Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [H-].[Na+].C(S)C.C[O:7][C:8]1[CH:9]=[CH:10][C:11]2[N:17]=[CH:16][CH:15]=[C:14]([C@@H:18]([OH:29])[C@H:19]3[N:24]4[CH2:25][C@H:26]([CH:27]=[CH2:28])[C@@H:21]([CH2:22][CH2:23]4)[CH2:20]3)[C:12]=2[CH:13]=1.Cl>CCCCCC.CN(C=O)C>[CH2:28]=[CH:27][C@@H:26]1[CH:21]2[CH2:20][C@@H:19]([C@H:18]([OH:29])[C:14]3[CH:15]=[CH:16][N:17]=[C:11]4[C:12]=3[CH:13]=[C:8]([OH:7])[CH:9]=[CH:10]4)[N:24]([CH2:23][CH2:22]2)[CH2:25]1
Reactant: C=C[C@H]1CN2CC[C@H]1C[C@H]2[C@H](O)c1ccnc2ccc(OC)cc12
Agent: Cl
Agent: [H-]
Agent: [Na+]
Solvent: CCS
Solvent: CN(C)C=O
Solvent: CCCCCC
Product: C=C[C@H]1CN2CCC1C[C@H]2[C@H](O)c1ccnc2ccc(O)cc12
Temperature: 100 °C
Reaction time: 13 h
Yield: 93.4 %

Procedure:
NaH (60% in mineral oil, 800 mg, 20.0 mmol, 10.0 equiv) was washed with hexane, dried, and suspended in DMF (20 mL). To this suspension at 0° C. was added ethanethiol (2.96 mL, 40.0 mmol, 20.0 equiv) dropwise over 5 min. The reaction mixture was stirred at 23° C. for 10 min before the addition of quinine (649 mg, 2.00 mmol, 1.00 equiv) in DMF (10 mL) and further stirred for 13 hr at 100° C. The reaction mixture was cooled to 23° C. and neutralized with aqueous 1N HCl. The phases were separated and the aqueous phase was extracted with CH2Cl2 (3×30 mL). The combined organic phases were washed with brine (50 mL) and dried (K2CO3). The filtrate was concentrated in vacuo and the residue was triturated with Et2O to afford 580 mg of the title compound as a colorless solid (93% yield).
Reaction SMILES: O[CH2:2][CH2:3][CH2:4][CH2:5][N:6]1[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[C:8]([C:15]2[C:16](=[O:32])[NH:17][C:18](=[O:31])[C:19]=2[C:20]2[C:28]3[O:27][CH:26]=[CH:25][C:24]=3[C:23]([O:29][CH3:30])=[CH:22][CH:21]=2)=[CH:7]1.C(Br)(Br)(Br)[Br:34].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>ClCCl>[Br:34][CH2:2][CH2:3][CH2:4][CH2:5][N:6]1[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[C:8]([C:15]2[C:16](=[O:32])[NH:17][C:18](=[O:31])[C:19]=2[C:20]2[C:28]3[O:27][CH:26]=[CH:25][C:24]=3[C:23]([O:29][CH3:30])=[CH:22][CH:21]=2)=[CH:7]1
Reactant: COc1ccc(C2=C(c3cn(CCCCO)c4ccccc34)C(=O)NC2=O)c2occc12
Reactant: BrC(Br)(Br)Br
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Product: COc1ccc(C2=C(c3cn(CCCCBr)c4ccccc34)C(=O)NC2=O)c2occc12
Reaction time: 0.17 h

Procedure:
Dissolve 3-[1-(4-hydroxybutyl)-1H-indol-3-yl]-4-(4-methoxybenzofur-7-yl)pyrrole-2,5-dione (0.1 g, 0.232 mmol) in 10 mL dichloromethane. Add carbon tetrabromide (0.077 g, 1 equivalent) and triphenyl phosphine (0.061 g, 1 equivalent). Stir for 10 min, add another equivalent of both reagents. Stir 10 min then dilute with dichloromethane and wash with water followed by brine. Dry over magnesium sulfate then filter and concentrate. Purification by column chromatography (2% methanol: dichloromethane) affords the title compound. MS (ES, m/z): 493.0 (M−1).
Reaction SMILES: [CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[OH:11].CCOCC.[C:17](O)(=[O:29])[CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH3:28].CS(O)(=O)=O>>[C:17]([O:11][C:2]1[CH:3]=[CH:4][C:5]2[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=2)[CH:1]=1)(=[O:29])[CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH3:28]
Reactant: CCCCCCCCCCCC(=O)O
Reactant: Oc1ccc2ccccc2c1
Agent: CS(=O)(=O)O
Solvent: CCOCC
Product: CCCCCCCCCCCC(=O)Oc1ccc2ccccc2c1
Temperature: 220 °C

Procedure:
To a four neck round bottom flask fitted with nitrogen inlet, mechanical stirrer, temperature probe and condenser is charged 1197.03 g (2.11 moles) of the Alkoxylate from example 18 and 402.97 g (2.01 moles) of Lauric Acid. A catalytic amount of Methanesulfonic Acid (1.6 g) is charged and the reaction mixture is heated to 220° C. under nitrogen sparge. The reaction is monitored by measuring the acid value to an AV of preferably less than 5. Once the AV is reached, the temperature is cooled to 85° C. and the catalyst is neutralized with an equivalent molar amount of 45% KOH and washed once with water. The reaction is dried under vacuum yielding the desired product.
Reaction SMILES: C(OC([N:8]1[CH2:13][CH2:12][CH:11]([CH3:14])[CH:10]([CH2:15][C:16]#[C:17][C:18]2[N:19]=[C:20]3[CH:26]=[CH:25][N:24]([CH2:27][O:28][CH2:29][CH2:30][Si:31]([CH3:34])([CH3:33])[CH3:32])[C:21]3=[N:22][CH:23]=2)[CH2:9]1)=O)(C)(C)C.C(N(C(C)C)C(C)C)C.[CH2:44]([S:46](Cl)(=[O:48])=[O:47])[CH3:45]>C(Cl)Cl.O1CCOCC1>[CH2:44]([S:46]([N:8]1[CH2:13][CH2:12][CH:11]([CH3:14])[CH:10]([CH2:15][C:16]#[C:17][C:18]2[N:19]=[C:20]3[CH:26]=[CH:25][N:24]([CH2:27][O:28][CH2:29][CH2:30][Si:31]([CH3:34])([CH3:32])[CH3:33])[C:21]3=[N:22][CH:23]=2)[CH2:9]1)(=[O:48])=[O:47])[CH3:45]
Reactant: CC1CCN(C(=O)OC(C)(C)C)CC1CC#Cc1cnc2c(ccn2COCC[Si](C)(C)C)n1
Reactant: CCS(=O)(=O)Cl
Solvent: CCN(C(C)C)C(C)C
Solvent: C1COCCO1
Solvent: ClCCl
Product: CCS(=O)(=O)N1CCC(C)C(CC#Cc2cnc3c(ccn3COCC[Si](C)(C)C)n2)C1
Temperature: 0 °C
Reaction time: 0.75 h
Yield: 79.7 %

Procedure:
To a flask containing a solution of (+/−)-4-methyl-3-{3-[5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-prop-2-ynyl}-piperidine-1-carboxylic acid tert-butyl ester (505 mg, 1.04 mmol) in methylene chloride (4 mL) was added a 25% solution of anhydrous HC1 in dioxane (3 mL). The mixture was lightly capped and stirred for 45 minutes. The solvent was stripped on the rotovap and the remainder was taken up in methylene chloride (15 mL) and stripped. This was repeated one more time to provide a yellow foamy solid. The crude material was taken up in dry methylene chloride and cooled to 0° C. (ice bath) under argon atmosphere. Ethyl diisopropyl amine was added and the material was stirred for 5 minutes. Ethane sulfonyl chloride (0.1 mL, 1.1 mmol) was slowly added via syringe and the material was stirred for 10 minutes. The cooling bath was removed and stirring continued for 1.5 hours. The crude mixture was taken up in water (40 mL) and methylene chloride (40 mL) and shaken in a reparatory funnel. The organic phase was collected and the aqueous phases were back extracted with methylene chloride (2×30 ml), the organics combined, dried (MgSO4), filtered and stripped. The remainder was purified by preparative TLC eluting with 50% ethyl acetate in hexanes. The product band was collected providing 395 mg of (+/−)-2-[3-(1-ethanesulfonyl-4-methyl-piperidin-3-yl)-prop-1-ynyl]-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine as a viscous yellow oil. MS (M+H)+=477.
Reaction SMILES: [NH2:1][CH2:2][CH:3]1[CH2:8][CH2:7][CH:6]([F:9])[CH2:5][N:4]1[C:10]([C:12]1[N:13]=[C:14]([CH3:23])[S:15][C:16]=1[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)=[O:11].[O:24]1[C:28]2=[CH:29][CH:30]=[CH:31][C:32]([C:33](O)=[O:34])=[C:27]2[CH:26]=[CH:25]1>>[F:9][CH:6]1[CH2:5][N:4]([C:10]([C:12]2[N:13]=[C:14]([CH3:23])[S:15][C:16]=2[C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[O:11])[CH:3]([CH2:2][NH:1][C:33]([C:32]2[CH:31]=[CH:30][CH:29]=[C:28]3[O:24][CH:25]=[CH:26][C:27]=23)=[O:34])[CH2:8][CH2:7]1
Reactant: O=C(O)c1cccc2occc12
Reactant: Cc1nc(C(=O)N2CC(F)CCC2CN)c(-c2ccccc2)s1
Product: Cc1nc(C(=O)N2CC(F)CCC2CNC(=O)c2cccc3occc23)c(-c2ccccc2)s1

Procedure:
N-((5-Fluoro-1-(2-methyl-5-phenylthiazole-4-carbonyl)piperidin-2-yl)methyl)benzofuran-4-carboxamide was prepared by following general procedure A using (2-(aminomethyl)-5-fluoropiperidin-1-yl)(2-methyl-5-phenylthiazol-4-yl)methanone and benzofuran-4-carboxylic acid. MS (ESI) 478 (M+H).
Reaction SMILES: C(OC(=O)[N:7]([C:14]1[C:15]2[N:16]([C:20](Br)=[CH:21][N:22]=2)[CH:17]=[CH:18][N:19]=1)[CH2:8][CH2:9][S:10]([CH3:13])(=[O:12])=[O:11])(C)(C)C.CS[C:27]1[N:32]=[C:31]([Sn](CCCC)(CCCC)CCCC)[CH:30]=[CH:29][N:28]=1.[NH2:46][CH:47]1[CH2:52][CH2:51][O:50][CH2:49][CH2:48]1>>[CH3:13][S:10]([CH2:9][CH2:8][NH:7][C:14]1[C:15]2[N:16]([C:20]([C:31]3[CH:30]=[CH:29][N:28]=[C:27]([NH:46][CH:47]4[CH2:52][CH2:51][O:50][CH2:49][CH2:48]4)[N:32]=3)=[CH:21][N:22]=2)[CH:17]=[CH:18][N:19]=1)(=[O:11])=[O:12]
Reactant: CC(C)(C)OC(=O)N(CCS(C)(=O)=O)c1nccn2c(Br)cnc12
Reactant: CCCC[Sn](CCCC)(CCCC)c1ccnc(SC)n1
Reactant: NC1CCOCC1
Product: CS(=O)(=O)CCNc1nccn2c(-c3ccnc(NC4CCOCC4)n3)cnc12

Procedure:
(2-Methanesulfonyl-ethyl)-{3-[2-(tetrahydro-pyran-4-ylamino)-pyrimidin-4-yl]-imidazo[1,2-a]pyrazin-8-yl}-amine was prepared by a process analogous to that described in Example 12 starting from (3-bromo-imidazo[1,2-a]pyrazin-8-yl)-(2-methanesulfonyl-ethyl)-carbamic acid tert-butyl ester (from Example 5 supra), 2-methylsulfanyl-4-tributylstannanyl-pyrimidine, and 4-amino-tetrahydropyran. LC-MS: [M+H]+ 418.2.
Reaction SMILES: [CH2:1]([N:8]1[CH2:13][CH2:12][C:11](=O)[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH:15]1[CH2:20][CH2:19][O:18][CH2:17][CH2:16]1.O>C1(C)C=CC=CC=1>[CH2:1]([N:8]1[CH2:13][CH2:12][C:11]([N:15]2[CH2:20][CH2:19][O:18][CH2:17][CH2:16]2)=[CH:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: C1COCCN1
Reactant: O=C1CCN(Cc2ccccc2)CC1
Solvent: O
Solvent: Cc1ccccc1
Product: C1=C(N2CCOCC2)CCN(Cc2ccccc2)C1
Yield: 100.2 %

Procedure:
A solution of 10.0 g (52.9 mmol) of 1-benzyl-4-piperidone and 4.61 g (52.9 mmol) of morpholine in 100 ml of toluene was subjected to azeotropic dehydration for 5 hours under heating and reflux by using a water separator. After the completion of the reaction, the solvent was distilled off under reduced pressure, whereby 13.7 g of 1-benzyl-4-morpholino-1,2,5,6-tetrahydropyridine were obtained in a quantitative yield. A solution of 1.52 g (34.6 mmol) of acetaldehyde in 20 ml of methylene chloride was cooled to -40° C. under an argon atmosphere, followed by the dropwise addition of 5.3 ml (43 mmol) of a boron trifluoride--ether complex and 7.44 g (28.8 mmol) of 1-benzyl-4-morpholino-1,2,5,6-tetrahydropyridine obtained above. After the completion of the dropwise addition, the temperature was raised gradually and the reaction mixture was allowed to stand overnight at room temperature. After the addition of water to terminate the reaction, the reaction mixture was extracted with methylene chloride. The organic layer was washed with saturated saline, dried over anhydrous sodium sulfate and concentrated by evaporation under reduced pressure. The residue was subjected to chromatography on a silica gel column (eluting solvent: toluene/ethyl acetate=4/1), whereby 4.68 g (yield: 69.7%) of 1-benzyl-3-(1-hydroxyethyl)-4-piperidone were obtained as a yellowish brown oil.
Reaction SMILES: [CH3:1][C:2]1[CH2:9][CH2:8][CH:7]=[C:6]([CH3:10])[CH2:5][CH2:4][CH:3]=1.[ClH:11].C(Cl)[Cl:13]>>[Cl:11][C:2]1([CH3:1])[CH2:9][CH2:8][CH2:7][C:6]([Cl:13])([CH3:10])[CH2:5][CH2:4][CH2:3]1
Reactant: Cl
Reactant: ClCCl
Reactant: CC1=CCCC(C)=CCC1
Product: CC1(Cl)CCCC(C)(Cl)CCC1
Reaction time: 4 h
Yield: 90 %

Procedure:
100 g (0.73 mol) of 1,5-dimethylcycloocta-1,5-diene together with 200 ml of methylene chloride were placed in a 500 ml four-necked flask. While cooling to an internal temperature of 0-5° C., 60 g (1.64 mol) of hydrogen chloride were fed in at atmospheric pressure over a period of 4 hours. Unreacted hydrogen chloride was subsequently removed by stripping with nitrogen. The solvent was then removed completely under reduced pressure. The product was finally purified by distillation (boiling point: 85-88° C. at 2 mbar) to give 137.1 g (90% of theory) of 1,5-dichloro-1,5-dimethylcyclooctane as a colorless liquid. 1H-NMR (CDCl3; 500 MHz): 2.40-2.25 (m); 2.20-1.95 (m); 1.8-1.7 (m); 1.7-1.5 (m). 13C{1H}-NMR (CDCl3; 400 MHz): 74.6 (s, 2C); 42.4 (s, 4C); 34.5 (s, 2C); 21.5 (s, 2C).
Reaction SMILES: [CH3:1][C:2]1[N:3]=[CH:4][S:5][C:6]=1[C:7]1[O:8][C:9]2[C:10](=[C:12]([C:16]([OH:18])=O)[CH:13]=[CH:14][CH:15]=2)[N:11]=1.[ClH:19].C(N=C=NCCCN(C)C)C.ON1C2C=CC=CC=2N=N1.Cl.Cl.[NH2:43][C@H:44]1[CH:49]2[CH2:50][CH2:51][N:46]([CH2:47][CH2:48]2)[CH2:45]1.C(N(CC)CC)C>CN(C=O)C.C(OCC)(=O)C>[ClH:19].[N:46]12[CH2:51][CH2:50][CH:49]([CH2:48][CH2:47]1)[C@H:44]([NH:43][C:16]([C:12]1[CH:13]=[CH:14][CH:15]=[C:9]3[O:8][C:7]([C:6]4[S:5][CH:4]=[N:3][C:2]=4[CH3:1])=[N:11][C:10]=13)=[O:18])[CH2:45]2
Reactant: N[C@@H]1CN2CCC1CC2
Reactant: Cc1ncsc1-c1nc2c(C(=O)O)cccc2o1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Solvent: CCOC(C)=O
Product: Cc1ncsc1-c1nc2c(C(=O)N[C@@H]3CN4CCC3CC4)cccc2o1
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 39 %

Procedure:
A mixture of 2-(4-methylthiazol-5-yl)benzoxazole-4-carboxylic acid (80 mg, 0.31 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (118 mg, 0.62 mmol), 1-hydroxybenzotriazole (84 mg, 0.62 mmol) and (S)-(−)-3-aminoquinuclidine dihydrochloride (73 mg, 0.39 mmol) in DMF (5 mL) was stirred at room temperature for 10 min, then triethylamine (0.18 mL, 4.0 mmol) was added. The resulting reaction mixture was stirred at room temperature overnight. The mixture was diluted with ethyl acetate (50 mL), and then washed with a saturated solution of sodium bicarbonate. The aqueous layer was further extracted with ethyl acetate (2×100 mL). The combined organics were washed with water (2×50 mL) and brine (2×50 mL), dried (Na2SO4), filtered and concentrated. The crude material was purified by column chromatography (silica gel, 90:9:1 dichloromethane/methanol/concentrated ammonium hydroxide) and recrystallization from acetonitrile to afford the desired product (49 mg, 45%) as a yellow solid: 1H NMR (500 MHz, CDCl3) δ 9.28 (d, J=7.3 Hz, 1H), 8.90 (s, 1H), 8.22 (dd, J=7.8, 1.0 Hz, 1H), 7.72 (dd, J=8.1, 1.0 Hz, 1H), 7.49 (t, J=8.0 Hz, 1H), 4.40-4.30 (m, 1H), 3.58-3.53 (m, 1H), 3.10-3.03 (m, 2H), 3.00 (s, 3H), 2.98-2.94 (m, 2H), 2.90-2.78 (m, 1H), 2.20-2.15 (m, 1H), 2.10-2.00 (m, 1H), 1.85-1.76 (m, 2H), 1.66-1.63 (m, 1H); MS (ESI+) m/z 369 (M+H).
Reaction SMILES: C(O[C:5](=[O:7])[CH3:6])(=O)C.Cl.[N+:9]([C:12]1[CH:13]=[C:14]([CH:17]=[CH:18][CH:19]=1)[CH2:15]N)([O-:11])=[O:10].C([N:22](CC)CC)C.Cl>C(Cl)Cl>[N+:9]([C:12]1[CH:13]=[C:14]([CH2:15][CH2:6][C:5]([NH2:22])=[O:7])[CH:17]=[CH:18][CH:19]=1)([O-:11])=[O:10]
Reactant: CC(=O)OC(C)=O
Reactant: CCN(CC)CC
Reactant: NCc1cccc([N+](=O)[O-])c1
Agent: Cl
Solvent: ClCCl
Product: NC(=O)CCc1cccc([N+](=O)[O-])c1
Temperature: 25 °C
Reaction time: 2 h
Yield: 71 %

Procedure:
Acetic anhydride (0.08 ml) was added dropwise to a solution of 3-nitrobenzylamine hydrochloride (139 mg) and triethylamine (0.22 ml) in methylene chloride (10 ml) and stirred at room temperature for 2 h. To the reaction mixture, 2 N HCl was added and extraction was performed with methylene chloride; then, the organic layer was washed successively with water and a saturated aqueous sodium chloride solution, dried with anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (eluent: ethyl acetate) to give 102 mg of the titled compound (yield, 71%).
Reaction SMILES: [NH2:1][C:2]1[CH:18]=[CH:17][CH:16]=[C:15]([CH3:19])[C:3]=1[C:4]([NH:6][CH:7]1[CH2:12][CH2:11][C:10](=[O:13])[NH:9][C:8]1=[O:14])=[O:5].C1N=CN([C:25](N2C=NC=C2)=[O:26])C=1>CN(C1C=CN=CC=1)C.C(#N)C>[OH:26][C:25]1[N:6]([CH:7]2[CH2:12][CH2:11][C:10](=[O:13])[NH:9][C:8]2=[O:14])[C:4](=[O:5])[C:3]2[C:2](=[CH:18][CH:17]=[CH:16][C:15]=2[CH3:19])[N:1]=1
Reactant: O=C(n1ccnc1)n1ccnc1
Reactant: Cc1cccc(N)c1C(=O)NC1CCC(=O)NC1=O
Agent: CN(C)c1ccncc1
Solvent: CC#N
Product: Cc1cccc2nc(O)n(C3CCC(=O)NC3=O)c(=O)c12
Yield: 81.5 %

Procedure:
A solution of 2-amino-N-(2,6-dioxo-piperidin-3-yl)-6-methyl-benzamide (1.00 g, 3.8 mmol), CDI (0.62 g, 3.8 mmol) and DMAP (0.10 g, 0.82 mmol) in acetonitrile (12 mL) was heated at 150° C. in a microwave oven for 10 minutes. The suspension was filtered and washed with acetonitrile (2×20 mL), water (2×20 mL), HCl (1N, 25 mL), water (25 mL), methanol (2×20 mL), and ethyl acetate (2×20 mL) to give 3-(2-hydroxy-5-methyl-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione as an off-white solid (0.89 g, 81% yield): HPLC: Waters Symmetry C18, 5 μm, 3.9×150 mm, 1 mL/min, 240 nm, 25/75 CH3CN/0.1% H3PO4, 5.72 min (99%); mp: 373-375° C.; 1H NMR (DMSO-d6) δ 1.90-1.97 (m, 1H, CHH), 2.49-2.58 (m, 2H, CH2), 2.61 (s, 1.5H, CH3), 2.69 (s, 1.5H, CH3), 2.81-2.92 (m, 1H, CHH), 5.55 (dd, J=5, 11 Hz, 0.5H, NCH), 5.72 (dd, J=5, 11 Hz, 0.5H, NCH), 6.99-7.08 (m, 2H, Ar), 7.50-7.55 (m, 1H, Ar), 10.92 (s, 0.5H, Oh), 11.42 (s, 0.5H, NH), 11.56 (s, 0.5H, NH) (observed at 350K); 13C NMR (DMSO-d6) δ 20.90, 21.38, 22.11, 22.41, 30.72, 30.77, 49.74, 50.99, 111.52, 112.15, 113.38, 125.67, 134.26, 134.34, 140.29, 140.63, 141.09, 141.45, 148.77, 149.99, 161.60, 162.39, 170.00, 170.38, 172.74; LCMS: MH=288; Anal. Calcd. for C14H13N3O4: C, 58.53; H, 4.56; N, 14.63. Found: C, 58.40; H, 4.32; N, 14.59.
Reaction SMILES: Br[CH2:2][CH2:3][O:4][C:5]1[CH:10]=[CH:9][C:8]([N+:11]([O-:13])=[O:12])=[CH:7][C:6]=1[O:14][CH3:15].[CH3:16][CH:17]1[CH2:22][CH2:21][CH2:20][CH:19]([CH3:23])[NH:18]1>ClCCl.CO>[CH3:15][O:14][C:6]1[CH:7]=[C:8]([N+:11]([O-:13])=[O:12])[CH:9]=[CH:10][C:5]=1[O:4][CH2:3][CH2:2][N:18]1[CH:19]([CH3:23])[CH2:20][CH2:21][CH2:22][CH:17]1[CH3:16]
Reactant: COc1cc([N+](=O)[O-])ccc1OCCBr
Reactant: CC1CCCC(C)N1
Solvent: CO
Solvent: ClCCl
Product: COc1cc([N+](=O)[O-])ccc1OCCN1C(C)CCCC1C

Procedure:
Prepared analogously to Example 1.1.c. from 1 g (3.622 mmol) of 1-(2-bromoethoxy)-2-methoxy-4-nitrobenzene and 1.5 mL (10.87 mmol) of 2,6-dimethylpiperidine. Yield: 0.85 g (76% of theory); C16H24N2O4 (M=308.37); calc.: molecular ion peak (M+H)+: 309; found: molecular ion peak (M+H)+: 309; Rf value: 0.55 (silica gel, dichloromethane/methanol (9:1)).
Reaction SMILES: FC(F)(F)S(O[C:7]1[CH:16]=[CH:15][C:14]2[C:9](=[CH:10][C:11](OS(C(F)(F)F)(=O)=O)=[CH:12][CH:13]=2)[CH:8]=1)(=O)=O.C1C=CC(P([C:40]2[CH:45]=CC=CC=2)C2C=CC=CC=2)=CC=1.[C:46]([Si:48]([CH3:51])([CH3:50])[CH3:49])#[CH:47]>N1CCCCC1.[Cu]I.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>[CH3:49][Si:48]([C:46]#[C:47][C:7]1[CH:16]=[CH:15][C:14]2[C:9](=[CH:10][C:11]([C:40]#[C:45][Si:48]([CH3:50])([CH3:49])[CH3:46])=[CH:12][CH:13]=2)[CH:8]=1)([CH3:51])[CH3:50]
Reactant: C#C[Si](C)(C)C
Reactant: O=S(=O)(Oc1ccc2ccc(OS(=O)(=O)C(F)(F)F)cc2c1)C(F)(F)F
Reactant: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Agent: [Cu]I
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCNCC1
Product: C[Si](C)(C)C#Cc1ccc2ccc(C#C[Si](C)(C)C)cc2c1

Procedure:
A mixture of naphthalene-2,7-diyl bis(trifluoromethanesulfonate) 1 (1.00 g, 1.19 mmol), CuI (0.023 g, 0.12 mmol), Pd(PPh3)4 (0.14 g, 0.12 mmol) and PPh3 (0.062 g, 0.24 mmol) was dissolved in piperidine (30 ml) in the presence of molecular sieves and under an Ar2 atmosphere. Ethynyltrimethylsilane (0.69 g, 7.06 mmol) was added and the stirred mixture heated at reflux overnight. The solvent was evaporated in vacuo and the resulting brown oil purified by flash column chromatography (5% EtOAc in hexane). 2,7-bis((trimethylsilyl)ethynyl)naphthalene 2 was obtained as a colourless solid (0.69 g, 90%); Rf 0.37 [3% EtOAc in hexane]; mp: 127-129° C. (Lit. 62.5° C., Crisp et al., 1997); δH (CDCl3, 400 MHz) 7.91 (2H, s, 2×ArH), 7.71 (2H, d, J=8.4 Hz, 2×ArH), 7.50 (2H, m, 2×ArH), 0.28 (18H, m, 6×CH3Si); δC (CDCl3, 100 MHz) 132.34 (Ar—C), 132.26 (Ar—C), 131.64 (2×Ar—CH), 129.48 (2×Ar—CH), 127.70 (2×Ar—CH), 121.17 (2×Ar—C), 105.01 (2×C≡C), 95.17 (2×C≡C), −0.03 (6×CH3Si); HRMS m/z calc. C20H25Si2 [M+H]+321.1495. found [M+H]+321.1499; anal.CHN calcd. C20H25Si2 C, 74.9%; H, 7.5%. found C, 74.6%; H, 7.5%.
Reaction SMILES: [NH2:1][C:2]1[C:3]([C:9]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=O)=[CH:4][C:5]([Cl:8])=[N:6][CH:7]=1.[CH3:17][NH2:18].C1COCC1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C1(C)C=CC(S(O)(=O)=O)=CC=1.ClCCl>[Cl:8][C:5]1[N:6]=[CH:7][C:2]([NH2:1])=[C:3]([CH:9]([NH:18][CH3:17])[C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[CH:4]=1
Reactant: Nc1cnc(Cl)cc1C(=O)c1ccccc1
Reactant: CN
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: Cc1ccc(S(=O)(=O)O)cc1
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CC(=O)O
Solvent: ClCCl
Product: CNC(c1ccccc1)c1cc(Cl)ncc1N

Procedure:
(5-Amino-2-chloro-pyridin-4-yl)-phenyl-methanone (360 mg, 1.547 mmol), methylamine in THF (4.5 mL, 2 M, 9.00 mmol), p-toluene sulfonic acid in acetic acid (225 mg, 12%, 0.157 mmol) are stirred at room temperature in dichloromethane (15 mL). Sodium triacetoxyborohydride (1.92 g, 9.06 mmol) is added in three separate portions over 24 hours. The reaction mixture is quenched with saturated sodium carbonate solution and extracted with ethyl acetate. The organic phase is dried over magnesium sulfate. The drying agent is removed by filtration. The solvent is removed in vacuo and the residue is purified by column chromatography on silica gel using a dichloromethane and methanol gradient. This provides the desired compound as a yellow solid.
Reaction SMILES: [N:1]([C:4]1[CH:12]=[CH:11][C:7]([C:8](Cl)=[O:9])=[CH:6][CH:5]=1)=[N+:2]=[N-:3].[CH3:13][O:14][C:15](=[O:29])[CH2:16][C:17]1[C:25]2[C:20](=[CH:21][CH:22]=[C:23]([O:26][CH3:27])[CH:24]=2)[NH:19][C:18]=1[CH3:28]>>[CH3:13][O:14][C:15](=[O:29])[CH2:16][C:17]1[C:25]2[C:20](=[CH:21][CH:22]=[C:23]([O:26][CH3:27])[CH:24]=2)[N:19]([C:8](=[O:9])[C:7]2[CH:11]=[CH:12][C:4]([N:1]=[N+:2]=[N-:3])=[CH:5][CH:6]=2)[C:18]=1[CH3:28]
Reactant: COC(=O)Cc1c(C)[nH]c2ccc(OC)cc12
Reactant: [N-]=[N+]=Nc1ccc(C(=O)Cl)cc1
Product: COC(=O)Cc1c(C)n(C(=O)c2ccc(N=[N+]=[N-])cc2)c2ccc(OC)cc12

Procedure:
The title compound is prepared by condensing 18.16 g (0.1 mole) of p-azidobenzoyl chloride with 0.1 mole of methyl-5-methoxy-2-methyl-3-indolylacetate following the procedure described in Example 2.
Reaction SMILES: [CH3:1][S:2]([C:5]1[S:6][C:7]([C:10](=O)[CH2:11][CH3:12])=[CH:8][N:9]=1)(=[O:4])=[O:3].[CH3:14][C:15]([S@:18]([NH2:20])=[O:19])([CH3:17])[CH3:16]>C1COCC1.C(OCC)C.O.CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-]>[CH3:1][S:2]([C:5]1[S:6][C:7](/[C:10](=[N:20]\[S:18]([C:15]([CH3:17])([CH3:16])[CH3:14])=[O:19])/[CH2:11][CH3:12])=[CH:8][N:9]=1)(=[O:4])=[O:3]
Reactant: CC(C)(C)[S@](N)=O
Reactant: CCC(=O)c1cnc(S(C)(=O)=O)s1
Agent: [Ti+4]
Agent: CC(C)[O-]
Solvent: O
Solvent: CCOCC
Solvent: C1CCOC1
Product: CC/C(=N/S(=O)C(C)(C)C)c1cnc(S(C)(=O)=O)s1
Temperature: 25 °C
Reaction time: 0.17 h

Procedure:
A mixture of 1-(2-methanesulfonyl-thiazol-5-yl)-propan-1-one (110 mg, 0.50 mmol), (R)-2-methyl-2-propanesulfinamide (70 mg, 0.6 mmol) and titanium (IV) isopropoxide (0.29 mL, 1.0 mmol) in THF (10 mL) was warmed at reflux for 18 hours. The mixture was cooled to room temperature and diluted with diethyl ether (100 mL) and water (6 mL). After 10 minutes with stifling, the solution was dried over sodium sulfate, filtered and concentrated. The crude product was purified by silica gel chromatography eluting with a gradient of 0-100% EtOAc in hexanes to afford 2-methyl-propane-2-sulfinic acid [1-(2-methanesulfonyl-thiazol-5-yl)-prop-(Z)-ylidene]-amide.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][CH:7]=1.[Cl:8][C:9]1[C:14]([O:15][CH3:16])=[CH:13][C:12]([O:17][CH3:18])=[C:11]([Cl:19])[C:10]=1[C:20]1[C:29]2[N:28]=[CH:27][C:26]([CH2:30][N:31]3[CH2:36][CH2:35][N:34]([CH2:37][CH3:38])[CH2:33][CH2:32]3)=[N:25][C:24]=2[C:23]([C:39](O)=[O:40])=[CH:22][CH:21]=1>C(Cl)Cl.CO>[N:4]1[CH:5]=[CH:6][CH:7]=[C:2]([NH:1][C:39]([C:23]2[C:24]3[N:25]=[C:26]([CH2:30][N:31]4[CH2:36][CH2:35][N:34]([CH2:37][CH3:38])[CH2:33][CH2:32]4)[CH:27]=[N:28][C:29]=3[C:20]([C:10]3[C:9]([Cl:8])=[C:14]([O:15][CH3:16])[CH:13]=[C:12]([O:17][CH3:18])[C:11]=3[Cl:19])=[CH:21][CH:22]=2)=[O:40])[CH:3]=1
Reactant: CCN1CCN(Cc2cnc3c(-c4c(Cl)c(OC)cc(OC)c4Cl)ccc(C(=O)O)c3n2)CC1
Reactant: Nc1cccnc1
Solvent: CO
Solvent: ClCCl
Product: CCN1CCN(Cc2cnc3c(-c4c(Cl)c(OC)cc(OC)c4Cl)ccc(C(=O)Nc4cccnc4)c3n2)CC1
Temperature: 25 °C
Reaction time: 12 h

Procedure:
The title compound was prepared in analogy to the procedure described in Step 14.1 but using 3-aminopyridine, 8-(2,6-dichloro-3,5-dimethoxy-phenyl)-3-(4-ethyl-piperazin-1-ylmethyl)-quinoxaline-5-carboxylic acid (Step 82.1) and stirring the reaction mixture for 12 h at rt. Title compound: ESI-MS: 581.0/583.2 [M+H]+; tR=3.24 min (System 1); TLC: Rf=0.38 (DCM/MeOH, 9:1).