Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: N[C:2]1[N:7]=[C:6]([S:8][CH2:9][C:10]2[CH:15]=[CH:14][N:13]=[C:12]([C:16]([NH:18][CH3:19])=[O:17])[CH:11]=2)[C:5]([C:20]#[N:21])=[C:4]([C:22]2[CH:27]=[CH:26][C:25]([F:28])=[C:24]([F:29])[CH:23]=2)[C:3]=1[C:30]#[N:31].N(OCCC(C)C)=O.[ClH:40]>C(#N)C.[Cu](Cl)Cl>[Cl:40][C:2]1[N:7]=[C:6]([S:8][CH2:9][C:10]2[CH:15]=[CH:14][N:13]=[C:12]([C:16]([NH:18][CH3:19])=[O:17])[CH:11]=2)[C:5]([C:20]#[N:21])=[C:4]([C:22]2[CH:27]=[CH:26][C:25]([F:28])=[C:24]([F:29])[CH:23]=2)[C:3]=1[C:30]#[N:31]
Reactant: CNC(=O)c1cc(CSc2nc(N)c(C#N)c(-c3ccc(F)c(F)c3)c2C#N)ccn1
Reactant: Cl
Agent: Cl[Cu]Cl
Agent: CC(C)CCON=O
Solvent: CC#N
Product: CNC(=O)c1cc(CSc2nc(Cl)c(C#N)c(-c3ccc(F)c(F)c3)c2C#N)ccn1
Temperature: 65 °C
Reaction time: 8 h

Procedure:
Under argon, 0.86 g (1.97 mmol) of 4-({[6-amino-3,5-dicyano-4-(3,4-difluorophenyl)pyridin-2-yl]sulfanyl}methyl)-N-methylpyridine-2-carboxamide (Example 4), 0.46 g (3.93 mmol) of isopentyl nitrite and 0.53 g (3.93 mmol) of copper(II) chloride were initially charged in 20 ml of acetonitrile and the mixture was stirred at 65° C. overnight. After a reaction time of 3 h, another 0.23 g (1.97 mmol) of isopentyl nitrite and 0.26 g (1.97 mmol) of copper(II) chloride were added to the reaction mixture. After cooling to RT, 3.93 ml of 1N hydrochloric acid were added. The aqueous phase was extracted three times with ethyl acetate. The combined organic phases were dried over sodium sulfate, filtered and evaporated. The residue was purified by preparative HPLC (Chromasil, water/acetonitrile+0.1% trifluoroacetic acid).
Reaction SMILES: [CH2:1]([SH:7])[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6].[H-].[Na+].[Cl:10][C:11]1[C:16](Cl)=[N:15][CH:14]=[CH:13][N:12]=1>C1COCC1>[Cl:10][C:11]1[C:16]([S:7][CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH3:6])=[N:15][CH:14]=[CH:13][N:12]=1
Reactant: CCCCCCS
Reactant: Clc1nccnc1Cl
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: CCCCCCSc1nccnc1Cl
Temperature: -5 °C
Reaction time: 0.5 h

Procedure:
Hexanethiol (4.7 g, 40 mmole) was added to a slurry of sodium hydride (0.96 g) in THF (60 ml), and the mixture stirred for 30 minutes. The slurry was cooled to -5° C. and a solution of 2,3-dichloropyrazine (6 g) added. The mixture was stirred for 1.5 hours, filtered and the filtrate evaporated. The residue was purified by column chromatography on silica gel using varying concentrations of methanol in chloroform. Fractions containing the desired product were evaporated, yielding 2-chloro-3-hexylsulfanyl pyrazine. as an oil.
Reaction SMILES: [O:1]=[C:2]1[CH2:11][CH2:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([C:12]3[CH:13]=[C:14]([CH2:18][NH:19][S:20]([CH2:23][CH3:24])(=[O:22])=[O:21])[CH:15]=[N:16][CH:17]=3)[CH:8]=2)[NH:3]1.[Cl:25]N1C(=O)CCC1=O.O>CN(C=O)C.CCOC(C)=O>[Cl:25][C:5]1[CH:6]=[C:7]([C:12]2[CH:13]=[C:14]([CH2:18][NH:19][S:20]([CH2:23][CH3:24])(=[O:22])=[O:21])[CH:15]=[N:16][CH:17]=2)[CH:8]=[C:9]2[C:4]=1[NH:3][C:2](=[O:1])[CH2:11][CH2:10]2
Reactant: O=C1CCC(=O)N1Cl
Reactant: CCS(=O)(=O)NCc1cncc(-c2ccc3c(c2)CCC(=O)N3)c1
Solvent: O
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: CCS(=O)(=O)NCc1cncc(-c2cc(Cl)c3c(c2)CCC(=O)N3)c1
Yield: 33.4 %

Procedure:
To a solution of ethanesulfonic acid [5-(2-oxo-1,2,3,4-tetrahydro-quinolin-6-yl)-pyridin-3-ylmethyl]-amide (example 55, 0.681 g, 0.197 mmol) in DMF (1 mL) heated to 65° C. was added N-chloro-succinimide (0.034 g, 0.256 mmol) and the reaction mixture was stirred at this temperature over night. The mixture was diluted with EtOAc, poured into water (5 mL) and extracted with EtOAc (2×10 mL). The combined organics were washed with brine, dried over Na2SO4, filtered and evaporated. The residue was purified by reverse phase HPLC on a Gemini-NX column, eluting with a MeOH—H2O (0.05% TEA) gradient to give the title compound (0.025 g, 33%) as a colorless amorphous solid. MS: 380.4 (M+H+).
Reaction SMILES: [S:1]1[CH2:8][CH2:7][CH2:6][C:5](=O)[CH2:4][CH2:3][CH2:2]1.[C:10]1([NH:16]N)[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1>C(O)(=O)C>[CH2:3]1[C:4]2[C:15]3[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=3[NH:16][C:5]=2[CH2:6][CH2:7][CH2:8][S:1][CH2:2]1
Reactant: NNc1ccccc1
Reactant: O=C1CCCSCCC1
Solvent: CC(=O)O
Product: c1ccc2c3c([nH]c2c1)CCCSCC3

Procedure:
A mixture of 7.2g (0.05 mole) of 1-thiacyclooctane-5-one and 6.0g (0.056 mole) of phenylhydrazine in 40 ml of glacial acetic acid is refluxed for three hours under nitrogen. On standing there is deposited 5.2g of a solid, m.p. 106°-107° C. Recrystallization from cyclohexane affords 4.9g (45%) of an analytical sample m.p. 109°-110° C.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:12])[CH2:4][C:5]1[CH:6]=[C:7]([CH3:11])[CH:8]=[CH:9][CH:10]=1.[Br:13]N1C(=O)CCC1=O.CC(N=NC(C#N)(C)C)(C#N)C.C([O-])(O)=O.[Na+]>C(Cl)(Cl)(Cl)Cl>[CH3:1][O:2][C:3](=[O:12])[CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([CH2:11][Br:13])[CH:6]=1
Reactant: O=C1CCC(=O)N1Br
Reactant: COC(=O)Cc1cccc(C)c1
Agent: CC(C)(C#N)N=NC(C)(C)C#N
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClC(Cl)(Cl)Cl
Product: COC(=O)Cc1cccc(CBr)c1
Temperature: 25 °C

Procedure:
A solution of m-tolyl-acetic acid methyl ester (11.41 g, 69.49 mmol), N-bromosuccinimide (12.59 g, 70.73 mmol), AIBN (100 mg) in CCl4 (200 mL) was heated at reflux for 16 h. The reaction was cooled to room temperature and aqueous NaHCO3 (satd) was added. The aqueous solution was extracted with CH2Cl2 (2×) and the organic solution was dried (MgSO4), filtered, and concentrated. Purification by flash chromatography (hexanes to 9:1 hexanes:EtOAc) provided the title compound as a clear and colorless liquid (11.99 g). 1H NMR (CDCl3 400 MHz) δ 7.27 (m, 4H), 4.47 (s, 2H), 3.69 (s, 3H), 3.62 (s, 2H).
Reaction SMILES: B.[Na].C[O:4][C:5](=O)[C@@H:6]1[CH2:10][CH2:9][CH2:8][N:7]1[C:11](=[O:29])[C@@H:12]1[CH2:16][CH2:15][CH2:14][N:13]1[C:17](=[O:28])[CH2:18][CH:19]1[C:27]2[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=2)[CH2:21][CH2:20]1.Cl>O1CCCC1.CO>[CH:19]1([CH2:18][C:17]([N:13]2[CH2:14][CH2:15][CH2:16][C@H:12]2[C:11]([N:7]2[CH2:8][CH2:9][CH2:10][C@H:6]2[CH2:5][OH:4])=[O:29])=[O:28])[C:27]2[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=2)[CH2:21][CH2:20]1
Reactant: COC(=O)[C@@H]1CCCN1C(=O)[C@@H]1CCCN1C(=O)CC1CCc2ccccc21
Agent: B
Agent: Cl
Agent: [Na]
Solvent: CO
Solvent: C1CCOC1
Product: O=C([C@@H]1CCCN1C(=O)CC1CCc2ccccc21)N1CCC[C@H]1CO
Temperature: 25 °C
Reaction time: 15 h
Yield: 68.5 %

Procedure:
0.57 g of sodium boron hydride was added with stirring to 9 ml of a 80% methanol solution under ice-cooling. To the mixture was added dropwise 1.15 g of 1-[1-(2-indanylacetyl)-L-prolyl]-L-proline methyl ester dissolved in a mixed solution of 5 ml of tetrahydrofuran and 5 ml of methanol. After addition, the mixture was stirred for 15 hours at room temperature. The reaction mixture was acidified by adding diluted hydrochloric acid and extracted with ether. The organic layer obtained was washed with brine and dried over anhydrous sodium sulfate. After evaporating the solvent under reduced pressure, the residue was purified by silica gel column chromatography to obtain 0.73 g of 1-[1-(2-indanylacetyl)-L-prolyl]-L-prolinol as an oily substance. (yield: 68%)
Reaction SMILES: [CH2:1](/[C:3](=[CH:7]\[C:8](=[O:10])[CH3:9])/[C:4]([NH2:6])=[O:5])[CH3:2].O.[BH4-].[Na+].Cl>CO>[CH2:1](/[C:3](=[CH:7]\[CH:8]([OH:10])[CH3:9])/[C:4]([NH2:6])=[O:5])[CH3:2]
Reactant: CC/C(=C\C(C)=O)C(N)=O
Agent: Cl
Agent: [BH4-]
Agent: [Na+]
Solvent: O
Solvent: CO
Product: CC/C(=C\C(C)O)C(N)=O
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 88 %

Procedure:
24 (ethyl (2E)-4-oxopent-2-enamide) (5.18 g, 36.7 mmol) is dissolved in MeOH (6 ml) and H2O (54 ml) and cooled to 0° C. NaBH4 is added to the resulting solution (426 mg, 11.3 mmol) in portions over 15 min. After 30 min of additional stirring at 0° C., the reaction mixture is acidified with 2 M HCl (1.15 ml) and extracted with AcOiPr (2×1 l). The organic phases are washed with brine (2×25 ml). The combined organic phases are dried with Na2SO4 and evaporated under reduced pressure at 40° C. The residue is purified by flash chromatography (MeOH:CH2Cl2 5:95 to 7.5:92.5) and yields 25 (rac-Ethyl (2E)-4-hydroxypent-2-enamide) (4.60 g, 88%) as a viscous brown oil.
Reaction SMILES: [C:1]([C:3]1[CH:4]=[C:5]([N:15]2[CH:19]=[C:18]([C:20]([O:22]CC)=[O:21])[CH:17]=[N:16]2)[CH:6]=[CH:7][C:8]=1[O:9][CH:10]([CH2:13][CH3:14])[CH2:11][CH3:12])#[N:2].[OH-].[Na+].O.C(O)(=O)C>C(O)C>[C:1]([C:3]1[CH:4]=[C:5]([N:15]2[CH:19]=[C:18]([C:20]([OH:22])=[O:21])[CH:17]=[N:16]2)[CH:6]=[CH:7][C:8]=1[O:9][CH:10]([CH2:11][CH3:12])[CH2:13][CH3:14])#[N:2]
Reactant: CCOC(=O)c1cnn(-c2ccc(OC(CC)CC)c(C#N)c2)c1
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CCO
Solvent: CC(=O)O
Product: CCC(CC)Oc1ccc(-n2cc(C(=O)O)cn2)cc1C#N
Temperature: 80 °C
Yield: 82 %

Procedure:
To a solution (10 ml) of ethyl 1-(3-cyano-4-(1-ethylpropoxy)phenyl)pyrazole-4-carboxylate (0.8 g) in ethanol was added 2 N aqueous sodium hydroxide solution (1.5 ml) with stirring, and the mixture was heated at 80° C. for 30 minutes. After the completion of the reaction, the reaction mixture was poured into water and neutralized with acetic acid. The precipitated crystals were recrystallized from a mixed solvent of ethyl alcohol and water to give 0.6 g of 1-(3-cyano-4-(1-ethylpropoxy)phenyl)pyrazole-4-carboxylic acid, melting point 142-144° C.
Reaction SMILES: [CH3:1][N:2]([CH3:21])[CH2:3][CH2:4][NH:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:19]=[CH:18][C:17](F)=[CH:16][CH:15]=2)[CH2:10][CH2:9]1)=[O:7].C(N1C=CN=C1)(N1C=CN=C1)=O.[Cl:34]C1C=CC=CC=1N1CCNCC1.O1CCCC1>Cl>[ClH:34].[Cl:34][C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][C:14]=1[N:11]1[CH2:12][CH2:13][N:8]([C:6]([NH:5][CH2:4][CH2:3][N:2]([CH3:21])[CH3:1])=[O:7])[CH2:9][CH2:10]1
Reactant: Clc1ccccc1N1CCNCC1
Reactant: CN(C)CCNC(=O)N1CCN(c2ccc(F)cc2)CC1
Agent: Cl
Agent: O=C(n1ccnc1)n1ccnc1
Solvent: C1CCOC1
Product: CN(C)CCNC(=O)N1CCN(c2ccccc2Cl)CC1

Procedure:
This compound was prepared according to the procedure used to synthesize the compound of Example 11. A mixture of 4.9 g (0.03 mole) of 1,1'-carbonyldiimidazole, 2.6 g (0.03 mole) of unsym-diethylethylenediamine, and 5.9 g (0.03 mole) of 1-(2-chlorophenyl)piperazine in a total of 200 ml of tetrahydrofuran gave an oil as residue. The hydrochloride was formed in ethereal hydrogen chloride and the collected solid was recrystallized from methanol-ethyl ether to yield 3.4 g (33%) of title compound as a white solid, m.p. 185°-188° C.
Reaction SMILES: [F:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[CH:5][N:6]2[C@@H:11]1[O:28][C@H:27]([CH2:29][O:30][C:31](=[O:33])[CH3:32])[C@@H:22]([O:23][C:24](=[O:26])[CH3:25])[C@H:17]([O:18][C:19](=[O:21])[CH3:20])[C@H:12]1[O:13][C:14](=[O:16])[CH3:15].[O:34]1[CH:38]=[CH:37][C:36]2[CH:39]=[C:40]([C:43](Cl)=[O:44])[CH:41]=[CH:42][C:35]1=2>>[F:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[C:4]([C:43]([C:40]1[CH:41]=[CH:42][C:35]3[O:34][CH:38]=[CH:37][C:36]=3[CH:39]=1)=[O:44])=[CH:5][N:6]2[C@@H:11]1[O:28][C@H:27]([CH2:29][O:30][C:31](=[O:33])[CH3:32])[C@@H:22]([O:23][C:24](=[O:26])[CH3:25])[C@H:17]([O:18][C:19](=[O:21])[CH3:20])[C@H:12]1[O:13][C:14](=[O:16])[CH3:15]
Reactant: CC(=O)OC[C@H]1O[C@@H](n2ccc3c(F)cccc32)[C@H](OC(C)=O)[C@@H](OC(C)=O)[C@@H]1OC(C)=O
Reactant: O=C(Cl)c1ccc2occc2c1
Product: CC(=O)OC[C@H]1O[C@@H](n2cc(C(=O)c3ccc4occc4c3)c3c(F)cccc32)[C@H](OC(C)=O)[C@@H](OC(C)=O)[C@@H]1OC(C)=O

Procedure:
4-Fluoro-1-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)-indole obtained in Example 2-(3) and benzo[b]furan-5-carbonyl chloride were treated in a manner similar to Example 2-(4) to give benzo[b]furan-5-yl 4-fluoro-1-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)indol-3-yl ketone as a colorless powder. APCI-Mass m/Z 627 (M+NH4), 610 (M+H). 1H-NMR (DMSO-d6) δ 1.73 (s, 3H), 1.96 (s, 3H), 1.98 (s, 3H), 2.03 (s, 3H), 4.10 (d, J=4.0 Hz, 2H), 4.28-4.31 (m, 1H), 5.28 (t, J=9.8 Hz, 1H), 5.54 (t, J=9.6 Hz, 1H), 5.77 (t, J=9.3 Hz, 1H), 6.35 (d, J=9.2 Hz, 1H), 7.04 (dd, J=10.8, 8.0 Hz, 1H), 7.09 (d, J=1.4 Hz, 1H), 7.39 (td, J=8.1, 4.7 Hz, 1H), 7.64 (d, J=8.3 Hz, 1H), 7.75-7.77 (m, 1H), 7.82-7.84 (m, 1H), 8.14-8.15 (m, 2H), 8.17 (s, 1H).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[N+:4]([O-:39])[CH:5]=[C:6]([Cl:38])[C:7]=1[CH2:8][C@@H:9]([C:23]1[CH:28]=[CH:27][C:26]([O:29][CH:30]([F:32])[F:31])=[C:25]([O:33][CH2:34][CH:35]2[CH2:37][CH2:36]2)[CH:24]=1)[O:10][C:11](OC1C=CC([N+]([O-])=O)=CC=1)=[O:12].Cl.[N+:41]([C:44]1[CH:49]=[CH:48][C:47]([CH2:50][NH2:51])=[CH:46][CH:45]=1)([O-:43])=[O:42]>C(Cl)Cl.CN(C1C=CN=CC=1)C>[Cl:38][C:6]1[CH:5]=[N+:4]([O-:39])[CH:3]=[C:2]([Cl:1])[C:7]=1[CH2:8][C@@H:9]([C:23]1[CH:28]=[CH:27][C:26]([O:29][CH:30]([F:31])[F:32])=[C:25]([O:33][CH2:34][CH:35]2[CH2:37][CH2:36]2)[CH:24]=1)[O:10][C:11](=[O:12])[NH:51][CH2:50][C:47]1[CH:46]=[CH:45][C:44]([N+:41]([O-:43])=[O:42])=[CH:49][CH:48]=1
Reactant: NCc1ccc([N+](=O)[O-])cc1
Reactant: O=C(Oc1ccc([N+](=O)[O-])cc1)O[C@@H](Cc1c(Cl)c[n+]([O-])cc1Cl)c1ccc(OC(F)F)c(OCC2CC2)c1
Agent: CN(C)c1ccncc1
Agent: Cl
Solvent: ClCCl
Product: O=C(NCc1ccc([N+](=O)[O-])cc1)O[C@@H](Cc1c(Cl)c[n+]([O-])cc1Cl)c1ccc(OC(F)F)c(OCC2CC2)c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 86.1 %

Procedure:
To a stirred solution of compound (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((4-nitrophenoxy)-carbonyloxy)ethyl)pyridine 1-oxide, (227 mg, 0.388 mmol) in DCM (10 ml), (4-nitrophenyl)methanamine hydrochloride (88 mg, 0.465 mmol), and DMAP (56.9 mg, 0.465 mmol) were added. The reaction mixture was stirred at RT overnight. After 20 hours, the mixture was diluted with DCM and washed with a solution of K2CO3. he organic layer was dried over Na2SO4, evaporated and the resulting crude was purified by flash chromatography on silica gel (DCM:MeOH 10:0.3) affording the desired product (200 mg, 0.334 mmol, 86% yield, MS/ESI+ 598.3 [MH]+).
Reaction SMILES: [NH:1]1[C:5]([C:6]2[CH:21]=[CH:20][C:9]3[O:10][CH2:11][C:12]4[CH:19]=[CH:18][CH:17]=[CH:16][C:13]=4[C:14](=[O:15])[C:8]=3[CH:7]=2)=[N:4][N:3]=[N:2]1.C(O)C.[BH4-].[Na+].Cl>O>[NH:4]1[C:5]([C:6]2[CH:21]=[CH:20][C:9]3[O:10][CH2:11][C:12]4[CH:19]=[CH:18][CH:17]=[CH:16][C:13]=4[CH:14]([OH:15])[C:8]=3[CH:7]=2)=[N:1][N:2]=[N:3]1
Reactant: O=C1c2ccccc2COc2ccc(-c3nnn[nH]3)cc21
Agent: Cl
Agent: [BH4-]
Agent: [Na+]
Solvent: O
Solvent: CCO
Product: OC1c2ccccc2COc2ccc(-c3nnn[nH]3)cc21

Procedure:
Suspend 1 gm. of 2-(1H-tetrazol-5-yl)-6,11-dihydro-11-oxodibenz[b,e]oxepin in 100 cc. of absolute ethanol and add excess sodium borohydride in portions. Dilute the resulting solution with water and acidify with aqueous conc. hydrochloric acid. Separate the solids by filtration. Crystallize from ethyl acetate to obtain the title product (m.p. 335° C.).
Reaction SMILES: C([Si:3](CC)([Si:13](CC)(CC)[Si:14](CC)(CC)[Si:15](CC)(CC)[Si:16](C)(C)C)[Si:4](C)(C)C1C=CC=CC=1)C.[F:34][C:35]([F:41])([F:40])[S:36]([OH:39])(=[O:38])=[O:37]>ClCCl>[F:34][C:35]([F:41])([F:40])[S:36]([O:39][SiH2:4][SiH2:3][SiH2:13][SiH2:14][SiH2:15][SiH3:16])(=[O:38])=[O:37]
Reactant: O=S(=O)(O)C(F)(F)F
Reactant: CC[Si](CC)([Si](C)(C)C)[Si](CC)(CC)[Si](CC)(CC)[Si](CC)(CC)[Si](C)(C)c1ccccc1
Solvent: ClCCl
Product: O=S(=O)(O[SiH2][SiH2][SiH2][SiH2][SiH2][SiH3])C(F)(F)F

Procedure:
In an argon atmosphere, to a tetrahydrofuran solution (1 ml) of 52 mg (0.15 mmol) of octaethylcyclotetrasilane was added 0.71 ml (0.10 mmol) of a tetrahydrofuran solution (0.14M) of phenyldimethylsilyllithium, and stirred at 0° C. for 15 minutes. Then, tetrahydrofuran was distilled out under vacuum, and hexane (1 ml) was added to give a hexane solution (Solution 1). A dichloromethane solution (1 ml) of 27 mg (0.05 mmol) of 2,2,3,3,4,4,5,5-octaethyl-1,1,6,6,6-pentamethyl-1-phenylhexasilane (2) obtained in Example 2 was treated with 7.5 mg (0.05 mmol) of trifluoromethanesulfonic acid at room temperature for 30 minutes to give 1-(trifluoromethanesulfonyloxy)hexasilane. Then, dichloromethane was distilled out under vacuum, and hexane (1 ml) was added to give a hexane solution (Solution 2). The Solution 1 was added to the Solution 2 at -78° C. and stirred for 15 minutes. Methanol (0.1 ml) and triethylamine (0.1 ml) were added, then saturated aqueous sodium bicarbonate solution (2 ml) was added, stirred, the hexane layer was separated, and dried with magnesium sulfate. The resulting crude product was purified by a silica gel column chromatography (hexane) to afford 41 mg (86% yield) of undecasilane (8) as a colorless crystal.
Reaction SMILES: N[C@H:2]([CH:7]=O)[CH2:3]CSC.[C:9]1([C:15]2[CH2:24][C:23](=[O:25])[C:22]3[C:17](=[CH:18][CH:19]=[C:20]([C:26]([OH:28])=[O:27])[CH:21]=3)[N:16]=2)[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.C(O)(=O)C>C(O)(C)C>[C:9]1([C:15]2[CH2:24][C:23](=[O:25])[C:22]3[C:17](=[CH:18][CH:19]=[C:20]([C:26]([O:28][CH:2]([CH3:7])[CH3:3])=[O:27])[CH:21]=3)[N:16]=2)[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=1
Reactant: CSCC[C@H](N)C=O
Reactant: O=C(O)c1ccc2c(c1)C(=O)CC(c1ccccc1)=N2
Solvent: CC(C)O
Solvent: CC(=O)O
Product: CC(C)OC(=O)c1ccc2c(c1)C(=O)CC(c1ccccc1)=N2
Temperature: 0 °C
Yield: 78.8 %

Procedure:
Metal sodium (0.33 gram) is dissolved in 40 ml of anhydrous isopropyl alcohol and the solution is heated to reflux for one hour with 2 grams of the 2-phenyl-4-quinolone-6-carboxylic acid obtained in Example 2. After cooling, the solution is mixed with ice water, acidified with acetic acid, the crystals which separate out therefrom are collected by filtration. The crystals are washed with water, washed with methanol, and dried to give 0.6 gram of isopropyl 2-phenyl-4-quinolone-6-carboxylate, colorless powder, melting at above 300° C.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[CH:9]=[C:8](Br)[CH:7]=[CH:6]2.[CH2:14]1[CH2:21][O:20][CH2:19][CH:16]([CH:17]=[CH2:18])[O:15]1.P>[Pd]>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[CH:9]=[C:8]([CH:18]=[CH:17][CH:16]1[O:15][CH2:14][CH2:21][O:20][CH2:19]1)[CH:7]=[CH:6]2
Reactant: C=CC1COCCO1
Reactant: COc1ccc2cc(Br)ccc2c1
Agent: [Pd]
Agent: P
Product: COc1ccc2cc(C=CC3COCCO3)ccc2c1

Procedure:
It has now been found that, by reacting 6-methoxy-2-bromonaphthalene with 3-ethylenedioxybutene (II) in the presence of a bivalent palladium salt and a phosphine, the reaction takes place extremely rapidly without operating under pressure and the 6-methoxy-2-(3-ethylenedioxybuten-1-yl)naphthalene (III) is obtained in optimum yields.
Reaction SMILES: [OH:1][CH:2]1[CH2:6][CH2:5][N:4]([CH2:7][C:8]([O:10]CC)=O)[C:3]1=[O:13].[NH2:14][CH2:15][CH2:16][N:17]1[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]1>>[N:17]1([CH2:16][CH2:15][NH:14][C:8](=[O:10])[CH2:7][N:4]2[CH2:5][CH2:6][CH:2]([OH:1])[C:3]2=[O:13])[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]1
Reactant: NCCN1CCCCC1
Reactant: CCOC(=O)CN1CCC(O)C1=O
Product: O=C(CN1CCC(O)C1=O)NCCN1CCCCC1

Procedure:
3.0 g of ethyl (R/S)-2-(3-hydroxy-2-oxo-1-pyrrolidinyl)acetate and 2.87 g of N-(2-aminoethyl)piperidine are heated to 100° for 4 hours under nitrogen. The excess N-(2-aminoethyl)piperidine is distilled in a high vacuum. The (R/S)-N-[2-(1-piperidinyl)ethyl]-2-(3-hydroxy-2-oxo-1-pyrrolidinyl)acetamide remaining as the residue has a melting point of 110°-111° after crystallization from ethyl acetate.
Reaction SMILES: [C:1]([C:5]1[N:6]=[C:7]([N:22]2CCO[CH2:24][CH2:23]2)[C:8]2[N:13]=[N:12][N:11]([CH2:14][C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=3[Cl:21])[C:9]=2[N:10]=1)([CH3:4])([CH3:3])[CH3:2].C(C1N=C(Cl)C2N=NN(CC3C=CC=CC=3Cl)C=2N=1)(C)(C)C.N1CC[C@H:52]([NH:55][C:56](=[O:58])[CH3:57])[CH2:51]1>>[C:1]([C:5]1[N:6]=[C:7]([N:22]2[CH2:23][CH2:24][C@H:52]([NH:55][C:56](=[O:58])[CH3:57])[CH2:51]2)[C:8]2[N:13]=[N:12][N:11]([CH2:14][C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=3[Cl:21])[C:9]=2[N:10]=1)([CH3:3])([CH3:4])[CH3:2]
Reactant: CC(C)(C)c1nc(N2CCOCC2)c2nnn(Cc3ccccc3Cl)c2n1
Reactant: CC(=O)N[C@H]1CCNC1
Agent: CC(C)(C)c1nc(Cl)c2nnn(Cc3ccccc3Cl)c2n1
Product: CC(=O)N[C@H]1CCN(c2nc(C(C)(C)C)nc3c2nnn3Cc2ccccc2Cl)C1

Procedure:
In analogy to the procedure described for the synthesis of 5-tert-butyl-3-(2-chlorobenzyl)-7-morpholin-4-yl-3H-[1,2,3]triazolo[4,5-d]pyrimidine (example 1, step c), the title compound was prepared from 5-tert-butyl-7-chloro-3-(2-chlorobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine and (S)—N-(pyrrolidin-3-yl)acetamide. MS (m/e): 428.3 (MH+).
Reaction SMILES: [Cl:1][C:2]1[N:3]=[N:4][C:5](Cl)=[CH:6][CH:7]=1.[CH3:9][N:10]1[CH:14]=[C:13](B2OC(C)(C)C(C)(C)O2)[CH:12]=[N:11]1.C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.O.C1C=CC([PH+]([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C1C=CC([PH+]([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C(Cl)Cl.Cl[Pd]Cl.[Fe]>[Cl:1][C:2]1[N:3]=[N:4][C:5]([C:13]2[CH:12]=[N:11][N:10]([CH3:9])[CH:14]=2)=[CH:6][CH:7]=1
Reactant: Cn1cc(B2OC(C)(C)C(C)(C)O2)cn1
Reactant: Clc1ccc(Cl)nn1
Agent: Cl[Pd]Cl
Agent: [Fe]
Agent: O=C([O-])[O-]
Solvent: ClCCl
Solvent: O
Solvent: C1COCCO1
Product: Cn1cc(-c2ccc(Cl)nn2)cn1
Temperature: 80 °C
Yield: 99.9 %

Procedure:
A mixture of 3,6-dichloropyridazine (20.1 g, 135 mmol), 1-methyl-4-pyrazoleboronic acid pinacol ester (22.46 g, 108 mmol) and K2CO3 (44.71 g, 324 mmol) in 500 mL of dioxane and 200 mL of H2O was degassed with nitrogen. To this mixture was added dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II) dichloromethane adduct (5.28 g, 7.2 mmol) and the resulting mixture was bubbled with nitrogen for another 20 min. The reaction mixture was heated at 80° C. for 4 h, then concentrated in vacuo. The residue was purified by flash column chromatography with dichloromethane as eluent to provide 21 g of 3-chloro-6-(1-methyl-1H-pyrazol-4-yl)-pyridazine (76% yield): 1H NMR (CDCl3) δ 3.99 (s, 3H), 7.45 (d, 1H), 7.56 (d, 1H), 7.97 (s, 1H), 8.11 (s, 1H).
Reaction SMILES: [CH3:1][C:2]([CH3:18])([N:7]1[C:15](=[O:16])[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[C:8]1=[O:17])[CH2:3][C:4]([OH:6])=O.[NH2:19][CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][N:22]=1>C(Cl)Cl>[N:22]1[CH:23]=[CH:24][CH:25]=[CH:26][C:21]=1[CH2:20][NH:19][C:4](=[O:6])[CH2:3][C:2]([CH3:1])([CH3:18])[N:7]1[C:15](=[O:16])[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[C:8]1=[O:17]
Reactant: NCc1ccccn1
Reactant: CC(C)(CC(=O)O)N1C(=O)c2ccccc2C1=O
Solvent: ClCCl
Product: CC(C)(CC(=O)NCc1ccccn1)N1C(=O)c2ccccc2C1=O
Reaction time: 24 h
Yield: 58.3 %

Procedure:
To a solution of β,β-dimethyl-1,3dioxo-2-isoindolinepropionic acid (5 g, 20.2 mmol) and N,N-dicyclohexylcarbodiimide (4.6 g, 22.24 mmol) in 50 ml of dry methylene chloride is added 2-(aminomethyl)pyridine (2.41 g, 2.3 ml, 22.24 mmol) at ambient temperature. The mixture is stirred for 24 hours. The precipitate of dicyclohexyl urea is filtered off and discarded. The filtrate is evaporated and the residue is purified via flash chromatography on silica gel using a methylene chloride/methylene chloride-ethanolic ammonia gradient (100 to 96:4) to give 3.97 g of N-[(2-pyridinyl)methyl]-1,3-dihydro-β,β-dimethyl-1,3-dioxo-2H-isoindole-2-propanamide (58%).
Reaction SMILES: Cl.[C:2]([C:7]1[CH:12]=[CH:11][C:10]([C:13]([CH3:25])=[C:14]([CH3:24])[CH2:15][N:16]2[CH2:21][CH:20]([CH3:22])[O:19][CH:18]([CH3:23])[CH2:17]2)=[CH:9][CH:8]=1)([CH2:5][CH3:6])([CH3:4])[CH3:3]>[Pd]>[C:2]([C:7]1[CH:12]=[CH:11][C:10]([CH:13]([CH3:25])[CH:14]([CH3:24])[CH2:15][N:16]2[CH2:21][CH:20]([CH3:22])[O:19][CH:18]([CH3:23])[CH2:17]2)=[CH:9][CH:8]=1)([CH2:5][CH3:6])([CH3:3])[CH3:4]
Reactant: CCC(C)(C)c1ccc(C(C)=C(C)CN2CC(C)OC(C)C2)cc1
Agent: [Pd]
Agent: Cl
Product: CCC(C)(C)c1ccc(C(C)C(C)CN2CC(C)OC(C)C2)cc1

Procedure:
1.8 Ml. of 32% hydrochloric acid and subsequently 1.5 g. of 5% palladium/carbon are added to a solution of 4.5 g. of 4-[3-(p-tert.-amyl-phenyl)-2,3-dimethyl-2-propenyl]2,6-dimethylmorpholine in 125 ml. of alcohol and the mixture is hydrogenated. After completion of the hydrogen uptake, the catalyst is removed by filtration, the filtrate is treated with 200 ml. of 10% sodium hydroxide and then extracted with ether. The combined ether extracts are washed neutral with water, dried and evaporated. By distillation, there is obtained pure 4-[3-(p-tert.-amyl-phenyl)-2,3-dimethyl-propyl]-2,6-dimethylmorpholine having a boiling point of 145° C./0.05 Torr.