Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [N:1]([CH:4]([CH3:21])[CH2:5][N:6]1[C:10]2=[CH:11][C:12]3[C:17]([C:16]([CH3:19])([CH3:18])[CH:15]=[CH:14][C:13]=3[CH3:20])=[C:9]2[CH:8]=[N:7]1)=[N+]=[N-].[C:22]([OH:29])(=[O:28])/[CH:23]=[CH:24]/[C:25]([OH:27])=[O:26]>C(O)C.C(OCC)C.CO.[Pt]=O>[C:22]([OH:29])(=[O:28])/[CH:23]=[CH:24]/[C:25]([OH:27])=[O:26].[CH3:19][C:16]1([CH3:18])[C:17]2[C:12]([CH:11]=[C:10]3[C:9]=2[CH:8]=[N:7][N:6]3[CH2:5][CH:4]([NH2:1])[CH3:21])=[C:13]([CH3:20])[CH:14]=[CH:15]1
Reactant: CC1=C2C=c3c(cnn3CC(C)N=[N+]=[N-])=C2C(C)(C)C=C1
Agent: O=[Pt]
Agent: O=C(O)/C=C/C(=O)O
Solvent: CCOCC
Solvent: CCO
Solvent: CO
Product: CC1=C2C=c3c(cnn3CC(C)N)=C2C(C)(C)C=C1
Temperature: 25 °C
Reaction time: 4 h
Yield: 69 %

Procedure:
1.1 g (3.9 mmol) of (RS)-1-(2-azido-propyl)-4,4,7-trimethyl-1,4-dihydro-indeno[2,1-c]pyrazole dissolved in 60 ml of anhydrous ethanol were hydrogenated over 110 mg of platinum oxide for 3 hours. The catalyst was subsequently filtered off, rinsed with ethanol and the solvent was removed in a vacuum. The colorless oil obtained was dissolved in 150 ml of anhydrous diethyl ether, filtered and treated while stirring with a solution of 453 mg (3.9 mmol) of fumaric acid in 10 ml of methanol. The mixture was stirred at room temperature for 4 hours and the white crystals were subsequently filtered off. 1 g (69%) of (RS)-2-(4,4,7-trimethyl-1,4-dihydroindeno[2,1-c]pyrazol-1-yl )-1-methyl-ethylamine fumarate (1:1) with m.p. 167° was obtained.
Reaction SMILES: [O:1]1[CH:11]2[CH:2]1[CH2:3][C:4]1[C:9]([CH2:10]2)=[CH:8][CH:7]=[CH:6][CH:5]=1.[N-:12]=[N+:13]=[N-:14].[Na+].S(=O)(=O)(O)O>CS(C)=O.C(OCC)(=O)C>[N:12]([C@@H:11]1[CH2:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][C@H:2]1[OH:1])=[N+:13]=[N-:14]
Reactant: [N-]=[N+]=[N-]
Reactant: c1ccc2c(c1)CC1OC1C2
Agent: O=S(=O)(O)O
Agent: [Na+]
Solvent: CS(C)=O
Solvent: CCOC(C)=O
Product: [N-]=[N+]=N[C@@H]1Cc2ccccc2C[C@H]1O
Reaction time: 60 h
Yield: 38 %

Procedure:
To a stirred solution of 2,3-epoxy-1,2,3,4-tetrahydronaphthalene (prepared in the manner disclosed in U.S. Pat. No. 4,076,843, 1.7 g, 11.6 mmol) in dimethyl sulfoxide (20 mL) at room temperature under nitrogen was added sodium azide (6.7 g, 0.10 mol) and concentrated sulfuric acid (0.2 mL). After 60 h, the reaction mixture was diluted with ethyl acetate. The organic layer was washed with brine three times, dried over anhydrous magnesium sulfate, and concentrated under vacuum to yield a residue. The residue was purified by silica gel chromatography (10% ethyl acetate in hexane was used) to obtain the title compound (0.43 g, 38%) and recovered starting material. 1H NMR (400 MHz, CDCl3) δ 7.07-7.18 (m, 4H), 3.92 (m, 1H), 3.73 (m, 1H), 3.22 (m, 2H), 2.87 (m, 2H), 2.35 (s, 1H).
Reaction SMILES: C1(P([N:15]=[N+:16]=[N-:17])(C2C=CC=CC=2)=O)C=CC=CC=1.[CH3:18][C:19]1[O:23][C:22]([CH:24]([CH:26]2[CH2:31][CH2:30][O:29][CH2:28][CH2:27]2)O)=[CH:21][CH:20]=1.N12CCCN=C1CCCCC2>C1(C)C=CC=CC=1>[N:15]([CH:24]([C:22]1[O:23][C:19]([CH3:18])=[CH:20][CH:21]=1)[CH:26]1[CH2:31][CH2:30][O:29][CH2:28][CH2:27]1)=[N+:16]=[N-:17]
Reactant: Cc1ccc(C(O)C2CCOCC2)o1
Reactant: [N-]=[N+]=NP(=O)(c1ccccc1)c1ccccc1
Solvent: C1CCC2=NCCCN2CC1
Solvent: Cc1ccccc1
Product: Cc1ccc(C(N=[N+]=[N-])C2CCOCC2)o1
Temperature: 0 °C
Reaction time: 22 h
Yield: 69.8 %

Procedure:
6.08 g (22 mmol, 1.1 eq) of diphenylphosphoryl azide were added dropwise to a solution of 4.43 g (20 mmol, 1 eq) of (5-methylfuran-2-yl)-(tetrahydropyran-4-yl)methanol at 89% in 60 ml of toluene. The reaction medium was cooled to 0° C. and then 3.3 ml (22 mmol, 1.1 eq) of 1,8-diazabicyclo[5.4.0]undec-7-ene were added dropwise. The reaction medium was stirred at ambient temperature for 22 hours. The reaction medium was separated by settling out and the organic phase was washed with water and then with 1 N hydrochloric acid, dried over magnesium sulfate, filtered and evaporated. The residue was chromatographed on silica gel (column Analogix SF40-240 g, Spot II) eluted with heptane/ethyl acetate (95/5). 3.09 g of 4-[azido-(5-methylfuran-2-yl)methyl]tetrahydropyran were obtained. Yield=70%.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][CH:7]=1.Cl[C:9]([O:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)=[O:10]>>[N:4]1[CH:5]=[CH:6][CH:7]=[C:2]([NH:1][C:9](=[O:10])[O:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH:3]=1
Reactant: O=C(Cl)Oc1ccccc1
Reactant: Nc1cccnc1
Product: O=C(Nc1cccnc1)Oc1ccccc1
Yield: 62 %

Procedure:
The title compound was prepared by following the procedure of example 462 step 6 using 3-aminopyridine and phenyl chloroformate. Yield 7 g, 62% yield.
Reaction SMILES: [C:1]([NH:5][C:6]([C:8]1[C:12]2=[N:13][C:14]([C:17]3[C:25]4[C:20](=[CH:21][C:22]([F:26])=[CH:23][CH:24]=4)[N:19]([CH2:27][CH2:28][CH:29]4[CH2:33][O:32]C(C)(C)[O:30]4)[N:18]=3)=[CH:15][N:16]=[C:11]2[N:10](C(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[CH:9]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].FC(F)(F)C(O)=O>ClCCl>[C:1]([NH:5][C:6]([C:8]1[C:12]2=[N:13][C:14]([C:17]3[C:25]4[C:20](=[CH:21][C:22]([F:26])=[CH:23][CH:24]=4)[N:19]([CH2:27][CH2:28][CH:29]([OH:30])[CH2:33][OH:32])[N:18]=3)=[CH:15][N:16]=[C:11]2[NH:10][CH:9]=1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)NC(=O)c1cn(C(c2ccccc2)(c2ccccc2)c2ccccc2)c2ncc(-c3nn(CCC4COC(C)(C)O4)c4cc(F)ccc34)nc12
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: CC(C)(C)NC(=O)c1c[nH]c2ncc(-c3nn(CCC(O)CO)c4cc(F)ccc34)nc12
Reaction time: 2 h
Yield: 54.5 %

Procedure:
To a stirred solution of N-tert-butyl-2-(1-(2-(2,2-dimethyl-1,3-dioxolan-4-yl)ethyl)-6-fluoro-1H-indazol-3-yl)-5-trityl-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide (90 mg, 0.125 mmol) in dichloromethane (2 mL) was added drop-wise trifluoroacetic acid (2 mL) at room temperature and the reaction mixture was stirred for 2 hours. The solvent was removed under reduced pressure. The residue was purified by preparative-HPLC (Gemini 5u C18 150×21.2 mm; inject volume: 3 mL/inj, flow rate: 20 mL/min; wavelength: 214 nm and 254 nm; the gradient conditions are: 30% acetonitrile/70% water (0.1% trifluoroacetic acid, v/v) initially, and then proceed to 70% acetonitrile/30% water (0.1% trifluoroacetic acid, v/v) in a linear fashion after just 9 min.) to give N-tert-butyl-2-(1-(3,4-dihydroxybutyl)-6-fluoro-1H-indazol-3-yl)-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide (30 mg, 54.5%) as a white solid. LCMS: (M+H)+=441, (M+Na)+=463; 1H NMR (300 MHz, DMSO): δ12.81 (s, 1H), 9.06 (s, 1H), 8.47-8.42 (m, 1H), 8.37 (s, 1H), 7.91 (s, 1H), 7.64 (d, 1H, J=9.9 Hz), 7.14 (dd, 1H, J1=9.0 Hz, J2=1.8 Hz), 4.57 (t, 2H, J=6.5 Hz), 3.46-3.24 (m, 5H), 2.10-2.08 (m, 1H), 2.06-1.77 (m, 1H), 1.51 (s, 9H).
Reaction SMILES: [C:1]1([C:7]2[O:11][N:10]=[C:9]([C:12](F)=[O:13])[C:8]=2[C:15]([F:18])([F:17])[F:16])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CCCC[N+](CCCC)(CCCC)CCCC.[F-].C1COCC1.[OH:42][C@@H:43]([C:56]1[CH:61]=[CH:60][C:59](/[C:62](=[N:64]/O)/[NH2:63])=[CH:58][CH:57]=1)[CH2:44][N:45]1[CH2:50][CH2:49][CH2:48][C@H:47]([C:51]([O:53][CH2:54][CH3:55])=[O:52])[CH2:46]1>C(#N)C.C(OCC)(=O)C>[OH:42][C@@H:43]([C:56]1[CH:61]=[CH:60][C:59]([C:62]2[N:64]=[C:12]([C:9]3[C:8]([C:15]([F:18])([F:17])[F:16])=[C:7]([C:1]4[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=4)[O:11][N:10]=3)[O:13][N:63]=2)=[CH:58][CH:57]=1)[CH2:44][N:45]1[CH2:50][CH2:49][CH2:48][C@H:47]([C:51]([O:53][CH2:54][CH3:55])=[O:52])[CH2:46]1
Reactant: CCOC(=O)[C@H]1CCCN(C[C@@H](O)c2ccc(/C(N)=N/O)cc2)C1
Reactant: O=C(F)c1noc(-c2ccccc2)c1C(F)(F)F
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Solvent: CC#N
Product: CCOC(=O)[C@H]1CCCN(C[C@@H](O)c2ccc(-c3noc(-c4noc(-c5ccccc5)c4C(F)(F)F)n3)cc2)C1
Reaction time: 2 h

Procedure:
5-Phenyl-4-(trifluoromethyl)isoxazole-3-carbonyl fluoride, Int-II-D (78 mg, 0.3 mmol) was dissolved in acetonitrile (5 mL) and (S)-ethyl 1-((S)-2-hydroxy-2-(4-((Z)—N′-hydroxycarbamimidoyl)phenyl)ethyl)piperidine-3-carboxylate, Preparation 14B (100 mg, 0.298 mmol) was added. After 2 hours, 1M TBAF in THF (298 μL, 0.298 mmol) was added and the reaction mixture was stirred overnight. The reaction mixture was diluted with ethyl acetate and washed with H2O. The organic layer was dried with MgSO4, filtered, and concentrated. The resulting material was purified on a silica gel cartridge using an EtOAc/hexanes gradient to yield 67 mg of (S)-ethyl 1-((S)-2-hydroxy-2-(4-(5-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-1,2,4-oxadiazol-3-yl)phenyl)ethyl)piperidine-3-carboxylate. MS (m+1)=557. HPLC Peak RT=3.32 minutes (Analytical Method A).
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:12])[C:5]1[CH:10]=[CH:9][C:8]([NH2:11])=[CH:7][CH:6]=1)[CH3:2].[C:13](Cl)(=[O:23])[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH3:22].CCN(CC)CC>C(Cl)Cl.CCOC(C)=O>[CH2:1]([O:3][C:4](=[O:12])[C:5]1[CH:10]=[CH:9][C:8]([NH:11][C:13](=[O:23])[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH3:22])=[CH:7][CH:6]=1)[CH3:2]
Reactant: CCCCCCCCCC(=O)Cl
Reactant: CCOC(=O)c1ccc(N)cc1
Solvent: ClCCl
Solvent: CCOC(C)=O
Solvent: CCN(CC)CC
Product: CCCCCCCCCC(=O)Nc1ccc(C(=O)OCC)cc1

Procedure:
(Scheme 3, Compound H) To a solution of 4-amino-benzoic acid ethyl ester (2.0 g, 12.1 mmol) and decanoyl chloride (2.35 g, 13.3 mmol) in methylene chloride (20 mL) was added Et3N (1.34 g, 13.3 mmol). The resultant mixture was stirred at room temperature for one hour and then was diluted with EtOAc, washed by H2O, dried over MgSO4. After filtration and concentration in vacuo, the product was directly used in the next step.
Reaction SMILES: [C:1]1([C:7]2(CO)[CH2:9][CH2:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C1(P([C:25]2[CH:30]=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(Br)(Br)(Br)[Br:32]>C1COCC1.CCOCC>[CH:7]1([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][C:6]=2[CH2:25][CH2:30][Br:32])[CH2:8][CH2:9]1
Reactant: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Reactant: OCC1(c2ccccc2)CC1
Reactant: BrC(Br)(Br)Br
Solvent: C1CCOC1
Solvent: CCOCC
Product: BrCCc1ccccc1C1CC1
Reaction time: 5 h
Yield: 64.7 %

Procedure:
To a solution of 1-phenyl-1-cyclopropane methanol (1 g, 6.8 mmol) in 35 mL of THF is added triphenylphosphine (1.7 g, 7.1 mmol) and carbon tetrabromide (2.34 g, 7.1 mmol). The solution is stirred at ambient temperatures for 5 hours. After this time, the solution is diluted with 100 mL of Et2O. The reaction mixture is filtered and the collected solution is concentrated. The crude product is purified by column chromatography eluting with hexane to afford the title compound (1 g, 4.4 mmol) as an oil.
Reaction SMILES: [CH:1]1([B:6]([O:11][CH:12]([CH3:14])[CH3:13])OC(C)C)[CH2:5][CH2:4][CH2:3][CH2:2]1.[C:15]([Li])#[C:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH3:22].Cl.[B].C=C(C)C>C(OCC)C>[CH:1]1([B:6]([C:15]#[C:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH3:22])[O:11][CH:12]([CH3:13])[CH3:14])[CH2:2][CH2:3][CH2:4][CH2:5]1
Reactant: CC(C)OB(OC(C)C)C1CCCC1
Reactant: [Li]C#CCCCCCC
Agent: C=C(C)C
Agent: Cl
Agent: [B]
Solvent: CCOCC
Product: CCCCCCC#CB(OC(C)C)C1CCCC1

Procedure:
Cyclopentyldiisopropoxyborane (2.33 g, 37 mmol) in ethyl ether (37 mL) was added to an ethereal solution of 1-octynyllithium (41 mmoL in 41 mL ethyl ether), then quenched with HCl in ethyl ether (12.0 mL, 41 mmol). Workup as described in Example 14 yielded 6.95 g (76%), bp 100°-102° C. (0.1 mm Hg); n20D 1.4557; proton NMR (CDCl3) δ4.63 (septet, J=18 Hz, 1H), 2.23 (triplet, 1H), 1.17 (d, J=18 Hz, 6H), 0.83 (triplet, 3H); boron NMR (EE) δ+41.2 ppm(s); mass spectrum (chemical ionization, isobutene) m/e 249 (M+H), 40%); IR (thin film) 2186, 1344 cm-1. Anal. Calcd. for C16H29BO: C, 77.42; H, 11.78. Found: C, 77.02; H, 11.92.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:11]=[CH:10][C:6]([C:7]([NH2:9])=[O:8])=[CH:5][CH:4]=1.[P:12]([Cl:17])(Cl)(Cl)(Cl)[Cl:13].Cl.C(O)=[O:20]>C(Cl)(Cl)(Cl)Cl>[Cl:13][P:12]([Cl:17])([NH:9][C:7](=[O:8])[C:6]1[CH:10]=[CH:11][C:3]([O:2][CH3:1])=[CH:4][CH:5]=1)=[O:20]
Reactant: COc1ccc(C(N)=O)cc1
Reactant: O=CO
Reactant: ClP(Cl)(Cl)(Cl)Cl
Agent: Cl
Solvent: ClC(Cl)(Cl)Cl
Product: COc1ccc(C(=O)NP(=O)(Cl)Cl)cc1
Reaction time: 0.5 h

Procedure:
A suspension of 47 g (0.31 mole) of 4-methoxybenzamide, 64.7 g (0.31 mole) of phosphorus pentachloride and 500 ml of AR carbon tetrachloride was heated at 60°-70° for 45 min. by which time the HCl evolution had nearly stopped. Cooled to room temperature where 14.8 g (0.31 mole) of 97% formic acid was added dropwise. The reaction was stirred for an additional 30 min., then filtered, washed with AR carbon tetrachloride and air-dried to give 73.4 g, m.p. 92°-93°.
Reaction SMILES: [CH:1]1[CH:2]=[CH:3][C:4]([C:7]2[O:20][C:12]3=[CH:13][C:14]([OH:19])=[C:15]([OH:18])[C:16]([OH:17])=[C:11]3[C:9](=[O:10])[CH:8]=2)=[CH:5][CH:6]=1.[CH2:21]=O.[OH:23][CH:24]1[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]1>CO>[OH:17][C:16]1[C:15]([OH:18])=[C:14]([OH:19])[C:13]([CH2:21][N:27]2[CH2:28][CH2:29][CH:24]([OH:23])[CH2:25][CH2:26]2)=[C:12]2[C:11]=1[C:9](=[O:10])[CH:8]=[C:7]([C:4]1[CH:3]=[CH:2][CH:1]=[CH:6][CH:5]=1)[O:20]2
Reactant: O=c1cc(-c2ccccc2)oc2cc(O)c(O)c(O)c12
Reactant: C=O
Reactant: OC1CCNCC1
Solvent: CO
Product: O=c1cc(-c2ccccc2)oc2c(CN3CCC(O)CC3)c(O)c(O)c(O)c12
Temperature: 51 °C
Reaction time: 4 h

Procedure:
The mixture of Baicalein (27 g), methanol (350 ml), 37% formaldehyde solution (8.04 ml), 4-hydroxy-piperidine (10.2 g) was stirred under for 4 hours at 51° C., then precipitates were removed by filtration and washed several times with methanol, after drying under reduced pressure at 55° C. to get the product as yellow solid 37.02 g of purity 99.2%. m.p.: 221° C. MS: (API-ES) m/z 384.2[M+H]+, 767.5[2M+H]+, 789.5 [2M+Na]+; 1H NMR (DMSO-d6, 400 MHz): δ 8.05˜8.07 (m, 2H, Ar-2′,6′-H), 7.58˜7.59 (m, 3H, Ar-3′,4′,5′-H), 6.87 (s, 1H, 3-H), 4.17 (s, 2H, CH2), 3.67 (m, 1H, CH), 2.68, 3.03 (m, 2H, CH2), 2.71, 3.05 (m, 2H, CH2), 1.52, 1.82 (m, 2H, CH2), 1.53, 1.84 (m, 2H, CH2).
Reaction SMILES: C1(C2CCN(C[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][N:19]3[CH:28]([OH:29])[C:27]4[CH:30]=[CH:31][CH:32]=[C:25]5[C:26]=4[C:21](=[CH:22][CH:23]=[CH:24]5)[C:20]3=[O:33])CC=2)C=CC=CC=1.[Br:34]CCCCCBr.BrCCCCCCBr>>[Br:34][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][N:19]1[C:28](=[O:29])[C:27]2[CH:30]=[CH:31][CH:32]=[C:25]3[C:26]=2[C:21](=[CH:22][CH:23]=[CH:24]3)[C:20]1=[O:33]
Reactant: O=C1c2cccc3cccc(c23)C(O)N1CCCCCCN1CC=C(c2ccccc2)CC1
Reactant: BrCCCCCBr
Agent: BrCCCCCCBr
Product: O=C1c2cccc3cccc(c23)C(=O)N1CCCCCBr

Procedure:
Following the procedure of part (a) of example 4 but substituting 1,5-dibromopentane for the 1,6-dibromohexane, one obtains 2-(5-bromopentyl)-1H-benz[de]isoquinoline-1,3(2H)-dione; m.p. 113°-115°.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:14]=[C:15]([Cl:17])[CH:16]=1)[O:5][NH:6][C:7](=[O:13])[N:8]([CH:10]([CH3:12])[CH3:11])[CH3:9].Cl[C:19]([O:21][CH3:22])=[O:20].O>O1CCCC1.N1C=CC=CC=1>[Cl:1][C:2]1[CH:3]=[C:4]([CH:14]=[C:15]([Cl:17])[CH:16]=1)[O:5][N:6]([C:19]([O:21][CH3:22])=[O:20])[C:7](=[O:13])[N:8]([CH:10]([CH3:12])[CH3:11])[CH3:9]
Reactant: COC(=O)Cl
Reactant: CC(C)N(C)C(=O)NOc1cc(Cl)cc(Cl)c1
Solvent: C1CCOC1
Solvent: O
Solvent: c1ccncc1
Product: COC(=O)N(Oc1cc(Cl)cc(Cl)c1)C(=O)N(C)C(C)C
Temperature: 25 °C
Reaction time: 2 h
Yield: 43.8 %

Procedure:
In a mixed solvent of 20 ml of tetrahydrofuran and 1.9 ml of pyridine was dissolved 2.15 g (7.76 mmoles) of 3-(3,5-dichlorophenoxy)-1-isopropyl-1-methylurea, and then 10 ml of a tetrahydrofuran solution of 1.47 g (15.5 mmoles) of methyl chloroformate was added. The mixture was stirred at 25° C. for 2 hours. Water (100 ml) was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with a saturated aqueous sodium chloride solution, and dried over anhydrous magnesium sulfate. The ethyl acetate was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (eluting solvent: ethyl acetate/hexane) to give 1.14 g (yield 44 %) of the desired compound as the yellow crystals
Reaction SMILES: I[C:2]1[N:3]([C:13]2[CH:14]=[CH:15][C:16]3[N:17]([CH3:26])[C:18]4[C:23]([C:24]=3[CH:25]=2)=[CH:22][CH:21]=[CH:20][CH:19]=4)[CH:4]=[C:5]([C:7]2[S:8][C:9]([CH3:12])=[CH:10][CH:11]=2)[N:6]=1.[CH3:27][C:28]1[S:32][C:31](B2OC(C)(C)C(C)(C)O2)=[CH:30][CH:29]=1.C([O-])([O-])=O.[Na+].[Na+]>O.CN(C=O)C>[CH3:27][C:28]1[S:32][C:31]([C:2]2[N:3]([C:13]3[CH:14]=[CH:15][C:16]4[N:17]([CH3:26])[C:18]5[C:23]([C:24]=4[CH:25]=3)=[CH:22][CH:21]=[CH:20][CH:19]=5)[CH:4]=[C:5]([C:7]3[S:8][C:9]([CH3:12])=[CH:10][CH:11]=3)[N:6]=2)=[CH:30][CH:29]=1
Reactant: Cc1ccc(-c2cn(-c3ccc4c(c3)c3ccccc3n4C)c(I)n2)s1
Reactant: Cc1ccc(B2OC(C)(C)C(C)(C)O2)s1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: Cc1ccc(-c2cn(-c3ccc4c(c3)c3ccccc3n4C)c(-c3ccc(C)s3)n2)s1
Temperature: 25 °C
Yield: 135.4 %

Procedure:
A mixture of 3-(2-iodo-4-(5-methylthiophen-2-yl)-1H-imidazol-1-yl)-9-methyl-9H-carbazole 10 (920 g, 2.0 mmol), 5-methylthiophene-2-boronic acid pinacol ester (880 mg, 3.9 mmol), Na2CO3 (1.03 g, 9.81 mmol) in H2O (5 mL) and DMF (20 mL) was degassed (N2 bubbling). Pd(PPh3)4 (60 mg) was added and the mixture was heated to reflux for 8 h. The mixture was allowed to cool to room temperature and concentrated. The residue was washed with H2O (3 times) and EtOAc (1 time). The solid material was transferred to a soxlet apparatus and the material extracted with EtOAc. The organic extract was concentrated to ˜10 mL and the solid material was collected and recrystallised (EtOAc) to give 3-(2,4-bis(5-methylthiophen-2-yl)-1H-imidazol-1-yl)-9-methyl-9H-carbazole 11 (1.19 g, 76%) as colourless crystals. A portion of this material was further purified by sublimation (220° C., 10−6 mBar): m.p. 248-255° C. (DSC)1H NMR (CDCl3, 400 MHz) δ 2.33 (s, 3H), 2.51 (d, J=0.6 Hz, 3H), 3.94 (s, 3H), 6.48 (br s, 1H), 6.72 (d, J=2.5 Hz, 1H), 7.22 (s, 1H), 7.30 (t, 7.6 Hz, 1H), 7.43 (dd, J 2.0, 8.6 Hz, 1H), 7.49 (d, 8.5 Hz, 2H), 7.57 (dt, J 1.0, 7.6 Hz, 1H), 8.08 (d, 7.7 Hz, 1H), 8.10 (d, J=1.8 Hz, 1H); 13C NMR (CDCl3, 100 MHz) δ 15.1, 15.4, 109.0, 109.2, 117.9, 119.2, 119.8, 120.8, 122.2, 123.3, 124.5, 125.9, 126.1, 126.9, 141.1, 141.8, 142.6; HRMS (EI) m/z 439.1163 C24H22N2S [M]+. requires 439.1171.
Reaction SMILES: C(Cl)(=O)C(Cl)=O.[Br:7][C:8]1[CH:16]=[CH:15][C:11]([C:12](O)=[O:13])=[CH:10][C:9]=1[F:17].Cl.[CH3:19][NH:20]OC.[C:23](=O)([O-])[O-].[K+].[K+]>ClCCl.O.CN(C)C=O>[Br:7][C:8]1[CH:16]=[CH:15][C:11]([C:12]([N:20]([CH3:19])[CH3:23])=[O:13])=[CH:10][C:9]=1[F:17]
Reactant: O=C([O-])[O-]
Reactant: O=C(O)c1ccc(Br)c(F)c1
Reactant: CNOC
Agent: Cl
Agent: O=C(Cl)C(=O)Cl
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Solvent: ClCCl
Product: CN(C)C(=O)c1ccc(Br)c(F)c1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
Oxalyl chloride (38.1 mL, 450 mmol) was slowly added to a mixture of 4-bromo-3-fluorobenzoic acid (49.3 g, 225 mmol) (Alfa Aesar, Cat.#B25475) in dichloromethane (300 mL). Subsequently, N,N-dimethylformamide (1.0 mL) was added and the reaction mixture was stirred at ambient temperature for 2 h. The reaction mixture was concentrated under reduced pressure and co-evaporated with toluene 3 times. The residue was then dissolved in dichloromethane (100 mL). The solution was added drop-wise to a mixture of N,O-dimethylhydroxylamine hydrochloride (30.7 g, 315 mmol) and potassium carbonate (120 g, 900 mmol) in dichloromethane (300 mL) and water (300 mL). The reaction mixture was stirred at ambient temperature for 2 hours. The organic layer was separated. The aqueous layer was extracted with dichloromethane (2×50 mL). The combined organic extracts were washed with brine, dried over magnesium sulfate, filtered and concentrated under reduced pressure to give the product. (58.5 g) LCMS (M+H)+: m/z=261.9/263.9.
Reaction SMILES: [CH2:1]=[C:2]1[CH2:6][CH2:5][CH:4]([C:7]([O:9]CC)=[O:8])[CH2:3]1.[OH-].[Li+:13]>C1COCC1.O>[CH2:1]=[C:2]1[CH2:6][CH2:5][CH:4]([C:7]([O-:9])=[O:8])[CH2:3]1.[Li+:13]
Reactant: C=C1CCC(C(=O)OCC)C1
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: C1CCOC1
Product: C=C1CCC(C(=O)[O-])C1
Temperature: 65 °C

Procedure:
A mixture of ethyl 3-methylenecyclopentanecarboxylate (900 mg, 5.84 mmol) and lithium hydroxide (280 mg, 11.67 mmol) in THF (15 mL) and water (6 mL) was heated at 65° C. for 18 hours. Analysis by TLC indicated that the starting ester had been completely consumed. The organic solvents were removed via rotary evaporator, and the remaining aqueous solution was freeze-dried to yield lithium 3-methylenecyclopentanecarboxylate. 1H NMR (400 MHz, CD3OD) δ ppm 4.84-4.73 (m, 2 H), 2.71-2.59 (m, 1 H), 2.57-2.35 (m, 3 H), 2.29-2.16 (m, 1 H), 2.01-1.91 (1 H, m), 1.84-1.72 (m, 1 H,).
Reaction SMILES: [S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[CH:3]=[C:2]1[C:10]([OH:12])=O.C(Cl)(=O)C([Cl:16])=O.CN(C=O)C>ClCCl>[S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[CH:3]=[C:2]1[C:10]([Cl:16])=[O:12]
Reactant: O=C(Cl)C(=O)Cl
Reactant: O=C(O)c1cc2ccccc2s1
Solvent: CN(C)C=O
Solvent: ClCCl
Product: O=C(Cl)c1cc2ccccc2s1
Yield: 23 %

Procedure:
Benzothiophene-2-carboxylic acid was treated with 1.5 equivalents of oxalyl chloride in dichloromethane in the presence of a catalytic amount of DMF to form benzothiophene-2-carbonyl chloride. Following procedures described for Example 1 and substituting this acyl chloride for 3-trifluoromethylbenzoyl chloride, compound 77 was prepared in 23% yield.
Reaction SMILES: [C:1]1(=[O:10])[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][CH2:2]1>C1C=CC=CC=1.CCOCC>[CH:1]1([OH:10])[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][CH2:2]1
Reactant: O=C1CCc2ccccc21
Solvent: c1ccccc1
Solvent: CCOCC
Product: OC1CCc2ccccc21
Temperature: 35 °C
Reaction time: 1 h
Yield: 74.4 %

Procedure:
20 g Indanone (obtained according to Example VIII) is added to a solution of 1.5 molequivalent NaAlH2 (OC2H4OCH3)2 in a mixture of benzene and ether in the course of which the temperature raises to 35° C. Then the reaction mixture is stirred during one hour, poured out into ice and extracted with ether. The solution in ether is washed with NaCl solution, dried and evaporated. The residue is distilled under diminished pressure yielding 15.1 g indanol. B.p. 115° C./1 mm Hg. The indanol is dissolved in 100 ml cyclohexane and during 30 min. gaseous HCl is introduced followed by N2 to remove the excess of HCl. The reaction mixture is evaporated and the residue is distilled under diminished pressure yielding 12.9 g indanyl chloride. B.p. 95° C./1 mm Hg.
Reaction SMILES: [C:1]([CH2:4][C:5]1[C:13]2[C:8](=[CH:9][CH:10]=[C:11]([F:14])[CH:12]=2)[N:7]([CH2:15][C:16]2[C:25]3[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=3)[CH:19]=[CH:18][CH:17]=2)C=1C(O)=O)([OH:3])=[O:2].[C:29](Cl)(=[O:31])[CH3:30]>>[F:14][C:11]1[CH:12]=[C:13]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH2:15][C:16]1[C:25]3[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=3)[CH:19]=[CH:18][CH:17]=1)[C:30]1[C:29](=[O:31])[O:3][C:1](=[O:2])[CH2:4][C:5]2=1
Reactant: O=C(O)Cc1c(C(=O)O)n(Cc2cccc3ccccc23)c2ccc(F)cc12
Reactant: CC(=O)Cl
Product: O=C1Cc2c(n(Cc3cccc4ccccc34)c3ccc(F)cc23)C(=O)O1

Procedure:
A mixture of 3-carboxymethyl-5-fluoro-1-naphthalen-1-ylmethyl-1H-indole-2-carboxylic acid (from Example 33, 0.5 g) in acetylchloride (6.2 ml) was heated to reflux for 5 h. The solution was evaporated and the residue triturated with diethylether to give 6-fluoro-9-naphthalen-1-ylmethyl-4,9-dihydro-pyrano[3,4-b]indole-1,3-dione as a pale yellow solid. MS: 377.4 ([M+NH4]+).