Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][C:3]1[C@@H:8]([CH:9]([CH3:11])[CH3:10])[N:7]=[C:6]([O:12][CH3:13])[CH2:5][N:4]=1.[Li]CCCC.[CH3:19][O:20][C:21]1[CH:32]=[CH:31][C:24](/[CH:25]=[CH:26]/[C:27]([O:29][CH3:30])=[O:28])=[CH:23][CH:22]=1.C(O)(=O)C>C1COCC1.CCOCC>[CH3:30][O:29][C:27](=[O:28])[CH2:26][C@@H:25]([C@H:5]1[C:6]([O:12][CH3:13])=[N:7][C@H:8]([CH:9]([CH3:11])[CH3:10])[C:3]([O:2][CH3:1])=[N:4]1)[C:24]1[CH:31]=[CH:32][C:21]([O:20][CH3:19])=[CH:22][CH:23]=1
Reactant: COC(=O)/C=C/c1ccc(OC)cc1
Reactant: COC1=N[C@H](C(C)C)C(OC)=NC1
Agent: [Li]CCCC
Solvent: CC(=O)O
Solvent: C1CCOC1
Solvent: CCOCC
Product: COC(=O)C[C@H](c1ccc(OC)cc1)[C@@H]1N=C(OC)[C@@H](C(C)C)N=C1OC
Temperature: -70 °C
Reaction time: 0.67 h
Yield: 81.3 %

Procedure:
To a solution of (R)-2,5-dimethoxy-3-isopropyl-3,6-dihydropyrazine (18.4 g, 100 mmol) in 250 mL of dry THF at −70° C. (internal temperature) was added dropwise a solution of n-BuLi (1.6 M in hexane, 63 mL, 100 mmol) over 3 hours so as to maintain the internal temperature below −70° C. After addition, the solution was stirred at −70° C. for 40 min. To the solution was then added 90 mL of a THF solution of methyl trans-4-methoxycinnamate (21.2 g, 110 mmol) over 1 hour. The resulting solution was stirred at −70° C. for additional 4 hours. The reaction was quenched by the addition of acetic acid (6.1 mL, 100 mmol) at −70° C. and the resulting suspension was warmed to room temperature to give a yellow solution. The solution was diluted with ether to 1000 mL and the organic layer was washed with water (3×80 mL) and brine (3×80 mL) and dried over MgSO4. After removal of the solvent, the residue (44.3 g) was purified by HPLC on silica gel, eluting with ethyl acetate/hexane (1:5.5) to give 3(R)-[(2S,5R)-2,5-dihydro-3,6-dimethoxy-5-(1-methylethyl)-2-pyrazinyl]-3-(4-methoxyphenyl)propanoic acid methyl ester (30.6 g, 81.3 mmol, 81.3%). TLC: Rf=0.3, ethyl acetate/hexane (1/5). HRMS, obs. 377.2071, calc. 377.2076. Anal. cacld for C20H26N2O5: C, 64.16; H, 7.00; N, 7.48. Found: C, 64.05; H, 7.28; N, 7.37.
Reaction SMILES: [NH2:1][CH:2]([C:7]([OH:9])=O)[CH2:3][C:4]([OH:6])=[O:5].[OH-].[Na+].[CH2:12]([N:16]=[C:17]=[O:18])[CH2:13][CH2:14][CH3:15]>>[CH2:12]([N:16]1[C:7](=[O:9])[CH:2]([CH2:3][C:4]([OH:6])=[O:5])[NH:1][C:17]1=[O:18])[CH2:13][CH2:14][CH3:15]
Reactant: CCCCN=C=O
Reactant: NC(CC(=O)O)C(=O)O
Agent: [Na+]
Agent: [OH-]
Product: CCCCN1C(=O)NC(CC(=O)O)C1=O
Reaction time: 2 h

Procedure:
DL-Aspartic acid (6.65 g, 0.05 mole) in 2N-NaOH (50 ml, 2 equiv.) was cooled to 0° C. and n-butyl isocyanate (7.5 g, 0.075 mole) added during 15 minutes to the stirred solution. Stirring was continued for 2 hours and the mixture left at room temperature overnight. The mixture was then filtered, acidified with concentrated hydrochloric acid (50 ml) and heated on a steam-bath for 30 minutes. The mixture was cooled, diluted with water and continuously extracted with ether for 21/2 hours. Removal of the ether gave a solid which was recrystallised from ether to yield the product as prisms, m.p. 132° C. Yield 8.8 g=82%.
Reaction SMILES: [CH3:1][C:2]1[CH:8]=[C:7]([N+:9]([O-:11])=[O:10])[CH:6]=[CH:5][C:3]=1[NH2:4].[CH:12](O)=[O:13]>>[CH:12]([NH:4][C:3]1[CH:5]=[CH:6][C:7]([N+:9]([O-:11])=[O:10])=[CH:8][C:2]=1[CH3:1])=[O:13]
Reactant: O=CO
Reactant: Cc1cc([N+](=O)[O-])ccc1N
Product: Cc1cc([N+](=O)[O-])ccc1NC=O
Temperature: 0 °C
Reaction time: 4 h
Yield: 94.9 %

Procedure:
1000 g of formic acid were introduced into a flask fitted with a stirrer and a reflux condenser. 151 g (1 mol) of 2-methyl-4-nitroaniline were added, and the resultant mixture was slowly heated to the reflux point. After four hours, the reaction mixture was poured into 5 l of ice water. The resultant precipitate was filtered off with suction, washed with water until neutral and then dried at 60° C. under reduced pressure. Recrystallization of the resultant crude product from 2.5 l of methanol or ethanol gave 171 g of N-formyl-2-methyl-4-nitroaniline (yield: 95%) as yellow crystals, which melted at 162° C.
Reaction SMILES: O[CH2:2][C:3]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:4].C([N+](CCCC)(CCCC)CCCC)CCC.[OH-].[Na+].C1(C)C=CC(S([O:39][CH2:40][CH2:41][CH2:42][Cl:43])(=O)=O)=CC=1>C(#N)C.C1C=CC=CC=1>[Cl:43][CH2:42][CH2:41][CH2:40][O:39][C:10]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[C:3](=[O:4])[CH3:2]
Reactant: Cc1ccc(S(=O)(=O)OCCCCl)cc1
Reactant: O=C(CO)c1ccccc1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [Na+]
Agent: [OH-]
Solvent: CC#N
Solvent: c1ccccc1
Product: CC(=O)c1ccccc1OCCCCl
Temperature: 80 °C

Procedure:
2 ml of 2-hydroxy-acetophenone were added with stirring to a mixture of 2.31 g of tetrabutylammonium acid sulfate, 20 ml of 50% sodium hydroxide solution, 40 ml of benzene and 20 ml of acetonitrile and after adding 8.26 of 3-chloro-propyl p-toluene sulfonate, the mixture was heated under an inert atmosphere at 80° C. for 17 hours. The decanted aqueous phase was extracted with benzene and the organic phase was washed with water, dried over a deshydrant, filtered and evaporated to dryness. The residue was chromatographed over silica and eluted with a 95-5 benzene-ethyl acetate mixture. Evaporation ofthe solvents yielded 3.38 g of 1-[2-{3-chloropropoxy}-phenyl]-ethanone.
Reaction SMILES: [O-2].[Na+].[Na+].C[Si](C)(C)[N:6]1[CH2:12][CH2:11][CH2:10][CH2:9][CH2:8][C:7]1=[O:13].[Na].C1(=O)NCCCCC1.[CH2:25](Br)[CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH3:36]>COCCOC>[CH2:36]([N:6]1[CH2:12][CH2:11][CH2:10][CH2:9][CH2:8][C:7]1=[O:13])[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31][CH2:30][CH2:29][CH2:28][CH2:27][CH2:26][CH3:25]
Reactant: CCCCCCCCCCCCBr
Reactant: C[Si](C)(C)N1CCCCCC1=O
Agent: O=C1CCCCCN1
Agent: [Na+]
Agent: [Na]
Solvent: COCCOC
Product: CCCCCCCCCCCCN1CCCCCC1=O

Procedure:
3.1 g (0.05 mol) of sodium oxide (Na2O) are suspended in 150 ml of 1,2-dimethoxyethane, and then 18.5 g (0.1 mol) of N-trimethylsilylcaprolactam are added. The reaction mixture is stirred at 50° C. for two hours, during which the voluminous precipitate of the sodium salt of the caprolactam forms. Then 24.9 g (0.1 mol) of n-dodecyl bromide are added, and the mixture is stirred and heated under reflux for 20 hours. The working-up is carried out as indicated in Example 1.
Reaction SMILES: [NH2:1][C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][C:9]=2[O:11][CH3:12])[N:4]([CH2:13][C:14]2[CH:22]=[CH:21][C:17]([C:18]([NH2:20])=[O:19])=[CH:16][CH:15]=2)[N:3]=1.[CH3:23][C:24]1[S:28][C:27]([S:29](Cl)(=[O:31])=[O:30])=[CH:26][CH:25]=1>N1C=CC=CC=1>[CH3:12][O:11][C:9]1[CH:8]=[CH:7][CH:6]=[C:5]2[C:10]=1[C:2]([NH:1][S:29]([C:27]1[S:28][C:24]([CH3:23])=[CH:25][CH:26]=1)(=[O:31])=[O:30])=[N:3][N:4]2[CH2:13][C:14]1[CH:15]=[CH:16][C:17]([C:18]([NH2:20])=[O:19])=[CH:21][CH:22]=1
Reactant: Cc1ccc(S(=O)(=O)Cl)s1
Reactant: COc1cccc2c1c(N)nn2Cc1ccc(C(N)=O)cc1
Solvent: c1ccncc1
Product: COc1cccc2c1c(NS(=O)(=O)c1ccc(C)s1)nn2Cc1ccc(C(N)=O)cc1
Reaction time: 3 h
Yield: 14 %

Procedure:
A solution of 4-{[3-amino-4-(methyloxy)-1H-indazol-1-yl]methyl}benzamide (32.4 mg, 0.2 mmol) in pyridine 3.6 mL) was added to 5-methyl-thiophenesulfonyl chloride (for a preparation see Intermediate 32) (0.30 mmol). The reaction mixture was shaken briefly and allowed to stand for 3 h at 21° C. prior to concentration by blowdown. The residue was dissolved in 1:1 MeOH-DMSO (0.6 mL) and purified by Mass Directed AutoPrep on Xbridge column using Acetonitrile Water with an ammonium carbonate modifier (Method C). The solvent was evaporated in vacuo using the Genevac to give the title compound (12.5 mg, 14%). LCMS (System A) RT=0.86 min, ES+ve m/z 457 (M+H)+.
Reaction SMILES: [O:1]=[C:2]1[C:7]2[CH:8]=[C:9]([C:11]3[CH:12]=[CH:13][CH:14]=[C:15]4[C:20]=3[N:19]=[C:18]([C:21](O)=[O:22])[CH:17]=[CH:16]4)[NH:10][C:6]=2[CH2:5][CH2:4][NH:3]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(CC)CC.[NH2:55][CH:56]1[CH2:61][CH2:60][O:59][CH2:58][CH2:57]1>CN(C=O)C.C(Cl)Cl.CCOC(C)=O>[O:1]=[C:2]1[C:7]2[CH:8]=[C:9]([C:11]3[CH:12]=[CH:13][CH:14]=[C:15]4[C:20]=3[N:19]=[C:18]([C:21]([NH:55][CH:56]3[CH2:61][CH2:60][O:59][CH2:58][CH2:57]3)=[O:22])[CH:17]=[CH:16]4)[NH:10][C:6]=2[CH2:5][CH2:4][NH:3]1
Reactant: O=C(O)c1ccc2cccc(-c3cc4c([nH]3)CCNC4=O)c2n1
Reactant: NC1CCOCC1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Solvent: ClCCl
Product: O=C(NC1CCOCC1)c1ccc2cccc(-c3cc4c([nH]3)CCNC4=O)c2n1
Temperature: 25 °C
Reaction time: 0.42 h
Yield: 32 %

Procedure:
8-(4-Oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)quinoline-2-carboxylic acid (Example 94e; 77 mg, 0.25 mmol) was dissolved in DMF (1.5 mL), HATU (114 mg, 0.30 mmol), Et3N (0.04 mL, 0.30 mmol), and 4-aminotetrahydropyran (Combi-Blocks Inc., San Diego, Calif.; 0.05 mL, 0.50 mmol) were added, and the resulting mixture was stirred at RT for 25 min. The mixture was then treated with EtOAc and washed with water. The organic layer was separated, and the aq. layer was extracted with EtOAc (2×). The combined organic layers were then dried over MgSO4, filtered, and concentrated. The residue was treated with DCM, and a precipitate formed. The DCM was heated, but the precipitate did not dissolve. The suspension was held at RT for 1 h, after which the solid was removed by filtration to give 8-(4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)-N-(tetrahydro-2H-pyran-4-yl)quinoline-2-carboxamide (31.2 mg, 0.08 mmol, 32% yield) as a bright yellow amorphous solid: 1H NMR (400 MHz, DMSO-d6) δ ppm 12.00 (br. s., 1H), 8.55-8.67 (m, 2H), 8.08-8.16 (m, 2H), 7.93 (d, J=7.8 Hz, 1H), 7.68-7.77 (m, 1H), 6.94-7.05 (m, 2H), 4.00-4.15 (m, 1H), 3.90 (d, J=11.7 Hz, 2H), 3.42-3.52 (m, 4H), 2.91 (t, J=6.7 Hz, 2H), 1.92 (d, J=12.1 Hz, 2H), 1.59-1.74 (m, 2H). m/z (ESI, +ve ion) 391.1 (M+H)+.
Reaction SMILES: C[O:2][C:3](=[O:33])[CH2:4][O:5][C:6]1[CH:15]=[CH:14][C:13]([F:16])=[C:12]2[C:7]=1[C:8]([CH3:32])=[C:9]([CH2:20][C:21]1[CH:26]=[CH:25][C:24]([N:27]3[CH:31]=[CH:30][CH:29]=[N:28]3)=[CH:23][CH:22]=1)[C:10]([CH:17]([CH3:19])[CH3:18])=[N:11]2.[OH-].[Li+].Cl>O1CCCC1.O>[F:16][C:13]1[CH:14]=[CH:15][C:6]([O:5][CH2:4][C:3]([OH:33])=[O:2])=[C:7]2[C:12]=1[N:11]=[C:10]([CH:17]([CH3:18])[CH3:19])[C:9]([CH2:20][C:21]1[CH:26]=[CH:25][C:24]([N:27]3[CH:31]=[CH:30][CH:29]=[N:28]3)=[CH:23][CH:22]=1)=[C:8]2[CH3:32]
Reactant: COC(=O)COc1ccc(F)c2nc(C(C)C)c(Cc3ccc(-n4cccn4)cc3)c(C)c12
Agent: Cl
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: C1CCOC1
Product: Cc1c(Cc2ccc(-n3cccn3)cc2)c(C(C)C)nc2c(F)ccc(OCC(=O)O)c12
Temperature: 25 °C
Reaction time: 24 h
Yield: 25 %

Procedure:
A solution of [8-fluoro-2-isopropyl-4-methyl-3-(4-pyrazol-1-ylbenzyl)quinolin-5-yloxy]acetic acid methyl ester (0.062 g) in tetrahydrofuran (0.70 mL) and water (0.70 mL) was treated with lithium hydroxide (0.033 g), and the resulting mixture was stirred at room temperature. After 24 hours, the mixture was treated with additional lithium hydroxide (0.033 g) and stirring continued for 16 hours. The mixture was cooled to 0° C., acidified with 1.0 M aqueous hydrochloric acid and extracted with ethyl acetate (3×5.0 mL). The combined extracts were washed with saturated aqueous sodium chloride solution (2.0 mL), dried over magnesium sulfate and concentrated under reduced pressure. Purification of the residue by preparative reverse-phase HPLC, eluting with a mixture of acetonitrile and water (40:60 to 19:1 by volume) gave title compound as a yellow solid (0.015 g).
Reaction SMILES: C(OC(=O)C)(=O)C.[N:8]1([CH2:17][CH:18]([OH:35])[CH2:19][O:20][C:21]2[CH:26]=[CH:25][C:24]([CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH3:34])=[CH:23][CH:22]=2)[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[CH:10]=[CH:9]1.C(=O)([O-])O.[Na+].[Na+].[Cl-]>CS(C)=O>[N:8]1([CH2:17][C:18](=[O:35])[CH2:19][O:20][C:21]2[CH:22]=[CH:23][C:24]([CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH3:34])=[CH:25][CH:26]=2)[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[CH:10]=[CH:9]1
Reactant: CCCCCCCCc1ccc(OCC(O)Cn2ccc3ccccc32)cc1
Agent: O=C([O-])O
Agent: [Cl-]
Agent: [Na+]
Solvent: CS(C)=O
Solvent: CC(=O)OC(C)=O
Product: CCCCCCCCc1ccc(OCC(=O)Cn2ccc3ccccc32)cc1
Temperature: 25 °C
Reaction time: 0.17 h

Procedure:
1.77 g (17.3 mmol) acetic anhydride are mixed with 10 ml absolute DMSO, stirred at room temperature for 10 min and added drop-wise to a solution of 0.164 g (0.432 mmol) 1-(indol-1-yl)-3-(4-octylphenoxy)propan-2-ol in 10 ml absolute DMSO. Having stirred for six hours, the solution is poured into a mixture of 5% sodium hydrogen carbonate solution and saturated NaCl solution (1:1, v/v) and hydrolyzed for 10 min. Four extractions with diethyl ether, combination of the organic phases, concentration to half the volume on the rotary evaporator, three wash steps with saturated NaCl solution, drying on sodium sulfate, filtration and reconcentration on the rotary evaporator leave as a crude product a yellow oil which is purified on silica gel by means of column chromatography (flow agent: petroleum ether/ethyl acetate 95:5) and recrystallized from petroleum ether and yields the product as a white solid.
Reaction SMILES: [F:1][C:2]([F:18])([F:17])[C:3]1[O:7][N:6]=[C:5]([C:8]2[S:12][C:11]([C:13]([OH:15])=O)=[CH:10][CH:9]=2)[C:4]=1[CH3:16].[NH:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1.C1COCC1.N1CCCCC1>C(N(CC)CC)C>[CH3:16][C:4]1[C:5]([C:8]2[S:12][C:11]([C:13]([N:19]3[CH2:24][CH2:23][O:22][CH2:21][CH2:20]3)=[O:15])=[CH:10][CH:9]=2)=[N:6][O:7][C:3]=1[C:2]([F:1])([F:18])[F:17]
Reactant: Cc1c(-c2ccc(C(=O)O)s2)noc1C(F)(F)F
Reactant: C1COCCN1
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Solvent: C1CCNCC1
Product: Cc1c(-c2ccc(C(=O)N3CCOCC3)s2)noc1C(F)(F)F
Yield: 95 %

Procedure:
Prepared from 5-(5-Trifluoromethyl-4-methyl-isoxazol-3-yl)-thiophene-2-carboxylic acid and morpholine by the method described in Example 2 Method B reversing the order of addition such that solid acid chloride was added to a THF solution of triethylamine and piperidine derivative. The reaction mixture was evaporated to a solid, triturated and filtered with the aid of water, then washed with a 1 N aqueous hydrochloric acid solution followed by water. The solid was air dried to afford product as a colorless solid (66 mg, 95%). 1H NMR (CDCl3) 2.34 (d, J=1.3, 3H), 3.71-3.77 (m, 8H), 7.32 (d, J=4.0, 1H), 7.43 (d, J=4.0, 1H). 13C NMR 7.9, ˜48 (br), 67.0, 114.7, 118.7 (q, J=271), 128.0, 129.5, 131.7, 139.5, 157.9, 162.8. 19F NMR −63.2. LC/MS 5.93 min, [M+1]+ 347.
Reaction SMILES: [CH3:1][C:2]([C:5]1[CH:6]=[C:7]([CH:11]=[C:12]([C:15]([CH3:18])([CH3:17])[CH3:16])[C:13]=1[OH:14])[C:8]([OH:10])=[O:9])([CH3:4])[CH3:3].[H-].[Na+].[CH3:21]I.Cl>O1CCCC1.CN(C)C=O.O>[CH3:4][C:2]([C:5]1[CH:6]=[C:7]([CH:11]=[C:12]([C:15]([CH3:18])([CH3:17])[CH3:16])[C:13]=1[O:14][CH3:21])[C:8]([OH:10])=[O:9])([CH3:1])[CH3:3]
Reactant: CC(C)(C)c1cc(C(=O)O)cc(C(C)(C)C)c1O
Reactant: CI
Agent: Cl
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: C1CCOC1
Solvent: O
Product: COc1c(C(C)(C)C)cc(C(=O)O)cc1C(C)(C)C
Reaction time: 19 h

Procedure:
To 50 g {200 mmol) of 3,5-bis(1,1-dimethylethyl)-4-hydroxy benzoic acid dissolved in 1.1 liters of a 10/1 tetrahydrofuran/dimethylformamide solution were added 24.0 g of a sodium hydride dispersion (60%, by weight, sodium hydride dispersed in mineral oil). The sodium hydride dispersion was added portionwise at a rate such that the reaction solution temperature was kept below 35° C. The resulting solution was stirred for 19 hours and then 28.4 g (220 mmol) of methyl iodide were added. The resulting solution was stirred for 22 hours and then 25 ml of water were added to quench the reaction. Four hundred milliliters of a 1N hydrochloric acid solution were then added in order to acidify the quenched solution. The acidic solution was then concentrated and extracted three times with ethyl acetate. The ethyl acetate extracts were combined, washed three times with water and once with a saturated brine solution and then concentrated to dryness to provide residue. This residue was crystallized from a hexane/methylene chloride solution to provide 34.62 of title product m.p. 192°-195° C.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[S:10][CH:11]=[CH:12][N:13]=2)=[CH:4][C:3]=1[OH:14].C([O-])([O-])=O.[Cs+].[Cs+].Br[CH2:22][C:23]1[S:24][CH:25]=[CH:26][N:27]=1>CC(C)=O>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[S:10][CH:11]=[CH:12][N:13]=2)=[CH:4][C:3]=1[O:14][CH2:22][C:23]1[S:24][CH:25]=[CH:26][N:27]=1
Reactant: BrCc1nccs1
Reactant: Oc1cc(Nc2nccs2)ccc1Cl
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CC(C)=O
Product: Clc1ccc(Nc2nccs2)cc1OCc1nccs1
Yield: 33 %

Procedure:
Following the general procedure for O-alkylation, Method B, a mixture of 2-chloro-5-(thiazol-2-ylamino)phenol (100 mg, 0.44 mmol) and Cs2CO3 (147 mg, 0.44 mmol) in acetone (4.4 mL) was treated with 2-bromomethylthiazole (88 mg, 0.44 mmol) at RT. Reaction control by TLC showed full conversion after 3 h. The title compound was obtained after purification by flash chromatography on silica gel (hexane:EtOAc 1/1) in 33% yield (47 mg).
Reaction SMILES: [H][H].[C:3]1([C:9]([CH2:11][C:12]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)([CH3:14])[CH3:13])=[CH2:10])[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1>C1COCC1>[C:15]1([C:12]([CH3:14])([CH2:11][CH:9]([C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH3:10])[CH3:13])[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1
Reactant: [H][H]
Reactant: C=C(CC(C)(C)c1ccccc1)c1ccccc1
Solvent: C1CCOC1
Product: CC(CC(C)(C)c1ccccc1)c1ccccc1
Reaction time: 0.08 h
Yield: 100 %

Procedure:
In Example 3, hydrogenation reaction was conducted under the same condition as Example 1 for THF diluted solution concentration of the substance to be reduced, its flow rate, and hydrogen 9 flow rate, using 2,4-diphenyl-4-methyl-1-pentene as the substance to be reduced. The reaction time was within five minutes. The analytical result of the reaction product by 1H-NMR showed almost complete hydrogenation of 2,4-diphenyl-4-methyl-1-pentene, and 2,4-diphenyl-2-methylpentane was obtained at about 100% yield (See FIG. 6.).
Reaction SMILES: [CH2:1]([NH2:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.Cl[C:17]1[N:22]=[C:21]([C:23]([O:25][CH2:26][CH3:27])=[O:24])[C:20]([C:28]([O:30][CH2:31][CH3:32])=[O:29])=[CH:19][CH:18]=1>C(O)CC>[CH2:1]([NH:8][C:17]1[N:22]=[C:21]([C:23]([O:25][CH2:26][CH3:27])=[O:24])[C:20]([C:28]([O:30][CH2:31][CH3:32])=[O:29])=[CH:19][CH:18]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: NCc1ccccc1
Reactant: CCOC(=O)c1ccc(Cl)nc1C(=O)OCC
Solvent: CCCO
Solvent: CCN(CC)CC
Product: CCOC(=O)c1ccc(NCc2ccccc2)nc1C(=O)OCC
Reaction time: 0.17 h

Procedure:
10.7 g (0.1 mol) of benzylamine and 10.1 g (0.1 mol) of triethylamine were added to a mixture of 25.8 g (0.1 mol) of diethyl 6-chloropyridine-2,3-dicarboxylate in 250 ml of propanol at 25° C. with stirring in the course of 10 minutes. After stirring under reflux for 12 hours, the reaction mixture was concentrated, the residue was taken up in methylene chloride and the solution was extracted with water. The organic phase was dried, filtered off with suction through neutral alumina and concentrated under reduced pressure. The residue was stirred in ether/pentane, filtered off with suction and dried, 23.3 g (71.1% of theory) of the title compound of m.p. 110°-114° C. being obtained.
Reaction SMILES: C[O:2][C:3]1[CH:4]=[C:5]([CH:15]=[C:16]([C:18]2[CH:27]=[CH:26][C:25]3[C:20](=[CH:21][CH:22]=[C:23]([O:28]C)[CH:24]=3)[CH:19]=2)[CH:17]=1)[C:6]([NH:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)=[O:7].B(Br)(Br)Br>>[OH:2][C:3]1[CH:4]=[C:5]([CH:15]=[C:16]([C:18]2[CH:27]=[CH:26][C:25]3[C:20](=[CH:21][CH:22]=[C:23]([OH:28])[CH:24]=3)[CH:19]=2)[CH:17]=1)[C:6]([NH:8][C:9]1[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=1)=[O:7]
Reactant: COc1cc(C(=O)Nc2ccccc2)cc(-c2ccc3cc(OC)ccc3c2)c1
Agent: BrB(Br)Br
Product: O=C(Nc1ccccc1)c1cc(O)cc(-c2ccc3cc(O)ccc3c2)c1
Yield: 11 %

Procedure:
The compound is prepared by reaction of 3-methoxy-5-(6-methoxynaphthalene-2-yl)-N-phenylbenzamide (300 mg, 0.78 mmol, 1 eq) with boron tribromide solution (5 eq) according to method G. Purification by column chromatography with hexane/dichloromethane 1/99 yielded the desired product in a yield of 11%, 32 mg.
Reaction SMILES: Cl[C:2]1[N:3]=[CH:4][C:5]2[N:11]([CH3:12])[C:10](=[O:13])[CH2:9][CH2:8][N:7]([CH:14]3[CH2:18][CH2:17][CH2:16][CH2:15]3)[C:6]=2[N:19]=1.[NH2:20][C:21]1[CH:29]=[CH:28][C:24]([C:25]([OH:27])=[O:26])=[CH:23][CH:22]=1>>[CH:14]1([N:7]2[CH2:8][CH2:9][C:10](=[O:13])[N:11]([CH3:12])[C:5]3[CH:4]=[N:3][C:2]([NH:20][C:21]4[CH:29]=[CH:28][C:24]([C:25]([OH:27])=[O:26])=[CH:23][CH:22]=4)=[N:19][C:6]2=3)[CH2:18][CH2:17][CH2:16][CH2:15]1
Reactant: CN1C(=O)CCN(C2CCCC2)c2nc(Cl)ncc21
Reactant: Nc1ccc(C(=O)O)cc1
Product: CN1C(=O)CCN(C2CCCC2)c2nc(Nc3ccc(C(=O)O)cc3)ncc21

Procedure:
Prepared from 2-chloro-9-cyclopentyl-8,9-dihydro-5-methyl-5H-pyrimido[4,5-b][1,4]diazepin-6(7H)-one and 4-aminobenzoic acid using method D. NMR DMSO D6 1.59-1.80 (6H, m), 1.90-1.98 (2H, m), 2.70-2.75 (2H m), 3.18 (3H, s), 3.71-3.75 (2H, m), 4.91 (1H, m), 7.77 (2H, d), 7.94 (2H, d), 8.17 (1H, s), 10.65 (1H, br s). HPLC rt(min): 6.39.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:11]2[NH:16][C:15](=[O:17])[N:14]([CH3:18])[C:13](=[O:19])[CH:12]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10].[H-].[Na+].[CH2:22](I)[CH2:23][CH3:24].O>CN(C)C=O>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:11]2[N:16]=[C:15]([O:17][CH2:22][CH2:23][CH3:24])[N:14]([CH3:18])[C:13](=[O:19])[CH:12]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10]
Reactant: COc1ccc(-c2cc(=O)n(C)c(=O)[nH]2)cc1OC
Reactant: CCCI
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: CCCOc1nc(-c2ccc(OC)c(OC)c2)cc(=O)n1C
Temperature: 60 °C
Reaction time: 0.33 h

Procedure:
To a solution of 6-(3,4-dimethoxyphenyl)-3-methyl-2,4(1H,3H)-pyrimidinedione (3.0 g) in N,N-dimethylformamide (30 ml) was added sodium hydride (60% in oil, 0.5 g). The mixture was heated at 60° C. with stirring for 20 minutes and cooled to 0° C. To the mixture was added n-propyl iodide (15 ml) with stirring, which was continued at 0° C. for 2 hours and at ambient temperature for 3 hours. After addition of water, the reaction mixture was extracted with ethyl acetate. The organic extract was washed with water, dried over magnesium sulfate and evaporated under reduced pressure. The residue was triturated with diisopropyl ether and the resulting precipitates were collected by filtration to give 6-(3,4-dimethoxyphenyl)-3-methyl-2-propoxy-4(3H)-pyrimidinone (1.15 g) as by-product.