Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([NH:8][CH2:9][CH2:10][N:11]([CH3:13])[CH3:12])[N:5]=[C:4]2[N:14]([C:19]3[C:24]([F:25])=[CH:23][CH:22]=[CH:21][C:20]=3[F:26])[C:15](=[O:18])[NH:16][CH2:17][C:3]=12.O.C(=O)([O-])[O-].[K+].[K+].CC1(C)C(C)(C)OB([C:42]2[CH:43]=[C:44]([CH:48]=[CH:49][CH:50]=2)[C:45]([OH:47])=[O:46])O1>O1CCOCC1.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>[F:26][C:20]1[CH:21]=[CH:22][CH:23]=[C:24]([F:25])[C:19]=1[N:14]1[C:4]2[N:5]=[C:6]([NH:8][CH2:9][CH2:10][N:11]([CH3:13])[CH3:12])[N:7]=[C:2]([C:42]3[CH:43]=[C:44]([CH:48]=[CH:49][CH:50]=3)[C:45]([OH:47])=[O:46])[C:3]=2[CH2:17][NH:16][C:15]1=[O:18]
Reactant: CN(C)CCNc1nc(Cl)c2c(n1)N(c1c(F)cccc1F)C(=O)NC2
Reactant: CC1(C)OB(c2cccc(C(=O)O)c2)OC1(C)C
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: C1COCCO1
Solvent: O
Product: CN(C)CCNc1nc(-c2cccc(C(=O)O)c2)c2c(n1)N(c1c(F)cccc1F)C(=O)NC2
Yield: 98.5 %

Procedure:
To a solution of 5-chloro-1-(2,6-difluorophenyl)-7-{[2-(dimethylamino)-ethyl]amino}-3,4-dihydropyrimido[4,5-d]pyrimidin-2(1H)-one (100 mg, 0.26 mmol) in dioxane (9 mL)/water (3 mL) were added potassium carbonate (217 mg, 1.57 mmol), tetrakis(triphenylphosphine)palladium(0) (15 mg, 0.013 mmol) and 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoic acid (65 mg, 0.39 mmol). The reaction mixture was bubbled with N2 for 5 mins, then microwaved at about 150° C. for about 30 mins. The reaction mixture was concentrated. To the concentrated mixture were added DMSO (2 mL), H2O (0.5 mL) and AcOH (0.05 mL). Separation via a HPLC then provided the title compound as a white solid (120 mg, 98%). LC-MS m/z 469 (M+H)+.
Reaction SMILES: [Na].C(O)C.[Cl:5][C:6]1[C:11]([Cl:12])=[CH:10][CH:9]=[CH:8][C:7]=1[CH2:13][C:14]#[N:15].[CH2:16]([O:18][C:19](=O)[O:20]CC)[CH3:17]>>[CH2:16]([O:18][C:19](=[O:20])[CH:13]([C:14]#[N:15])[C:7]1[CH:8]=[CH:9][CH:10]=[C:11]([Cl:12])[C:6]=1[Cl:5])[CH3:17]
Reactant: CCOC(=O)OCC
Reactant: N#CCc1cccc(Cl)c1Cl
Agent: [Na]
Solvent: CCO
Product: CCOC(=O)C(C#N)c1cccc(Cl)c1Cl

Procedure:
Sodium (1.2 g) was added portionwise to ethanol (50 ml) with stirring. After the sodium had dissolved a solution of 2,3-dichlorophenylacetonitrile (9.4 g) in diethylcarbonate (25 ml) was added dropwise. The reaction mixture was heated until EtOH distilled over. The rate of addition was controlled such that it equalled the rate of distillation. After the completion of the addition, the reaction mixture was heated and distilled for a further 4 hours. The cooled reaction mixture was partitioned between water and EtOAc (300 ml each). The organic layer was dried and evaporated in vacuo and the residue was purified by flash column chromatography to give the title product. (5 g, 39%).
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.Br[CH2:8][C:9]([O:11][CH2:12][CH3:13])=[O:10]>C1C=CC=CC=1.C(OCC)C>[N:1]1([CH2:8][C:9]([O:11][CH2:12][CH3:13])=[O:10])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: C1CCNCC1
Reactant: CCOC(=O)CBr
Solvent: CCOCC
Solvent: c1ccccc1
Product: CCOC(=O)CN1CCCCC1
Temperature: 25 °C
Reaction time: 2 h
Yield: 81.8 %

Procedure:
Piperidine(1.87 ml, 18.9 mmol) was added dropwise to a solution of ethyl bromoacetate(1 ml, 9.0 mmol) in benzene(9 ml), stirred for 2 hours at a room temperature, diluted with ethyl ether, washed with saturated NaCl solution. The separated organic layer was dried over anhydrous sodium sulfate and concentrated under a reduced pressure to give 1.26 g of the titled compound. (Yield 81.8%)
Reaction SMILES: [O:1]=[C:2]1[N:13]2[C:14]3[C:10]([CH:11]=[CH:12]2)=[CH:9][C:8]([C:15]2[CH:22]=[CH:21][C:18]([CH:19]=O)=[CH:17][CH:16]=2)=[CH:7][C:6]=3[CH2:5][NH:4][CH2:3]1.[CH3:23][NH2:24]>>[CH3:23][NH:24][CH2:19][C:18]1[CH:17]=[CH:16][C:15]([C:8]2[CH:9]=[C:10]3[C:14]4=[C:6]([CH2:5][NH:4][CH2:3][C:2](=[O:1])[N:13]4[CH:12]=[CH:11]3)[CH:7]=2)=[CH:22][CH:21]=1
Reactant: O=Cc1ccc(-c2cc3c4c(ccn4C(=O)CNC3)c2)cc1
Reactant: CN
Product: CNCc1ccc(-c2cc3c4c(ccn4C(=O)CNC3)c2)cc1
Yield: 71 %

Procedure:
Using the reductive amination procedure described in Example 82, the title compound was synthesized from 4-(1-oxo-1,2,3,4-tetrahydro-[1,4]diazepino[6,7,1-hi]indol-6-yl)-benzaldehyde and methylamine in 71% yield as a pale-yellow solid: mp 178-180° C.; 1H NMR (DMSO-d6) δ 2.29 (s, 3H), 3.48 (br s, 2H), 3.70 (s, 2H), 4.30-4.33 (m, 2H), 6.68 (s, 1H), 7.16 (t, 1H, J=9.0 Hz), 7.45 (d, 2H, J=6.0 Hz), 7.55 (d, 2H, J=6.0 Hz), 7.77 (d, 1H, J=9.0 Hz), 7.80 (d, 1H, J=9.0 Hz), 8.36 (t, 1H, J=6.0 Hz). HRMS calcd. for C19H19N3O 305.3828 (M+), found 305.1536. Anal. (C19H19N3O.0.1H2O) C, H, N.
Reaction SMILES: [H-].[Al+3].[Li+].[H-].[H-].[H-].[CH3:7][N:8]1[CH:12]=[C:11]([C:13]([F:16])([F:15])[F:14])[C:10]([C:17](O)=[O:18])=[N:9]1>C1COCC1>[OH:18][CH2:17][C:10]1[C:11]([C:13]([F:16])([F:15])[F:14])=[CH:12][N:8]([CH3:7])[N:9]=1
Reactant: Cn1cc(C(F)(F)F)c(C(=O)O)n1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Product: Cn1cc(C(F)(F)F)c(CO)n1
Temperature: 25 °C
Reaction time: 5 h
Yield: 76.6 %

Procedure:
Lithium aluminium hydride (1M in THF) (11 ml, 11 mmol) was added dropwise to a solution of 1-methyl-4-trifluoromethyl-1H-pyrazole-3-carboxylic acid (1.94 g, 10 mmol) in THF (20 ml) under nitrogen. More THF (20 ml) was added to facilitate the stirring. After stirring for 5 hours at room temperature the reaction was quenched by addition of water (0.5 ml), 15% aqueous sodium hydroxide (0.5 ml), and more water (0.5 ml). Ethyl acetate (50 ml) and magnesium sulfate (25 g) were added and the mixture stored at room temperature for 18 hours. Kieselguhr (30 g) was added, the mixture filtered and the solids washed with ethyl acetate. The combined filtrate and washings were concentrated to give the product as a pale yellow oily solid (1.38 g, 77% yield). 1H-NMR (400 MHz, CDCl3): 2.3 (1H, bs, OH), 3.91 (3H, s, Me), 4.75 (2H, s, CH2), 7.62 (1H, s, CH).
Reaction SMILES: Cl[C:2]1[C:7]([C:8]([OH:10])=[O:9])=[CH:6][N:5]=[CH:4][CH:3]=1.[CH3:11][O:12][C:13]1[CH:20]=[CH:19][C:16]([CH2:17][SH:18])=[CH:15][CH:14]=1.[H-].[Na+]>CN(C)C=O>[CH3:11][O:12][C:13]1[CH:20]=[CH:19][C:16]([CH2:17][S:18][C:2]2[C:7]([C:8]([OH:10])=[O:9])=[CH:6][N:5]=[CH:4][CH:3]=2)=[CH:15][CH:14]=1
Reactant: COc1ccc(CS)cc1
Reactant: O=C(O)c1cnccc1Cl
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: COc1ccc(CSc2ccncc2C(=O)O)cc1
Temperature: 0 °C

Procedure:
A stirred and ice-cooled mixture of 788 mg (0.005 mole) 4-chloronicotinic acid [prepared by the process set forth in W. C. J. Ross, J. Chem. Soc.(C), 1816 (1966)] and 771 mg (0.005 mole) of 4-methoxybenzylmercaptan in 6 mL of dry N,N-dimethylformamide was treated with 480 mg (0.012 mole) of 60% sodium hydride dispersion. The reaction was stirred at room temperature for 4 hours during which a thick solid formed, which was taken up in 75 mL of ice water. After extraction with 25 mL of hexane, the aqueous layer was acidified with 2.5N hydrochloric acid to precipitate 4-(4-methoxybenzylthio)-nicotinic acid; yield 1.2 g (89% of theory), m.p. 230° C.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([OH:11])[CH:6]=[C:7]([O:9][CH3:10])[CH:8]=1.N1C=CN=C1.[C:17]([Si:21](Cl)([C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)([CH3:20])([CH3:19])[CH3:18].O>CN(C)C=O>[O:11]([C:5]1[CH:6]=[C:7]([O:9][CH3:10])[CH:8]=[C:3]([O:2][CH3:1])[CH:4]=1)[Si:21]([C:17]([CH3:20])([CH3:19])[CH3:18])([C:28]1[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=1)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1
Reactant: CC(C)(C)[Si](Cl)(c1ccccc1)c1ccccc1
Reactant: COc1cc(O)cc(OC)c1
Agent: c1c[nH]cn1
Solvent: CN(C)C=O
Solvent: O
Product: COc1cc(OC)cc(O[Si](c2ccccc2)(c2ccccc2)C(C)(C)C)c1
Temperature: 50 °C
Reaction time: 4 h
Yield: 94.1 %

Procedure:
To a solution of 6.73 g (43.7 mmol) of 3,5-dimethoxyphenol in anhydrous dimethylformamide (50 mL) were added 5.95 g (87.4 mmol) of imidazole and 15.0 g (54.6 mmol) of t-butylchlorodiphenylsilane. The mixture was stirred at 50° C. for 4 hours. Water was added and the mixture was extracted with ethyl acetate-hexane (1:2). The organic layer was washed with water, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel, whereby 16.14 g of 1-t-butyldiphenylsiloxy-3,5-dimethoxybenzene was obtained as a colorless crystalline powder (mp: 95.5 to 96.5° C., yield: 94%).
Reaction SMILES: [CH3:1][C:2]1[C:3]([CH3:12])=[CH:4][C:5]2[S:9][C:8]([NH2:10])=[N:7][C:6]=2[CH:11]=1.O.[NH2:14]N.Cl.NN>>[CH3:1][C:2]1[C:3]([CH3:12])=[CH:4][C:5]2[S:9][C:8]([NH:10][NH2:14])=[N:7][C:6]=2[CH:11]=1
Reactant: NN
Reactant: Cc1cc2nc(N)sc2cc1C
Agent: Cl
Solvent: O
Product: Cc1cc2nc(NN)sc2cc1C
Yield: 82 %

Procedure:
5,6-Dimethyl-2-aminobenzothiazole (5.0 g., 0.028 mole), 85% hydrazine hydrate (3.49 g.; 0.056 mole) and hydrazine monohydrochloride (1.99 g.; 0.028 mole) were reacted in the procedures of Example 1. 5,6-Dimethyl-2-hydrazinobenzothiazole was obtained in 82% yield, m.p. 223°-228°C. Assay (titration) 97.2%. Recrystallization from ethanol gave material melting 235°-237°C. (dec.).
Reaction SMILES: [C:1]([C:4]12[CH2:11][CH2:10][C:7]([NH:12][CH2:13][C:14]([N:16]3[CH2:20][C@@H:19]([F:21])[CH2:18][C@H:17]3[C:22]#[N:23])=[O:15])([CH2:8][CH2:9]1)[CH2:6][CH2:5]2)([OH:3])=O.[NH2:24][C:25]1[S:26][CH:27]=[C:28]([CH:30]2[CH2:32][CH2:31]2)[N:29]=1>>[CH:30]1([C:28]2[N:29]=[C:25]([NH:24][C:1]([C:4]34[CH2:11][CH2:10][C:7]([NH:12][CH2:13][C:14]([N:16]5[CH2:20][C@@H:19]([F:21])[CH2:18][C@H:17]5[C:22]#[N:23])=[O:15])([CH2:6][CH2:5]3)[CH2:8][CH2:9]4)=[O:3])[S:26][CH:27]=2)[CH2:32][CH2:31]1
Reactant: Nc1nc(C2CC2)cs1
Reactant: N#C[C@@H]1C[C@H](F)CN1C(=O)CNC12CCC(C(=O)O)(CC1)CC2
Product: N#C[C@@H]1C[C@H](F)CN1C(=O)CNC12CCC(C(=O)Nc3nc(C4CC4)cs3)(CC1)CC2
Yield: 62.6 %

Procedure:
In a similar manner to Example 87, (2S,4S)-1-[[N-(4-carboxybicyclo[2.2.2]oct-1-yl)amino]acetyl]-4-fluoropyrrolidine-2-carbonitrile (50.0 mg) and 2-amino-4-cyclopropylthiazole (47.7 mg) were used to obtain (2S,4S)-1-[[N-[4-[N-(4-cyclopropylthiazol-2-yl)amino]carbonylbicyclo[2.2.2]oct-1-yl]amino]acetyl]-4-fluoropyrrolidine-2-carbonitrile (43.1 mg).
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.F[C:8]1[CH:15]=[CH:14][CH:13]=[CH:12][C:9]=1[C:10]#[N:11].C(=O)([O-])[O-].[K+].[K+].O>CS(C)=O>[N:1]1([C:8]2[CH:15]=[CH:14][CH:13]=[CH:12][C:9]=2[C:10]#[N:11])[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1
Reactant: N#Cc1ccccc1F
Reactant: C1CNCCN1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CS(C)=O
Solvent: O
Product: N#Cc1ccccc1N1CCNCC1
Temperature: 25 °C
Reaction time: 16 h
Yield: 87.8 %

Procedure:
Piperazine (6.0 g, 69 mmol) was dissolved in dimethylsulfoxide (50 ml), 2-fluorobenzonitrile (0.95 ml, 9 mmol) and potassium carbonate (2.2 g, 17 mmol) were added and the mixture was stirred at room temperature for 16 h. Water (100 ml) was added and the mixture was extracted with toluene (2×100 ml). The combined organic extracts were washed with 1N sodium hydroxide (3×75 ml), dried (MgSO4) and concentrated in vacuo to give 1.48 g (88%) 2-(1-piperazinyl)benzonitrile as an oil.
Reaction SMILES: [Br-:1].[Li+].[OH:3][C@@H:4]1[C@H:8]2[N:9]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:10][C@@H:11](OS(C3C=CC(C)=CC=3)(=O)=O)[C@H:7]2[O:6][CH2:5]1.C(Cl)Cl>CN(C=O)C>[Br:1][C@H:11]1[CH2:10][N:9]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[C@@H:8]2[C@@H:4]([OH:3])[CH2:5][O:6][C@H:7]12
Reactant: Cc1ccc(S(=O)(=O)O[C@@H]2CN(C(=O)OC(C)(C)C)[C@H]3[C@@H]2OC[C@@H]3O)cc1
Reactant: [Br-]
Agent: [Li+]
Solvent: ClCCl
Solvent: CN(C)C=O
Product: CC(C)(C)OC(=O)N1C[C@H](Br)[C@H]2OC[C@H](O)[C@H]21
Temperature: 130 °C
Yield: 52.6 %

Procedure:
Lithium bromide (11.51 g, 132 mmol) was added to a stirred solution of tosylate (35b) (5.28 g, 13.2 mmol) in anhydrous DMF (75 mL) and the mixture heated at 130° C. for 4 hours. The black solution was left to cool to ambient temperature then reduced in vacuo. The residue was taken into DCM (100 mL) and washed with H2O (100 mL). The organic layer was dried (Na2SO4), filtered and reduced in vacuo to leave a black tar (Yield 3.3 g). Flash chromatography over silica, eluting with ethyl acetate:heptane mixtures 5:95 to 30:70 gave bromide (111) (2.14 g, 52.6%) as a pale green solid. TLC (Rf=0.4, EtOAc:heptane 3:1), analytical HPLC main peak, Rt=9.34 min., HPLC-MS 252.1/254.1 [M+H−56]+, 308.1/310.1 [M+H]+; 330.0/332.0 [M+Na]+; [α]D22 −90.2° (c=2.33, CHCl3); δC (125 MHz, CDCl3) 28.35/28.44 ((CH3)3C), 48.26/48.75 (BrCHCH), 53.48/54.14 (BocNCH2), 67.78/68.29 (BocNCH), 75.48/75.63 (OCH2CHOH), 75.24/76.08 (OCH2CHOH), 80.78/81.07 ((CH3)3C quaternary), 87.01/87.85 (BrCHCH), 153.83/154.61 (Boc C═O).
Reaction SMILES: I[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([C:11]([NH:13][CH2:14][CH2:15][C:16]([O:18][CH2:19][CH3:20])=[O:17])=[O:12])[CH2:6][CH2:5]2.[CH:21]#[C:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH3:28]>[Cu]I>[C:21]([C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([C:11]([NH:13][CH2:14][CH2:15][C:16]([O:18][CH2:19][CH3:20])=[O:17])=[O:12])[CH2:6][CH2:5]2)#[C:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH3:28]
Reactant: C#CCCCCCC
Reactant: CCOC(=O)CCNC(=O)N1CCc2cc(I)ccc21
Agent: [Cu]I
Product: CCCCCCC#Cc1ccc2c(c1)CCN2C(=O)NCCC(=O)OCC
Temperature: 25 °C
Reaction time: 2 h
Yield: 65.8 %

Procedure:
A mixture of the product of Step B (0.16 g; 0.41 mmol), 1-octyne (0.073 ml; 0.49 mmol), Cl2Pd(PPh3)2 (0.02 g; 0.028 mmol) and CuI (0.005 g; 0.026 mmol) was degassed under reduced pressure and saturated with dry N2. After addition of DIPEA (0.5 ml), the resulting mixture was stirred for 2 h at room temperature under N2. The solvents were removed in vacuo and the residue was diluted to 15 ml with EtOAc and washed with 5% citric acid, 5% NaHCO3, H2O, brine and dried over anhydrous MgSO4 and filtered. The filtrate was evaporated to dryness under reduced pressure and the residue was purified by FCC (SiO2; CH2Cl2) to give the title compound (0.1 g; 65%) as a brownish solid. 1H-NMR (CDCl3) 7.75 (d, 1H, J=8.4 Hz); 7.16 (d, 1H, J=8.4 Hz); 7.1 (s, 1H); 5.34 (1, 1H, J=5.8 Hz); 4.11 (q, 2H, J=7.1 Hz); 3.82 (t, 2H, J=8.8 Hz); 3.52 (m, 2H); 3.06 (t, 2H, J=8.8 Hz); 2.56 (t, 2H, J=5.8 Hz); 2.33 (t, 2H, J=7.1 Hz); 1.53 (m, 2H); 1.52 (m, 2H); 1.26 (m, 6H); 1.23 (t, 2H, J=7.1 Hz); 0.86 (1, 3H, J=6.9 Hz).
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=1.[Br:8][C:9]1[CH:17]=[CH:16][C:12]([CH2:13][CH2:14]N)=[CH:11][CH:10]=1.O>C(O)CCC>[Br:8][C:9]1[CH:17]=[CH:16][C:12]([CH2:13][CH2:14][C:7]2[C:2]([NH2:1])=[N:3][CH:4]=[CH:5][CH:6]=2)=[CH:11][CH:10]=1
Reactant: Nc1ccccn1
Reactant: NCCc1ccc(Br)cc1
Solvent: CCCCO
Solvent: O
Product: Nc1ncccc1CCc1ccc(Br)cc1
Temperature: 230 °C
Yield: 24.8 %

Procedure:
In a sealed tube, a mixture of 1.9 g (20.4 mmol) of 2-aminopyridine and 6.1 g (30.6 mmol) of 4-bromophenethylamine dissolved in butanol (10 ml) is heated at 230° C. for 1 hour by microwave. The mixture, cooled to room temperature, is poured into water (50 ml) and extracted with ethyl acetate (3×100 ml), and the combined organic phases are dried over sodium sulfate, filtered and concentrated. The residue is purified by flash chromatography on a column of silica gel (eluent: dichloromethane/ethyl acetate, from 0% to 50% ethyl acetate). 1.4 g of product are obtained in the form of a white powder. Yield: 24%. Melting point: 71° C. MH+: 278.1 (tr: 3.71 min., condition 1).
Reaction SMILES: [CH2:1]=[C:2]([CH2:6][CH2:7][CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)[C:3]([OH:5])=[O:4].[C:15]([OH:18])(=[S:17])[CH3:16]>>[C:15]([S:17][CH2:1][CH:2]([CH2:6][CH2:7][CH2:8][C:9]1[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=1)[C:3]([OH:5])=[O:4])(=[O:18])[CH3:16]
Reactant: CC(O)=S
Reactant: C=C(CCCc1ccccc1)C(=O)O
Product: CC(=O)SCC(CCCc1ccccc1)C(=O)O
Temperature: 100 °C
Yield: 100 %

Procedure:
3-Phenylpropylialonic acid (6.14 g) was converted to 2-methylene-5-phenylpentanoic acid (2.1 g, 40%) by the method described in Example 32a). δH (CDCl3) 1.88 (2 H, m, CH2), 2.37 (2 H, t, J 7.6 Hz, CH2), 2.67 (2 H, t, J 7.6 Hz, CH2), 5.68 and 6.33 (2 H, 2×s, ##STR9## 7.26 (5 H, m, Ph). The solid was dissolved in thioacetic acid (5 ml) and heated at 100° C. for 2 hours. Evaporated to give the title compound (2.9 g, 100%); δH (CDCl3) 1.71 (4 H, m, 2×CH2), 2.33 (3 H, s, COCH3), 2.64 (3 H, m, CH, CH2), 3.08 (2 H, m, CH2), 7.27 (5 H, m, Ph).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:13]=[CH:12][C:11]([OH:14])=[CH:10][N:9]=2)=[CH:4][CH:3]=1.[CH2:15]([O:17][C:18]([C:20]1([CH2:34]I)[CH2:24][CH2:23][N:22]([C:25](=[O:33])[C:26]2[CH:31]=[CH:30][C:29]([F:32])=[CH:28][CH:27]=2)[CH2:21]1)=[O:19])[CH3:16]>>[CH2:15]([O:17][C:18]([C:20]1([CH2:34][O:14][C:11]2[CH:12]=[N:13][C:8]([C:5]3[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=3)=[N:9][CH:10]=2)[CH2:24][CH2:23][N:22]([C:25](=[O:33])[C:26]2[CH:27]=[CH:28][C:29]([F:32])=[CH:30][CH:31]=2)[CH2:21]1)=[O:19])[CH3:16]
Reactant: CCOC(=O)C1(CI)CCN(C(=O)c2ccc(F)cc2)C1
Reactant: Oc1cnc(-c2ccc(Cl)cc2)nc1
Product: CCOC(=O)C1(COc2cnc(-c3ccc(Cl)cc3)nc2)CCN(C(=O)c2ccc(F)cc2)C1

Procedure:
The title compound was prepared according to the method described for Preparation 29 using 2-(4-chloro-phenyl)-pyrimidin-5-ol (Preparation 27) and 1-(4-fluoro-benzoyl)-3-iodomethyl-pyrrolidine-3-carboxylic acid ethyl ester (Preparation 12) to afford the racemate as a pale yellow solid (89 mg, 37%)
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]1[N:11]=[C:10]([C:12]2[CH:17]=[C:16]([CH:18]=[CH2:19])[CH:15]=[C:14]([C:20]#[N:21])[CH:13]=2)[O:9][N:8]=1.C12CCCC(CCC1)B12[H]B2(C3CCCC2CCC3)[H]1.B1([O-])O[O:43]1.O.O.O.O.[Na+]>ClCCl.O>[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]1[N:11]=[C:10]([C:12]2[CH:17]=[C:16]([CH2:18][CH2:19][OH:43])[CH:15]=[C:14]([C:20]#[N:21])[CH:13]=2)[O:9][N:8]=1
Reactant: [O-]B1OO1
Reactant: C=Cc1cc(C#N)cc(-c2nc(-c3ccccn3)no2)c1
Agent: [Na+]
Solvent: O
Solvent: ClCCl
Product: N#Cc1cc(CCO)cc(-c2nc(-c3ccccn3)no2)c1
Temperature: 25 °C
Reaction time: 4 h
Yield: 3.9 %

Procedure:
A mixture of 3-(2-pyridyl)-5-(3-cyano-5-vinylphenyl)-1,2,4-oxadiazole (83 mg, 0.30 mmol) in dichloromethane (2 mL) was treated with 9-BBN dimer (40 mg, 0.16 mmol) and the reaction mixture stirred at room temperature for 4 hours. Sodium perborate tetrahydrate (157 mg, 1.02 mmol) and water (1 mL) were added and the resulting biphasic mixture was stirred vigorously for 18 hours. The mixture was diluted with dichloromethane and water and the organic layer dried by filtration through an EX-TUBE. Silica gel chromatography using a gradient of 20% to 75% ethyl acetate in hexane, followed by trituration in 10% ethyl acetate in hexane afforded 3.4 mg (3.7%) of 3-(2-pyridyl)-5-(3-cyano-5-(2-hydroxyethyl)phenyl)-1,2,4-oxadiazole: 1H-NMR (CDCl3), δ (ppm): □□ 8.85 (d, 1H), 8.43 (s, 2H), 8.22 (d, 1H), 7.90 (t, 1H), 7.80 (s, 1H), 7.48 (m, 1H), 3.99 (m, 2H), 3.02 (t, 2H).
Reaction SMILES: [CH3:1][S:2]([NH:5][C:6]1[CH:11]=[CH:10][C:9]([N+:12]([O-:14])=[O:13])=[CH:8][CH:7]=1)(=[O:4])=[O:3].CC(C)([O-])C.[K+].Br[CH2:22][C:23]#[N:24]>CS(C)=O>[C:23]([CH2:22][N:5]([S:2]([CH3:1])(=[O:3])=[O:4])[C:6]1[CH:7]=[CH:8][C:9]([N+:12]([O-:14])=[O:13])=[CH:10][CH:11]=1)#[N:24]
Reactant: N#CCBr
Reactant: CS(=O)(=O)Nc1ccc([N+](=O)[O-])cc1
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: CS(C)=O
Product: CS(=O)(=O)N(CC#N)c1ccc([N+](=O)[O-])cc1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
3.24 g (15 mmol) of N-methylsulphonyl-4-nitroaniline are dissolved in 25 ml of DMSO and a total of 2.0 g (18 mmol) of potassium tert.butoxide are added batchwise. After 1 hour stirring at ambient temperature 2.7 g (23 mmol) of bromoacetonitrile are added dropwise. After 3 hours stirring at ambient temperature the mixture is poured onto ice water and extracted with ethyl acetate. The organic phase is washed with water and the solvent is eliminated in vacuo. The residue thus obtained is recrystallised from ethanol.
Reaction SMILES: [NH:1]1[C:5]2=[N:6][CH:7]=[CH:8][CH:9]=[C:4]2[CH2:3][C:2]1=[O:10].[N:11]1[CH:16]=[CH:15][CH:14]=[C:13](/[CH:17]=[CH:18]/[C:19]2[C:27]3[C:22](=[CH:23][C:24]([CH:28]=O)=[CH:25][CH:26]=3)[NH:21][N:20]=2)[CH:12]=1>>[N:11]1[CH:16]=[CH:15][CH:14]=[C:13](/[CH:17]=[CH:18]/[C:19]2[C:27]3[C:22](=[CH:23][C:24]([CH:28]=[C:3]4[C:4]5[C:5](=[N:6][CH:7]=[CH:8][CH:9]=5)[NH:1][C:2]4=[O:10])=[CH:25][CH:26]=3)[NH:21][N:20]=2)[CH:12]=1
Reactant: O=Cc1ccc2c(/C=C/c3cccnc3)n[nH]c2c1
Reactant: O=C1Cc2cccnc2N1
Product: O=C1Nc2ncccc2C1=Cc1ccc2c(/C=C/c3cccnc3)n[nH]c2c1
Yield: 80.7 %

Procedure:
The title compound (59 mg, 81%) was synthesized as an orange solid according to the method described for Example A67 (oil temp 75° C., reflux 90 min) using 1H-pyrrolo[2,3-b]pyridin-2(3H)-one (26.8 mg, 0.2 mmol) and (E)-3-(2-(pyridin-3-yl)vinyl)-1H-indazole-6-carbaldehyde (49.8 mg, 0.2 mmol). 1H NMR indicated 5:2 mixture of Z/E isomers. 1H NMR (400 MHz, DMSO-d6) δ 13.60 (s, 1H, NH), 11.30 (s, 1H, NH), 8.95 (s, 1H), 8.91 (d, 1H), 8.47 (d, J=4.4 Hz, 1H), 8.31 (d, J=8.4 Hz, 1H), 8.19 (d, J=7.2 Hz, 1H), 8.13-8.07 (m, 4H), 7.72 (d, J=16.8 Hz, 1H), 7.59 (d, J=17.2 Hz, 1H), 7.42 (dd, J=8.0 Hz, 4.4 Hz, 1H), 7.50 (dd, J=7.2 Hz, 5.6 Hz, 1H); MS ESI 444.3 [M+H]+, calcd for [C22H15N5O+H]+ 366.1.
Reaction SMILES: CCN(C(C)C)C(C)C.[CH3:10][O:11][C:12]1[CH:13]=[CH:14][CH:15]=[C:16]2[C:21]=1[O:20][C:19](=[O:22])[C:18]([C:23]([OH:25])=O)=[CH:17]2.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH3:50][O:51][C:52]1[C:57]([C:58]2[CH:59]=[C:60]([NH2:64])[CH:61]=[CH:62][CH:63]=2)=[CH:56][CH:55]=[CH:54][N:53]=1>CN(C=O)C>[CH3:50][O:51][C:52]1[C:57]([C:58]2[CH:59]=[C:60]([NH:64][C:23]([C:18]3[C:19](=[O:22])[O:20][C:21]4[C:16]([CH:17]=3)=[CH:15][CH:14]=[CH:13][C:12]=4[O:11][CH3:10])=[O:25])[CH:61]=[CH:62][CH:63]=2)=[CH:56][CH:55]=[CH:54][N:53]=1
Reactant: COc1cccc2cc(C(=O)O)c(=O)oc12
Reactant: COc1ncccc1-c1cccc(N)c1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: COc1ncccc1-c1cccc(NC(=O)c2cc3cccc(OC)c3oc2=O)c1
Temperature: 25 °C
Yield: 91.8 %

Procedure:
DIEA (0.012 mL, 0.071 mmol) was added to 8-methoxy-3-carboxy-coumarin (0.014 g, 0.065 mmol) and HATU (0.027 g, 0.071 mmol) in 0.5 mL of DMF with constant stirring at room temperature until a clear solution resulted. Subsequently, 3-(2-methoxy-pyridin-3-yl)-phenylamine (0.013 g, 0.065 mmol) was added and allowed to react overnight when a solid precipitated out of solution. The resulting precipitate was filtered, dried under suction, and finally dried overnight in vacuo to give 0.024 g of product in 92% yield: LCMS (ESI) m/z 403 (MH+).
Reaction SMILES: [CH:1]1[C:14]2[CH:13]=[C:12](B(O)O)[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[CH:4]=[CH:3][CH:2]=1.[Br:18][C:19]1[CH:20]=[C:21](I)[CH:22]=[CH:23][CH:24]=1>>[Br:18][C:19]1[CH:24]=[C:23]([C:12]2[C:11]3[C:6]([C:5]4[CH:4]=[CH:3][CH:2]=[CH:1][C:14]=4[CH:13]=2)=[CH:7][CH:8]=[CH:9][CH:10]=3)[CH:22]=[CH:21][CH:20]=1
Reactant: OB(O)c1cc2ccccc2c2ccccc12
Reactant: Brc1cccc(I)c1
Product: Brc1cccc(-c2cc3ccccc3c3ccccc23)c1

Procedure:
9-(3-Bromophenyl)phenanthrene was synthesized by the same method, except that in Synthetic Example 1, 9-phenanthreneboronic acid was used in place of 2-naphthaleneboronic acid and that 3-bromoiodobenzene was used in place of 4-bromoiodobenzene.