) and concentrated. The residue was chromatographed on silica gel eluting with 2% MeOH/ethyl acetate to give 34 mg (34% yield) of 2-[[3-(2-amino-2-oxoethyl)-1-(phenylmethyl)-1H-indol-4-yl]oxy]acetic acid methyl ester.
Reaction SMILES: [CH2:1]([O:8][N:9]=[C:10]([C:14](=[N:16][O:17][CH3:18])[CH3:15])[C:11](O)=[O:12])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.S(Cl)(Cl)=O.[CH3:23][NH:24][CH3:25].O>C1(C)C=CC=CC=1.CN(C)C=O>[CH2:1]([O:8][N:9]=[C:10]([C:14](=[N:16][O:17][CH3:18])[CH3:15])[C:11]([N:24]([CH3:25])[CH3:23])=[O:12])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CON=C(C)C(=NOCc1ccccc1)C(=O)O
Reactant: CNC
Solvent: Cc1ccccc1
Solvent: CN(C)C=O
Solvent: O
Product: CON=C(C)C(=NOCc1ccccc1)C(=O)N(C)C
Temperature: 60 °C
Reaction time: 1 h
Yield: 53 %

Procedure:
To a solution of 0.9 g (3.6 mmol) of 2-benzyloxyimino-3-methoxyiminobutyric acid in 15 ml of toluene, 0.5 g (4.0 mmol) of thionyl chloride and one drop of N,N-dimethylformamide were added and the mixture was stirred for 1 hour at 60° C. After cooling with an ice, 5 ml of 50% dimethylamine solution was added and the mixture was stirred for 0.5 hour at room temperature. 30 ml of water was added and the mixture was extracted three times with 50 ml of diethylether. After washing with water and a saturated aqueous sodium chloride, the organic layer was dried over with anhydrous magnesium sulfate and the solvent was distilled off to obtain a residue, which was then purified by a column chromatography on a silica gel (n-hexane/ethyl acetate) to obtain 0.53 g (yield: 53%) of 2-benzyloxyimino-3-methoxyimino-N,N-dimethylbutyramide as a colorless oil.
Reaction SMILES: [CH3:1][O:2][C:3]1[C:8]([CH3:9])=[C:7]([CH3:10])[C:6]([O:11][CH3:12])=[C:5]([CH3:13])[C:4]=1[CH2:14]/[CH:15]=[C:16](\[CH3:22])/[CH2:17][CH2:18][CH2:19][CH2:20][OH:21].[CH3:23][C:24](OC(C)=O)=[O:25]>N1C=CC=CC=1>[C:24]([O:21][CH2:20][CH2:19][CH2:18][CH2:17]/[C:16](/[CH3:22])=[CH:15]/[CH2:14][C:4]1[C:5]([CH3:13])=[C:6]([O:11][CH3:12])[C:7]([CH3:10])=[C:8]([CH3:9])[C:3]=1[O:2][CH3:1])(=[O:25])[CH3:23]
Reactant: CC(=O)OC(C)=O
Reactant: COc1c(C)c(C)c(OC)c(C/C=C(\C)CCCCO)c1C
Solvent: c1ccncc1
Product: COc1c(C)c(C)c(OC)c(C/C=C(\C)CCCCOC(C)=O)c1C
Reaction time: 8 h
Yield: 62.3 %

Procedure:
(E)-7-(2,5-dimethoxy-3,4,6-trimethylphenyl)-5-methylhept-5-en-1-ol in pyridine (2 mL) was treated with Ac2O (2 mL) at 0° C. and let stir overnight. The reaction was quenched with H2O (10 mL) followed by addition of EtOAc (10 mL) and separated. The aqueous phase was extracted with EtOAc (3×10 mL) and the combined organics washed with brine (15 mL), dried over anhydrous Na2SO4 and concentrated to a yellow oil. Flash chromatography on silica yielded 77.9 mg (62.3%) of (E)-7-(2,5-dimethoxy-3,4,6-trimethylphenyl)-5-methylhept-5-enyl acetate as a clear oil.
Reaction SMILES: I.CS[C:4](=[N:18][CH2:19][CH3:20])[NH:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=1[N:12]1[CH2:17][CH2:16][O:15][CH2:14][CH2:13]1.[CH2:21]([NH2:25])[CH2:22][CH2:23][CH3:24]>C(O)(C)(C)C>[CH2:21]([NH:25][C:4]([NH:18][CH2:19][CH3:20])=[N:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=1[N:12]1[CH2:17][CH2:16][O:15][CH2:14][CH2:13]1)[CH2:22][CH2:23][CH3:24]
Reactant: CCCCN
Reactant: CCN=C(Nc1ccccc1N1CCOCC1)SC
Agent: I
Solvent: CC(C)(C)O
Product: CCCCNC(=Nc1ccccc1N1CCOCC1)NCC

Procedure:
A mixture of 2-methyl-1-(2-morpholinophenyl)-3-ethyl-2-thiopseudourea hydriodide (10 g prepared as described in Example 212), n-butylamine (2.7 g) and t-butanol (75 ml) was heated at 90°-95° C. for 172 hours to yield 1-(n-butyl)-2-(2-morpholinophenyl)-3-ethylguanidine which was converted into its monofumarate salt (m.p. 159°-160° ) which was recrystallised from a 1:2 mixture of methanol and ether.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:6]=[C:7]([Cl:9])[CH:8]=1)[NH2:5].[C:10](OCC)(OCC)([O:13][CH2:14][CH3:15])[CH2:11][CH3:12]>>[Cl:1][C:2]1[CH:3]=[C:4]([N:5]=[C:10]([O:13][CH2:14][CH3:15])[CH2:11][CH3:12])[CH:6]=[C:7]([Cl:9])[CH:8]=1
Reactant: CCOC(CC)(OCC)OCC
Reactant: Nc1cc(Cl)cc(Cl)c1
Product: CCOC(CC)=Nc1cc(Cl)cc(Cl)c1

Procedure:
This is prepared by the reaction of equimolar amounts of 3,5-dichloroaniline and triethyl orthopropionate, as generally described in Chemical Reviews 61, 185 (1961), to give an 86% weight yield of product distilling at 89° C./0.15 mm.
Reaction SMILES: C([O:8][N:9]1[C:15](=[O:16])[N:14]2[CH2:17][C@H:10]1[CH2:11][CH2:12][C@H:13]2[C:18]([NH:20][C:21]1[CH:35]=[CH:34][C:24]([CH2:25][NH:26][C:27](=[O:33])[O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[CH:23][CH:22]=1)=[O:19])C1C=CC=CC=1>[Pd].CO>[C:29]([O:28][C:27](=[O:33])[NH:26][CH2:25][C:24]1[CH:23]=[CH:22][C:21]([NH:20][C:18]([C@@H:13]2[CH2:12][CH2:11][C@@H:10]3[CH2:17][N:14]2[C:15](=[O:16])[N:9]3[OH:8])=[O:19])=[CH:35][CH:34]=1)([CH3:32])([CH3:30])[CH3:31]
Reactant: CC(C)(C)OC(=O)NCc1ccc(NC(=O)[C@@H]2CC[C@@H]3CN2C(=O)N3OCc2ccccc2)cc1
Agent: [Pd]
Solvent: CO
Product: CC(C)(C)OC(=O)NCc1ccc(NC(=O)[C@@H]2CC[C@@H]3CN2C(=O)N3O)cc1
Reaction time: 8 h

Procedure:
Palladium on carbon (7.8 mg; 10% Pd/C) was added to a solution of the product of step 1 (35 mg, 0.073 mmol) in methanol (2 mL), and the resulting mixture was stirred under hydrogen (balloon) overnight. LC-MS analysis showed the reaction was complete. The reaction mixture was filtered through a microfilter and the filtrate was concentrated under vacuum which was azeotroped from toluene to afford the title compound as a white solid.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][CH2:9][C:10]2[CH:11]=[N:12][CH:13]=[CH:14][CH:15]=2)=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].[CH3:22][N:23]([CH3:28])[S:24](Cl)(=[O:26])=[O:25]>ClCCl>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]([CH2:9][C:10]2[CH:11]=[N:12][CH:13]=[CH:14][CH:15]=2)[S:24]([N:23]([CH3:28])[CH3:22])(=[O:26])=[O:25])=[CH:6][CH:7]=1
Reactant: CN(C)S(=O)(=O)Cl
Reactant: Clc1ccc(NCc2cccnc2)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: ClCCl
Product: CN(C)S(=O)(=O)N(Cc1cccnc1)c1ccc(Cl)cc1
Temperature: 25 °C
Reaction time: 24 h

Procedure:
A 2.8 g. portion of 3-(4-chlorophenylaminomethyl)pyridine was dissolved in dichloromethane, and to it was added 2.1 g. of potassium carbonate and 1.6 ml. of dimethylsulfamoyl chloride. The mixture was stirred at ambient temperature for 1 day, and was then stirred under gentle heating for 3 days. The solvent was then evaporated under vacuum, and the oily residue was purified by chromatography on silica gel in chloroform to obtain 3.9 g. of the desired product. Its elemental analysis was as follows.
Reaction SMILES: [CH3:1][O:2][N:3]=[C:4]([C:9](=[O:11])[CH3:10])[C:5]([O:7][CH3:8])=[O:6].[I-].[Na+].C(N(CC)CC)C.[C:21]([Si:25]([CH3:28])([CH3:27])Cl)([CH3:24])([CH3:23])[CH3:22]>C(#N)C>[Si:25]([O:11][C:9](=[CH2:10])[C:4](=[N:3][O:2][CH3:1])[C:5]([O:7][CH3:8])=[O:6])([C:21]([CH3:24])([CH3:23])[CH3:22])([CH3:28])[CH3:27]
Reactant: CON=C(C(C)=O)C(=O)OC
Reactant: CC(C)(C)[Si](C)(C)Cl
Agent: [I-]
Agent: [Na+]
Solvent: CCN(CC)CC
Solvent: CC#N
Product: C=C(O[Si](C)(C)C(C)(C)C)C(=NOC)C(=O)OC

Procedure:
In 20 ml of acetonitrile were dissolved 795 mg of methyl 2-methoxyimino-3-oxobutyrate and 2.25 g of sodium iodide, followed by addition of 2.1 ml of triethylamine. Then, a solution of 1.13 g tert-butyldimethylchlorosilane in 10 ml acetonitrile was added dropwise and the mixture was refluxed for 6.5 hours. The reaction mixture was concentrated under reduced pressure and 20 ml of hexane and 20 ml of water were added to dissolve the residue. The organic layer was separated, washed with 20 ml of 5% aqueous sodium hydrogen carbonate solution, 20 ml of 1N hydrochloric acid and 20 ml of water in the order mentioned, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was chromatographed on a silica gel column and elution was carried out with 100 ml of hexane-ether (5:1, v/v). The eluate was concentrated under reduced pressure to give methyl 3-tert-butyldimethylsilyloxy-2-methoxyimino-3-butenoate as oil.
Reaction SMILES: Br[C:2]1[NH:3][C:4]2[C:9]([C:10]=1[CH:11]1[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]1)=[CH:8][CH:7]=[C:6]([C:17]([O:19][CH3:20])=[O:18])[CH:5]=2.[CH3:21][O:22][CH2:23][O:24][C:25]1[CH:30]=[C:29]([O:31][S:32]([C:35]2[CH:40]=[CH:39][C:38]([CH3:41])=[CH:37][CH:36]=2)(=[O:34])=[O:33])[CH:28]=[CH:27][C:26]=1B(O)O.[Cl-].C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1>[CH:11]1([C:10]2[C:9]3[C:4](=[CH:5][C:6]([C:17]([O:19][CH3:20])=[O:18])=[CH:7][CH:8]=3)[NH:3][C:2]=2[C:26]2[CH:27]=[CH:28][C:29]([O:31][S:32]([C:35]3[CH:40]=[CH:39][C:38]([CH3:41])=[CH:37][CH:36]=3)(=[O:34])=[O:33])=[CH:30][C:25]=2[O:24][CH2:23][O:22][CH3:21])[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]1
Reactant: COC(=O)c1ccc2c(C3CCCCC3)c(Br)[nH]c2c1
Reactant: COCOc1cc(OS(=O)(=O)c2ccc(C)cc2)ccc1B(O)O
Agent: O=C([O-])[O-]
Agent: [Cl-]
Agent: [Na+]
Solvent: C1COCCO1
Product: COCOc1cc(OS(=O)(=O)c2ccc(C)cc2)ccc1-c1[nH]c2cc(C(=O)OC)ccc2c1C1CCCCC1
Temperature: 100 °C
Reaction time: 8 h
Yield: 58 %

Procedure:
Methyl 2-bromo-3-cyclohexyl-1H-indole-6-carboxylate (prepared as in International patent application WO 2004/087714), (2-(methoxymethoxy)-4-{[(4-methylphenyl)-sulfonyl]oxy}phenyl)boronic acid (1 eq) and bis(triphenylphosphinepalladium(II) chloride (0.1 eq) were dissolved in dioxane (0.08M). The solution was degassed and flushed with argon. A 2M aqueous solution of Na2CO3 (1 eq) was added and the mixture was heated to 100° C. After 3 h the temperature was raised to 110° C. Heating was continued overnight. All volatiles were evaporated and the residual material was dissolved in EtOAc. The solution was washed with 1N aqueous HCl, sat. aq. NaHCO3 and brine. After drying over Na2SO4 all volatiles were evaporated in vacuo. The residual material was subjected to FC (PE:EtOAc, 8:2). After evaporation of the product fractions the product was obtained as a light orange amorphous solid (58%). (ES+) m/z 564 (M+H)+.
Reaction SMILES: [CH:1]([C@H:4]1[CH2:8][O:7][C:6](=[O:9])[NH:5]1)([CH3:3])[CH3:2].[Li]CCCC.[Cl:15][C:16]1[CH:21]=[CH:20][C:19]([CH2:22][C:23](Cl)=[O:24])=[CH:18][CH:17]=1>C1COCC1>[Cl:15][C:16]1[CH:21]=[CH:20][C:19]([CH2:22][C:23]([N:5]2[C@@H:4]([CH:1]([CH3:3])[CH3:2])[CH2:8][O:7][C:6]2=[O:9])=[O:24])=[CH:18][CH:17]=1
Reactant: O=C(Cl)Cc1ccc(Cl)cc1
Reactant: CC(C)[C@H]1COC(=O)N1
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: CC(C)[C@H]1COC(=O)N1C(=O)Cc1ccc(Cl)cc1
Temperature: -78 °C
Reaction time: 0.25 h
Yield: 53.5 %

Procedure:
To a solution of (4S)-4-iso propyl-1,3-oxazolidin-2-one (2.0 g, 15.5 mmol) in dry THF (20 mL) at −78° C. under argon, was added dropwise a 2.5M solution of n-BuLi in hexanes (6.2 mL, 15.5 mmol). After stirring at −78° C. for 15 min, (4-chlorophenyl)acetyl chloride (2.70 mL, 21.8 mmol) was added. The resulting reaction mixture was stirred at −78° C. for 30 min and 0° C. for 15 min, quenched with saturated NH4Cl (5 mL) and concentrated in vacuo. The residue was dissolved in EtOAc (100 mL) and washed with saturated Na2CO3 following by brine, dried over MgSO4, filtered and concentrated in vacuo. The crude material was purified by flash chromatography (10%–15% EtOAc/hexane) to give 2.33 g (8.29 mmol, 53%) of (4S)-3-[(4-chlorophenyl)acetyl]-4-isopropyl-1,3-oxazolidin-2-one: 1H NMR (400 MHz, CDCl3) δ 7.31–7.22 (m, 4H), 4.45–4.41 (m, 1H), 4.35–4.16 (m, 4H), 2.39–2.29 (m, 1H), 0.89 d, 3H, J=7.2 Hz), 0.80 (d, 3H, J=7.2 Hz); ESMS m/e: 282.2 (M+H)+.
Reaction SMILES: [NH:1]([C:57]([O:59][C:60]([CH3:63])([CH3:62])[CH3:61])=[O:58])[C@H:2]([C:12]([NH:14][C@H:15]([C:20]([N:22]1[CH2:56][CH2:55][CH2:54][C@H:23]1[C:24]([NH:26][C@H:27]([C:37]([N:39]1[CH2:53][CH2:52][CH2:51][C@H:40]1[C:41]([O:43]CC1C=CC=CC=1)=[O:42])=[O:38])[CH2:28][O:29][CH2:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)=[O:25])=[O:21])[CH2:16][CH:17]([CH3:19])[CH3:18])=[O:13])[CH2:3][O:4][CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.[OH-].[Na+].Cl>CO>[NH:1]([C:57]([O:59][C:60]([CH3:62])([CH3:61])[CH3:63])=[O:58])[C@H:2]([C:12]([NH:14][C@H:15]([C:20]([N:22]1[CH2:56][CH2:55][CH2:54][C@H:23]1[C:24]([NH:26][C@H:27]([C:37]([N:39]1[CH2:53][CH2:52][CH2:51][C@H:40]1[C:41]([OH:43])=[O:42])=[O:38])[CH2:28][O:29][CH2:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)=[O:25])=[O:21])[CH2:16][CH:17]([CH3:18])[CH3:19])=[O:13])[CH2:3][O:4][CH2:5][C:6]1[CH:7]=[CH:8][CH:9]=[CH:10][CH:11]=1
Reactant: CC(C)C[C@H](NC(=O)[C@H](COCc1ccccc1)NC(=O)OC(C)(C)C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](COCc1ccccc1)C(=O)N1CCC[C@H]1C(=O)OCc1ccccc1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: CC(C)C[C@H](NC(=O)[C@H](COCc1ccccc1)NC(=O)OC(C)(C)C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](COCc1ccccc1)C(=O)N1CCC[C@H]1C(=O)O
Temperature: 25 °C
Reaction time: 3 h
Yield: 80.6 %

Procedure:
The substance [20] (74.4 g, 85.4 mM) was dissolved in methanol (300 ml), and 1 N NaOH (110 ml, 1.3 molar excess) was added dropwise at 0° C., and the mixture was stirred at room temperature for three hours. After neutralizing at 0° C. by adding 1 N HCl (26 ml), the methanol was distilled off in vacuo. The aqueous layer was washed twice with ether, 1 N HCl (86 ml) was added at 0° C. and then was extracted with ethyl acetate. The ethyl acetate layer was washed twice with water, dried with anhydrous magnesium sulfate and concentrated in vacuo. Hexane was added to the residue and the thus-formed precipitate was filtered. The precipitate was dissolved in a small amount of chloroform and charged on a column of silica gel packed with chloroform. Elution was carried out with chloroform, chloroform-ethyl acetate (1:1) and chloroform-ethanol-ethyl acetate (5:1:5). The fractions corresponding to the substance as checked by TLC were collected and dried in vacuo to obtain the substance [21] (53.75 g, yield: 81%).