Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][C:3]1[C:12]([N+:13]([O-])=O)=[CH:11][CH:10]=[CH:9][C:4]=1[C:5]([O:7][CH3:8])=[O:6]>CO.[Ni]>[NH2:13][C:12]1[C:3]([O:2][CH3:1])=[C:4]([CH:9]=[CH:10][CH:11]=1)[C:5]([O:7][CH3:8])=[O:6]
Reactant: COC(=O)c1cccc([N+](=O)[O-])c1OC
Agent: [Ni]
Solvent: CO
Product: COC(=O)c1cccc(N)c1OC
Reaction time: 3.5 h
Yield: 96.8 %

Procedure:
To a solution of methyl 2-methoxy-3-nitrobenzoate (28.4 g, 134 mmol) in MeOH (150 mL) was added Raney Ni (3 g). The mixture was stirred under H2 atmosphere (50 psi/25 IC) for 3.5 h. The catalyst was filtered, and the filtrate was concentrated under the reduced pressure to dryness to give the crude product, which was purified by recrystallization in EtOAc to afford the title compound of Step C, methyl 3-amino-2-methoxybenzoate (23.5 g, 96.4% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 6.80-6.93 (m, 3H), 5.10-5.25 (br, 2H), 3.78 (s, 3H), 3.67 (s, 3H).
Reaction SMILES: [CH2:1]([CH:5]([Sn])C=C(CCCC)CCCC)[CH2:2]CC.Br[C:18]1[C:19]([F:38])=[CH:20][CH:21]=[C:22]2[C:26]=1[NH:25][C:24]1[C:27]([CH2:36][CH3:37])([CH2:31][C:32]([O:34][CH3:35])=[O:33])[O:28][CH2:29][CH2:30][C:23]2=1>C1C=CC=CC=1.[Pd].CCOCC.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH2:36]([C:27]1([CH2:31][C:32]([O:34][CH3:35])=[O:33])[C:24]2[NH:25][C:26]3[C:22]([C:23]=2[CH2:30][CH2:29][O:28]1)=[CH:21][CH:20]=[C:19]([F:38])[C:18]=3[CH2:5][CH:1]=[CH2:2])[CH3:37]
Reactant: CCCCC(=CC([Sn])CCCC)CCCC
Reactant: CCC1(CC(=O)OC)OCCc2c1[nH]c1c(Br)c(F)ccc21
Agent: [Pd]
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: c1ccccc1
Solvent: CCOCC
Product: C=CCc1c(F)ccc2c3c([nH]c12)C(CC)(CC(=O)OC)OCC3
Temperature: 80 °C
Reaction time: 42 h
Yield: 78 %

Procedure:
According to the procedure of Kosugi et al, Chem. Letters 301 (1977) tetrakis-(triphenylphosphine) palladium [O] (60 mg) was added to a mixture of tributylallyltin (1.75 g, 0.0053 mol) and 8-bromo-1-ethyl-7-fluoro-1,3,4,9-tetrahydro-pyrano[3,4-b]indole-1-acetic acid, methyl ester (1.6 g, 0.0043 mol) in benzene (4.0 mL) under N2. The sealed tube was then heated to 80° C. for 15 hours, more palladium catalyst was added (30 mg), and heating continued for 42 hours at 110°-120° C. The cooled reaction mixture was diluted with Et2O, then filtered through a glass wool plug. The ether was washed twice with brine, then dried (MgSO4) to yield an oil that was purified via flash chromatography. Using 1:7 EtOAc:hexane to afford 1.12 g, (~78%) of 1-ethyl-7-fluoro-1,3,4,9-tetrahydro-8-(2-propenyl)-pyrano[3,4-b]indole-1-acetic acid, methyl ester as a colorless oil. The oil was dissolved in ethanol (40 mL) and 1N sodium hydroxide added (15 mL). The mixture was heated to reflux for 2 hours then cooled and concentrated. 1N HCl was added and the aqueous solution extracted with ether. The ether layers were washed (brine), dried (MgSO4) and concentrated to yield a foamy oil. This was purified by flash chromatography on SiO2 -pretreated with 2% H3PO4 -MeOH. Using 1:2 EtOAc:hexane to give 1 g (73%) of 1-ethyl-7-fluoro-1,3,4,9-tetrahydro-8-(2-propenyl)-pyrano[3,4-b]indole-1-acetic acid as a colorless oil which crystallized from toluene:petroleum ether, m.p. 123°-125° C.
Reaction SMILES: [CH2:1]([O:5][C:6]1[C:7]([C:11]2[CH:12]=[N:13][CH:14]=[CH:15][CH:16]=2)=[N:8][NH:9][CH:10]=1)[CH2:2][CH:3]=[CH2:4].[CH3:17]SC1C(C2C=NC=CC=2)=NNC=1>>[CH2:1]([O:5][C:6]1[C:7]([C:11]2[CH2:12][N:13]([CH3:17])[CH2:14][CH2:15][CH:16]=2)=[N:8][NH:9][CH:10]=1)[CH2:2][CH:3]=[CH2:4]
Reactant: C=CCCOc1c[nH]nc1-c1cccnc1
Reactant: CSc1c[nH]nc1-c1cccnc1
Product: C=CCCOc1c[nH]nc1C1=CCCN(C)C1

Procedure:
Compound 32D was converted to the title compound (33D), using the methodology described for the conversion of 21A to 22A (see Scheme 3).
Reaction SMILES: C(OC(=O)[NH:7]/[C:8](/[NH:17][C:18]1[C:19]([CH3:33])=[N:20][CH:21]=[C:22]([CH:24]2[CH2:29][CH2:28][N:27]([CH3:30])[CH2:26][C:25]2([CH3:32])[CH3:31])[CH:23]=1)=[N:9]\C(=O)OC(C)(C)C)(C)(C)C.Cl>C(Cl)Cl>[CH3:33][C:19]1[C:18]([NH:17][C:8]([NH2:9])=[NH:7])=[CH:23][C:22]([CH:24]2[CH2:29][CH2:28][N:27]([CH3:30])[CH2:26][C:25]2([CH3:32])[CH3:31])=[CH:21][N:20]=1
Reactant: Cc1ncc(C2CCN(C)CC2(C)C)cc1N/C(=N/C(=O)OC(C)(C)C)NC(=O)OC(C)(C)C
Agent: Cl
Solvent: ClCCl
Product: Cc1ncc(C2CCN(C)CC2(C)C)cc1NC(=N)N
Temperature: 25 °C
Reaction time: 8 h
Yield: 170.2 %

Procedure:
To a solution of di-tert-butyl((Z)-{[2-methyl-5-(1,3,3-trimethylpiperidin-4-yl)pyridine-3-yl]amino}methylylidene)biscarbamate (0.78 g, 1.60 mmol) in DCM (10 mL) was added hydrochloric acid (4.0 M in 1,4-dioxane, 20 mL). The reaction mixture was allowed to stir at rt overnight. The reaction mixture was concentrated to give the hydrochloride salt of N-[2-methyl-5-(1,3,3-trimethylpiperidin-4-yl)pyridine-3-yl]guanidine (750 mg, 110%) as a white solid.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][C:3]=1[O:11][CH3:12].[CH3:13][C:14]1[CH:15]=[C:16](B(O)O)[CH:17]=[CH:18][CH:19]=1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:12][O:11][C:3]1[CH:4]=[C:5]([N+:8]([O-:10])=[O:9])[CH:6]=[CH:7][C:2]=1[C:18]1[CH:17]=[CH:16][CH:15]=[C:14]([CH3:13])[CH:19]=1
Reactant: Cc1cccc(B(O)O)c1
Reactant: COc1cc([N+](=O)[O-])ccc1Br
Agent: [Pd+2]
Agent: CC(=O)[O-]
Product: COc1cc([N+](=O)[O-])ccc1-c1cccc(C)c1

Procedure:
The title compound was prepared by reaction of 1-bromo-2-methoxy-4-nitrobenzene with 3-methylphenylboronic acid in the presence of palladium acetate.
Reaction SMILES: [CH3:1][N:2]1[C:6]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)=[N:5][N:4]=[C:3]1[CH2:13][CH2:14][CH2:15][CH:16]=C.[OH2:18]>C1COCC1.O.O=[Os](=O)(=O)=O>[CH3:1][N:2]1[C:6]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)=[N:5][N:4]=[C:3]1[CH2:13][CH2:14][CH2:15][CH:16]=[O:18]
Reactant: C=CCCCc1nnc(-c2ccccc2)n1C
Reactant: O
Agent: O=[Os](=O)(=O)=O
Solvent: C1CCOC1
Product: Cn1c(CCCC=O)nnc1-c1ccccc1

Procedure:
To a solution of 4-methyl-3-(4-penten-1-yl)-5-phenyl-4H-1,2,4-triazole (196 mg, 0.86 mmol) in THF/H2O (7.5/1.5 ml) were added OsO4 (4% solution in water, 0.04 mmol) and NalO4 (2.6 mmol). The solution was stirred o.n. at r.t. Water was added and product was extract with DCM. The organic phase was separated, dried over Na2SO4 and filtered. Volatiles were evaporated in vacuo to give 178 mg of the title compound as an oil, which was used in the subsequent step without further purification.
Reaction SMILES: [CH2:1]([NH2:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl[CH2:10][Si:11]([CH3:14])([CH3:13])[CH3:12]>[OH-].[Na+].CCOCC>[CH2:1]([NH:8][CH2:10][Si:11]([CH3:14])([CH3:13])[CH3:12])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: NCc1ccccc1
Reactant: C[Si](C)(C)CCl
Agent: [Na+]
Agent: [OH-]
Solvent: CCOCC
Product: C[Si](C)(C)CNCc1ccccc1
Temperature: 200 °C
Yield: 74.3 %

Procedure:
Benzylamine (51.5 g, 480 mmol) was added to (chloromethyl)trimethylsilane (19.64 g, 160 mmol) and heated at 200° C. for 2 hours. The reaction mixture was diluted with 1 N sodium hydroxide solution and ether and the organic layer was dried over magnesium sulfate and concentrated under reduced pressure. The residue was distilled under reduced pressure to afford 23.00 g of N-benzyl-N-trimethylsilanylmethyl-amine.
Reaction SMILES: [C:1]([NH:4][C@@H:5]1[C@@H:10]([OH:11])[C@H:9]([OH:12])[C@@H:8]([CH2:13][OH:14])[O:7][CH:6]1[NH:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH3:27])(=[O:3])[CH3:2].[C:28](Cl)(=[O:46])[CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH3:45]>>[CH2:16]([N:15]([CH:6]1[O:7][C@H:8]([CH2:13][OH:14])[C@@H:9]([OH:12])[C@H:10]([OH:11])[C@H:5]1[NH:4][C:1](=[O:3])[CH3:2])[C:28](=[O:46])[CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH3:45])[CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH3:27]
Reactant: CCCCCCCCCCCCCCCCCC(=O)Cl
Reactant: CCCCCCCCCCCCNC1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1NC(C)=O
Product: CCCCCCCCCCCCCCCCCC(=O)N(CCCCCCCCCCCC)C1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1NC(C)=O

Procedure:
3 g of N-(2-acetamido-2-deoxy-D-glucopyranosyl)-dodecylamine, the preparation of which is described in Example 55, were reacted with stearoyl chloride as described in Example 55.
Reaction SMILES: [CH3:1][CH:2]([N:9]1[CH2:12][CH:11]([OH:13])[CH2:10]1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[OH-].[Na+].[H-].[Na+].[F:18][C:19]([F:28])([F:27])[C:20]1[CH:25]=[CH:24][C:23](F)=[CH:22][CH:21]=1>CN(C)C=O.C1C=CC=CC=1>[CH3:1][CH:2]([N:9]1[CH2:12][CH:11]([O:13][C:23]2[CH:24]=[CH:25][C:20]([C:19]([F:28])([F:27])[F:18])=[CH:21][CH:22]=2)[CH2:10]1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1
Reactant: Fc1ccc(C(F)(F)F)cc1
Reactant: CC(c1ccccc1)N1CC(O)C1
Agent: [H-]
Agent: [Na+]
Agent: [OH-]
Solvent: c1ccccc1
Solvent: CN(C)C=O
Product: CC(c1ccccc1)N1CC(Oc2ccc(C(F)(F)F)cc2)C1
Temperature: 90 °C
Yield: 39.8 %

Procedure:
The maleate salt of 1-(α-methylbenzyl)-3-hydroxyazetidine (78.6 g., 0.20 mole) was partitioned between benzene and dilute sodium hydroxide, the benzene layer dried, filtered, and concentrated at reduced pressure. The residue was dissolved in 100 ml. of dry dimethylformamide and added at a rapid dropwise rate, to a stirring suspension of 10.1 g. (0.22 mole) of sodium hydride (50% in mineral oil) in 150 ml. of dry dimethylformamide at 90° C. The solution was heated at 90° C. for one hour and then treated dropwise with 32.0 g. (0.20 mole) of 4-trifluoromethylfluorobenzene. The solution was refluxed for three hours. The cooled solution was partitioned between water and isopropyl ether, and the ether layer extracted with dilute hydrochloric acid. The aqueous acid layer was made basic with concentrated sodium hydroxide and ice, and extracted with isopropyl ether. The ether layer was concentrated and the residue distilled at 150°-160° C./0.2 mm. to give 25.6 g of product.
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][C:2]1=[O:10].[CH2:11]([N:13]([CH2:28][CH3:29])[CH2:14][CH2:15][CH2:16][C:17]1[CH:18]=[C:19]2[C:23](=[CH:24][CH:25]=1)[NH:22][C:21]([CH:26]=O)=[CH:20]2)[CH3:12].N1CCCCC1>C(O)C>[CH2:28]([N:13]([CH2:11][CH3:12])[CH2:14][CH2:15][CH2:16][C:17]1[CH:18]=[C:19]2[C:23](=[CH:24][CH:25]=1)[NH:22][C:21]([CH:26]=[C:3]1[C:4]3[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=3)[NH:1][C:2]1=[O:10])=[CH:20]2)[CH3:29]
Reactant: O=C1Cc2ccccc2N1
Reactant: CCN(CC)CCCc1ccc2[nH]c(C=O)cc2c1
Solvent: CCO
Solvent: C1CCNCC1
Product: CCN(CC)CCCc1ccc2[nH]c(C=C3C(=O)Nc4ccccc43)cc2c1
Temperature: 95 °C
Yield: 18.3 %

Procedure:
A mixture of oxindole (26 mg, 0.19 mmol), 5-(3-diethylamino-propyl)-1H-indole-2-carbaldehyde (50 mg, 0.19 mmol) and piperidine (0.1 mL) in ethanol (1 mL) was heated in a sealed tube at 95° C. for 20 hours. The precipitate was collected by vacuum filtration, washed with ethanol and dried to give 13 mg (18%) of the title compound as an orange crystalline solid.
Reaction SMILES: [C:1]([C:3]1[CH:7]=[CH:6][NH:5][N:4]=1)#[N:2].[CH2:8]=[O:9]>CC(C)=O>[OH:9][CH2:8][N:5]1[CH:6]=[CH:7][C:3]([C:1]#[N:2])=[N:4]1
Reactant: N#Cc1cc[nH]n1
Reactant: C=O
Solvent: CC(C)=O
Product: N#Cc1ccn(CO)n1
Temperature: 130 °C
Reaction time: 7 h
Yield: 78.2 %

Procedure:
The mixture of 0.86 g of 3-cyano-1H-pyrazole and 0.55 g of paraformaldehyde was stirred at 130° C. for 7 hours. After the reaction mixture was cooled to room temperature, acetone was added to the reaction mixture. After the mixture was filtered, the filterate was concentrated under reduced pressure to obtain 0.89 g of 1-(hydroxymethyl)-3-cyano-1H-pyrazole.
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][CH:4]([C:7]2[CH:15]=[CH:14][C:10]([C:11]([OH:13])=[O:12])=[CH:9][CH:8]=2)[CH2:3][CH2:2]1.C=O.[BH3-][C:19]#N.[Na+].Cl>CO>[CH3:19][N:1]1[CH2:6][CH2:5][CH:4]([C:7]2[CH:15]=[CH:14][C:10]([C:11]([OH:13])=[O:12])=[CH:9][CH:8]=2)[CH2:3][CH2:2]1
Reactant: O=C(O)c1ccc(C2CCNCC2)cc1
Reactant: [BH3-]C#N
Agent: C=O
Agent: Cl
Agent: [Na+]
Solvent: CO
Product: CN1CCC(c2ccc(C(=O)O)cc2)CC1
Temperature: 25 °C
Reaction time: 96 h
Yield: 60.8 %

Procedure:
4-piperidin-4yl-benzoic acid (110 mg, 0.54 mmol, reference example 109) was added to paraformaldehyde (180 mg, 6 mmol) in MeOH (10 mL) and NaCNBH3 (120 mg, 1.94 mmol). The reaction was stirred at room temperature for 4 days, at which time HPLC shows no remaining starting material. The solution was acidified to pH 2 with concentrated HCl, evaporated, dissolved in water (20 mL), and extracted with ether (3×20 mL). Then the solution was brought to pH 12 with KOH pellets, extracted with dichloromethane (3×20 mL) and finally brought to pH5 with acetic acid. The mixture was lyophilized and the solid was extracted with MeOH (3×15 mL). The combined methanol extracts were evaporated and the residue chromatographed (reverse-phase HPLC, C18 column, 10-100% CH3CN/water) to yield, after lyophilization, 72 mg of the desired product (61%). 1H NMR (CD3OD): δ 7.98 (d, 2H), 7.38 (d, 2H), 3.60 (m, 2H), 3.18 (t, 2H), 2.94 (s, 3H), 2.85-2.95 (m, 2H), 2.08-2.18 (m, 2H), 1.90-2.02 (m, 2H). MS (ion spray) m/z 220 (M+H+). >98% pure by analytical HPLC.
Reaction SMILES: [F:1][C:2]([F:15])([F:14])[C:3]1[NH:4][C:5]2[C:10]([CH:11]=1)=[CH:9][C:8]([CH2:12][NH2:13])=[CH:7][CH:6]=2.[Cl:16][C:17]1[CH:22]=[C:21](Cl)[N:20]=[CH:19][N:18]=1.C(=O)([O-])[O-].[K+].[K+].CS(C)=O>O>[Cl:16][C:17]1[N:18]=[CH:19][N:20]=[C:21]([NH:13][CH2:12][C:8]2[CH:9]=[C:10]3[C:5](=[CH:6][CH:7]=2)[NH:4][C:3]([C:2]([F:1])([F:14])[F:15])=[CH:11]3)[CH:22]=1
Reactant: NCc1ccc2[nH]c(C(F)(F)F)cc2c1
Reactant: Clc1cc(Cl)ncn1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CS(C)=O
Product: FC(F)(F)c1cc2cc(CNc3cc(Cl)ncn3)ccc2[nH]1
Temperature: 140 °C
Yield: 74.2 %

Procedure:
{[2-(Trifluoromethyl)-1H-indol-5-yl]methyl}amine (Intermediate 34, 600 mg, 2.394 mmol), 4,6-dichloropyrimidine (357 mg, 2.394 mmol) and potassium carbonate (993 mg, 7.18 mmol) were added to DMSO (13 mL). The reaction mixture was heated in the microwave for 1.5 hours at 140° C. The LC/MS showed product. The reaction mixture was poured into water and extracted with ethyl acetate. Traces of water were removed with a phase separator and the solvent removed under reduced pressure to give the title compound (580 mg);
Reaction SMILES: [NH2:1][CH:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][N:10]2[C:19]3[C:14](=[CH:15][CH:16]=[C:17]([O:20][CH3:21])[CH:18]=3)[N:13]=[CH:12][C:11]2=[O:22])[CH2:4][CH2:3]1.[O:23]=[C:24]1[CH2:29][S:28][C:27]2[CH:30]=[CH:31][C:32]([CH:34]=O)=[N:33][C:26]=2[NH:25]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].CO>ClCCl>[CH3:21][O:20][C:17]1[CH:18]=[C:19]2[C:14]([N:13]=[CH:12][C:11](=[O:22])[N:10]2[CH2:9][CH2:8][N:5]2[CH2:4][CH2:3][CH:2]([NH:1][CH2:34][C:32]3[CH:31]=[CH:30][C:27]4[S:28][CH2:29][C:24](=[O:23])[NH:25][C:26]=4[N:33]=3)[CH2:7][CH2:6]2)=[CH:15][CH:16]=1
Reactant: O=Cc1ccc2c(n1)NC(=O)CS2
Reactant: COc1ccc2ncc(=O)n(CCN3CCC(N)CC3)c2c1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: ClCCl
Solvent: CO
Product: COc1ccc2ncc(=O)n(CCN3CCC(NCc4ccc5c(n4)NC(=O)CS5)CC3)c2c1
Yield: 57.7 %

Procedure:
1-[2-(4-Aminopiperidin-1-yl)ethyl]-7-methoxyquinoxalin-2(1H)-one (Intermediate 146, 250 mg crude, 0.83 mmol), 3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazine-6-carbaldehyde (WO 2004/058144) (160 mg, 0.83 mmol), and sodium triacetoxy borohydride (530 mg, 2.50 mmol) were reacted as described according to Example 69. Chromatography on silica gel with 10% methanol in dichloromethane containing 0.25% ammonium hydroxide afforded the free base of the product. This was triturated with dichloromethane and the precipitate was collected by filtration giving 230 mg (58%) of the title compound as a colorless solid.
Reaction SMILES: [O:1]1[CH:5]=[CH:4][CH:3]=[C:2]1B(O)O.Br[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:10]1([C:2]2[O:1][CH:5]=[CH:4][CH:3]=2)[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1
Reactant: Brc1ccccc1
Reactant: OB(O)c1ccco1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=P([O-])([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: C1COCCO1
Product: c1ccc(-c2ccco2)cc1
Temperature: 95 °C
Reaction time: 3 h
Yield: 62.2 %

Procedure:
To a solution of (furan-2-yl)boronic acid (3.0 g, 26.81 mmol) in dioxane (50.0 mL) and water (1.0 mL) was added bromobenzene (2.10 g, 13.38 mmol), K3PO4 (9.3 g, 43.81 mmol) and Pd(PPh3)4 (767 mg, 0.66 mmol) with stirring for 3 h at 95° C. in an oil bath under an inert atmosphere of nitrogen. The reaction mixture was concentrated under reduced pressure to give the residue, which was purified by silica gel column chromatography (1% ethyl acetate in petroleum ether) to afford 2-phenylfuran as colorless oil (1.20 g, 62%).
Reaction SMILES: [OH-].[K+].[C:3]([O:7][C:8]([N:10]1[CH2:15][CH2:14][O:13][CH:12]([C:16]([O:18]C)=[O:17])[CH2:11]1)=[O:9])([CH3:6])([CH3:5])[CH3:4].O.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>CO>[C:3]([O:7][C:8]([N:10]1[CH2:15][CH2:14][O:13][CH:12]([C:16]([OH:18])=[O:17])[CH2:11]1)=[O:9])([CH3:6])([CH3:4])[CH3:5]
Reactant: COC(=O)C1CN(C(=O)OC(C)(C)C)CCO1
Agent: O=C(O)CC(O)(CC(=O)O)C(=O)O
Agent: [K+]
Agent: [OH-]
Solvent: O
Solvent: CO
Product: CC(C)(C)OC(=O)N1CCOC(C(=O)O)C1
Temperature: 25 °C
Reaction time: 8 h
Yield: 92.8 %

Procedure:
A 1 mol/L aqueous potassium hydroxide solution (3 mL) was added to methyl 4-(tert-butoxycarbonyl)morpholine-2-carboxylate (251 mg, 1.02 mmol) in methanol (15 mL). The mixture was stirred at room temperature for 8 hours. Subsequently, water was added to the mixture, followed by addition of a 5% aqueous citric acid solution to make the mixture acidic. The mixture was then extracted with ethyl acetate. The extract was washed with brine and was dried over magnesium sulfate. Evaporation of the solvent gave 219 mg (93%) of the desired compound as a colorless powder.
Reaction SMILES: [NH:1]1[CH:5]=[C:4]([C:6]2[CH:11]=[CH:10][N:9]=[C:8]3[N:12]([CH2:15][O:16][CH2:17][CH2:18][Si:19]([CH3:22])([CH3:21])[CH3:20])[CH:13]=[CH:14][C:7]=23)[CH:3]=[N:2]1.[C:23]([CH:25]=[C:26]1[CH2:29][N:28]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH2:27]1)#[N:24].N12CCCN=C1CCCCC2>C(#N)C>[C:23]([CH2:25][C:26]1([N:1]2[CH:5]=[C:4]([C:6]3[CH:11]=[CH:10][N:9]=[C:8]4[N:12]([CH2:15][O:16][CH2:17][CH2:18][Si:19]([CH3:22])([CH3:21])[CH3:20])[CH:13]=[CH:14][C:7]=34)[CH:3]=[N:2]2)[CH2:29][N:28]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH2:27]1)#[N:24]
Reactant: CC(C)(C)OC(=O)N1CC(=CC#N)C1
Reactant: C[Si](C)(C)CCOCn1ccc2c(-c3cn[nH]c3)ccnc21
Solvent: C1CCC2=NCCCN2CC1
Solvent: CC#N
Product: CC(C)(C)OC(=O)N1CC(CC#N)(n2cc(-c3ccnc4c3ccn4COCC[Si](C)(C)C)cn2)C1
Temperature: 50 °C
Yield: 99.5 %

Procedure:
A mixture of 4-(1H-pyrazol-4-yl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridine (0.527 g, 1.68 mmol), tert-butyl 3-(cyanomethylene)azetidine-1-carboxylate (0.358 g, 1.84 mmol) and 1,8-diazabicyclo[5.4.0]undec-7-ene (135 μL, 0.903 mmol) in acetonitrile (4.0 mL) was heated at 50° C. for 1 hour. After cooling, the solvent was removed under reduced pressure. The residue was diluted with ethyl acetate, neutralized with 0.5 N HCl aqueous solutions, washed brine, dried over Na2SO4, filtered and concentrated under reduced pressure to afford the desired product (0.85 g, quantitative) which was directly used in next step reaction without further purification. LCMS (M+H)+: m/z=509.3.
Reaction SMILES: [N:1]1[NH:2][C:3]2[CH:17]=[CH:16][CH:15]=[C:5]3[C:6](=[O:14])[C:7]4[CH:13]=[CH:12][CH:11]=[CH:10][C:8]=4[C:9]=1[C:4]=23.[N-:18]=[N+]=[N-].[Na+].C(OCC)(=O)C.O1CCCC1>S(=O)(=O)(O)O>[N:1]1[NH:2][C:3]2[CH:17]=[CH:16][CH:15]=[C:5]3[C:6](=[O:14])[NH:18][C:7]4[CH:13]=[CH:12][CH:11]=[CH:10][C:8]=4[C:9]=1[C:4]=23
Reactant: [N-]=[N+]=[N-]
Reactant: O=C1c2ccccc2-c2n[nH]c3cccc1c23
Agent: O=S(=O)(O)O
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: O=C1Nc2ccccc2-c2n[nH]c3cccc1c23
Temperature: 25 °C
Reaction time: 72 h
Yield: 25.3 %

Procedure:
To a solution of 100 mg of 2,6-dihydrodibenzo[cd,g]indazol-6-one [CAS No. 129-56-6] in 0.6 ml concentrated sulfuric acid was added 78 mg of sodium azide [CAS No. 26628-22-8], followed by stirring at room temperature for 3 days. After adding ice, the reaction mixture was poured into a mixture solution of 100 ml of ethyl acetate and 10 ml of tetrahydrofuran and washed with saturated sodium hydrogen carbonate solution. The organic layer was washed with brine, dried over anhydrous magnesium sulfate, and the solvent was evaporated. The residue was dissolved in tetrahydrofuran, adsorbed by 3.5 g of silica gel and subjected to silica gel chromatography [Wako Gel C-200, 2 g]. The fractions of tetrahydrofuran-toluene [19:1 to 9:1] were concentrated, and the resulting powder was suspended in tetrahydrofuran-toluene. A powder was collected by filtration, and recrystallized from dimethylformamide-water, to give 27 mg of 6,7-dihydro-2H-benzo[6,7]azepino[5,4,3-cd]indazol-6-one as green needles.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([S:11][CH2:12][C@@H:13]2[C@:22]3([CH3:23])[C@H:17]([C:18]([CH3:25])([CH3:24])[CH2:19][CH2:20][CH2:21]3)[CH2:16][CH2:15][C@@:14]2([CH3:27])O)[CH:6]=[C:7]([O:9][CH3:10])[CH:8]=1.Cl[Sn](Cl)(Cl)Cl.O>C(Cl)Cl>[CH3:10][O:9][C:7]1[CH:8]=[C:3]([O:2][CH3:1])[CH:4]=[C:5]2[C:6]=1[C@@:14]1([CH3:27])[C@H:13]([CH2:12][S:11]2)[C@:22]2([CH3:23])[C@H:17]([C:18]([CH3:24])([CH3:25])[CH2:19][CH2:20][CH2:21]2)[CH2:16][CH2:15]1
Reactant: COc1cc(OC)cc(SC[C@@H]2[C@@]3(C)CCCC(C)(C)[C@@H]3CC[C@@]2(C)O)c1
Agent: Cl[Sn](Cl)(Cl)Cl
Solvent: O
Solvent: ClCCl
Product: COc1cc(OC)c2c(c1)SC[C@@H]1[C@@]3(C)CCCC(C)(C)[C@@H]3CC[C@@]21C
Temperature: 0 °C
Reaction time: 2 h
Yield: 80.6 %

Procedure:
To a solution of (1R,2R,4aS,8aS)-1-{[(3,5-dimethoxyphenyl)sulfanyl]-methyl}-2,5,5,8a-tetramethyl-decahydronaphthalen-2-ol (21) (1.0 g, 2.55 mmol) in CH2Cl2 (50 mL) was added dropwise SnCl4 (1 M in CH2Cl2, 10.2 mL, 10.19 mmol) at −78° C. over 5 min. After complete addition, the reaction mixture was allowed to warm to 0° C. for 1 h, then room temperature for 2 h. Water (20 mL) was added at room temperature followed by CH2Cl2 (50 mL). The organic layer was separated, dried (Na2SO4), and concentrated. Trituration with MeOH gave (1R,10R,11S,16S)-3,5-dimethoxy-1,11,15,15-tetramethyl-8-thiatetracyclo[8.8.0.02,7.011,16]octadeca-2,4,6-triene (Compound No. 22) (0.77 g, 81%) as a white solid. 1H NMR (CDCl3): δ 6.22 (d, 1H), 6.18 (d, 1H), 3.78 (s, 3H), 3.78 (s, 3H), 3.25 (m, 1H), 2.90 (m, 1H), 2.78 (m, 1H), 1.84-1.38 (m, 7H), 1.37 (s, 3H), 1.36-1.00 (m, 3H), 0.95 (s, 3H), 0.90 (m, 1H), 0.85 (s, 3H), 0.85 (s, 3H). MS m/z 375 (C23H34O2S+H+).
Reaction SMILES: [CH2:1]1[CH:5]2[CH:6]3[CH:10]=[CH:9][CH:8]([CH:4]2[CH:3]=[CH:2]1)[CH2:7]3.[CH2:11]=[CH:12][C:13]1C=CC=CC=1>C1(C)C=CC=CC=1>[C:1]1([CH:5]2[CH2:4][CH:8]3[CH2:7][CH:6]2[CH:10]=[CH:9]3)[CH:2]=[CH:3][CH:13]=[CH:12][CH:11]=1
Reactant: C=Cc1ccccc1
Reactant: C1=CC2C3C=CC(C3)C2C1
Solvent: Cc1ccccc1
Product: C1=CC2CC1CC2c1ccccc1
Temperature: 150 °C

Procedure:
Dicyclopentadiene (180 g), styrene (140 g), toluene (36 g), and N,N-diethylbydroxylamine (0.35 g) (added as a polymerization inhibitor) were added to a stainless steel reactor. The mixture was heated to 150° C. for 6 hours. The low boiling fraction was removed from the resulting reaction mixture on the roto-vap. The remaining higher boiling fraction was fractionally distilled. The fraction distilling at 130° C. @ 4 mm Hg was analyzed by GC and found to be 96% 5-phenylnorbornene.