Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [S:1]1[CH:5]=[CH:4][C:3]([CH2:6][C:7]#[N:8])=[CH:2]1.Br[CH2:10][CH2:11]Cl.[H-].[Na+].Cl>CS(C)=O.O>[S:1]1[CH:5]=[CH:4][C:3]([C:6]2([C:7]#[N:8])[CH2:11][CH2:10]2)=[CH:2]1
Reactant: N#CCc1ccsc1
Reactant: ClCCBr
Agent: Cl
Agent: [H-]
Agent: [Na+]
Solvent: CS(C)=O
Solvent: O
Product: N#CC1(c2ccsc2)CC1

Procedure:
A solution of thiophene-3-acetonitrile (30 g) and 1-bromo-2-chloroethane (40.8 ml) in dimethyl sulphoxide (120 ml) was added slowly dropwise to a well stirred suspension of sodium hydride (60% dispersion in mineral oil; 38.8 g) in dimethyl sulphoxide (800 ml) at 30°-35° C. The solution was stirred at ambient temperature for 21 hours then water (100 ml) was carefully added followed by hydrochloric acid (2M; 100 ml). The mixture was extracted with ether (6×80 ml) and the combined extracts washed with water (2×100 ml) then brine and then dried over magnesium sulphate. The solvent was removed in vacuo and the residue washed with petroleum ether (bp 60°-80° C.) before distillation under reduced pressure which gave 1-(3-thienyl)cyclopropanecarbonitrile as an oil (26.3 g), bp 82°-86° C./2 mbar.
Reaction SMILES: [C:1]1([CH2:7][C:8]#[N:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CC1C=CC(S(O[CH2:21][C@@H:22]([OH:32])[CH2:23][O:24][CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)(=O)=O)=CC=1.C([Li])CCC>C1COCC1.CCOC(C)=O>[OH:32][C@@H:22]([CH2:23][O:24][CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)[CH2:21][CH:7]([C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1)[C:8]#[N:9]
Reactant: N#CCc1ccccc1
Reactant: Cc1ccc(S(=O)(=O)OC[C@@H](O)COCc2ccccc2)cc1
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: N#CC(C[C@@H](O)COCc1ccccc1)c1ccccc1
Temperature: -78 °C
Reaction time: 4 h

Procedure:
Phenylacetonitrile (4.59 g, 39.2 mmol) and (2S)-2-hydroxy-3-[(phenylmethyl)oxy]propyl 4-methylbenzenesulfonate (13.20 g, 39.2 mmol, 1 eq) were dissolved in 50 mL THF, cooled to −78° C., and treated with 2.5M butyllithium in hexanes (35 mL, 86.3 mmol, 2.2 eq) added dropwise over 30 min. The reaction mixture was stirred 4 h at −78° C., allowed to warm to ambient temperature and stirred an additional 16 h. The reaction mixture was diluted with EtOAc, washed successively with water and brine, dried over MgSO4, filtered and concentrated to give the diastereomeric product as an orange oil in quantitative yield which was carried on without purification. ES-LCMS m/z 304.33 (M+Na).
Reaction SMILES: Cl.[CH3:2][N:3]([CH3:23])[S:4]([C:7]1[CH:8]=[C:9]([CH:13]=[CH:14][C:15]=1[N:16]1[CH2:21][CH2:20][N:19]([CH3:22])[CH2:18][CH2:17]1)[C:10](Cl)=[O:11])(=[O:6])=[O:5].[CH2:24]([NH:31][CH2:32][C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.C(N(CC)CC)C>O1CCCC1.[OH-].[Na+]>[CH2:32]([N:31]([CH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)[C:10](=[O:11])[C:9]1[CH:13]=[CH:14][C:15]([N:16]2[CH2:21][CH2:20][N:19]([CH3:22])[CH2:18][CH2:17]2)=[C:7]([S:4](=[O:6])(=[O:5])[N:3]([CH3:23])[CH3:2])[CH:8]=1)[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1
Reactant: CN1CCN(c2ccc(C(=O)Cl)cc2S(=O)(=O)N(C)C)CC1
Reactant: c1ccc(CNCc2ccccc2)cc1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: CN1CCN(c2ccc(C(=O)N(Cc3ccccc3)Cc3ccccc3)cc2S(=O)(=O)N(C)C)CC1

Procedure:
40 Grams of 3-dimethylsulfamoyl-4-(4-methylpiperazine-1-yl)-benzoylchloride-hydrochloride (0.1 mole) were added portionwise at room temperature, while stirring, to a solution of 22 g of dibenzylamine and 20 g of triethylamine in 0.2 l of tetrahydrofurane. Subsequently the reaction mixture was heated for another hour under reflux, and then the tetrahydrofurane was eliminated in vacuo. The amorphous residue was dispersed in 0.5 l of acetic ester and 0.5 l of 1N NaOH. The acetic ester phase was separated and was dried over magnesium sulfate. The acetic ester solution was then concentrated to half its volume and was mixed with the same volume of petroleum ether under heat. Upon trituration the final product crystallized and was suction-filtered after having been cooled with ice water for 1 hour.
Reaction SMILES: C([O:3][C:4](=[O:44])[CH:5]([C:10]1[CH:11]=[C:12]([C:34]2[CH:39]=[CH:38][C:37]([C:40]([F:43])([F:42])[F:41])=[CH:36][CH:35]=2)[CH:13]=[C:14]([CH:16]2[CH2:21][CH2:20][CH2:19][N:18]([C:22](=[O:33])[C:23]3[CH:28]=[CH:27][C:26]([C:29]([F:32])([F:31])[F:30])=[CH:25][CH:24]=3)[CH2:17]2)[CH:15]=1)[CH2:6][CH:7]([CH3:9])[CH3:8])C.[OH-].[K+]>CCO>[CH3:8][CH:7]([CH3:9])[CH2:6][CH:5]([C:10]1[CH:11]=[C:12]([C:34]2[CH:39]=[CH:38][C:37]([C:40]([F:43])([F:41])[F:42])=[CH:36][CH:35]=2)[CH:13]=[C:14]([CH:16]2[CH2:21][CH2:20][CH2:19][N:18]([C:22](=[O:33])[C:23]3[CH:28]=[CH:27][C:26]([C:29]([F:31])([F:32])[F:30])=[CH:25][CH:24]=3)[CH2:17]2)[CH:15]=1)[C:4]([OH:44])=[O:3]
Reactant: CCOC(=O)C(CC(C)C)c1cc(-c2ccc(C(F)(F)F)cc2)cc(C2CCCN(C(=O)c3ccc(C(F)(F)F)cc3)C2)c1
Agent: [K+]
Agent: [OH-]
Solvent: CCO
Product: CC(C)CC(C(=O)O)c1cc(-c2ccc(C(F)(F)F)cc2)cc(C2CCCN(C(=O)c3ccc(C(F)(F)F)cc3)C2)c1
Temperature: 78 °C

Procedure:
To a solution of compound 43a, 4-Methyl-2-{4′-trifluoromethyl-5-[1-(4-trifluoromethyl-benzoyl)-piperidin-3-yl]-biphenyl-3-yl}-pentanoic acid ethyl ester 60.0 mg, 0.097 mmol) in EtOH (4.8 ml) was added 2M KOH (0.48 ml, 0.48 mmol). The reaction was heated to 78° C. for 1.5 hours, cooled to room temperature, and concentrated in vacuo. Purification via Gilson HPLC, gave the product as a white lyophilate, (21.7 mg, 38%). 1H NMR (300 MHz, MeOD) δ ppm 0.88-0.96 (m, 6 H) 1.42-2.15 (m, 6 H) 2.70-3.24 (m, 3 H) 3.66-3.80 (m, 3 H) 4.68-7.71 (m, 1 H) 7.17 (s, 1 H) 7.32-7.81 (m, 10 H), Calcd for C32H31F6NO3 (M+H) 591.58, Found 592.3.
Reaction SMILES: [I:1][C:2]1[N:11]=[C:10]2[N:4]([CH2:5][CH2:6][C:7]3[CH:23]=[CH:22][CH:21]=[CH:20][C:8]=3[CH:9]2[O:12][CH:13]2[CH2:18][CH2:17][N:16]([CH3:19])[CH2:15][CH2:14]2)[C:3]=1[C:24]#[N:25].[OH-].[Na+].OO.[O-:30]S([O-])(=S)=O.[Na+].[Na+]>CO>[I:1][C:2]1[N:11]=[C:10]2[N:4]([CH2:5][CH2:6][C:7]3[CH:23]=[CH:22][CH:21]=[CH:20][C:8]=3[CH:9]2[O:12][CH:13]2[CH2:14][CH2:15][N:16]([CH3:19])[CH2:17][CH2:18]2)[C:3]=1[C:24]([NH2:25])=[O:30]
Reactant: CN1CCC(OC2c3ccccc3CCn3c2nc(I)c3C#N)CC1
Reactant: O=S([O-])([O-])=S
Agent: OO
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: CN1CCC(OC2c3ccccc3CCn3c2nc(I)c3C(N)=O)CC1
Temperature: 0 °C
Reaction time: 1 h

Procedure:
To a solution of 2-iodo-4-(1-methylpiperidin-4-yloxy)-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulene-1-carbonitrile (example 221A) (220 mg, 0.5 mmole) in MeOH (3 mL) cooled at 0° C. is added dropwise a solution of 1N NaOH (1 mL) and 30% H2O2 (0.1 mL). The reaction mixture is stirred at 0° C. for 1 hour, then aqueous 1N Na2S2O3 is added. The aqueous phase is extracted with AcOEt. The organic phase is dried over MgSO4, filtered and the solvent removed under reduced pressure. The residue is purified by silica gel chromatography eluting with (CH2Cl2:MeOH:NH4OH) from (100:0:0) to (90:10:1) to give 2-iodo-4-(1-methylpiperidin-4-yloxy)-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulene-1-carboxylic acid amide melting at 85° C.
Reaction SMILES: Cl[CH2:2][C:3]1[CH:28]=[CH:27][C:6]([O:7][CH2:8][C:9]2[N:10]=[C:11]([C:15]3[CH:20]=[CH:19][C:18]([CH2:21][C:22]([O:24][CH2:25][CH3:26])=[O:23])=[CH:17][CH:16]=3)[O:12][C:13]=2[CH3:14])=[C:5]([O:29][CH3:30])[CH:4]=1.Cl.[CH:32]([C:35]1[O:36][CH:37]=[C:38](/[CH:40]=[CH:41]/[C:42]2[C:43]([OH:53])=[N:44][N:45]([C:47]3[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=3)[CH:46]=2)[N:39]=1)([CH3:34])[CH3:33].C(=O)([O-])[O-].[K+].[K+].CN(C)C=O>O>[CH:32]([C:35]1[O:36][CH:37]=[C:38](/[CH:40]=[CH:41]/[C:42]2[C:43]([O:53][CH2:2][C:3]3[CH:28]=[CH:27][C:6]([O:7][CH2:8][C:9]4[N:10]=[C:11]([C:15]5[CH:20]=[CH:19][C:18]([CH2:21][C:22]([O:24][CH2:25][CH3:26])=[O:23])=[CH:17][CH:16]=5)[O:12][C:13]=4[CH3:14])=[C:5]([O:29][CH3:30])[CH:4]=3)=[N:44][N:45]([C:47]3[CH:48]=[CH:49][CH:50]=[CH:51][CH:52]=3)[CH:46]=2)[N:39]=1)([CH3:34])[CH3:33]
Reactant: CC(C)c1nc(/C=C/c2cn(-c3ccccc3)nc2O)co1
Reactant: CCOC(=O)Cc1ccc(-c2nc(COc3ccc(CCl)cc3OC)c(C)o2)cc1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: CCOC(=O)Cc1ccc(-c2nc(COc3ccc(COc4nn(-c5ccccc5)cc4/C=C/c4coc(C(C)C)n4)cc3OC)c(C)o2)cc1
Temperature: 90 °C
Reaction time: 1.5 h
Yield: 15.6 %

Procedure:
A mixture of ethyl (4-{4-[(4-chloromethyl-2-methoxyphenoxy)methyl]-5-methyl-1,3-oxazol-2-yl}phenyl)acetate (0.976 g), 4-[(E)-2-(2-isopropyl-1,3-oxazol-4-yl)ethenyl]-1-phenyl-1H-pyrazol-3-ol hydrochloride (0.83 g), potassium carbonate (0.691 g) and N,N-dimethylformamide (20 mL) was stirred at 90° C. for 1.5 hrs. Water was poured into the reaction mixture, and the mixture was extracted with ethyl acetate-tetrahydrofuran. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate and concentrated. The residue was subjected to silica gel column chromatography and eluted with acetone-hexane (1:5-1:4-1:3, v/v) to give ethyl {4-[4-({4-[({4-[(E)-2-(2-isopropyl-1,3-oxazol-4-yl)ethenyl]-1-phenyl-1H-pyrazol-3-yl}oxy)methyl]-2-methoxyphenoxy}methyl)-5-methyl-1,3-oxazol-2-yl]phenyl}acetate (244 mg, yield 16%) as colorless crystals. Recrystallization from acetone-hexane gave colorless prism crystals. melting point: 106-108° C.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]([C:15]2[N:16]([CH3:41])[C:17]3[C:22]([N:23]=2)=[C:21]([N:24]2[CH2:29][CH2:28][O:27][CH2:26][CH2:25]2)[N:20]=[C:19]([N:30]2[C:34]4[CH:35]=[CH:36][CH:37]=[CH:38][C:33]=4[N:32]=[C:31]2[CH2:39][CH3:40])[N:18]=3)([OH:14])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].I[CH3:45]>C1COCC1.C1OCCOCCOCCOCCOC1>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][C:11]([C:15]2[N:16]([CH3:41])[C:17]3[C:22]([N:23]=2)=[C:21]([N:24]2[CH2:25][CH2:26][O:27][CH2:28][CH2:29]2)[N:20]=[C:19]([N:30]2[C:34]4[CH:35]=[CH:36][CH:37]=[CH:38][C:33]=4[N:32]=[C:31]2[CH2:39][CH3:40])[N:18]=3)([O:14][CH3:45])[CH2:12][CH2:13]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: CI
Reactant: CCc1nc2ccccc2n1-c1nc(N2CCOCC2)c2nc(C3(O)CCN(C(=O)OC(C)(C)C)CC3)n(C)c2n1
Agent: C1COCCOCCOCCOCCO1
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: CCc1nc2ccccc2n1-c1nc(N2CCOCC2)c2nc(C3(OC)CCN(C(=O)OC(C)(C)C)CC3)n(C)c2n1
Reaction time: 20 h
Yield: 68.7 %

Procedure:
To a solution of 4-[2-(2-ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purin-8-yl]-4-hydroxypiperidine-1-carboxylic acid tert-butyl ester (1.3 g, 2.31 mmol) in THF (50 mL) was added NaH (112 mg, 2.80 mmol, 60% dispersion in mineral oil) and the resulting mixture allowed to stir for 5 min before the addition of iodomethane (175 μL, 2.80 mmol) and 15-Crown-5 (5 drops). The resulting mixture was stirred for 20 h quenched with H2O and extracted with 2-methyl THF. The organic phase was washed with brine, then dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, EtOAc:cyclohexane, 40-80%) affording 4-[2-(2-Ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purin-8-yl]-4-methoxypiperidine-1-carboxylic acid tert-butyl ester (915 mg, 69%). LCMS (method H): RT 3.40 min [M+H]+ 577.5
Reaction SMILES: [CH3:1][N:2]([CH3:21])[CH2:3][CH2:4][NH:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:19]=[CH:18][C:17](F)=[CH:16][CH:15]=2)[CH2:10][CH2:9]1)=[O:7].CN(CCN)C.[CH3:28][O:29]C1C=CC=CC=1N1CCNCC1>O1CCCC1>[CH3:1][N:2]([CH3:21])[CH2:3][CH2:4][NH:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[O:29][CH3:28])[CH2:10][CH2:9]1)=[O:7]
Reactant: CN(C)CCNC(=O)N1CCN(c2ccc(F)cc2)CC1
Reactant: COc1ccccc1N1CCNCC1
Agent: CN(C)CCN
Solvent: C1CCOC1
Product: COc1ccccc1N1CCN(C(=O)NCCN(C)C)CC1
Yield: 49 %

Procedure:
This compound was prepared according to the procedure used to synthesize the compound of Example 11. A mixture of 4.9 g (0.03 mole) of 1,1'-carbonydiimidazole, 2.6 g (0.03 mole) of unsym-dimethylethylenediamine and 5.8 g (0.03 mole) of 1-(2-methoxyphenyl)piperazine in a total volume of 200 ml of tetrahydrofuran gave an oil which solidified. After trituration with petroleum ether (30°-60° C.), the collected solid was recrystallized from benzene-petroleum ether to yield 4.5 g (49%) of the title compound as an off-white solid, m.p. 98°-100° C.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:12]2[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=2)[C:9]([OH:11])=O)=[CH:4][CH:3]=1.[NH2:19][CH2:20][CH2:21][CH2:22][N:23]1[CH2:28][CH2:27][CH:26]([C:29]2[CH:30]=[C:31]([NH:35][C:36](=[O:40])[CH2:37][CH2:38][CH3:39])[CH:32]=[CH:33][CH:34]=2)[CH2:25][CH2:24]1>>[F:18][C:15]1[CH:16]=[CH:17][C:12]([CH:8]([C:5]2[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=2)[C:9]([NH:19][CH2:20][CH2:21][CH2:22][N:23]2[CH2:28][CH2:27][CH:26]([C:29]3[CH:30]=[C:31]([NH:35][C:36](=[O:40])[CH2:37][CH2:38][CH3:39])[CH:32]=[CH:33][CH:34]=3)[CH2:25][CH2:24]2)=[O:11])=[CH:13][CH:14]=1
Reactant: CCCC(=O)Nc1cccc(C2CCN(CCCN)CC2)c1
Reactant: O=C(O)C(c1ccc(F)cc1)c1ccc(F)cc1
Product: CCCC(=O)Nc1cccc(C2CCN(CCCNC(=O)C(c3ccc(F)cc3)c3ccc(F)cc3)CC2)c1

Procedure:
Example 27 was prepared from bis(4-fluorophenyl)acetic acid and N-{3-[1-(3-aminopropyl)-4-piperidinyl]phenyl}butanamide according to the procedures described in Scheme 10: 1H NMR (400 MHz, CDCl3) δ 8.14 (s, 1H), 7.69 (t, 1H, J=5.2 Hz), 7.52 (s, 1H), 7.38 (d, 1H, J=8.0 Hz), 7.30–7.27 (m, 4H), 7.20 (t, 1H, J=8.0 Hz), 7.00–6.95 (m, 4H), 6.89 (d, 1H, J=8.0 Hz), 4.90 (s, 1H), 3.37 (dd, 2H, J=6.0, 11.6 Hz), 3.05 (d, 2H, J=11.2 Hz), 2.55 (t, 2H, J=6.8 Hz), 2.49 (m, 1H), 2.33 (t, 2H, J=7.2 Hz), 2.17 (m, 2H), 1.79–1.69 (m, 8H), 0.97 (t, 3H, J=7.6 Hz); ESMS m/e: 534.4 (M+H)+.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[C:11]([N:13]1[CH2:17][CH:16]=[CH:15][CH2:14]1)=[O:12])[C:5]([OH:7])=O.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.C(N(C(C)C)CC)(C)C.[Cl:49][C:50]1[CH:62]=[CH:61][C:53]2[NH:54][C:55]([C@@H:57]([NH2:60])[CH2:58][OH:59])=[N:56][C:52]=2[CH:51]=1.ClBr>O1CCCC1.ClCCl.CO>[Br:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[C:11]([N:13]1[CH2:17][CH:16]=[CH:15][CH2:14]1)=[O:12])[C:5]([NH:60][C@H:57]([C:55]1[NH:54][C:53]2[CH:61]=[CH:62][C:50]([Cl:49])=[CH:51][C:52]=2[N:56]=1)[CH2:58][OH:59])=[O:7]
Reactant: O=C(O)c1ccc(C(=O)N2CC=CC2)c(Br)c1
Reactant: N[C@@H](CO)c1nc2cc(Cl)ccc2[nH]1
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: ClBr
Agent: F[B-](F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Solvent: C1CCOC1
Product: O=C(N[C@@H](CO)c1nc2cc(Cl)ccc2[nH]1)c1ccc(C(=O)N2CC=CC2)c(Br)c1
Yield: 84 %

Procedure:
Prepared analogously to Example 1g from 3-bromo-4-(2,5-dihydropyrrol-1-ylcarbonyl)benzoic acid, TBTU, diisopropylethylamine, and (1R)-1-(5-chloro-1H-benzimidazol-2-yl)-2-hydroxyethylamine in tetrahydrofuran. Yield: 84%; Rf value: 0.40 (silica gel; dichloromethane/methanol=95:5); C21H18BrClN4O3 (489.76); mass spectrum: (M+H)+=489/491/493 (chlorobromine isotope).
Reaction SMILES: [O:1]1[CH2:6][CH2:5][CH:4]([N:7]2[CH2:11][CH2:10][CH2:9][C@H:8]2[C:12]([OH:14])=O)[CH2:3][CH2:2]1.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)C.[CH3:47][C:48]([C:58]1[CH:62]=[C:61]([NH2:63])[O:60][N:59]=1)([CH3:57])[CH2:49][O:50][CH:51]1[CH2:56][CH2:55][CH2:54][CH2:53][O:52]1.[H-].[Na+]>CN(C)C=O>[CH3:57][C:48]([C:58]1[CH:62]=[C:61]([NH:63][C:12]([C@@H:8]2[CH2:9][CH2:10][CH2:11][N:7]2[CH:4]2[CH2:3][CH2:2][O:1][CH2:6][CH2:5]2)=[O:14])[O:60][N:59]=1)([CH3:47])[CH2:49][O:50][CH:51]1[CH2:56][CH2:55][CH2:54][CH2:53][O:52]1
Reactant: O=C(O)[C@@H]1CCCN1C1CCOCC1
Reactant: CC(C)(COC1CCCCO1)c1cc(N)on1
Agent: CCN(CC)C(C)C
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Product: CC(C)(COC1CCCCO1)c1cc(NC(=O)[C@@H]2CCCN2C2CCOCC2)on1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 17.7 %

Procedure:
(S)-1-(Tetrahydro-pyran-4-yl)-pyrrolidine-2-carboxylic acid (0.2 g; 1.004 mmol) is dissolved in 5 mL of dimethyl formamide and O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium PF6 (0.573 g, 1.506 mmol) and diethylisopropyl amine (0.626 mL, 3.514 mmol) are added. The mixture is stirred at room temperature for 30 minutes. 3-[1,1-dimethyl-2-(tetrahydro-pyran-2-yloxy)-ethyl]isoxazole-5-yl amine (0.241 g, 1.004 mmol) is dissolved in 5 mL of dimethylformamide and sodium hydride (60% in mineral oil, 0.1 g, 2.510 mmol) is added at 0° C. The above solution is added and the mixture warmed to room temperature and stirred for 1 h. The reaction is quenched with water and methanol and concentrated under reduced pressure. The crude mixture is purified by flash chromatraphy (SiO2) to afford 0.075 g of title compound as an oil. 18% yield, ESI m/z 422=MH+.
Reaction SMILES: C(=O)([O-])[O-].[K+].[K+].[CH2:7](Br)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.CN(C)C=O.[CH3:20][C:21]1[NH:22][C:23]2[C:28]([C:29]=1[CH2:30][C:31]([OH:33])=[O:32])=[CH:27][CH:26]=[CH:25][CH:24]=2>O>[CH2:7]([O:33][C:31](=[O:32])[CH2:30][C:29]1[C:28]2[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=2)[NH:22][C:21]=1[CH3:20])[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1
Reactant: BrCc1ccccc1
Reactant: Cc1[nH]c2ccccc2c1CC(=O)O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: Cc1[nH]c2ccccc2c1CC(=O)OCc1ccccc1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
Under argon gas, potassium carbonate (2.52 g) and benzyl bromide (1.2 mL) were added to dimethyl formamide (20 mL) solution containing 2-(2-methylindol-3-yl)acetic acid (1.73 g), which was stirred at room temperature for 2 hours. The reaction mixture was radiationally cooled and water was added, and then the mixture was extracted by ethyl acetate. The extract was sequentially washed with water and saturated brine and dried by sulfuric anhydride sodium, and concentrated. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=4:1) to give a title compound (2.63 g) having the following physical properties was obtained.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:9]=[CH:10][C:11]=1[O:12][CH3:13])[C:6]([NH2:8])=[NH:7].[CH:14](=[C:21]([C:24]#[N:25])[C:22]#[N:23])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1>>[NH2:25][CH2:24][C:21]1[C:22]([NH2:23])=[N:7][C:6]([C:5]2[CH:9]=[CH:10][C:11]([O:12][CH3:13])=[C:3]([O:2][CH3:1])[CH:4]=2)=[N:8][C:14]=1[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1
Reactant: COc1ccc(C(=N)N)cc1OC
Reactant: N#CC(C#N)=Cc1ccccc1
Product: COc1ccc(-c2nc(N)c(CN)c(-c3ccccc3)n2)cc1OC

Procedure:
The title compound, MS: m/e=336.8 (M+H+), was prepared from 3,4-dimethoxybenzamidine and 2-benzylidene-malononitrile in analogy to the process described in Example 11 as a solid.
Reaction SMILES: [N:1]([CH:4]1[C:12]2[C:7](=[C:8]([CH3:13])[CH:9]=[CH:10][CH:11]=2)[CH2:6][CH2:5]1)=[N+]=[N-].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.Cl>C1COCC1.O>[CH3:13][C:8]1[CH:9]=[CH:10][CH:11]=[C:12]2[C:7]=1[CH2:6][CH2:5][CH:4]2[NH2:1]
Reactant: Cc1cccc2c1CCC2N=[N+]=[N-]
Agent: Cl
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Solvent: O
Product: Cc1cccc2c1CCC2N
Temperature: 25 °C

Procedure:
1.0 g (5.8 mmol) 1-azido-4-methyl-indane is treated with 4.54 g (17.3 mmol) triphenylphosphine in 26 ml THF and 1.4 ml H2O at room temperature overnight. Completion of the reaction is achieved by heating up the mixture for additional 2.5 hours. The reaction mixture is then cooled to room temperature and diluted with water. The pH is adjusted to 2 by adding cold (ca 0° C.) aqueous HCl (1M). After extraction with EtOAc the aqueous layer is separated, basified with NaOH (2M) and extracted into EtOAc. The organic layer is then dried (MgSO4) and concentrated in vacuo to give 4-methyl-indan-1-yl-amine as a light yellow liquid.
Reaction SMILES: Br[C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[CH:4][CH:3]=1.BrC1C=CC(N(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[CH3:30][N:31]1[C:35]([Sn](CCCC)(CCCC)CCCC)=[CH:34][CH:33]=[C:32]1[C:49]1[CH:67]=[CH:66][C:52]([N:53]([C:60]2[CH:65]=[CH:64][CH:63]=[CH:62][CH:61]=2)[C:54]2[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=2)=[CH:51][CH:50]=1.CN1C=CC=C1[Sn](CCCC)(CCCC)CCCC>>[C:54]1([N:53]([C:60]2[CH:65]=[CH:64][CH:63]=[CH:62][CH:61]=2)[C:52]2[CH:66]=[CH:67][C:49]([C:32]3[N:31]([CH3:30])[C:35]([C:2]4[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[CH:4][CH:3]=4)=[CH:34][CH:33]=3)=[CH:50][CH:51]=2)[CH:55]=[CH:56][CH:57]=[CH:58][CH:59]=1
Reactant: O=Cc1ccc(Br)cc1
Reactant: CCCC[Sn](CCCC)(CCCC)c1ccc(-c2ccc(N(c3ccccc3)c3ccccc3)cc2)n1C
Agent: Brc1ccc(N(c2ccccc2)c2ccccc2)cc1
Agent: CCCC[Sn](CCCC)(CCCC)c1cccn1C
Product: Cn1c(-c2ccc(C=O)cc2)ccc1-c1ccc(N(c2ccccc2)c2ccccc2)cc1

Procedure:
The compound of the present example was synthesized by the same method as described in example 1, except that 1.85 parts of 4-bromo-benzaldehyde was used to substitute 4-bromo-N,N-diphenylaniline, and 6.63 parts of 4-(1-methyl-5-(tributylstannyl)-1H-pyrrole-2-yl)-N,N-diphenylaniline (13) was used to substitute 1-methyl-2-(tributylstannyl)-1H-pyrrole, wherein 4-(1-methyl-5-(tributylstannyl)-1H-pyrrole-2-yl)-N,N-diphenylaniline (13) was synthesized according to the method illustrated in Armaroli, N.; Balzani, V. Angew. Chem. Int. Ed. 2007, 46, 52.
Reaction SMILES: [NH2:1][C:2](=[C:12](C(OC)=O)[C:13]([O:15][CH3:16])=[O:14])[C:3]1[CH:8]=[CH:7][CH:6]=[C:5]([N+:9]([O-:11])=[O:10])[CH:4]=1.[OH-].[K+]>CO.O>[NH2:1][C:2]([C:3]1[CH:8]=[CH:7][CH:6]=[C:5]([N+:9]([O-:11])=[O:10])[CH:4]=1)=[CH:12][C:13]([O:15][CH3:16])=[O:14]
Reactant: COC(=O)C(C(=O)OC)=C(N)c1cccc([N+](=O)[O-])c1
Agent: [K+]
Agent: [OH-]
Solvent: O
Solvent: CO
Product: COC(=O)C=C(N)c1cccc([N+](=O)[O-])c1
Yield: 52.8 %

Procedure:
A mixture of dimethyl (α-amino-3-nitrobenzylidene)-malonate (120 g) and potassium hydroxide in a mixture of methanol (1.2 l) and water(120 ml) was refluxed for 8 hours. The reaction mixture was concentrated under reduced pressure to a volume of 200 ml. The resulting crystals were collected by filtration and recrystallized from methanol to give methyl 3-amino-3-(3-nitrophenyl)-acrylate (50.2 g).
Reaction SMILES: [OH:1][C:2]1[C:7]([OH:8])=[CH:6][CH:5]=[CH:4][N:3]=1.[Cl:9][C:10]1[CH:16]=[CH:15][C:13]([NH2:14])=[CH:12][CH:11]=1>O.CC(C)=O>[Cl:9][C:10]1[CH:16]=[CH:15][C:13]([NH:14][C:5]2[C:4]([NH:14][C:13]3[CH:15]=[CH:16][C:10]([Cl:9])=[CH:11][CH:12]=3)=[N:3][C:2](=[O:1])[C:7](=[O:8])[CH:6]=2)=[CH:12][CH:11]=1
Reactant: Oc1cccnc1O
Reactant: Nc1ccc(Cl)cc1
Solvent: O
Solvent: CC(C)=O
Product: O=C1C=C(Nc2ccc(Cl)cc2)C(Nc2ccc(Cl)cc2)=NC1=O
Reaction time: 2 h
Yield: 42 %

Procedure:
2,3-dihydroxypyridine (0.0027 mol), p-chloroaniline (0.0054 mol), and NaIO3 (0.0009 mol) were dissolved in 160 ml water/acetone (80:1, v/v) solvent. The reaction mixture was stirred for 2 hours, and maintained still overnight. It was then filtered and recrystallized with chloroform. The final product was 5,6-di(p-chlorophenylamino)-2,3-pyridindione in a yellow powder. The yield was 42%-60%.
Reaction SMILES: [CH2:1]([O:4][CH:5]1[CH2:10][CH2:9][CH2:8][CH2:7][O:6]1)[C:2]#[CH:3].Br[CH2:12][CH2:13][CH2:14][CH2:15][O:16][Si:17]([C:30]([CH3:33])([CH3:32])[CH3:31])([C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1>>[C:30]([Si:17]([C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1)([C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)[O:16][CH2:15][CH2:14][CH2:13][CH2:12][C:3]#[C:2][CH2:1][O:4][CH:5]1[CH2:10][CH2:9][CH2:8][CH2:7][O:6]1)([CH3:31])([CH3:32])[CH3:33]
Reactant: C#CCOC1CCCCO1
Reactant: CC(C)(C)[Si](OCCCCBr)(c1ccccc1)c1ccccc1
Product: CC(C)(C)[Si](OCCCCC#CCOC1CCCCO1)(c1ccccc1)c1ccccc1
Yield: 64.9 %

Procedure:
2-(Prop-2-ynyloxy)tetrahydro-2H-pyran (5.6 g, 36.36 mmol) was alkylated with (4-bromobutoxy)(tert-butyl)diphenylsilane (18.5 g, 47.2 mmol) as described above to give tert-butyldiphenyl(7-(tetrahydro-2H-pyran-2-yloxy)hept-5-ynyloxy)silane (10.64 g, 65%) and used after extractive isolation without further purification. TLC: 10% EtOAc/hexanes, Rf≈0.5.