Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([C:8]1[CH:29]=[CH:28][C:11]([CH2:12][C:13]2[C:18]([Cl:19])=[CH:17][C:16]([N:20]3[C:25](=[O:26])[NH:24][CH2:23][CH:22]=[N:21]3)=[CH:15][C:14]=2[Cl:27])=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Cr](Cl)([O-])(=O)=[O:31].[NH+]1C=CC=CC=1>ClCCl>[CH2:1]([C:8]1[CH:9]=[CH:10][C:11]([CH2:12][C:13]2[C:14]([Cl:27])=[CH:15][C:16]([N:20]3[C:25](=[O:26])[NH:24][C:23](=[O:31])[CH:22]=[N:21]3)=[CH:17][C:18]=2[Cl:19])=[CH:28][CH:29]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: O=[Cr](=O)([O-])Cl
Reactant: O=C1NCC=NN1c1cc(Cl)c(Cc2ccc(Cc3ccccc3)cc2)c(Cl)c1
Agent: c1cc[nH+]cc1
Solvent: ClCCl
Product: O=c1cnn(-c2cc(Cl)c(Cc3ccc(Cc4ccccc4)cc3)c(Cl)c2)c(=O)[nH]1
Temperature: 25 °C
Reaction time: 12 h
Yield: 50.8 %

Procedure:
In 20 ml of dichloromethane was dissolved 438 mg of 2-[4-(4-benzylbenzyl)-3,5-dichlorophenyl]-4,5-dihydro-1,2,4-triazine-3(2H)-one followed by addition of 1.0 g of pyridinium chlorochromate, and the mixture was stirred at room temperature for 12 hours. After completion of the reaction, the reaction mixture was filtered to remove the insoluble substance. The filtrate was concentrated and purified by silica gel chromatography (ethyl acetate/hexane=2/1) to provide 230 mg of the title compound as colorless crystals.
Reaction SMILES: [F-].C([N+](CCCC)(CCCC)CCCC)CCC.O1CCCC1.[Si]([O:41][CH2:42][C:43]1[CH:48]=[CH:47][C:46]([CH2:49][CH2:50][CH2:51][CH2:52][CH3:53])=[CH:45][C:44]=1[Cl:54])(C(C)(C)C)(C1C=CC=CC=1)C1C=CC=CC=1.O>O1CCCC1>[Cl:54][C:44]1[CH:45]=[C:46]([CH2:49][CH2:50][CH2:51][CH2:52][CH3:53])[CH:47]=[CH:48][C:43]=1[CH2:42][OH:41]
Reactant: CCCCCc1ccc(CO[Si](c2ccccc2)(c2ccccc2)C(C)(C)C)c(Cl)c1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: O
Solvent: C1CCOC1
Product: CCCCCc1ccc(CO)c(Cl)c1
Reaction time: 2 h
Yield: 82.2 %

Procedure:
A solution (1.0 M, 2.4 ml) of tetrabutylammonium fluoride/tetrahydrofuran was added to a solution of 1-((tert-butyldiphenylsilyloxy)methyl)-2-chloro-4-(n-pentyl)benzene (890 mg) in tetrahydrofuran (4.5 ml) under ice-cooling, and the mixture was stirred for 2 hr. Water was added to the reaction mixture and the resulting product was extracted three times with ethyl acetate. The organic layers were combined and washed successively with diluted hydrochloric acid, a saturated aqueous solution of sodium hydrogencarbonate and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated and the residue was purified by silica gel column chromatography (hexane/ethyl acetate=7/1) to give the objective compound (345 mg) as a colorless oil.
Reaction SMILES: [CH3:1][CH:2]1[NH:6][CH2:5][C:4]2([CH2:11][CH2:10][N:9]([CH3:12])[CH2:8][CH2:7]2)[O:3]1.C1(N=C=NC2CCCCC2)CCCCC1.[NH:28]1[C:36]2[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=2)[C:30]([CH2:37][CH2:38][C:39](O)=[O:40])=[CH:29]1>ClCCl>[CH3:1][CH:2]1[N:6]([C:39](=[O:40])[CH2:38][CH2:37][C:30]2[C:31]3[C:36](=[CH:35][CH:34]=[CH:33][CH:32]=3)[NH:28][CH:29]=2)[CH2:5][C:4]2([CH2:11][CH2:10][N:9]([CH3:12])[CH2:8][CH2:7]2)[O:3]1
Reactant: O=C(O)CCc1c[nH]c2ccccc12
Reactant: CC1NCC2(CCN(C)CC2)O1
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Solvent: ClCCl
Product: CC1OC2(CCN(C)CC2)CN1C(=O)CCc1c[nH]c2ccccc12
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a stirred solution of 2,8-dimethyl-1-oxa-3,8-diaza-spiro[4.5]decane (991.2 mg, 5.8 mmol) in dichloromethane (110 ml) at room temperature were added dicyclohexylcarbodiimide (1.61 g, 7.8 mmol) and 3-indolepropionic acid (1.43 g, 7.6 mmol). The resulting solution was stirred at room temperature overnight. A white solid precipitated during the reaction. After filtration the solvent was evaporated and the crude product was purified by flash chromatography (silica, CH2Cl2/EtOH/NH4OH 90/10/1). After evaporation and drying under vacuum, AF711 (716 mg, 99.6% chemical purity) was obtained as a white solid. 1H NMR (CDCl3, 500 MHz) δ 8.50, 8.46 (2 br s, 1H, NH indole), 7.61 (d, J=7.55 Hz, 1H, CHC arom), 7.33 (d, J=7.85 Hz, 1H, CHCNH arom), 7.18 (app t, J=7.24, 7.85 Hz, 1H, CHCHC arom), 7.11 (app t, J=7.55, 7.24 Hz, 1H, CHCHC arom), 7.02 (d, J=1.86 Hz, 1H, CHNH indole), 5.32, 5.15 (2q, J=5.09 and J=5.16 Hz, 1H, CHCH3), 3.99, 3.22 (2d, J=11 and J=9.5 Hz, 1H, CHHNCO), 3.19 (m, 1H), 3.13-3.08 (m, 1H), 3.03, 2.97 (2d, J=9.5 and J=11 Hz, 1H, CHHNCO), 2.72-2.60 (m, 2H), 2.51-2.20 (m, 4H), 2.25, 2.23 (2s, 3H, NCH3), 1.78-1.64 (m, 2H), 1.43, 1.31 (2d, J=5.15 and J=5.15 Hz, 3H, CH3CH), 1.39, 1.28 (2m, 1H), 1.14 (m, 1H) ppm; 13C NMR (CDCl3, 500 MHz) δ 170.50, 169.85 (C), 136.30, 136.25 (C), 127.07, 126.99 (C), 121.93 (CH), 121.85 (CH), 119.24 (CH), 118.55, 118.52 (CH), 114.73 (C), 111.20, 111.12 (CH), 84.69, 84.06 (CH), 77.98 (C), 54.18 (CH2), 52.18 (CH2), 51.86 (CH2), 45.89, 45.83 (CH3), 36.38 (CH2), 34.98 (CH2), 32.99, 32.41 (CH2), 22.70, 20.50 (CH3), 20.96, 20.73 (CH2) ppm.
Reaction SMILES: [NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[NH:10][CH:11]1[CH2:16][CH2:15][N:14]([C:17]([O:19][CH2:20][CH3:21])=[O:18])[CH2:13][CH2:12]1.O1CCCC1.C[Si]([N-][Si](C)(C)C)(C)C.[K+].CS([CH2:41][CH2:42][O:43][CH2:44][C:45]1[O:46][CH:47]=[CH:48][CH:49]=1)(=O)=O>O>[O:46]1[CH:47]=[CH:48][CH:49]=[C:45]1[CH2:44][O:43][CH2:42][CH2:41][N:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[NH:10][CH:11]1[CH2:16][CH2:15][N:14]([C:17]([O:19][CH2:20][CH3:21])=[O:18])[CH2:13][CH2:12]1
Reactant: CCOC(=O)N1CCC(Nc2nc3ccccc3[nH]2)CC1
Reactant: CS(=O)(=O)CCOCc1ccco1
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [K+]
Solvent: C1CCOC1
Solvent: O
Product: CCOC(=O)N1CCC(Nc2nc3ccccc3n2CCOCc2ccco2)CC1
Temperature: -78 °C
Reaction time: 0.5 h

Procedure:
Combine (1H-benzimidazol-2-yl)(1-ethoxycarbonylpiperidin-4-yl)amine (0.5 g, 1.6 mmol) and tetrahydrofuran (10 mL). Cool to -78° C. Add dropwise, a solution of potassium bis(trimethylsilyl)amide (3.6 mL, 0.5M in toluene, 1.8 mmol). After 30 minutes, add fur-2-ylmethyl 2-methanesulfonylethyl ether (1.8 mmol). Warm to ambient temperature and heat to reflux. After 18 hours, cool to ambient temperature and add water. Separate the organic layer and extract the aqueous layer with dichloromethane. Dry the combined organic layers over Na2SO4, filter, and evaporate in vacuo to give (1-(2-(fur-2-ylmethoxy)ethyl)-1H-benzimidazol-2-yl)(1-ethoxycarbonylpiperidin-4-yl)amine: Rf =0.55 (2% triethylamine/10% methanol/ethyl acetate).
Reaction SMILES: C(O[C:4](=[O:12])[CH2:5][CH2:6][CH2:7][CH2:8][C:9]([OH:11])=[O:10])C.[CH:13]1([NH2:19])[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]1>O>[CH:13]1([NH:19][C:4](=[O:12])[CH2:5][CH2:6][CH2:7][CH2:8][C:9]([OH:11])=[O:10])[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]1
Reactant: CCOC(=O)CCCCC(=O)O
Reactant: NC1CCCCC1
Solvent: O
Product: O=C(O)CCCCC(=O)NC1CCCCC1
Temperature: 80 °C

Procedure:
34.8 g (0.2 mol) of adipic acid monoethyl ester are added dropwise and with stirring to 19.8 g (0.2 mol) of cyclohexylamine. The temperature rises to 60° C. The reaction mixture is heated to 80° C. for 1 h. After cooling, the solution is poured into 200 ml of water and then extracted with 300 ml of ethyl ether. The ether phase is stirred into 150 ml of potassium hydrogen carbonate solution. After separation of the ether phase when settling has taken place, the aqueous phase is acidified to pH 1 with concentrated hydrochloric acid. The precipitate is drained, washed with water, dried and recrystallised in acetonitrile.
Reaction SMILES: [C:1]1([N:7]=[C:8]=[S:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:10]([NH:18][NH2:19])(=O)[C:11]1[CH:16]=[CH:15][N:14]=[CH:13][CH:12]=1.[OH-].[Na+].Cl>C(O)C.O>[C:1]1([N:7]2[C:10]([C:11]3[CH:16]=[CH:15][N:14]=[CH:13][CH:12]=3)=[N:18][N:19]=[C:8]2[SH:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: NNC(=O)c1ccncc1
Reactant: S=C=Nc1ccccc1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CCO
Product: Sc1nnc(-c2ccncc2)n1-c1ccccc1
Temperature: 25 °C
Reaction time: 18 h

Procedure:
A one liter round bottomed flask, fitted with a reflux condenser, nitrogen inlet and magnetic stirrer bar, is charged with 40.5 g (0.30 mol) of phenyl isothiocyanate and 41.845 g (0.30 mol) of isonicotinic acid hydrazide in 300 ml of absolute ethanol. The mixture is heated to reflux for 3 hours. The resulting solid is filtered and washed with ethanol and then added to an aqueous solution of sodium hydroxide (prepared by dissolving 16.8 g, 0.42 mol, of sodium hydroxide in 240 ml of water). The mixture is heated to reflux for 5 hours and then stirred at ambient temperature for 18 hours. The solution is treated with 100 ml of distilled water to dissolve the gel which has formed. The solution is made acidic (to pH 2) with concentrated HCl and cooled with ice. The solid is filtered, taken up in 600 ml of warm absolute ethanol and filtered again to afford approximately 70 g (92%) of slightly wet titled product with a melting point of 288°-290° C. IR (nujol shows a peak at 1900 cm-1 ; UV (95% ethanol) shows peaks at 257 nm and 317 nm; NMR (DMSO-d6 δ) 8.5 and 7.2-7.6; the mass spectra shows a strong molecular ion peak at m/e 254, with fragment ions at 253, 195 and 149.
Reaction SMILES: [NH2:1][C:2]1[N:24]=[C:5]2[C:6]([C:11]3[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13][CH:12]=3)=[CH:7][C:8]([CH3:10])=[CH:9][N:4]2[N:3]=1.[CH3:25][C:26]1[N:31]=[CH:30][N:29]=[C:28]([N:32]2[CH2:37][CH2:36][C:35](=O)[CH2:34][CH2:33]2)[CH:27]=1.C(Cl)Cl>C(Cl)Cl.CO>[CH3:10][C:8]1[CH:7]=[C:6]([C:11]2[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:21])([CH3:23])[CH3:22])=[O:18])[CH2:13][CH:12]=2)[C:5]2[N:4]([N:3]=[C:2]([NH:1][CH:35]3[CH2:36][CH2:37][N:32]([C:28]4[CH:27]=[C:26]([CH3:25])[N:31]=[CH:30][N:29]=4)[CH2:33][CH2:34]3)[N:24]=2)[CH:9]=1
Reactant: Cc1cc(C2=CCN(C(=O)OC(C)(C)C)CC2)c2nc(N)nn2c1
Reactant: Cc1cc(N2CCC(=O)CC2)ncn1
Solvent: ClCCl
Solvent: CO
Product: Cc1cc(C2=CCN(C(=O)OC(C)(C)C)CC2)c2nc(NC3CCN(c4cc(C)ncn4)CC3)nn2c1

Procedure:
Prepared in analogy to example 1h, starting from tert-butyl 4-(2-amino-6-methyl-[1,2,4]triazolo[1,5-a]pyridin-8-yl)-5,6-dihydropyridine-1(2H)-carboxylate and 1-(6-methylpyrimidin-4-yl)piperidin-4-one (see example 93b). The title compound was obtained as a light yellow solid (yield: 32%) after column chromatography on silica gel using a gradient from methylene chloride to methylene chloride/methanol 19:1 (v/v) as eluent.
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:14][CH3:15])=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[CH:4][CH:3]=1.[C:16]([C:19]1[CH:24]=[C:23]([CH3:25])[CH:22]=[CH:21][C:20]=1[OH:26])(=[O:18])[CH3:17].O>ClC1C=CC=CC=1Cl>[CH3:13][O:12][C:9]1[CH:10]=[C:11]2[C:6](=[CH:7][C:8]=1[O:14][CH3:15])[N:5]=[CH:4][CH:3]=[C:2]2[O:26][C:20]1[CH:21]=[CH:22][C:23]([CH3:25])=[CH:24][C:19]=1[C:16](=[O:18])[CH3:17]
Reactant: CC(=O)c1cc(C)ccc1O
Reactant: COc1cc2nccc(Cl)c2cc1OC
Solvent: O
Solvent: Clc1ccccc1Cl
Product: COc1cc2nccc(Oc3ccc(C)cc3C(C)=O)c2cc1OC
Temperature: 170 °C
Reaction time: 144 h
Yield: 3.6 %

Procedure:
4-Chloro-6,7-dimethoxyquinoline (220 mg) and 2-acetyl-4-methylphenol (300 mg) were suspended in o-dichlorobenzene (2 ml), and the suspension was stirred at 170° C. for 6 days. The reaction solution was cooled to room temperature, water was then added to the reaction solution, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was then washed with water and saturated brine and was dried over anhydrous sodium sulfate. The solvent was removed therefrom by distillation under the reduced pressure, and the residue was purified by thin layer chromatography using acetone-chloroform to give the title compound (12 mg, yield 4%).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:26]=[CH:27][CH:28]=1)[CH2:6][CH2:7][N:8]([CH3:25])[CH2:9][CH2:10][CH2:11][CH:12]([C:15]1[CH:20]=[C:19]([O:21][CH3:22])[CH:18]=[C:17]([O:23][CH3:24])[CH:16]=1)[C:13]#[N:14].[NH2-].[Na+].[CH:31](Br)([CH3:33])[CH3:32].O>C1(C)C=CC=CC=1>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:26]=[CH:27][CH:28]=1)[CH2:6][CH2:7][N:8]([CH3:25])[CH2:9][CH2:10][CH2:11][C:12]([C:15]1[CH:20]=[C:19]([O:21][CH3:22])[CH:18]=[C:17]([O:23][CH3:24])[CH:16]=1)([CH:31]([CH3:33])[CH3:32])[C:13]#[N:14]
Reactant: COc1cccc(CCN(C)CCCC(C#N)c2cc(OC)cc(OC)c2)c1
Reactant: CC(C)Br
Agent: [NH2-]
Agent: [Na+]
Solvent: Cc1ccccc1
Solvent: O
Product: COc1cccc(CCN(C)CCCC(C#N)(c2cc(OC)cc(OC)c2)C(C)C)c1
Reaction time: 2 h
Yield: 110.5 %

Procedure:
38.3 g (0.1 mole) of 5-[(3-methoxyphenethyl)-methylamino]-2-(3,5-dimethoxyphenyl)-valeronitrile were dissolved in 200 ml of toluene, and the stirred solution was refluxed with 4.7 g (0.12 mole) of powdered sodium amide for 1 hour. Thereafter, a solution of 15.7 g (0.12 mole) of isopropylbromide in 30 ml of toluene was added dropwise in the course of 60 minutes, and refluxing was continued for a further 2 hours. The cooled reaction mixture was poured into water, the toluene phase was washed several times with water and the toluene was then distilled off. The residue was dissolved in 100 ml of isopropanol, and ethanolic hydrochloric acid was added. The hydrochloride was recrystallized from isopropanol. 46.9 g (92%) of a hydrochloride of melting point 141°-143° C. were isolated.
Reaction SMILES: [NH:1]1[CH2:5][CH2:4][CH2:3][C:2]1=[O:6].C[Si]([N-][Si](C)(C)C)(C)C.[K+].S(O[CH2:22][C:23]1[CH:28]=[C:27]([O:29][CH3:30])[C:26]([O:31][CH3:32])=[C:25]([O:33][CH3:34])[CH:24]=1)(=O)(=O)C.C(OCC)(=O)C>O1CCCC1>[CH3:34][O:33][C:25]1[CH:24]=[C:23]([CH:28]=[C:27]([O:29][CH3:30])[C:26]=1[O:31][CH3:32])[CH2:22][N:1]1[CH2:5][CH2:4][CH2:3][C:2]1=[O:6]
Reactant: COc1cc(COS(C)(=O)=O)cc(OC)c1OC
Reactant: O=C1CCCN1
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [K+]
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: COc1cc(CN2CCCC2=O)cc(OC)c1OC
Temperature: -78 °C
Reaction time: 0.75 h

Procedure:
Combine 2-pyrrolidinone (2.85 g, 33.5 mmol) and tetrahydrofuran (70 mL). Cool to −78° C. using a dry-ice/acetone bath. Add a solution of potassium bis(trimethylsilyl)amide (67 mL, 0.5 M in toluene, 33.5 mol). After 45 minutes, add a solution of 3,4,5-trimethoxybenzyl mesylate (8.8 g, 32.02 mmol) in tetrahydrofuran (60 mL). After the addition of 3,4,5-trimethoxybenzyl mesylate is complete, heat to reflux. After 18 hours, cool the reaction mixture and partition between water and ethyl acetate. Separate the aqueous layer and extract 4 times with ethyl acetate. Dry the combined organic layers over Na2SO4, filter, and concentrate in vacuo to obtain a residue. Chromatograph the residue on silica gel eluting with ethyl acetate to give the title compound: Rf=0.35 (silica gel, ethyl acetate).
Reaction SMILES: Cl[CH2:2][Si:3]([C:6]1[CH:11]=[CH:10][C:9]([Cl:12])=[CH:8][C:7]=1[Cl:13])([CH3:5])[CH3:4].[Na].[NH:15]1[CH:19]=[CH:18][N:17]=[CH:16]1>CN(C)C=O>[Cl:13][C:7]1[CH:8]=[C:9]([Cl:12])[CH:10]=[CH:11][C:6]=1[Si:3]([CH3:5])([CH3:4])[CH2:2][N:15]1[CH:19]=[CH:18][N:17]=[CH:16]1
Reactant: C[Si](C)(CCl)c1ccc(Cl)cc1Cl
Reactant: c1c[nH]cn1
Agent: [Na]
Solvent: CN(C)C=O
Product: C[Si](C)(Cn1ccnc1)c1ccc(Cl)cc1Cl
Reaction time: 2 h
Yield: 68.4 %

Procedure:
A mixture of 5.1 g (0.020 mol) of chloromethyl(2,4-dichlorophenyl)dimethylsilane and 2.0 g (0.022 mol) of imidazole sodium salt in 10 ml of dry dimethylformamide was stirred at 80°-90° for 2 hours and worked up as in Example 23 to give 3.9 g (69%) of the title compound as a brown oil: nD23 1.5637; ir (neat) 1560, 1500, 1450, 1355, 1250, 1105, 1095, 1075, 1025, 840, 780, 735 cm-1 ; nmr (CDCl3) 0.4 (6H, s), 3.9 (2H, s), 6.7 (1H, broad s), 7.0 (1H, broad s) 7.2-7.5 (4H, m).
Reaction SMILES: S(=O)(=O)(O)O.[C:6]([OH:15])(=O)[C:7]1[C:8](=[CH:10][CH:11]=[CH:12][CH:13]=1)[SH:9].[C:16]1([OH:22])[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1>O>[OH:22][C:16]1[CH:21]=[CH:20][C:19]2[S:9][C:8]3[C:7](=[CH:13][CH:12]=[CH:11][CH:10]=3)[C:6](=[O:15])[C:18]=2[CH:17]=1
Reactant: O=C(O)c1ccccc1S
Reactant: Oc1ccccc1
Agent: O=S(=O)(O)O
Solvent: O
Product: O=c1c2ccccc2sc2ccc(O)cc12
Reaction time: 0.08 h

Procedure:
Concentrated sulphuric acid (300 ml) was slowly added to thiosalicylic acid (30.9 g) and the mixture was stirred for 5 minutes to ensure thorough mixing. Phenol (94 g.) was added slowly to the stirred mixture over a period of 30 minutes. After the addition, the addition was stirred at room temperature for 1 hour, then at 80° C. for two hours, after which it was left to stand at room temperature overnight. The resulting mixture was poured carefully with stirring into 10 times its volume of boiling water which was then boiled for a further 5 mins. The solution was cooled and filtered. The residue was recrystallised from acetone to give 2-hydroxythioxanthone as a yellow product.
Reaction SMILES: [CH3:1][C:2]1[CH:11]=[C:10]([O:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[C:9]2[C:4](=[C:5](Br)[CH:6]=[CH:7][CH:8]=2)[N:3]=1.[CH3:20][C:21]1[CH:26]=[C:25]([CH3:27])[CH:24]=[C:23]([CH3:28])[C:22]=1B(O)O.O>COCCOC.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>[CH3:1][C:2]1[CH:11]=[C:10]([O:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[C:9]2[C:4](=[C:5]([C:22]3[C:23]([CH3:28])=[CH:24][C:25]([CH3:27])=[CH:26][C:21]=3[CH3:20])[CH:6]=[CH:7][CH:8]=2)[N:3]=1
Reactant: Cc1cc(Oc2ccccc2)c2cccc(Br)c2n1
Reactant: Cc1cc(C)c(B(O)O)c(C)c1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: COCCOC
Solvent: O
Product: Cc1cc(C)c(-c2cccc3c(Oc4ccccc4)cc(C)nc23)c(C)c1
Temperature: 80 °C
Yield: 72 %

Procedure:
Part C: To a solution of 5.2 g (16.5 mmol) of 2-methyl-4-phenoxy-8-bromo-quinoline in 175 ml DME-water (6:1), 3.3 g (20 mmol) of 2,4,6-tri-methyl-phenyl-boronic acid, 12.6 g (40 mmol) of Ba(OH)2.8H2O and 0.46 g (0.4 mmol) of tetrakis(triphenylphosphine)palladium were added. After heating at 80° C. for 16 hours the mixture was cooled to room temperature, water was added and the mixture was extracted with CH2Cl2. The organic layer was dried over magnesium sulphate and concentrated in vacuo. The product was purified on a silicagel column using CH2Cl2 as the eluent. A total of 4.2 g of 2-methyl-4-phenoxy-8-(2,4,6-trimethylphenyl)-quinoline was obtained (73% yield)
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[N:3][C:2]=1[C:7]1[N:12]=[C:11]([CH3:13])[C:10]([C:14]([OH:16])=O)=[CH:9][N:8]=1.[F:17][C:18]1[N:23]=[C:22]2[C:24]([CH3:28])=[CH:25][N:26]([NH2:27])[C:21]2=[CH:20][CH:19]=1.CCN(C(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>[F:17][C:18]1[N:23]=[C:22]2[C:24]([CH3:28])=[CH:25][N:26]([NH:27][C:14]([C:10]3[C:11]([CH3:13])=[N:12][C:7]([C:2]4[N:1]=[CH:6][CH:5]=[CH:4][N:3]=4)=[N:8][CH:9]=3)=[O:16])[C:21]2=[CH:20][CH:19]=1
Reactant: Cc1nc(-c2ncccn2)ncc1C(=O)O
Reactant: Cc1cn(N)c2ccc(F)nc12
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: Cc1nc(-c2ncccn2)ncc1C(=O)Nn1cc(C)c2nc(F)ccc21
Yield: 24.4 %

Procedure:
A solution of 2-pyrimidin-2-yl-4-methyl-pyrimidine-5-carboxylic acid (1.41 mmol), 5-fluoro-3-methyl-pyrrolo[3,2-b]pyridin-1-ylamine (1.41 mmol), DIPEA (158 mg, 4.22 mmol) and HATU (1.69 mmol) in anhydrous DMF (8 mL) is stirred at 90° C. for 16 hours. DMF is evaporated off in vacuo. The residue is dissolved in EtOAc (40 mL), washed with water (3×10 mL) and brine (10 mL), dried (Na2SO4), filtered, and concentrated in vacuo. The residue is purified by silica gel chromatography eluting with 1-20% MeOH in DCM to afford 4-methyl-[2,2′]bipyrimidinyl-5-carboxylic acid (5-fluoro-3-methyl-pyrrolo[3,2-b]pyridin-1-yl)-amide (125 mg) as a solid. MS: 364 (M+H); 1H NMR (300 MHz, CD3OD): δ 2.31 (s, 3H), 2.87 (s, 3H), 6.87 (d, H), 7.50 (s, H), 7.66 (t, H), 7.96 (t, H), 9.04 (d, 2H), 9.27 (s, H).
Reaction SMILES: [CH:1]([N:3]1[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1)=[O:2].[CH3:9][OH:10]>F[B-](F)(F)F.C[N+](C)(C)C>[CH:1]([N:3]1[CH2:8][CH2:7][CH2:6][CH2:5][CH:4]1[O:10][CH3:9])=[O:2]
Reactant: O=CN1CCCCC1
Reactant: CO
Agent: C[N+](C)(C)C
Agent: F[B-](F)(F)F
Product: COC1CCCCN1C=O
Reaction time: 0.25 h
Yield: 95 %

Procedure:
In the cell and device as described in Example 2 a mixture of 480 g of 1-formylpiperidine, 1,360 g of methanol and 6.80 g of tetramethylammonium tetrafluoroborate was electrolyzed for 34 hours and 15 minutes at 1 A (corresponding to 240 Ahr), 98 volts and 25° C. By distillative work up, 577 g of 1-formyl-2-methoxypiperidine could be isolated from the clear electrolyte, corresponding to a current efficiency of 90.2% of the theory.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][NH:9][C:10]2[N:11]([CH2:20][CH:21]([CH3:23])[CH3:22])[C:12]3[N:13]([CH2:17][CH2:18][N:19]=3)[C:14](=[O:16])[CH:15]=2)=[CH:4][CH:3]=1.[N:24]([O-])=[O:25].[Na+]>C(O)(=O)C>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][NH:9][C:10]2[N:11]([CH2:20][CH:21]([CH3:23])[CH3:22])[C:12]3[N:13]([CH2:17][CH2:18][N:19]=3)[C:14](=[O:16])[C:15]=2[N:24]=[O:25])=[CH:4][CH:3]=1
Reactant: CC(C)CN1C(NCc2ccc(Cl)cc2)=CC(=O)N2CCN=C21
Reactant: O=N[O-]
Agent: [Na+]
Solvent: CC(=O)O
Product: CC(C)CN1C2=NCCN2C(=O)C(N=O)=C1NCc1ccc(Cl)cc1
Temperature: 0 °C

Procedure:
A suspension of the product of Procedure 86 (0.1 mol) in 150 ml. 25% aqueous acetic acid is cooled to 0° C. and treated by dropwise addition of an aqueous solution of sodium nitrite (0.11 mol). After stirring at 0° C. for an hour, the mixture is warmed to room temperature, the solid collected by filtration, washed with water and air dried.
Reaction SMILES: [CH3:1][N:2]1[CH2:7][CH2:6][C:5](=O)[CH2:4][CH2:3]1.[CH3:9][C:10]1[CH:17]=[CH:16][C:13]([CH2:14][NH2:15])=[CH:12][CH:11]=1.C(O)(=O)C.[BH3-]C#N.[Na+]>CO>[CH3:9][C:10]1[CH:17]=[CH:16][C:13]([CH2:14][NH:15][CH:5]2[CH2:6][CH2:7][N:2]([CH3:1])[CH2:3][CH2:4]2)=[CH:12][CH:11]=1
Reactant: CN1CCC(=O)CC1
Reactant: Cc1ccc(CN)cc1
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: CO
Solvent: CC(=O)O
Product: Cc1ccc(CNC2CCN(C)CC2)cc1
Yield: 93 %

Procedure:
1-Methyl-4-piperidone (1.13 g, 10 mmol) was dissolved in 20 ml of methanol and added to a 100 ml flask. 4-Methylbenzylamine (1.21 g, 10 mmol) in 10 ml of methanol was added. Acetic acid (˜1.5 ml) was added until pH˜5. NaCNBH3 (1.26 g, 20 mmol) was slowly added. After 20 hrs magnetic stirring methanol was partly removed on Rotavapor (40° C.). Dichloromethane, water and 2M NaOH were added until pH˜10. The phases were separated and aq. phase was extracted twice with dichloromethane. The combined organic phases were washed with brine and dried over MgSO4. Concentration on Rotavapor (40° C.) yielded 2.06 g crude (93%) 47AKU-5. TLC (20% methanol in dichloromethane): Rf=0.3. HPLC-MS (Method A): M+=219.1 (UV/MS(%)=89/98).
Reaction SMILES: Br[C:2]1[S:22][C:5]2=[N:6][C:7]([CH3:21])=[CH:8][C:9]([NH:10][S:11]([C:14]3[CH:19]=[CH:18][CH:17]=[C:16]([Cl:20])[CH:15]=3)(=[O:13])=[O:12])=[C:4]2[C:3]=1[CH3:23].[O:24]1[C:28]2[CH:29]=[CH:30][CH:31]=[CH:32][C:27]=2[CH:26]=[C:25]1B(O)O.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[O:24]1[C:28]2[CH:29]=[CH:30][CH:31]=[CH:32][C:27]=2[CH:26]=[C:25]1[C:2]1[S:22][C:5]2=[N:6][C:7]([CH3:21])=[CH:8][C:9]([NH:10][S:11]([C:14]3[CH:19]=[CH:18][CH:17]=[C:16]([Cl:20])[CH:15]=3)(=[O:13])=[O:12])=[C:4]2[C:3]=1[CH3:23]
Reactant: OB(O)c1cc2ccccc2o1
Reactant: Cc1cc(NS(=O)(=O)c2cccc(Cl)c2)c2c(C)c(Br)sc2n1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: C1COCCO1
Product: Cc1cc(NS(=O)(=O)c2cccc(Cl)c2)c2c(C)c(-c3cc4ccccc4o3)sc2n1
Temperature: 100 °C
Yield: 10 %

Procedure:
To solution of N-(2-bromo-3,6-dimethylthieno[2,3-b]pyridin-4-yl)-3-chlorobenzenesulfonamide (Example 77) (100 mg, 0.232 mmol) in 1,4-dioxane (2 mL) and water (1 mL) was added 1-benzofuran-2-ylboronic acid (56.3 mg, 0.347 mmol), bis(triphenylphosphine)palladium(II) chloride (16.26 mg, 0.023 mmol) and potassium carbonate (112 mg, 0.811 mmol) and the reaction mixture heated at 100° C. using a microwave reactor for 30 min. The mixture was then filtered through celite, washing with DCM (20 mL×2) and the filtrate dried (phase separation cartridge) and concentrated. The residue was then purified by MDAP (acidic conditions), followed by MDAP (basic conditions) to afford the title compound (10.89 mg). LCMS (A) m/z: 469 [M+1]+, Rt 1.42 min (acidic).