Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: F[C:2]1[C:3]([C:8]2[O:12][N:11]=[C:10]([C:13]3[N:18]=[C:17]([N:19]([CH3:26])[C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=4)[N:16]=[C:15]([NH2:27])[N:14]=3)[N:9]=2)=[N:4][CH:5]=[CH:6][CH:7]=1.[CH:28]1([CH2:31][NH2:32])[CH2:30][CH2:29]1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.C(Cl)Cl>[CH:28]1([CH2:31][NH:32][C:2]2[C:3]([C:8]3[O:12][N:11]=[C:10]([C:13]4[N:18]=[C:17]([N:19]([CH3:26])[C:20]5[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=5)[N:16]=[C:15]([NH2:27])[N:14]=4)[N:9]=3)=[N:4][CH:5]=[CH:6][CH:7]=2)[CH2:30][CH2:29]1
Reactant: NCC1CC1
Reactant: CN(c1ccccc1)c1nc(N)nc(-c2noc(-c3ncccc3F)n2)n1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: ClCCl
Product: CN(c1ccccc1)c1nc(N)nc(-c2noc(-c3ncccc3NCC3CC3)n2)n1
Reaction time: 3 h
Yield: 44 %

Procedure:
6-[5-(3-Fluoropyridin-2-yl)-[1,2,4]oxadiazol-3-yl]-N-methyl-N-phenyl-[1,3,5]triazine-2,4-diamine (prepared in an analogous manner to Example 482, 50 mg, 0.137 mmol), 1-cyclopropylmethanamine (24 μL, 0.274 mmol) and potassium carbonate (57 mg, 0.411 mmol) were suspended in anhydrous DMF (2 mL) in a sealed tube at room temperature under nitrogen. The reaction mixture was stirred at 90 C for 3 h and then at 100 C for 18 h. The mixture was diluted with DCM (10 mL) and then washed with saturated aq. ammonium chloride (3×5 mL) and then brine (5 mL). The organic layer was dried over sodium sulfate and evaporated under vacuum. The crude residue was purified by flash chromatography (0-1% (7M ammonia in MeOH) in DCM) to afford the title compound (25 mg, 44%).
Reaction SMILES: [CH2:1]([N:8]1[CH2:18][CH2:17][C:11]2[N:12]=[CH:13][N:14]=[C:15](Cl)[C:10]=2[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[F:19][C:20]([F:30])([F:29])[C:21]1[N:26]=[CH:25][C:24]([CH2:27][NH2:28])=[CH:23][CH:22]=1.C(N(CC)C(C)C)(C)C>C(#N)C>[CH2:1]([N:8]1[CH2:18][CH2:17][C:11]2[N:12]=[CH:13][N:14]=[C:15]([NH:28][CH2:27][C:24]3[CH:25]=[N:26][C:21]([C:20]([F:30])([F:19])[F:29])=[CH:22][CH:23]=3)[C:10]=2[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: Clc1ncnc2c1CN(Cc1ccccc1)CC2
Reactant: NCc1ccc(C(F)(F)F)nc1
Solvent: CCN(C(C)C)C(C)C
Solvent: CC#N
Product: FC(F)(F)c1ccc(CNc2ncnc3c2CN(Cc2ccccc2)CC3)cn1
Yield: 86 %

Procedure:
Two 20 mL microwave vials were each charged with a half portion of 6-benzyl-4-chloro-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine (5.62 g, 21.6 mmol), (6-(trifluoromethyl)pyridin-3-yl)methanamine (5.0 g, 28 mmol), N,N-diisopropylethylamine (7.6 mL, 44 mmol) and acetonitrile (10 mL), and the mixture was subjected to a microwave irradiation at 200° C. for 3.5 h. LC-MS analysis showed the reaction was complete for both samples. The samples were combined, and partitioned between CH2Cl2 (150 mL) and 0.5M NaH2PO4 (pH 4; 120 mL). The organic layer was extracted with 2M HCl (60 mL, 30 mL). The combined acid extracts were basified with 50% KOH (25 mL), extracted with CH2Cl2 (2×100 mL), dried (Na2SO4), filtered and concentrated to yield a light brown oil, which was absorbed on silica (40 g) and purified by column (120 g silica gel, 0-7.5% MeOH/CH2Cl2) to afford a light yellow foam (7.42 g, 86%).
Reaction SMILES: OOS([O-])=O.[K+].[Na+].[Br-:8].CC(C)=O.[CH3:13][O:14][C:15]1[CH:20]=[CH:19][C:18]([C:21](=[O:23])[CH3:22])=[C:17]([CH3:24])[CH:16]=1>C(OCC)(=O)C.O>[Br:8][C:20]1[C:15]([O:14][CH3:13])=[CH:16][C:17]([CH3:24])=[C:18]([C:21](=[O:23])[CH3:22])[CH:19]=1
Reactant: [Br-]
Reactant: COc1ccc(C(C)=O)c(C)c1
Agent: O=S([O-])OO
Agent: [K+]
Agent: [Na+]
Solvent: CC(C)=O
Solvent: CCOC(C)=O
Solvent: O
Product: COc1cc(C)c(C(C)=O)cc1Br
Temperature: 25 °C
Reaction time: 1 h
Yield: 90.7 %

Procedure:
Alternatively, 5-bromo-4-methoxy-2-methylbenzoic acid can be synthesized from 4′-hydroxy-2′-methylacetophenone as a starting material. Potassium carbonate (0.720 mg, 5.21 mmol) and methyl iodide (0.542 g, 3.82 mmol) were added to an acetone (10 mL) solution of 4′-hydroxy-2′-methylacetophenone (0.552 g, 3.47 mmol) and stirred at room temperature for 12 hours. Methyl iodide (0.24 g, 1.73 mmol) was further added, and the mixture was heated to reflux for two hours. After cooled to room temperature, the solvent was evaporated under reduced pressure. After chloroform was added to the residue, insolubles were filtered off and the filtrate was concentrated to obtain 4′-methoxy-2′-methylacetophenone (0.57 g). Then, oxone (0.79 g, 1.27 mmol) and NaBr (0.13 g, 1.27 mmol) were added to an acetone (4 mL) water (4 mL) solution of 4′-methoxy-2′-methylacetophenone (0.21 g, 1.27 mmol), and stirred at room temperature for one hour. After water and ethyl acetate were added to the reaction mixture, the organic layer was separated and washed with water, a saturated sodium carbonate aqueous solution and brine and dried with anhydrous magnesium sulfate. After the desiccant was filtered off, the solvent was evaporated under reduced pressure to obtain 4:1 mixture (0.28 g) of 5′-bromo-4′-methoxy-2′-methylacetophenone and 3′-bromo-4′-methoxy-2′-methylacetophenone. Then, 4:1 mixture (0.26 g) of 5′-bromo-4′-methoxy-2′-methylacetophenone and 3′-bromo-4′-methoxy-2′-methylacetophenone was added with 5% NaOCl solution (3 mL) and potassium hydroxide (0.92 g) and heated to reflux for 2.5 hours. After cooled to room temperature, the reaction mixture was made acidic with 2M HCl. After the mixture was extracted with ethyl acetate, the organic phase was washed with 1M HCl, brine and then dried with anhydrous magnesium sulfate. After the desiccant was filtered off, the residue obtained by evaporating the solvent under reduced pressure was washed with methanol to obtain 5-bromo-4-methoxy-2-methylbenzoic acid (112 mg) as a colorless powder.
Reaction SMILES: Br[CH2:2][C:3]([N:5]([CH2:8][CH3:9])[CH2:6][CH3:7])=[O:4].[NH2:10][C:11]1[CH:16]=[CH:15][C:14]([CH3:17])=[CH:13][CH:12]=1.[Cl:18][C:19]1[CH:20]=[C:21]([S:26](Cl)(=[O:28])=[O:27])[CH:22]=[CH:23][C:24]=1[CH3:25]>>[Cl:18][C:19]1[CH:20]=[C:21]([S:26]([N:10]([C:11]2[CH:16]=[CH:15][C:14]([CH3:17])=[CH:13][CH:12]=2)[CH2:2][C:3]([N:5]([CH2:8][CH3:9])[CH2:6][CH3:7])=[O:4])(=[O:28])=[O:27])[CH:22]=[CH:23][C:24]=1[CH3:25]
Reactant: CCN(CC)C(=O)CBr
Reactant: Cc1ccc(N)cc1
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1Cl
Product: CCN(CC)C(=O)CN(c1ccc(C)cc1)S(=O)(=O)c1ccc(C)c(Cl)c1

Procedure:
prepared by reaction of 2-bromo-N,N-diethylacetamide with p-toluidine and 3-chloro-4-methyl-benzenesulfonyl chloride
Reaction SMILES: [CH3:1][NH:2][CH3:3].[C:4]1([C:10]2([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[CH2:12][CH:11]2[CH2:13]Cl)[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.C(N(CC)CC)C>C(O)C>[CH3:1][N:2]([CH2:13][CH:11]1[CH2:12][C:10]1([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[CH3:3]
Reactant: ClCC1CC1(c1ccccc1)c1ccccc1
Reactant: CNC
Solvent: CCN(CC)CC
Solvent: CCO
Product: CN(C)CC1CC1(c1ccccc1)c1ccccc1
Reaction time: 32 h

Procedure:
To a solution of 40% aqueous dimethylamine (10 ml) in ethanol (10 ml) was added a solution of 2,2-diphenylcyclopropylmethyl chloride (0.50 g) in ethanol (10 ml) and triethylamine (1.0 g) at room temperature, and stirring was carried out at 35°-40° C for 32 hours. The reaction mixture was evaporated and poured into a 10% aqueous sodium hydroxide solution. The etheral extract was dried and chromatographed to afford N,N-dimethyl-2,2-diphenylcyclopropylmethylamine as an oily substance. M.P. 231°-233° C (hydrochloride).
Reaction SMILES: [CH3:1][NH2:2].[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].[CH3:17][S:18]([N:21]1[CH2:26][CH2:25][C:24](=O)[CH2:23][CH2:22]1)(=[O:20])=[O:19].[OH-].[Na+]>CC#N>[CH3:1][NH:2][CH:24]1[CH2:25][CH2:26][N:21]([S:18]([CH3:17])(=[O:20])=[O:19])[CH2:22][CH2:23]1
Reactant: CN
Reactant: CS(=O)(=O)N1CCC(=O)CC1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Agent: [OH-]
Solvent: CC#N
Product: CNC1CCN(S(C)(=O)=O)CC1
Temperature: 25 °C
Reaction time: 1 h
Yield: 63 %

Procedure:
1-Methylsuylfonyl-4-piperidone (40.00 g, 0.226 mol), CH3CN (240 ml) and 40% CH3NH2 (20.4 ml, 0.263 mol) were added to a round bottom flask, and the mixture was stirred at room temperature for 1 hour. To another round bottom flask, NaBH(OAc)3 (60.00 g, 0.283 mol) and 120 ml of CH3CN were added. This solution was stirred at −10° C., to which the first mixture (derived from 1-methylsulfonyl-4-piperidone) was added slowly via an additional funnel. After the addition, the reaction was allowed to warm to room temperature and stirred overnight. The reaction mixture was concentarted to a small volume, to which 1N aq. NaOH (282 ml) was added. This resulting solution was extracted with CH2Cl2 (3×500 ml) followed by extraction with toluene until no product remained in the extraction solution. The combined organic layers were dried over Na2SO4. After filtration, the solution was concentrated in vacuo to give the product (29.0 g, 63%). 1H NMR (CDCl3) δ 3.66 (m, 2H), 2.84 (m, 2H), 2.76 (s, 3H), 2.52 (m, 1H), 2.42 (s, 3H), 1.96 (m, 2H), 1.45 (m, 2H). MS m/e 193 (M+H)+.
Reaction SMILES: [Cl:1][C:2]1[CH:8]=[C:7]([O:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:22][CH3:23])=[C:17]([O:20][CH3:21])[CH:18]=3)[N:13]=[CH:12][CH:11]=2)[CH:6]=[CH:5][C:3]=1[NH2:4].[C:24]1([CH3:33])[C:25]([N:30]=[C:31]=[O:32])=[CH:26][CH:27]=[CH:28][CH:29]=1.CO>C(Cl)(Cl)Cl>[Cl:1][C:2]1[CH:8]=[C:7]([O:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:22][CH3:23])=[C:17]([O:20][CH3:21])[CH:18]=3)[N:13]=[CH:12][CH:11]=2)[CH:6]=[CH:5][C:3]=1[NH:4][C:31]([NH:30][C:25]1[CH:26]=[CH:27][CH:28]=[CH:29][C:24]=1[CH3:33])=[O:32]
Reactant: COc1cc2nccc(Oc3ccc(N)c(Cl)c3)c2cc1OC
Reactant: Cc1ccccc1N=C=O
Solvent: ClC(Cl)Cl
Solvent: CO
Product: COc1cc2nccc(Oc3ccc(NC(=O)Nc4ccccc4C)c(Cl)c3)c2cc1OC
Temperature: 25 °C
Reaction time: 8 h
Yield: 34.5 %

Procedure:
2-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (122 mg) was dissolved in chloroform (10 ml), and o-toluyl isocyanate (59 mg) was added to the solution. The mixture was stirred at room temperature overnight. Methanol was added to the reaction solution, and the solvent was removed by distillation under the reduced pressure. The residue was dissolved in a minor amount of chloroform, and a large amount of ether was added to the solution to precipitate a crystal. The crystal was collected by filtration to give 59 mg (yield 34%) of the title compound.
Reaction SMILES: [Si]([C:5]#[N:6])(C)(C)C.[NH2:7][C:8]1[CH:13]=[CH:12][C:11]([CH2:14][CH2:15][CH2:16][C:17]([NH:19][CH3:20])=[O:18])=[CH:10][CH:9]=1.[CH3:21][C:22]([CH3:24])=O>>[C:5]([C:22]([NH:7][C:8]1[CH:9]=[CH:10][C:11]([CH2:14][CH2:15][CH2:16][C:17]([NH:19][CH3:20])=[O:18])=[CH:12][CH:13]=1)([CH3:24])[CH3:21])#[N:6]
Reactant: C[Si](C)(C)C#N
Reactant: CC(C)=O
Reactant: CNC(=O)CCCc1ccc(N)cc1
Product: CNC(=O)CCCc1ccc(NC(C)(C)C#N)cc1

Procedure:
TMSCN (0.1 mL, 0.78 mmol) was added to a mixture of the compound 30 (50 mg, 0.26 mmol), acetone (0.12 mL, 1.56 mmol) and 12 (4 mg, 0.03 mmol) with stirring. The reaction mixture was stirred at 40° C. for 1 h, and concentrated in vacuo. The residue was diluted with aqNa2SO3, and extracted with ethyl acetate. The combined organic layers were washed with aqNa2SO3 and brine, dried over Na2SO4 and concentrated to dryness to give compound 31 as light yellow oil. The crude product was used directly for the next step without purification. 1H NMR (400 MHz, CDCl3) δ7.07 (d, 2H, J=8.4 Hz), 6.88 (d, 2H, J=8.4 Hz), 5.33 (br s, 1H), 2.79 (d, 3H, J=4.8 Hz), 2.59 (t, 2H, J=7.4 Hz), 2.16 (t, 2H, J=7.4 Hz), 1.85-1.95 (m, 2H), 1.68 (s, 6H).
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][CH:7]=1.[Br:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][N:13]=[C:12]2[C:18](O)=[O:19].C(N(CC)C(C)C)(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[Br:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][N:13]=[C:12]2[C:18]([NH:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][CH:7]=1)=[O:19]
Reactant: Nc1cccnc1
Reactant: O=C(O)c1n[nH]c2ccc(Br)cc12
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: O=C(Nc1cccnc1)c1n[nH]c2ccc(Br)cc12
Temperature: 0 °C
Reaction time: 2 h
Yield: 30.4 %

Procedure:
To a stirring solution of 3-aminopyridine (CXXV) (0.195 g, 0.2.07 mmol) in DMF (10 mL) was added 5-bromo-1H-indazole-3-carboxylic acid (CXV) (0.500 g, 0.2.07 mmol) and N,N-diisopropylethylamine (0.723 mL, 4.15 mmol). The reaction mixture was cooled to 0° C. and added with HATU (0.787 g, 2.07 mmol). The reaction mixture was allowed to warm to room temperature and stirred for an additional 2 h. The solution was concentrated under vacuum. The residue was purified by column chromatography (1:99 MeOH[7N NH3]:CHCl3→4:96 MeOH[7N NH3]:CHCl3) to afford 5-bromo-N-(pyridin-3-yl)-1H-indazole-3-carboxamide (CXXXV) (0.200 g, 0.63 mmol, 30% yield) as a white solid. ESIMS found for C13H9BrN4O m/z 318.0 (M+H).
Reaction SMILES: [Br:1][C:2]1[N:7]=[C:6]([NH2:8])[CH:5]=[CH:4][C:3]=1[Cl:9].N1C=CC=CC=1.[C:16](Cl)(=[O:23])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1>ClCCl>[Br:1][C:2]1[N:7]=[C:6]([NH:8][C:16](=[O:23])[C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH:5]=[CH:4][C:3]=1[Cl:9]
Reactant: Nc1ccc(Cl)c(Br)n1
Reactant: O=C(Cl)c1ccccc1
Solvent: c1ccncc1
Solvent: ClCCl
Product: O=C(Nc1ccc(Cl)c(Br)n1)c1ccccc1
Reaction time: 2 h

Procedure:
To a solution of Example 11A (400 mg, 1.928 mmol) in dichloromethane (20 mL) was added pyridine (0.468 mL, 5.78 mmol) followed by benzoyl chloride (0.325 g, 2.314 mmol) and the mixture was stirred for 2 hours. The mixture was concentrated and the residue was dissolved in ethyl acetate, washed with sodium bicarbonate solution, water and brine, and dried over anhydrous sodium sulfate. Filtration, concentration and purification by column chromatography (silica gel, 10% ethyl acetate in hexane) afforded the title compound. LCMS: 311 (M+H)+.
Reaction SMILES: Cl.[C:2]1([C:8]2[N:9]=[C:10]([CH2:13][NH:14]C(=O)C3C=CC=CC=3)[S:11][CH:12]=2)[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(Cl)(Cl)Cl.CO>O1CCOCC1>[C:2]1([C:8]2[N:9]=[C:10]([CH2:13][NH2:14])[S:11][CH:12]=2)[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: O=C(NCc1nc(-c2ccccc2)cs1)c1ccccc1
Agent: Cl
Solvent: C1COCCO1
Solvent: CO
Solvent: ClC(Cl)Cl
Product: NCc1nc(-c2ccccc2)cs1
Temperature: 100 °C
Reaction time: 24 h
Yield: 77.3 %

Procedure:
6N HCl (4.5 mL) was added to a solution of N-((4-phenylthiazol-2-yl)methyl)benzamide (150 mg, 0.51 mmol) in dioxane (10 mL) and the reaction mixture was stirred at 100° C. for 24 h (reaction monitored by TLC, eluant CHCl3/MeOH). Reaction mixture was concentrated under reduced pressure and the residue was dissolved in water. The aqueous layer was washed twice with EtOAc. The pH of the aqueous layer was then adjusted to pH ˜9 using 10% NaHCO3 and the organic product was extracted with EtOAc. The organic layer was washed with brine and concentrated under reduced pressure to yield (4-phenylthiazol-2-yl)methanamine (75 mg, yield 77%) as orange colored liquid, which was carried through without further purification. 1H NMR (300 MHz, CDCl3) δ 7.91-7.88 (m, 2H), 7.45-7.40 (m, 3H), 7.36-7.31 (m, 1H), 4.25 (br s, 2H), 3.79-3.75 (m, 1H), 3.68-3.63 (m, 1H). MS (ESI) m/z: Calculated for C10H10N2S: 190.06. found: 191.2 (M+H)+.
Reaction SMILES: [C:1]([O:6]O)([CH2:4][CH3:5])([CH3:3])[CH3:2].[C:8]([O:14]CC)([CH2:11][CH2:12][CH3:13])([CH3:10])[CH3:9]>>[C:8]([O:14][O:6][C:1]([CH2:4][CH3:5])([CH3:3])[CH3:2])([CH2:11][CH2:12][CH3:13])([CH3:9])[CH3:10]
Reactant: CCCC(C)(C)OCC
Reactant: CCC(C)(C)OO
Product: CCCC(C)(C)OOC(C)(C)CC

Procedure:
In similar manner, although optimal conditions may vary, hydrogen peroxide may be reacted with methyl t-amyl ether to provide t-amyl hydroperoxide or di-t-amyl peroxide; with methyl t-hexyl ether to provide t-hexyl hydroperoxide or di-t-hexyl peroxide; with ethyl t-butyl ether to provide t-butyl hydroperoxide or di-t-butyl peroxide; with ethyl t-amyl ether to provide t-amyl hydroperoxide or di-t-amyl peroxide; with ethyl t-hexyl ether to provide t-hexyl hydroperoxide or di-t-hexyl peroxide; with n-propyl t-butyl ether to provide t-butyl hydroperoxide or di-t-butyl peroxide; with n-propyl t-amyl ether to provide t-amyl hydroperoxide or di t-amyl peroxide; or with n-propyl t-hexyl ether to provide t-hexyl hydroperoxide or di-t-hexyl peroxide. Illustrative of reactions employing hydroperoxide reactants are the reaction of t-butyl hydroperoxide with methyl t-butyl ether to provide di-t-butyl peroxide; the reaction of t-hexyl hydroperoxide with methyl t-hexyl ether to provide di-t-hexyl peroxide; the reaction of t-butyl hydroperoxide with methyl t-amyl ether to provide t-butyl t-amyl peroxide; the reaction of t-butyl hydroperoxide with methyl t-hexyl ether to provide t-butyl t-hexyl peroxide; and the reaction of t-amyl hydroperoxide with ethyl t-hexyl ether to provide t-amyl t-hexyl peroxide.
Reaction SMILES: [CH3:1]C1C(O)=CC=CN=1.[CH2:9]([O:16][C:17]1[CH:18]=[C:19]2[C:24](=[CH:25][CH:26]=1)[O:23][CH2:22][CH:21]([O:27][C:28]1[C:29](C)=[N:30][CH:31]=[CH:32][CH:33]=1)[C:20]2=[O:35])[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1>C(Cl)(Cl)Cl>[CH2:9]([O:16][C:17]1[CH:18]=[C:19]2[C:24](=[CH:25][CH:26]=1)[O:23][CH2:22][CH:21]([O:27][C:28]1[CH:29]=[N:30][C:31]([CH3:1])=[CH:32][CH:33]=1)[C:20]2=[O:35])[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1
Reactant: Cc1ncccc1O
Reactant: Cc1ncccc1OC1COc2ccc(OCc3ccccc3)cc2C1=O
Solvent: ClC(Cl)Cl
Product: Cc1ccc(OC2COc3ccc(OCc4ccccc4)cc3C2=O)cn1

Procedure:
By the same methods, 2-methyl-3-hydroxypyridine (7.30 g, 0.067 mol) was converted to 1.17 g of 6-benzyloxy-3-(2-methyl-3-pyridyloxy)-4-chromanone [1H-NMR includes delta 2.48 (s, 3H), 4.6 (m, 2H) and 4.93 (dd, 1H); MS includes 361 (M+) and base peak at 91; IR (CHCl3) 1697, 1486 cm-1 ].
Reaction SMILES: Br[C:2]1[C:10]2[CH:11]=[C:12]3[C:20]([C:21]([CH3:23])([CH3:22])[C:9]=2[C:8]2[C:3]=1[CH:4]=[CH:5][CH:6]([C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)[CH:7]=2)=[C:19]1[C:14]([CH:15]=[CH:16][CH:17]=[CH:18]1)=[N:13]3.[C:30]1([N:36]([C:46]2[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=2)[C:37]2[CH:42]=[CH:41][C:40](B(O)O)=[CH:39][CH:38]=2)[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1.C1(C)C=CC=CC=1.C(O)C.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.O.C1(C)C=CC=CC=1>[CH3:22][C:21]1([CH3:23])[C:20]2[C:12]([N:13]=[C:14]3[C:19]=2[CH:18]=[CH:17][CH:16]=[CH:15]3)=[CH:11][C:10]2[C:2]([C:40]3[CH:41]=[CH:42][C:37]([N:36]([C:30]4[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=4)[C:46]4[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=4)=[CH:38][CH:39]=3)=[C:3]3[C:8]([C:9]1=2)=[CH:7][CH:6]([C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)[CH:5]=[CH:4]3
Reactant: CC1(C)C2=C(C=C3N=c4ccccc4=C31)C(Br)=C1C=CC(c3ccccc3)C=C12
Reactant: OB(O)c1ccc(N(c2ccccc2)c2ccccc2)cc1
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: CCO
Solvent: Cc1ccccc1
Solvent: O
Product: CC1(C)C2=C(C=C3N=c4ccccc4=C31)C(c1ccc(N(c3ccccc3)c3ccccc3)cc1)=C1C=CC(c3ccccc3)C=C12
Temperature: 73 °C
Reaction time: 5 h
Yield: 58.2 %

Procedure:
7-Bromo-12,12-dimethyl-10-phenyl-10,12-dihydroindeno[2,1-b]carbazole synthesized in Example 1 (2.0 g), 4-diphenylamino-phenylboronic acid (1.32 g), a toluene/ethanol (4/1, v/v) mixed solvent (15 ml), and a 2M potassium carbonate aqueous solution (3.4 ml) were added to a nitrogen-substituted reaction vessel and aerated with nitrogen gas for 30 min under ultrasonic irradiation. The mixture was heated after adding tetrakis(triphenylphosphine)palladium (0.26 g), and stirred at 73° C. for 5 hours. After the mixture was cooled to a room temperature, toluene (30 ml) and water (20 ml) were added to perform liquid separation in order to collect an organic layer. The organic layer was washed with saturated brine, dehydrated with anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain a crude product. The crude product was purified by column chromatography (carrier: silica gel; eluent: toluene/n-hexane) to obtain a pale yellowish white powder of 12,12-dimethyl-10-phenyl-7-(4-diphenylamino-phenyl)-10,12-dihydroindeno[2,1-b]carbazole (1.6 g; yield 58.4%).
Reaction SMILES: COC1C=C(C=C[N:11]2[CH:20]=[CH:19][C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[C:12]2=[O:21])C=CN=1.[CH3:22][OH:23]>[Pd]>[CH3:22][O:23][C:12]1[CH:13]=[C:18]([CH2:17][CH2:16][C:19]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[C:12](=[O:21])[NH:11][CH:20]=2)[CH:19]=[CH:20][N:11]=1
Reactant: COc1cc(C=Cn2ccc3ccccc3c2=O)ccn1
Reactant: CO
Agent: [Pd]
Product: COc1cc(CCc2c[nH]c(=O)c3ccccc23)ccn1

Procedure:
1.1 g of the above (E/Z) mixture of 4-[2-(2-methoxy-pyridin-4-yl)-vinyl-2H-isoquinolin-1-one in 20 ml of methanol are hydrogenated in the presence of 0.6 g of Pd/C (10%). Filtration through Celite, washing with a lot of methanol, concentrating by evaporation and column chromatography (SiO2, methylene chloride/acetone 3:1→acetone) yield 4-[2-(2-methoxy-pyridin-4-yl)-ethyl]-2H-isoquinolin-1-one; 1H NMR (DMSO-d6) δ11.10 (sb, HN), 8.22 (d, 1H), 8.03 (d, 1H), 7.81 (d, 1H), 7.75 (t, 1H), 7.50 (t, 1H), 6.92 (m, 1H), 6.88 (d, 1H), 6.70 (s, 1H), 3.80 (s, H3C), 2.93 (m, 2H), 2.84 (m, 2H).
Reaction SMILES: CO[C:3](=[O:22])[C:4]1[CH:9]=[CH:8][C:7]([NH:10][CH2:11][C:12]2[C:13]([CH2:18][CH2:19][CH2:20][CH3:21])=[N:14][O:15][C:16]=2[CH3:17])=[N:6][CH:5]=1.[NH2:23][CH:24]([CH3:27])[CH2:25][OH:26]>>[CH2:18]([C:13]1[C:12]([CH2:11][NH:10][C:7]2[CH:8]=[CH:9][C:4]([C:3]([NH:23][CH:24]([CH3:27])[CH2:25][OH:26])=[O:22])=[CH:5][N:6]=2)=[C:16]([CH3:17])[O:15][N:14]=1)[CH2:19][CH2:20][CH3:21]
Reactant: CCCCc1noc(C)c1CNc1ccc(C(=O)OC)cn1
Reactant: CC(N)CO
Product: CCCCc1noc(C)c1CNc1ccc(C(=O)NC(C)CO)cn1
Temperature: 50 °C
Yield: 52.9 %

Procedure:
A mixture of 6-[(3-butyl-5-methyl-isoxazol-4-ylmethyl)-amino]-nicotinic acid methyl ester (90 mg, 0.3 mmol), rac-2-amino-1-propanol (27 mg, 0.36 mmol) and TBD (12 mg, 0.09 mmol) was heated at 50° C. for 4 h under argon. The reaction mixture was concentrated onto silica then purified by chromatography (silica, 0 to 7% methanol in ethyl acetate) to give the title compound (55 mg, 54%) as a colourless oil. MS: m/e=347.3 [M+H]+.
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]1[CH2:7][OH:8].C(N(CC)CC)C.[CH3:16][O:17][C:18]1[CH:23]=[C:22]([CH3:24])[C:21]([S:25](Cl)(=[O:27])=[O:26])=[C:20]([CH3:29])[CH:19]=1.Cl>ClCCl>[CH3:16][O:17][C:18]1[CH:19]=[C:20]([CH3:29])[C:21]([S:25]([N:1]2[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]2[CH2:7][OH:8])(=[O:26])=[O:27])=[C:22]([CH3:24])[CH:23]=1
Reactant: OCC1CCCCN1
Reactant: COc1cc(C)c(S(=O)(=O)Cl)c(C)c1
Agent: Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: COc1cc(C)c(S(=O)(=O)N2CCCCC2CO)c(C)c1
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 20 %

Procedure:
Piperidin-2-ylmethanol (1.1 eq) was dissolved in dichloromethane (4 ml/mmol), cooled, and triethylamine (2.5 eq) was added. A solution of 4-methoxy-2,6-dimethylbenzenesulfonyl chloride (1 eq) in dichloromethane (2 ml/mmol) was added dropwise at 0° C., then the mixture was stirred for 90 min at room temperature. Hydrogen chloride solution (eq, 0.5 mol/l, 2 ml/mmol) was added, the mixture stirred for 15 min and the phases separated. The organic phase was washed with water, dried over sodium sulfate and concentrated to small volume under vacuum. The crude product was used in the next stage with no further purification. Yield: 20%