Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([O:8][C:9]([NH:11][CH2:12][CH2:13][CH2:14][CH2:15][C@@H:16]([C:18]([OH:20])=[O:19])[NH2:17])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O1CCOCC1.[N+:27]([C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=1[S:36](Cl)(=[O:38])=[O:37])([O-:29])=[O:28].[CH:40]1([NH:46][CH:47]2[CH2:52][CH2:51][CH2:50][CH2:49][CH2:48]2)[CH2:45][CH2:44][CH2:43][CH2:42][CH2:41]1>[OH-].[Na+].C(OCC)C>[CH:47]1([NH:46][CH:40]2[CH2:41][CH2:42][CH2:43][CH2:44][CH2:45]2)[CH2:48][CH2:49][CH2:50][CH2:51][CH2:52]1.[N+:27]([C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=1[S:36]([NH:17][C@H:16]([C:18]([OH:20])=[O:19])[CH2:15][CH2:14][CH2:13][CH2:12][NH:11][C:9]([O:8][CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)=[O:10])(=[O:38])=[O:37])([O-:29])=[O:28]
Reactant: O=[N+]([O-])c1ccccc1S(=O)(=O)Cl
Reactant: N[C@@H](CCCCNC(=O)OCc1ccccc1)C(=O)O
Agent: C1CCC(NC2CCCCC2)CC1
Agent: [Na+]
Agent: [OH-]
Solvent: CCOCC
Solvent: C1COCCO1
Product: O=C(NCCCC[C@H](NS(=O)(=O)c1ccccc1[N+](=O)[O-])C(=O)O)OCc1ccccc1
Yield: 82.3 %

Procedure:
Nε -benzyloxycarbonyl-L-lysine (4.42 g, 16 mmole) was dissolved in 1N aqueous sodium hydroxide (16 ml), and dioxane (10 ml) solution of o-nitrobenzene sulfonyl chloride (3.50 g, 16 mmole) was added dropwise to the solution while keeping the pH value thereof to between 10 and 11 with 1N aqueous sodium hydroxide while cooling with ice and stirring. The mixture was further stirred for 2.5 hours at room temperature, and insoluble matter was removed by filtration. The filtrate thus obtained was washed with two 100 ml portions of diethyl ether. To the water layer, ethyl acetate (150 ml) was added and the solution was adjusted to pH 1.0 with 1N aqueous hydrochloric acid under vigorous stirring. The ethyl acetate layer was separated and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure and the oily residue thus obtained was dissolved in diethyl ether (50 ml). To the solution, with stirring, dicyclohexylamine 2.99 g, 17 mmole) was added to obtain Nα -o-nitrobenzenesulfonyl-Nε -benzyloxycarbonyl-L-lysine dicyclohexylamine salt (yield:8.52 g; 83.4%)
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([N:16]2[CH2:20][C@H:19]([CH2:21][OH:22])[O:18][C:17]2=[O:23])[CH:5]=[CH:6][C:7]=1[N:8]1[CH2:13][CH2:12][N:11]([CH3:14])[C:10](=[O:15])[CH2:9]1.C(N(CC)CC)C.[CH3:31][S:32](Cl)(=[O:34])=[O:33]>N1C=CC=CC=1>[F:1][C:2]1[CH:3]=[C:4]([N:16]2[CH2:20][C@H:19]([CH2:21][O:22][S:32]([CH3:31])(=[O:34])=[O:33])[O:18][C:17]2=[O:23])[CH:5]=[CH:6][C:7]=1[N:8]1[CH2:13][CH2:12][N:11]([CH3:14])[C:10](=[O:15])[CH2:9]1
Reactant: CS(=O)(=O)Cl
Reactant: CN1CCN(c2ccc(N3C[C@H](CO)OC3=O)cc2F)CC1=O
Solvent: CCN(CC)CC
Solvent: c1ccncc1
Product: CN1CCN(c2ccc(N3C[C@H](COS(C)(=O)=O)OC3=O)cc2F)CC1=O
Temperature: 0 °C
Reaction time: 2 h

Procedure:
(5R)-3-(3-Fluoro-4-{4-methyl-3-oxopiperazin-1-yl}phenyl)-5-hydroxymethyloxazolidin-2-one (900 mg) was dissolved in pyridine (20 ml), and cooled to 0° C. Triethylamine (0.5 ml) and methanesulfonyl chloride (0.24 ml) were added, and stirring continued at 5° C. for 2 hours. Solvent was evaporated, and the residue chromatographed on silica, using as eluant a gradient increasing in polarity from 0 to 3% methanol in dichloromethane. Relevant fractions were combined and evaporated to give (5R)-3-(3-fluoro-4-{4-methyl-3-oxopiperazin-1-yl}phenyl)-5-(methanesulfonyloxymethyl)oxazolidin-2-one (990 mg).
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[N:10]1[CH2:14][CH2:13][CH2:12][CH2:11]1)[CH2:5][NH2:6].[N:15]([C:18]1[CH:27]=[CH:26][CH:25]=[C:24]2[C:19]=1[CH:20]=[C:21]([CH3:28])[N:22]=[CH:23]2)=[C:16]=[O:17].N(C1C=CC=C2C=1C=CN=C2)=C=O>>[F:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[N:10]1[CH2:14][CH2:13][CH2:12][CH2:11]1)[CH2:5][NH:6][C:16]([NH:15][C:18]1[CH:27]=[CH:26][CH:25]=[C:24]2[C:19]=1[CH:20]=[C:21]([CH3:28])[N:22]=[CH:23]2)=[O:17]
Reactant: NCc1ccc(N2CCCC2)c(F)c1
Reactant: Cc1cc2c(N=C=O)cccc2cn1
Agent: O=C=Nc1cccc2cnccc12
Product: Cc1cc2c(NC(=O)NCc3ccc(N4CCCC4)c(F)c3)cccc2cn1

Procedure:
The title compound was prepared using the procedure described in Example 61B using 3-fluoro-4-(1-pyrrolidinyl)benzylamine and the product from Example 154A instead of 4-cyanobenzyl alcohol and the product from Example 61A. 1H NMR (300 MHz, DMSO-d6) δ 9.17 (s, 1H), 8.59 (s, 1H), 8.22 (d, 1H, J=7.5 Hz), 7.73 (s, 1H), 7.69 (d, 1H, J=7.5 Hz), 7.50 (t, 1H, J=7.5 Hz), 7.03 (m, 2H), 6.93 (t, 1H, J=6 Hz), 6.72 (m, 1H), 4.24 (d, 2H, J=6 Hz), 3.28 (m, 4H), 2.64 (s, 3H), 1.88 (m, 4H); MS (ESI) 379 (M+H)+; Anal. Calcd for C22H23FN4O: C, 69.82; H, 6.13; N, 14.80. Found: C, 69.76; H, 6.06; N, 14.69.
Reaction SMILES: [Li]CCCC.CC1(C)CCCC(C)(C)N1.[Cl:16][C:17]1[CH:22]=[N:21][CH:20]=[CH:19][N:18]=1.[CH2:23]([O:30][C:31]1[CH:32]=[C:33]([CH:36]=[CH:37][CH:38]=1)[CH:34]=[O:35])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1>CCOC(C)=O.C1COCC1>[Cl:16][C:17]1[C:22]([CH:34]([C:33]2[CH:36]=[CH:37][CH:38]=[C:31]([O:30][CH2:23][C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[CH:32]=2)[OH:35])=[N:21][CH:20]=[CH:19][N:18]=1
Reactant: Clc1cnccn1
Reactant: O=Cc1cccc(OCc2ccccc2)c1
Agent: CC1(C)CCCC(C)(C)N1
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: OC(c1cccc(OCc2ccccc2)c1)c1nccnc1Cl
Temperature: 0 °C

Procedure:
A THF (20 mL) solution of 2M n-BuLi in cyclohexanes was cooled to −78° C. and charged with 2,2,6,6-tetramethylpiperidine (1.8 mL, 10.48 mmol). The reaction vessel was removed from the cooling bath and allowed to warm to 0° C. for 15 min, then cooled back to −78° C. and charged with 2-chloropyrazine (1.0 g, 8.73 mmol) dropwise. The reaction was allowed to react for 15 min, and charged with a 10.0 mL THF solution of 3-benzyloxybenzaldehyde (2.0 g, 9.60 mmol) slowly at −78° C. The reaction was allowed to react for 2 h (TLC analysis (30% EtOAc:Hex)) and quenched with HClconc. (2.0 mL), and H2O (30.0 mL). The crude product was extracted from the aqueous/THF layer 4× with CH2Cl2. The organic layers were combined and washed 1× with H2O, 1×brine, dried over Na2SO4 and concentrated in vacuo, to yield the crude product as a brown oil. High performance flash chromatography (HPFC) with a 70 g Jones silica gel column (30% EtOAc:Hex) was applied to yield the desired product as a pale yellow solid; 1H NMR (CDCl3, 400 MHz) δ 5.01 (s, 3H), 6.00 (s, 2H), 6.90-6.96 (m, 3H), 7.23-7.41 (m, 6H), 8.36 (d, 1H, J=2.4 Hz), 8.54 (d, 1H, J=2.5 Hz); MS (ES) 327.16 (M+1), 329.16 (M+3).
Reaction SMILES: [CH:1]1([CH2:4][O:5][C:6]2[CH:23]=[CH:22][C:9]([C:10]([NH:12][C:13]3[C:18]([OH:19])=[CH:17][C:16]([OH:20])=[CH:15][C:14]=3[F:21])=O)=[CH:8][C:7]=2[F:24])[CH2:3][CH2:2]1.ClC(Cl)(Cl)C(Cl)(Cl)Cl.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(N(CC)CC)C>C(#N)C>[CH:1]1([CH2:4][O:5][C:6]2[CH:23]=[CH:22][C:9]([C:10]3[O:19][C:18]4[CH:17]=[C:16]([OH:20])[CH:15]=[C:14]([F:21])[C:13]=4[N:12]=3)=[CH:8][C:7]=2[F:24])[CH2:3][CH2:2]1
Reactant: O=C(Nc1c(O)cc(O)cc1F)c1ccc(OCC2CC2)c(F)c1
Agent: ClC(Cl)(Cl)C(Cl)(Cl)Cl
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CC#N
Solvent: CCN(CC)CC
Product: Oc1cc(F)c2nc(-c3ccc(OCC4CC4)c(F)c3)oc2c1
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 5.1 %

Procedure:
To a solution of 4-(cyclopropylmethoxy)-3-fluoro-N-(2-fluoro-4,6-dihydroxyphenyl)benzamide (2.29 g), hexachloroethane (4.04 g) and triphenylphosphine (4.48 g) in acetonitrile (50 mL) was added triethylamine (2.86 mL) at 0° C., and the mixture was stirred at room temperature for 15 min, and then with heating at 80° C. for 1 hr. The reaction mixture was filtered, the solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (hexane/ethyl acetate) to give the title compound (110 mg). 1H NMR (300 MHz, CDCl3) δ 0.37-0.45 (2H, m), 0.65-0.74 (2H, m), 1.24-1.44 (1H, m), 3.97 (2H, d, J=7.2 Hz), 5.26 (1H, d, J=3.4 Hz), 6.97-7.10 (2H, m), 7.38 (1H, dd, J=8.5, 1.3 Hz), 7.87-7.98 (2H, m).
Reaction SMILES: Br[C:2]1[CH:3]=[N:4][CH:5]=[CH:6][CH:7]=1.[F:8][C:9]([F:19])([F:18])[C:10]1[CH:17]=[CH:16][C:13]([CH:14]=[O:15])=[CH:12][CH:11]=1.N1C=CC=CC=1C=O>>[N:4]1[CH:5]=[CH:6][CH:7]=[C:2]([CH:14]([C:13]2[CH:12]=[CH:11][C:10]([C:9]([F:8])([F:18])[F:19])=[CH:17][CH:16]=2)[OH:15])[CH:3]=1
Reactant: Brc1cccnc1
Reactant: O=Cc1ccc(C(F)(F)F)cc1
Agent: O=Cc1ccccn1
Product: OC(c1ccc(C(F)(F)F)cc1)c1cccnc1

Procedure:
The title compound was prepared analogously to the method in Intermediate 25: step a using 3-bromopyridine and 4-(trifluoromethyl)benzaldehyde in place of 5-bromo-1-methyl-1H-imidazole and picolinaldehyde, respectively.
Reaction SMILES: [CH3:1][O:2][C:3]([C@@H:5]1[CH2:9][CH2:8][CH2:7][C@H:6]1[C:10]([OH:12])=O)=[O:4].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[NH2:46][C:47]1[S:48][CH:49]=[C:50]([C:52]2[CH:63]=[CH:62][C:55]([C:56]([NH:58][CH:59]3[CH2:61][CH2:60]3)=[O:57])=[CH:54][CH:53]=2)[N:51]=1>CN(C=O)C>[CH3:1][O:2][C:3]([C@@H:5]1[CH2:9][CH2:8][CH2:7][C@H:6]1[C:10](=[O:12])[NH:46][C:47]1[S:48][CH:49]=[C:50]([C:52]2[CH:53]=[CH:54][C:55]([C:56](=[O:57])[NH:58][CH:59]3[CH2:61][CH2:60]3)=[CH:62][CH:63]=2)[N:51]=1)=[O:4]
Reactant: COC(=O)[C@@H]1CCC[C@H]1C(=O)O
Reactant: Nc1nc(-c2ccc(C(=O)NC3CC3)cc2)cs1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: COC(=O)[C@@H]1CCC[C@H]1C(=O)Nc1nc(-c2ccc(C(=O)NC3CC3)cc2)cs1
Reaction time: 0.25 h

Procedure:
Rac-trans-cyclopentane-1,2-dicarboxylic acid monomethyl ester (86 mg) was dissolved in DMF (5 mL) and treated with HATU (1.1 eq. 214 mg) and DIEA (3 eq, 267 μL) and stirred for 15 minutes. Then 4-(2-amino-thiazol-4-yl)-N-cyclopropyl-benzamide (1 eq, 129.5 mg) was added and the mixture stirred at ambient temperature overnight. The reaction was cooled, filtered and the solvents removed. The resulting mixture was redissolved in 5 ml of 90% DMF, 10% water with 0.1% TFA and purified by reverse phase HPLC to give the product. Yield 14 mg. MS: 414.5 (M+H+); H1-NMR (DMSO-d6): δ(ppm) 12.4 (s, 1H), 8.4 (m, 2H), 7.9-7.7 (m, 5H), 3.6 (s, 3H), 3.2 (m, 2H), 2.8 (m, 1H), 2.0 (m, 2H), 1.7 (m, 4H) 0.7-0.6 (m, 4H).
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][CH2:4][CH:3]([C:7]2[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[NH:9][CH:8]=2)[CH2:2]1.[CH3:16][N:17]([CH3:31])[C:18]1([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[CH2:23][CH2:22][C:21](=O)[CH2:20][CH2:19]1.C(O)(=O)C>ClCCCl>[NH:9]1[C:10]2[C:15](=[CH:14][CH:13]=[CH:12][CH:11]=2)[C:7]([CH:3]2[CH2:4][CH2:5][CH2:6][N:1]([CH:21]3[CH2:20][CH2:19][C:18]([N:17]([CH3:31])[CH3:16])([C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=4)[CH2:23][CH2:22]3)[CH2:2]2)=[CH:8]1
Reactant: c1ccc2c(C3CCCNC3)c[nH]c2c1
Reactant: CN(C)C1(c2ccccc2)CCC(=O)CC1
Solvent: ClCCCl
Solvent: CC(=O)O
Product: CN(C)C1(c2ccccc2)CCC(N2CCCC(c3c[nH]c4ccccc34)C2)CC1
Temperature: 25 °C
Reaction time: 24 h

Procedure:
3-piperidine-3-yl-1H-indole (233 mg, 1.16 mmole) and 4-dimethylamino-4-phenylcyclohexanone (253 mg, 1.16 mmole) were dissolved in dry 1,2-dichloroethane (20 ml). Glacial acetic acid (1.16 mmole) and sodium triacetoxy boron hydride (350 mg, 1.63 mmole) were added to this mixture. The mixture was then stirred for 24 hours at RT. The reaction mixture was worked up by distilling off the 1,2-dichloroethane and diluting with water (20 ml). The reaction mixture was adjusted to pH 11 with 5M NaOH and extracted with EE (3×20 ml). The organic phase was dried with Na2SO4 and concentrated by evaporation. The product was a mixture of two diastereoisomeric compounds, which were separated by chromatography with methanol. The non-polar diastereoisomer was obtained as a colourless oil in a yield of 208 mg (45%) and the polar diastereoisomer was obtained as a colourless oil in a yield of 50 mg (11%).
Reaction SMILES: [H-].[Li+].[F:3][C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][CH:13]=1)[NH:10][C:9](=[O:14])[CH:8]=[N:7]2.Br[CH2:16][CH2:17][CH:18]1[O:22][CH2:21][CH2:20][O:19]1.O>CN(C)C=O>[O:19]1[CH2:20][CH2:21][O:22][CH:18]1[CH2:17][CH2:16][N:10]1[C:11]2[C:6](=[CH:5][C:4]([F:3])=[CH:13][CH:12]=2)[N:7]=[CH:8][C:9]1=[O:14]
Reactant: BrCCC1OCCO1
Reactant: O=c1cnc2cc(F)ccc2[nH]1
Agent: [H-]
Agent: [Li+]
Solvent: O
Solvent: CN(C)C=O
Product: O=c1cnc2cc(F)ccc2n1CCC1OCCO1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 31.5 %

Procedure:
Lithium hydride (57 mg, 7.3 mmol) was added to a solution of 6-fluoroquinoxalin-2(1H)one (1 g, 6.0 mmol) in N,N-dimethylformamide (6 ml) under cooling on ice and the mixture was stirred at room temperature for 30 minutes. The mixture was cooled on ice again and a solution of 2-(2-bromoethyl)-1,3-dioxolane (0.88 ml, 7.3 mmol) in N,N-dimethylformamide (2 ml) was gradually added thereto and the mixture was stirred for 4 hours. Water was added thereto, the mixture was then extracted with ethyl acetate, and the extract was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate) to yield 0.5 g (32%) of the title compound.
Reaction SMILES: FC(F)(F)S(O[C:7]1[CH:12]=[CH:11][C:10]([O:13][CH3:14])=[CH:9][C:8]=1[CH2:15][CH2:16][C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])(=O)=O.[CH2:26]([Sn](CCCC)(CCCC)CCCC)[CH:27]=[CH2:28].[Cl-].[Li+]>CN(C=O)C.C1(C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)[Pd][P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH:26]([C:7]1[CH:12]=[CH:11][C:10]([O:13][CH3:14])=[CH:9][C:8]=1[CH2:15][CH2:16][C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])=[CH:27][CH3:28]
Reactant: COc1ccc(OS(=O)(=O)C(F)(F)F)c(CCC(=O)OC(C)(C)C)c1
Reactant: C=CC[Sn](CCCC)(CCCC)CCCC
Agent: c1ccc([P]([Pd][P](c2ccccc2)(c2ccccc2)c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: [Cl-]
Agent: [Li+]
Solvent: CN(C)C=O
Product: CC=Cc1ccc(OC)cc1CCC(=O)OC(C)(C)C
Temperature: 95 °C
Yield: 171.6 %

Procedure:
Argon was passed through a solution of tert-butyl 3-(2-trifluoromethylsulfonyloxy-5-methoxyphenyl)propionate (15 g, 39 mmol), allyltributyl tin (15.8 mL, 51 mmol), and lithium chloride (2.1 g, 51 mmol) in DMF (120 mL) for 10 min, and bis(triphenylphosphine)palladium dchloride (1.5 g, 2.2 mmol) was added. The reaction mixture was heated at 95° C. for 1.5 h and evaporated. The residue was partitioned between 10% KF aquoues solution and ether. The combined extracts were dried and evaporated to give the titled compound (18.5 g).
Reaction SMILES: [C:1]([C:4]1[C:32]([OH:33])=[CH:31][C:7]([O:8][CH2:9][CH2:10][CH2:11][O:12][C:13]2[CH:27]=[CH:26][C:16]3[CH2:17][CH2:18][CH:19]([C:21]([O:23]CC)=[O:22])[O:20][C:15]=3[C:14]=2[CH2:28][CH2:29][CH3:30])=[C:6]([CH2:34][CH3:35])[CH:5]=1)(=[O:3])[CH3:2].[OH-].[Na+:37]>O1CCOCC1.CO>[Na+:37].[C:1]([C:4]1[C:32]([OH:33])=[CH:31][C:7]([O:8][CH2:9][CH2:10][CH2:11][O:12][C:13]2[CH:27]=[CH:26][C:16]3[CH2:17][CH2:18][CH:19]([C:21]([O-:23])=[O:22])[O:20][C:15]=3[C:14]=2[CH2:28][CH2:29][CH3:30])=[C:6]([CH2:34][CH3:35])[CH:5]=1)(=[O:3])[CH3:2]
Reactant: CCCc1c(OCCCOc2cc(O)c(C(C)=O)cc2CC)ccc2c1OC(C(=O)OCC)CC2
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: C1COCCO1
Product: CCCc1c(OCCCOc2cc(O)c(C(C)=O)cc2CC)ccc2c1OC(C(=O)[O-])CC2
Temperature: 25 °C
Yield: 68 %

Procedure:
A solution of ethyl 7-[3-(4-acetyl-2-ethyl-5-hydroxyphenoxy)propoxy]-3,4-dihydro-8-propyl-2H-1-benzopyran-2-carboxylate in dioxane (3.5M solution) was treated with 2N NaOH (3.0 eqv) and stirred at room temperature. After stirring for 4 hours, the dioxane was removed from the reaction, and the remaining solution was diluted with water and acidified with 5N HC1. The resulting milky solution was extracted with EtOAc. The ethyl acetate extract was dried over MgSO4 and filtered. Solvent removal gave a white solid. The free acid was stirred in methanol and treated with 3 eqv. of NaOH(aq). The solvent was removed from the reaction and the product was purified by CHP-20 reverse phase chromatography eluting with a water/methanol gradient. The pure product was obtained in 68% yield by lyophilization of the product containing fractions.
Reaction SMILES: [Si:1]([O:8][CH2:9][CH2:10][NH:11][S:12]([CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)(=[O:14])=[O:13])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[Li][CH2:23]CCC.ClCI>O1CCCC1>[Si:1]([O:8][CH2:9][CH2:10][NH:11][S:12]([C:15]([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)=[CH2:23])(=[O:14])=[O:13])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]
Reactant: CC(C)(C)[Si](C)(C)OCCNS(=O)(=O)Cc1ccccc1
Reactant: [Li]CCCC
Agent: ClCI
Solvent: C1CCOC1
Product: C=C(c1ccccc1)S(=O)(=O)NCCO[Si](C)(C)C(C)(C)C
Temperature: -78 °C
Reaction time: 2 h
Yield: 70.1 %

Procedure:
To a solution of N-[2-[tert-butyl(dimethyl)silyl]oxyethyl]-1-phenyl-methanesulfonamide (33 g, 100.2 mmol) in tetrahydrofuran (334 mL) at −78° C. was slowly added n-BuLi (2.5 M in hexanes) (100 mL, 250 mmol) via cannula and the reaction was stirred at −78° C. was 2 hours. Chloroiodomethane (8.3 mL, 110 mmol) was then slowly added and the reaction was stirred at −78° C. for one hour, then allowed to warm to room temperature and aged for 16 hours. The reaction was then quenched with saturated NH4Cl and extracted with dichloromethane, dried with MgSO4, concentrated and purified by silica gel column chromatography (0-60% EtOAc in heptane) to give N-[2-[tert-butyl(dimethyl)silyl]oxyethyl]-1-phenyl-ethenesulfonamide (24 g, 70% yield). LCMS (ESI), m/z, 342. [M+H]+.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[CH:4][C:5](=[O:11])[N:6]([CH2:8][CH2:9]Br)[CH:7]=1.[CH3:12][O:13][C:14]1[CH:15]=[C:16]2[C:21](=[CH:22][C:23]=1[O:24][CH3:25])[N:20]=[CH:19][CH:18]=[C:17]2[OH:26].C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C>[Br:1][C:2]1[CH:3]=[CH:4][C:5](=[O:11])[N:6]([CH2:8][CH2:9][N:20]2[C:21]3[C:16](=[CH:15][C:14]([O:13][CH3:12])=[C:23]([O:24][CH3:25])[CH:22]=3)[C:17](=[O:26])[CH:18]=[CH:19]2)[CH:7]=1
Reactant: COc1cc2nccc(O)c2cc1OC
Reactant: O=c1ccc(Br)cn1CCBr
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Product: COc1cc2c(=O)ccn(CCn3cc(Br)ccc3=O)c2cc1OC
Temperature: 23 °C
Reaction time: 18 h

Procedure:
A suspension of 5-bromo-1-(2-bromoethyl)pyridin-2(1 H)-one (100 mg, 356 μmol), 6,7-dimethoxyquinolin-4-ol (88 mg, 427 μmol), and cesium carbonate (290 mg, 890 μmol) in DMF (2 mL) was stirred at 23° C. for 18 h. The reaction mixture was partitioned between CH2Cl2 and 5% NaHCO3. The aqueous was extracted with CH2Cl2 (2×10 mL) and the combined organics were dried over MgSO4. The solvents were concentrated to an oil from toluene and purified on silica (12 g) eluting with 0-100% of 6% (2M NH3 in MeOH/CH2Cl2). MS (ESI pos. ion) m/z (MH+): 405/407. Calc'd exact mass for C18H17BrN2O4: 404. 1H NMR (400 MHz, DMSO-d6) δ ppm 3.84 (s, 3 H) 4.00 (s, 3 H) 4.25 (t, J=7.04 Hz, 2 H) 4.47 (t, J=7.04 Hz, 2 H) 5.97 (d, J=7.63 Hz, 1 H) 6.44 (d, J=9.59 Hz, 1 H) 7.41 (s, 1 H) 7.50-7.60 (m, 2 H) 7.74 (d, J=7.63 Hz, 1 H) 7.87 (d, J=2.54 Hz, 1H). 13C NMR (101 MHz, DMSO-d6) δ ppm 47.43, 49.21, 55.39, 56.01, 96.58, 98.22, 105.09, 108.26, 120.40, 120.95, 135.41, 139.10, 142.58, 142.96, 146.31, 153.03, 160.30, 175.10.
Reaction SMILES: [CH3:1][NH:2][C:3]1[CH:8]=[C:7]([O:9][CH3:10])[CH:6]=[CH:5][C:4]=1[N+:11]([O-])=O.C(O)(C)(C)C.[BH4-].[Na+].C(=O)([O-])O.[Na+]>C(OCC)(=O)C>[CH3:10][O:9][C:7]1[CH:6]=[CH:5][C:4]([NH2:11])=[C:3]([NH:2][CH3:1])[CH:8]=1
Reactant: CNc1cc(OC)ccc1[N+](=O)[O-]
Agent: O=C([O-])O
Agent: [BH4-]
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: CC(C)(C)O
Product: CNc1cc(OC)ccc1N
Temperature: 60 °C
Reaction time: 2 h
Yield: 74.9 %

Procedure:
346 g of stannous chloride were added to a mixture of 35 g of N-methyl-5-methoxy-2-nitroaniline (prepared as described in Preparation 8), 900 ml of t-butanol and 100 ml of ethyl acetate at room temperature, and the resulting mixture was stirred at 60° C. for 2 hours, after which 11 g of sodium borohydride were added in portions at 60° C. over a period of about 1 hour. The reaction mixture was then stirred at 60° C. for 3 hours, after which it was allowed to stand at room temperature for 2 days. It was then poured into ice-water and the aqueous mixture was neutralized by the addition of sodium hydrogencarbonate. The mixture was extracted with ethyl acetate, and the extract was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous sodium sulfate. The solvent was removed from the mixture by distillation under reduced pressure, and the resulting residue was purified by column chromatography through silica gel using a 3:2 by volume mixture of ethyl acetate and hexane as the eluent, to give 21.9 g of the title compound having an Rf value=0.18 (on thin layer chromatography on silica gel; developing solvent: a 1:1 by volume mixture of ethyl acetate and hexane).
Reaction SMILES: [C:1]1([CH:7]([C:9]2[CH:17]=[CH:16][CH:15]=[C:14]3[C:10]=2[C:11]([CH:26]=[CH:27][C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)=[N:12][N:13]3[CH2:18][O:19][CH2:20][CH2:21][Si:22]([CH3:25])([CH3:24])[CH3:23])[OH:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O>ClCCl.CCCCCC>[C:1]1([C:7]([C:9]2[CH:10]=[C:14]3[C:15]([C:11]([CH:26]=[CH:27][C:28]4[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=4)=[N:12][N:13]3[CH2:18][O:19][CH2:20][CH2:21][Si:22]([CH3:25])([CH3:24])[CH3:23])=[CH:16][CH:17]=2)=[O:8])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: C[Si](C)(C)CCOCn1nc(C=Cc2ccccc2)c2c(C(O)c3ccccc3)cccc21
Agent: CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21
Solvent: ClCCl
Solvent: CCCCCC
Product: C[Si](C)(C)CCOCn1nc(C=Cc2ccccc2)c2ccc(C(=O)c3ccccc3)cc21
Temperature: 23 °C
Reaction time: 1 h
Yield: 79.2 %

Procedure:
To a solution of phenyl-{3-styryl-1-[2-(trimethyl-silanyl)-ethoxymethyl]-1H-indazol-yl}-methanol (68 mg, 0.15 mmol) in dichloromethane (3 mL) at 23° C. under an atmosphere of argon was added periodinane (Dess-Martin reagent) (190 mg, 0.45 mmol). The resulting mixture was stirred at 23° C. for 1 hour. The solution was then diluted with hexane (3 mL) then filtered through Celite and concentrated under reduced pressure to a solid. The crude mixture was purified by silica gel chromatography (eluting with hexane:EtOAc 9:1) to give phenyl-{3-styryl-1-[2-(trimethyl-silanyl)-ethoxymethyl]-1H-indazol-6-yl}-methanone (54 mg, 79% yield). Rf sm=0.41, Rf p=0.63 (7:3 hexane:EtOAc); FTIR (thin film) 3059, 2952, 2894, 1659, 1474, 1448, 1307, 1249, 1078, 836, 649 cm−1. MS (ESI) [M+H]/z Calc'd 455, found 455.
Reaction SMILES: Br[C:2]1[S:3][CH:4]=[C:5]([Br:7])[CH:6]=1.[C:8]([Si:12]([CH3:33])([CH3:32])[O:13][CH:14]1[C:22]2[C:17](=[C:18](B3OC(C)(C)C(C)(C)O3)[CH:19]=[CH:20][CH:21]=2)[CH2:16][CH2:15]1)([CH3:11])([CH3:10])[CH3:9].C(=O)([O-])[O-].[K+].[K+]>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.COCCOC.O>[Br:7][C:5]1[CH:6]=[C:2]([C:18]2[CH:19]=[CH:20][CH:21]=[C:22]3[C:17]=2[CH2:16][CH2:15][CH:14]3[O:13][Si:12]([C:8]([CH3:11])([CH3:10])[CH3:9])([CH3:32])[CH3:33])[S:3][CH:4]=1
Reactant: CC1(C)OB(c2cccc3c2CCC3O[Si](C)(C)C(C)(C)C)OC1(C)C
Reactant: Brc1csc(Br)c1
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: O
Solvent: COCCOC
Product: CC(C)(C)[Si](C)(C)OC1CCc2c(-c3cc(Br)cs3)cccc21

Procedure:
Prepared using General Procedure 1. A 2 mL microwave vial was charged with 2,4-dibromothiophene (15 mg, 0.06 mmol), tert-butyldimethyl((4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-dihydro-1H-inden-1-yl)oxy)silane IND INT-8 (23 mg, 0.06 mmol), potassium carbonate (26 mg, 0.18 mmol) and 3:1 mixture of DME/H2O (2 mL). The reaction mixture was degassed by bubbling N2 through the stirred solution for 10 min. Pd(PPh3)4 (5 mg, 0.004 mmol) was added and the solution degassed for an additional 2 min. The vial was subjected to microwave irradiation at 70° C. for 30 min or until starting material consumed. The resulting ((4-(4-bromothiophen-2-yl)-2,3-dihydro-1H-inden-1-yl)oxy)(tert-butyl)dimethylsilane THIO INT-4 was carried onto the next experiment without workup and purification. LCMS-ESI (m/z) calculated for C19H25BrOSSi: 408.1; no M+ found, tR=6.50 min (Method 1).