Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C:2]1[C:7](B2OC(C)(C)C(C)(C)O2)=[CH:6][CH:5]=[CH:4][C:3]=1[NH2:17].Cl[C:19]1[N:20]=[C:21]([N:28]2[CH2:33][CH2:32][O:31][CH2:30][CH2:29]2)[C:22]2[S:27][CH:26]=[CH:25][C:23]=2[N:24]=1>>[CH3:1][C:2]1[C:7]([C:19]2[N:20]=[C:21]([N:28]3[CH2:33][CH2:32][O:31][CH2:30][CH2:29]3)[C:22]3[S:27][CH:26]=[CH:25][C:23]=3[N:24]=2)=[CH:6][CH:5]=[CH:4][C:3]=1[NH2:17]
Reactant: Cc1c(N)cccc1B1OC(C)(C)C(C)(C)O1
Reactant: Clc1nc(N2CCOCC2)c2sccc2n1
Product: Cc1c(N)cccc1-c1nc(N2CCOCC2)c2sccc2n1

Procedure:
Reaction of 2-methyl-3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenylamine with 2-chloro-4-morpholin-4-yl-thieno[3,2-d]pyrimidine under Suzuki conditions yielded 2-methyl-3-(4-morpholin-4-yl-thieno[3,2-d]pyrimidin-2-yl)-phenylamine. To a solution of 2-methyl-3-(4-morpholin-4-yl-thieno[3,2-d]pyrimidin-2-yl)-phenylamine (80 mg) in chloroform (8 mL) and acetic acid (4 mL) was added isoamyl nitrite (36 μL). The reaction mixture was stirred for 1 day at room temperature. The mixture was then quenched with sodium bicarbonate solution and extracted in to chloroform and reduced in vacuo. The residue was purified using flash chromatography to yield 270. MS: ESI MH+ 338
Reaction SMILES: F[C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[CH:4][C:3]=1[N+:11]([O-:13])=[O:12].C([O-])([O-])=O.[K+].[K+].[C:20]1([CH3:32])[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=1[N:26]1[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]1>CN(C=O)C>[N+:11]([C:3]1[CH:4]=[C:5]([CH:9]=[CH:10][C:2]=1[N:29]1[CH2:30][CH2:31][N:26]([C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][C:20]=2[CH3:32])[CH2:27][CH2:28]1)[C:6]([OH:8])=[O:7])([O-:13])=[O:12]
Reactant: O=C(O)c1ccc(F)c([N+](=O)[O-])c1
Reactant: Cc1ccccc1N1CCNCC1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: Cc1ccccc1N1CCN(c2ccc(C(=O)O)cc2[N+](=O)[O-])CC1
Temperature: 25 °C
Reaction time: 16 h

Procedure:
To a solution of 4-fluoro-3-nitro-benzoic acid (6.0 g, 32.4 mmol) in DMF (20 mL), K2CO3 (8.94 g, 64.8 mmol) was added, followed by 1-o-tolyl-piperazine (6.85 g, 38.9 mmol), and the reaction mixture was stirred at room temperature for 16 h. DMF (5.0 mL) was added and filtered. The solid was washed with MeOH (300 mL) and methanol layer was evaporated to give the acid 3-nitro-4-(4-o-tolyl-piperazin-1-yl)-benzoic acid in the first crop (4.0 g, 36%).
Reaction SMILES: Cl[C:2]1[N:11]=[C:10]([OH:12])[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([Cl:13])[CH:8]=2)[N:3]=1.[NH2:14][C:15]1[C:20]2[CH2:21][C:22]([CH3:25])([CH3:24])[O:23][C:19]=2[C:18]([C:26]([NH:28][CH:29]2[CH2:34][CH2:33][N:32]([CH2:35][CH2:36][NH2:37])[CH2:31][CH2:30]2)=[O:27])=[CH:17][C:16]=1[Cl:38].[O-2].[Ca+2]>CN(C)C(=O)C>[NH2:14][C:15]1[C:20]2[CH2:21][C:22]([CH3:24])([CH3:25])[O:23][C:19]=2[C:18]([C:26]([NH:28][CH:29]2[CH2:30][CH2:31][N:32]([CH2:35][CH2:36][NH:37][C:2]3[N:11]=[C:10]([OH:12])[C:9]4[C:4](=[CH:5][CH:6]=[C:7]([Cl:13])[CH:8]=4)[N:3]=3)[CH2:33][CH2:34]2)=[O:27])=[CH:17][C:16]=1[Cl:38]
Reactant: CC1(C)Cc2c(N)c(Cl)cc(C(=O)NC3CCN(CCN)CC3)c2O1
Reactant: Oc1nc(Cl)nc2ccc(Cl)cc12
Agent: [Ca+2]
Agent: [O-2]
Solvent: CC(=O)N(C)C
Product: CC1(C)Cc2c(N)c(Cl)cc(C(=O)NC3CCN(CCNc4nc(O)c5cc(Cl)ccc5n4)CC3)c2O1
Temperature: 140 °C
Reaction time: 3 h
Yield: 18.2 %

Procedure:
A mixture of 2.6 g of 2,6-dichloro-4-quinazolinol (described in J.Med.Chem., 1968, p.130), 3.7 g of 4-amino-N-[1-(2-aminoethyl)-4-piperidinyl]-5-chloro-2,3-dihydro-2,2-dimethyl-7-benzofurancarboxamide (described in EP-0, 445, 862), 0.8 g of calcium oxide and 5.64 g of N,N-dimethylacetamide was stirred for 3 hours at 140° C. After cooling, the reaction mixture was evaporated and the residue was taken up in a mixture of dichloromethane and methanol. The whole was washed with water. The partly precipitated product was filtered off (first fraction). The organic layer was decanted, dried, filtered and evaporated (second fraction). The combined fractions were purified twice by column chromatography (silica gel; CH2Cl2 /CH3OH(NH3) 95:5; CH2Cl2 /CH3OH 92:8). The eluent of the desired fraction was evaporated and the residue was crystallized from acetonitrile. At 0° C., the product was filtered off and dried in vacuo at 60° C., yielding 1 g (18.3%) of 4-amino-5-chloro-N-[1-[2-[(6-chloro-4-hydroxy-2-quinazolinyl)amino]ethyl]-4-piperidinyl]-2,3-dihydro-2,2-dimethyl-7-benzofurancarboxamide; mp. 206.6° C. (comp. 21).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:12]=[C:11]2[C:6]([CH:7]=[CH:8][CH:9]=[C:10]2[CH2:13][CH2:14][N:15]2C(=O)C3C(=CC=CC=3)C2=O)=[CH:5][CH:4]=1.[BH4-].[Na+].C(O)(=O)C>CC(O)C.O>[CH3:1][O:2][C:3]1[CH:12]=[C:11]2[C:6]([CH:7]=[CH:8][CH:9]=[C:10]2[CH2:13][CH2:14][NH2:15])=[CH:5][CH:4]=1
Reactant: COc1ccc2cccc(CCN3C(=O)c4ccccc4C3=O)c2c1
Agent: [BH4-]
Agent: [Na+]
Solvent: CC(=O)O
Solvent: CC(C)O
Solvent: O
Product: COc1ccc2cccc(CCN)c2c1
Temperature: 25 °C

Procedure:
In a reactor, 1 g of the compound obtained in Step C and 5 eq. of NaBH4 are introduced into a 2-propanol/water 6/1 mixture, and the mixture is stirred at ambient temperature. Acetic acid (0.2 eq.) is then added and the reaction mixture is heated at 80° C. for 8 hours. After evaporating off the solvents and co-evaporation of water with toluene, the crude residue obtained is used directly in the acetylation reaction without further purification.
Reaction SMILES: [CH3:1][N:2]1[CH:6]=[C:5]([NH:7][C:8]2[N:13]=[C:12]([NH:14][C:15]3[CH:16]=[N:17][N:18]([CH3:20])[CH:19]=3)[C:11]([NH2:21])=[CH:10][N:9]=2)[CH:4]=[N:3]1.S(=O)(=O)(O)O.[N:27]([O-])=O.[Na+]>O>[CH3:1][N:2]1[CH:6]=[C:5]([NH:7][C:8]2[N:9]=[CH:10][C:11]3[N:21]=[N:27][N:14]([C:15]4[CH:16]=[N:17][N:18]([CH3:20])[CH:19]=4)[C:12]=3[N:13]=2)[CH:4]=[N:3]1
Reactant: Cn1cc(Nc2ncc(N)c(Nc3cnn(C)c3)n2)cn1
Reactant: O=N[O-]
Agent: O=S(=O)(O)O
Agent: [Na+]
Solvent: O
Product: Cn1cc(Nc2ncc3nnn(-c4cnn(C)c4)c3n2)cn1
Temperature: 25 °C
Reaction time: 1.5 h

Procedure:
A suspension of 80 mg (0.28 mmol) N2,N4-bis-(1-methyl-1H-pyrazol-4-yl)-pyrimidine-2,4,5-triamine in 23 ml water is treated with 4 ml concentrated sulfuric acid and then with 39 mg (0.56 mmol) sodium nitrite. The reaction mixture is stirred for 90 minutes at room temperature. The reaction mixture is partitioned between water and dichloromethane. The organic phase is dried over sodium sulfate and evaporated. The residue is chromatographed on a silica gel column with methanol/dichloromethane as eluent giving “A21” as off-white crystals; HPLC/MS (A) 1.42 min, [M+H] 297;
Reaction SMILES: C[Si](C)(C)[N-][Si](C)(C)C.[Li+].[I-].[CH:12]1([CH2:17][P+](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[CH2:16][CH2:15][CH2:14][CH2:13]1.[Cl:37][C:38]1[CH:39]=[CH:40][C:41]([C:46]([C:48]2[CH:53]=[CH:52][C:51]([S:54][CH3:55])=[CH:50][CH:49]=2)=O)=[N:42][C:43]=1[O:44][CH3:45].O>O1CCCC1>[Cl:37][C:38]1[C:43]([O:44][CH3:45])=[N:42][C:41](/[C:46](/[C:48]2[CH:53]=[CH:52][C:51]([S:54][CH3:55])=[CH:50][CH:49]=2)=[CH:17]/[CH:12]2[CH2:16][CH2:15][CH2:14][CH2:13]2)=[CH:40][CH:39]=1
Reactant: c1ccc([P+](CC2CCCC2)(c2ccccc2)c2ccccc2)cc1
Reactant: COc1nc(C(=O)c2ccc(SC)cc2)ccc1Cl
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [I-]
Agent: [Li+]
Solvent: C1CCOC1
Solvent: O
Product: COc1nc(/C(=C/C2CCCC2)c2ccc(SC)cc2)ccc1Cl
Temperature: 25 °C
Reaction time: 1 h
Yield: 58 %

Procedure:
A solution of lithiumhexamethyldisilazide in tetrahydrofuran (1 M, 5.22 mL) was added to a solution of (cyclopentylmethyl)triphenylphosphonium iodide (described in WO 2001044216) (2.46 g) in tetrahydrofuran (20 mL) in a nitrogen atmosphere under ice-cooling, and the mixture was stirred at room temperature for one hour. The reaction solution was ice-cooled again and a solution of (5-chloro-6-methoxypyridin-2-yl)[4-(methylsulfanyl)phenyl]methanone obtained in Reference Example 1-1 (1.0 g) in tetrahydrofuran (10 mL) was added, after which the mixture was stirred at room temperature for one hour. The reaction solution was poured into water, followed by extraction with ethyl acetate. The organic layer was washed with brine, dried over anhydrous magnesium sulfate and filtered. The solvent was then evaporated under reduced pressure. The residue was purified by silica gel column chromatography (chloroform:hexane=1:1) to give 3-chloro-6-{(E)-2-cyclopentyl-1-[4-(methylsulfanyl)phenyl]ethenyl}-2-methoxypyridine (710 mg, 58%) as a colorless oil.
Reaction SMILES: [C:1]1([CH2:7][CH2:8][C:9]2[N:19]3[C:20]4[C:15]([CH:16]([NH2:21])[CH2:17][CH2:18]3)=[CH:14][CH:13]=[CH:12][C:11]=4[N:10]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH3:22][C:23]([CH3:25])=O.Cl.CO.C([BH3-])#N.[Na+]>CO>[C:1]1([CH2:7][CH2:8][C:9]2[N:19]3[C:20]4[C:15]([CH:16]([NH:21][CH:23]([CH3:25])[CH3:22])[CH2:17][CH2:18]3)=[CH:14][CH:13]=[CH:12][C:11]=4[N:10]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: NC1CCn2c(CCc3ccccc3)nc3cccc1c32
Reactant: CC(C)=O
Agent: Cl
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: CO
Product: CC(C)NC1CCn2c(CCc3ccccc3)nc3cccc1c32
Temperature: 25 °C
Reaction time: 96 h

Procedure:
A portion (1.0 g) of 5,6-dihydro-2-(2-phenylethyl)-4H-imidazo[4,5,1-ij]quinolin-6-amine obtained in step 2 of Example 17 was dissolved in methanol (10 mL) and, following the addition of acetone (0.53 mL) and 10% HCl-methanol solution (0.1 mL), the mixture was stirred at room temperature for 4 days. The reaction solution was cooled with ice and, following the addition of sodium cyanoborohydride (0.23 g), the mixture was stirred at room temperature for 24 hrs. The reaction mixture was concentrated and, to the residue was added water followed by extraction with ethyl acetate; the organic layer was washed with saturated brine and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure and the residue was purified by silica gel column chromatography (eluent: dichloromethane/methanol) to yield the titled compound as pale yellow crystals (0.80 g).
Reaction SMILES: [CH2:1]([N:8]1[C:25]([CH3:26])=[C:11]2[C:12](=[O:24])[NH:13][C:14]3[CH:15]=[C:16]4[CH2:23][CH2:22][CH2:21][CH2:20][C:17]4=[CH:18][C:19]=3[C:10]2=[N:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].Br[CH2:34][CH:35]([F:45])[CH2:36][NH:37][C:38](=[O:44])[O:39][C:40]([CH3:43])([CH3:42])[CH3:41]>CN(C=O)C>[CH2:1]([N:8]1[C:25]([CH3:26])=[C:11]2[C:12](=[O:24])[N:13]([CH2:34][CH:35]([F:45])[CH2:36][NH:37][C:38](=[O:44])[O:39][C:40]([CH3:42])([CH3:41])[CH3:43])[C:14]3[CH:15]=[C:16]4[CH2:23][CH2:22][CH2:21][CH2:20][C:17]4=[CH:18][C:19]=3[C:10]2=[N:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CC(C)(C)OC(=O)NCC(F)CBr
Reactant: Cc1c2c(=O)[nH]c3cc4c(cc3c2nn1Cc1ccccc1)CCCC4
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Product: Cc1c2c(=O)n(CC(F)CNC(=O)OC(C)(C)C)c3cc4c(cc3c2nn1Cc1ccccc1)CCCC4
Temperature: 40 °C
Reaction time: 16 h

Procedure:
To a mixture of 2-benzyl-3-methyl-2,5,7,8,9,10-hexahydro-4H-benzo[g]pyrazolo[4,3-c]quinolin-4-one (1-7) (8.0 g, 23 mmol, 1 equiv) and cesium carbonate (37 g, 110 mmol, 4.9 equiv) in DMF (100 mL) was added tert-butyl 3-bromo-2-fluoropropylcarbamate (1-9) (7.1 g, 27.7 mmol, 1.2 equiv) and the resulting mixture was stirred at 40° C. for 16 h. The reaction mixture was filtered and the filtrate concentrated and purified by silica gel chromatography (100% hexanes to 100% ethyl acetate over 1 h) to yield tert-butyl 3-(2-benzyl-3-methyl-4-oxo-2,4,7,8,9,10-hexahydro-5H-benzo[g]pyrazolo[4,3-c]quinolin-5-yl)-2-fluoropropylcarbamate (1-10) as a white solid. LRMS m/z (M+H) 519.2 found, 519.3 required.
Reaction SMILES: [OH-].[Na+].[F:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]2[O:11][C:12]3[CH:23]=[C:22]([N+:24]([O-:26])=[O:25])[C:21]([O:27][CH:28]([CH3:30])[CH3:29])=[CH:20][C:13]=3[C:14]=2[C:15]([O:17]CC)=[O:16])=[CH:6][CH:5]=1.C1COCC1>O>[F:3][C:4]1[CH:5]=[CH:6][C:7]([C:10]2[O:11][C:12]3[CH:23]=[C:22]([N+:24]([O-:26])=[O:25])[C:21]([O:27][CH:28]([CH3:30])[CH3:29])=[CH:20][C:13]=3[C:14]=2[C:15]([OH:17])=[O:16])=[CH:8][CH:9]=1
Reactant: CCOC(=O)c1c(-c2ccc(F)cc2)oc2cc([N+](=O)[O-])c(OC(C)C)cc12
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: C1CCOC1
Product: CC(C)Oc1cc2c(C(=O)O)c(-c3ccc(F)cc3)oc2cc1[N+](=O)[O-]
Temperature: 50 °C
Reaction time: 0.08 h

Procedure:
An aqueous solution of sodium hydroxide (7.74 mL, 15.48 mmol, 2.0 M) was added to a mixture of ethyl 2-(4-fluorophenyl)-5-isopropoxy-6-nitrobenzofuran-3-carboxylate (1.5 g, 3.87 mmol) in a THF (50 mL)/Water (10 mL) mixture at room temperature. The reaction mixture was heated to 50° C. and maintained at the same temperature overnight. The reaction mixture was then concentrated to remove the solvent. The residue was diluted with water, acidified with 1.5 N HCl, stirred for 5 min and filtered. The solid was dried under suction to obtained title compound as a white solid. Yield: 1.35 g, (97%). 1H NMR (400 MHz, DMSO-d6) δ ppm: 8.35 (s, 1H) 8.02-8.16 (m, 2H) 7.78 (s, 1H) 7.33-7.49 (m, 2H) 4.69-4.85 (m, 1H) 1.27-1.40 (m, 6H).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5](/[CH:8]=[CH:9]/[C:10]2[S:14][C:13]([C:15]([O:17][CH3:18])=[O:16])=[CH:12][C:11]=2[N+:19]([O-])=O)=[CH:4][CH:3]=1>P(OCC)(OCC)OCC>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[NH:19][C:11]3[CH:12]=[C:13]([C:15]([O:17][CH3:18])=[O:16])[S:14][C:10]=3[CH:9]=2)=[CH:4][CH:3]=1
Reactant: COC(=O)c1cc([N+](=O)[O-])c(/C=C/c2ccc(Cl)cc2)s1
Agent: CCOP(OCC)OCC
Product: COC(=O)c1cc2[nH]c(-c3ccc(Cl)cc3)cc2s1
Yield: 16 %

Procedure:
A solution (1 M) of methyl 5-[(E)-2-(4-chlorophenyl)vinyl]4-nitrothiophene-2-carboxylate in triethyl phosphite was heated to reflux for 20 h. After cooling down a part of the solvent was evaporated under high vacuum (2 mbar, water bath 60° C.) then the residue was purified by flash chromatography on silica gel (1:20 acetone/toluene). Fractions containing the title compound along with some phosphorous impurities were concentrated to give a residue that was triturated with AcOEt/petroleum ether (1:9) and filtered to afford the title compound (16%) as a solid.
Reaction SMILES: [OH:1][C:2]1[C:11]2[C:6](=[C:7]([O:12][CH3:13])[CH:8]=[CH:9][CH:10]=2)[CH:5]=[CH:4][CH:3]=1.Br[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.C(=O)([O-])[O-].[K+].[K+]>N1C=CC=CC=1.[Cu-]=O.[Cu]=O>[CH3:13][O:12][C:7]1[C:6]2[C:11](=[C:2]([O:1][C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[CH:3]=[CH:4][CH:5]=2)[CH:10]=[CH:9][CH:8]=1
Reactant: COc1cccc2c(O)cccc12
Reactant: Brc1ccccc1
Agent: O=[Cu-]
Agent: O=[Cu]
Agent: O=C([O-])[O-]
Solvent: c1ccncc1
Product: COc1cccc2c(Oc3ccccc3)cccc12
Reaction time: 16 h
Yield: 11 %

Procedure:
In a 3-neck flask fitted with a mechanical stirrer, 26.1 g of the 1-hydroxy-5-methoxynaphthalene prepared as above was treated with 16 ml bromobenzene, 41.4 g potassium carbonate, and 24.g of copper(I)oxide in 300 ml pyridine at reflux under argone. After 16 hours, an additional 3.2 mL of bromobenzene and 4.8 g of copper oxide were added and the reaction was continued for 4 hours. The reaction was cooled and filtered over supercel with an ethyl acetate washing. The combined filtrate was concentrated under vacuum, diluted with ethyl acetate, and shaken twice with cold dilute hydrochloric acid. The organic layer was dried over magnesium sulfate and evaporated under vacuum to an oil. The crude product was dissolved in 30 ml methylene chloride, and the resulting solution filtered and diluted with hexane to cloudiness. On cooling in the freezer, 3.98 g (11%) of crystalline 1-methoxy-5-phenoxynaphthalene was obtained.
Reaction SMILES: F[C:2]1[C:3]([CH3:22])=[N:4][C:5]2[C:10]([N:11]=1)=[C:9]([C:12]1[NH:20][C:19]3[CH2:18][CH2:17][NH:16][C:15](=[O:21])[C:14]=3[CH:13]=1)[CH:8]=[CH:7][CH:6]=2.Cl.[CH3:24][C:25]1([CH2:28][NH2:29])[CH2:27][CH2:26]1.CCN(C(C)C)C(C)C.C(O)(C(F)(F)F)=O.C([O-])(O)=O.[Na+]>CS(C)=O.CC#N.O>[CH3:22][C:3]1[C:2]([NH:29][CH2:28][C:25]2([CH3:24])[CH2:27][CH2:26]2)=[N:11][C:10]2[C:5](=[CH:6][CH:7]=[CH:8][C:9]=2[C:12]2[NH:20][C:19]3[CH2:18][CH2:17][NH:16][C:15](=[O:21])[C:14]=3[CH:13]=2)[N:4]=1
Reactant: Cc1nc2cccc(-c3cc4c([nH]3)CCNC4=O)c2nc1F
Reactant: CC1(CN)CC1
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O
Solvent: O=C(O)C(F)(F)F
Solvent: CC#N
Product: Cc1nc2cccc(-c3cc4c([nH]3)CCNC4=O)c2nc1NCC1(C)CC1
Yield: 8.8 %

Procedure:
A solution of 2-(3-fluoro-2-methylquinoxalin-5-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (126) (46 mg, 0.16 mmol), (1-methylcyclopropyl)methanamine hydrochloride (37.8 mg, 0.310 mmol) (Princeton Bio, Princeton, N.J.), and DIEA (136 μL, 0.776 mmol) in DMSO (1.5 mL) was heated at 100° C. for 1.5 h. The crude product was diluted in DMSO (˜20 mg/mL) and injected (3×1.0 mL) onto the Shimadzu preparatory LC (Phenomenex Gemini C18, 10 μm, 150×30 mm; 10-100% MeCN/water with 0.1% TFA); the pure fractions were combined, basicified with NaHCO3 (saturated, aq.), extracted with DCM, separated, dried over Na2SO4, and concentrated via rotary evaporation to give 2-(2-methyl-3-(((1-methylcyclopropyl)methyl)amino)quinoxalin-5-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (335) (5 mg, 0.014 mmol, 9% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 0.25-0.29 (m, 2H) 0.57-0.62 (m, 2H) 1.20 (s, 3H) 2.56 (s, 3H) 2.89 (t, J=6.75 Hz, 2H) 3.45 (td, J=6.75, 2.35 Hz, 2H) 3.57 (d, J=5.87 Hz, 2H) 6.97 (br. s., 1H) 7.14 (d, J=1.96 Hz, 1H) 7.19 (t, J=5.87 Hz, 1H) 7.32 (t, J=7.82 Hz, 1H) 7.57 (dd, J=8.02, 1.17 Hz, 1H) 7.87 (dd, J=7.53, 1.08 Hz, 1H) 12.04 (br. s., 1H). MS (ESI, pos. ion) m/z: 362.1 (M+1).
Reaction SMILES: [CH2:1]([O:11][C:12]1[CH:13]=[C:14]2[C:19](=[CH:20][CH:21]=1)[CH:18]=[C:17]([CH2:22][OH:23])[CH:16]=[CH:15]2)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH3:10]>C(Cl)(Cl)Cl.[O-2].[O-2].[Mn+4]>[CH2:1]([O:11][C:12]1[CH:13]=[C:14]2[C:19](=[CH:20][CH:21]=1)[CH:18]=[C:17]([CH:22]=[O:23])[CH:16]=[CH:15]2)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH3:10]
Reactant: CCCCCCCCCCOc1ccc2cc(CO)ccc2c1
Agent: [Mn+4]
Agent: [O-2]
Solvent: ClC(Cl)Cl
Product: CCCCCCCCCCOc1ccc2cc(C=O)ccc2c1
Temperature: 25 °C
Reaction time: 12 h

Procedure:
In 10 ml of chloroform, 84 mg (0.43 mmol) of the thus obtained 6-decyloxy-2-hydroxymethylnaphthalene was dissolved, and 235 mg (2.57 mmol) of activated manganese dioxide powder was added. The oxidation reaction was carried out with vigorous stirring at room temperature for 12 hours.
Reaction SMILES: [CH2:1]([SH:8])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH3:7].[CH2:9]([O:16][C:17]1[C:26]2[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=2)[N:20]=[C:19]([CH2:27]OS(C2C=CC(C)=CC=2)(=O)=O)[C:18]=1[CH3:39])[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1>CO.C[O-].[Na+].CO.C1COCC1>[CH2:9]([O:16][C:17]1[C:26]2[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=2)[N:20]=[C:19]([CH2:27][S:8][CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH3:7])[C:18]=1[CH3:39])[C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1
Reactant: CCCCCCCS
Reactant: Cc1ccc(S(=O)(=O)OCc2nc3ccccc3c(OCc3ccccc3)c2C)cc1
Agent: C[O-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CO
Product: CCCCCCCSCc1nc2ccccc2c(OCc2ccccc2)c1C
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 90.2 %

Procedure:
1-Heptanethiol (250 mg) was dissolved in methanol (5 mL), to which a solution of 28% sodium methoxide in methanol (0.37 mL) was then added, followed by stirring at room temperature for 15 minutes. The reaction mixture was added to a solution of p-toluenesulfonic acid [4-(benzyloxy)-3-methylquinolin-2-yl]methyl ester (464 mg) in methanol-THF (1:1, 10 mL), followed by stirring at room temperature for 30 minutes. The reaction mixture was concentrated under reduced pressure, and water (100 mL) was added to the resulting residue, followed by extraction with ethyl acetate (100 mL). The organic layer was washed with saturated brine, and then dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (eluent: hexane/ethyl acetate=5/1) to obtain 4-(benzyloxy)-2-[(heptylsulfanyl)methyl]-3-methylquinoline (380 mg).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([C:8]2[CH:13]=[CH:12][C:11]([C:14]([F:17])([F:16])[F:15])=[CH:10][CH:9]=2)[N:3]=1.[Li+].CC([N-]C(C)C)C.[CH3:26][S:27]SC>C1COCC1>[F:1][C:2]1[C:7]([S:27][CH3:26])=[CH:6][CH:5]=[C:4]([C:8]2[CH:13]=[CH:12][C:11]([C:14]([F:15])([F:16])[F:17])=[CH:10][CH:9]=2)[N:3]=1
Reactant: CSSC
Reactant: Fc1cccc(-c2ccc(C(F)(F)F)cc2)n1
Agent: CC(C)[N-]C(C)C
Agent: [Li+]
Solvent: C1CCOC1
Product: CSc1ccc(-c2ccc(C(F)(F)F)cc2)nc1F
Temperature: -20 °C
Yield: 41.8 %

Procedure:
To a solution of 2-fluoro-6-(4'-trifluoromethyl-phenyl)pyridine (2.4 g, 10 mmol, prepared according to example 17) in dry THF (35 mL) is added dropwise a solution of 2M LDA in THF (7.5 mL, 15 mmol) at -70° C. After 2 hours at -70° C. dimethyl disulfide (1.41 g, 15 mmol) is added and the reaction mixture is allowed to warm at -20 ° C. The mixture is hydrolysed and extracted with diethylether. After separation the organic layer is dried with anhydrous magnesium sulphate. The solvents are removed and the crude product is purified by flash column chromatography (silica gel). Elution with hexane/ethyl acetate (20/1 v/v) gives the title compound (1.2 g, 42%) with mp 70°-73° C.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6](B(O)O)=[CH:5][CH:4]=1.[OH:12][C:13]1[CH:14]=[C:15]([CH:30]=[CH:31][CH:32]=1)[CH:16]=[C:17]1[CH2:22][CH2:21][N:20]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:19][CH2:18]1.C(N(CC)CC)C>ClCCl.C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([O:12][C:13]2[CH:14]=[C:15]([CH:30]=[CH:31][CH:32]=2)[CH:16]=[C:17]2[CH2:18][CH2:19][N:20]([C:23]([O:25][C:26]([CH3:29])([CH3:27])[CH3:28])=[O:24])[CH2:21][CH2:22]2)=[CH:5][CH:4]=1
Reactant: COc1ccc(B(O)O)cc1
Reactant: CC(C)(C)OC(=O)N1CCC(=Cc2cccc(O)c2)CC1
Agent: [Cu+2]
Agent: CC(=O)[O-]
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: COc1ccc(Oc2cccc(C=C3CCN(C(=O)OC(C)(C)C)CC3)c2)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 32.3 %

Procedure:
To a mixture of 4-methoxyphenylboronic acid (1.57 g, 10.36 mmole) and tert-butyl 4-(3-hydroxybenzylidene)piperidine-1-carboxylate (2.5 g, 8.6 mmole) in dichloromethane (75 mL) were added copper acetate (1.63 g, 8.6 mmole), triethyl amine (5.219 g, 51.6 mmol) and molecular sieves. The mixture was stirred at room temperature overnight. The reaction mixture was filtered through celite pad. The filtrate was evaporated and purified by column chromatography to give the title compound (1.1 g, 32%). 1H NMR (500 MHz, CDCl3): δ ppm 7.26 (t, 1H), 6.99 (d, 2H), 6.89 (t, 3H), 6.79 (t, 2H), 6.29 (s, 1H), 3.80 (s, 3H), 3.48 (s, 2H), 3.38 (s, 2H), 2.42 (s, 2H), 2.29 (s, 2H), 1.47 (s, 9H).
Reaction SMILES: [CH3:1][C:2]([C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)([CH3:6])[C:3]([OH:5])=[O:4].[C:13](=O)([O-])O.[Na+].CI.Cl>CN(C)C=O>[CH3:13][O:4][C:3](=[O:5])[C:2]([CH3:1])([C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)[CH3:6]
Reactant: O=C([O-])O
Reactant: CC(C)(C(=O)O)c1ccccc1
Agent: Cl
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: CI
Product: COC(=O)C(C)(C)c1ccccc1
Temperature: 25 °C
Reaction time: 40 h
Yield: 74.9 %

Procedure:
9.00 g (55 mmol) 2-methyl-2-phenyl-propionic acid was dissolved in 90 ml N,N-dimethylformamide, 11.51 g (2.5 eq.) of sodium hydrogencarbonate was added followed by 6.89 mL (15.72 g 2 eq.) of methyl iodide. The mixture was stirred at rt for 40 hours, then poured into ice water, the pH was adjusted to ˜3.0 with aq. HCl (1N) and the mixture extracted 3 times with ether; the organic phases were washed with water, dried over MgSO4, filtered and evaporated to give 7.34 g of the crude title compound as yellow oil. MS: 178.1 (M+).