Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C1(P(C2CCCCC2)C2C=CC=CC=2C2C(N(C)C)=CC=CC=2)CCCCC1.[CH2:29]([O:36][C:37]1[C:42](Br)=[CH:41][CH:40]=[CH:39][N:38]=1)[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1.[N:44]1([C:50]([O:52][CH2:53][C:54]2[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=2)=[O:51])[CH2:49][CH2:48][NH:47][CH2:46][CH2:45]1.CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1.O.C1(/C=C/C(=O)/C=C/C2C=CC=CC=2)C=CC=CC=1.[Pd]>[CH2:29]([O:36][C:37]1[C:42]([N:47]2[CH2:46][CH2:45][N:44]([C:50]([O:52][CH2:53][C:54]3[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=3)=[O:51])[CH2:49][CH2:48]2)=[CH:41][CH:40]=[CH:39][N:38]=1)[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1
Reactant: O=C(OCc1ccccc1)N1CCNCC1
Reactant: Brc1cccnc1OCc1ccccc1
Agent: [Pd]
Agent: CC(C)(C)[O-]
Agent: CN(C)c1ccccc1-c1ccccc1P(C1CCCCC1)C1CCCCC1
Solvent: Cc1ccccc1
Solvent: O
Product: O=C(OCc1ccccc1)N1CCN(c2cccnc2OCc2ccccc2)CC1
Temperature: 80 °C
Reaction time: 0.33 h
Yield: 54.4 %

Procedure:
To a stirred suspension of 0.011 g (0.012 mmol) of (1E,4E)-1,5-diphenylpenta-1,4-dien-3-one-palladium (3:2) in 3 mL of anhydrous toluene under an atmosphere of nitrogen was added 0.015 g (0.037 mmol) of 2′-(dicyclohexylphosphino)-N,N-dimethylbiphenyl-2-amine and the resulting mixture was allowed to stir for 20 min. Next, 0.11 g (0.41 mmol) of 2-(benzyloxy)-3-bromopyridine was added followed by 0.11 g (0.49 mmol) of benzyl piperazine-1-carboxylate and 0.059 g (0.61 mmol) of sodium tert-butoxide. The resulting mixture was then heated to 80° C. overnight. After cooling to ambient temperature, the reaction mixture was diluted with water and extracted with ethyl acetate. The combined organic layers were washed with water then brine, dried over magnesium sulfate and evaporated to dryness in vacuo. The residue was purified by silica gel chromatography eluting with a 0-100% acetone in hexanes gradient to afford the title compound as clear gum (0.090 g, 55%). 1H-NMR (500 MHz, CDCl3) δ 7.84 (dd, J=4.9, 1.6 Hz, 1H), 7.47-7.29 (m, 10H), 7.09 (dd, J=7.5, 1.6 Hz, 1H), 6.87 (dd, J=7.5, 4.9 Hz, 1H), 5.46 (s, 2H), 5.16 (s, 2H), 3.67-3.65 (m, 4H), 3.07 (br s, 4H). LC-MS: m/z (ES) 404.0 (MH)+.
Reaction SMILES: [CH3:1][N:2]([CH2:4][C:5]#[CH:6])[CH3:3].C(NC(C)C)(C)C.I[C:15]1[CH:20]=[CH:19][C:18](/[C:21](/[C:38]2[CH:43]=[CH:42][C:41]([C:44]([F:47])([F:46])[F:45])=[CH:40][CH:39]=2)=[CH:22]\[CH2:23][O:24][C:25]2[CH:36]=[CH:35][C:28]([O:29][CH2:30][C:31]([O:33][CH3:34])=[O:32])=[C:27]([CH3:37])[CH:26]=2)=[CH:17][CH:16]=1>O1CCCC1.[Cu]I.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH3:37][C:27]1[CH:26]=[C:25]([O:24][CH2:23]/[CH:22]=[C:21](\[C:18]2[CH:17]=[CH:16][C:15]([C:6]#[C:5][CH2:4][N:2]([CH3:3])[CH3:1])=[CH:20][CH:19]=2)/[C:38]2[CH:43]=[CH:42][C:41]([C:44]([F:47])([F:46])[F:45])=[CH:40][CH:39]=2)[CH:36]=[CH:35][C:28]=1[O:29][CH2:30][C:31]([O:33][CH3:34])=[O:32]
Reactant: C#CCN(C)C
Reactant: COC(=O)COc1ccc(OC/C=C(\c2ccc(I)cc2)c2ccc(C(F)(F)F)cc2)cc1C
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Cu]I
Solvent: C1CCOC1
Solvent: CC(C)NC(C)C
Product: COC(=O)COc1ccc(OC/C=C(\c2ccc(C#CCN(C)C)cc2)c2ccc(C(F)(F)F)cc2)cc1C
Temperature: 25 °C
Reaction time: 20 h

Procedure:
N,N-Dimethylpropargylamine (0.11 mL, 1.03 mmol) and diisopropylamine (0.34 mL, 2.42 mmol) were added to a solution of methyl (Z)-[4-[3-(4-iodophenyl)-3-(4-trifluoromethylphenyl)allyloxy]-2-methylphenoxy]acetate (300 mg, 0.515 mmol; example 4) in tetrahydrofuran (10 mL). The mixture was degassed and copper(I) iodide (8 mg, 0.042 mmol) and bis(triphenylphosphine)palladium(II) dichloride (18 mg, 0.026 mmol) were added. The reaction mixture was stirred at ambient temperature for 20 h and evaporated in vacuo. The residue was purified by flash column chromatography (silica gel Fluka 60, dichloromethane-/methanol 98:2) yielding methyl (E)-[2-methyl-4-[3-[4-[3-(N,N-dimethylamino)propynyl]-phenyl]-3-(4-trifluoromethylphenyl)allyloxy]phenoxy]acetate as brown oil.
Reaction SMILES: [F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].[C:8]([C:10]1[CH:11]=[C:12]([C:20]2[O:24][N:23]=[C:22]([C:25]3[C:26]([CH3:42])=[C:27]4[C:32](=[CH:33][CH:34]=3)[CH2:31][N:30](C(OC(C)(C)C)=O)[CH2:29][CH2:28]4)[N:21]=2)[CH:13]=[CH:14][C:15]=1[O:16][CH:17]([CH3:19])[CH3:18])#[N:9]>ClCCl>[F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].[CH3:19][CH:17]([O:16][C:15]1[CH:14]=[CH:13][C:12]([C:20]2[O:24][N:23]=[C:22]([C:25]3[C:26]([CH3:42])=[C:27]4[C:32](=[CH:33][CH:34]=3)[CH2:31][NH:30][CH2:29][CH2:28]4)[N:21]=2)=[CH:11][C:10]=1[C:8]#[N:9])[CH3:18]
Reactant: Cc1c(-c2noc(-c3ccc(OC(C)C)c(C#N)c3)n2)ccc2c1CCN(C(=O)OC(C)(C)C)C2
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: Cc1c(-c2noc(-c3ccc(OC(C)C)c(C#N)c3)n2)ccc2c1CCNC2
Temperature: 0 °C
Reaction time: 0.5 h

Procedure:
Trifluoroacetic acid (3 ml) was added to an ice cooled solution of 1,1-dimethylethyl 6-(5-{3-cyano-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-5-methyl-3,4-dihydro-2(1H)-isoquinolinecarboxylate (Preparation 22; 486 mg, 1.02 mmol) in dichloromethane (3 ml). The reaction mixture was stirred at 0° C. for 30 minutes. The solvent was evaporated and the residue co-evaporated from toluene (×2). Trituration of the residue with diethyl ether gave the title compound as a colourless solid which was filtered off and dried (485 mg). 1H NMR (400 MHz, CDCl3) δ: 1.48 (6H, d), 2.54 (3H, s), 3.09 (2H, m), 3.5 (2H, obscured by residual solvent), 4.36 (2H, s), 4.80 (1H, m), 7.08-7.15 (2H, m), 7.85 (1H, d), 8.33 (1H, d), 8.42 (1H, s), 10.20 (2H, br s). MS m/z 375 [MH]+.
Reaction SMILES: [OH:1][CH2:2][C@H:3]([NH:21][C:22](=[O:28])[O:23][C:24]([CH3:27])([CH3:26])[CH3:25])[C@H:4]([OH:20])[C:5]#[C:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH3:19].C1(C)C=CC=CC=1.[H-].COCCO[Al+]OCCOC.[Na+].[H-].Cl>C1COCC1>[C:24]([O:23][C:22]([NH:21][C@H:3]([C@@H:4](/[CH:5]=[CH:6]/[CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH3:19])[OH:20])[CH2:2][OH:1])=[O:28])([CH3:27])([CH3:26])[CH3:25]
Reactant: CCCCCCCCCCCCCC#C[C@@H](O)[C@H](CO)NC(=O)OC(C)(C)C
Agent: COCCO[Al+]OCCOC
Agent: Cl
Agent: [H-]
Solvent: Cc1ccccc1
Solvent: C1CCOC1
Product: CCCCCCCCCCCCC/C=C/[C@@H](O)[C@H](CO)NC(=O)OC(C)(C)C
Temperature: 0 °C
Reaction time: 2.5 h
Yield: 62 %

Procedure:
The tert-butyl (2S,3R)-1,3-dihydroxyoctadec-4-yn-2-ylcarbamate (85 mg, 0.21 mmol) obtained in the above-described reaction was dissolved in THF (21 ml) and cooled to 0° C.; a 65% toluene solution of sodium bis(2-methoxyethoxy)aluminium hydride (Red-Al) (258 μl, 0.850 mmol) was subsequently added dropwise. The resulting mixture was heated to room temperature and stirred for 2.5 hours. 1 M hydrochloric acid was subsequently added to the mixture, and the reaction was stopped; the mixture was extracted with diethylether, and the organic layer was dried over anhydrous sodium sulfate, filtered and concentrated. The concentrate was purified by silica gel column chromatography to produce N-tert-butoxycarbonyl sphingosine (52 mg, 64%).
Reaction SMILES: [CH:1]1([C:8](=O)[CH:9]([C:15]2[C:20]([F:21])=[CH:19][C:18]([F:22])=[CH:17][C:16]=2[F:23])[C:10](OCC)=[O:11])[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:25][C:26]1[N:30]=[CH:29][NH:28][N:27]=1.C(N(CCCC)CCCC)CCC>C(OCC)(=O)C>[CH:1]1([C:8]2[N:27]3[N:28]=[CH:29][N:30]=[C:26]3[N:25]=[C:10]([OH:11])[C:9]=2[C:15]2[C:20]([F:21])=[CH:19][C:18]([F:22])=[CH:17][C:16]=2[F:23])[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: Nc1nc[nH]n1
Reactant: CCOC(=O)C(C(=O)C1CCCCCC1)c1c(F)cc(F)cc1F
Solvent: CCCCN(CCCC)CCCC
Solvent: CCOC(C)=O
Product: Oc1nc2ncnn2c(C2CCCCCC2)c1-c1c(F)cc(F)cc1F
Temperature: 160 °C
Reaction time: 2.5 h
Yield: 62.1 %

Procedure:
A mixture of ethyl 3-cycloheptyl-3-oxo-2-(2,4,6-trifluorophenyl)propanoate (342 mg, 1.0 mmol), 3-amino-1,2,4-triazole (84 mg, 1.0 mmol), and tributylamine (185 mg, 1.0 mmol) is stirred under nitrogen atmosphere at 160° C. for 2.5 h and cooled to room temperature. The mixture is dissolved in ethyl acetate and the organic layer is washed with 1.0 N hydrochloric acid and saturated sodium chloride, dried over magnesium sulfate, and concentrated to a solid. The solid thus obtained is washed with hexanes to give crude 7-cycloheptyl-6-(2,4,6-trifluorophenyl)[1,2,4]triazolo[1,5-a]pyrimidin-5-ol as a light tan solid (225 mg). MS: m/z 363.2 (M+H).
Reaction SMILES: [C:1]1([CH:7]([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[N:8]2[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[CH:10]([C:17]3[C:27]([OH:28])=[CH:26][C:20]4[O:21][CH2:22][CH2:23][CH2:24][O:25][C:19]=4[CH:18]=3)[C:9]2=[O:29])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:36]1(C(C2C=CC=CC=2)N2C3C(=CC=CC=3)C(C3C=C(C)C(OC)=CC=3O)C2=O)C=CC=CC=1>>[C:30]1([CH:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[N:8]2[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[C:10]3([C:17]4=[CH:18][C:19]5[O:25][CH2:24][CH2:23][CH2:22][O:21][C:20]=5[CH:26]=[C:27]4[O:28][CH2:36]3)[C:9]2=[O:29])[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=1
Reactant: COc1cc(O)c(C2C(=O)N(C(c3ccccc3)c3ccccc3)c3ccccc32)cc1C
Reactant: O=C1C(c2cc3c(cc2O)OCCCO3)c2ccccc2N1C(c1ccccc1)c1ccccc1
Product: O=C1N(C(c2ccccc2)c2ccccc2)c2ccccc2C12COc1cc3c(cc12)OCCCO3

Procedure:
Following the procedure as described in EXAMPLE 2 and making non-critical variations using 1-(diphenylmethyl)-3-(8-hydroxy-3,4-dihydro-2H-1,5-benzo-dioxepin-7-yl)-1,3-dihydro-2H-indol-2-one to replace 1-(diphenylmethyl)-3-(2-hydroxy-4-methoxy-5-methylphenyl)-1,3-dihydro-2H-indol-2-one, 1′-(diphenylmethyl)-3,4-dihydro-2H-spiro[furo[2,3-h][1,5]benzodioxepine-9,3′-indol]-2′(1H)-one was obtained (75%) as a pale pink solid: mp 165-168° C. (ethyl acetate/methanol); 1H NMR (300 MHz, CDCl3) δ 7.42-7.28 (m, 10H), 7.15 (dd, J=7.2, 1.4 Hz, 1H), 7.06 (s, 1H), 7.04-6.94 (m, 2H), 6.61 (s, 1H), 6.50 (d, J=7.5 Hz, 1H), 6.35 (s, 1H), 4.98 (d, J=9.0 Hz, 1H), 4.71 (d, J=9.0 Hz, 1H), 4.29-4.22 (m, 1H), 4.16-4.03 (m, 2H), 4.01-3.93 (m, 1H), 2.24-2.01 (m, 2H); 13C NMR (75 MHz, CDCl3) δ177.7, 156.9, 153.1, 146.4, 141.8, 137.7, 137.6, 132.5, 128.9, 128.8, 128.6, 128.44, 128.41, 128.0, 124.0, 123.4, 123.2, 116.1, 112.3, 103.6, 80.7, 70.92, 70.88, 58.8, 57.8, 32.3; MS (ES+) m/z 476.1 (M+1).
Reaction SMILES: O[C:2]1[C:11]2[C:6](=[CH:7][C:8]([C:12]([F:15])([F:14])[F:13])=[CH:9][CH:10]=2)[N:5]=[CH:4][CH:3]=1.[Cl:16]CCl>O=P(Cl)(Cl)Cl>[Cl:16][C:2]1[C:11]2[C:6](=[CH:7][C:8]([C:12]([F:15])([F:14])[F:13])=[CH:9][CH:10]=2)[N:5]=[CH:4][CH:3]=1
Reactant: Oc1ccnc2cc(C(F)(F)F)ccc12
Reactant: ClCCl
Solvent: O=P(Cl)(Cl)Cl
Product: FC(F)(F)c1ccc2c(Cl)ccnc2c1

Procedure:
A solution of 4-hydroxy-7-trifluoromethylquinoline (1 g) in dichloromethane (10 mL) and POCl3 (1 mL) was refluxed for half an hour. Then the reaction mixture was quenched with water (80 mL) and sodium bicarbonate to pH 7. The aqueous solution was extracted with dichloromethane (2×60 mL). The organic layers were combined, dried, evaporated to give 4-chloro-7-trifluoromethylquinoline. LCMS: ret. time: 31.51 min.; purity: 100%; MS (m/e): 232 (MH+).
Reaction SMILES: [CH2:1]([N:4]([CH2:6][CH2:7][CH2:8][CH2:9][O:10][C:11]1[CH:12]=[C:13]2[C:17](=[CH:18][CH:19]=1)[NH:16][C:15]([CH3:20])=[C:14]2[CH3:21])[CH3:5])[CH:2]=[CH2:3].F[C:23]1[CH:28]=[CH:27][C:26]([Br:29])=[CH:25][CH:24]=1>>[CH2:1]([N:4]([CH2:6][CH2:7][CH2:8][CH2:9][O:10][C:11]1[CH:12]=[C:13]2[C:17](=[CH:18][CH:19]=1)[N:16]([C:23]1[CH:28]=[CH:27][C:26]([Br:29])=[CH:25][CH:24]=1)[C:15]([CH3:20])=[C:14]2[CH3:21])[CH3:5])[CH:2]=[CH2:3]
Reactant: C=CCN(C)CCCCOc1ccc2[nH]c(C)c(C)c2c1
Reactant: Fc1ccc(Br)cc1
Product: C=CCN(C)CCCCOc1ccc2c(c1)c(C)c(C)n2-c1ccc(Br)cc1

Procedure:
In analogy to example 9.1, Allyl-[4-(2,3-dimethyl-1H-indol-5-yloxy)-butyl]-methyl-amine and 1-fluoro-4-bromobenzene were converted to yield Allyl-{4-[1-(4-bromo-phenyl)-2,3-dimethyl-1H-indol-5-yloxy]-butyl}-methyl-amine as orange oil, MS: 441 (MH+,1 Br).
Reaction SMILES: [CH2:1]([N:4](C(OC(C)(C)C)=O)[CH2:5][CH2:6][CH2:7][N:8](C(OC(C)(C)C)=O)[CH2:9]/[CH:10]=[CH:11]/[CH2:12][N:13](C(OC(C)(C)C)=O)[CH2:14][CH2:15][CH2:16][N:17]([CH2:25][C:26]#[CH:27])C(OC(C)(C)C)=O)[CH:2]=[CH2:3].[ClH:49]>>[ClH:49].[ClH:49].[ClH:49].[ClH:49].[CH2:1]([NH:4][CH2:5][CH2:6][CH2:7][NH:8][CH2:9]/[CH:10]=[CH:11]/[CH2:12][NH:13][CH2:14][CH2:15][CH2:16][NH:17][CH2:25][C:26]#[CH:27])[CH:2]=[CH2:3]
Reactant: C#CCN(CCCN(C/C=C/CN(CCCN(CC=C)C(=O)OC(C)(C)C)C(=O)OC(C)(C)C)C(=O)OC(C)(C)C)C(=O)OC(C)(C)C
Agent: Cl
Product: C#CCNCCCNC/C=C/CNCCCNCC=C

Procedure:
A mixture of 0.22 g (0.324 mmol) of (E)-1-allyl-14-propargyl-1,5,10,14-tetra-BOC-1,5,10,14-tetraazatetradec-7-ene and 3.3 ml of 3N methanolic hydrochloric acid is reacted analogously to Example 8. The resulting title compound melts at >260° C. 1H-NMR (D2O): δ2.07-2.19(m,4H); 3.02(t,1H); 3.08-3.34(m,8H); 3.69(d,2H); 3.77(d,4H); 3.96(d,2H); 5.48-5.55(m,2H); 5.84-5.97(m,1H); 6.04-6.07(m,2H).
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([C:11]([NH2:13])=[O:12])[CH:10]=1)[NH:7][CH:6]=[C:5]2[C@@H:14]1[CH2:19][CH2:18][S:17](=[O:21])(=[O:20])[C@@H:16]([CH:22]([CH3:24])[CH3:23])[CH2:15]1.[O:25]1[CH2:30][CH2:29]O[CH2:27][CH2:26]1.O1C=CC=C1B(O)O.C([O-])([O-])=O.[K+].[K+]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].O>[O:25]1[CH:30]=[CH:29][CH:27]=[C:26]1[C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([C:11]([NH2:13])=[O:12])[CH:10]=1)[NH:7][CH:6]=[C:5]2[C@@H:14]1[CH2:19][CH2:18][S:17](=[O:21])(=[O:20])[C@@H:16]([CH:22]([CH3:23])[CH3:24])[CH2:15]1
Reactant: CC(C)[C@H]1C[C@H](c2c[nH]c3c(C(N)=O)cc(Br)cc23)CCS1(=O)=O
Reactant: C1COCCO1
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: O=C([O-])[O-]
Solvent: O
Product: CC(C)[C@H]1C[C@H](c2c[nH]c3c(C(N)=O)cc(-c4ccco4)cc23)CCS1(=O)=O
Reaction time: 0.08 h

Procedure:
(racemic)-5-Bromo-3-[trans-2-(1-methylethyl)-1,1-dioxidotetrahydro-2H-thiopyran-4-yl]-1H-indole-7-carboxamide (60 mg, 0.145 mmol) was placed in a microwave vial and dissolved with 1,4-Dioxane (2 mL) and Water (1 mL). 2-Furanylboronic acid (33 mg, 0.29 mmol) and K2CO3 (60 mg, 0.44 mmol) were added. Argon was bubbled into the mixture for 10 mins, stirring. PdCl2(dppf) (5.60 mg, 0.012 mmol) was added, and argon was bubbled another 10 mins. The vial was sealed and put under microwave 5 mins at 100° C. with high absorption parameter. The crude was run through a thiol-SPE cartridge eluting with 2 mL of methanol and the eluted solvents are evaporated. The brown oil was dissolved in 2-3 mL of DMSO, and on a Gilson HPLC. The desired fractions were concentrated, giving 32 mg of the title compound.
Reaction SMILES: Cl[SiH](Cl)Cl.[C:5]1([PH:11](=O)[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1.C(N(CC)CC)C.[OH-].[Na+]>C1(C)C=CC=CC=1.C(Cl)Cl>[C:12]1([PH:11][C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1
Reactant: O=[PH](c1ccccc1)c1ccccc1
Agent: Cl[SiH](Cl)Cl
Agent: [Na+]
Agent: [OH-]
Solvent: Cc1ccccc1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: c1ccc(Pc2ccccc2)cc1
Yield: 79 %

Procedure:
Trichlorosilane (0.1 ml, 1 mmol) was added, at room temperature, to a suspension of (1H, 1H, 2H, 2H-perfluorooctyl)diphenylphosphine oxide (55 mg, 0.1 mmol) and triethylamine (0.1 ml, 0.7 mmol) in toluene (5 ml). The mixture was then heated at 100 C. overnight and then allowed to cool. Aqueous sodium hydroxide (40 ml of a 1M solution) was added and the resulting mixture extracted with ether (4×25 ml). The organic fractions were combined, dried (MgSO4) and concentrated in vacuo to give the crude product. The product was purified by flash column chromatography on silica gel, eluting with hexane to give a white crystalline solid (42 mg, 0.079 mmol, 79%), mp (CH2Cl2) 44-45° C. (Found: M+,532.0600. C20H14F13P requires M+, 532.0625).
Reaction SMILES: C(OC([N:8]1[CH2:13][CH2:12][CH2:11][CH2:10][CH:9]1[CH2:14][CH2:15][O:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1[CH2:23][CH2:24][CH2:25][CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[C:29]([O:33][CH3:34])[CH:28]=1)=O)(C)(C)C.[ClH:35]>O1CCOCC1>[ClH:35].[CH3:34][O:33][C:29]1[CH:28]=[C:27]([CH2:26][CH2:25][CH2:24][CH2:23][C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][C:17]=2[O:16][CH2:15][CH2:14][CH:9]2[CH2:10][CH2:11][CH2:12][CH2:13][NH:8]2)[CH:32]=[CH:31][CH:30]=1
Reactant: COc1cccc(CCCCc2ccccc2OCCC2CCCCN2C(=O)OC(C)(C)C)c1
Agent: Cl
Solvent: C1COCCO1
Product: COc1cccc(CCCCc2ccccc2OCCC2CCCCN2)c1
Reaction time: 0.5 h
Yield: 80 %

Procedure:
400 mg of 1-t-butoxycarbonyl-2-(2-{2-[4-(3-methoxyphenyl)butyl]phenoxy}ethyl)piperidine [prepared as described in step (a) above] were dissolved in 2 ml of dioxane, and 2 ml of a 4N solution of hydrogen chloride in dioxane were added to the solution, which was then allowed to stand at room temperature for 30 minutes. At the end of this time, the solution was concentrated by distillation under reduced pressure, and the resulting oil was dissolved in diethyl ether and allowed to stand at room temperature. The crystals which precipitated were collected by filtration and dried in vacuo, to give 276 mg (yield 80%) of the title compound as a colorless solid, melting at 76°-79° C.
Reaction SMILES: [C:1]([O:5]CC)(=O)[CH:2]=[CH2:3].[Cl:8][C:9]1[CH:14]=[C:13]([Cl:15])[CH:12]=[CH:11][C:10]=1[NH:16][NH2:17].[O-]CC.[Na+].C(O)C>C1(C)C=CC=CC=1>[Cl:8][C:9]1[CH:14]=[C:13]([Cl:15])[CH:12]=[CH:11][C:10]=1[N:16]1[CH2:3][CH2:2][C:1](=[O:5])[NH:17]1
Reactant: NNc1ccc(Cl)cc1Cl
Reactant: C=CC(=O)OCC
Agent: CC[O-]
Agent: [Na+]
Solvent: Cc1ccccc1
Solvent: CCO
Product: O=C1CCN(c2ccc(Cl)cc2Cl)N1
Reaction time: 1 h

Procedure:
105.0 g (1.05 mol) of ethyl acrylate is added dropwise to a mixture of 37.3 g (211 mmol) of 2,4-dichlorophenylhydrazine, 18.6 g (273 mmol) of sodium ethoxide, 150 ml of ethanol and 150 ml of toluene and the mixture is subsequently stirred for 1 hour. The reaction mixture is evaporated to 100 ml and the residue is taken up in water. The organic phase is separated off and extracted with 5% strength NaOH. The combined aqueous phases are adjusted to a pH of 6.5 and the solid formed is filtered off with suction, washed with water and dried under reduced pressure.
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:8][C:9]([NH:11][CH3:12])=[O:10].[N+](C1C=C(S(O[CH2:26][C@@H:27]2[CH2:29][O:28]2)(=O)=O)C=CC=1)([O-])=O.C(=O)([O-])[O-].[Cs+].[Cs+]>CN1CCCC1=O.O>[CH3:12][NH:11][C:9](=[O:10])[CH2:8][C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=1[O:1][CH2:26][C@@H:27]1[CH2:29][O:28]1
Reactant: CNC(=O)Cc1ccccc1O
Reactant: O=[N+]([O-])c1cccc(S(=O)(=O)OC[C@@H]2CO2)c1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: O
Solvent: CN1CCCC1=O
Product: CNC(=O)Cc1ccccc1OC[C@@H]1CO1
Temperature: 25 °C
Reaction time: 8 h
Yield: 28.9 %

Procedure:
A mixture of 2-(2-hydroxyphenyl)-N-methylacetamide (1.00 g, 6.1 mmol) prepared according to a known procedure (Bernd, Peschke, Eur. J. Med. Chem., 2000, 35, 599-618), (2S)-oxiran-2-ylmethyl 3-nitrobenzenesulfonate (1.58 g, 6.1 mmol) and cesium carbonate (2.37 g, 7.3 mmol) in 1-methylpyrrolidin-2-one (15 ml) was stirred at room temperature overnight. The mixture was diluted with water and extracted with ethyl acetate, the combined organic layers were dried with sodium sulphate, volatiles were removed in vacuo. The residue was purified by recrystillaziation from ethyl acetate/heptane; (390 mg) of the subtitle compound was obtained.
Reaction SMILES: [CH2:1]=[O:2].Br[CH2:4][CH:5]([C:7]1[CH:12]=[CH:11][C:10]([C:13]2[CH:18]=[CH:17][C:16]([F:19])=[CH:15][C:14]=2[F:20])=[CH:9][CH:8]=1)[CH3:6].[Mg]>C1COCC1>[F:20][C:14]1[CH:15]=[C:16]([F:19])[CH:17]=[CH:18][C:13]=1[C:10]1[CH:11]=[CH:12][C:7]([CH:5]([CH3:6])[CH2:4][CH2:1][OH:2])=[CH:8][CH:9]=1
Reactant: C=O
Reactant: CC(CBr)c1ccc(-c2ccc(F)cc2F)cc1
Agent: [Mg]
Solvent: C1CCOC1
Product: CC(CCO)c1ccc(-c2ccc(F)cc2F)cc1
Reaction time: 120 h

Procedure:
0.3 g. of paraformaldehyde is added to Grignard solution prepared from 3.11 g. of 4-(1-bromo-2-propyl)-2',4'-difluorobiphenyl and 0.26 g. of magnesium powder in 40 ml. of THF and the mixture is allowed to stand for 5 days. It is worked up in the customary manner, using ice/dilute hydrochloric acid, to give 3-(2',4'-difluoro-4-biphenylyl)butan-1-ol.
Reaction SMILES: [CH2:1]([N:3]1[C:12]2[C:11](=O)[NH:10][CH2:9][C:8]([C:14]3[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=3)=[N:7][C:6]=2[C:5]([CH3:22])=[N:4]1)[CH3:2].COC1C=CC(P2(SP(C3C=CC(OC)=CC=3)(=S)S2)=[S:32])=CC=1>C1(C)C=CC=CC=1>[CH2:1]([N:3]1[C:12]2[C:11](=[S:32])[NH:10][CH2:9][C:8]([C:14]3[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=3)=[N:7][C:6]=2[C:5]([CH3:22])=[N:4]1)[CH3:2]
Reactant: COc1ccc(P2(=S)SP(=S)(c3ccc(OC)cc3)S2)cc1
Reactant: CCn1nc(C)c2c1C(=O)NCC(c1ccc(OC)cc1)=N2
Solvent: Cc1ccccc1
Product: CCn1nc(C)c2c1C(=S)NCC(c1ccc(OC)cc1)=N2
Yield: 86 %

Procedure:
(R1=methyl; R2=ethyl; R3=4-methoxyphenyl) 2.2 g (7.4 mmol) of 1-ethyl-5-(4-methoxyphenyl)-3-methyl-6,7-dihydro-1H-pyrazolo[4,3-e][1,4]diazepin-8-one are refluxed in toluene with 6 g (14.8 mmol) of Lawesson's reagent to give 2 g (87%) of an expected compound of type E (see Scheme 1).
Reaction SMILES: [H-].[Na+].C1([C@H]([N:11]2[C@H:15]3[CH2:16][O:17][C:18](=[O:19])[C@H:14]3[NH:13][C:12]2=[O:20])C)C=CC=CC=1.[CH2:21](Br)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1>C(COC)OC>[CH2:21]([N:13]1[CH:14]2[C:18](=[O:19])[O:17][CH2:16][CH:15]2[NH:11][C:12]1=[O:20])[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1
Reactant: BrCc1ccccc1
Reactant: C[C@H](c1ccccc1)N1C(=O)N[C@@H]2C(=O)OC[C@@H]21
Agent: [H-]
Agent: [Na+]
Solvent: COCCOC
Product: O=C1OCC2NC(=O)N(Cc3ccccc3)C12
Reaction time: 0.5 h

Procedure:
48 ml of dimethoxyethane and 0.39 g (16.2 mmol) of sodium hydride were placed in a 100-ml three-neck flask equipped with a magnetic stirrer under argon and with complete exclusion of moisture. Then 3.24 g (13.2 mmol) of (3aS,6aR)-1-[(R)-(1-phenylethyl)]-dihydro-1H-furo-[3,4-d]-imidazol-2,4(3H,3aH)-dione was added. After a stirring time of 10 min., 2.76 g (16.2 mmol) of benzyl bromide was added and the suspension was stirred for 30 min. Then the reaction mixture was evaporated. The residue was dissolved with 25 ml of dichloromethane and 25 ml of water. The phases were separated and the aqueous phase was washed three times, each time with 15 ml of water. The organic phases were combined, dried with 5 g of magnesium sulfate and evaporated. (3aS,6aR)-1-[R)-(1-phenylethyl)]-3-benzyl-dihydro-1H-furo-[3,4-d]-imidazol--2,4(3H,3aH)-dione was obtained as a beige product in a yield of 3.56 g (80.5 percent).
Reaction SMILES: C1(S([CH:9]([C:14]2[C:23]3[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=3)[CH:17]=[CH:16][C:15]=2[O:24][CH3:25])[CH2:10][NH:11][CH:12]=[O:13])=O)C=CC=CC=1.C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1>[CH:12]([NH:11]/[CH:10]=[CH:9]/[C:14]1[C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[CH:17]=[CH:16][C:15]=1[O:24][CH3:25])=[O:13]
Reactant: COc1ccc2ccccc2c1C(CNC=O)S(=O)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: Cc1ccccc1
Product: COc1ccc2ccccc2c1/C=C/NC=O
Yield: 90 %

Procedure:
To a solution of 1-(1-phenylsulfinyl-2-formylaminoethyl)-2-methoxynaphthalene (3534 mg, 10 mmol) in toluene (60 ml) is added sodium carbonate (1060 mg, 10 mmol) and the mixture heated at reflux for 6 h. Then the mixture is filtered after cooling and the filtrate concentrated in vacuo. The residue is subjected to column chromatography over silica gel using as eluant cyclohexane/ethyl acetate (1:1) to give pure title compound with m.p. 160°-2° C., in 90% yield (1850 mg).