Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][N:2]1[CH:6]=[C:5]([C:7]2[CH:8]=[C:9]([O:16][CH2:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][N:19]=3)[C:10]3[N:11]([N:13]=[CH:14][CH:15]=3)[CH:12]=2)[CH:4]=[N:3]1.IN1C(=O)CCC1=O.[I-].C(N(CC)CC)C.[CH:40]1([C:43]#[CH:44])[CH2:42][CH2:41]1>CN(C=O)C.[Cu]I.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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH:40]1([C:43]#[C:44][C:15]2[CH:14]=[N:13][N:11]3[CH:12]=[C:7]([C:5]4[CH:4]=[N:3][N:2]([CH3:1])[CH:6]=4)[CH:8]=[C:9]([O:16][CH2:17][C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][N:19]=4)[C:10]=23)[CH2:42][CH2:41]1
Reactant: C#CC1CC1
Reactant: Cn1cc(-c2cc(OCc3ccccn3)c3ccnn3c2)cn1
Agent: [Cu]I
Agent: [Pd]
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: Cn1cc(-c2cc(OCc3ccccn3)c3c(C#CC4CC4)cnn3c2)cn1
Temperature: 25 °C
Reaction time: 0.33 h

Procedure:
6-(1-methyl-1H-pyrazol-4-yl)-4-(pyridin-2-ylmethoxy)pyrazolo[1,5-a]pyridine (10.0 mg, 0.033 mmol) and N-iodosuccinimide (8.8 mg, 0.04 mmol) were dissolved in DMF (1 ml). After 20 minutes, LCMS analysis indicated complete conversion to the iodide. At this time, copper (I) iodide (3.7 mg, 0.02 mmol), tetrakis(triphenylphosphine)palladium (0) (3.8 mg, 3.2 μmol), triethylamine (0.014 ml, 0.098 mmol), and cyclopropylacetylene (6.5 mg, 0.10 mmol) was added, followed by 0.5 mL of DMF to wash down the sides of the flask. The mixture was sparged with argon for 10 minutes then allowed to stir at ambient temperature overnight. The reaction mixture was diluted in ethyl acetate, washed with saturated aqueous sodium hydrogen carbonate and brine then dried over sodium sulfate, filtered and concentrated. The residue was purified by preparative HPLC Reverse phase (C-18), eluting with Acetonitrile/Water+0.05% TFA. The fractions containing product were combined and diluted in ethyl acetate, then washed with aqueous sodium bicarbonate and dried over sodium sulfate. The solution was filtered and concentrated to afford 3-(cyclopropylethynyl)-6-(1-methyl-1H-pyrazol-4-yl)-4-(pyridin-2-ylmethoxy)pyrazolo[1,5-a]pyridine. 1H NMR (500 MHz, DMSO-d6) δ 8.66 (s, 1H); 8.61 (d, 1H); 8.33 (s, 1H); 8.05 (s, 1H); 8.01 (s, 1H); 7.88-7.95 (m, 2H); 7.36-7.40 (m, 1H); 7.15 (s, 1H); 5.38 (s, 2H); 3.86 (s, 3H), 1.51-1.58 (m, 1H); 0.81-0.88 (m, 2H); 0.56-0.60 (m, 2H). LRMS (ESI) calculated for C22H20N5O [M+H]+, 370.2; found 370.1.
Reaction SMILES: [C:1]1([CH3:11])[CH:6]=[CH:5][C:4]([S:7](Cl)(=[O:9])=[O:8])=[CH:3][CH:2]=1.[C:12]([O:15][C:16]1[CH:21]=[CH:20][C:19]([CH2:22][CH2:23][OH:24])=[CH:18][C:17]=1[O:25][CH3:26])(=[O:14])[CH3:13]>N1C=CC=CC=1.O>[C:12]([O:15][C:16]1[CH:21]=[CH:20][C:19]([CH2:22][CH2:23][O:24][S:7]([C:4]2[CH:5]=[CH:6][C:1]([CH3:11])=[CH:2][CH:3]=2)(=[O:9])=[O:8])=[CH:18][C:17]=1[O:25][CH3:26])(=[O:14])[CH3:13]
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Reactant: COc1cc(CCO)ccc1OC(C)=O
Solvent: O
Solvent: c1ccncc1
Product: COc1cc(CCOS(=O)(=O)c2ccc(C)cc2)ccc1OC(C)=O
Reaction time: 72 h

Procedure:
p-Toluenesulfonyl chloride (2.14 mL, 11.2 mmol) was added to a stirred solution of 4-(2-hydroxyethyl)-2-methoxyphenyl acetate (1.18 g, 5.61 mmol) in dry pyridine (20 mL) at 0° C. under N2. The reaction was stored at 4° C. for 3 days. The reaction was diluted with water (50 mL) and extracted with EtOAc (3×50 mL). The combined extracts were dried (MgSO4) and concentrated in vacuo to afford 2-methoxy-4-(2-{[(4-methylphenyl)sulfonyl]oxy}ethyl)phenyl acetate, as an oil. Product was a 6:4 mixture of desired product and starting material but carried forward regardless. LCMS calc.=387.1; found=386.8 (M+Na)+.
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]3([CH2:13][CH2:12]3)[C:7](=O)[NH:8]2)=[CH:4][CH:3]=1.CO>C1COCC1>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]3([CH2:13][CH2:12]3)[CH2:7][NH:8]2)=[CH:4][CH:3]=1
Reactant: O=C1Nc2cc(Cl)ccc2C12CC2
Solvent: C1CCOC1
Solvent: CO
Product: Clc1ccc2c(c1)NCC21CC1
Yield: 52.7 %

Procedure:
A mixture of 6′ chloro-spiro[cyclopropane-1,3′-[3H]indol]-2′(1′H)-one (0.291 g, 1.5 mmol) and borane-dimethyl sulfide complex in THF (2 M, 3.0 mL) was heated at reflux under nitrogen for 2 h. The mixture was cooled and MeOH (3 mL) was added dropwise (caution!). The resulting mixture was heated at reflux for 2 h, then was cooled and solvent evaporated in vacuo. Chromatography (SiO2; gradient elution with 0-100% Et2O in petrol) gave the title compound (0.142 g). MS: [M+H]+=180.
Reaction SMILES: [N-:1]=[N+:2]=[N-:3].[Na+].Cl[CH2:6][C:7]#[C:8][CH2:9][N:10]1[CH2:15][CH2:14][CH2:13][C@H:12]([O:16][CH2:17][C:18]2[CH:23]=[C:22]([C:24]([F:27])([F:26])[F:25])[CH:21]=[C:20]([N:28]3[C:32]([CH3:33])=[N:31][N:30]=[N:29]3)[CH:19]=2)[C@@H:11]1[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1.C(=O)([O-])O.[Na+].O>CS(C)=O>[N:1]([CH2:6][C:7]#[C:8][CH2:9][N:10]1[CH2:15][CH2:14][CH2:13][C@H:12]([O:16][CH2:17][C:18]2[CH:23]=[C:22]([C:24]([F:25])([F:26])[F:27])[CH:21]=[C:20]([N:28]3[C:32]([CH3:33])=[N:31][N:30]=[N:29]3)[CH:19]=2)[C@@H:11]1[C:34]1[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=1)=[N+:2]=[N-:3]
Reactant: Cc1nnnn1-c1cc(CO[C@H]2CCCN(CC#CCCl)[C@H]2c2ccccc2)cc(C(F)(F)F)c1
Reactant: [N-]=[N+]=[N-]
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O
Solvent: CS(C)=O
Product: Cc1nnnn1-c1cc(CO[C@H]2CCCN(CC#CCN=[N+]=[N-])[C@H]2c2ccccc2)cc(C(F)(F)F)c1
Temperature: 25 °C
Reaction time: 16 h
Yield: 96.9 %

Procedure:
Sodium azide (14 mg, 0.21 mmol) was added to a solution of [2S,3S]-1-(4-chlorobut-2-yn-1-yl)-2-phenyl-3-[3-(5-methyltetrazol-1-yl)-5-(trifluoromethyl)phenylmethoxy]piperidine (90 mg, 0.18 mmol) in dimethyl sulphoxide (3 ml) and the solution was stirred at room temperature for 16 hours. Saturated aqueous sodium hydrogen carbonate (20 ml) and water (10 ml) were added and and the mixture was extracted with ethyl acetate (3×20 ml). The combined organic fractions were washed with saturated aqueous sodium hydrogen carbonate (4×20 ml) and brine (20 ml), dried (MgSO4) and the solvent was evaporated under reduced pressure to give [2S,3S]-1-(4-azidobut-2-yn-1-yl)-2-phenyl-3-[3-(5-methyltetrazol-1-yl)-5-(trifluoromethyl)phenylmethoxy]piperidine as a yellow oil (89 mg, 98%) 1H (CDCl3) δ 7.54 (2H, s), 7.43-7.08 (6H, m), 4.62 (1H, d, J=13.2 Hz), 4.18 (1H, d, J=13.2 Hz), 3.92 (2H, s), 3.61-3.30 (4H, m), 3.02 (1H, m), 2.69 (1H, m), 2.55 (3H, s), 2.14 (2H, m), and 1.62 (2H, m). m/z 511 (M+H+).
Reaction SMILES: Br[C:2]1[S:3][C:4]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[CH:5][C:6]=1[CH:7]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])[C:8]([O:10][CH3:11])=[O:9].CC1(C)C(C)(C)OB([C:31]2[CH:32]=[C:33]3[C:38](=[CH:39][CH:40]=2)[O:37][CH2:36][CH2:35][CH2:34]3)O1.C(=O)([O-])[O-].[Na+].[Na+].C(O)C>C1(C)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Pd].O>[C:13]([O:12][CH:7]([C:6]1[CH:5]=[C:4]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[S:3][C:2]=1[C:31]1[CH:40]=[CH:39][C:38]2[O:37][CH2:36][CH2:35][CH2:34][C:33]=2[CH:32]=1)[C:8]([O:10][CH3:11])=[O:9])([CH3:16])([CH3:15])[CH3:14]
Reactant: CC1(C)OB(c2ccc3c(c2)CCCO3)OC1(C)C
Reactant: COC(=O)C(OC(C)(C)C)c1cc(-c2ccccc2)sc1Br
Agent: [Pd]
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O
Solvent: CCO
Solvent: Cc1ccccc1
Product: COC(=O)C(OC(C)(C)C)c1cc(-c2ccccc2)sc1-c1ccc2c(c1)CCCO2
Temperature: 95 °C
Yield: 70 %

Procedure:
A solution of methyl 2-(2-bromo-5-phenylthiophen-3-yl)-2-(tert-butoxy)acetate (11i) (77 mg, 0.20 mmol), 6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)chroman (94 mg, 0.36 mmol) and sodium carbonate (85 mg, 0.80 mmol) in a mixture of toluene (1.26 mL), ethanol (0.6 mL) and water (0.5 mL) was bubbled with nitrogen for 5 minutes. Palladium tetrakis(triphenylphosphine) (12 mg, 0.01 mmol) was added and the reaction mixture was heated a 95° C. for 4 h. After cooling to room temperature, water (2 mL) was added. The aqueous layer was extracted with toluene (2×8 mL). The organic layers were washed with brine (5 mL), dried over sodium sulfate and concentrated in vacuo. The residue was purified by flash chromatography on silica gel (cyclohexane/ethyl acetate 85/15) to provide the desired product (11j) (60 mg, 0.14 mmol, 68%).
Reaction SMILES: O=[O+][O-].[CH2:4]([C:7]1[CH:16]=[CH:15][C:10]2[C:11](=[O:14])[O:12][CH2:13][C:9]=2[CH:8]=1)[CH:5]=C.[O:17]=[C:18]1[CH2:23][NH:22][CH2:21][CH2:20][N:19]1[CH:24]1[CH2:33][CH2:32][C:31]2[CH:30]=[C:29]([C:34]#[N:35])[CH:28]=[CH:27][C:26]=2[CH2:25]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl>[O:17]=[C:18]1[CH2:23][N:22]([CH2:5][CH2:4][C:7]2[CH:16]=[CH:15][C:10]3[C:11](=[O:14])[O:12][CH2:13][C:9]=3[CH:8]=2)[CH2:21][CH2:20][N:19]1[CH:24]1[CH2:33][CH2:32][C:31]2[CH:30]=[C:29]([C:34]#[N:35])[CH:28]=[CH:27][C:26]=2[CH2:25]1
Reactant: N#Cc1ccc2c(c1)CCC(N1CCNCC1=O)C2
Reactant: C=CCc1ccc2c(c1)COC2=O
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: O=[O+][O-]
Agent: [Na+]
Solvent: ClCCl
Product: N#Cc1ccc2c(c1)CCC(N1CCN(CCc3ccc4c(c3)COC4=O)CC1=O)C2
Temperature: 25 °C
Reaction time: 24 h

Procedure:
Ozone was bubbled into a solution of 5-(prop-2-en-1-yl)-2-benzofuran-1(3H)-one (102 mg, 0.59 mmol) in DCM until the color changed to orange. Excess ozone was removed by bubbling nitrogen through the reaction, which was followed by addition of 6-(2-Oxopiperazin-1-yl)-5,6,7,8-tetrahydronaphthalene-2-carbonitrile (50 mg, 0.20 mmol) and sodium triacetoxyborohydride (210 mg, 0.98 mmol). The reaction was allowed to stir at RT for 24 hours. The reaction was diluted with DCM, washed with brine, dried over MgSO4, and purified by prep-TLC to afford the title product. LC-MS (IE, m/z): 416 [M+1]+.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([C@@H:7]([NH2:11])[CH2:8][CH2:9][CH3:10])[CH:2]=1.[Cl:12][C:13]1[N:18]=[C:17](Cl)[C:16]([CH3:20])=[CH:15][N:14]=1.C(N(C(C)C)CC)(C)C>C(O)C>[Cl:12][C:13]1[N:18]=[C:17]([NH:11][C@H:7]([C:3]2[CH:2]=[N:1][CH:6]=[CH:5][CH:4]=2)[CH2:8][CH2:9][CH3:10])[C:16]([CH3:20])=[CH:15][N:14]=1
Reactant: CCC[C@H](N)c1cccnc1
Reactant: Cc1cnc(Cl)nc1Cl
Solvent: CCO
Solvent: CCN(C(C)C)C(C)C
Product: CCC[C@H](Nc1nc(Cl)ncc1C)c1cccnc1

Procedure:
To a solution of (1S)-1-pyridin-3-ylbutan-1-amine (600 mg, 4.0 mmol) in ethanol (20 mL) was added 2,4-dichloro-5-methylpyrimidine (717 mg, 4.4 mmol) and diisopropylethylamine (1.4 mL, 8 mmol). The solution was heated at reflux for 24 h after which time the solvent was removed under reduced pressure. The residue was dissolved in ethyl acetate (30 mL) and washed with H2O (2×15 mL), brine (15 mL) and dried (Na2SO4). The residue remaining after concentration in vacuo was chromatographed using ethyl acetate-hexanes (9:1) as eluant to separate the desired product (370 mg).
Reaction SMILES: [CH:1]1([N:4]2[C:13]3[C:8](=[CH:9][C:10]([F:20])=[C:11]([N:14]4[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]4)[CH:12]=3)[C:7](=[O:21])[C:6]([C:22]([OH:24])=[O:23])=[CH:5]2)[CH2:3][CH2:2]1.[CH:25]([C:27]([CH3:29])=[O:28])=[CH2:26]>C(O)C>[CH:1]1([N:4]2[C:13]3[C:8](=[CH:9][C:10]([F:20])=[C:11]([N:14]4[CH2:19][CH2:18][N:17]([CH2:26][CH2:25][C:27](=[O:28])[CH3:29])[CH2:16][CH2:15]4)[CH:12]=3)[C:7](=[O:21])[C:6]([C:22]([OH:24])=[O:23])=[CH:5]2)[CH2:2][CH2:3]1
Reactant: C=CC(C)=O
Reactant: O=C(O)c1cn(C2CC2)c2cc(N3CCNCC3)c(F)cc2c1=O
Solvent: CCO
Product: CC(=O)CCN1CCN(c2cc3c(cc2F)c(=O)c(C(=O)O)cn3C2CC2)CC1
Yield: 62.3 %

Procedure:
3.31 g (0.01 mol) of 1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylic acid and 3.9 g of methyl vinyl ketone are heated under reflux in 50 ml of ethanol for 2 hours. The solid is filtered off with suction and washed with methanol to give 2.5 g (62.3% of theory) of 1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-[4-(3-oxobutyl)-1-piperazinyl]-3-quinolinecarboxylic acid of decomposition point 185°-187° C.
Reaction SMILES: [OH:1][C@H:2]([CH2:15][NH:16][C:17]1[CH:22]=[CH:21][C:20]([N:23]2[CH2:28][CH2:27][O:26][CH2:25][C:24]2=[O:29])=[CH:19][CH:18]=1)[CH2:3][N:4]1[C:12](=[O:13])[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]1=[O:14].[CH2:30]([OH:32])C>C1(C)C=CC=CC=1>[O:32]=[C:30]1[N:16]([C:17]2[CH:22]=[CH:21][C:20]([N:23]3[CH2:28][CH2:27][O:26][CH2:25][C:24]3=[O:29])=[CH:19][CH:18]=2)[CH2:15][C@H:2]([CH2:3][N:4]2[C:12](=[O:13])[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]2=[O:14])[O:1]1
Reactant: CCO
Reactant: O=C1c2ccccc2C(=O)N1C[C@H](O)CNc1ccc(N2CCOCC2=O)cc1
Solvent: Cc1ccccc1
Product: O=C1c2ccccc2C(=O)N1C[C@H]1CN(c2ccc(N3CCOCC3=O)cc2)C(=O)O1
Temperature: 27.5 °C

Procedure:
2641 g of 2-((2R)-2-hydroxy-3-{[4-(3-oxo-4-morpholinyl)phenyl]amino}propyl)-1H-isoindole-1,3(2H)-dione (V) are suspended in 22 l of toluene and, at 19° C., 1300 g of N,N-carbonyl-diimidazole are added. The reaction mixture is subsequently heated under reflux for one hour and then, at 60° C., 4.5 l of ethanol are added. After cooling to 25 to 30° C., the precipitated reaction product is filtered off with suction, washed with ethanol and then dried.
Reaction SMILES: [I:1][C:2]1[N:6]2[CH:7]=[CH:8][C:9]([C:11]([NH:13][NH2:14])=[O:12])=[CH:10][C:5]2=[N:4][CH:3]=1.[C:15](N1C=CN=C1)(N1C=CN=C1)=[O:16].C(N(CC)CC)C>C1COCC1>[I:1][C:2]1[N:6]2[CH:7]=[CH:8][C:9]([C:11]3[O:12][C:15](=[O:16])[NH:14][N:13]=3)=[CH:10][C:5]2=[N:4][CH:3]=1
Reactant: NNC(=O)c1ccn2c(I)cnc2c1
Reactant: O=C(n1ccnc1)n1ccnc1
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: O=c1[nH]nc(-c2ccn3c(I)cnc3c2)o1
Reaction time: 3 h
Yield: 115.2 %

Procedure:
To a solution of 3-Iodo-imidazo[1,2-a]pyridine-7-carboxylic acid hydrazide (196 mg, 0.5 mmol) (prepared as described in Example 329 steps a-c) in THF (10 ml) was added carbonyldiimidazole (243 mg, 1.5 mmol) and triethylamine (0.35 ml, 2.5 mmol) and the reaction mixture left to stir for 3 h. The precipitate formed in the reaction was filtered off, washed with Et2O and dried to afford the desired product (189 mg). MS: [M+H]+=329.
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([F:12])=[CH:9][CH:10]=2)[N:5]=[C:4]([N:13]2[CH2:17][CH2:16][CH2:15][C:14]2=[O:18])[C:3]=1[CH3:19].[O:20]1[CH2:25][CH2:24][N:23]([C:26]2[CH:27]=[C:28]3[NH:34][CH2:33][C:32]4([CH2:39][CH2:38][O:37][CH2:36][CH2:35]4)[C:29]3=[N:30][CH:31]=2)[CH2:22][CH2:21]1.CC(C)([O-])C.[Na+]>CC(C1C=C(C(C)C)C(C2C(P(C3CCCCC3)C3CCCCC3)=CC=CC=2)=C(C(C)C)C=1)C.C1C=[C-]C(CCN)=CC=1.Cl[Pd+].C1(C)C=CC=CC=1>[F:12][C:8]1[CH:7]=[C:6]2[C:11]([C:2]([N:34]3[C:28]4[C:29](=[N:30][CH:31]=[C:26]([N:23]5[CH2:24][CH2:25][O:20][CH2:21][CH2:22]5)[CH:27]=4)[C:32]4([CH2:39][CH2:38][O:37][CH2:36][CH2:35]4)[CH2:33]3)=[C:3]([CH3:19])[C:4]([N:13]3[CH2:17][CH2:16][CH2:15][C:14]3=[O:18])=[N:5]2)=[CH:10][CH:9]=1
Reactant: c1nc2c(cc1N1CCOCC1)NCC21CCOCC1
Reactant: Cc1c(N2CCCC2=O)nc2cc(F)ccc2c1Cl
Agent: Cl[Pd+]
Agent: CC(C)(C)[O-]
Agent: CC(C)c1cc(C(C)C)c(-c2ccccc2P(C2CCCCC2)C2CCCCC2)c(C(C)C)c1
Solvent: Cc1ccccc1
Product: Cc1c(N2CCCC2=O)nc2cc(F)ccc2c1N1CC2(CCOCC2)c2ncc(N3CCOCC3)cc21

Procedure:
Prepared according to procedure Y by stirring 1-(4-chloro-7-fluoro-3-methylquinolin-2-yl)pyrrolidin-2-one (50 mg, 0.179 mmol), 6′-morpholino-1′,2,2′,3,5,6-hexahydrospiro[pyran-4,3′-pyrrolo[3,2-b]pyridine] (49.4 mg, 0.179 mmol), XPhos precatalyst (26.5 mg, 0.036 mmol), sodium tert-butoxide (34.5 mg, 0.359 mmol), and toluene (1.5 mL) at 95° C. for 2 h. Purification by reverse phase HPLC (0-70% acetonitrile in water) gave 1-(7-fluoro-3-methyl-4-(6′-(4-morpholinyl)-2,3,5,6-tetrahydrospiro[pyran-4,3′-pyrrolo[3,2-b]pyridin]-1′(2′H)-yl)-2-quinolinyl)-2-pyrrolidinone. 1H NMR (400 MHz, chloroform-d) δ ppm 7.76 (1H, dd, J=9.1, 6.0 Hz), 7.61-7.69 (2H, m), 7.21-7.26 (1H, m), 5.89 (1H, s), 4.13 (4H, d, J=6.8 Hz), 4.04-4.10 (1H, m), 3.93 (1H, d, J=9.6 Hz), 3.70-3.83 (4H, m), 3.51-3.66 (2H, m), 3.03 (4H, dd, J=5.7, 3.7 Hz), 2.65 (2H, t, J=8.0 Hz), 2.24-2.42 (4H, m), 2.18 (3H, s), 1.83 (1H, d, J=13.7 Hz), 1.73 (1H, d, J=13.3 Hz). Mass Spectrum (ESI) m/e=518.2 (M+1).
Reaction SMILES: [CH2:1]=[CH:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[CH2:9]([O:11][SiH:12]([O:16][CH2:17][CH3:18])[O:13][CH2:14][CH3:15])[CH3:10].FC(F)(F)C(O)=O.C([Si](C=C)(C)O[Si](C)(C)C)=C>C1(C)C=CC=CC=1>[CH2:1]([Si:12]([O:16][CH2:17][CH3:18])([O:13][CH2:14][CH3:15])[O:11][CH2:9][CH3:10])[CH2:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1
Reactant: C=Cc1ccccc1
Reactant: CCO[SiH](OCC)OCC
Agent: C=C[Si](C)(C=C)O[Si](C)(C)C
Solvent: O=C(O)C(F)(F)F
Solvent: Cc1ccccc1
Product: CCO[Si](CCc1ccccc1)(OCC)OCC
Temperature: 50 °C
Yield: 30.5 %

Procedure:
208 mg Of styrene, 328 mg of triethoxysilane, and 52 mg of toluene were placed in a glass reaction tube and 0.005 ml of trifluoroacetic acid was added. Then, 0.002 ml of a toluene solution of a 0-valent platinum complex of divinyltetramethyldisiloxane (platinum content: 0.4 Wt. %) was added to this mixture. The reaction tube was sealed with Teflon tape and heated for 1 hour in an oil bath at 50° C. When the tube contents were analyzed by GC-MS following cooling, the conversion rate of styrene was 41.4% and phenethyltriethoxysilane was produced at a yield of 30.5%. The yield of (α-methylbenzyl)triethoxysilane was 1.2%.
Reaction SMILES: [CH:1]1[C:11]2[C:10]3[CH:12]=[CH:13][CH:14]=[CH:15][C:9]=3[CH2:8][N:7]([C:16](=[NH:20])[O:17][CH2:18][CH3:19])[CH2:6][C:5]=2[CH:4]=[CH:3][CH:2]=1.C(N(CC)CC)C.Cl[C:29]([O:31][CH3:32])=[O:30]>C(Cl)Cl>[CH3:32][O:31][C:29]([N:20]=[C:16]([N:7]1[CH2:6][C:5]2[CH:4]=[CH:3][CH:2]=[CH:1][C:11]=2[C:10]2[CH:12]=[CH:13][CH:14]=[CH:15][C:9]=2[CH2:8]1)[O:17][CH2:18][CH3:19])=[O:30]
Reactant: CCOC(=N)N1Cc2ccccc2-c2ccccc2C1
Reactant: COC(=O)Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CCOC(=NC(=O)OC)N1Cc2ccccc2-c2ccccc2C1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
2.66 g of ethyl 5,7-dihydro-6H-dibenz[c,e]azepine-6-carboximidate are placed in 15 ml of methylene chloride with 1 g of triethylamine. 0.95 g of methyl chloroformate is added dropwise while cooling with an ice bath. The mixture is then left to stir at room temperature for 2 hours. The reaction mixture is poured on to ice-water and extracted twice with methylene chloride. The extracts are washed with water, dried over anhydrous sodium sulfate and evaporated under reduced pressure. The oily residue is chromatographed on silica gel with n-hexane-ethyl acetate (1:1) as the eluent, and there is obtained ethyl N-methoxycarbonyl-5,7-dihydro-6H-dibenz[c,e]azepine-6-carboximidate as an oil, mass spectrum m/e: M+ 324 (6), 295 (20), 263 (70), 194 (100), 178 (35), 165 (49).
Reaction SMILES: [C:1]([O:5][C:6](=[O:30])[CH2:7][O:8][C:9]1[CH:18]=[CH:17][C:16]([F:19])=[C:15]2[C:10]=1[C:11]([CH3:29])=[C:12]([CH2:21][C:22]1[CH:27]=[CH:26][C:25]([Br:28])=[CH:24][CH:23]=1)[C:13](=[O:20])[NH:14]2)([CH3:4])([CH3:3])[CH3:2].Cl[CH:32]([F:34])[F:33]>>[C:1]([O:5][C:6](=[O:30])[CH2:7][O:8][C:9]1[CH:18]=[CH:17][C:16]([F:19])=[C:15]2[C:10]=1[C:11]([CH3:29])=[C:12]([CH2:21][C:22]1[CH:23]=[CH:24][C:25]([Br:28])=[CH:26][CH:27]=1)[C:13]([O:20][CH:32]([F:34])[F:33])=[N:14]2)([CH3:4])([CH3:2])[CH3:3]
Reactant: Cc1c(Cc2ccc(Br)cc2)c(=O)[nH]c2c(F)ccc(OCC(=O)OC(C)(C)C)c12
Reactant: FC(F)Cl
Product: Cc1c(Cc2ccc(Br)cc2)c(OC(F)F)nc2c(F)ccc(OCC(=O)OC(C)(C)C)c12

Procedure:
The title compound was prepared by the method of Preparation 10c using [3-(4-bromobenzyl)-8-fluoro-4-methyl-2-oxo-1,2-dihydroquinolin-5-yloxy]acetic acid tert-butyl ester and chlorodifluoromethane.
Reaction SMILES: [C:1]1([CH3:12])[CH:6]=[CH:5][C:4]([CH:7]=[CH:8][C:9](=[O:11])[CH3:10])=[CH:3][CH:2]=1.C[O:14][C:15]1C=CC=C[C:16]=1C1CC(=O)CC(=O)C1>>[C:1]1([CH3:12])[CH:2]=[CH:3][C:4]([CH:7]2[CH2:8][C:9](=[O:11])[CH2:10][C:15](=[O:14])[CH2:16]2)=[CH:5][CH:6]=1
Reactant: COc1ccccc1C1CC(=O)CC(=O)C1
Reactant: CC(=O)C=Cc1ccc(C)cc1
Product: Cc1ccc(C2CC(=O)CC(=O)C2)cc1

Procedure:
The title compound was prepared from 4-p-tolyl-but-3-en-2-one stage 1 (4.8 g, 30.0 mmol), following the procedure describing the synthesis of 5-(2-methoxy-phenyl)-cyclohexane-1,3-dione (example 1/a stage 2).
Reaction SMILES: [CH3:1][C@@H:2]1[CH2:6][C:5](=[O:7])[NH:4][C@@H:3]1[C:8]([OH:10])=O.C1C=CC2N(O)N=NC=2C=1.C1CCC(N=C=NC2CCCCC2)CC1.[NH2:36][C@H:37]([C:44]([N:46]1[CH2:53][CH2:52][CH2:51][C@H:47]1[C:48]([NH2:50])=[O:49])=[O:45])[CH2:38][C:39]1[N:43]=[CH:42][NH:41][CH:40]=1>CN(C=O)C>[CH3:1][C@@H:2]1[CH2:6][C:5](=[O:7])[NH:4][C@@H:3]1[C:8]([NH:36][C@H:37]([C:44]([N:46]1[CH2:53][CH2:52][CH2:51][C@H:47]1[C:48]([NH2:50])=[O:49])=[O:45])[CH2:38][C:39]1[N:43]=[CH:42][NH:41][CH:40]=1)=[O:10]
Reactant: NC(=O)[C@@H]1CCCN1C(=O)[C@@H](N)Cc1c[nH]cn1
Reactant: C[C@@H]1CC(=O)N[C@@H]1C(=O)O
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: On1nnc2ccccc21
Solvent: CN(C)C=O
Product: C[C@@H]1CC(=O)N[C@@H]1C(=O)N[C@@H](Cc1c[nH]cn1)C(=O)N1CCC[C@H]1C(N)=O
Temperature: 0 °C
Reaction time: 8 h

Procedure:
cis-3-Methylpyroglutamic acid [A. B. Mauger, J. Org. Chem. 46, 1032 (1981)] (1.5 g) was dissolved in DMF (30 ml), and HOBT (1.6 g) was added to the solution, followed by addition of DCC (2.81 g) under cooling at 0° C. The mixture was stirred at the same temperature overnight. The above-mentioned DMF solution of L-histidyl-L-prolinamide was added to the mixture, and the mixture was stirred at 5° C. overnight. After the resulting precipitation was filtered off, the filtrate was concentrated to dryness under reduced pressure and the residue was subjected to silica gel column chromatography with chloroform-methanol-ammonia water (40:10:1) as eluent. The eluted fractions were combined and concentrated to dryness to give Nα -(cis-3-methylpyroglutamyl)-L-histidyl-L-prolinamide (2.2 g) as powders.
Reaction SMILES: FC(F)(F)S([O:6][CH2:7][C:8]([F:11])([F:10])[F:9])(=O)=O.[C:14]1([CH:21]=[CH:20][C:18]([OH:19])=[CH:17][CH:16]=1)O>CC(C)=O>[F:9][C:8]([F:11])([F:10])[CH2:7][O:19][C:18]1[CH:20]=[CH:21][C:14]([O:6][CH2:7][C:8]([F:9])([F:10])[F:11])=[CH:16][CH:17]=1
Reactant: O=S(=O)(OCC(F)(F)F)C(F)(F)F
Reactant: Oc1ccc(O)cc1
Solvent: CC(C)=O
Product: FC(F)(F)COc1ccc(OCC(F)(F)F)cc1
Reaction time: 2 h
Yield: 88 %

Procedure:
To a mixture of 2.42 moles (334.4 g.) of potassium carbonates, 2.2 moles (510.6 g.) of 2,2,2-trifluoroethyl trifluoromethanesulfonate in 1.02 liter of acetone is added a solution of 1.0 mole (110 g.) of hydroquinone in 1.1 liter of acetone, slowly over a 2 hour period. The reaction is then heated at reflux for 24 hours, the reaction mixture is evaporated, and 2 liters of chloroform and 2 liters of water are added to the residue. The chloroform layer is separated, the aqueous layer is washed twice with 1 liter of chloroform, and the combined chloroform solution is washed with 1 liter of water. The chloroform solution is dried over magnesium sulfate, then concentrated under vacuum. Hexane is added to the residue and the solid product is collected by filtration and washed with hexane. Additional material is collected from the concentrated residues. A yield of 88 percent, 241 g. of 1,4-bis(2,2,2-trifluoroethoxy)benzene, m.p. 75°-77° C. is obtained.