Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [O:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]1[O:7][CH2:8][CH2:9][C:10]#[C:11][C:12]1[CH:13]=[CH:14][C:15]2[CH2:21][CH:20]([CH2:22][C:23]([O:25][CH2:26][CH3:27])=[O:24])[C:19]3[CH:28]=[CH:29][CH:30]=[CH:31][C:18]=3[CH2:17][C:16]=2[CH:32]=1>[Pd].CCOC(C)=O>[O:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]1[O:7][CH2:8][CH2:9][CH2:10][CH2:11][C:12]1[CH:13]=[CH:14][C:15]2[CH2:21][CH:20]([CH2:22][C:23]([O:25][CH2:26][CH3:27])=[O:24])[C:19]3[CH:28]=[CH:29][CH:30]=[CH:31][C:18]=3[CH2:17][C:16]=2[CH:32]=1
Reactant: CCOC(=O)CC1Cc2ccc(C#CCCOC3CCCCO3)cc2Cc2ccccc21
Agent: [Pd]
Solvent: CCOC(C)=O
Product: CCOC(=O)CC1Cc2ccc(CCCCOC3CCCCO3)cc2Cc2ccccc21
Temperature: 25 °C
Reaction time: 3 h
Yield: 87.7 %

Procedure:
A mixture of ethyl (±)-10,11-dihydro-3-[4-(2-tetrahydropyranyloxy)-1-butyn-1-yl]-5H-dibenzo[a,d]cycloheptene-10-acetate (1.2 g, 2.77 mmole), 10% Pd/C (0.3 g, 0.28 mmole), and EtOAc (28 mL) was shaken at RT under hydrogen (50 psi) on a Parr apparatus. After 3 hr, the reaction was filtered through celite® and the filtrate was concentrated. Silica gel chromatography (10% EtOAc/hexanes) gave the title compound (1.06 g, 88%) as a colorless oil: TLC (20% EtOAc/hexanes) Rf0.51; 1H NMR (400 MHz, CDCl3) δ7.05-7.20 (m, 4 H), 6.92-7.03 (m, 3 H), 4.53-4.60 (m, 1 H), 4.34 (d, J=15.1 Hz, 1 H), 4.12-4.26 (m, 2 H), 3.80-3.90 (m, 3 H), 3.71-3.80 (m, 1 H), 3.44-3.53 (m, 1 H), 3.35-3.44 (m, 1 H), 3.33 (dd, J=15.1, 4.1 Hz, 1 H), 2.95 (dd, J=15.1, 9.4 Hz, 1 H), 2.65 (dd, J=15.5, 4.9 Hz, 1 H), 2.49-2.61 (m, 3 H), 1.77-1.90 (m, 1 H), 1.45-1.77 (m, 9 H), 1.27 (t, J=7.1 Hz, 3 H); MS (ES) m/e 459 (M+Na)+.
Reaction SMILES: C[C:2]1[C:7]([CH:8]=O)=[CH:6][C:5](OC)=[C:4](OC)[CH:3]=1.[CH2:14]([Mg]Cl)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.O>C1COCC1>[C:15]1([CH2:14][CH2:8][C:7]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1
Reactant: COc1cc(C)c(C=O)cc1OC
Reactant: Cl[Mg]Cc1ccccc1
Solvent: C1CCOC1
Solvent: O
Product: c1ccc(CCc2ccccc2)cc1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To 10 g of 6-methylveratraldehyde under a nitrogen atmosphere in 75 ml dry THF was added dropwise 1.5 equivalents benzylmagnesium chloride in 20 ml dry THF. After stirring overnight at room temperature, 20 ml water was added. The residue remaining after most of the THF had been distilled off was added to an additional 100 ml water and extracted with ether to give a yellow oil. Distillation under reduced pressure gave bibenzyl resulting from coupling of the Grignard reagent and a quantitative yield of the adduct 12 as a colorless viscous oil, bp 170°-175°(0.05 mm Hg). Nmr (δ): 2.08 (s, 3H), 2.88 (distorted doublet, J - 6 cps, integration for 3 H suggests coincidence with the alcohol proton), 3.75 (s, 6H), 4.96 (t, J = 6 cps, 1H), 6.52 (s, 1H), 7.00 (s, 1H), 7.15 (s, 5H),. Anal. Calcd. for C17H 20 O3 : C, 74.97; H, 7.40. Found: C, 75.38; H, 7.43.
Reaction SMILES: [Br:1][C:2]1[CH:10]=[CH:9][C:5]([CH2:6][CH2:7][NH2:8])=[CH:4][CH:3]=1.C(N(CC)CC)C.[CH3:18][S:19](Cl)(=[O:21])=[O:20]>ClCCl>[Br:1][C:2]1[CH:10]=[CH:9][C:5]([CH2:6][CH2:7][NH:8][S:19]([CH3:18])(=[O:21])=[O:20])=[CH:4][CH:3]=1
Reactant: NCCc1ccc(Br)cc1
Reactant: CS(=O)(=O)Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CS(=O)(=O)NCCc1ccc(Br)cc1
Reaction time: 2 h
Yield: 100.7 %

Procedure:
To a 0° C. solution of of 4-bromophenethylamine (10.0 g, 50.0 mmol) and triethylamine (7.7 mL, 55.0 mmol) in 150 mL of dichloromethane was added dropwise methanesulfonyl chloride (4.3 mL 55.0 mmol) in 20 mL of dichloromethane. After two hours, the reaction mixture was washed once with 100 mL of 10% aqueous sodium bisulfate. The organic portion was separated and the aqueous portion was extracted three times with 50 mL each of dichloromethane. The combined organics were dried (Na2SO4), filtered and concentrated in vacuo to afford 14.0 g (100%) of the intermediate title compound.
Reaction SMILES: C1(COC(=O)[N:10]([CH2:12][C:13]2[N:22](COCC[Si](C)(C)C)[C:16]3=[N:17][CH:18]=[C:19](Br)[CH:20]=[C:15]3[N:14]=2)[CH3:11])C=CC=CC=1.[CH3:32][C:33]1([CH3:57])[CH2:42][CH2:41][C:40]2[N:39]=[CH:38][N:37]=[C:36]([N:43]3[CH2:49][C:48]4[CH:50]=[C:51](B(O)O)[CH:52]=[CH:53][C:47]=4[O:46][CH2:45][CH2:44]3)[C:35]=2[CH2:34]1>>[CH3:32][C:33]1([CH3:57])[CH2:42][CH2:41][C:40]2[N:39]=[CH:38][N:37]=[C:36]([N:43]3[CH2:49][C:48]4[CH:50]=[C:51]([C:19]5[CH:20]=[C:15]6[NH:14][C:13]([CH2:12][NH:10][CH3:11])=[N:22][C:16]6=[N:17][CH:18]=5)[CH:52]=[CH:53][C:47]=4[O:46][CH2:45][CH2:44]3)[C:35]=2[CH2:34]1
Reactant: CN(Cc1nc2cc(Br)cnc2n1COCC[Si](C)(C)C)C(=O)OCc1ccccc1
Reactant: CC1(C)CCc2ncnc(N3CCOc4ccc(B(O)O)cc4C3)c2C1
Product: CNCc1nc2ncc(-c3ccc4c(c3)CN(c3ncnc5c3CC(C)(C)CC5)CCO4)cc2[nH]1

Procedure:
Prepared according to the method of example 5 by using phenylmethyl{[6-bromo-3-({[2-(trimethylsilyl)ethyl]oxy}methyl)-3H-imidazo[4,5-b]pyridin-2-yl]methyl}methylcarbamate (reagent preparation 19) and [4-(6,6-dimethyl-5,6,7,8-tetrahydroquinazolin-4-yl)-2,3,4,5-tetrahydro-1,4-benzoxazepin-7-yl]boronic acid (reagent preparation 23) in step 1. 1H NMR (400 MHz, Methanol-d4): 8.62 (br, 1H), 8.35 (s, 1H), 8.10 (s, 1H), 7.62 (br, 1H), 7.53 (d, 1H), 7.09 (d, 1H), 4.74 (s, 2H), 4.38 (m, 2H), 4.22 (s, 2H), 3.97 (m, 2H), 2.77 (t, 2H), 2.59 (s, 3H), 2.48 (s, 2H), 1.68 (t, 2H), 0.88 (s, 6H); MS (EI) for C27H31N7O: 470 (MH+).
Reaction SMILES: [CH2:1]([N:8]1[C:16]2[CH:15]=[C:14]([CH3:17])[N:13]=[C:12]([N:18](CC3C=CC=CC=3)CC3C=CC=CC=3)[C:11]=2[NH:10][C:9]1=[O:33])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1>C(O)C.[OH-].[OH-].[Pd+2]>[NH2:18][C:12]1[C:11]2[NH:10][C:9](=[O:33])[N:8]([CH2:1][C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)[C:16]=2[CH:15]=[C:14]([CH3:17])[N:13]=1
Reactant: Cc1cc2c([nH]c(=O)n2Cc2ccccc2)c(N(Cc2ccccc2)Cc2ccccc2)n1
Agent: [Pd+2]
Agent: [OH-]
Solvent: CCO
Product: Cc1cc2c([nH]c(=O)n2Cc2ccccc2)c(N)n1
Reaction time: 6 h

Procedure:
1-Benzyl-4-dibenzylamino-6-methyl-1,3-dihydro-imidazo[4,5-c]pyridin-2-one (34 mg, 0.08 mmol) was suspended in ethanol (5 mL) and hydrogenated over 10% Pd(OH)2 (7 mg) at room temperature, 60 psi for 6 hours. The reaction mixture was filtered through a short plug of Arbocel and the filtrate was then evaporated in vacuo to an opaque gum. The gum was dissolved in methanol and preabsorbed onto silica gel and was then purified by column chromatography, eluting with 5% methanol in EtOAc. Appropriate fractions were combined and evaporated in vacuo to give the title compound as a white solid, 7 mg.
Reaction SMILES: [O:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[CH2:6][NH:7][S:8]([C:11]1[CH:12]=[C:13]2[C:17](=[CH:18][CH:19]=1)[NH:16][C:15](=[O:20])[C:14]2=O)(=[O:10])=[O:9].[N+:22]([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=1[NH:31][NH2:32])([O-:24])=[O:23]>Cl.C(O)C>[O:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[CH2:6][NH:7][S:8]([C:11]1[CH:12]=[C:13]2[C:17](=[CH:18][CH:19]=1)[NH:16][C:15](=[O:20])[C:14]2=[N:32][NH:31][C:26]1[CH:27]=[CH:28][CH:29]=[CH:30][C:25]=1[N+:22]([O-:24])=[O:23])(=[O:10])=[O:9]
Reactant: O=C1Nc2ccc(S(=O)(=O)NCc3ccco3)cc2C1=O
Reactant: NNc1ccccc1[N+](=O)[O-]
Agent: Cl
Solvent: CCO
Product: O=C1Nc2ccc(S(=O)(=O)NCc3ccco3)cc2C1=NNc1ccccc1[N+](=O)[O-]
Temperature: 120 °C

Procedure:
A mixture of rpm161 (0.040 g, 0.114 mmol) 2-nitrophenylhydrazine (0.021 g, 0.126 mmol, 1.1 eq) and HCl (aq 4 M, 2 drops) in ethanol (3 mL) was heated in the CEM microwave at 120° C. for 15 min. After cooling to room temperature, pure product rpm168 was collected as an orange precipitate by filtration and dried in vacuo. The pure compound rpm168 was obtained without further purification (0.048 g, 0.099 mmol, 86%). MS (API-ES): m/z 459 (M+NH4)+; HRMS (API-ES) m/z Found: 459.1082 (M+NH4)+.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([N:8]2[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]2)[C:3]=1[C:14](=[O:16])[CH3:15].[O:17]=[C:18]1[NH:27][C:26]2[N:25]=[C:24]([O:28][CH2:29][CH2:30][CH2:31][CH:32]=O)[CH:23]=[CH:22][C:21]=2[CH:20]=[CH:19]1>>[C:14]([C:3]1[C:2]([F:1])=[CH:7][CH:6]=[CH:5][C:4]=1[N:8]1[CH2:13][CH2:12][N:11]([CH2:32][CH2:31][CH2:30][CH2:29][O:28][C:24]2[N:25]=[C:26]3[C:21]([CH:20]=[CH:19][C:18](=[O:17])[NH:27]3)=[CH:22][CH:23]=2)[CH2:10][CH2:9]1)(=[O:16])[CH3:15]
Reactant: CC(=O)c1c(F)cccc1N1CCNCC1
Reactant: O=CCCCOc1ccc2ccc(=O)[nH]c2n1
Product: CC(=O)c1c(F)cccc1N1CCN(CCCCOc2ccc3ccc(=O)[nH]c3n2)CC1

Procedure:
In a manner similar to that of other examples above, 1-(2-fluoro-6-piperazin-1-yl-phenyl)-ethanone was coupled by reductive amination to 4-(7-oxo-7,8-dihydro-[1,8]naphthyridin-2-yloxy)-butyraldehyde followed by typical workup and purification to give the title compound. MS: APCI: M+1: 439.2 (Exact Mass: 438.21).
Reaction SMILES: Br[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][P:14](=[O:21])([O:18][CH2:19][CH3:20])[O:15][CH2:16][CH3:17].NC(N)=[S:24].[OH-].[Na+].Cl>O>[SH:24][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][P:14](=[O:21])([O:18][CH2:19][CH3:20])[O:15][CH2:16][CH3:17]
Reactant: NC(N)=S
Reactant: CCOP(=O)(CCCCCCCCCCCCBr)OCC
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: CCOP(=O)(CCCCCCCCCCCCS)OCC
Temperature: 25 °C
Reaction time: 12 h
Yield: 73.5 %

Procedure:
In the second step, diethyl 12-bromododecylphosphonate (20.01 g; 51.9 mmol) is reacted, under an inert atmosphere, with thiourea (4 g; 51.9 mmol) in 200 ml of water at 100° C. with stirring for 12 hours. After cooling, a solution of sodium hydroxide (2.07 g; 51.9 mmol) in 100 ml of water is added dropwise and the reaction mixture is refluxed for 3 hours. After cooling to room temperature, hydrochloric acid solution (32%) is added dropwise to pH 1. The solution is then stirred for 24 hours. The organic phase is then recovered with 100 ml of CH2Cl2, washed with distilled water, dried over sodium sulfate, filtered and evaporated under reduced pressure. The yellow oil obtained is purified by chromatography on a column of silica gel (eluent: hexane/8% EtOAc) to give 10.8 g (n=38.16 mmol) of diethyl 12-mercaptododecylphosphonate (52% yield).
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:25])[CH2:5][C:6]1[CH:11]=[CH:10][C:9]([O:12][CH3:13])=[C:8]([C:14]2[C:19]([CH2:20][NH:21][CH2:22][CH3:23])=[CH:18][C:17]([CH3:24])=[CH:16][N:15]=2)[CH:7]=1)[CH3:2].FC(F)(F)C([O-])=O.[CH2:33]([N:40]=[C:41]=[O:42])[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1.C(N(CC)CC)C>C(Cl)Cl>[CH2:1]([O:3][C:4](=[O:25])[CH2:5][C:6]1[CH:11]=[CH:10][C:9]([O:12][CH3:13])=[C:8]([C:14]2[C:19]([CH2:20][N:21]([CH2:22][CH3:23])[C:41]([NH:40][CH2:33][C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=3)=[O:42])=[CH:18][C:17]([CH3:24])=[CH:16][N:15]=2)[CH:7]=1)[CH3:2]
Reactant: CCNCc1cc(C)cnc1-c1cc(CC(=O)OCC)ccc1OC
Reactant: O=C=NCc1ccccc1
Agent: O=C([O-])C(F)(F)F
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CCOC(=O)Cc1ccc(OC)c(-c2ncc(C)cc2CN(CC)C(=O)NCc2ccccc2)c1

Procedure:
[3-(3-Ethylaminomethyl-5-methyl-pyridin-2-yl)-4-methoxy-phenyl]-acetic acid ethyl ester, trifluoroacetate (0.36 mmol) was reacted with benzyl isocyanate (0.05 mL, 0.44 mmol) and triethylamine (0.152 mL, 1.09 mmol) in CH2Cl2 to give the title compound.
Reaction SMILES: [OH-].[Na+].[I-].[CH3:4][S+](C)(C)=O.[CH3:9][CH:10]([C:13](=[O:23])[CH:14]=[CH:15][C:16]1[CH:21]=[CH:20][CH:19]=[C:18]([OH:22])[CH:17]=1)[CH2:11][CH3:12]>CS(C)=O>[CH3:9][CH:10]([C:13]([CH:14]1[CH2:4][CH:15]1[C:16]1[CH:21]=[CH:20][CH:19]=[C:18]([OH:22])[CH:17]=1)=[O:23])[CH2:11][CH3:12]
Reactant: CCC(C)C(=O)C=Cc1cccc(O)c1
Reactant: C[S+](C)(C)=O
Agent: [I-]
Agent: [Na+]
Agent: [OH-]
Solvent: CS(C)=O
Product: CCC(C)C(=O)C1CC1c1cccc(O)c1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 84.1 %

Procedure:
To a 250 ml round bottom flask equipped with magnetic stirrer, nitrogen inlet, thermometer and addition funnel was charged 1.6 g (0.039 moles) of powdered sodium hydroxide, 8.7 g (0.039 moles) of trimethyl sulfoxonium iodide, and 50 mls of anhydrous DMSO. The mixture was then stirred at ambient temperature for 30 minutes. The mixture was then cooled to 15° C., and a solution of 1-(1-methylpropyl)-3-(3-hydroxyphenyl)-2-propene-1-one (4.0 g, 0.0196 moles) was added dropwise in 50 mls of DMSO. The reaction was stirred for 1 hour at 15° C., then allowed to warm to ambient temperature, and stirred for an additional 16 hours. The reaction mixture was the quenched with 100 mls of 0.1 N HCl, and extracted with 3×100 mls of ethyl ether. The combined ether extracts were washed successively with 2×100 mls of water, and 100 mls of saturated aqueous sodium chloride solution. The ether extract was then dried over anhydrous magnesium sulfate, filtered and concentrated to dryness under reduced pressure with a rotary evaporator at 45 ° C. to afford 3.6 g of the title compound, 2-(3-hydroxyphenyl)cyclopropyl 1-methylpropyl ketone, as a thick amber oil in an 85% crude yield.
Reaction SMILES: [CH2:1]([O:3][CH2:4][C:5]1[N:6]([CH2:18][C:19]2([OH:24])[CH2:23][CH2:22][CH2:21][CH2:20]2)[C:7]2[C:16]3[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=3[N:10]=[CH:9][C:8]=2[N:17]=1)[CH3:2].C1C=C(Cl)C=C(C(OO)=O)C=1.[OH-].[NH4+:37].S(Cl)(C1C=CC(C)=CC=1)(=O)=O>ClCCl.O>[NH2:37][C:9]1[C:8]2[N:17]=[C:5]([CH2:4][O:3][CH2:1][CH3:2])[N:6]([CH2:18][C:19]3([OH:24])[CH2:23][CH2:22][CH2:21][CH2:20]3)[C:7]=2[C:16]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[N:10]=1
Reactant: CCOCc1nc2cnc3ccccc3c2n1CC1(O)CCCC1
Reactant: [NH4+]
Agent: Cc1ccc(S(=O)(=O)Cl)cc1
Agent: O=C(OO)c1cccc(Cl)c1
Agent: [OH-]
Solvent: ClCCl
Solvent: O
Product: CCOCc1nc2c(N)nc3ccccc3c2n1CC1(O)CCCC1
Temperature: 25 °C
Reaction time: 1 h
Yield: 50 %

Procedure:
To a solution of 1-{[2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl]methyl}cyclopentanol (3.00 g, 9.22 mmol) in dichloromethane (60 mL) at rt was added m-CPBA (2.89 g, 9.22 mmol). After 1 h, concentrated ammonium hydroxide (60 mL) was added and the mixture was cooled in an ice bath. To the mixture was added TsCl (1.85 g, 9.68 mmol). The reaction was stirred rapidly overnight at rt. Additional TsCl (0.21 g) was added in the morning and the mixture was stirred 45 min. Water (75 mL) was added and the mixture was extracted with dichloromethane (3×100 mL). The combined organic phases were washed with brine and dried over MgSO4, filtered, and concentrated. The resulting foam was treated with acetonitrile and a white solid formed. The solid was recrystallized from acetonitrile and dried under vacuum to yield 1-{[4-amino-2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl]methyl}cyclopentanol as fine tan crystals (1.57 g, 50%), mp 156.5-158.0° C. 1H NMR (300 MHz, d6-DMSO) δ 8.27 (dm, J=8.4 Hz, 1H), 7.59 (dd, J=8.4, 1.2 Hz, 1H), 7.40 (m, 1H), 7.20 (m, 1H), 6.54 (br s, 2H), 4.89 (br s, 2H), 4.82 (br s, 2H), 4.78 (s, 1H), 3.52 (q, J=7.0 Hz, 2H), 1.75-1.43 (m, 8H), 1.14 (t, J=7.0 Hz, 3H). MS (APCI) m/z 341 (M+H+). Anal. calcd for C19H24N4O2: C, 67.04; H, 7.11; N, 16.46. Found: C, 67.12; H, 6.94; N, 16.36.
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][C:7]([C:10]2[O:11][C:12]3[CH:13]=[N:14][CH:15]=[CH:16][C:17]=3[N:18]=2)=[CH:6][CH:5]=1)([O-])=O.[NH4+].[Cl-].O>[Fe].CO>[N:18]1[C:17]2[CH:16]=[CH:15][N:14]=[CH:13][C:12]=2[O:11][C:10]=1[C:7]1[CH:6]=[CH:5][C:4]([NH2:1])=[CH:9][CH:8]=1
Reactant: O=[N+]([O-])c1ccc(-c2nc3ccncc3o2)cc1
Agent: [Fe]
Agent: [Cl-]
Agent: [NH4+]
Solvent: O
Solvent: CO
Product: Nc1ccc(-c2nc3ccncc3o2)cc1
Yield: 64.4 %

Procedure:
A mixture of 2-(4-nitrophenyl)oxazolo[5,4-c]pyridine (610 mg, 2.5 mmol), NH4Cl (1.2 g, 22.4 mmol), iron powder (0.76 g, 13.6 mmol), H2O (13 mL) and methanol (51 mL) was heated to reflux for 6 h under N2. The mixture was concentrated in vacuo and purified by chromatography on silica gel (eluted with EA/PE=3:1) to give 4-(oxazolo[5,4-c]pyridin-2-yl)benzenamine as light brown powder (340 mg, yield 64%). 1H NMR (400MHz, DMSO-d6) δ:8.95 (1H, s); 8.46 (1H, d, J=5.2); 7.92 (2H, d, J=8.8); 7.69 (1H,d, J=5.6), 6.71 (2H,d, J=8.8), 6.19 (2H, s); MS(ESI) calcd for C12H9N3O (m/z): 211, found: 212 [M+H]+.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][CH2:10][OH:11])[CH:5]=[CH:6][C:7]=1[Cl:8].Cl[C:13]1[CH:29]=[C:17]2[N:18](C(OC(C)(C)C)=O)[CH2:19][CH2:20][CH2:21][N:16]2[C:15](=[O:30])[N:14]=1>>[Cl:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][C:7]=1[Cl:8])[CH2:9][CH2:10][O:11][C:13]1[CH:29]=[C:17]2[NH:18][CH2:19][CH2:20][CH2:21][N:16]2[C:15](=[O:30])[N:14]=1
Reactant: OCCc1ccc(Cl)c(Cl)c1
Reactant: CC(C)(C)OC(=O)N1CCCn2c1cc(Cl)nc2=O
Product: O=c1nc(OCCc2ccc(Cl)c(Cl)c2)cc2n1CCCN2

Procedure:
The title compound or its salt was prepared by a procedure similar to that described for E111 starting from 2-(3,4-dichlorophenyl)ethanol and tert-butyl 8-chloro-6-oxo-2,3,4,6-tetrahydro-1H-pyrimido[1,6-a]pyrimidine-1-carboxylate.
Reaction SMILES: [Br-].[C:2]1(C([PH3+])(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C([Li])CCC.[C:27]([C:32]([C:41]([O:43][CH2:44][CH3:45])=[O:42])([CH2:38][CH:39]=[CH2:40])[CH2:33][CH2:34][C:35](=O)[CH3:36])([O:29][CH2:30][CH3:31])=[O:28]>C1COCC1>[CH2:38]([C:32]([CH2:33][CH2:34][C:35]([CH3:2])=[CH2:36])([C:41]([O:43][CH2:44][CH3:45])=[O:42])[C:27]([O:29][CH2:30][CH3:31])=[O:28])[CH:39]=[CH2:40]
Reactant: [PH3+]C(c1ccccc1)(c1ccccc1)c1ccccc1
Reactant: C=CCC(CCC(C)=O)(C(=O)OCC)C(=O)OCC
Agent: [Br-]
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: C=CCC(CCC(=C)C)(C(=O)OCC)C(=O)OCC
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 89.1 %

Procedure:
To a THF suspension (4.2 ml) containing triphenylmethylphosphonium bromide (0.536 g, 1.5 mmol) was added dropwise at 0° C. butyl lithium (1.4 mmol in 0.88 ml of 1.6M hexane solution). The reaction liquid was stirred at 0° C. for 30 minutes and then given 5,5-dicarboethoxy-7-octen-2-on (0.27 g, 1.0 mmol), followed by stirring at 0° C. for 1 hour. After treatment and purification as in Referential Example 9, there was obtained 0.239 g of diethyl allyl(3-methyl-3-butenyl)malonate (yields: 89%). Characteristic Values of allyl(3-methyl-3-butenyl)malonate
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[CH:9][CH2:10][OH:11])=[CH:4][CH:3]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH2:37]([O:39][C:40](=[O:53])[C@@H:41]([O:50][CH2:51][CH3:52])[CH2:42][C:43]1[CH:48]=[CH:47][C:46](O)=[CH:45][CH:44]=1)[CH3:38].N(C(OCC)=O)=NC(OCC)=O>>[CH2:37]([O:39][C:40](=[O:53])[C@@H:41]([O:50][CH2:51][CH3:52])[CH2:42][C:43]1[CH:48]=[CH:47][C:46]([O:11][CH2:10]/[CH:9]=[C:8](\[C:5]2[CH:4]=[CH:3][C:2]([Br:1])=[CH:7][CH:6]=2)/[C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=2)=[CH:45][CH:44]=1)[CH3:38]
Reactant: OCC=C(c1ccccc1)c1ccc(Br)cc1
Reactant: CCOC(=O)[C@H](Cc1ccc(O)cc1)OCC
Agent: CCOC(=O)N=NC(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Product: CCOC(=O)[C@H](Cc1ccc(OC/C=C(/c2ccccc2)c2ccc(Br)cc2)cc1)OCC
Yield: 43.2 %

Procedure:
Reaction of 3-(4-bromophenyl)-3-phenyl-prop-2-en-1-ol (145 mg, 0.50 mmol), triphenylphosphine (144 mg, 0.55 mmol), (2S)-2-ethoxy-3-(4-hydroxy-phenyl)-propionic acid ethyl ester (119 mg, 0.50 mmol) and diethyl azodicarboxylate (96 mg, 0.55 mmol) in an identical manner to example 1 gave the title compound (110 mg, 43%).
Reaction SMILES: [OH:1][CH2:2][P:3]([CH2:6][OH:7])(=[O:5])[OH:4].[OH-].[CH2:9]([N+:13]([CH2:22][CH2:23][CH2:24][CH3:25])([CH2:18][CH2:19][CH2:20][CH3:21])[CH2:14][CH2:15][CH2:16][CH3:17])[CH2:10][CH2:11][CH3:12]>O.CC(O)C>[OH:1][CH2:2][P:3]([CH2:6][OH:7])(=[O:4])[O-:5].[CH2:22]([N+:13]([CH2:9][CH2:10][CH2:11][CH3:12])([CH2:14][CH2:15][CH2:16][CH3:17])[CH2:18][CH2:19][CH2:20][CH3:21])[CH2:23][CH2:24][CH3:25]
Reactant: O=P(O)(CO)CO
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [OH-]
Solvent: O
Solvent: CC(C)O
Product: O=P([O-])(CO)CO

Procedure:
To a flask were added 0.48 g bis(hydroxymethyl)phosphinic acid, 1.6 g of a 55-60% solution of tetrabutylammonium hydroxide in water and 10 ml 2-propanol. After heating to 50 C under nitrogen for 1 hour, the solvent was removed and another 10 ml of 2 propanol were added and removed by distillation under reduced pressure. An oil was obtained.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][C:5]([S:8](Cl)(=[O:10])=[O:9])=[CH:4][CH:3]=1.[NH2:12][C:13]1[CH:14]=[C:15]([CH:19]2[CH2:28][C:27]([CH3:30])([CH3:29])[C:26]3[C:21](=[CH:22][CH:23]=[C:24]([C:31]#[N:32])[CH:25]=3)[NH:20]2)[CH:16]=[CH:17][CH:18]=1.N1C=CC=CC=1>ClCCl>[C:31]([C:24]1[CH:25]=[C:26]2[C:21](=[CH:22][CH:23]=1)[NH:20][CH:19]([C:15]1[CH:14]=[C:13]([NH:12][S:8]([C:5]3[CH:6]=[CH:7][C:2]([CH3:1])=[CH:3][CH:4]=3)(=[O:10])=[O:9])[CH:18]=[CH:17][CH:16]=1)[CH2:28][C:27]2([CH3:30])[CH3:29])#[N:32]
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Reactant: CC1(C)CC(c2cccc(N)c2)Nc2ccc(C#N)cc21
Solvent: ClCCl
Solvent: c1ccncc1
Product: Cc1ccc(S(=O)(=O)Nc2cccc(C3CC(C)(C)c4cc(C#N)ccc4N3)c2)cc1
Reaction time: 8 h
Yield: 38.6 %

Procedure:
4-Methyl-benzenesulfonyl chloride (103 mg, 0.54 mmol) was added dropwise to a mixture of 2-(3-amino-phenyl)-4,4-dimethyl-1,2,3,4-tetrahydro-quinoline-6-carbonitrile (100 mg, 0.36 mmol) and pyridine (51 mg, 0.65 mmol) in dichloromethane (5 mL). The resultant mixture was allowed to stir overnight. The reaction mixture was washed by water, dried over magnesium sulfate. Filtered and concentrated to provide the crude product. It was purified by column chromatography (silica gel, petroleum ether:ethyl acetate=5:1) to afford N-[3-(6-cyano-4,4-dimethyl-1,2,3,4-tetrahydro-quinolin-2-yl)-phenyl]-4-methyl-benzenesulfonamide as off-white solid (60 mg, yield: 38.6%). MS (ESI+APCI) M+1=432.2.
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][CH:4]([C:7]2[CH:15]=[CH:14][CH:13]=[C:12]3[C:8]=2[CH2:9][C:10](=[O:16])[NH:11]3)[CH2:3][CH2:2]1.[N:17]1[CH:22]=[CH:21][C:20]([CH2:23][NH:24][C:25]([C:27]2[C:31]([CH3:32])=[C:30]([CH:33]=O)[NH:29][CH:28]=2)=[O:26])=[CH:19][CH:18]=1>N1CCCCC1.C(O)C>[N:17]1[CH:18]=[CH:19][C:20]([CH2:23][NH:24][C:25]([C:27]2[C:31]([CH3:32])=[C:30]([CH:33]=[C:9]3[C:8]4[C:12](=[CH:13][CH:14]=[CH:15][C:7]=4[CH:4]4[CH2:3][CH2:2][NH:1][CH2:6][CH2:5]4)[NH:11][C:10]3=[O:16])[NH:29][CH:28]=2)=[O:26])=[CH:21][CH:22]=1
Reactant: O=C1Cc2c(cccc2C2CCNCC2)N1
Reactant: Cc1c(C(=O)NCc2ccncc2)c[nH]c1C=O
Solvent: CCO
Solvent: C1CCNCC1
Product: Cc1c(C(=O)NCc2ccncc2)c[nH]c1C=C1C(=O)Nc2cccc(C3CCNCC3)c21
Temperature: 25 °C
Reaction time: 168 h

Procedure:
A mixture of 4-piperidin-4-yl-1,3-dihydroindol-2-one (54 mg, 0.25 mmol), 5-formyl-4-methyl-1H-pyrrole-3-carboxylic acid (pyridin-4-ylmethyl)-amide (64 mg, 0.2625 mmol) and piperidine (2 drops) in ethanol (0.5 mL) was stirred at room temperature for 7 days. The precipitate which formed was collected by vacuum filtration, washed with ethanol and dried to give the title compound.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([CH3:12])[C:5]([C:8](OC)=[O:9])=[N:6][CH:7]=1.BrN1C(=O)CCC1=O.C(OOC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1.[NH2:39][NH2:40]>C(Cl)(Cl)(Cl)Cl.CO>[Br:1][C:2]1[CH:7]=[N:6][C:5]2[C:8](=[O:9])[NH:39][N:40]=[CH:12][C:4]=2[CH:3]=1
Reactant: NN
Reactant: COC(=O)c1ncc(Br)cc1C
Agent: O=C(OOC(=O)c1ccccc1)c1ccccc1
Agent: O=C1CCC(=O)N1Br
Solvent: ClC(Cl)(Cl)Cl
Solvent: CO
Product: O=c1[nH]ncc2cc(Br)cnc12
Temperature: 77 °C

Procedure:
To a solution of methyl 5-bromo-3-methylpicolinate (1.785 g, 7.76 mmol) in 30 mL of CCl4 was added N-bromosuccinimide (4.23 g, 23.8 mmol) and benzoyl peroxide (0.199 g, 0.822 mmol). The reaction was heated at 77° C. for 6 h. The reaction mixture was cooled to RT, filtered through a pad of Celite and washed with CCl4. The filtrate was evaporated in vacuo to give a yellow oil. The oil was dissolved in 40 mL MeOH and anhydrous hydrazine (3.00 ml, 95.6 mmol) was added dropwise at 25° C. Upon complete addition the reaction mixture was heated at 78° C. overnight. The reaction mixture was cooled to RT and the solid was filtered, washed with MeOH and CHCl3 and dried by suction. The filtrate was evaporated onto silica gel and purified flash chromatography eluting with 2M NH3 in MeOH:CHCl3 (0:1→3:47) to give the title compound as a light-yellow amorphous solid. MS m/z: 225.9, 227.9 [M+1].