Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]2[CH:18]=[C:17]3[C:12]([C:13]([OH:36])=[C:14]([C:31](OCC)=[O:32])[C:15](=[O:30])[N:16]3[CH2:19][CH2:20][CH2:21][N:22]3[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24][C:23]3=[O:29])=[N:11][CH:10]=2)=[CH:4][CH:3]=1.[NH2:37][CH2:38][CH2:39][CH2:40][N:41]1[CH2:45][CH2:44][CH2:43][C:42]1=[O:46]>>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:8][C:9]2[CH:18]=[C:17]3[C:12]([C:13]([OH:36])=[C:14]([C:31]([NH:37][CH2:38][CH2:39][CH2:40][N:41]4[CH2:45][CH2:44][CH2:43][C:42]4=[O:46])=[O:32])[C:15](=[O:30])[N:16]3[CH2:19][CH2:20][CH2:21][N:22]3[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24][C:23]3=[O:29])=[N:11][CH:10]=2)=[CH:6][CH:7]=1
Reactant: NCCCN1CCCC1=O
Reactant: CCOC(=O)c1c(O)c2ncc(Cc3ccc(F)cc3)cc2n(CCCN2CCCCCC2=O)c1=O
Product: O=C(NCCCN1CCCC1=O)c1c(O)c2ncc(Cc3ccc(F)cc3)cc2n(CCCN2CCCCCC2=O)c1=O

Procedure:
This compound was prepared from ethyl 7-[(4-fluorophenyl)methyl]-4-hydroxy-2-oxo-1-[3-(2-oxohexahydro-1H-azepin-1-yl)propyl]-1,2-dihydro-1,5-naphthyridine-3-carboxylate and 1-(3-aminopropyl)-2-pyrrolidinone using methods similar to Example 563 to provide an off-white solid: 1H NMR (300 MHz, DMSO-d6) δ ppm 1.54 (d, J=3.58 Hz, 4 H), 1.59-1.65 (m, 2 H), 1.65-1.81 (m, 4 H), 1.84-1.97 (m, 2 H), 2.21 (t, J=8.21 Hz, 2 H), 2.35-2.47 (m, 2 H), 3.24 (t, J=6.74 Hz, 2 H), 3.35 (td, J=7.05, 2.95 Hz, 8 H), 4.15-4.25 (m, 4 H), 7.14 (t, J=8.95 Hz, 2 H), 7.31-7.54 (m, 2 H), 8.00 (s, 1 H), 8.56 (d, J=1.47 Hz, 1 H), 10.31 (t, J=5.90 Hz, 1 H), 17.15 (s, 1 H); ES+ MS: 592 (M+H+).
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([NH:10][C:11]2[CH:20]=[CH:19][C:18]3[CH2:17][N:16]([CH:21]4[CH2:24][O:23][CH2:22]4)[CH2:15][CH2:14][C:13]=3[N:12]=2)[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=1.[C:25]([O:28][CH2:29][C:30]1[C:35]([N:36]2[CH2:47][CH2:46][N:45]3[C:38](=[CH:39][C:40]4[CH2:41][C:42]([CH3:49])([CH3:48])[CH2:43][C:44]=43)[C:37]2=[O:50])=[CH:34][C:33]([F:51])=[CH:32][C:31]=1B1OC(C)(C)C(C)(C)O1)(=[O:27])[CH3:26]>C([O-])([O-])=O.[Na+].[Na+].COCCOC.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>[F:51][C:33]1[CH:32]=[C:31]([C:2]2[CH:3]=[C:4]([NH:10][C:11]3[CH:20]=[CH:19][C:18]4[CH2:17][N:16]([CH:21]5[CH2:24][O:23][CH2:22]5)[CH2:15][CH2:14][C:13]=4[N:12]=3)[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=2)[C:30]([CH2:29][O:28][C:25](=[O:27])[CH3:26])=[C:35]([N:36]2[CH2:47][CH2:46][N:45]3[C:38](=[CH:39][C:40]4[CH2:41][C:42]([CH3:48])([CH3:49])[CH2:43][C:44]=43)[C:37]2=[O:50])[CH:34]=1
Reactant: CC(=O)OCc1c(B2OC(C)(C)C(C)(C)O2)cc(F)cc1N1CCn2c(cc3c2CC(C)(C)C3)C1=O
Reactant: Cn1cc(Br)cc(Nc2ccc3c(n2)CCN(C2COC2)C3)c1=O
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: COCCOC
Product: CC(=O)OCc1c(-c2cc(Nc3ccc4c(n3)CCN(C3COC3)C4)c(=O)n(C)c2)cc(F)cc1N1CCn2c(cc3c2CC(C)(C)C3)C1=O
Temperature: 125 °C
Reaction time: 0.17 h
Yield: 11.5 %

Procedure:
In a 10-mL microwave reaction vessel equipped with a magnetic stirring bar were placed 5-bromo-1-methyl-3-(6-(oxetan-3-yl)-5,6,7,8-tetrahydro-1,6-naphthyridin-2-ylamino)pyridin-2(1H)-one 219a (250 mg, 0.64 mmol), 10-[2-(acetoxymethyl)-3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-5-fluorophenyl]-4,4-dimethyl-1,10-diazatricyclo[6.4.0.02,6]dodeca-2(6),7-dien-9-one 230a (635 mg, 1.3 mmol), Pd(PPh3)4 (37 mg, 0.03 mmol) in 2 N Na2CO3 (2 mL) and 1,2-dimethoxyethane (2 mL). After the reaction mixture was stirred at 125° C. for 10 minutes, it was purified by flash chromatography (dichloromethane:methanol, 3:1) to give 12% (50 mg) of 292a as a solid.
Reaction SMILES: [C:1]([NH:4][CH:5](Br)[C:6]([NH:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)=[O:7])(=[O:3])[CH3:2].[NH2:17][OH:18]>C1COCC1>[C:1]([NH:4][CH:5]([NH:17][OH:18])[C:6]([NH:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)=[O:7])(=[O:3])[CH3:2]
Reactant: CC(=O)NC(Br)C(=O)NCc1ccccc1
Reactant: NO
Solvent: C1CCOC1
Product: CC(=O)NC(NO)C(=O)NCc1ccccc1
Temperature: -10 °C
Reaction time: 0.5 h

Procedure:
2-Acetamido-N-benzyl-2-bromoacetamide (prepared from 2-acetamido-N-benzyl-2-ethoxyacetamide (3.00 g, 12.0 mmol) and BBr3 (1M in CH2Cl2, 17.2 mL, 17.2 rental)) was dissolved in THF (250 mL), cooled (-10° C.), and then added dropwise (30 min) to a suspension of NH2OH (5-6 equiv) in THF (50 mL) at -10° C. The reaction mixture was stirred (30 min) at this temperature and then allowed to warm to room temperature (1 h). The insoluble materials were filtered and the filtrate was concentrated in vacuo. The residue was separated into two components by flash column chromatography on SiO2 gel (7.5% MeOH/CHCl3).
Reaction SMILES: [O:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6]1[CH:7]=[C:8]([CH:22]=[CH:23][CH:24]=1)[CH2:9][CH:10]1[C:17]2[CH:16]=[C:15]([C:18]([O:20]C)=[O:19])[NH:14][C:13]=2[CH2:12][CH2:11]1.[OH-].[Li+].CO>C1COCC1>[O:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6]1[CH:7]=[C:8]([CH:22]=[CH:23][CH:24]=1)[CH2:9][CH:10]1[C:17]2[CH:16]=[C:15]([C:18]([OH:20])=[O:19])[NH:14][C:13]=2[CH2:12][CH2:11]1
Reactant: COC(=O)c1cc2c([nH]1)CCC2Cc1cccc(-c2ccco2)c1
Agent: [Li+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CO
Product: O=C(O)c1cc2c([nH]1)CCC2Cc1cccc(-c2ccco2)c1
Yield: 61 %

Procedure:
The title compound was synthesized from methyl 4-(3-(furan-2-yl)benzyl)-1,4,5,6-tetrahydrocyclopenta[b]pyrrole-2-carboxylate (0.024 g, 0.075 mmol) and lithium hydroxide (0.032 g, 0.76 mmol), according to General Procedure 7. A 1:1 mixture of methanol (MeOH) and THF (1.5 mL) was used. The resulting product was purified by reverse phase HPLC, eluting with a gradient of 40-100% MeOH: water (with 0.1% formic acid) to afford a light pink solid: 14 mg, 61% yield. LCMS-MS (ESI−) 306.0 (M−H); HPLC (UV=93.7%), (ELSD=100%).
Reaction SMILES: [NH2:1][NH2:2].[CH2:3]([C:7]1[CH:14]=[CH:13][C:10]([CH:11]=O)=[CH:9][CH:8]=1)[CH2:4][CH:5]=[CH2:6].ClCCl>CO>[CH2:3]([C:7]1[CH:14]=[CH:13][C:10]([CH:11]=[N:1][N:2]=[CH:11][C:10]2[CH:13]=[CH:14][C:7]([CH2:3][CH2:4][CH:5]=[CH2:6])=[CH:8][CH:9]=2)=[CH:9][CH:8]=1)[CH2:4][CH:5]=[CH2:6]
Reactant: C=CCCc1ccc(C=O)cc1
Reactant: NN
Solvent: ClCCl
Solvent: CO
Product: C=CCCc1ccc(C=NN=Cc2ccc(CCC=C)cc2)cc1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
8.4 g of a monohydrate of hydrazine and 45 g of 4-(3-butenyl)benzaldehyde were dissolved in 80 ml of methanol. The mixture was stirred at room temperature for 2 hours. To the mixture was then added 150 ml of dichloromethane. The mixture was then washed with saturated aqueous solution of sodium bicarbonate twice. The mixture was then dehydrated and dried over anhydrous sodium sulfate. The solvent was then distilled off under reduced pressure. The resulting crude reaction product was purified through basic alumina column chromatography, and then recrystallized from methanol to obtain 42 g of 1,2-bis[4-(3-butenyl)benzylidene]hydrazine. The compound thus obtained had a melting point of 57° C. and exhibited nematic phase up to 116° C.
Reaction SMILES: CS([C:4]1[C:5]2[CH:28]=[CH:27][NH:26][C:6]=2[N:7]=[C:8]([NH:10][C:11]2[CH:16]=[CH:15][C:14]([N:17]3[CH2:22][CH2:21][N:20]([C:23](=[O:25])[CH3:24])[CH2:19][CH2:18]3)=[CH:13][CH:12]=2)[N:9]=1)=O.[NH2:29][CH:30]1[CH2:35][CH2:34][CH:33]([NH2:36])[CH2:32][CH2:31]1.C(N(C(C)C)CC)(C)C>CS(C)=O>[NH2:29][CH:30]1[CH2:35][CH2:34][CH:33]([NH:36][C:4]2[C:5]3[CH:28]=[CH:27][NH:26][C:6]=3[N:7]=[C:8]([NH:10][C:11]3[CH:16]=[CH:15][C:14]([N:17]4[CH2:22][CH2:21][N:20]([C:23](=[O:25])[CH3:24])[CH2:19][CH2:18]4)=[CH:13][CH:12]=3)[N:9]=2)[CH2:32][CH2:31]1
Reactant: NC1CCC(N)CC1
Reactant: CC(=O)N1CCN(c2ccc(Nc3nc(S(C)=O)c4cc[nH]c4n3)cc2)CC1
Solvent: CS(C)=O
Solvent: CCN(C(C)C)C(C)C
Product: CC(=O)N1CCN(c2ccc(Nc3nc(NC4CCC(N)CC4)c4cc[nH]c4n3)cc2)CC1
Temperature: 116 °C
Yield: 13.1 %

Procedure:
To a solution of 1-(4-(4-(4-(methylsulfinyl)-7H-pyrrolo[2,3-d]pyrimidin-2-ylamino)phenyl)piperazin-1-yl)ethanone (34 mg, 0.085 mmol) in DMSO (1 mL), 1,4-diaminocyclohexane (cis and trans mixture, 35 mg, 0.31 mmol) and diisopropylethylamine (0.060 mL, 0.35 mmol) were added. The mixture was heated at 116° C. overnight. It was then purified by HPLC to give the titled compound (5 mg). MS 449.3 (M+H); UV 208.5, 265.1, 305.5 nm.
Reaction SMILES: [Cl:1][C:2]1[N:7]=[C:6](Cl)[C:5]([O:9][CH2:10][CH3:11])=[CH:4][N:3]=1.[NH:12]1[CH2:17][CH2:16][O:15][CH2:14][CH2:13]1.[NH4+].[Cl-]>C1(C)C=CC=CC=1>[Cl:1][C:2]1[N:7]=[C:6]([N:12]2[CH2:17][CH2:16][O:15][CH2:14][CH2:13]2)[C:5]([O:9][CH2:10][CH3:11])=[CH:4][N:3]=1
Reactant: CCOc1cnc(Cl)nc1Cl
Reactant: C1COCCN1
Agent: [Cl-]
Agent: [NH4+]
Solvent: Cc1ccccc1
Product: CCOc1cnc(Cl)nc1N1CCOCC1
Temperature: 25 °C
Reaction time: 8 h
Yield: 73.5 %

Procedure:
2,4-dichloro-5-ethoxy-pyrimidin (2.83 g, 1.0 eq) was stirred in toluene (20 ml) and a solution of morpholine (1.93 ml, 1.5 eq) in toluene (20 ml) was added dropwise at −10˜0° C. After stirring the resulting solution overnight at r.t., NH4Cl(aq) was added to the solution and the solution was extracted with EA. The combined organic layers were washed with brine, dried and evaporated in vacuo. A product was obtained as a white solid (2.7 g, 73.5%).
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[N:7]1[CH2:12][CH2:11][NH:10][CH2:9][CH2:8]1.C=O.[CH3:15][C:16]1[C:24]([CH3:25])=[CH:23][CH:22]=[CH:21][C:17]=1[C:18]([NH2:20])=[O:19].[C:26](=O)([O-])[O-].[K+].[K+]>C(O)C>[CH3:15][C:16]1[C:24]([CH3:25])=[CH:23][CH:22]=[CH:21][C:17]=1[C:18]([NH:20][CH2:26][N:10]1[CH2:9][CH2:8][N:7]([C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=2)[CH2:12][CH2:11]1)=[O:19]
Reactant: O=C([O-])[O-]
Reactant: Cc1cccc(C(N)=O)c1C
Reactant: c1ccc(N2CCNCC2)nc1
Agent: C=O
Agent: [K+]
Solvent: CCO
Product: Cc1cccc(C(=O)NCN2CCN(c3ccccn3)CC2)c1C
Temperature: 25 °C
Yield: 89.4 %

Procedure:
A mixture of 1-pyridin-2-ylpiperazine (16 mg, 0.1 mmol, Aldrich), paraformaldehyde (30 mg, 1 mmol), 2,3-dimethylbenzamide (75 mg, 0.5 mmol, Lancaster), and 42 mg of potassium carbonate (0.3 mmol) in 2 mL absolute ethyl alcohol was heated to reflux under nitrogen overnight. The mixture was cooled to room temperature, filtered, and the solvent was removed. The residue was purified by flash column chromatography on silica gel (10% methanol:ethyl acetate) to give 29 mg (88%) pure compound. 1H NMR (500 MHz, DMSO-d6) δ 2.20 (s, 3H), 2.24 (s, 3H), 2.61 (t, J=4 Hz, 4H), 3.48 (t, J=4 Hz, 4.15 (d, J=5 Hz, 1H), 6.62 (t, J=5 Hz, 1H), 6.81 (d, J=6 Hz, 1H), 7.03 (m, 2H), 7.21 (t, J=5 Hz, 1H), 7.51 (t, J=6 Hz, 1H), 8.12 (d, J=5 Hz, 1H), 8.52 (t, J=5 Hz, 1H); MS (ESI/APCI−) m/e 323 (M−H)+.
Reaction SMILES: [N:1]1([CH2:6][CH:7]2[CH2:12][CH2:11][CH2:10][CH2:9][NH:8]2)[CH2:5][CH2:4][CH2:3][CH2:2]1.[Cl:13][C:14]1[CH:19]=[CH:18][C:17]([CH2:20][C:21](O)=[O:22])=[CH:16][CH:15]=1>>[ClH:13].[Cl:13][C:14]1[CH:19]=[CH:18][C:17]([CH2:20][C:21]([N:8]2[CH2:9][CH2:10][CH2:11][CH2:12][CH:7]2[CH2:6][N:1]2[CH2:5][CH2:4][CH2:3][CH2:2]2)=[O:22])=[CH:16][CH:15]=1
Reactant: O=C(O)Cc1ccc(Cl)cc1
Reactant: C1CCC(CN2CCCC2)NC1
Product: Cl
Product: O=C(Cc1ccc(Cl)cc1)N1CCCCC1CN1CCCC1

Procedure:
Prepared from 2-(1-pyrrolidinylmethyl)piperidine and 4-chlorophenylacetic acid.
Reaction SMILES: [N+:1]([C:4]1[CH:14]=[CH:13][CH:12]=[C:6]2[C:7]([O:9][C:10](=[O:11])[C:5]=12)=O)([O-:3])=[O:2].[NH2:15][CH2:16][C:17]([OH:19])=[O:18]>>[N+:1]([C:4]1[CH:14]=[CH:13][CH:12]=[C:6]2[C:7]([N:15]([CH2:16][C:17]([OH:19])=[O:18])[C:10](=[O:11])[C:5]=12)=[O:9])([O-:3])=[O:2]
Reactant: NCC(=O)O
Reactant: O=C1OC(=O)c2c1cccc2[N+](=O)[O-]
Product: O=C(O)CN1C(=O)c2cccc([N+](=O)[O-])c2C1=O
Yield: 79.9 %

Procedure:
3-nitrophthalic anhydride (0.5 g, 0.0026 mol) and glycine (0.19 g, 0.0026 mol) were refluxed as above overnight. The clear solution was concentrated under vacuum with a rotary evaporator and the crude material triturated with hot 1,4-dioxane. Undissolved material was filtered through a Buchner funnel and washed twice with 1 ml hot 1,4-dioxane. The filtrate was diluted with water. A white solid appeared which was filtered through a Buchner and washed three times with 3-5 ml water. The product was dried in air for a short time and then in vacuo for 48-72 hours to afford 0.52 g (81%) 120 as off white crystals: mp=200-202° C.; Rf0.73 (A): Rf0.77 (C): Rf0.23 (D): IR (cm−1): 2800-3200 (OH), 3096 (C═CH), 2652 (C—H), 1779 (C═O), 1724 (C═O), 1690 (C═O), 1648 (C═C), 1544 (N═O), 1470 (C═C), 1448 (C═C), 1412 (C—O), 1368 (N═O), 1260 (C—O), 722 (C═CH); MS m/z (rel intensity) 250 (15), 249 (100), 205 (89).
Reaction SMILES: [CH3:1][O:2][C:3](=[O:38])[CH2:4][N:5]([C:11]1[CH:16]=[CH:15][C:14]([F:17])=[CH:13][C:12]=1[O:18][CH2:19][CH2:20][O:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=1[NH:28][CH:29]([C:34]([O:36][CH3:37])=[O:35])[C:30]([O:32][CH3:33])=[O:31])[CH2:6][C:7]([O:9][CH3:10])=[O:8].[N+:39]([O-])([OH:41])=[O:40].S(=O)(=O)(O)O>C(O)(=O)C>[CH3:1][O:2][C:3](=[O:38])[CH2:4][N:5]([C:11]1[CH:16]=[CH:15][C:14]([F:17])=[CH:13][C:12]=1[O:18][CH2:19][CH2:20][O:21][C:22]1[CH:27]=[C:26]([N+:39]([O-:41])=[O:40])[CH:25]=[CH:24][C:23]=1[NH:28][CH:29]([C:34]([O:36][CH3:37])=[O:35])[C:30]([O:32][CH3:33])=[O:31])[CH2:6][C:7]([O:9][CH3:10])=[O:8]
Reactant: O=[N+]([O-])O
Reactant: COC(=O)CN(CC(=O)OC)c1ccc(F)cc1OCCOc1ccccc1NC(C(=O)OC)C(=O)OC
Agent: O=S(=O)(O)O
Solvent: CC(=O)O
Product: COC(=O)CN(CC(=O)OC)c1ccc(F)cc1OCCOc1cc([N+](=O)[O-])ccc1NC(C(=O)OC)C(=O)OC
Temperature: 30 °C

Procedure:
2.5 g ((2-(2-(2-(Bis-methoxycarbonylmethyl-amino)-phenoxy)-ethoxy)-4-fluoro-phenyl)-methoxycabonylmethyl-amino)-acetic acid methyl ester were dissolved in 30 ml glacial acetic acid. Under vigorous stirring 4.54 ml 1 molar nitric acid in glacial acetic acid was added and in a second step 11.35 ml of concentrated sulfuric acid was added. The temperature increased up to 30° C. The reaction mixture was directly poured in a 250 ml ice/water mixture. The residue was filtered off, washed several times with water and dried under vacuum. The crude product was further purified by column chromatography on silica gel first with hexane/acetic acid ethyl ester (1:1) as eluent and a second time with toluene/acetonitrile (1:1) as eluent. Yield: 0.82 g.
Reaction SMILES: Cl.[C:2]([C:4]1[CH:5]=[C:6]([C:15]2[CH:20]=[CH:19][N:18]=[C:17]([NH:21][C:22]3[CH:26]=[CH:25][N:24]([CH:27]4[CH2:32][CH2:31][N:30](C(OC(C)(C)C)=O)[CH2:29][CH2:28]4)[N:23]=3)[CH:16]=2)[CH:7]=[CH:8][C:9]=1[O:10][CH2:11][CH:12]1[CH2:14][CH2:13]1)#[N:3]>O1CCOCC1>[CH:12]1([CH2:11][O:10][C:9]2[CH:8]=[CH:7][C:6]([C:15]3[CH:20]=[CH:19][N:18]=[C:17]([NH:21][C:22]4[CH:26]=[CH:25][N:24]([CH:27]5[CH2:28][CH2:29][NH:30][CH2:31][CH2:32]5)[N:23]=4)[CH:16]=3)=[CH:5][C:4]=2[C:2]#[N:3])[CH2:13][CH2:14]1
Reactant: CC(C)(C)OC(=O)N1CCC(n2ccc(Nc3cc(-c4ccc(OCC5CC5)c(C#N)c4)ccn3)n2)CC1
Agent: Cl
Solvent: C1COCCO1
Product: N#Cc1cc(-c2ccnc(Nc3ccn(C4CCNCC4)n3)c2)ccc1OCC1CC1
Temperature: 25 °C
Reaction time: 6 h
Yield: 89.6 %

Procedure:
HCl in dioxane (10 ml) are added to a solution of tert-butyl 4-{3-[4-(3-cyano-4-cyclopropylmethoxyphenyl)pyridin-2-ylamino]pyrazol-1-yl}piperidine-1-carboxylate (0.12 g, 0.23 mmol) in 1,4-dioxane (10 ml). The entire mixture is stirred at room temperature for 6 h. The reaction solution is evaporated in a rotary evaporator and rendered basic using 10% sodium bicarbonate solution (20 ml). The mixture is stirred for 10 min. The solid is filtered off, washed with diethyl ether (20 ml) and dried, giving 85.4 mg of the desired material as brown solid;
Reaction SMILES: [C:1]([C:5]1[CH:10]=[CH:9][C:8]([N:11]2[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[C:13]([CH:20]=[O:21])=[C:12]2Cl)=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[C:23]([N:30]1[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]1)([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24]>>[C:26]([O:25][C:23]([N:30]1[CH2:35][CH2:34][N:33]([C:12]2[N:11]([C:8]3[CH:9]=[CH:10][C:5]([C:1]([CH3:4])([CH3:3])[CH3:2])=[CH:6][CH:7]=3)[C:19]3[C:14]([C:13]=2[CH:20]=[O:21])=[CH:15][CH:16]=[CH:17][CH:18]=3)[CH2:32][CH2:31]1)=[O:24])([CH3:29])([CH3:27])[CH3:28]
Reactant: CC(C)(C)OC(=O)N1CCNCC1
Reactant: CC(C)(C)c1ccc(-n2c(Cl)c(C=O)c3ccccc32)cc1
Product: CC(C)(C)OC(=O)N1CCN(c2c(C=O)c3ccccc3n2-c2ccc(C(C)(C)C)cc2)CC1
Yield: 70 %

Procedure:
1-(4-tert-Butylphenyl)-2-chloro-1H-indole-3-carboxaldehyde is reacted with 1-Boc-piperazine as described in Step 2 of Example 29 to afford 4-[1-(4-tert-butylphenyl)-3-formyl-1H-indol-2-yl]piperazine-1-carboxylic acid tert-butyl ester (70% yield) as a light yellow solid. TLC (heptane-30% ethyl acetate) Rf=0.19; ESI/MS 462 (M+H); RT=4.42 min.; NMR10.13 (1H, s); 8.13 (1H, d, J=9 Hz); 7.68 (2H, d); 7.49 (2H, d); 7.21 (2H, m); 6.95 (1H, d, J=9 Hz); 3.20 (8H, m); 1.37 (18H, s).
Reaction SMILES: [CH2:1]([N:5]([CH2:24][CH2:25][CH2:26][CH3:27])[C:6]1[CH:11]=[CH:10][C:9]([CH:12]=[CH:13][C:14]2[CH:21]=[CH:20][C:17]([CH:18]=O)=[CH:16][CH:15]=2)=[C:8]([O:22][CH3:23])[CH:7]=1)[CH2:2][CH2:3][CH3:4].[C:28]([C:30]1[C:31](=[C:38]([C:41]#[N:42])[C:39]#[N:40])[O:32][C:33]([CH3:37])([CH3:36])[C:34]=1[CH3:35])#[N:29].C([O-])(=O)C.[NH4+]>C(O)C.O1CCCC1>[CH2:24]([N:5]([CH2:1][CH2:2][CH2:3][CH3:4])[C:6]1[CH:11]=[CH:10][C:9]([CH:12]=[CH:13][C:14]2[CH:21]=[CH:20][C:17]([CH:18]=[CH:35][C:34]3[C:33]([CH3:36])([CH3:37])[O:32][C:31](=[C:38]([C:39]#[N:40])[C:41]#[N:42])[C:30]=3[C:28]#[N:29])=[CH:16][CH:15]=2)=[C:8]([O:22][CH3:23])[CH:7]=1)[CH2:25][CH2:26][CH3:27]
Reactant: CCCCN(CCCC)c1ccc(C=Cc2ccc(C=O)cc2)c(OC)c1
Reactant: CC1=C(C#N)C(=C(C#N)C#N)OC1(C)C
Agent: CC(=O)[O-]
Agent: [NH4+]
Solvent: CCO
Solvent: C1CCOC1
Product: CCCCN(CCCC)c1ccc(C=Cc2ccc(C=CC3=C(C#N)C(=C(C#N)C#N)OC3(C)C)cc2)c(OC)c1
Temperature: 25 °C
Reaction time: 23 h
Yield: 92.5 %

Procedure:
In 15 ml of ethanol and 5 ml of tetrahydrofuran were dissolved 500 mg (1.37 mmol) of 4-[2-(4-dibutylamino-2-methoxyphenyl)vinyl]benzaldehyde and 300 mg (1.51 mmol) of 2-(3-cyano-4,5,5-trimethyl-2(5H)-furanylidene) propanedinitrile. To this mixture was added 106 mg of ammonium acetate, and the mixture was stirred at room temperature for 23 hours. The solvent was evaporated off in a reduced pressure. The residue was washed with ethanol and then purified by silica gel column chromatography. The crystal was washed with ethanol to give 693 mg of a black powder (yield: 92.6%; mp: 258-260° C.)
Reaction SMILES: [CH2:1]([NH2:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:9]([CH2:11][C:12](OC)=[O:13])#[N:10]>>[CH2:1]([NH:8][C:12](=[O:13])[CH2:11][C:9]#[N:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: NCc1ccccc1
Reactant: COC(=O)CC#N
Product: N#CCC(=O)NCc1ccccc1
Temperature: 100 °C
Yield: 40 %

Procedure:
To benzylamine (1.07 g, 0.01 mol) was added methyl cyanoacetate (0.99 g, 0.01 mol) and the mixture was heated for 16 h at 100° C. without condenser to allow evaporation of the methanol formed. Cooling gave a dark red solid which was triturated with ethanol, filtered and recrystallized from ethanol to give pure title compound in about 40% yield (0.70 g). mp 123°-4° C.
Reaction SMILES: [CH:1]([O:4][C:5]1[CH:13]=[CH:12][C:11]([S:14]([CH3:17])(=[O:16])=[O:15])=[CH:10][C:6]=1[C:7]([OH:9])=O)([CH3:3])[CH3:2].[CH2:18]1[C:26]2[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=2)[CH2:20][NH:19]1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C>[CH2:18]1[C:26]2[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=2)[CH2:20][N:19]1[C:7]([C:6]1[CH:10]=[C:11]([S:14]([CH3:17])(=[O:16])=[O:15])[CH:12]=[CH:13][C:5]=1[O:4][CH:1]([CH3:2])[CH3:3])=[O:9]
Reactant: CC(C)Oc1ccc(S(C)(=O)=O)cc1C(=O)O
Reactant: c1ccc2c(c1)CNC2
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[B-](F)(F)F
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: CC(C)Oc1ccc(S(C)(=O)=O)cc1C(=O)N1Cc2ccccc2C1
Temperature: 25 °C
Reaction time: 2 h
Yield: 88 %

Procedure:
A mixture of 0.387 mmol 2-isopropoxy-5-methanesulfonyl-benzoic acid (example B1), 0.464 mmol 2,3-Dihydro-1H-isoindole (commercial), 0.426 mmol TBTU and 1.935 mmol DIPEA in 1.4 ml DMF was stirred at RT for 2 h. The reaction mixture was evaporated in vacuo. The residue was taken in water and extracted with ethylacetate. The combined organic phases were washed with saturated sodium bicarbonate solution, dried over sodium sulfate, filtered and concentrated in vacuo. The residue was purified by chromatography (SiO2, heptane/ethyl acetate) to yield the title compound as a light brown solid (88% yield). MS (m/e): 360.2 [M+H]+, 100%)
Reaction SMILES: [C:1]([C:5]1[CH2:9][C:8]([CH:11]=O)([CH3:10])[O:7][N:6]=1)([CH3:4])([CH3:3])[CH3:2].C1(P(C2C=CC=CC=2)(C2C=CC=CC=2)=[CH:20][C:21](=[O:23])[CH3:22])C=CC=CC=1.COC(C)(C)C>ClCCl>[C:1]([C:5]1[CH2:9][C:8]([CH:11]=[CH:20][C:21](=[O:23])[CH3:22])([CH3:10])[O:7][N:6]=1)([CH3:2])([CH3:3])[CH3:4]
Reactant: CC(=O)C=P(c1ccccc1)(c1ccccc1)c1ccccc1
Reactant: CC1(C=O)CC(C(C)(C)C)=NO1
Solvent: ClCCl
Solvent: COC(C)(C)C
Product: CC(=O)C=CC1(C)CC(C(C)(C)C)=NO1
Reaction time: 8 h
Yield: 97.8 %

Procedure:
35.0 g (0.21 mole) of 3-tert-butyl-5-formyl-5-methylisoxazoline were added dropwise to a solution of 79 g (0.25 mole) of 1-triphenylphosphoranylidene-2-propanone in 200 ml of dichloromethane. The reaction mixture was kept at 40° C. for 8 hours and then stirred with tert-butyl methyl ether. The residue was filtered off under suction and the filtrate was evaporated down to give 43 g of a yellow oil which slowly crystallized.
Reaction SMILES: [C:1]1([C:7]2[CH:13]=[CH:12][CH:11]=[CH:10][C:8]=2[NH2:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH2:14]1[C:27]2[C:18](=[N:19][C:20]3[C:21](=O)[CH2:22][CH2:23][CH2:24][C:25]=3[CH:26]=2)[C:17](=O)[CH2:16][CH2:15]1>>[C:1]1([C:7]2[CH:13]=[CH:12][CH:11]=[CH:10][C:8]=2[N:9]=[C:17]2[C:18]3[C:27](=[CH:26][C:25]4[CH2:24][CH2:23][CH2:22][C:21](=[N:9][C:8]5[CH:10]=[CH:11][CH:12]=[CH:13][C:7]=5[C:1]5[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=5)[C:20]=4[N:19]=3)[CH2:14][CH2:15][CH2:16]2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: O=C1CCCc2cc3c(nc21)C(=O)CCC3
Reactant: Nc1ccccc1-c1ccccc1
Product: c1ccc(-c2ccccc2N=C2CCCc3cc4c(nc32)C(=Nc2ccccc2-c2ccccc2)CCC4)cc1

Procedure:
was synthesized by methods similar to those in Examples 3 and 4: 2-phenylaniline was condensed with 2,3,7,8-tetrahydro-1H,6H-acridine-4,5-dione to yield 4,5-bis(2-phenylphenylimino)-1,2,3,4,5,6,7,8-octahydroacridine (7). The complexation of (7) with FeCl2.4H2O was carried out with azeotropic removal of methanol in benzene. The structure of the final complex was proved by direct probe GC. Exact mass direct probe calculated for C37H31Cl2FeN3: 643.12. Found: 643.12.
Reaction SMILES: [OH:1][C@H:2]1[C@@H:7]2[C@@:5]([CH3:8])([CH2:6]2)[C@@H:4]([C:9]([O:11][CH2:12][CH3:13])=[O:10])[CH2:3]1.[OH:14][C@@H:15]1[C@H:20]2[C@:18]([CH3:21])([CH2:19]2)[C@H:17]([C:22]([O:24][CH2:25][CH3:26])=[O:23])[CH2:16]1>>[CH3:8][C@@:5]12[CH2:6][C@@H:7]1[C:2](=[O:1])[CH2:3][C@@H:4]2[C:9]([O:11][CH2:12][CH3:13])=[O:10].[CH3:21][C@:18]12[CH2:19][C@H:20]1[C:15](=[O:14])[CH2:16][C@H:17]2[C:22]([O:24][CH2:25][CH3:26])=[O:23]
Reactant: CCOC(=O)[C@@H]1C[C@H](O)[C@@H]2C[C@]12C
Reactant: CCOC(=O)[C@H]1C[C@@H](O)[C@H]2C[C@@]12C
Product: CCOC(=O)[C@@H]1CC(=O)[C@@H]2C[C@@]21C
Product: CCOC(=O)[C@H]1CC(=O)[C@H]2C[C@]21C
Yield: 65 %

Procedure:
A mixture of (1R,2S,4R,5S)-ethyl 4-hydroxy-1-methylbicyclo[3.1.0]hexane-2-carboxylate and (1S,2R,4S,5R)-ethyl 4-hydroxy-1-methylbicyclo[3.1.0]hexane-2-carboxylate (0.59 g, 3.2 mmol) was subjected to General Procedure T to give (1R,2S,5S)-ethyl 1-methyl-4-oxobicyclo[3.1.0]hexane-2-carboxylate and (1S,2R,5R)-ethyl 1-methyl-4-oxobicyclo[3.1.0]hexane-2-carboxylate (0.38 g, 65%) after purification by silica gel chromatography eluting with a gradient of 20-50% EtOAc/pentane: 1H NMR (400 MHz, CDCl3) δ 4.35-4.15 (m, 2H), 3.12 (t, J=9.3 Hz, 1H), 2.60 (dd, J=9.2, 18.3 Hz, 1H), 2.37-2.23 (m, 1H), 1.68 (dd, J=3.4, 9.2 Hz, 1H), 1.48 (s, 3H), 1.41 (dd, J=3.4, 5.2 Hz, 1H), 1.34 (t, J=7.1 Hz, 3H), 1.14 (dd, J=5.3, 9.2 Hz, 1H).