Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C([N-]C(C)C)(C)C.[Li+].[Br:9][C:10]1[CH:11]=[C:12]([CH2:15][O:16][CH3:17])[S:13][CH:14]=1.[C:18]([O:22][C:23]([N:25]1[CH2:30][CH2:29][CH:28]([C:31](=[O:36])N(OC)C)[CH2:27][CH2:26]1)=[O:24])([CH3:21])([CH3:20])[CH3:19]>O1CCCC1>[C:18]([O:22][C:23]([N:25]1[CH2:30][CH2:29][CH:28]([C:31]([C:14]2[S:13][C:12]([CH2:15][O:16][CH3:17])=[CH:11][C:10]=2[Br:9])=[O:36])[CH2:27][CH2:26]1)=[O:24])([CH3:21])([CH3:20])[CH3:19]
Reactant: CON(C)C(=O)C1CCN(C(=O)OC(C)(C)C)CC1
Reactant: COCc1cc(Br)cs1
Agent: CC(C)[N-]C(C)C
Agent: [Li+]
Solvent: C1CCOC1
Product: COCc1cc(Br)c(C(=O)C2CCN(C(=O)OC(C)(C)C)CC2)s1
Temperature: -78 °C
Reaction time: 1 h
Yield: 90.2 %

Procedure:
Add lithium diisopropyl amide (13.20 mL, 26.37 mmol, 1.05 equivalents) to a stirred, cold (−78° C.) solution of 4-bromo-2-methoxymethyl-thiophene (5.20 g, 25.11 mmol, 1.00 equivalents) in tetrahydrofuran (dry, 24.30 mL). Stir at −78° C. for 1 hour and add a solution of 4-(methoxy-methyl-carbamoyl)-piperidine-1-carboxylic acid tert-butyl ester (6.84 g, 25.11 mmol, 1.00 equivalents) in tetrahydrofuran (dry, 16.40 mL), dropwise. Stir the resulting solution at −78° C. for 3 hours. Quench the reaction mixture with saturated sodium chloride (aqueous, 50 mL). Allow the resulting mixture to warm to room temperature and extract with a mixture of ethyl acetate: diethyl ether (1:1, 3×35 mL). Combine the extracts, dry over magnesium sulfate, filter and evaporate. Purify the residue via flash column chromatography eluting with a mixture of n-heptane:ethyl acetate (4:1) to yield the desired product as a yellow oil (9.47 g). LC/MS (ESI), m/e 362 (M-56) and 418 (MH+), retention time 2.08 minutes. Condition II.
Reaction SMILES: [OH:1][CH2:2][CH2:3][N:4]([CH2:23][CH2:24][OH:25])[C:5]1[CH:10]=[CH:9][C:8]([C:11]2[NH:12][C:13]3[CH:19]=[C:18]([C:20]([OH:22])=O)[CH:17]=[CH:16][C:14]=3[N:15]=2)=[CH:7][CH:6]=1.[C:26]1([NH2:33])[CH:31]=[CH:30][C:29]([NH2:32])=[CH:28][CH:27]=1>>[C:26]1([NH:33][C:20]([C:18]2[CH:17]=[CH:16][C:14]3[NH:15][C:11]([C:8]4[CH:7]=[CH:6][C:5]([N:4]([CH2:3][CH2:2][OH:1])[CH2:23][CH2:24][OH:25])=[CH:10][CH:9]=4)=[N:12][C:13]=3[CH:19]=2)=[O:22])[CH:31]=[CH:30][C:29]([NH:32][C:20]([C:18]2[CH:17]=[CH:16][C:14]3[NH:15][C:11]([C:8]4[CH:7]=[CH:6][C:5]([N:4]([CH2:3][CH2:2][OH:1])[CH2:23][CH2:24][OH:25])=[CH:10][CH:9]=4)=[N:12][C:13]=3[CH:19]=2)=[O:22])=[CH:28][CH:27]=1
Reactant: Nc1ccc(N)cc1
Reactant: O=C(O)c1ccc2nc(-c3ccc(N(CCO)CCO)cc3)[nH]c2c1
Product: O=C(Nc1ccc(NC(=O)c2ccc3[nH]c(-c4ccc(N(CCO)CCO)cc4)nc3c2)cc1)c1ccc2[nH]c(-c3ccc(N(CCO)CCO)cc3)nc2c1

Procedure:
Compound 282 was prepared according to the procedure similar to that described in Scheme V from 2-(4-di(2-hydroxyethyl)aminophenyl)benzimidazole-5-carboxylic acid and 1,4-phenylenediamine. [M+H]+ calcd for C42H42N8O6: 755.32; found: 755.16.
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([C:24]#[C:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[CH:8][C:9]=1[NH:10][C:11]1[CH:16]=[CH:15][C:14]([O:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][N:19]=2)=[CH:13][CH:12]=1)=[O:4].C[Si]([N-][Si](C)(C)C)(C)C.[K+].[CH3:40][C@H:41]1[CH2:46][CH2:45][C@H:44]([C:47](Cl)=[O:48])[CH2:43][CH2:42]1>C1COCC1>[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([C:24]#[C:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[CH:8][C:9]=1[N:10]([C:47]([CH:44]1[CH2:45][CH2:46][CH:41]([CH3:40])[CH2:42][CH2:43]1)=[O:48])[C:11]1[CH:12]=[CH:13][C:14]([O:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][N:19]=2)=[CH:15][CH:16]=1)=[O:4]
Reactant: C[C@H]1CC[C@H](C(=O)Cl)CC1
Reactant: COC(=O)c1sc(C#CC(C)(C)C)cc1Nc1ccc(Oc2ccccn2)cc1
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [K+]
Solvent: C1CCOC1
Product: COC(=O)c1sc(C#CC(C)(C)C)cc1N(C(=O)C1CCC(C)CC1)c1ccc(Oc2ccccn2)cc1
Temperature: 25 °C
Yield: 60 %

Procedure:
To a cooled (0° C.) THF (5 mL) solution of 5-(3,3-Dimethyl-but-1-ynyl)-3-[4-(pyridin-2-yloxy)-phenylamino]-thiophene-2-carboxylic acid methyl ester (0.225 g, 0.55 mmol) was first added KHMDS (0.66 mmol, 0.5 M in toluene), followed by neat trans-4-methyl-cyclohexanecarbonyl chloride (0.132 g, 0.825 mmol). The reaction was warmed slowly to room temperature and quenched with saturated ammonium chloride solution. The reaction mixture was diluted with EtOAc, washed with water, brine, dried over sodium sulfate, filtrated and concentrated. The crude material was purified by silica gel column chromatography to give 5-(3,3-dimethyl-but-1-ynyl)-3-{(4-methyl-cyclohexanecarbonyl)-[4-(pyridin-2-yloxy)-phenyl]-amino}-thiophene-2-carboxylic acid methyl ester in 60% yield.
Reaction SMILES: [CH3:1][C:2]([C:4]1[C:9]([F:10])=[CH:8][CH:7]=[CH:6][C:5]=1[F:11])=[O:3].C[Si]([N-][Si](C)(C)C)(C)C.[Li+].Br[CH2:23][C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25]>C1COCC1.CN1C(=O)N(C)CCC1.CCOC(C)=O>[F:11][C:5]1[CH:6]=[CH:7][CH:8]=[C:9]([F:10])[C:4]=1[C:2](=[O:3])[CH2:1][CH2:23][C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25]
Reactant: CC(C)(C)OC(=O)CBr
Reactant: CC(=O)c1c(F)cccc1F
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Li+]
Solvent: CN1CCCN(C)C1=O
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: CC(C)(C)OC(=O)CCC(=O)c1c(F)cccc1F
Temperature: -60 °C
Reaction time: 0.17 h

Procedure:
To a stirred solution of 2,6-Difluoroacetophenone (5 g, 32 mmol) in dry THF (40 ml) and DMPU (8 ml) was added a solution of lithium bis(trimethylsilyl)amide (1.0M, 45 ml) at −60° C. under argon. After stirring for 10 minutes at −60° C., tert-Butyl bromoacetate (6.99 g, 35.8 mmol) was added rapidly. The reaction mixture was stirred for an additional 10 minutes and then warmed to room temperature for 4 hours. The crude mixture was taken in EtOAc and washed with water and brine. The aqueous layer Was extracted one more time with EtOAc. The combined organic layers were dried over Na2SO4, filtered, concentrated and purified by flash chromatography on a silica gel column. (hex:ethyl acetate, 2:1) to provide the title compound.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(=O)(O)[O-].[Na+].[C:13]1([S:19](Cl)(=[O:21])=[O:20])[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1>O>[C:2]1([NH:1][S:19]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)(=[O:21])=[O:20])[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: Nc1ccccc1
Reactant: O=S(=O)(Cl)c1ccccc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O
Product: O=S(=O)(Nc1ccccc1)c1ccccc1
Yield: 68 %

Procedure:
The title compound was synthesized by triturating aniline (0.5 g, 5.36 mmol), powdered sodium bicarbonate (0.9 g, 1.07 mmol) and benzene sulfonyl chloride (0.95 g, 5.36 mmol) for 10 min at rt. Then reaction mixture was stirred with water at 60° C. for 30 minutes, filtered, washed with water and dried to gave 17 (0.85 g, 68%). Product was purified by FCC by using eluent as in 15 to give 17 as white flakes (0.79 g), mp: 107-109° C. (lit33A 110° C.); IR (CHCl3) 3256, 1599, 1331, 1162, cm−1; 1H NMR (500 MHz, DMSOD6) δ 6.4 (br, 1H, NH), and 7.04-7.77 (m, 10H, aromatic). HRMS calcd 256.04027 (C12H11NO2S.Na+), found 256.04016.
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[C:7](=O)[NH:8][C:9]([C:20]2[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][CH:21]=2)=[C:10]([N+:17]([O-:19])=[O:18])[C:11]=1[C:12]([O:14][CH2:15][CH3:16])=[O:13])=[O:5])[CH3:2].P(Cl)(Cl)([Cl:31])=O.C(=O)([O-])O.[Na+]>CN(C=O)C>[Cl:31][C:7]1[C:6]([C:4]([O:3][CH2:1][CH3:2])=[O:5])=[C:11]([C:12]([O:14][CH2:15][CH3:16])=[O:13])[C:10]([N+:17]([O-:19])=[O:18])=[C:9]([C:20]2[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][CH:21]=2)[N:8]=1
Reactant: CCOC(=O)c1c([N+](=O)[O-])c(-c2ccc(OC)cc2)[nH]c(=O)c1C(=O)OCC
Reactant: O=P(Cl)(Cl)Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CN(C)C=O
Product: CCOC(=O)c1c(Cl)nc(-c2ccc(OC)cc2)c([N+](=O)[O-])c1C(=O)OCC
Temperature: 100 °C

Procedure:
To 300 mg of 3,4-diethoxycarbonyl-6-(4-methoxyphenyl)-5-nitro-2(1H)pyridone were added 0.5 ml of phosphorus oxychloride and two drops of DMF. The mixture was heated at 100° C. for 1 hour. After ice water was added, the mixture was neutralized with sodium hydrogencarbonate, followed by extraction with ethyl acetate. The organic layer was washed with water and a saturated aqueous solution of sodium chloride and dried. The solvent was distilled off. The residue was purified by silica gel column chromatography (eluent:ethyl acetate/hexane 1:1).
Reaction SMILES: [CH3:1][O:2][C:3]1[C:16]2[C:15](=[O:17])[C:14]3[C:9](=CC=[CH:12][C:13]=3OC)[C:8](=[O:20])[C:7]=2[CH:6]=[C:5]([C:21]([OH:23])=O)[CH:4]=1.CN1[CH2:30][CH2:29][O:28][CH2:27]C1.C(OC(Cl)=O)C(C)C.Br.[CH3:40][NH:41][O:42][CH2:43][C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1>O1CCCC1>[CH2:43]([O:42][N:41]([CH3:40])[C:21]([C:5]1[CH:4]=[C:3]([O:2][CH3:1])[C:16]2[C:15](=[O:17])[C:30]3[C:9](=[CH:14][CH:13]=[CH:12][C:29]=3[O:28][CH3:27])[C:8](=[O:20])[C:7]=2[CH:6]=1)=[O:23])[C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1
Reactant: CN1CCOCC1
Reactant: CNOCc1ccccc1
Reactant: COc1cccc2c1C(=O)c1c(OC)cc(C(=O)O)cc1C2=O
Agent: Br
Agent: CC(C)COC(=O)Cl
Solvent: C1CCOC1
Product: COc1cccc2c1C(=O)c1c(OC)cc(C(=O)N(C)OCc3ccccc3)cc1C2=O
Temperature: -15 °C
Reaction time: 1 h

Procedure:
To a stirred solution of 9,10-dihydro-4,5-dimethoxy-9,10-dioxoanthracene-2-carboxylic acid (2.00 g) in tetrahydrofuran (900 ml) at room temperature under nitrogen was added N-methyl morpholine (1.36 g) dropwise. The solution was then cooled to -15° C. and a solution of isobutylchloroformate (0.92 g) in tetrahydrofuran (5 ml) added during 5 minutes. The clear solution became cloudy. The mixture was stirred at -15° C. for 1 hour. To this was added portionwise over 5 minutes N-methyl O-benzylhydroxylamine hydrobromide (1.50 g). The cloudy mixture was stirred at -15° C. for 3 hours and then allowed to warm to room temperature. After 16 hours at room temperature, the mixture was filtered and the filtrate concentrated in vacuo. The resulting yellow solid was taken up in ethyl acetate (800 ml) and filtered to remove insolubles. The solution was washed with 10% aqueous sodium carbonate solution (three times), water (twice), dried (MgSO4), filtered and evaporated to yield the title compound as a bright yellow powder, m.p. 170°-171° C.
Reaction SMILES: Br[CH2:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[O:9]=[C:10]1[CH2:17][CH:16]2[CH:12]([CH2:13][CH:14]([C:18]([OH:20])=[O:19])[CH2:15]2)[CH2:11]1.CCN(C(C)C)C(C)C>C(#N)C.C(Cl)(Cl)Cl>[O:9]=[C:10]1[CH2:17][CH:16]2[CH:12]([CH2:13][CH:14]([C:18]([O:20][CH2:2][C:3]3[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=3)=[O:19])[CH2:15]2)[CH2:11]1
Reactant: O=C1CC2CC(C(=O)O)CC2C1
Reactant: BrCc1ccccc1
Solvent: CCN(C(C)C)C(C)C
Solvent: CC#N
Solvent: ClC(Cl)Cl
Product: O=C1CC2CC(C(=O)OCc3ccccc3)CC2C1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
Neat (bromomethyl)benzene (531 mg) was added to a stirred mixture of 5-oxooctahydropentalene-2-carboxylic acid (435 mg) and DIPEA (0.542 mL) in acetonitrile (2.5 mL) and CHCl3 (2.5 mL) and the mixture was stirred at rt overnight. Reaction mixture was evaporated to dryness and purified by silica gel FCC (0-1% MeOH in DCM) to afford benzyl 5-oxooctahydropentalene-2-carboxylate which was isolated as an endo/exo isomeric mixture.
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][CH:4]([OH:7])[CH2:3][CH2:2]1.[C:8]([O:12][C:13](=O)[O:14]C(C)(C)C)([CH3:11])([CH3:10])[CH3:9]>O1CCCC1>[C:8]([O:12][C:13]([N:1]1[CH2:6][CH2:5][CH:4]([OH:7])[CH2:3][CH2:2]1)=[O:14])([CH3:11])([CH3:10])[CH3:9]
Reactant: OC1CCNCC1
Reactant: CC(C)(C)OC(=O)OC(C)(C)C
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)N1CCC(O)CC1
Temperature: 25 °C
Reaction time: 8 h
Yield: 90.5 %

Procedure:
To a solution of 25 g (247 mmol) 4-piperidinol in 350 mL dry tetrahydrofuran (THF) at 0° C. was added dropwise 60.2 g (276 mmol) di-t-butylcarbonate in 350 mL dry THF. The reaction was allowed to warm to room temperature (rt) and stirred overnight. The solvent was removed under reduced pressure, the resulting residue dissolved in 700 mL CH2Cl2 and the solution extracted with H2O (1×400 mL), dried over MgSO4, filtered and rotary evaporated to yield 45 g (91%) of N-(t-butoxycarbonyl)-4-piperidinol as an oil which slowly solidified to white crystals. 1H NMR (CDCl3) δ 3.75-3.96 (m, 3H); 2.92-3.13 (m, 2H); 1.80-1.93 (m, 4H); and 1.48 (s, 9H).
Reaction SMILES: [CH2:1]([S:19]([C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)(=[O:21])=[O:20])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8]/[CH:9]=[CH:10]\[CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18].[CH2:28]([Li])[CH2:29][CH2:30][CH3:31].O1CCC[CH2:34]1>>[C:22]1([S:19]([CH:1]([CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8]/[CH:9]=[CH:10]\[CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18])[CH2:31][CH2:30][CH2:29][CH2:28][CH3:34])(=[O:21])=[O:20])[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1
Reactant: CCCCCCCC/C=C\CCCCCCCCS(=O)(=O)c1ccccc1
Reactant: C1CCOC1
Reactant: [Li]CCCC
Product: CCCCCCCC/C=C\CCCCCCCC(CCCCC)S(=O)(=O)c1ccccc1
Temperature: -30 °C
Reaction time: 2 h
Yield: 93 %

Procedure:
1.96 g (5.10- 3 mole) oleylphenylsulfone in solution in 10cm3 tetrahydrofuran are treated by the equivalent of butyl lithium at -78° C. The temperature is then allowed to rise progressively to 20° C. During this rise in temperature, the lithiated sulfone crystallises in the medium in the form of white crystals. The reaction mixture is once more cooled to -30° C. and 0.76 g (5.10-3 mole n. pentyl bromide in solution in 5 cm3 tetrahydrofuran are added thereto. After having kept the mixture at -30° C. for 10 minutes, the temperature is allowed to rise to 20° C. and stirring is continued for 2 hours. The reaction mixture is then hydrolyzed by a saturated aqueous solution of ammonium chloride and extracted three times with 50 cm3 ether. The combined ethereal extracts are washed three times with a saturated aqueous solution of sodium chloride, dried over magnesium sulphate and concentrated. 2.14 g (yield: 93%) of 6-phenylsulfonyl-cis-tricos-14-ene identified by thin layer chromatography and spectrography are thus obtained.
Reaction SMILES: [CH2:1]([OH:3])[CH3:2].[CH3:4][O:5][C:6]1[CH:11]=[CH:10][C:9]([C:12](=[O:15])[CH2:13][CH3:14])=[CH:8][CH:7]=1.C(OCC)(OCC)O[CH2:18][CH3:19].C(=O)(O)[O-]>C1(C)C=CC(S(O)(=O)=O)=CC=1.C(N(CC)CC)C>[CH2:1]([O:3][C:12]([O:15][CH2:18][CH3:19])([C:9]1[CH:10]=[CH:11][C:6]([O:5][CH3:4])=[CH:7][CH:8]=1)[CH2:13][CH3:14])[CH3:2]
Reactant: CCO
Reactant: CCOC(OCC)OCC
Reactant: CCC(=O)c1ccc(OC)cc1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Agent: O=C([O-])O
Solvent: CCN(CC)CC
Product: CCOC(CC)(OCC)c1ccc(OC)cc1
Temperature: 25 °C
Reaction time: 22 h
Yield: 21 %

Procedure:
40 ml of absolute ethanol and 0.75 g of p-toluenesulphonic acid are placed in a round flask which is fitted with a stirrer, thermometer, condenser and dropping funnel. Now, there are added dropwise within 15 minutes while stirring 120 g of p-methoxy-propiophenone and subsequently within 1 hour 108 g of triethyl orthoformate. The temperature is held below 3° C. The mixture is subsequently stirred for a further 22 hours at room temperature. The mixture is adjusted to pH 8 with 3.6 g of triethylamine and then poured into 40 ml of 5% bicarbonate solution and 60 g of ice. The aqueous phase is separated and extracted with ether. The combined organic phases are washed with 5% bicarbonate solution and, after the addition of 0.2 g of sodium carbonate, the solvent is removed by evaporation under a vacuum and the residue is distilled over a 15 cm column. There are obtained 36.7 g of p-methoxy-propiophenone diethyl ketal (yield: 21% of theory). B.p.= 83°-84° C./0.4 mmHg; nD20 =1.4858; d420 =0.9988.
Reaction SMILES: Cl.Cl[C:3]1[N:8]2[N:9]=[C:10]([CH:12]3[CH2:17][CH2:16][N:15]([CH:18]([CH3:20])[CH3:19])[CH2:14][CH2:13]3)[N:11]=[C:7]2[CH:6]=[C:5]([C:21]2[CH:26]=[CH:25][C:24]([F:27])=[CH:23][C:22]=2[Cl:28])[N:4]=1.Cl.[NH2:30][C:31]1[C:36]([C:37]#[N:38])=[CH:35][CH:34]=[C:33]([NH:39][CH:40]2[CH2:45][CH2:44][CH2:43][NH:42][CH2:41]2)[N:32]=1.C(N(CC)C(C)C)(C)C>CS(C)=O>[NH2:30][C:31]1[C:36]([C:37]#[N:38])=[CH:35][CH:34]=[C:33]([NH:39][CH:40]2[CH2:45][CH2:44][CH2:43][N:42]([C:3]3[N:8]4[N:9]=[C:10]([CH:12]5[CH2:13][CH2:14][N:15]([CH:18]([CH3:19])[CH3:20])[CH2:16][CH2:17]5)[N:11]=[C:7]4[CH:6]=[C:5]([C:21]4[CH:26]=[CH:25][C:24]([F:27])=[CH:23][C:22]=4[Cl:28])[N:4]=3)[CH2:41]2)[N:32]=1
Reactant: N#Cc1ccc(NC2CCCNC2)nc1N
Reactant: CC(C)N1CCC(c2nc3cc(-c4ccc(F)cc4Cl)nc(Cl)n3n2)CC1
Agent: Cl
Solvent: CCN(C(C)C)C(C)C
Solvent: CS(C)=O
Product: CC(C)N1CCC(c2nc3cc(-c4ccc(F)cc4Cl)nc(N4CCCC(Nc5ccc(C#N)c(N)n5)C4)n3n2)CC1
Temperature: 130 °C

Procedure:
80 mg (0.17 mmol) of 5-chloro-7-(2-chloro-4-fluorophenyl)-2-[1-(propan-2-yl)piperidin-4-yl][1,2,4]triazolo[1,5-c]pyrimidine hydrochloride (Example 52A), 56.3 mg (0.2 mmol) of 2-amino-6-(piperidin-3-ylamino)pyridine-3-carbonitrile hydrochloride (Example 20A) and 0.17 ml (0.99 mmol) of N,N-diisopropylethylamine were initially charged in 1 ml of DMSO. The mixture was heated in the microwave at 130° C. for 30 min. This gave, after purification of the crude product by preparative HPLC (Method 11), 47 mg (44% of theory) of the product as a solid.
Reaction SMILES: Br[C:2]1[C:3]2[C:8]([CH:9]=[C:10]3[C:15]=1[CH:14]=[CH:13][CH:12]=[CH:11]3)=[CH:7][CH:6]=[CH:5][CH:4]=2.[CH:16]1[C:25]2[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=2)[CH:19]=[CH:18][C:17]=1OB(O)O.C(=O)([O-])[O-].[Na+].[Na+].C(O)C>C1(C)C=CC=CC=1.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>[CH:16]1[C:25]2[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=2)[CH:19]=[CH:18][C:17]=1[C:2]1[C:15]2[C:10]([CH:9]=[C:8]3[C:3]=1[CH:4]=[CH:5][CH:6]=[CH:7]3)=[CH:11][CH:12]=[CH:13][CH:14]=2
Reactant: OB(O)Oc1ccc2ccccc2c1
Reactant: Brc1c2ccccc2cc2ccccc12
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: [Na+]
Solvent: CCO
Solvent: O
Solvent: Cc1ccccc1
Product: c1ccc2cc(-c3c4ccccc4cc4ccccc34)ccc2c1
Temperature: 25 °C

Procedure:
9-Bromoanthracene (2.57 g, 10.00 mmol), 2-naphthyl boric acid (1.80 g, 12.65 mmol) and sodium carbonate (2.34 g, 22.1 mmol) were suspended in a mixture of toluene (20 mL), ethanol (3 mL) and water (10 mL). To the suspension, was added tetrakis(triphenylphosphine)palladium (0.25 g, 0.22 mmol). The mixture was stirred under reflux for about 24 hours, and then the refluxed mixture was cooled to room temperature. The organic layer was separated and washed with water, and the aqueous layer was extracted by chloroform. The organic extract was dried over magnesium sulfate, and concentrated in vacuo to prepare a 9-(2-naphthyl)anthracene compound C-1 (2.55 g, yield 84).
Reaction SMILES: [O:1]=[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[N:9][CH:10]=2)[NH:5][CH:4]([CH3:12])[CH2:3]1.C(N(CC)CC)C.[C:20](OC(=O)C)(=[O:22])[CH3:21]>ClCCl>[C:20]([N:5]1[C:6]2[C:11](=[CH:10][N:9]=[CH:8][CH:7]=2)[C:2](=[O:1])[CH2:3][CH:4]1[CH3:12])(=[O:22])[CH3:21]
Reactant: CC(=O)OC(C)=O
Reactant: CC1CC(=O)c2cnccc2N1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CC(=O)N1c2ccncc2C(=O)CC1C
Temperature: 40 °C
Reaction time: 8 h

Procedure:
[Step 4] 30 mg of the 4-oxo-2-methyl-2,3-dihydro-1H-[1,6]naphthyridine were dissolved in 2 mL of dichloromethane followed by adding 0.1 mL of triethylamine and 35 μL of acetic anhydride and stirring overnight at 40° C. Following completion of the reaction, the solution was concentrated under reduced pressure and the resulting residue was purified using silica gel chromatography (ethyl acetate) to obtain 7 mg of 1-acetyl-4-oxo-2-methyl-2,3-dihydro-1H-[1,6]naphthyridine in the form of a pale yellow oil (18%).
Reaction SMILES: [C:1]1([C:7]([CH2:9]C=O)=N)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[NH2:12][C:13]([NH2:15])=[O:14].Cl.[OH-].[NH4+].[CH2:19](O)C>>[C:1]1([C:7]2[CH:9]=[N:12][C:13]([OH:14])=[N:15][CH:19]=2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: N=C(CC=O)c1ccccc1
Reactant: NC(N)=O
Reactant: CCO
Agent: Cl
Agent: [NH4+]
Agent: [OH-]
Product: Oc1ncc(-c2ccccc2)cn1

Procedure:
A mixture of 20.0 g. of (phenyl)formimidoylacetaldehyde and 5.0 g. of urea is heated under reflux in 50 ml. of ethanol and 10 ml. of concentrated hydrochloric acid for 5 hours. The cooled mixture is swamped with 20% aqueous ammonium hydroxide and the precipitate is collected and washed with water. The precipitate is crystallized from ethanol to give 8.0 g. of the product of the Example, m.p. 239°-241° C.
Reaction SMILES: [CH2:1]([N:17]([CH3:19])[CH3:18])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16].C(#N)C.[Br:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH3:29]>>[Br-:23].[CH2:1]([N+:17]([CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH3:29])([CH3:19])[CH3:18])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16]
Reactant: CCCCCCCCCCCCCCCCN(C)C
Reactant: CCCCCCBr
Solvent: CC#N
Product: CCCCCCCCCCCCCCCC[N+](C)(C)CCCCCC
Product: [Br-]
Temperature: 85 °C

Procedure:
An apparatus as described in Example 1 is used. The following are added successively to the flask with stirring: 164.8 g (0.6 mol) of N-hexadecyl-N,N-dimethylamine, 268.8 g (6.55 mol) of acetonitrile and 104.0 g (0.63 mol) of 1-bromohexane. The mixture is heated to 85° C. with stirring in the course of 4 hours and is then cooled to room temperature, and the residual amine content is determined in a sample and an amine conversion of 99.1% is determined from this. Working-up by means of a rotary evaporator and subsequent treatment in an oil pump vacuum is carried out as described in Example 1. The N-hexadecyl-N-hexyl-N,N-dimethylammonium bromide (2) thus obtained is used for the viscosity measurements described below. The following contents are determined analytically:
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5](B(O)O)=[CH:4][CH:3]=1.[CH3:11][O:12][C:13](=[O:37])[C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([CH2:20][N:21]([C:29](=[O:36])[C:30]#[C:31][C:32]([CH3:35])([CH3:34])[CH3:33])[C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=2I)[CH:15]=1>>[CH3:11][O:12][C:13](=[O:37])[C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([CH2:20][N:21]2[C:22]3[C:27](=[CH:26][CH:25]=[CH:24][CH:23]=3)/[C:30](=[C:31](/[C:5]3[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=3)\[C:32]([CH3:35])([CH3:34])[CH3:33])/[C:29]2=[O:36])[CH:15]=1
Reactant: COC(=O)c1cccc(CN(C(=O)C#CC(C)(C)C)c2ccccc2I)c1
Reactant: OB(O)c1ccc(Cl)cc1
Product: COC(=O)c1cccc(CN2C(=O)/C(=C(\c3ccc(Cl)cc3)C(C)(C)C)c3ccccc32)c1

Procedure:
The title compound was prepared in analogy to Example 84 starting from 4-chlorophenylboronic acid (commercially available) and 3-{[(4,4-dimethyl-pent-2-ynoyl)-(2-iodo-phenyl)-amino]-methyl}-benzoic acid methyl ester. 1H NMR (400 MHz, MeOD) δppm 1.38 (s, 9H) 3.86 (s, 3H) 4.83 (d, 2H) 6.81 (d, J=7.83 Hz, 1H) 6.99 (d, J=7.83 Hz, 2H) 7.10 (t, J=7.58 Hz, 1H) 7.22 (t, J=7.71 Hz, 1H) 7.33-7.42 (m, 4H) 7.84-7.88 (m, 2H) 7.93 (d, J=7.83 Hz, 1H).
Reaction SMILES: [Br:1][CH2:2][C:3](Br)=[O:4].[CH:6]([N:9]([C:16]1[CH:21]=[CH:20][C:19]2[O:22][CH2:23][O:24][C:18]=2[CH:17]=1)C1C=CC=CC=1)([CH3:8])[CH3:7].C(N(CC)CC)C>C(Cl)Cl>[CH:6]([N:9]([C:16]1[CH:21]=[CH:20][C:19]2[O:22][CH2:23][O:24][C:18]=2[CH:17]=1)[C:3](=[O:4])[CH2:2][Br:1])([CH3:8])[CH3:7]
Reactant: O=C(Br)CBr
Reactant: CC(C)N(c1ccccc1)c1ccc2c(c1)OCO2
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CC(C)N(C(=O)CBr)c1ccc2c(c1)OCO2
Reaction time: 8 h

Procedure:
Bromoacetyl bromide (6.0 mL) in methylene chloride (100 mL) is added dropwise to a 0° C. solution of N-Isopropyl-N-(3,4-methylenedioxy-phenyl) aniline, prepared as in Part A, (12.0 g) in methylene chloride (100 mL) and triethylamine (9.41 mL) and the resultant mixture is allowed to attain RT overnight. The reaction mixture is washed with 1N hydrochloric acid (3×80 mL), water (2×80 mL), brine (80 mL), dried, (MgSO4) and concentrated in vacuo to afford crude N-Isopropyl-N-(3,4-methylenedioxy-phenyl) bromoacetamide (16.3 g) as a black mobile oil which is used without further purification: 1H NMR (300 MHz, CDCl3) δ6.82 (d, 1H, J=8.2), 6.61 (m, 2H), 4.90 (m, 1H, J=6.8), 3.58 (s, 2H), 1.07 (m, 6H).