Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Br:1][C:2]1[C:3]([CH3:8])=[N:4][NH:5][C:6]=1[CH3:7].C([O-])([O-])=O.[Cs+].[Cs+].Cl[CH2:16][O:17][CH2:18][CH2:19][Si:20]([CH3:23])([CH3:22])[CH3:21]>CC(N(C)C)=O.CCOC(C)=O>[Br:1][C:2]1[C:3]([CH3:8])=[N:4][N:5]([CH2:16][O:17][CH2:18][CH2:19][Si:20]([CH3:23])([CH3:22])[CH3:21])[C:6]=1[CH3:7]
Reactant: Cc1n[nH]c(C)c1Br
Reactant: C[Si](C)(C)CCOCCl
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CC(=O)N(C)C
Solvent: CCOC(C)=O
Product: Cc1nn(COCC[Si](C)(C)C)c(C)c1Br
Reaction time: 1 h
Yield: 99.9 %

Procedure:
To a stirring suspension of 4-bromo-3,5-dimethyl-1H-pyrazole (3.5 g, 20 mmol) and Cs2CO3 (13 g, 40 mmol) in 40 mL DMA was added (2-chloromethoxy-ethyl)-trimethyl-silane (5.3 mL, 30 mmol) at room temperature. The resulting mixture was stirred for 1 hour and was diluted with 100 mL EtOAc. The organic layer was washed with brine, dried (Na2SO4), filtered, and concentrated in vacuo. The residue was then purified by SiO2 chromatography (eluting with EtOAc/Heptane system) to give 4-bromo-3,5-dimethyl-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazole 6.1 g (100%). MS(ESI) m/z 307.3 (M+H)+. Step 2 was performed using General procedure L (Suzuki) to give the product. MS(ESI) m/z 386.4 (M+H)+.
Reaction SMILES: [CH2:1]([N:3]([CH2:28][CH3:29])[C:4](=[O:27])[CH:5]([N:12]1[CH2:17][CH2:16][N:15]([C:18]2[CH:23]=[CH:22][C:21]([CH2:24]O)=[CH:20][C:19]=2[F:26])[CH2:14][CH2:13]1)[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)[CH3:2].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[C:49]1(=[O:59])[NH:53][C:52](=[O:54])[C:51]2=[CH:55][CH:56]=[CH:57][CH:58]=[C:50]12.N(C(OCC)=O)=NC(OCC)=O>C1COCC1>[O:54]=[C:52]1[C:51]2[C:50](=[CH:58][CH:57]=[CH:56][CH:55]=2)[C:49](=[O:59])[N:53]1[CH2:24][C:21]1[CH:22]=[CH:23][C:18]([N:15]2[CH2:14][CH2:13][N:12]([CH:5]([C:6]3[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=3)[C:4]([N:3]([CH2:28][CH3:29])[CH2:1][CH3:2])=[O:27])[CH2:17][CH2:16]2)=[C:19]([F:26])[CH:20]=1
Reactant: O=C1NC(=O)c2ccccc21
Reactant: CCN(CC)C(=O)C(c1ccccc1)N1CCN(c2ccc(CO)cc2F)CC1
Agent: CCOC(=O)N=NC(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: CCN(CC)C(=O)C(c1ccccc1)N1CCN(c2ccc(CN3C(=O)c4ccccc4C3=O)cc2F)CC1
Temperature: 25 °C
Reaction time: 16 h
Yield: 60.4 %

Procedure:
A solution of N,N-diethyl-2-[4-(2-fluoro-4-hydroxymethyl-phenyl)-piperazin-1-yl]-2-phenyl-acetamide (0.14 g, 0.362 mmol) in THF (3 mL) was added triphenylphosphine (96.5 mg), phthalimide (76.9 mg), and diethyl azodicarboxylate (50 μL), and the mixture stirred at rt. After 16 h, the solvent was removed and the residue purified on SiO2EtOAc/hexanes) to provide 115.5 mg of the title compound. MS (ESI): mass calcd. for C31H33FN4O3, 528.62. m/z found, 529.6 [M+H]+.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([CH2:8][O:9][Si:10]([C:13]([CH3:16])([CH3:15])[CH3:14])([CH3:12])[CH3:11])=[CH:4][N:3]=1.[CH:17]([Sn](CCCC)(CCCC)CCCC)=[CH2:18].N#N>O1CCOCC1.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>[Si:10]([O:9][CH2:8][C:5]1[CH:6]=[CH:7][C:2]([CH:17]=[CH2:18])=[N:3][CH:4]=1)([C:13]([CH3:16])([CH3:15])[CH3:14])([CH3:12])[CH3:11]
Reactant: C=C[Sn](CCCC)(CCCC)CCCC
Reactant: CC(C)(C)[Si](C)(C)OCc1ccc(Br)nc1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: N#N
Solvent: C1COCCO1
Product: C=Cc1ccc(CO[Si](C)(C)C(C)(C)C)cn1
Temperature: 25 °C
Yield: 83.8 %

Procedure:
A solution of 2-bromo-5-(tert-butyldimethylsilyloxymethyl)pyridine (1.0 g, 3.3 mmol) and vinyltributylstannane (2.09 g, 6.6 mmol) in 1,4-dioxane (30 ml) was degassed with a stream of N2 for 15 min and then Pd(PPh3)2Cl2 (116 mg, 5 mol %) was added and the reaction mixture heated at reflux under N2 for 20 h. After cooling to room temperature, the solvent were removed under reduced pressure and the mixture was azeotroped with xylene (2×10 ml). The residue was purified by column chromatography on silica using 20% EtOAc/iso-hexanes as eluent to yield the desired vinylpyridine (690 mg, 84%). 1H NMR (400 MHz, CDCl3) δ 8.40 (1H, s), 7.51 (1H, d, J=8.0 Hz), 7.21 (1H, d, J=8.0 Hz), 6.71 (1H, dd, J=17.5, 10.8 Hz), 6.06 (1H, d, J=17.5 Hz), 5.34 (1H, d, J=10.8 Hz), 4.64 (2H, s), 0.81 (9H, s), 0.00 (6H, s). m/z (ES+) 250 (M+H+).
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([N:8]2[C:16]3[CH:15]=[CH:14][C:13]([CH3:17])=[CH:12][C:11]=3[C:10]3[CH2:18][N:19]([CH3:22])[CH2:20][CH2:21][C:9]2=3)[CH:5]=[CH:6][CH:7]=1.[OH:23][C:24]1[N:29]=[CH:28][C:27](B2OC(C)(C)C(C)(C)O2)=[CH:26][CH:25]=1.C([O-])([O-])=O.[K+].[K+].O>COCCOC.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:22][N:19]1[CH2:20][CH2:21][C:9]2[N:8]([C:4]3[CH:5]=[C:6]([C:27]4[CH:26]=[CH:25][C:24]([OH:23])=[N:29][CH:28]=4)[CH:7]=[CH:2][CH:3]=3)[C:16]3[CH:15]=[CH:14][C:13]([CH3:17])=[CH:12][C:11]=3[C:10]=2[CH2:18]1
Reactant: CC1(C)OB(c2ccc(O)nc2)OC1(C)C
Reactant: Cc1ccc2c(c1)c1c(n2-c2cccc(Br)c2)CCN(C)C1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: COCCOC
Solvent: O
Product: Cc1ccc2c(c1)c1c(n2-c2cccc(-c3ccc(O)nc3)c2)CCN(C)C1
Temperature: 90 °C
Reaction time: 0.75 h

Procedure:
To a de-aerated solution of 5-(3-bromophenyl)-2,8-dimethyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole (100 mg, 0.281 mmol), 6-hydroxypyridine-3-boronic acid pinacol ester (124 mg, 0.557 mmol) and K2CO3 (116 mg, 0.845 mmol) in DME (4 mL)-water (2 mL) was added Pd(PPh3)4 (16 mg, 0.013 mmol). The reaction mixture was stirred at 90° C. for 45 min. The reaction mixture concentrated under reduced pressure. The residue was dissolved in EtOAc (50 mL) and washed with water (20 mL). The organic layer was dried over anhydrous sodium sulfate, concentrated under reduced pressure to afford crude material, which was purified by reverse phase HPLC to yield 5-(3-(2,8-dimethyl-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)phenyl)pyridin-2-ol. 1H NMR (TFA salt, CD3OD) d (ppm): 8.0 (d, 1H), 7.8 (d, 1H), 7.68 (m, 2H), 7.6 (s, 1H), 7.4 (dd, 1H), 7.36 (s, 1H), 7.17 (d, 1H), 7.08 (d, 1H), 6.62 (d, 1H), 4.7 (d, 1H), 4.4 (d, 1H), 3.8 (m, 1H), 3.56 (m, 1H), 3.18 (m, 4H), 3.02 (m, 1H), 2.4 (s, 3H).
Reaction SMILES: [CH3:1][S:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[O:13][N:12]=[CH:11][C:10]=2[CH2:14]O)=[CH:5][CH:4]=1.O1CCCC1.S(Cl)([Cl:23])=O>C1(C)C=CC=CC=1>[Cl:23][CH2:14][C:10]1[CH:11]=[N:12][O:13][C:9]=1[C:6]1[CH:7]=[CH:8][C:3]([S:2][CH3:1])=[CH:4][CH:5]=1
Reactant: CSc1ccc(-c2oncc2CO)cc1
Reactant: O=S(Cl)Cl
Solvent: C1CCOC1
Solvent: Cc1ccccc1
Product: CSc1ccc(-c2oncc2CCl)cc1
Temperature: 25 °C
Reaction time: 2 h
Yield: 96.7 %

Procedure:
To a mixture of 5-(4-methylthiophenyl)-4-isoxazolylmethanol (7.35 g), tetrahydrofuran (20 ml) and toluene (80 ml) was added dropwise thionyl chloride (5.93 g) at 0° C. and the mixture was stirred at room temperature for 2 hr. The reaction mixture was concentrated, saturated aqueous sodium hydrogencarbonate was added to the residue, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine, dried (MgSO4) and concentrated. The residue was subjected to silica gel column chromatography, and 4-chloromethyl-5-(4-methylthiophenyl)isoxazole (7.70 g, yield 97%) was obtained as crystals from a fraction eluted with ethyl acetate-hexane (1:3, volume ratio) and recrystallized from diethyl ether-hexane to give a colorless prism. melting point: 73–74° C.
Reaction SMILES: C(C1N=C(N2CCC(F)(F)C2)C2C(=NN(CC)N=2)N=1)(C)(C)C.[C:23]([C:27]1[N:28]=[C:29]([N:36]2[CH2:40][C:39]([F:42])([F:41])[C:38]([F:44])([F:43])[CH2:37]2)[C:30]2[N:35]=[N:34][NH:33][C:31]=2[N:32]=1)([CH3:26])([CH3:25])[CH3:24].Cl[CH2:46][C:47]1[O:51][N:50]=[C:49]([CH3:52])[N:48]=1>>[C:23]([C:27]1[N:28]=[C:29]([N:36]2[CH2:40][C:39]([F:41])([F:42])[C:38]([F:43])([F:44])[CH2:37]2)[C:30]2[C:31](=[N:33][N:34]([CH2:46][C:47]3[O:51][N:50]=[C:49]([CH3:52])[N:48]=3)[N:35]=2)[N:32]=1)([CH3:26])([CH3:24])[CH3:25]
Reactant: Cc1noc(CCl)n1
Reactant: CC(C)(C)c1nc(N2CC(F)(F)C(F)(F)C2)c2nn[nH]c2n1
Agent: CCn1nc2nc(C(C)(C)C)nc(N3CCC(F)(F)C3)c2n1
Product: Cc1noc(Cn2nc3nc(C(C)(C)C)nc(N4CC(F)(F)C(F)(F)C4)c3n2)n1

Procedure:
In analogy to the procedure described for the synthesis of 5-tert-butyl-7-(3,3-difluoro-pyrrolidin-1-yl)-2-ethyl-2H-[1,2,3]triazolo[4,5-d]pyrimidine (example 3, step b), the title compound was prepared from 5-tert-Butyl-7-(3,3,4,4-tetrafluoro-pyrrolidin-1-yl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine and 5-(chloromethyl)-3-methyl-1,2,4-oxadiazole and isolated as light yellow gum. MS (m/e): 415.3 (MH+).
Reaction SMILES: [CH3:1][N:2]1[CH:6]=[CH:5][N:4]=[CH:3]1.[Cl:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH3:13]>>[Cl-:7].[CH2:8]([N+:4]1[CH:5]=[CH:6][N:2]([CH3:1])[CH:3]=1)[CH2:9][CH2:10][CH2:11][CH2:12][CH3:13]
Reactant: Cn1ccnc1
Reactant: CCCCCCCl
Product: CCCCCC[n+]1ccn(C)c1
Product: [Cl-]
Temperature: 100 °C
Reaction time: 4 h

Procedure:
Dry 1-methylimidazole (9.03 g, 0.11 mol) was mixed with 1-chlorohexane (12.06 g, 0.1 mol) and placed in a Corius tube inside a dry box. The Corius tube was then closed using a super seal in the dry box and sealed under vacuum. The two components formed two layers, inside the Corius tube, and this mixture was heated at 100° C. for a week. The resulting product was allowed to cool to room temperature when it formed a viscous product. The viscous product was transferred from the dry box to a Schlenk round bottomed flask where it was left under vacuum for 4 hours to form a viscous liquid.
Reaction SMILES: [Si]([O:18][CH2:19][C@@H:20]([S:49][CH2:50][P:51]([O:56][CH2:57][CH3:58])([O:53][CH2:54][CH3:55])=[O:52])[CH2:21][O:22][N:23]1[CH:31]=[N:30][C:29]2[C:24]1=[N:25][C:26]([N:34](C(OC(C)(C)C)=O)C(OC(C)(C)C)=O)=[N:27][C:28]=2[O:32][CH3:33])(C(C)(C)C)(C1C=CC=CC=1)C1C=CC=CC=1.FC(F)(F)C(O)=O.N>O>[NH2:34][C:26]1[N:25]=[C:24]2[C:29]([N:30]=[CH:31][N:23]2[O:22][CH2:21][C@@H:20]([S:49][CH2:50][P:51]([O:56][CH2:57][CH3:58])([O:53][CH2:54][CH3:55])=[O:52])[CH2:19][OH:18])=[C:28]([O:32][CH3:33])[N:27]=1
Reactant: CCOP(=O)(CS[C@@H](COn1cnc2c(OC)nc(N(C(=O)OC(C)(C)C)C(=O)OC(C)(C)C)nc21)CO[Si](c1ccccc1)(c1ccccc1)C(C)(C)C)OCC
Agent: N
Solvent: O
Solvent: O=C(O)C(F)(F)F
Product: CCOP(=O)(CS[C@@H](CO)COn1cnc2c(OC)nc(N)nc21)OCC
Temperature: 25 °C
Reaction time: 3 h
Yield: 73 %

Procedure:
(R)- or (S)-9-[3-t-butyldiphenylsilyloxy-2-(diethoxyphosphorylmethylthio)propoxy]di-t-butoxycarbonylamino-6-methoxypurine (0.45%, 0.52 mmol) was added to a mixture of water (1.5 ml) and trifluoroacetic acid (4.5 ml), and the mixture was stirred at room temperature for 3 hr. The solution was then treated with saturated ethanolic ammonia solution to bring the pH to 11. The solution was extracted with chloroform (3×50 ml) and the organic layers were combined and dried (MgSO4). After filtration and evaporation in vacuo the residue was purified by column chromatography on silica, eluting with chloroform : methanol (95:5) to give (R) or (S)-2-Amino-9-[2-(diethoxyphosphorylmethylthio)-3-hydroxypropoxy]-6-methoxypurine as a colourless gum (0.16 g, 72%). υmax (film) 3340, 3220, 3120, 2980, 1620, 1585, 1500, 1480, 1450, 1390, 1330 and 1260 cm-1 ; 1H NMR δH [(CD)3SO] 1.22 (δH t, J 6Hz, CH3 × 2) 3.06 (2H,d, J=12.5Hz, PCH2S), 3.35 (1H, m, CH of CH2), 3.66 (1H, m, CH of CH2), 3.8 (1H, m, CH),3.96 (3H, s, OCH3), 4.02 (4H, m, CH2 ×2), 4.46 (2H, m, CH2), 5.06 (1H, t, J ™5.5Hz, D2O exchangeable OH), 6.6 (2H, brs, D2O exchangeable NH2), 8.1 (1H, s, 8-H): (Found: C, 39.03; H,5.70; N15.89 %. C14H24N5O6PS (0.5 H2O ) requires: C,39.06; H,5.80, N,16.24%; MS.(70eV): m/z=422 (MH+); [α] 25 CHCl3) (S)-enantiomer ™+1.8°; (R)-enantiomer=-1.3°.
Reaction SMILES: [C@@H:1]1([N:10]2[C:20]3[N:19]=[C:17]([NH2:18])[NH:16][C:14](=[O:15])[C:13]=3[N:12]=[CH:11]2)[O:9][C@H:6]([CH2:7][OH:8])[C@@H:4]([OH:5])[C@H:2]1[OH:3].C[Si](Cl)(C)C.[C:26]1([CH2:32][C:33](Cl)=[O:34])[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.[NH3:36].[K+].[Br-]>N1C=CC=CC=1.CCO.O>[N:36]#[N:10].[C:26]1([CH2:32][C:33]([C@@:1]2([N:10]3[C:20]4[N:19]=[C:17]([NH2:18])[NH:16][C:14](=[O:15])[C:13]=4[N:12]=[CH:11]3)[O:9][C@H:6]([CH2:7][OH:8])[C@@H:4]([OH:5])[C@H:2]2[OH:3])=[O:34])[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1
Reactant: N
Reactant: O=C(Cl)Cc1ccccc1
Reactant: Nc1nc2c(ncn2[C@@H]2O[C@H](CO)[C@@H](O)[C@H]2O)c(=O)[nH]1
Agent: C[Si](C)(C)Cl
Agent: [Br-]
Agent: [K+]
Solvent: c1ccncc1
Solvent: CCO
Solvent: O
Product: N#N
Product: Nc1nc2c(ncn2[C@]2(C(=O)Cc3ccccc3)O[C@H](CO)[C@@H](O)[C@H]2O)c(=O)[nH]1
Temperature: 25 °C
Reaction time: 1 h
Yield: 59 %

Procedure:
Guanosine 5 (10.19 g, 36 mmoles) was dried three times by coevaporation with dry pyridine and suspended in 200 ml of dry pyridine. To this was added trimethylsilyl chloride (24 ml, 180 mmoles) at room temperature. After the solution was stirred for 1 hour at room temperature, phenylacetyl chloride (24 ml, 180 mmoles) was added dropwise and the solution was maintained at room temperature with mechanical stirring for 15 hours. The reaction mixture was cooled in an ice bath, and 75 ml of cold water added. After 30 minutes, 75 ml of 29% aqueous ammonia was added and the reaction mixture was stirred for 30 minutes. The solution was then evaporated to near dryness, and the residue was dissolved in 300 ml water and 300 ml methylene chloride. The product crystallizing out of the aqueous solution upon extraction with CH2Cl2 was filtered off, washed with CH2Cl2 (3×70 ml) and ether (3×70 ml) and air dried to yield 8.5 g (59% yield) of Ribo GPA 6. The product was characterized as follows: m.p. 160°-170° C. (dec.); UV (EtOH): λ max 280 nm and 258 nm; IR (KBr): ν 1680 (vs, C=O of amide), 1722 (s, C=O of amide ring), and 3000-3500 (NHOH) cm-1 ; 1H-NMR (DMSO-d6): δ 3.53 and 3.57 (2m, 2H, C5, CH2), 3.81 (s, 2H, C6H5CH2), 3.91 (d, 1H, C4'H), 4.13 (m, 1H, C3' H), 4.42 (d, 1H, C2' H), 5.08 (br, s, 1H, C5' OH), 5.21 (br, s, 1H, C3' OH), 5.81 (d, 1H, J1',2' =5.64 Hz, C1' H), 7.26-7.41 (m, 5H, C6H5), 8.28 (s, 1H, C8H), 11.99 and 12.01 (2s, 2H, 2×NHCO). Calcd for C18H19N5O6 (401.37): C, 53.86; H, 4.77; N, 17.45. Found: C, 53.49; H, 5.11; N, 17.36
Reaction SMILES: I[CH2:2][CH2:3][CH:4]1[CH2:13][CH2:12][C:7]2([O:11][CH2:10][CH2:9][O:8]2)[CH2:6][CH2:5]1.CN(C=O)C.CC(C)([O-])C.[K+].CCCCCCC>O>[CH:3]([CH:4]1[CH2:13][CH2:12][C:7]2([O:8][CH2:9][CH2:10][O:11]2)[CH2:6][CH2:5]1)=[CH2:2]
Reactant: ICCC1CCC2(CC1)OCCO2
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: O
Solvent: CCCCCCC
Solvent: CN(C)C=O
Product: C=CC1CCC2(CC1)OCCO2
Temperature: 3 °C
Yield: 81.5 %

Procedure:
Fifth Step: 223.0 g of the compound (14) and 800 mL of DMF were added to a reactor under nitrogen atmosphere, and stirred at 3° C. under cooling with ice. 92.9 g of potassium t-butoxide (t-BuOK) was added thereto by dividing into 10 portions at a temperature range of from 3 to 10° C., followed by further stirring at 0° C. for 3 hours. After confirming that the reaction had been completed by GC analysis, the reaction mixture was poured into and mixed with a mixture of 1,500 mL of heptane and 1,500 mL of water at 0° C. The mixture was separated into an organic layer and an aqueous layer by standing still, so as to attain extraction to the organic layer. The resulting organic layer was fractionated and washed with water, followed by drying over anhydrous magnesium sulfate. The resulting organic layer was purified by silica gel column chromatography using heptane as eluent, and the solvent was removed by distillation under reduced pressure. The resulting residue was distilled under reduced pressure to obtain 103.3 g of 8-vinyl-1,4-dioxaspiro[4,5]decane (15) as a colorless transparent liquid.
Reaction SMILES: [CH3:1][CH:2]1[CH2:16][C:15]2[C:4]([CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH:14]=2)=[CH:3]1>C1(C)C=CC=CC=1.[Pd]>[CH3:1][CH:2]1[CH2:3][C:4]2[CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][C:15]=2[CH2:16]1
Reactant: CC1C=C2CCCCCCCCCC=C2C1
Agent: [Pd]
Solvent: Cc1ccccc1
Product: CC1CC2=C(CCCCCCCCCC2)C1
Yield: 87 %

Procedure:
6.48 g of 14-methyl-bicyclo[10.3.0]pentadeca-1,12-diene--crude material; see Example 3--in 40 ml of toluene were hydrogenated in the presence of 0.65 g of 10% palladium on charcoal as indicated in Example 5. After the above treatments of filtration and distillation, there were obtained 5.69 g (86% yield) of the desired title compound having a purity of 95% according to the vapour phase chromatography analysis (CARBOWAX 10%--1.6 m--140°). The compound thus prepared was found identical with a sample prepared according to Chem. Abstr. 70, 88108 v (1970).
Reaction SMILES: [CH2:1]([O:5][CH:6]([O:30][CH2:31][CH2:32][CH2:33][CH3:34])[CH:7]([CH2:23][CH2:24][CH2:25][NH:26][C:27](=[NH:29])[NH2:28])[NH:8][C:9](=[O:22])[CH2:10][NH:11]C(OCC1C=CC=CC=1)=O)[CH2:2][CH2:3][CH3:4]>CO.[Pd]>[CH2:31]([O:30][CH:6]([O:5][CH2:1][CH2:2][CH2:3][CH3:4])[CH:7]([CH2:23][CH2:24][CH2:25][NH:26][C:27](=[NH:28])[NH2:29])[NH:8][C:9](=[O:22])[CH2:10][NH2:11])[CH2:32][CH2:33][CH3:34]
Reactant: CCCCOC(OCCCC)C(CCCNC(=N)N)NC(=O)CNC(=O)OCc1ccccc1
Agent: [Pd]
Solvent: CO
Product: CCCCOC(OCCCC)C(CCCNC(=N)N)NC(=O)CN
Yield: 84.1 %

Procedure:
644 mg of the obtained N-benzyloxycarbonyl-glycyl-D,L-argininal dibutyl acetal was dissolved in 30 ml of methanol and subjected to catalytic reduction with palladium black for four hours. After the completion of the reaction, the palladium black was removed and the solvent was distilled off in vacuo to give 390 mg of glycyl-D,L-argininal dibutyl acetal in the form of a powder.
Reaction SMILES: [F:1][C:2]1[C:3]([F:9])=[N:4][C:5](F)=[N:6][CH:7]=1.C(=O)([O-])[O-].[K+].[K+].[F:16][C:17]1[CH:18]=[C:19]([OH:23])[CH:20]=[CH:21][CH:22]=1.O>C(#N)C>[F:1][C:2]1[CH:7]=[N:6][C:5]([O:23][C:19]2[CH:20]=[CH:21][CH:22]=[C:17]([F:16])[CH:18]=2)=[N:4][C:3]=1[F:9]
Reactant: Oc1cccc(F)c1
Reactant: Fc1ncc(F)c(F)n1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CC#N
Product: Fc1cccc(Oc2ncc(F)c(F)n2)c1
Temperature: 10 °C
Reaction time: 18 h

Procedure:
11.38 g (0.085 mol) of trifluoropyrimidine are dissolved in 240 ml of acetonitrile and admixed with 15.26 g (0.11 mol) of potassium carbonate, and the mixture is cooled to 10° C. Under argon, a solution of 9.52 g (0.085 mol) of 3-fluorophenol in 80 ml of acetonitrile is added dropwise. The mixture is then stirred under argon, without further cooling, for another 18 hours. The mixture is poured into 1 litre of water and extracted three times with in each case 150 ml of ethyl acetate, and the organic phase is dried over sodium sulphate and concentrated under reduced pressure. The residue is subjected to kugelrohr distillation. This gives 15.2 g (79.1% of theory) of 5,6-difluoro-(3-fluorophenoxy)-pyrimidine of boiling point 95° C. at 0.5 mbar.
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[N:7][CH:8]=[CH:9][CH:10]=2)[N:5]=[C:4]([C:12]2[CH:17]=[C:16]([Cl:18])[CH:15]=[CH:14][C:13]=2[F:19])[CH:3]=1.[CH:20]1[C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[C:23](B(O)O)=[CH:22][N:21]=1.C(=O)([O-])[O-].[Na+].[Na+].O1CCOCC1>O>[Cl:18][C:16]1[CH:15]=[CH:14][C:13]([F:19])=[C:12]([C:4]2[CH:3]=[C:2]([C:23]3[C:24]4[C:29](=[CH:28][CH:27]=[CH:26][CH:25]=4)[CH:20]=[N:21][CH:22]=3)[C:11]3[C:6](=[N:7][CH:8]=[CH:9][CH:10]=3)[N:5]=2)[CH:17]=1
Reactant: OB(O)c1cncc2ccccc12
Reactant: Fc1ccc(Cl)cc1-c1cc(Cl)c2cccnc2n1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: C1COCCO1
Solvent: O
Product: Fc1ccc(Cl)cc1-c1cc(-c2cncc3ccccc23)c2cccnc2n1
Yield: 77.8 %

Procedure:
426 mg 4-chloro naphthyridine from example 1, 682 mg 4-isoquinoline boronic acid pinacole ester, 945 mg sodium carbonate were dissolved with 30 ml dioxan and 3 ml water, flushed with nitrogen, and 172 mg tetrakistriphenylphosphine palladium(0) were added. After 105 min reflux workup as in example 20 yielded a brownish oil, which was crystallized with ether to give 436 mg of product with correct LC-MS: M+H+ 386 and Rf˜2.22 min.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:15]2[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=2)[N:9]2[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]2)=[CH:4][CH:3]=1.[F:22][C:23]1[CH:24]=[C:25]([NH:29][C:30](=[O:34])[CH:31](Br)[CH3:32])[CH:26]=[CH:27][CH:28]=1.C(=O)([O-])[O-].[K+].[K+].C(OCC)(=O)C>O1CCCC1.CN(C)C=O>[F:21][C:18]1[CH:19]=[CH:20][C:15]([CH:8]([C:5]2[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=2)[N:9]2[CH2:10][CH2:11][N:12]([CH:31]([C:30](=[O:34])[NH:29][C:25]3[CH:26]=[CH:27][CH:28]=[C:23]([F:22])[CH:24]=3)[CH3:32])[CH2:13][CH2:14]2)=[CH:16][CH:17]=1
Reactant: CC(Br)C(=O)Nc1cccc(F)c1
Reactant: Fc1ccc(C(c2ccc(F)cc2)N2CCNCC2)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: C1CCOC1
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: CC(C(=O)Nc1cccc(F)c1)N1CCN(C(c2ccc(F)cc2)c2ccc(F)cc2)CC1
Temperature: 90 °C
Reaction time: 2 h

Procedure:
A mixture of 300 mg of 1-[bis(4-fluorophenyl)methyl]piperazine and 256 mg of N-(3-fluorophenyl) -2-bromopropionamide was dissolved in 20 ml of a 1:1 by volume mixture of tetrahydrofuran and N,N-dimethylformamide, and 100 mg of anhydrous potassium carbonate were added to the resulting solution. The reaction mixture was then stirred at 90° C. for 2 hours. At the end of this time, ethyl acetate was added, and the organic layer was separated. The organic layer was washed three times with water, and then dried over anhydrous magnesium sulfate. The solvent was removed by evaporation under reduced pressure, and the residue was subjected to silica gel thin layer chromatography using a 1:1 by volume mixture of cyclohexane and ethyl acetate as the developing solvent, to give 1-[bis(4-fluorophenyl)methyl]-4-[1-(3-fluorophenylcarbamoyl)ethyl]piperazine.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([N+:10]([O-:12])=[O:11])[CH:5]=[C:6]([F:9])[C:7]=1F.[Cl:13][C:14]1[CH:19]=[CH:18][C:17]([OH:20])=[CH:16][CH:15]=1.C([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C>[Cl:13][C:14]1[CH:19]=[CH:18][C:17]([O:20][C:7]2[C:6]([F:9])=[CH:5][C:4]([N+:10]([O-:12])=[O:11])=[CH:3][C:2]=2[F:1])=[CH:16][CH:15]=1
Reactant: O=[N+]([O-])c1cc(F)c(F)c(F)c1
Reactant: Oc1ccc(Cl)cc1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Product: O=[N+]([O-])c1cc(F)c(Oc2ccc(Cl)cc2)c(F)c1
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 106.9 %

Procedure:
A mixture of 3,4,5-trifluoronitrobenzene (6.6 g, 37 mmol), dry DMF (30 ml), 4-chlorophenol (5.26 g, 41 mmol), and Cs2CO3 (18.8 g, 58 mmol) was stirred under N2 at 60-70 C for 1-2 hrs. After cooling to room temperature, the reaction mixture was partitioned between H2O and EtOAc. The phases were separated and the aqueous phase was further extracted with EtOAc (2×). The EtOAc extractions were washed with sat'd NaCl (1×), dried over Na2SO4, and concentrated in vacuo to give 4-(4-chlorophenoxy)-3,5-difluoronitrobenzene (11.3 g, 106%) which was used in the next step without further purification. 1H NMR (CDCl3): δ 6.90 (d, 2H, J=7.6 Hz), 7.28 (d, 2H, J=7.6 Hz), 7.94 (d, 2H, J=6.4 Hz). Note: K2CO3/acetonitrile can be used in lieu of Cs2CO3/DMF.