Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([C:5]1([O:16][Si:17]([CH3:20])([CH3:19])[CH3:18])[CH:9]([CH:10](O)[CH2:11][CH2:12][CH3:13])[C:8](=[O:15])[CH:7]=[CH:6]1)[CH2:2][CH2:3][CH3:4].S(Cl)(C)(=O)=O.C1CCN2C(=NCCC2)CC1>N1C=CC=CC=1.C(OCC)(=O)C.CCCCCC.C1C=CC=CC=1.O>[CH2:1]([C:5]1([O:16][Si:17]([CH3:19])([CH3:20])[CH3:18])[CH:6]=[CH:7][C:8](=[O:15])/[C:9]/1=[CH:10]/[CH2:11][CH2:12][CH3:13])[CH2:2][CH2:3][CH3:4]
Reactant: CCCCC1(O[Si](C)(C)C)C=CC(=O)C1C(O)CCC
Agent: CS(=O)(=O)Cl
Solvent: CCCCCC
Solvent: O
Solvent: c1ccncc1
Product: CCC/C=C1/C(=O)C=CC1(CCCC)O[Si](C)(C)C
Reaction time: 8 h
Yield: 49.4 %

Procedure:
40 mg (0.13 mmole) of 4-butyl-5-(1-hydroxybutyl)-4-trimethylsilyloxy-2-cyclopentenone was dissolved in 2 ml of pyridine, and at room temperature, 0.1 ml (1.3 mmoles) of mesyl chloride was added. The mixture was stirred for 8 hours. After the reaction, water was added, and the mixture was extracted with methylene chloride. The extract was dried, and concentrated, and 2 ml of benzene and 0.2 ml (1.3 mmoles) of DBU were added. The mixture was stirred at room temperature for 2 hours. Water was added, and the mixture was exracted with benzene. The extract was dried and concentrated, and the residue was chromatographed on a silica gel column (Merck silica gel 4 g, hexane:ethyl acetate=20:1) to give 18 mg (yield 48%) of 4-butyl-5-[(E)-butylidene]-4-trimethylsilyloxy-2-cyclopentenone (Rf=0.7, hexane:ethyl actate=3:1) and 5 mg (yield 14%) of its Z-isomer (Rf=0.75, hexane:ethyl acetate=3:1).
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([CH2:15][C:16]([O:18]C(C)(C)C)=[O:17])=[C:11]([O:23][CH3:24])[CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([CH2:15][C:16]([OH:18])=[O:17])=[C:11]([O:23][CH3:24])[CH:10]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: COc1cc(OCc2ccccc2)ccc1CC(=O)OC(C)(C)C
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: COc1cc(OCc2ccccc2)ccc1CC(=O)O
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
A solution of tert-butyl [4-(benzyloxy)-2-methoxyphenyl]acetate (2.2 g, 6.70 mmol) in DCM (10 ml) was treated with TFA (10.3 ml, 134 mmol) and the mixture stirred at RT for 30 min. The volatiles were removed in vacuo to afford the title compound. LC/MS (m/z): 273 (M+H)+.
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]2([C:13]3=[CH:14][C:15]4[O:19][CH2:18][O:17][C:16]=4[CH:20]=[C:12]3[O:11][CH2:10]2)[C:2]1=[O:21].[Cl:22][C:23]1[S:27][C:26]([CH2:28]O)=[N:25][N:24]=1.C(P(CCCC)CCCC)CCC.CN(C)C(N=NC(N(C)C)=O)=O>O1CCCC1>[Cl:22][C:23]1[S:27][C:26]([CH2:28][N:1]2[C:9]3[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=3)[C:3]3([C:13]4=[CH:14][C:15]5[O:19][CH2:18][O:17][C:16]=5[CH:20]=[C:12]4[O:11][CH2:10]3)[C:2]2=[O:21])=[N:25][N:24]=1
Reactant: O=C1Nc2ccccc2C12COc1cc3c(cc12)OCO3
Reactant: OCc1nnc(Cl)s1
Agent: CCCCP(CCCC)CCCC
Agent: CN(C)C(=O)N=NC(=O)N(C)C
Solvent: C1CCOC1
Product: O=C1N(Cc2nnc(Cl)s2)c2ccccc2C12COc1cc3c(cc12)OCO3
Reaction time: 0.25 h
Yield: 24.3 %

Procedure:
To a solution of spiro[furo[2,3-f][1,3]benzodioxole-7,3′-indol]-2′(1′H)-one (0.56 g, 1.99 mmol) and (5-chloro-1,3,4-thiadiazol-2-yl)methanol (0.30 g, 1.99 mmol) in anhydrous tetrahydrofuran (12.0 mL) was added tributylphosphine (0.60 g, 2.99 mmol) at 0° C. The reaction mixture was stirred for 15 min followed by the addition of N,N,N′,N′-tetramethylazodicarboxamide (0.51 g, 2.99 mmol). The reaction mixture was stirred at ambient temperature overnight, quenched with aqueous ammonium chloride (10.0 mL) and diluted with ethyl acetate (350 mL). The organic layer was washed with aqueous saturated sodium chloride (2×25.0 mL), dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo to dryness. The residue was subjected to column chromatography (ethyl acetate/hexane, 1/2) to give the title compound (0.20 g, 24%) as a yellowish solid: mp 194-197° C.; 1H NMR (300 MHz, DMSO-d6,) δ 7.30 (dt, 1H), 7.20-7.12 (m, 2H), 7.05 (dt, 1H), 6.67 (s, 1H), 6.28 (s, 1H), 5.90 (s, 2H), 5.43 (d, 1H), 5.34 (d, 1H), 4.78 (d, 1H), 4.67 (d, 1H); 13C NMR (75 MHz, DMSO-d6) δ 177.2, 168.3, 155.8, 155.4, 148.9, 142.2, 141.9, 132.2, 129.4, 124.2, 124.0, 120.1, 109.8, 103.7, 101.9, 93.8, 80.1, 67.5, 57.9, 25.6; MS (ES+) m/z 414.2 (M +1), 416.2 (M+1).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([CH3:13])[C:5]([CH2:8][CH2:9][CH2:10][CH2:11][NH2:12])=[N:6][CH:7]=1.[N+](N[C:18]1[NH:23][C:22](=[O:24])[C:21]([CH2:25][C:26]2[CH:27]=[N:28][C:29]([CH3:33])=[CH:30][C:31]=2[CH3:32])=[CH:20][N:19]=1)([O-])=O>C1(OC)C=CC=CC=1>[Br:1][C:2]1[CH:3]=[C:4]([CH3:13])[C:5]([CH2:8][CH2:9][CH2:10][CH2:11][NH:12][C:18]2[NH:23][C:22](=[O:24])[C:21]([CH2:25][C:26]3[CH:27]=[N:28][C:29]([CH3:33])=[CH:30][C:31]=3[CH3:32])=[CH:20][N:19]=2)=[N:6][CH:7]=1
Reactant: Cc1cc(C)c(Cc2cnc(N[N+](=O)[O-])[nH]c2=O)cn1
Reactant: Cc1cc(Br)cnc1CCCCN
Solvent: COc1ccccc1
Product: Cc1cc(C)c(Cc2cnc(NCCCCc3ncc(Br)cc3C)[nH]c2=O)cn1
Yield: 60.3 %

Procedure:
A mixture of 5-bromo-2-(4-aminobutyl)-3-methyl pyridine, (0.68 g) and 2-nitroamino-5-(4,6-dimethyl-3-pyridylmethyl)-4-pyrimidone (0.83 g) in anisole (25 ml) were refluxed for 4 hrs. Petroleum ether was added to precipitate the product which was then chromatographed on a silica gel column eluting with chloroform. The product was crystallised from ethyl acetate to give 2-[4-(5-bromo-3-methylpyrid-2-yl)-butylamino]-5-(4,6-dimethyl-3-pyridylmethyl)-4-pyrimidone (0.77 g) m.p. 110°-112° C.
Reaction SMILES: [C:1]([N:6]=C=O)(=[O:5])C(C)=C.[C:9]([O:14][CH3:15])(=[O:13])[C:10]([CH3:12])=[CH2:11].[CH2:16]=[CH:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.[C:24]([O:28][CH2:29][CH2:30][CH2:31][CH3:32])(=[O:27])[CH:25]=[CH2:26].N(C(C)(CC(C)C)C#N)=NC(C)(CC(C)C)C#N>C(OCCCC)(=O)C>[N-:6]=[C:1]=[O:5].[C:9]([O:14][CH3:15])(=[O:13])[C:10]([CH3:12])=[CH2:11].[CH2:16]=[CH:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.[C:24]([O:28][CH2:29][CH2:30][CH2:31][CH3:32])(=[O:27])[CH:25]=[CH2:26]
Reactant: C=C(C)C(=O)N=C=O
Agent: C=C(C)C(=O)OC
Agent: C=CC(=O)OCCCC
Agent: CC(C)CC(C)(C#N)N=NC(C)(C#N)CC(C)C
Solvent: C=Cc1ccccc1
Solvent: CCCCOC(C)=O
Product: [N-]=C=O
Temperature: 100 °C
Reaction time: 2 h

Procedure:
Into a reaction vessel, butyl acetate (40 g) was charged, and heating was made to 100° C. A mixture of methacryloyl isocyanate (7.5 g), methyl methacrylate (17.5 g), styrene (15.0 g), n-butyl acrylate (10.0 g) and 2,2'-azobis(2,4-dimethylvaleronitrile) (0.5 g) was dropwise added thereto in 2 hours. After stirring at 100° C. for 30 minutes, a solution of 2,2'-azobis(2,4-dimethylvalernoitrile) (0.25 g) in butyl acetate (10 g) was dropwise added thereto at 100° C. in 30 minutes, followed by stirring at 100° C. in 1.5 hours to give a copolymer of methcaryloyl isocyanate with methyl methacrylate, styrene and n-butyl acrylate. Number average molecular weight, 10,500. Non-volatile content, 42.3%. Viscosity (determined by Gardner bubble viscometer), K<<L.
Reaction SMILES: [CH:1]1([O:7][CH:8]2[CH2:13][CH2:12][N:11](C(OCC3C=CC=CC=3)=O)[CH2:10][CH2:9]2)[CH2:6][CH2:5][CH2:4][CH:3]=[CH:2]1.[H][H]>[Pd].CO>[CH:1]1([O:7][CH:8]2[CH2:9][CH2:10][NH:11][CH2:12][CH2:13]2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: O=C(OCc1ccccc1)N1CCC(OC2C=CCCC2)CC1
Reactant: [H][H]
Agent: [Pd]
Solvent: CO
Product: C1CCC(OC2CCNCC2)CC1
Yield: 109.6 %

Procedure:
A solution of 4-(2-cyclohexenyloxy)-N-(benzyloxycarbonyl)piperidine (3.80 g), and 10% palladium on carbon (50% wet) (1.0 g) in methanol (40 ml) was hydrogenated under an atmospheric pressure of hydrogen at ambient temperature for 6 hours. The catalyst was filtered off, and the filtrate was evaporated in vacua and dried in vacuo to give 4-(cyclohexyloxy)piperidine (2.42 g).
Reaction SMILES: [C:1]([O:5][C:6]([C:8]1[C:9]([C:14]2[CH:19]=[CH:18][C:17]([CH2:20]Br)=[CH:16][CH:15]=2)=[CH:10][CH:11]=[CH:12][CH:13]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[NH2:22][CH2:23][CH2:24][NH:25][C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27].C(=O)([O-])[O-].[K+].[K+]>C1COCC1>[C:1]([O:5][C:6]([C:8]1[C:9]([C:14]2[CH:19]=[CH:18][C:17]([CH2:20][NH:22][CH2:23][CH2:24][NH:25][C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])=[CH:16][CH:15]=2)=[CH:10][CH:11]=[CH:12][CH:13]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(C)(C)OC(=O)NCCN
Reactant: CC(C)(C)OC(=O)c1ccccc1-c1ccc(CBr)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)NCCNCc1ccc(-c2ccccc2C(=O)OC(C)(C)C)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 98.4 %

Procedure:
A solution of 4′-bromomethylbiphenyl-2-carboxylic acid t-butyl ester made as described in Preparation 2 (7.2 g, 20.8 mmol), N-(2-aminoethyl)(t-butoxy)carboxamide (10 g, 62.4 mmol), and potassium carbonate (4.3 g, 31.2 mmol) in THF (40 mL) was stirred at room temperature overnight. The mixture was concentrated then extracted with EtOAc (3×150 mL) and water (80 mL). The combined organic extracts were dried over Na2SO4, filtered, and concentrated in vacuo to afford crude intermediate (3a) (98.4% yield), which was used in the next step without further purification.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([C:8]([C:10]2[C:18]3[CH:17]=[N:16][CH:15]=[N:14][C:13]=3[N:12]([C:19]([CH3:30])([CH3:29])[CH2:20][O:21][Si:22]([C:25]([CH3:28])([CH3:27])[CH3:26])([CH3:24])[CH3:23])[CH:11]=2)=[O:9])[CH:5]=[N:6][CH:7]=1.[N:31]1[C:40]2[C:35](=[CH:36][CH:37]=[C:38]([CH2:41][C:42](O)=[O:43])[CH:39]=2)[CH:34]=[CH:33][CH:32]=1.CCN(C(C)C)C(C)C>>[Si:22]([O:21][CH2:20][C:19]([N:12]1[C:13]2[N:14]=[CH:15][N:16]=[CH:17][C:18]=2[C:10]([C:8]([C:4]2[CH:3]=[C:2]([NH:1][C:42](=[O:43])[CH2:41][C:38]3[CH:39]=[C:40]4[C:35]([CH:34]=[CH:33][CH:32]=[N:31]4)=[CH:36][CH:37]=3)[CH:7]=[N:6][CH:5]=2)=[O:9])=[CH:11]1)([CH3:30])[CH3:29])([C:25]([CH3:28])([CH3:27])[CH3:26])([CH3:23])[CH3:24]
Reactant: CC(C)(CO[Si](C)(C)C(C)(C)C)n1cc(C(=O)c2cncc(N)c2)c2cncnc21
Reactant: O=C(O)Cc1ccc2cccnc2c1
Solvent: CCN(C(C)C)C(C)C
Product: CC(C)(CO[Si](C)(C)C(C)(C)C)n1cc(C(=O)c2cncc(NC(=O)Cc3ccc4cccnc4c3)c2)c2cncnc21

Procedure:
Prepared according to the method described for Example 1 using (5-aminopyridin-3-yl)[7-(2-{[tert-butyl(dimethyl)silyl]oxy}-1,1-dimethylethyl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl]methanone (Preparation 38), and 2-quinolin-7-ylacetic acid with DIPEA as base.
Reaction SMILES: [Cl:1][C:2]1[C:3]([S:14][C:15]2[S:16][C:17]3[CH:23]=[CH:22][C:21]([C:24]([F:27])([F:26])[F:25])=[CH:20][C:18]=3[N:19]=2)=[C:4]([C:11](=[O:13])[CH3:12])[CH:5]=[C:6]([N+:8]([O-])=O)[CH:7]=1.O.O.[Sn](Cl)(Cl)(Cl)Cl>>[NH2:8][C:6]1[CH:7]=[C:2]([Cl:1])[C:3]([S:14][C:15]2[S:16][C:17]3[CH:23]=[CH:22][C:21]([C:24]([F:26])([F:25])[F:27])=[CH:20][C:18]=3[N:19]=2)=[C:4]([C:11](=[O:13])[CH3:12])[CH:5]=1
Reactant: CC(=O)c1cc([N+](=O)[O-])cc(Cl)c1Sc1nc2cc(C(F)(F)F)ccc2s1
Agent: Cl[Sn](Cl)(Cl)Cl
Solvent: O
Product: CC(=O)c1cc(N)cc(Cl)c1Sc1nc2cc(C(F)(F)F)ccc2s1
Yield: 112.2 %

Procedure:
The title compound was prepared using the method of example 270, starting with 1-[3-chloro-5-nitro-2-(5-trifluoromethyl-benzothiazol-2-ylsulfanyl)-phenyl]-ethanone (259) (750 mg, 1.67 mmol), tin chloride dihydrate (Aldrich, 1.89 g, 8.37 mmol). Compound 271 (755 mg, 100%) was obtained as a yellowish solid.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([CH:27]=[CH:28][C:29]=1[CH3:30])[C:5]([NH:7][C:8]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[C:11]([O:18][CH2:19][CH2:20][N:21]2[CH2:26][CH2:25][O:24][CH2:23][CH2:22]2)=[CH:10][CH:9]=1)=[O:6].[NH:31]1[CH2:36][CH2:35][O:34][CH2:33][CH2:32]1>>[CH3:30][C:29]1[CH:28]=[CH:27][C:4]([C:5]([NH:7][C:8]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[C:11]([O:18][CH2:19][CH2:20][N:21]3[CH2:26][CH2:25][O:24][CH2:23][CH2:22]3)=[CH:10][CH:9]=2)=[O:6])=[CH:3][C:2]=1[N:31]1[CH2:36][CH2:35][O:34][CH2:33][CH2:32]1
Reactant: C1COCCN1
Reactant: Cc1ccc(C(=O)Nc2ccc(OCCN3CCOCC3)c3ccccc23)cc1Br
Product: Cc1ccc(C(=O)Nc2ccc(OCCN3CCOCC3)c3ccccc23)cc1N1CCOCC1

Procedure:
Compound is formed by reacting 3-bromo-4-methyl-N-[4-(2-morpholin-4-yl-ethoxy)-naphthalen-1-yl]-benzamide with morpholine under conditions described in general procedure B. 1H NMR (300 MHz, CDCl3) δ 8.32 (m, 1H), 7.98 (broad s, 1H), 7.86 (m, 1H), 7.74 (m, 2H), 7.53 (m, 3H), 7.32 (m, 1H), 6.87 (t, 1H, J=7.5), 4.34 (m, 2H), 3.88 (m, 4H), 3.77 (m, 4H), 2.97 (m, 6H), 2.68 (m, 4H), 2.42 (d, 3H, J=5.7). MS: 476.2 (M+1).
Reaction SMILES: [F:1][C:2]1[CH:10]=[CH:9][C:8]2[NH:7][C:6]3[CH:11]4[CH2:17][CH2:16][N:14]([CH2:15][C:5]=3[C:4]=2[CH:3]=1)[CH2:13][CH2:12]4.C([Li])CCC.C(P(C(C)(C)C)C(C)(C)C)(C)(C)C.Br/[CH:37]=[CH:38]/[C:39]1[CH:40]=[CH:41][C:42]([CH3:45])=[N:43][CH:44]=1>C1(C)C=CC=CC=1.COCCOC.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd]>[F:1][C:2]1[CH:10]=[CH:9][C:8]2[N:7](/[CH:37]=[CH:38]/[C:39]3[CH:44]=[N:43][C:42]([CH3:45])=[CH:41][CH:40]=3)[C:6]3[CH:11]4[CH2:12][CH2:13][N:14]([CH2:15][C:5]=3[C:4]=2[CH:3]=1)[CH2:16][CH2:17]4
Reactant: Cc1ccc(/C=C/Br)cn1
Reactant: Fc1ccc2[nH]c3c(c2c1)CN1CCC3CC1
Agent: [Pd]
Agent: CC(C)(C)P(C(C)(C)C)C(C)(C)C
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Solvent: COCCOC
Solvent: Cc1ccccc1
Product: Cc1ccc(/C=C/n2c3c(c4cc(F)ccc42)CN2CCC3CC2)cn1
Temperature: 70 °C
Reaction time: 0.5 h

Procedure:
A solution of 9-fluoro-3,4,5,6-tetrahydro-1H-2,5-ethanoazepino[4,3-b]indole (100 mg, 0.434 mmol; Example 161) in a mixture of toluene (4 mL) and 1,2-dimethoxyethane (1 mL) was degassed with nitrogen. n-Butyllithium (2 M in cyclohexane; 217 mL, 0.434 mmol; Aldrich) was added at room temperature and the mixture stirred for 30 minutes. Bis(dibenzylidene-acetone)palladium (19.98 mg, 0.035 mmol; Aldrich), tri-tert-butylphosphine (1 M in toluene; 0.069 mL, 0.069 mmol; Aldrich) and (E)-5-(2-bromovinyl)-2-methylpyridine (86 mg, 0.434 mmol; Example 23C) were added. The reaction mixture was heated at 70° C. for 18 hours. After cooling, the mixture was filtered through a pad of diatomaceous earth and concentrated in vacuo, and the residue was purified by flash chromatography (silica gel, Isco SF15-24, using a of chloroform/methanol/concentrated NH4OH, 90/9/1) to afford the title compound: 1H NMR (300 MHz, methanol-d4) δ 2.20 (m, 4H), 2.55 (s, 3H), 3.23 (m, 4H), 3.52 (m, 1H), 4.39 (s, 2H), 6.82 (d, J=14.5 Hz, 1H), 6.97 (td, J=2.5, 9.0 Hz, 1H), 7.10 (dd, J=2.5, 9.0 Hz, 1H), 7.32 (d, J=8 Hz, 1H), 7.64 (dd, J=4.0, 9.0 Hz, 1H), 7.72 (d, J=14.5 Hz, 1H), 7.99 (dd, J=2.3, 8.0 Hz, 1H), 8.55 (d, J=2.1 Hz, 1H); MS (ESI) m/z 348 (M+H)+.
Reaction SMILES: [Cl:1][C:2]1[C:3]([C:10]([O:12]C)=[O:11])=[N:4][C:5]([Cl:9])=[CH:6][C:7]=1[Cl:8].[OH-].[Na+]>CO>[Cl:1][C:2]1[C:3]([C:10]([OH:12])=[O:11])=[N:4][C:5]([Cl:9])=[CH:6][C:7]=1[Cl:8]
Reactant: COC(=O)c1nc(Cl)cc(Cl)c1Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: O=C(O)c1nc(Cl)cc(Cl)c1Cl
Temperature: 25 °C
Reaction time: 1 h
Yield: 93.1 %

Procedure:
To methyl 3,4,6-Trichloropicolinate (3.57 g, 14.85 mmol) in 20 mL of methanol was added 1N NaOH (14.85 mL, 14.85 mmol). The reaction mixture was stirred at room temperature for 1 hr and then concentrated to dryness in vacuo. 100 mL each of diethyl ether and H2O were added. Aqueous layer was acidified with 1N HCl until pH=2. Methylene chloride was added and the aqueous phase was extracted with additional CH2Cl2 (2×100 mL). The combined extracts were dried (MgSO4) and concentrated to give 3.13 g of a white solid. 1H NMR(CDCl3): δ 7.50 (s, 1H).
Reaction SMILES: [CH2:1]([C:3]1([CH3:14])[CH:8]([CH3:9])[C:7](=[O:10])[CH2:6][C:5]([CH2:12][CH3:13])([CH3:11])[NH:4]1)[CH3:2].C(O)C>>[CH2:1]([C:3]1([CH3:14])[CH:8]([CH3:9])[CH:7]([OH:10])[CH2:6][C:5]([CH2:12][CH3:13])([CH3:11])[NH:4]1)[CH3:2]
Reactant: CCC1(C)CC(=O)C(C)C(C)(CC)N1
Solvent: CCO
Product: CCC1(C)CC(O)C(C)C(C)(CC)N1
Temperature: 50 °C
Reaction time: 2 h

Procedure:
To a solution of 118.2 g (0.6 mol) 2,6-diethyl-2,3,6-trimethyl-4-oxopiperidine in 1000 ml ethanol 18.2 g (0.4 mol) sodium borohydride are added in portions and the temperature is kept below 30° C. Subsequently the solution is stirred for 2 hours at 50° C. Ethanol is distilled off, 500 ml water are added to the residue which is subsequently extracted several times with CH2Cl2. The extract is dried over Na2SO4 and the solution is filtered. After removing the solvent 116 g (97%) 2,6-diethyl-2,3,6-trimethyl-4-hydroxypiperidine are obtained as yellowish liquid.
Reaction SMILES: [CH2:1]([C:5]1[N:6]([CH2:20][C:21]2[CH:26]=[CH:25][C:24]([C:27]3[C:28]([C:33]#[N:34])=[CH:29][CH:30]=[CH:31][CH:32]=3)=[CH:23][CH:22]=2)[C:7](=[O:19])[C:8]([CH2:12][C:13](=[O:18])[C:14]([CH3:17])([CH3:16])[CH3:15])=[C:9]([CH3:11])[N:10]=1)[CH2:2][CH2:3][CH3:4].C(OCC)(=O)C.O>C(O)C>[CH2:1]([C:5]1[N:6]([CH2:20][C:21]2[CH:22]=[CH:23][C:24]([C:27]3[C:28]([C:33]#[N:34])=[CH:29][CH:30]=[CH:31][CH:32]=3)=[CH:25][CH:26]=2)[C:7](=[O:19])[C:8]([CH2:12][CH:13]([OH:18])[C:14]([CH3:16])([CH3:17])[CH3:15])=[C:9]([CH3:11])[N:10]=1)[CH2:2][CH2:3][CH3:4]
Reactant: CCCCc1nc(C)c(CC(=O)C(C)(C)C)c(=O)n1Cc1ccc(-c2ccccc2C#N)cc1
Solvent: CCOC(C)=O
Solvent: CCO
Solvent: O
Product: CCCCc1nc(C)c(CC(O)C(C)(C)C)c(=O)n1Cc1ccc(-c2ccccc2C#N)cc1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
To a solution of 4′-{[2-butyl-5-(3,3-dimethyl-2-oxobutyl)-4-methyl-6-oxopyrimidin-1(6H)-yl]methyl}biphenyl-2-carbonitrile (0.33 g) in ethanol (4 mL) was added sodium tetrahydroboron (0.053 g), and the mixture was stirred at room temperature for 3 hr. Ethyl acetate and water were added to the reaction mixture, and the aqueous layer was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated and the residue was purified by silica gel column chromatography to give the title compound as a pale-yellow viscous substance (0.20 g, 62%).
Reaction SMILES: Br[C:2]1[CH:3]=[CH:4][C:5](=[O:8])[NH:6][CH:7]=1.[S-:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.[K+]>CN1CCCC1=O.O>[C:10]1([S:9][C:2]2[CH:3]=[CH:4][C:5](=[O:8])[NH:6][CH:7]=2)[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1
Reactant: O=c1ccc(Br)c[nH]1
Reactant: [S-]c1ccccc1
Agent: [K+]
Solvent: CN1CCCC1=O
Solvent: O
Product: O=c1ccc(Sc2ccccc2)c[nH]1

Procedure:
A solution of 5-bromo-2-pyridone (17.3 g 0.1 mole) in N-methylpyrrolidinone (250 ml.) and potassium thiophenoxide (18.1 g, 0.12 mole) is heated at reflux for 12 hours under a nitrogen atmosphere. The reaction mixture is cooled and diluted with water. The product is collected by filtration, washed with water and dried to yeild 5-(phenylthio)-2-pyridone.
Reaction SMILES: [CH2:1]([N:8]1[C:20]2[CH:19]=[CH:18][C:17]([C:21]3[CH:30]=[CH:29][C:24]([O:25][CH2:26][C:27]#[N:28])=[CH:23][CH:22]=3)=[CH:16][C:15]=2[C:14]2[CH2:13][CH2:12][CH2:11][CH2:10][C:9]1=2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[N-:31]=[N+:32]=[N-:33].[Na+].[NH4+].[Cl-]>CN(C=O)C>[CH2:1]([N:8]1[C:9]2[CH2:10][CH2:11][CH2:12][CH2:13][C:14]=2[C:15]2[C:20]1=[CH:19][CH:18]=[C:17]([C:21]1[CH:22]=[CH:23][C:24]([O:25][CH2:26][C:27]3[NH:33][N:32]=[N:31][N:28]=3)=[CH:29][CH:30]=1)[CH:16]=2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: [N-]=[N+]=[N-]
Reactant: N#CCOc1ccc(-c2ccc3c(c2)c2c(n3Cc3ccccc3)CCCC2)cc1
Agent: [Cl-]
Agent: [NH4+]
Agent: [Na+]
Solvent: CN(C)C=O
Product: c1ccc(Cn2c3c(c4cc(-c5ccc(OCc6nnn[nH]6)cc5)ccc42)CCCC3)cc1

Procedure:
The desired product was prepared using a procedure similar to step 6 of example 3. Thus, [4-(9-benzyl-6,7,8,9-tetrahydro-5H-carbazol-3-yl)-phenoxy]-acetonitrile (0.357 g, 0.910 mmol) was reacted with NaN3 (0.296 g, 4.548 mmol) and NH4Cl (0.243 g, 4.548 mmol) in DMF (10 ml) to give the product (0.329 g, 0.755 mmol, 83%) as a white solid, dec. 228-230° C. 1H NMR (DMSO-d6) δ 1.79-1.85 (m, 4H), 2.64-2.71 (m, 4H), 5.33 (s, 2H), 5.50 (s, 2H), 7.03 (d, J=7.6 Hz, 2H), 7.11 (d, J=8.7 Hz, 2H), 7.21 (t, J=7.2 Hz, 1H), 7.27-7.30 (m, 3H), 7.39 (d, J=8.6 Hz, 1H), 7.59-7.61 (m, 3H), 16.80 (broad s, 1H); IR (solid) 3030, 2920, 2590, 1520, 1470 and 1240 cm−1; [ESI(+)], m/z 436 (M+H)+; Anal. Calcd. for C27H25N5O: C, 74.46; H, 5.79; N, 16.08; Found: C, 74.34; H, 5.46; N, 16.26.
Reaction SMILES: [NH2:1][C:2]1[C:3]2[C:8]([C:9]3[CH:10]=[CH:11][CH:12]=[CH:13][C:14]=3[CH:15]=1)=[CH:7][CH:6]=[CH:5][CH:4]=2.[CH3:16][C:17](=[CH2:20])[CH:18]=O.[OH-].[Na+]>[Cl-].[Zn+2].[Cl-].C(O)(=O)C>[CH3:20][C:17]1[CH:16]=[N:1][C:2]2[C:15]([CH:18]=1)=[C:14]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]1=[C:8]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=21
Reactant: Nc1cc2ccccc2c2ccccc12
Reactant: C=C(C)C=O
Agent: [Cl-]
Agent: [Na+]
Agent: [OH-]
Solvent: CC(=O)O
Product: Cc1cnc2c3ccccc3c3ccccc3c2c1
Yield: 41 %

Procedure:
1.58 g of 9-aminophenanthrene (8.2 mmol) was added into a two-necked bottle and placed in a drying oven. After 1.33 g of ferric chloride (8.2 mmol) and 1.12 g of zinc chloride (8.2 mmol) were added, a nitrogen gas was conducted. Next, 18 ml of acetic acid was slowly added. 690 mg of methyl propenal (9.8 mmol) was then added with thermal reflux for three hours. After cooling, 15% of the NaOH aqueous solution was slowly added under an ice bath to neutralize the pH level to 7. Next, the resulting solution was extracted by adding ethyl acetate and a saturated NaHCO3 aqueous solution. Following, water was removed by adding dried magnesium sulfate and solvent was removed by using filtration and concentration processes. The result was next purified using column chromatography using n-hexane/ethyl acetate (4:1) as an eluent. 817 mg of a white 3-methyl dibenzo[h,f]quinoline (3 mDBQ) solid was obtained, with a yield of 41%.
Reaction SMILES: [CH3:1][O:2][CH2:3][C:4]1([CH2:17][OH:18])[C:16]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[C:10]2[C:5]1=[CH:6][CH:7]=[CH:8][CH:9]=2.C(N(CC)CC)C.[CH3:26][Si:27](Cl)([CH3:34])[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1>ClCCl>[CH3:1][O:2][CH2:3][C:4]1([CH2:17][O:18][Si:27]([CH3:34])([CH3:26])[C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[C:16]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[C:10]2[C:5]1=[CH:6][CH:7]=[CH:8][CH:9]=2
Reactant: C[Si](C)(Cl)c1ccccc1
Reactant: COCC1(CO)c2ccccc2-c2ccccc21
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: COCC1(CO[Si](C)(C)c2ccccc2)c2ccccc2-c2ccccc21
Temperature: 0 °C
Reaction time: 0.08 h
Yield: 92.4 %

Procedure:
1 g of 9-methoxymethyl-9-hydroxymethyl-fluorene (4.2 mmol) was dissolved in 20 ml of dichloromethane. The solution was cooled in ice-water bath, and 1 ml of triethyl amine (7 mmol) was added thereto. After stirring for 5 minutes, 1 ml of dimethylphenylsilyl chloride (6.2 mmol) was added drop-wise, and the mixture was stirred for further 2 hours, followed by stirring at room temperature for 1 hour. The reaction mixture was washed with water, and the organic layer separated was dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated, and the remainder was purified through column chromatography to give 1.44 g of concentrate (yield 92.4%).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[N:10]=[C:11](Cl)[C:12]3[C:17]([CH:18]=2)=[CH:16][CH:15]=[CH:14][CH:13]=3)=[CH:5][CH:4]=1.[Cl-].[NH4+].O1CCC[CH2:23]1>Cl[Ni]1(Cl)[P](C2C=CC=CC=2)(C2C=CC=CC=2)CCC[P]1(C1C=CC=CC=1)C1C=CC=CC=1>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[N:10]=[C:11]([CH3:23])[C:12]3[C:17]([CH:18]=2)=[CH:16][CH:15]=[CH:14][CH:13]=3)=[CH:5][CH:4]=1
Reactant: C1CCOC1
Reactant: COc1ccc(-c2cc3ccccc3c(Cl)n2)cc1
Agent: Cl[Ni]1(Cl)[P](c2ccccc2)(c2ccccc2)CCC[P]1(c1ccccc1)c1ccccc1
Agent: [Cl-]
Agent: [NH4+]
Product: COc1ccc(-c2cc3ccccc3c(C)n2)cc1
Yield: 100 %

Procedure:
3-(4-Methoxyphenyl)-1-chloroisoquinoline (3.25 g) was dissolved in tetrahydrofuran (30 ml), followed by the addition of 3.0M ethylmagnesium bromide diethyl ether solution (12 ml) and NiCl2(dppp) (50 mg) at 0° C. After the mixture was reacted overnight at room temperature, the resulting reaction solution was poured into an aqueous solution of saturated ammonium chloride and extracted with ethyl acetate. The resulting organic layer was washed with water and brine, dried and evaporated, to give 3-(4-methoxyphenyl)-1-methylisoquinoline as an oil (3.3 g, yield; 100%).
Reaction SMILES: [CH3:1][C:2](=[CH:4][CH2:5][CH2:6]/[C:7](=[CH:9]/[CH2:10][OH:11])/[CH3:8])[CH3:3].OC/C=C(/C)\CCC=C(C)C>>[CH3:1][C:2](=[CH:4][CH2:5][CH2:6][CH:7]([CH2:9][CH2:10][OH:11])[CH3:8])[CH3:3]
Reactant: CC(C)=CCC/C(C)=C/CO
Agent: CC(C)=CCC/C(C)=C\CO
Product: CC(C)=CCCC(C)CCO

Procedure:
geraniol and nerol: 92.0