Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1](Cl)(=[O:3])[CH3:2].[CH3:5][C:6]1[CH:34]=[CH:33][C:9]([CH2:10][N:11]2[C:19]3[C:14](=[CH:15][C:16]([C:20]4[CH:25]=[CH:24][C:23]([O:26][C:27]([F:30])([F:29])[F:28])=[CH:22][CH:21]=4)=[CH:17][CH:18]=3)[CH:13]=[C:12]2[CH2:31][OH:32])=[CH:8][CH:7]=1.C(N(CC)C(C)C)(C)C>C(Cl)Cl>[C:1]([O:32][CH2:31][C:12]1[N:11]([CH2:10][C:9]2[CH:8]=[CH:7][C:6]([CH3:5])=[CH:34][CH:33]=2)[C:19]2[C:14]([CH:13]=1)=[CH:15][C:16]([C:20]1[CH:25]=[CH:24][C:23]([O:26][C:27]([F:29])([F:30])[F:28])=[CH:22][CH:21]=1)=[CH:17][CH:18]=2)(=[O:3])[CH3:2]
Reactant: Cc1ccc(Cn2c(CO)cc3cc(-c4ccc(OC(F)(F)F)cc4)ccc32)cc1
Reactant: CC(=O)Cl
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: CC(=O)OCc1cc2cc(-c3ccc(OC(F)(F)F)cc3)ccc2n1Cc1ccc(C)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 99.9 %

Procedure:
Acetyl chloride (0.222 mL, 3.08 mmol) was added to a stirring solution of {1-(4-methylbenzyl)-5-[4-(trifluoromethoxy)phenyl]-1H-indol-2-yl}methanol (0.507 g, 1.23 mmol) and N,N-diisopropylethylamine (0.547 mL, 3.08 mmol) in methylene chloride (8 mL) at 0° C. under a nitrogen atmosphere over a period of 5 minutes. After the reaction mixture was stirred at room temperature overnight, the reaction quenched carefully with water. The aqueous mixture was extracted with ethyl acetate. The organic extract was washed with water and brine, dried over anhydrous magnesium sulfate and evaporated to afford the title compound as a solid (0.557 g, 99.6%), mp: 125-126° C. Mass spectrum (ESI, [M+H]+) m/z 454. 1HNMR (400 MHz, DMSO-d6): δ 7.86 (s, 1H), 8.77 (d, 2H, J=8.96 Hz), 7.48-7.40 (m, 4H), 7.09 (d, 2H, J=7.94 Hz), 6.90 (d, 2H, J=7.94 Hz), 6.70 (s, 1H), 5.44 (s, 2H), 5.23 (s, 2H), 2.23 (s, 3H), and 1.85 ppm (s, 3H).
Reaction SMILES: CCCC[N+](CCCC)(CCCC)CCCC.[F-].[Si]([O:26][CH2:27][CH2:28][N:29]1[CH:33]=[C:32]([C:34]2[N:39]=[C:38]([NH:40][C:41]3[CH:46]=[C:45]([C:47]([F:50])([F:49])[F:48])[CH:44]=[CH:43][N:42]=3)[CH:37]=[C:36]([CH3:51])[CH:35]=2)[CH:31]=[N:30]1)(C(C)(C)C)(C)C>ClCCl>[CH3:51][C:36]1[CH:37]=[C:38]([NH:40][C:41]2[CH:46]=[C:45]([C:47]([F:50])([F:48])[F:49])[CH:44]=[CH:43][N:42]=2)[N:39]=[C:34]([C:32]2[CH:31]=[N:30][N:29]([CH2:28][CH2:27][OH:26])[CH:33]=2)[CH:35]=1
Reactant: Cc1cc(Nc2cc(C(F)(F)F)ccn2)nc(-c2cnn(CCO[Si](C)(C)C(C)(C)C)c2)c1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: ClCCl
Product: Cc1cc(Nc2cc(C(F)(F)F)ccn2)nc(-c2cnn(CCO)c2)c1
Reaction time: 8 h

Procedure:
TBAF (1.0 M, 0.11 mL, 0.11 mmol) was added to a solution of 6-[1-(2-{[tert-butyl(dimethyl)silyl]oxy}ethyl)-1H-pyrazol-4-yl]-4-methyl-N-[4-(trifluoromethyl)pyridin-2-yl]pyridin-2-amine in dichloromethane (2 mL). The reaction mixture was stirred overnight and then concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (0 to 10% MeOH/dichloromethane) to afford 2-[4-(4-methyl-6-{[4-(trifluoromethyl)pyridin-2-yl]amino}pyridin-2-yl)-1H-pyrazol-1-yl]ethanol. MS ESI C17H16F3N5O [M+H]+ 364. found 364.
Reaction SMILES: Cl[C:2]1[CH:11]=[CH:10][C:9]2[N:8]=[CH:7][C:6]3[N:12]=[N:13][N:14]([CH:15]4[CH2:20][CH2:19][N:18]([C:21](=[O:25])[CH:22]([CH3:24])[CH3:23])[CH2:17][CH2:16]4)[C:5]=3[C:4]=2[N:3]=1.CC1(C)C(C)(C)OB([C:34]2[CH:35]=[C:36]([C:41]([F:44])([F:43])[F:42])[C:37]([NH2:40])=[N:38][CH:39]=2)O1.C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[NH2:40][C:37]1[N:38]=[CH:39][C:34]([C:2]2[CH:11]=[CH:10][C:9]3[N:8]=[CH:7][C:6]4[N:12]=[N:13][N:14]([CH:15]5[CH2:20][CH2:19][N:18]([C:21](=[O:25])[CH:22]([CH3:24])[CH3:23])[CH2:17][CH2:16]5)[C:5]=4[C:4]=3[N:3]=2)=[CH:35][C:36]=1[C:41]([F:44])([F:42])[F:43]
Reactant: CC(C)C(=O)N1CCC(n2nnc3cnc4ccc(Cl)nc4c32)CC1
Reactant: CC1(C)OB(c2cnc(N)c(C(F)(F)F)c2)OC1(C)C
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: O=C([O-])[O-]
Solvent: O
Solvent: C1COCCO1
Product: CC(C)C(=O)N1CCC(n2nnc3cnc4ccc(-c5cnc(N)c(C(F)(F)F)c5)nc4c32)CC1
Yield: 55.9 %

Procedure:
A mixture of 1-(4-(8-chloro-1H-[1,2,3]triazolo[4,5-c][1,5]naphthyridin-1-yl)piperidin-1-yl)-2-methylpropan-1-one (60 mg, 0.17 mmol), 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-(trifluoromethyl)pyridin-2-amine (53 mg, 0.18 mmol), K2CO3 (70 mg, 0.51 mmol) and Pd(dppf)Cl2 (6 mg) in dioxane/H2O (3:1, 4 mL) was stirred and microwaved at 160° C. for 0.5 h. The solvent was removed, and the residue was purified by ISCO (MeOH/H2O=20%-80%) to afford 1-(4-(8-(6-amino-5-(trifluoromethyl)pyridin-3-yl)-1H-[1,2,3]triazolo[4,5-c][1,5]naphthyridin-1-yl)piperidin-1-yl)-2-methylpropan-1-one as white solid (46 mg). 1HNMR (400 MHz, dmso) δ 9.61 (s, 1H), 9.21 (d, J=2.1 Hz, 1H), 8.66 (dd, J=12.5, 5.5 Hz, 2H), 8.55 (d, J=8.9 Hz, 1H), 7.10 (s, 2H), 6.17-6.01 (m, 1H), 4.78-4.59 (m, 1H), 4.35-4.26 (m, 1H), 3.40-3.37 (m, 2H), 3.05-2.97 (m, 1H), 2.93-2.82 (m, 1H), 2.64-2.52 (m, 1H), 2.39-2.21 (m, 1H), 2.16-1.96 (m, 1H), 1.07 (s, 6H). MS (m/z): 485 (M+H)+.
Reaction SMILES: O=[C:2]1[C:11]2[C:10]([C:12]([O:14]C)=O)=[CH:9][CH:8]=[CH:7][C:6]=2[NH:5][CH:4]([C:16]2[CH:17]=[N:18][CH:19]=[CH:20][CH:21]=2)[CH:3]1[C:22]1[CH:23]=[N:24][CH:25]=[CH:26][CH:27]=1.O=C1C2C(C(OCC)=O)=CC=CC=2NC(C2C=NC=CC=2)C1C1C=NC=CC=1.O.[NH2:57][NH2:58]>CO>[N:18]1[CH:19]=[CH:20][CH:21]=[C:16]([CH:4]2[NH:5][C:6]3[C:11]4[C:2](=[N:57][NH:58][C:12](=[O:14])[C:10]=4[CH:9]=[CH:8][CH:7]=3)[CH:3]2[C:22]2[CH:23]=[N:24][CH:25]=[CH:26][CH:27]=2)[CH:17]=1
Reactant: COC(=O)c1cccc2c1C(=O)C(c1cccnc1)C(c1cccnc1)N2
Reactant: NN
Agent: CCOC(=O)c1cccc2c1C(=O)C(c1cccnc1)C(c1cccnc1)N2
Solvent: CO
Solvent: O
Product: O=c1[nH]nc2c3c(cccc13)NC(c1cccnc1)C2c1cccnc1
Temperature: 25 °C
Yield: 68 %

Procedure:
A mixture of methyl 4-oxo-2,3-di(pyridin-3-yl)-1,2,3,4-tetrahydroquinoline-5-carboxylate and ethyl 4-oxo-2,3-di(pyridin-3-yl)-1,2,3,4-tetrahydroquinoline-5-carboxylate (480 mg, 1.34 mmol) in hydrazine monohydrate (20 mL) and methanol (5 mL) was heated to reflux for 2 hr. The mixture was then cooled to room temperature and filtered to give 8,9-di(pyridin-3-yl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one (320 mg, yield 68%) as a light yellow solid. 1H-NMR (400 MHz, DMSO-d6) 4.51-4.53 (d, J=8.4 Hz, 1H), 4.89-4.91 (d, J=8.4 Hz, 1H), 7.18-7.20 (m, 1H), 7.24-7.27 (m, 1H), 7.31-7.33 (m, 1H), 7.43-7.44 (m, 1H), 7.60 (s, 1H), 7.58-7.63 (m, 2H), 7.79-7.81 (m, 1H), 8.32-8.34 (m, 2H), 8.41-8.43 (m, 1 H), 8.45-8.46 (d, J=1.6 Hz, 1H); LC-MS (ESI) m/z: 342 (M+1)+.
Reaction SMILES: [CH:1]([C:4]1[N:5]=[C:6](/[CH:9]=[CH:10]/[C:11]2[CH:37]=[CH:36][N:14]3[C:15](=[O:35])[C:16](/[CH:26]=[CH:27]/[C:28]([O:30]C(C)(C)C)=[O:29])=[C:17]([O:19][CH2:20][CH:21]4[CH2:25][CH2:24][O:23][CH2:22]4)[N:18]=[C:13]3[CH:12]=2)[S:7][CH:8]=1)([CH3:3])[CH3:2].Cl>O1CCOCC1>[CH:1]([C:4]1[N:5]=[C:6](/[CH:9]=[CH:10]/[C:11]2[CH:37]=[CH:36][N:14]3[C:15](=[O:35])[C:16](/[CH:26]=[CH:27]/[C:28]([OH:30])=[O:29])=[C:17]([O:19][CH2:20][CH:21]4[CH2:25][CH2:24][O:23][CH2:22]4)[N:18]=[C:13]3[CH:12]=2)[S:7][CH:8]=1)([CH3:3])[CH3:2]
Reactant: CC(C)c1csc(/C=C/c2ccn3c(=O)c(/C=C/C(=O)OC(C)(C)C)c(OCC4CCOC4)nc3c2)n1
Agent: Cl
Solvent: C1COCCO1
Product: CC(C)c1csc(/C=C/c2ccn3c(=O)c(/C=C/C(=O)O)c(OCC4CCOC4)nc3c2)n1
Temperature: 25 °C
Reaction time: 16.25 h
Yield: 85.4 %

Procedure:
The tert-butyl (E)-3-{8-[(E)-2-(4-isopropyl-1,3-thiazol-2-yl)-1-ethenyl]-4-oxo-2-(tetrahydro-3-furanylmethoxy)-4H-pyrido[1,2-a]pyrimidin-3-yl}-2-propenoate (101 mg, 0.193 mmol) obtained in (B) was dissolved in 1,4-dioxane (1.6 ml), added with 4 N hydrochloric acid in 1,4-dioxane (3.2 ml), and then the mixture was stirred at room temperature for 16.25 hours. The reaction solution was concentrated, added with saturated aqueous sodium hydrogencarbonate, neutralized with phosphate buffer (pH 7-8), and then extracted with a mixture of chloroform/methanol (10:1, v/v). The organic layer was dried over magnesium sulfate, and then the solvent was evaporated under reduced pressure. The residue was purified by thin layer chromatography (chloroform:methanol=20:1, v/v) to obtain the title compound (77.1 mg, 86%).
Reaction SMILES: S(Cl)(Cl)=O.O[CH:6]([NH:11][C:12](=[O:20])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[OH:19])[C:7]([Cl:10])([Cl:9])[Cl:8].C(Cl)(Cl)(Cl)[Cl:22]>CN(C)C=O>[Cl:22][CH:6]([NH:11][C:12](=[O:20])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[OH:19])[C:7]([Cl:10])([Cl:9])[Cl:8]
Reactant: O=C(NC(O)C(Cl)(Cl)Cl)c1ccccc1O
Reactant: ClC(Cl)(Cl)Cl
Solvent: O=S(Cl)Cl
Solvent: CN(C)C=O
Product: O=C(NC(Cl)C(Cl)(Cl)Cl)c1ccccc1O

Procedure:
5 g of thionyl chloride was added dropwise to the mixture of 10 g of N-(1-hydroxy-2,2,2-trichloroethyl)-2-hydroxybenzamide, 50 ml of carbon tetrachloride and 0.1 g of N,N-dimethylformamide under stirring. After effecting the reaction under reflux for one hour, the solvent was distilled off under reduced pressure to obtain N-(1,2,2,2-tetrachloroethyl)-2-hydroxybenzamide (m.p.: 113°-113.5° C.). Without taking out the compound thus resulted, thereto were added 50 ml of acetone and also 7.2 g of octyl thioglycolate (n), and the mixture was stirred at room temperature for one hour. The solvent was distilled off and the rest was purified by silica gel column chromatography to obtain 3.0 g of N-(1-n-octyloxycarbonylmethylthio-2,2,2-trichloroethyl)-2-hydroxybenzamide as a light yellow oily substance. nD25 1.5031
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([N:11]2[CH2:15][CH2:14][CH2:13][C:12]2=[O:16])[CH:10]=1)[C:5]([OH:7])=O.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.[CH3:31][C:32]([CH3:53])([CH3:52])[CH2:33][CH2:34][NH:35][C:36](=[O:51])[C@H:37]([CH3:50])[CH2:38][C@H:39]([OH:49])[C@@H:40]([NH2:48])[CH2:41][C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1>CN(C=O)C>[CH2:41]([C@H:40]([NH:48][C:5](=[O:7])[C:4]1[CH:8]=[C:9]([N:11]2[CH2:15][CH2:14][CH2:13][C:12]2=[O:16])[CH:10]=[C:2]([OH:1])[CH:3]=1)[C@@H:39]([OH:49])[CH2:38][C@H:37]([C:36](=[O:51])[NH:35][CH2:34][CH2:33][C:32]([CH3:31])([CH3:52])[CH3:53])[CH3:50])[C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1
Reactant: O=C(O)c1cc(O)cc(N2CCCC2=O)c1
Reactant: C[C@H](C[C@H](O)[C@@H](N)Cc1ccccc1)C(=O)NCCC(C)(C)C
Agent: On1nnc2ccccc21
Solvent: ClCCCl
Solvent: CN(C)C=O
Product: C[C@H](C[C@H](O)[C@H](Cc1ccccc1)NC(=O)c1cc(O)cc(N2CCCC2=O)c1)C(=O)NCCC(C)(C)C
Temperature: 25 °C
Reaction time: 20 h

Procedure:
To a stirred solution of 3-hydroxy-5-(2-oxopyrrolidin-1-yl)benzoic acid (D6) (0.449 g, 2.03 mmol), EDC (0.389 g, 2.03 mmol) and HOBT (0.311 g, 2.03 mmol) in DMF (8 ml) was added (2R,4S,5S)-5-amino-4-hydroxy-2-methyl-6-phenylhexanoic acid (3,3-dimethylbutyl)amide (D2(0.50 g, 1.56 mmol). After stirring for 20 hrs at room temperature, the DMF was evaporated and ethyl acetate and water were added. The product was extracted into ethyl acetate and the combined extracts were washed with 2N HCl, saturated aqueous sodium bicarbonate solution and brine and then dried over sodium sulfate and evaporated. Purification by column chromatography on silica gel (elution with 2–5% methanol in dichloromethane) gave the product, 0.588 g.
Reaction SMILES: [O-]S(S([O-])=O)=O.[Na+].[Na+].[Br:9][C:10]1[CH:15]=[C:14]([CH3:16])[C:13]([S:17][C:18]2[C:23]([N+]([O-])=O)=[C:22](/[CH:27]=[CH:28]/[N:29](C)C)[N:21]=[C:20]([N:32]([C:40]3[CH:45]=[CH:44][C:43]([C:46]#[N:47])=[CH:42][CH:41]=3)[C:33](=[O:39])[O:34][C:35]([CH3:38])([CH3:37])[CH3:36])[N:19]=2)=[C:12]([CH3:48])[CH:11]=1>O.C1COCC1>[Br:9][C:10]1[CH:11]=[C:12]([CH3:48])[C:13]([S:17][C:18]2[C:23]3[NH:29][CH:28]=[CH:27][C:22]=3[N:21]=[C:20]([N:32]([C:40]3[CH:45]=[CH:44][C:43]([C:46]#[N:47])=[CH:42][CH:41]=3)[C:33](=[O:39])[O:34][C:35]([CH3:38])([CH3:37])[CH3:36])[N:19]=2)=[C:14]([CH3:16])[CH:15]=1
Reactant: Cc1cc(Br)cc(C)c1Sc1nc(N(C(=O)OC(C)(C)C)c2ccc(C#N)cc2)nc(/C=C/N(C)C)c1[N+](=O)[O-]
Agent: O=S([O-])S(=O)[O-]
Agent: [Na+]
Solvent: O
Solvent: C1CCOC1
Product: Cc1cc(Br)cc(C)c1Sc1nc(N(C(=O)OC(C)(C)C)c2ccc(C#N)cc2)nc2cc[nH]c12
Temperature: 25 °C
Reaction time: 48 h

Procedure:
A solution of Na2S2O4 (230 mmol) in water (100 ml) is added to a solution of tert-butyl 4-(4-bromo-2,6-dimethylphenylthio)-6-((E)-2-(dimethylamino)vinyl)-5-nitropyrimidin-2-yl4-cyanophenylcarbamate (46 mmol) in THF (300 ml). The mixture is stirred at room temperature for 2 days and then concentrated. The residue is washed with water and extracted with ethyl acetate. The organic layer is concentrated and the product obtained by crystallization from a mixture of water and methanol.
Reaction SMILES: Br[C:2]1[CH:3]=[N:4][N:5]2[CH:10]=[CH:9][C:8]([N:11]3[C@H:15]4[C:16]5[CH:17]=[CH:18][CH:19]=[CH:20][C:21]=5[CH2:22][C@H:14]4[O:13][C:12]3=[O:23])=[N:7][C:6]=12.[F:24][C:25]1[CH:30]=[C:29](B2OC(C)(C)C(C)(C)O2)[CH:28]=[CH:27][C:26]=1[C:40]1[N:44]=[CH:43][N:42]([CH2:45][O:46][CH2:47][CH2:48][Si:49]([CH3:52])([CH3:51])[CH3:50])[N:41]=1.CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1.C([O-])([O-])=O.[Na+].[Na+]>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].O.CCOC(C)=O.O1CCOCC1>[F:24][C:25]1[CH:30]=[C:29]([C:2]2[CH:3]=[N:4][N:5]3[CH:10]=[CH:9][C:8]([N:11]4[C@H:15]5[C:16]6[CH:17]=[CH:18][CH:19]=[CH:20][C:21]=6[CH2:22][C@H:14]5[O:13][C:12]4=[O:23])=[N:7][C:6]=23)[CH:28]=[CH:27][C:26]=1[C:40]1[N:44]=[CH:43][N:42]([CH2:45][O:46][CH2:47][CH2:48][Si:49]([CH3:52])([CH3:51])[CH3:50])[N:41]=1
Reactant: CC1(C)OB(c2ccc(-c3ncn(COCC[Si](C)(C)C)n3)c(F)c2)OC1(C)C
Reactant: O=C1O[C@@H]2Cc3ccccc3[C@@H]2N1c1ccn2ncc(Br)c2n1
Agent: [Pd]
Agent: CC1(C)c2cccc(P(c3ccccc3)c3ccccc3)c2Oc2c(P(c3ccccc3)c3ccccc3)cccc21
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Solvent: CCOC(C)=O
Solvent: O
Solvent: C1COCCO1
Product: C[Si](C)(C)CCOCn1cnc(-c2ccc(-c3cnn4ccc(N5C(=O)O[C@@H]6Cc7ccccc7[C@@H]65)nc34)cc2F)n1
Temperature: 80 °C
Reaction time: 2 h
Yield: 28.7 %

Procedure:
To (3aS,8aR)-3-(3-bromopyrazolo[1,5-a]pyrimidin-5-yl)-3,3a,8,8a-tetrahydro-2H-indeno[1,2-d]oxazol-2-one (100 mg, 0.269 mmol) were added 3-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-1,2,4-triazole (147 mg, 0.350 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (15.6 mg, 0.0269 mmol), Pd2 dba3 (12.3 mg, 0.0135 mmol), dioxane (1.2 mL) and 2M Na2CO3 (0.2 mL). The reaction was stirred for 2 hours at 80° C. in a sealed tube. After cooling, EtOAc and water were added. The organic phase was washed with brine and dried over MgSO4. The residue was purified by reverse phase chromatography (SP4, 12M, water/CH3CN 90:10 to 0:100, 20 column volumes) to yield (3aS,8aR)-3-(3-(3-fluoro-4-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-1,2,4-triazol-3-yl)phenyl)pyrazolo[1,5-a]pyrimidin-5-yl)-3,3a,8,8a-tetrahydro-2H-indeno[1,2-d]oxazol-2-one (45 mg, 28.6% yield) as a pale yellow solid.
Reaction SMILES: [C:1]([CH:3]([CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH3:14])[CH3:4])#[N:2].[CH2:15](N)[CH2:16][NH2:17]>C(=S)=S>[CH3:4][CH:3]([C:1]1[NH:2][CH2:15][CH2:16][N:17]=1)[CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH3:14]
Reactant: NCCN
Reactant: CCCCCCCCCCC(C)C#N
Solvent: S=C=S
Product: CCCCCCCCCCC(C)C1=NCCN1
Yield: 65 %

Procedure:
19.53 g (100 mmoles) of 2-cyanododecane, 8.5ml (127 mmoles) of ethylenediamine and 0.5 ml of carbon disulfide are reacted according to Example 29 and the reaction mixture is worked up as mentioned therein. Distillation of the residue gives 15.5 g (65%) of the product.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:16])[C:4](=O)[CH:5](Cl)[C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([Cl:12])[C:7]=1[Cl:13].[C:17]([NH2:20])(=[S:19])[CH3:18]>>[CH3:1][O:2][C:3]([C:4]1[N:20]=[C:17]([CH3:18])[S:19][C:5]=1[C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([Cl:12])[C:7]=1[Cl:13])=[O:16]
Reactant: COC(=O)C(=O)C(Cl)c1cccc(Cl)c1Cl
Reactant: CC(N)=S
Product: COC(=O)c1nc(C)sc1-c1cccc(Cl)c1Cl

Procedure:
prepared by reaction of 3-chloro-3-(2,3-dichloro-phenyl)-2-oxo-propionic acid methyl ester with thioacetamide. LC-MS: tR=0.97 min; [M+H]+=302.2.
Reaction SMILES: CCN(C(C)C)C(C)C.[OH:10][C:11]1[CH:12]=[CH:13][CH:14]=[C:15]2[C:20]=1[O:19][C:18](=[O:21])[C:17]([C:22]([OH:24])=O)=[CH:16]2.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[N:49]1[CH:54]=[CH:53][CH:52]=[C:51]([C:55]2[CH:56]=[C:57]([CH:59]=[CH:60][CH:61]=2)[NH2:58])[CH:50]=1>CN(C=O)C>[N:49]1[CH:54]=[CH:53][CH:52]=[C:51]([C:55]2[CH:56]=[C:57]([NH:58][C:22]([C:17]3[C:18](=[O:21])[O:19][C:20]4[C:15]([CH:16]=3)=[CH:14][CH:13]=[CH:12][C:11]=4[OH:10])=[O:24])[CH:59]=[CH:60][CH:61]=2)[CH:50]=1
Reactant: O=C(O)c1cc2cccc(O)c2oc1=O
Reactant: Nc1cccc(-c2cccnc2)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: O=C(Nc1cccc(-c2cccnc2)c1)c1cc2cccc(O)c2oc1=O
Temperature: 25 °C
Yield: 32.5 %

Procedure:
DIEA (0.028 mL, 0.160 mmol) was added to 8-hydroxy-3-carboxy-coumarin (0.030 g, 0.146 mmol) and HATU (0.061 g, 0.160 mmol) in 0.5 mL of DMF with constant stirring at room temperature until a clear solution resulted. Subsequently, 3-pyridin-3-ylaniline (0.025 g, 0.146 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 0.017 g of product in 32% yield: LCMS (ESI) m/z 359 (MH+).
Reaction SMILES: ClC1C=C(C2SC(C(O)=O)=CC=2C2C=CC=C(C#N)C=2)C=C(F)C=1.[Cl:25][C:26]1[CH:27]=[C:28]([C:33]2[CH:34]=[C:35]([C:46]([O:48]CC)=[O:47])[S:36][C:37]=2[C:38]2[CH:43]=[C:42]([F:44])[CH:41]=[C:40]([Cl:45])[CH:39]=2)[CH:29]=[CH:30][C:31]=1[F:32]>>[Cl:25][C:26]1[CH:27]=[C:28]([C:33]2[CH:34]=[C:35]([C:46]([OH:48])=[O:47])[S:36][C:37]=2[C:38]2[CH:43]=[C:42]([F:44])[CH:41]=[C:40]([Cl:45])[CH:39]=2)[CH:29]=[CH:30][C:31]=1[F:32]
Reactant: CCOC(=O)c1cc(-c2ccc(F)c(Cl)c2)c(-c2cc(F)cc(Cl)c2)s1
Agent: N#Cc1cccc(-c2cc(C(=O)O)sc2-c2cc(F)cc(Cl)c2)c1
Product: O=C(O)c1cc(-c2ccc(F)c(Cl)c2)c(-c2cc(F)cc(Cl)c2)s1

Procedure:
The preparation of the title compound takes place in analogy to the synthesis of the compound from Example 19A starting with the compound from Example 12A. The organic phase is concentrated and purified by flash chromatography (mobile phase: cyclohexane/ethyl acetate/ethyl acetate:methanol 1:1 gradient) on silica gel. 0.43 g (100% of theory) of the title compound are obtained.
Reaction SMILES: C(O[C:4]([C:6]1[N:18]=[C:17]([CH3:19])[C:16]2[C:15]3[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=3[N:9]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[C:8]=2[C:7]=1[OH:26])=[O:5])C.[NH2:27][CH2:28][C:29]([OH:31])=[O:30].C[O-].[Na+].CO>>[OH:26][C:7]1[C:8]2[N:9]([C:20]3[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=3)[C:10]3[CH:11]=[CH:12][CH:13]=[CH:14][C:15]=3[C:16]=2[C:17]([CH3:19])=[N:18][C:6]=1[C:4]([NH:27][CH2:28][C:29]([OH:31])=[O:30])=[O:5]
Reactant: NCC(=O)O
Reactant: CCOC(=O)c1nc(C)c2c3ccccc3n(-c3ccccc3)c2c1O
Agent: C[O-]
Agent: [Na+]
Solvent: CO
Product: Cc1nc(C(=O)NCC(=O)O)c(O)c2c1c1ccccc1n2-c1ccccc1

Procedure:
Prepared in analogy to that of Example 1(e) from 4-hydroxy-1-methyl-5-phenyl-5H-pyrido[4,3-b]indole-3-carboxylic acid ethyl ester, glycine and NaOMe/HOMe. The title compound, ESI MS (m/z): 376 (M+H)+.
Reaction SMILES: Cl.[C:2]([NH2:10])(=[NH:9])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.O[CH:12]1[CH2:17][CH2:16][CH2:15][CH2:14][C:13]1=O>[OH-].[NH4+]>[C:3]1([C:2]2[NH:9][C:12]3[CH2:17][CH2:16][CH2:15][CH2:14][C:13]=3[N:10]=2)[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1
Reactant: N=C(N)c1ccccc1
Reactant: O=C1CCCCC1O
Agent: Cl
Agent: [NH4+]
Agent: [OH-]
Product: c1ccc(-c2nc3c([nH]2)CCCC3)cc1
Temperature: 90 °C
Yield: 37.6 %

Procedure:
To a solution of 6.3 g benzamidine hydrochloride in 60 mL ammonium hydroxide was added 4.6 g 2-hydroxycyclohexanone. The reaction mixture was heated to 90° C. for 7 hours in a sealed tube. On cooling to room temperature the crystals formed were collected by filtration and after drying yielded 3.0 g 2-phenyl-4,5,6,7,-tetrahydrobenzimidazole (Compound 136), m.p. 300-301° C.
Reaction SMILES: CC(C)([O-])C.[K+].[OH:7][C@H:8]1[CH2:13][CH2:12][C@H:11]2[C@H:14]3[C@H:25]([CH2:26][CH2:27][C@:9]12[CH3:10])[C@:22]1([CH2:23][OH:24])[C:17](=[CH:18][C:19](=[O:28])[CH2:20][CH2:21]1)[CH2:16][C@H:15]3[CH3:29].[Cl-].[NH4+]>CS(C)=O>[OH:7][C@H:8]1[CH2:13][CH2:12][C@H:11]2[C@H:14]3[C@H:25]([CH2:26][CH2:27][C@:9]12[CH3:10])[C@:22]1([CH2:23][OH:24])[C:17]([CH2:18][C:19](=[O:28])[CH2:20][CH2:21]1)=[CH:16][C@H:15]3[CH3:29]
Reactant: C[C@@H]1CC2=CC(=O)CC[C@]2(CO)[C@H]2CC[C@]3(C)[C@@H](O)CC[C@H]3[C@H]12
Agent: CC(C)(C)[O-]
Agent: [Cl-]
Agent: [K+]
Solvent: CS(C)=O
Product: C[C@@H]1C=C2CC(=O)CC[C@]2(CO)[C@H]2CC[C@]3(C)[C@@H](O)CC[C@H]3[C@H]12
Reaction time: 0.25 h

Procedure:
To a solution of potassium t-butoxide in dimethylsulfoxide at 25° C. under nitrogen is added with stirring a solution of 17β,19-dihydroxy-7α-methyl-4-androsten-3-one in dimethylsulfoxide. After standing for 15 minutes, the mixture is poured onto a cold aqueous ammonium chloride solution. The solid which forms is rapidly filtered, washed well with water and dissolved in ether. The ether solution is washed well with water and dried over sodium sulfate. The ether is removed at room temperature to yield 17β,19-dihydroxy-7α-methyl-5-androsten-3-one.
Reaction SMILES: [C:1]([CH2:3][CH2:4][C:5]1[CH:10]=[CH:9][C:8]([C:11]2[CH:16]=[CH:15][C:14](OS(C(F)(F)F)(=O)=O)=[C:13]([CH2:25][C:26]3[C:35]4[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=4)[CH:29]=[CH:28][CH:27]=3)[CH:12]=2)=[C:7]([CH2:36][CH:37]([CH3:39])[CH3:38])[CH:6]=1)#[N:2].[CH2:40]([C:44]1[CH:45]=[C:46](B2OC(C)(C)C(C)(C)O2)[CH:47]=[CH:48][C:49]=1[O:50][CH3:51])[CH:41]([CH3:43])[CH3:42].C([O-])([O-])=O.[Na+].[Na+].C(Cl)Cl>COCCOC.CCO.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>[CH2:40]([C:44]1[CH:45]=[C:46]([C:14]2[CH:15]=[CH:16][C:11]([C:8]3[CH:9]=[CH:10][C:5]([CH2:4][CH2:3][C:1]#[N:2])=[CH:6][C:7]=3[CH2:36][CH:37]([CH3:38])[CH3:39])=[CH:12][C:13]=2[CH2:25][C:26]2[C:35]3[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=3)[CH:29]=[CH:28][CH:27]=2)[CH:47]=[CH:48][C:49]=1[O:50][CH3:51])[CH:41]([CH3:42])[CH3:43]
Reactant: COc1ccc(B2OC(C)(C)C(C)(C)O2)cc1CC(C)C
Reactant: CC(C)Cc1cc(CCC#N)ccc1-c1ccc(OS(=O)(=O)C(F)(F)F)c(Cc2cccc3ccccc23)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: [Na+]
Solvent: ClCCl
Solvent: CCO
Solvent: COCCOC
Product: COc1ccc(-c2ccc(-c3ccc(CCC#N)cc3CC(C)C)cc2Cc2cccc3ccccc23)cc1CC(C)C
Temperature: 80 °C
Yield: 93.8 %

Procedure:
439.6 mg (0.80 mmol) Trifluoro-methanesulfonic acid 4′-(2-cyano-ethyl)-2′-isobutyl-3-naphthalen-1-ylmethyl-biphenyl-4-yl-ester (67), 266.2 mg (0.92 mmol, 1.15 eq.) 2-(3-isobutyl-4-methoxyphenyl)-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane (11, FIG. 6) and 140.4 mg (121.4 μmol, 0.15 eq.) Pd(Ph3P)4 were dissolved in 15 ml DME/EtOH (9+1). To this yellow solution 0.80 ml (1.60 mmol, 2.00 eq.) of a 2 M aq. Na2CO3-solution was added and the resulting mixture was heated at 80° C. for 9 h. After concentrating the mixture in vacuo the residue was taken up in water and extracted with CH2Cl2. The comb. org. fractions were dried over MgSO4 and evaporated. Column chromatography (CH2Cl2) yielded 426.5 mg (0.75 mmol, 94.23%) 3-(3,2″-Diisobutyl-4-methoxy-2′-naphthalen-1-ylmethyl-[1,1′:4′,1″]-terphenyl-4″-yl)propionitrile (68) as a clear oil. Rf (hexanes/EtOAc (6+1))=0.12. 1H-NMR (500 MHz, CDCl3): δ=0.52 (d, 6H, J=6.62 Hz, 2*CH3), 0.77 (d, 6H, J=6.62 Hz, 2*CH3), 1.47 (m, 1H, CH), 1.74 (m, 1H, CH), 2.24 (d, 2H, J=7.41 Hz, CH2), 2.41 (d, 2H, J=7.25 Hz, CH2), 2.58 (t, 2H, J=7.41 Hz, CH2CH2CN), 2.90 (t, 2H, J=7.41 Hz, CH2CH2CN), 3.79 (s, 3H, OCH3), 4.39 (s, 2H, CH2Naphthyl), 6.83 (d, 1H, J=8.36 Hz), 6.96 (m, 2H), 6.99 (dd, 1H, J1=7.88 Hz, J2=1.89 Hz), 7.08 (d, 1H, J=7.57 Hz), 7.11-7.17 (m, 3H), 7.22 (m, 1H), 7.30-7.35 (m, 3H), 7.38 (m, 1H), 7.67 (dm, 1H, J=7.88 Hz), 7.72 (dm, 1H, J=8.20 Hz), 7.78 (dm, 1H, J=8.20 Hz). MS (EI): m/z=565 (14), 452 (11), 410 (10), 404 (19), 403 (59), 349 (24), 306 (10), 290 (13), 247 (35), 191 (13), 142 (14), 141 (100). HR-MS (EI): Calcd. for C41H43NO: 565.334464. Found: 565.334575.