Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C1(B2[O:12][CH2:11][C:10]3[CH:13]=[CH:14][C:15]([S:17][C:18]([F:21])([F:20])[F:19])=[CH:16][C:9]=3[O:8]2)C=CC=CC=1.OO.OCC1C(SC(F)(F)F)=CC=CC=1O>C1COCC1>[OH:12][CH2:11][C:10]1[CH:13]=[CH:14][C:15]([S:17][C:18]([F:19])([F:20])[F:21])=[CH:16][C:9]=1[OH:8]
Reactant: FC(F)(F)Sc1ccc2c(c1)OB(c1ccccc1)OC2
Agent: OCc1c(O)cccc1SC(F)(F)F
Agent: OO
Solvent: C1CCOC1
Product: OCc1ccc(SC(F)(F)F)cc1O
Yield: 27.9 %

Procedure:
A solution of 2-phenyl-7-[(trifluoromethyl)thio]-4H-1,3,2-benzodioxaborinin (14.0 g, 44 mmol) and H2O2 (30% in water, 27.0 ml, 264 mmol) in THF (100 ml) was stirred at ambient temperature for 3 h, before it was quenched at 0° C. with a aquous solution of Na2SO3 (19.0 g). The mixture was acidified with HCl (10%), extracted with EtOAc and the combined organic layers were evaporated to dryness (no drying agent). The crude product was purified on flash column chromatography (isooctane/EtOAc 4:1 and isooctane/EtOAc 7:3) to afford two different fractions. One fraction with the stereoisomer as a by-product, 2-(hydroxymethyl)-3-[(trifluoromethyl)thio]phenol (4.1 g) and one with the title product (2.75 g). 1H-NMR (400 MHz, MeOH): δ 7.40 (1H, d, J 8.0 Hz), δ 7.13 (1H, d, J 8.0 Hz), δ 7.12 (1H, s), δ 4.66 (2H, s).
Reaction SMILES: [F:1][C:2]([F:28])([F:27])[C:3]1[CH:26]=[CH:25][C:6]2=[N:7][N:8]([C:10]3[CH:15]=[C:14]([C:16]([CH2:19][C:20]([CH3:23])([CH3:22])[CH3:21])([CH3:18])[CH3:17])[CH:13]=[CH:12][C:11]=3[OH:24])[N:9]=[C:5]2[CH:4]=1.[CH2:29]([Sn:33](=[O:38])[CH2:34][CH2:35][CH2:36][CH3:37])[CH2:30][CH2:31][CH3:32]>>[CH2:29]([Sn:33]([CH2:34][CH2:35][CH2:36][CH3:37])([O:38][C:11]1[CH:12]=[CH:13][C:14]([C:16]([CH2:19][C:20]([CH3:23])([CH3:22])[CH3:21])([CH3:18])[CH3:17])=[CH:15][C:10]=1[N:8]1[N:7]=[C:6]2[CH:25]=[CH:26][C:3]([C:2]([F:1])([F:27])[F:28])=[CH:4][C:5]2=[N:9]1)[O:24][C:11]1[CH:12]=[CH:13][C:14]([C:16]([CH2:19][C:20]([CH3:21])([CH3:22])[CH3:23])([CH3:17])[CH3:18])=[CH:15][C:10]=1[N:8]1[N:7]=[C:6]2[CH:25]=[CH:26][C:3]([C:2]([F:1])([F:27])[F:28])=[CH:4][C:5]2=[N:9]1)[CH2:30][CH2:31][CH3:32]
Reactant: CCCC[Sn](=O)CCCC
Reactant: CC(C)(C)CC(C)(C)c1ccc(O)c(-n2nc3ccc(C(F)(F)F)cc3n2)c1
Product: CCCC[Sn](CCCC)(Oc1ccc(C(C)(C)CC(C)(C)C)cc1-n1nc2ccc(C(F)(F)F)cc2n1)Oc1ccc(C(C)(C)CC(C)(C)C)cc1-n1nc2ccc(C(F)(F)F)cc2n1

Procedure:
Following the synthetic procedure of Example 25, the title compound is prepared by reaction of the corresponding equivalent amounts of 5-trifluoromethyl-2-(2-hydroxy-5-tert-octylphenyl)-2H-benzotriazole and dibutyltin oxide to give the title compound as a yellow resin (38 g, 99% yield) whose structure is consistent with 1Hnmr and 19Fnmr.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([C:8]2[CH:9]=[C:10]([C:14]3([C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=4)[C:26]4[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=4[C:20]4[C:15]3=[CH:16][CH:17]=[CH:18][CH:19]=4)[CH:11]=[CH:12][CH:13]=2)[CH:5]=[CH:6][CH:7]=1.CC(C)([O-])C.[Na+].[NH2:39][C:40]1[CH:45]=[CH:44][CH:43]=[C:42]([CH3:46])[CH:41]=1.C(P(C(C)(C)C)C(C)(C)C)(C)(C)C>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].CCCCCC.C1(C)C=CC=CC=1>[CH3:46][C:42]1[CH:41]=[C:40]([NH:39][C:6]2[CH:7]=[CH:2][CH:3]=[C:4]([C:8]3[CH:13]=[CH:12][CH:11]=[C:10]([C:14]4([C:27]5[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=5)[C:15]5[CH:16]=[CH:17][CH:18]=[CH:19][C:20]=5[C:21]5[C:26]4=[CH:25][CH:24]=[CH:23][CH:22]=5)[CH:9]=3)[CH:5]=2)[CH:45]=[CH:44][CH:43]=1
Reactant: Cc1cccc(N)c1
Reactant: Brc1cccc(-c2cccc(C3(c4ccccc4)c4ccccc4-c4ccccc43)c2)c1
Agent: [Pd]
Agent: CC(C)(C)P(C(C)(C)C)C(C)(C)C
Agent: CC(C)(C)[O-]
Solvent: CCCCCC
Solvent: Cc1ccccc1
Product: Cc1cccc(Nc2cccc(-c3cccc(C4(c5ccccc5)c5ccccc5-c5ccccc54)c3)c2)c1
Temperature: 80 °C
Reaction time: 2.5 h
Yield: 88.1 %

Procedure:
In a 50 mL three-neck flask were put 1.2 g (2.5 mmol) of 9-[3-(3-bromophenyl)phenyl]-9-phenylfluorene and 0.7 g (7.4 mmol) of sodium tert-butoxide. The air in the flask was replaced with nitrogen. To this mixture were added 12.5 mL of toluene, 0.3 mL (2.5 mmol) of m-toluidine, and 0.2 mL of a 10% hexane solution of tri(tert-butyl)phosphine. The temperature of this mixture was set to 60° C., and 20.0 mg (0.03 mmol) of bis(dibenzylideneacetone)palladium(0) was added to the mixture. The temperature of the mixture was raised to 80° C., followed by stirring for 2.5 hours. After the stirring, the mixture was suction-filtered through Florisil, Celite, and alumina to give a filtrate. The filtrate was concentrated to give a solid, which was then purified by silica gel column chromatography (the developing solvent has a 2:3 ratio of hexane to toluene). Accordingly, 1.1 g of a solid was obtained in 91% yield, which was the substance to be produced. The synthesis scheme of this Step 3 is shown in the following (E18-3).
Reaction SMILES: F[C:2]1[CH:16]=CC(F)=C[C:3]=1[CH2:4][P:5](=[O:12])([O:9][CH2:10][CH3:11])[O:6][CH2:7][CH3:8].[Br:18][C:19]1[N:24]=C(CBr)C=C[N:20]=1>>[CH2:7]([O:6][P:5]([CH2:4][C:3]1[CH:2]=[CH:16][N:24]=[C:19]([Br:18])[N:20]=1)(=[O:12])[O:9][CH2:10][CH3:11])[CH3:8]
Reactant: BrCc1ccnc(Br)n1
Reactant: CCOP(=O)(Cc1cc(F)ccc1F)OCC
Product: CCOP(=O)(Cc1ccnc(Br)n1)OCC

Procedure:
Prepared according to the same procedure as diethyl 2,5-difluorobenzylphosphonate, starting with 2-bromo-4-(bromomethyl)pyrimidine. 1H NMR (500 MHz, DMSO-d6) δ 8.69-8.58 (m, 1H), 7.67-7.44 (m, 1H), 4.14-3.91 (m, 4H), 3.62-3.43 (m, 2H), 1.42-1.09 (m, 6H), Mass spec.: 310.1 (MH)+.
Reaction SMILES: [F:1][C:2]([F:33])([F:32])[C:3]1[CH:4]=[C:5]([CH2:13][O:14][C@H:15]2[CH2:20][CH2:19][CH2:18][N:17]([CH2:21][C:22]([O:24]C)=[O:23])[C@H:16]2[C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[OH-].[K+]>O1CCCC1.O>[F:12][C:9]([F:10])([F:11])[C:7]1[CH:6]=[C:5]([CH2:13][O:14][C@H:15]2[CH2:20][CH2:19][CH2:18][N:17]([CH2:21][C:22]([OH:24])=[O:23])[C@H:16]2[C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[CH:4]=[C:3]([C:2]([F:32])([F:33])[F:1])[CH:8]=1
Reactant: COC(=O)CN1CCC[C@H](OCc2cc(C(F)(F)F)cc(C(F)(F)F)c2)[C@@H]1c1ccccc1
Agent: [K+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: O
Product: O=C(O)CN1CCC[C@H](OCc2cc(C(F)(F)F)cc(C(F)(F)F)c2)[C@@H]1c1ccccc1

Procedure:
The methyl ester (1.8 g; Example 8) was dissolved in tetrahydrofuran (25 ml) and a solution of potassium hydroxide (0.6 g) in water (25 ml) was added. The reaction mixture was heated at reflux for 18 H, then the organic layer was removed in vacuo and the aqueous layer removed by freeze-drying. The residue was dissolved in the minimum volume of water and the pH adjusted to 7.0 by the addition of 2M hydrochloric acid. The precipitated solid was isolated by filtration and washed with water and then recrystallised from ethanol, m.p.=60°-63° C. Found: C, 53.11; H, 4.54; N, 3.05. Calcd. for C22H21F6NO3.HCl C, 53.08; H, 4.45; N, 2.81%. m/z (CI+) 462 (MH).
Reaction SMILES: [CH:1]([C:4]1[C:10]2=[C:11]3[C:15](=[CH:16][CH:17]=[C:9]2[O:8][CH2:7][CH2:6][N:5]=1)[N:14]([S:18]([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)(=[O:20])=[O:19])[CH:13]=[CH:12]3)([CH3:3])[CH3:2].[BH3-]C#N.[Na+]>CCO>[CH:1]([CH:4]1[C:10]2=[C:11]3[C:15](=[CH:16][CH:17]=[C:9]2[O:8][CH2:7][CH2:6][NH:5]1)[N:14]([S:18]([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)(=[O:20])=[O:19])[CH:13]=[CH:12]3)([CH3:3])[CH3:2]
Reactant: CC(C)C1=NCCOc2ccc3c(ccn3S(=O)(=O)c3ccccc3)c21
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: CCO
Product: CC(C)C1NCCOc2ccc3c(ccn3S(=O)(=O)c3ccccc3)c21
Temperature: 70 °C
Yield: 28.6 %

Procedure:
To 1-isopropyl-8-(phenylsulfonyl)-3,8-dihydro-4H-[1,4]oxazepino[6,7-e]indole (Intermediate 38, 120 mg, 0.330 mmol) dissolved in EtOH (5 mL), NaCNBH3 (41 mg, 0.65 mmol) was added and the reaction mixture was heated at 70° C. for 30 minutes. The reaction was quenched by addition of water and the solvent was removed under reduced pressure. The crude product was purified by preparative HPLC (XTerra C18, 50 mM NH4HCO3 pH 10-CH3CN) to give the title compound (35 mg). MS m/z 371 [M+H]+.
Reaction SMILES: [C:1]1(=[O:12])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]1=[O:11].[Si:13]([O:30][CH2:31][CH:32]([OH:35])[CH2:33][SH:34])([C:26]([CH3:29])([CH3:28])[CH3:27])([C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.C(N(C(C)C)CC)(C)C.C(OCC)(=O)C>C(#N)C>[Si:13]([O:30][CH2:31][CH:32]1[O:35][C:4]2[C:5]3[C:10]([C:1](=[O:12])[C:2](=[O:11])[C:3]=2[S:34][CH2:33]1)=[CH:9][CH:8]=[CH:7][CH:6]=3)([C:26]([CH3:29])([CH3:27])[CH3:28])([C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1
Reactant: CC(C)(C)[Si](OCC(O)CS)(c1ccccc1)c1ccccc1
Reactant: O=C1C=Cc2ccccc2C1=O
Solvent: CCOC(C)=O
Solvent: CC#N
Solvent: CCN(C(C)C)C(C)C
Product: CC(C)(C)[Si](OCC1CSC2=C(O1)c1ccccc1C(=O)C2=O)(c1ccccc1)c1ccccc1
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 187.4 %

Procedure:
To a solution of naphthalene-1,2-dione (0.103 g, 0.65 mmol) in acetonitrile (4.0 mL) was added 1-{[tert-butyl(diphenyl)silyl]oxy}-3-mercaptopropan-2-ol (0.226 g, 0.065 mmol) followed by diisopropylethylamine (0.114 mL, 0.065 mmol). The reaction mixture was stirred for 10 minutes at room temperature followed by addition of ethyl acetate (10 mL). The organic layer was washed with water (10 mL) and 1.0 N HCl (5 mL). The organic layer was dried with sodium sulfate and concentrated under reduced pressure. (ii) To the residue was added p-toluenesulfonic acid (0.48 g, mmol) followed by acetonitrile (5 mL). The reaction mixture was stirred at room temperature for 2 hours. To the reaction mixture was added ethyl acetate (10 mL) and the organic layer was extracted with water (10 mL). The organic layer was dried with sodium sulfate and concentrated under reduced pressure. The crude mixture was purified by flash column chromatography (SiO2, 100% dichloromethane) to give the product as a purple solid (0.061 g, 18%). M.p.=205-210° C.; 400 MHz 1H NMR (CDCl3) δ: 8.4-8.1 (m, 1H), 7.75-7.5 (m, 6H), 7.49-7.3 (m, 7H), 4.65-4.58 (m, 1H), 4.1-3.93 (m, 2H), 3.2-3.05 (m, 2H), 1.08 (s, 9H); LCMS: 501 [M+H].
Reaction SMILES: [C:1]1([CH:7]2[CH2:10][CH:9]([C:11]([OH:13])=[O:12])[CH2:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH3:14]O>>[C:1]1([CH:7]2[CH2:8][CH:9]([C:11]([O:13][CH3:14])=[O:12])[CH2:10]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: CO
Reactant: O=C(O)C1CC(c2ccccc2)C1
Product: COC(=O)C1CC(c2ccccc2)C1

Procedure:
A mixture of the cis and trans isomers of 3-phenylcyclobutane carboxylic acid (6.8g.) in methanol (100ml.) and concentrated suphuric acid (0.5ml.) was refluxed overnight. The solution was concentrated to about 15ml., water was added and the mixture was extracted with ethyl acetate. The ethyl acetate extracts were combined and dried over anhydrous magnesium sulphate, the solvent was evaporated and the residue was distilled, to give methyl 3-phenylcyclobutanecarboxylate as a mixture of cis- and trans-isomers, b.p. 100°-120° C./0.2 mm. Hg.
Reaction SMILES: [CH3:1][C:2]([CH3:46])=[CH:3][CH2:4][CH2:5][C@@:6]1([CH3:45])[O:15][C:14]2[C:13]([CH2:16][CH:17]=[C:18]([CH3:20])[CH3:19])=[C:12]3[O:21][C@@:22]45[C@@:32]6([CH2:37]/[CH:38]=[C:39](\[C:41]([OH:43])=[O:42])/[CH3:40])[O:33][C:34]([CH3:36])([CH3:35])[C@@H:23]4[CH2:24][C@H:25]([C:30]6=[O:31])[CH:26]=[C:27]5[C:28](=[O:29])[C:11]3=[C:10]([OH:44])[C:9]=2[CH:8]=[CH:7]1.CCC(C)[BH-](C(C)CC)C(C)CC.[Li+].C1COCC1>C(Cl)Cl>[CH3:1][C:2]([CH3:46])=[CH:3][CH2:4][CH2:5][C@@:6]1([CH3:45])[O:15][C:14]2[C:13]([CH2:16][CH:17]=[C:18]([CH3:19])[CH3:20])=[C:12]3[O:21][C@@:22]45[C@@:32]6([CH2:37]/[CH:38]=[C:39](\[C:41]([OH:43])=[O:42])/[CH3:40])[O:33][C:34]([CH3:35])([CH3:36])[C@@H:23]4[CH2:24][C@H:25]([C:30]6=[O:31])[CH2:26][CH:27]5[C:28](=[O:29])[C:11]3=[C:10]([OH:44])[C:9]=2[CH:8]=[CH:7]1
Reactant: CC(C)=CCC[C@]1(C)C=Cc2c(O)c3c(c(CC=C(C)C)c2O1)O[C@]12C(=C[C@@H]4C[C@H]1C(C)(C)O[C@@]2(C/C=C(/C)C(=O)O)C4=O)C3=O
Agent: CCC(C)[BH-](C(C)CC)C(C)CC
Agent: [Li+]
Solvent: ClCCl
Solvent: C1CCOC1
Product: CC(C)=CCC[C@]1(C)C=Cc2c(O)c3c(c(CC=C(C)C)c2O1)O[C@]12C(C[C@@H]4C[C@H]1C(C)(C)O[C@@]2(C/C=C(/C)C(=O)O)C4=O)C3=O
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 3.7 %

Procedure:
To a solution of gambogic acid (17 mg, 0.027 mmol) in methylenechloride (2 mL) was added L-selectride solution in THF (1.0 mL, 0.5 mmol) dropwise at −78° C. After 30 min of stirring, the reaction was quenched with 1 mL of 2 N HCl. The mixture was then allowed to warm to room temperature and was diluted with 1:1 hexane/EtOAc (50 mL). The resulting mixture was washed with water and brine, dried over Na2SO4 and concentrated in vacuo. The residue was purified by chromatography (2:3 hexane/EtOAc/) to give the title compound as an oil (0.6 mg, 0.001 mmol, 4%). 1H NMR (CDCl3): 11.96 (s, 1H), 6.67 (d, J=10.2, 1H), 6.54 (t, J=6.6, 1H), 5.46 (d, J=10.2, 1H), 5.13-5.05 (m, 2H), 3.33-3.16 (m, 3H), 2.85 (d, J=13.8, 1H), 2.60 (d, J=8.7, 1H), 2.43 (s, 1H), 2.08 (m, 1H), 1.97 (s, 3H), 1.74 (s, 3H), 1.67 (s, 6H), 1.64 (s, 3H), 1.57 (s, 3H), 1.37 (s, 3H), 1.36 (d, J=6.9, 3H), 1.31-1.22 (m, 5H), 1.14 (s, 3H).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([F:14])[CH:9]=2)=[CH:4][C:3]=1[CH2:15][NH:16][C:17]1[C:18]([F:31])=[C:19]([CH:27]=[CH:28][C:29]=1[F:30])[O:20][CH2:21][C:22]([O:24]CC)=[O:23].[OH-].[Na+]>C1COCC1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([F:14])[CH:9]=2)=[CH:4][C:3]=1[CH2:15][NH:16][C:17]1[C:18]([F:31])=[C:19]([CH:27]=[CH:28][C:29]=1[F:30])[O:20][CH2:21][C:22]([OH:24])=[O:23]
Reactant: CCOC(=O)COc1ccc(F)c(NCc2cc(-c3cccc(F)c3)ccc2Cl)c1F
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Product: O=C(O)COc1ccc(F)c(NCc2cc(-c3cccc(F)c3)ccc2Cl)c1F
Temperature: 25 °C
Reaction time: 2 h
Yield: 87.8 %

Procedure:
To a solution of ethyl 2-[3-[[2-chloro-5-(3-fluorophenyl)phenyl]methylamino]-2,4-difluoro-phenoxy]acetate (120 mg, 0.27 mmol, 1.0 eq) in THF (8 mL) was added NaOH (1M aqueous solution, 3 mL, 3 mmol, 11.0 eq). The reaction was stirred at room temperature for 2 h. The THF was removed in vacuo and the residue acidified to pH 5 by addition of 1M HCl. The precipitate that formed was collected by filtration, washed with water and dried to give the title compound (I(l)) (100 mg, 88%).
Reaction SMILES: F[C:2](F)(F)[C:3]([O-:5])=[O:4].FC(F)(F)C([O-])=O.[C:15]1(C)[CH:20]=[CH:19][C:18]([Tl+2])=[CH:17][CH:16]=1.FC(F)(F)C(O)=O.FC(F)(F)C(OC(=O)C(F)(F)F)=O>C1(C)C=CC=CC=1>[CH3:18][C:17]1[CH:16]=[CH:15][CH:20]=[CH:19][C:2]=1[C:3]([OH:5])=[O:4]
Reactant: O=C([O-])C(F)(F)F
Reactant: Cc1ccc([Tl+2])cc1
Solvent: O=C(OC(=O)C(F)(F)F)C(F)(F)F
Solvent: O=C(O)C(F)(F)F
Solvent: Cc1ccccc1
Product: Cc1ccccc1C(=O)O
Temperature: 25 °C

Procedure:
A 75 ml Fisher-Porter tube was charged with 2.5 gms of p-tolyl thallium bis(trifluoroacetate), 10 ml of toluene, 5 ml of trifluoroacetic acid and 5 ml of trifluoroacetic anhydride. The reaction mixture was stirred at room temperature under 84 psig of CO pressure. There was no appreciable uptake of CO nor could any toluic acid be isolated from the reaction product after the workup procedure of Example 1.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[C:6]([N+:8]([O-])=O)[CH:5]=[CH:4][C:3]=1[F:11].[C:12](OC(=O)C)(=[O:14])[CH3:13]>[Fe]>[Br:1][C:2]1[CH:7]=[C:6]([NH:8][C:12](=[O:14])[CH3:13])[CH:5]=[CH:4][C:3]=1[F:11]
Reactant: O=[N+]([O-])c1ccc(F)c(Br)c1
Reactant: CC(=O)OC(C)=O
Agent: [Fe]
Product: CC(=O)Nc1ccc(F)c(Br)c1

Procedure:
By the reaction in the same manner as in Example 33-(i) using 2-bromo-1-fluoro-4-nitrobenzene (2.27 g), iron powder (2.90 g) and acetic anhydride (2.0 ml), the title compound (2.28 g) was obtained as colorless powder crystals.
Reaction SMILES: [OH:1][N:2]=[C:3]1[CH:8]=[CH:7][C:6](=[C:9]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[C:10]#[N:11])[CH:5]=[CH:4]1.C(N(CC)CC)C.[CH3:25][S:26](Cl)(=[O:28])=[O:27].O>O1CCCC1>[CH3:25][S:26]([O:1][N:2]=[C:3]1[CH:8]=[CH:7][C:6](=[C:9]([C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=2)[C:10]#[N:11])[CH:5]=[CH:4]1)(=[O:28])=[O:27]
Reactant: CS(=O)(=O)Cl
Reactant: N#CC(=C1C=CC(=NO)C=C1)c1ccccc1
Solvent: C1CCOC1
Solvent: O
Solvent: CCN(CC)CC
Product: CS(=O)(=O)ON=C1C=CC(=C(C#N)c2ccccc2)C=C1
Temperature: 25 °C
Reaction time: 1 h
Yield: 69.6 %

Procedure:
10 g (45 mmol) of (4-Hydroxyimino-cyclohexa-2,5-dienylidene)-phenyl-acetonitrile are dissolved in 100 ml of tetrahydrofuran (THF) and cooled in an ice bath. After adding 9.41 ml (68 mmol) of triethylamine to the solution, 3.83 ml (50 mmol) of methanesulfonyl chloride are added dropwise, keeping the temperature below 5° C. The reaction mixture is gradually warmed to room temperature, and stirred for 1 hr. The reaction mixture is poured into 200 ml of water, and extracted with ethyl acetate. The organic phase is washed with hydrochloric acid solution, water, and sodium chloride solution. The organic phase is dried over MgSO4, the solvent is distilled off, and the residue is purified by recrystallization from toluene. 9.4 g (70%) of (4-Methylsulfonyloxyimino-cyclohexa-2,5-dienylidene)-phenyl-acetonitrile are obtained in the form of a yellow-green crystal having a melting point of 137-139° C. (dec.). 1H-NMR shows that the product is a 82:18 mixture of the E and Z isomers (two dxd signals for H-C(2 or 6) at 6.78 and 6.91 ppm.
Reaction SMILES: C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.BrN1C(=O)CCC1=O.[Cl:28][C:29]1[CH:37]=[C:36]2[C:32]([C:33]([C:41]([OH:43])=O)=[CH:34][N:35]2[CH:38]([CH3:40])[CH3:39])=[CH:31][CH:30]=1.[CH3:44][C:45]1[N:46]=[C:47]([NH2:50])[S:48][CH:49]=1.Cl>C(Cl)Cl.O.C(OCC)(=O)C>[CH3:44][C:45]1[N:46]=[C:47]([NH:50][C:41]([C:33]2[C:32]3[C:36](=[CH:37][C:29]([Cl:28])=[CH:30][CH:31]=3)[N:35]([CH:38]([CH3:39])[CH3:40])[CH:34]=2)=[O:43])[S:48][CH:49]=1
Reactant: Cc1csc(N)n1
Reactant: CC(C)n1cc(C(=O)O)c2ccc(Cl)cc21
Agent: Cl
Agent: O=C1CCC(=O)N1Br
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: O
Solvent: CCOC(C)=O
Solvent: ClCCl
Product: Cc1csc(NC(=O)c2cn(C(C)C)c3cc(Cl)ccc23)n1
Temperature: 0 °C
Reaction time: 0.08 h
Yield: 23.8 %

Procedure:
A solution of triphenylphosphine (251 mg, 0.82 mmol) in methylene chloride (3 mL) cooled to 0° C. was treated with N-bromosuccinimide (146 mg, 0.82 mmol). This solution was stirred at 0° C. for 5 min. At this time, the reaction was treated with 6-chloro-1-isopropyl-1H-indole-3-carboxylic acid (150 mg, 0.63 mmol). This solution was stirred at 0° C. for 5 min and then was allowed to warm to 25° C. where it was stirred for 30 min. The reaction was then treated with 4-methyl-thiazol-2-ylamine (166 mg, 1.45 mmol) and was stirred at 25° C. for 2 d. At this time, the reaction was diluted with water (25 mL) and ethyl acetate (25 mL) and treated with a 1N aqueous hydrochloric acid solution (10 mL). The organic layer was separated and was washed with a saturated aqueous sodium bicarbonate solution (1×20 mL) and a saturated aqueous sodium chloride solution (1×20 mL). The organic layer was dried over magnesium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 40S, Silica, 1/1 hexanes/ethyl acetate) afforded 6-chloro-1-isopropyl-1H-indole-3-carboxylic acid (4-methyl-thiazol-2-yl)-amide (50 mg, 24%) as a yellow solid: mp 201-203° C.; (ES)+-HRMS m/e calcd for C16H16ClN3OS (M+) 333.0703, found 333.0704.
Reaction SMILES: [CH3:1][C:2]1([CH3:20])[C:10]2[C:5](=[CH:6][CH:7]=[C:8](OS(C(F)(F)F)(=O)=O)[CH:9]=2)[C:4](=[O:19])[CH2:3]1.[C:21]([C:23]1[CH:28]=[CH:27][C:26](B(O)O)=[CH:25][CH:24]=1)#[N:22]>>[CH3:1][C:2]1([CH3:20])[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([C:26]3[CH:27]=[CH:28][C:23]([C:21]#[N:22])=[CH:24][CH:25]=3)[CH:9]=2)[C:4](=[O:19])[CH2:3]1
Reactant: N#Cc1ccc(B(O)O)cc1
Reactant: CC1(C)CC(=O)c2ccc(OS(=O)(=O)C(F)(F)F)cc21
Product: CC1(C)CC(=O)c2ccc(-c3ccc(C#N)cc3)cc21

Procedure:
The title compound was prepared from trifluoro-methanesulfonic acid 3,3-dimethyl-1-oxo-indan-5-yl ester and 4-cyanophenyl boronic acid according to the procedure described in example 21. MS (ESI) m/z 262; HRMS: calcd for C18H15NO+H+, 262.12264; found (ESI, [M+H]+), 262.1237.
Reaction SMILES: [O-2].[Ca+2].[C:3]([O:9][CH3:10])(=[O:8])[CH2:4][C:5]([CH3:7])=[O:6].[C:11](Cl)(=O)[CH2:12]CC.[Cl-].[NH4+].N.Cl>C(Cl)Cl.O>[C:5]([CH2:4][C:3]([O:9][CH3:10])=[O:8])(=[O:6])[CH2:7][CH2:11][CH3:12]
Reactant: COC(=O)CC(C)=O
Reactant: CCCC(=O)Cl
Agent: Cl
Agent: N
Agent: [Ca+2]
Solvent: ClCCl
Solvent: O
Product: CCCC(=O)CC(=O)OC
Reaction time: 1 h
Yield: 97.8 %

Procedure:
56 g (1 mol) of calcium oxide were placed in 650 ml of methylene chloride, and 116 g (1 mol) of methyl acetoacetate were added dropwise at 20° to 30° C. over 0.5 hour. Stirring was then continued for 1 hour at this temperature. 116 g (1.05 mol) of butyryl chloride were then metered in at a temperature of 30°-35° C. over one hour and stirring was then continued for 3 hours at this temperature. 54 g (1 mol) of ammonium chloride in 300 ml of water were then added to the viscous suspension at 30° C. and the resulting mixture was stirred for 30 minutes. The pH of the reaction mixture was adjusted to 9 with aqueous ammonia and stirring was continued for 3 hours at 30° C. After the reaction mixture had been acidified with concentrated hydrochloric acid (pH<1), it was washed with sodium bicarbonate solution and water. After separation of the water phase, the solvent was distilled off on an evaporator. This gave 141 g (GC purity 73%) of methyl butyrylacetate (yield 71%).
Reaction SMILES: [Br:1][C:2]1[N:3]=[C:4]2[C:10]([N+:11]([O-])=O)=[CH:9][N:8]([C:14]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[C:5]2=[N:6][CH:7]=1.[In].Cl>O1CCCC1.O>[Br:1][C:2]1[N:3]=[C:4]2[C:10]([NH2:11])=[CH:9][N:8]([C:14]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)([C:27]3[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=3)[C:21]3[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=3)[C:5]2=[N:6][CH:7]=1
Reactant: O=[N+]([O-])c1cn(C(c2ccccc2)(c2ccccc2)c2ccccc2)c2ncc(Br)nc12
Agent: Cl
Agent: [In]
Solvent: C1CCOC1
Solvent: O
Product: Nc1cn(C(c2ccccc2)(c2ccccc2)c2ccccc2)c2ncc(Br)nc12

Procedure:
2-bromo-7-nitro-5-trityl-pyrrolo[2,3-b]pyrazine (5 g, 10.30 mmol) dissolved in tetrahydrofuran (200.0 mL)/water (50.00 mL) and indium (11.83 g, 103.0 mmol) then HCl (20.60 mL of 6 M, 123.6 mmol) added. Indium dissolves then precipitates out over 5 minutes. Reaction mixture is filtered through celite, washing with EtOAc. Filtrate basified by careful addition of NaHCO3. Emulsion forms and mixture is filtered again before layers separated. Aqueous is extracted with EtOAc. Combined organics dried and concentrated in vacuo to a black foam. Residue is taken up in DCM and purified by chromatography eluting with 0-50% EtOAc—petroleum ether). Product obtained as a green/brown foam. Dried on high vacuum and taken directly on to acylation reaction. (3.43 g, 73%). 1H NMR (400.0 MHz, DMSO) δ 8.46 (s, 1H), 8.40 (s, 1H), 7.38-7.36 (m, H), 7.23-7.20 (m, 8H) and 3.32 (s, 7H) ppm; MS (ES+) 457.0
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([CH:8]2[C:12]3[NH:13][C:14]([C:16]([O:18]C)=[O:17])=[CH:15][C:11]=3[CH2:10][CH2:9]2)[CH:5]=[CH:6][CH:7]=1.[OH-].[Li+].CO>C1COCC1>[Br:1][C:2]1[CH:3]=[C:4]([CH:8]2[C:12]3[NH:13][C:14]([C:16]([OH:18])=[O:17])=[CH:15][C:11]=3[CH2:10][CH2:9]2)[CH:5]=[CH:6][CH:7]=1
Reactant: COC(=O)c1cc2c([nH]1)C(c1cccc(Br)c1)CC2
Agent: [Li+]
Agent: [OH-]
Solvent: CO
Solvent: C1CCOC1
Product: O=C(O)c1cc2c([nH]1)C(c1cccc(Br)c1)CC2
Yield: 48 %

Procedure:
The title compound was synthesized from methyl 6-(3-bromophenyl)-1,4,5,6-tetrahydrocyclopenta[b]pyrrole-2-carboxylate (0.213 g, 0.67 mmol) and lithium hydroxide (0.281 g, 6.70 mmol in 4 mL water), according to General Procedure 7. A 1:2 mixture of methanol (MeOH) and THF (6 mL) was used. The resulting product was purified reverse phase HPLC, eluting with a gradient of 40-100% MeOH: water (with 0.1% formic acid) to afford a light pink solid: 0.098 g (48% yield). 1H NMR (400 MHz, METHANOL-d4) δ ppm 2.23 (ddt, J=13.14, 8.21, 5.27, 5.27 Hz, 1H), 2.62 (ddd, J=14.31, 8.65, 5.34 Hz, 1H), 2.69-2.78 (m, 1H), 2.87-2.98 (m, 1H), 4.24 (dd, J=8.40, 5.17 Hz, 1H), 6.67 (s, 1H), 7.07 (d, J=7.61 Hz, 1H), 7.18 (t, J=7.81 Hz, 1H), 7.25 (s, 1H), 7.33 (d, J=7.86 Hz, 1H); LCMS (ESI+) 306.0 (M+H); HPLC (UV=96.1%), (ELSD=99.3%).