Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C@:2]12[C@@:19]3([CH3:20])[C@@H:10]([C@:11]4([CH3:38])[C@@H:16]([CH2:17][CH2:18]3)[C:15]([CH3:22])([CH3:21])[C:14]([C:23]3[CH:37]=[CH:36][C:26]([C:27]([O:29][CH2:30][CH2:31][Si:32]([CH3:35])([CH3:34])[CH3:33])=[O:28])=[CH:25][CH:24]=3)=[CH:13][CH2:12]4)[CH2:9][CH2:8][C@@H:7]1[C@H:6]1[C@H:39]([C:42]([CH3:44])=[CH2:43])[CH2:40][CH2:41][C@:5]1([C:45](=[O:58])[NH:46][CH2:47][CH2:48][C:49](=[O:57])[O:50][CH2:51][CH2:52][Si:53]([CH3:56])([CH3:55])[CH3:54])[CH2:4][CH2:3]2.[H][H]>C(OCC)(=O)C.CO.[Pd]>[CH:42]([C@H:39]1[C@@H:6]2[C@@H:7]3[C@@:2]([CH3:1])([CH2:3][CH2:4][C@@:5]2([C:45](=[O:58])[NH:46][CH2:47][CH2:48][C:49](=[O:57])[O:50][CH2:51][CH2:52][Si:53]([CH3:54])([CH3:55])[CH3:56])[CH2:41][CH2:40]1)[C@@:19]1([CH3:20])[C@@H:10]([C@:11]2([CH3:38])[C@@H:16]([CH2:17][CH2:18]1)[C:15]([CH3:21])([CH3:22])[C@@H:14]([C:23]1[CH:37]=[CH:36][C:26]([C:27]([O:29][CH2:30][CH2:31][Si:32]([CH3:33])([CH3:34])[CH3:35])=[O:28])=[CH:25][CH:24]=1)[CH2:13][CH2:12]2)[CH2:9][CH2:8]3)([CH3:44])[CH3:43]
Reactant: C=C(C)[C@@H]1CC[C@]2(C(=O)NCCC(=O)OCC[Si](C)(C)C)CC[C@]3(C)[C@H](CC[C@@H]4[C@@]5(C)CC=C(c6ccc(C(=O)OCC[Si](C)(C)C)cc6)C(C)(C)[C@@H]5CC[C@]43C)[C@@H]12
Reactant: [H][H]
Agent: [Pd]
Solvent: CO
Solvent: CCOC(C)=O
Product: CC(C)[C@@H]1CC[C@]2(C(=O)NCCC(=O)OCC[Si](C)(C)C)CC[C@]3(C)[C@H](CC[C@@H]4[C@@]5(C)CC[C@H](c6ccc(C(=O)OCC[Si](C)(C)C)cc6)C(C)(C)[C@@H]5CC[C@]43C)[C@@H]12
Temperature: 25 °C
Reaction time: 3 h

Procedure:
2-(trimethylsilyl)ethyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-5a,5b,8,8,11a-pentamethyl-3a-(3-oxo-3-(2-(trimethylsilyl)ethoxy)propylcarbamoyl)-1-(prop-1-en-2-yl)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1H-cyclopenta[a]chrysen-9-yl)benzoate (15 mg, 0.018 mmol) was dissolved in a mixture of ethyl acetate and methanol (2 ml, 1:1) and treated with palladium (10% in carbon, 1 mg, 9.40 mmol) and a balloon with hydrogen. The mixture was stirred at rt for 3 h. The solvent was removed in vacuo and the residue was dissolved in methylene chloride and filtered through a fine pad of celite. The solvent was removed in vacuo and the crude was purified in silica gel to afford 2-(trimethylsilyl)ethyl 4-((1S,3aS,5aR,5bR,7aS,11aS,11bR,13aR,13bR)-1-isopropyl-5a,5b,8,8,11a-pentamethyl-3a-(3-oxo-3-(2-(trimethylsilyl)ethoxy)propylcarbamoyl)icosahydro-1H-cyclopenta[a]chrysen-9-yl) (12 mg, 80%) as a clear oil. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 7.92 (d, J=8.28 Hz, 2H), 7.23 (d, J=8.53 Hz, 2H), 6.22 (t, J=6.15 Hz, 1H), 4.50-4.36 (m, 2H), 4.24-4.16 (m, 2H), 3.51 (td, J=11.48, 6.40 Hz, 2H), 2.59-2.49 (m, 2H), 2.40 (dd, J=12.92, 2.89 Hz, 2H), 2.35-2.24 (m, 1H), 2.18-2.04 (m, 1H), 2.03-1.95 (m, 1H), 1.89-0.91 (m, 26H), 0.99 (s, 3H), 0.96 (s, 6H), 0.88 (d, J=7.03 Hz, 3H), 0.77 (d, J=7.03 Hz, 3H), 0.76 (s, 3H), 0.70 (s, 3H), 0.09 (s, 9H), 0.06 (s, 9H).
Reaction SMILES: [NH:1](C(OCC1C=CC=CC=1)=O)[C@H:2]([C:4]([NH:6][C@@H:7]([C:13]([O:15][CH2:16][CH2:17][CH2:18][CH3:19])=[O:14])[CH2:8][CH2:9][C:10](=[O:12])[NH2:11])=[O:5])[CH3:3].Cl.C(OCC)(=O)C.N1C=CC=CC=1CC(O)=O.O>C(O)(=O)C.[Pd]>[NH2:1][C@H:2]([C:4]([NH:6][C@@H:7]([C:13]([O:15][CH2:16][CH2:17][CH2:18][CH3:19])=[O:14])[CH2:8][CH2:9][C:10](=[O:12])[NH2:11])=[O:5])[CH3:3]
Reactant: CCCCOC(=O)[C@@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)OCc1ccccc1
Agent: [Pd]
Agent: Cl
Agent: O=C(O)Cc1ccccn1
Solvent: O
Solvent: CC(=O)O
Solvent: CCOC(C)=O
Product: CCCCOC(=O)[C@@H](CCC(N)=O)NC(=O)[C@H](C)N

Procedure:
330 mg (0.8 mM) of (II), dissolved in 30 ml of glacial acetic acid, are hydrogenated for 4 hours, in the presence of 330 mg of Pd (5%) on charcoal and of 1 ml (1 mM) of N HCl. It is checked, by thin layer chromatography on silica gel in the system ethyl acetate-pyridine-acetic acid-water (6:2:0.6:1), that the hydrogenation is complete, then the catalyst is filtered off and the solvent concentrated. The residual oil is dried carefully under vacuum (dessicator, with P2O5) and used as such in the following step.
Reaction SMILES: C[O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[NH:8][CH:7]([CH2:12][N:13]1[CH2:18][CH2:17][C:16]([CH2:20][C:21]3[CH:26]=[CH:25][C:24]([CH3:27])=[CH:23][CH:22]=3)([OH:19])[CH2:15][CH2:14]1)[CH2:6]2.B(Br)(Br)Br.C(Cl)Cl.CO.C([O-])(O)=O.[Na+]>C(Cl)Cl>[OH:19][C:16]1([CH2:20][C:21]2[CH:22]=[CH:23][C:24]([CH3:27])=[CH:25][CH:26]=2)[CH2:15][CH2:14][N:13]([CH2:12][CH:7]2[CH2:6][C:5]3[C:9](=[CH:10][CH:11]=[C:3]([OH:2])[CH:4]=3)[NH:8]2)[CH2:18][CH2:17]1
Reactant: COc1ccc2c(c1)CC(CN1CCC(O)(Cc3ccc(C)cc3)CC1)N2
Agent: BrB(Br)Br
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CO
Solvent: ClCCl
Product: Cc1ccc(CC2(O)CCN(CC3Cc4cc(O)ccc4N3)CC2)cc1
Temperature: 25 °C
Reaction time: 48 h
Yield: 0.1 %

Procedure:
To (RS)-1-(5-methoxy-2,3-dihydro-1H-indol-2-ylmethyl)-4-(4-methyl-benzyl)-piperidin-4-ol (131 mg, 0.357 mol) in CH2Cl2 (10 ml) was added 1M BBr3—CH2Cl2 (2.14 ml, 2.74 mmol, 6 eq.) at −78° C. over 5 min. The reaction was stirred at RT for 48 hr., then MeOH (20 ml) was added followed by 10% NaHCO3 (20 ml), and the aqueous phase extracted with CH2Cl2 (2×50 ml) and the combined extracts washed with satd. NaCl solution (50 ml), dried over (Na2SO4) filtered and evaporated. Purification of the crude product over SiO2 (Merck 230-400 mesh) eluting with CH2Cl2-MeOH (9:1) afforded (RS)-2-[4-hydroxy-4-(4-methyl-benzyl)-piperidin-1-ylmethyl]-2,3-dihydro-1H-indol-5-ol as a brown solid (64.6 mg, 0.183 mmol, 51%), Mp. 90-94° C., MS: m/e=353.3 (M+H+).
Reaction SMILES: [Cl:1][C:2]1[CH:17]=[CH:16][C:5]([O:6][CH2:7][C:8]([NH:11][C:12](=[O:15])[CH:13]=[CH2:14])([CH3:10])[CH3:9])=[CH:4][CH:3]=1.[NH:18]1[CH:22]=[CH:21][N:20]=[CH:19]1.[OH-].O1CCOCC1>CO>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:6][CH2:7][C:8]([NH:11][C:12](=[O:15])[CH2:13][CH2:14][N:18]2[CH:22]=[CH:21][N:20]=[CH:19]2)([CH3:9])[CH3:10])=[CH:16][CH:17]=1
Reactant: C=CC(=O)NC(C)(C)COc1ccc(Cl)cc1
Reactant: c1c[nH]cn1
Agent: [OH-]
Solvent: CO
Solvent: C1COCCO1
Product: CC(C)(COc1ccc(Cl)cc1)NC(=O)CCn1ccnc1
Temperature: 95 °C

Procedure:
A mixture of N-[2-(4-chlorophenoxy)-1,1dimethylethyl]acrylamide (4.5 g), imidazole (1.24 g), benzyltrimethylanmonium hydroxide (0.62 ml of a 40% solution in methanol, Triton®B) and 1,4-dioxane (40 ml) was heated at 95° C. for 7 hours. The solvent was removed under reduced pressure and the residue was dissolved in dichloromethane. This solution was extracted with SM hydrochloric acid. The combined acid extracts were basified with 10M sodium hydroxide solution and extracted with dichloromethane to give N-[2-(4-chlorophenoxy)-1,1-dimethylethyl]-3-(imidazol-1-yl)propionamide.
Reaction SMILES: [C:1]([N:20]1[CH:24]=[C:23]([C:25]2[CH:29]=[C:28]([C:30](O)=[O:31])[NH:27][N:26]=2)[N:22]=[CH:21]1)([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:33][C@@H:34]([CH3:50])[CH2:35][N:36]1[CH:40]=[CH:39][C:38]([C:41]2[CH:48]=[CH:47][C:44]([C:45]#[N:46])=[C:43]([Cl:49])[CH:42]=2)=[N:37]1.CN(C=O)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C(Cl)Cl>[Cl:49][C:43]1[CH:42]=[C:41]([C:38]2[CH:39]=[CH:40][N:36]([CH2:35][C@@H:34]([NH:33][C:30]([C:28]3[NH:27][N:26]=[C:25]([C:23]4[N:22]=[CH:21][N:20]([C:1]([C:8]5[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=5)([C:14]5[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=5)[C:2]5[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=5)[CH:24]=4)[CH:29]=3)=[O:31])[CH3:50])[N:37]=2)[CH:48]=[CH:47][C:44]=1[C:45]#[N:46]
Reactant: O=C(O)c1cc(-c2cn(C(c3ccccc3)(c3ccccc3)c3ccccc3)cn2)n[nH]1
Reactant: C[C@H](N)Cn1ccc(-c2ccc(C#N)c(Cl)c2)n1
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: ClCCl
Product: C[C@@H](Cn1ccc(-c2ccc(C#N)c(Cl)c2)n1)NC(=O)c1cc(-c2cn(C(c3ccccc3)(c3ccccc3)c3ccccc3)cn2)n[nH]1
Yield: 128.7 %

Procedure:
The title compound was prepared using the procedure described in Example 3(h) starting from 3-(1-trityl-1H-imidazol-4-yl)-1H-pyrazole-5-carboxylic acid (2.493 mmol, 1048 mg) and (S)-4-(1-(2-aminopropyl)-1H-pyrazol-3-yl)-2-chloro-benzonitrile (1.918 mmol, 500 mg) using a mixture of DCM (10 ml) and DMF (1 ml) as the solvent. HBTU (0.384 mmol, 145 mg) was used instead of HOBt. The reaction mixture was diluted with DCM and washed with 1 M Na2CO3 and water. The separated organic phase was dried, filtered and evaporated. 1.637 g of the title compound was obtained. 1H-NMR (400 MHz, DMSO-d6): δ 1.12 (d, 3H), 4.17-4.52 (m, 3H), 6.75 (bs., 1H), 6.92 (d, 1H), 7.12-7.19 (m, 7H), 7.35-7.53 (m, 12H), 7.80 (d, 1H), 7.97 (bs, 1H), 8.04 (s, 1H), 8.21 (d, 1H), 13.38 (bs., 1H).
Reaction SMILES: Cl[C:2]1[CH:11]=[CH:10][N:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][C:6]([CH3:12])=[N:7]2.[NH2:13][C:14]1[CH:19]=[C:18]([O:20][CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[C:24]([Br:28])[CH:23]=2)[CH:17]=[CH:16][C:15]=1[S:29][C:30]1[CH:35]=[CH:34][C:33]([NH:36][C:37](=[O:39])[CH3:38])=[CH:32][CH:31]=1>C(O)C>[Br:28][C:24]1[CH:23]=[C:22]([CH:27]=[CH:26][CH:25]=1)[CH2:21][O:20][C:18]1[CH:17]=[CH:16][C:15]([S:29][C:30]2[CH:31]=[CH:32][C:33]([NH:36][C:37](=[O:39])[CH3:38])=[CH:34][CH:35]=2)=[C:14]([NH:13][C:2]2[C:3]3[C:8](=[N:7][C:6]([CH3:12])=[CH:5][CH:4]=3)[N:9]=[CH:10][CH:11]=2)[CH:19]=1
Reactant: Cc1ccc2c(Cl)ccnc2n1
Reactant: CC(=O)Nc1ccc(Sc2ccc(OCc3cccc(Br)c3)cc2N)cc1
Solvent: CCO
Product: CC(=O)Nc1ccc(Sc2ccc(OCc3cccc(Br)c3)cc2Nc2ccnc3nc(C)ccc23)cc1

Procedure:
The product from Example 1d (18 mg, 0.085 mmol) was reacted in ethanol (1 mL) with the product from Example 154a (37 mg, 0.085 mmol) for 18 h following the procedure from Example 1g giving the crude title compound which was purified by HPLC with TFA providing the product as a trifluoroacetic acid salt (15 mg, 30%). 1H NMR (300 MHz, DMSO-d6) δ ppm: 0.97 (t, J=7.35 Hz, 3H) 1.65-1.90 (m, 2 H) 2.02 (s, 3 H) 2.99 (t, J=7.54 Hz, 2 H) 5.17 (s, 2 H) 6.29 (d, J=6.99 Hz, 1 H) 7.14 (d, J=8.82 Hz, 2 H) 7.17-7.27 (m, 2 H) 7.28-7.40 (m, 3 H) 7.42 (d, J=8.46 Hz, 2 H) 7.55 (d, J=7.72 Hz, 1 H) 7.66 (s, 1 H) 7.80 (d, J=8.46 Hz, 1 H) 8.37 (d, J=6.99 Hz, 1 H) 8.97 (d, J=8.82 Hz, 1H) 9.98 (s, 1 H) 11.00 (s, 1 H) 14.37 (s, 1 H); MS (ESI+) m/z 613(M+H)+.
Reaction SMILES: I[Si](C)(C)C.C([O:8][P:9](OCC)([O:11][C:12]1[CH:17]=[CH:16][C:15](/[C:18](/[CH3:34])=[CH:19]/[C:20]([O:22][C:23]2[C:28]([Cl:29])=[C:27]([Cl:30])[C:26]([Cl:31])=[C:25]([Cl:32])[C:24]=2[Cl:33])=[O:21])=[CH:14][CH:13]=1)=O)C.C[Si](N([Si](C)(C)C)C(=O)C(F)(F)F)(C)C>C(Cl)Cl>[PH2:9]([O:11][C:12]1[CH:13]=[CH:14][C:15](/[C:18](/[CH3:34])=[CH:19]/[C:20]([O:22][C:23]2[C:24]([Cl:33])=[C:25]([Cl:32])[C:26]([Cl:31])=[C:27]([Cl:30])[C:28]=2[Cl:29])=[O:21])=[CH:16][CH:17]=1)=[O:8]
Reactant: CCOP(=O)(OCC)Oc1ccc(/C(C)=C/C(=O)Oc2c(Cl)c(Cl)c(Cl)c(Cl)c2Cl)cc1
Agent: C[Si](C)(C)I
Agent: C[Si](C)(C)N(C(=O)C(F)(F)F)[Si](C)(C)C
Solvent: ClCCl
Product: C/C(=C\C(=O)Oc1c(Cl)c(Cl)c(Cl)c(Cl)c1Cl)c1ccc(O[PH2]=O)cc1
Reaction time: 1 h

Procedure:
Iodotrimethylsilane (2.0 mL, 14.2 mmol) in 5 mL of dry CH2Cl2 was added dropwise to a solution of 11b1 (2.0 g, 3.55 mmol) and bis(trimethylsilyl)trifluoroacetamide (1.8 mL, 7.1 mmol) in 20 mL of dry CH2Cl2 at 0° C. under argon. Stirring was continued for 1 h at 0° C. and 1 h at room temperature. The solution was concentrated in vacuo. The residue was treated with 20 mL of MeCN/H2O (9:1) and 5 drops of conc. HCl for 30 min and concentrated in vacuo. Toluene (5 mL) was added and evaporated twice. On addition of Et2O solids separated, which were collected by filtration and washed with the same solvent to give, after drying over P2O5 in vacuo, 1.6 g of 12b as a white powder (88%). It was used without further purification. 1H NMR (DMSO-d6, 300 MHz) δ 2.6 (s, 3H), 6.6 (s, 1H), 7.24 (d, J=8.7 Hz, 2H), 7.75 (d, J=8.7 Hz, 2H). HRMS (M+H) calc, 503.8658; found, 503.8691.
Reaction SMILES: Cl.[NH2:2][CH:3]1[CH2:11][C:10]2[C:5](=[CH:6][CH:7]=[C:8]([O:12][CH2:13][C:14]([O:16]C)=[O:15])[CH:9]=2)[CH2:4]1.O.C(=O)([O-])[O-].[K+].[K+].[Cl:25][C:26]1[CH:31]=[CH:30][C:29]([S:32](Cl)(=[O:34])=[O:33])=[CH:28][CH:27]=1>C(OCC)(=O)C>[Cl:25][C:26]1[CH:31]=[CH:30][C:29]([S:32]([NH:2][CH:3]2[CH2:11][C:10]3[C:5](=[CH:6][CH:7]=[C:8]([O:12][CH2:13][C:14]([OH:16])=[O:15])[CH:9]=3)[CH2:4]2)(=[O:34])=[O:33])=[CH:28][CH:27]=1
Reactant: COC(=O)COc1ccc2c(c1)CC(N)C2
Reactant: O=S(=O)(Cl)c1ccc(Cl)cc1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: O
Product: O=C(O)COc1ccc2c(c1)CC(NS(=O)(=O)c1ccc(Cl)cc1)C2
Reaction time: 2 h
Yield: 93.5 %

Procedure:
2.71 g of methyl (2-aminoindan-5-yl)oxyacetate hydrochloride are added to a mixture of 80 ml of ethyl acetate, 40 ml of water and 415 mg of potassium carbonate and a solution of 2.11 g of 4-chlorophenylsulfonyl chloride in 40 ml of ethyl acetate is added dropwise thereto. The mixture is stirred for 2 hours and the ethyl acetate layer is separated. The ethyl acetate layer is washed successively with an aqueous 10% hydrochloric acid solution, an aqueous saturated sodium bicarbonate solution and an aqueous sodium chloride solution, dried and evaporated to remove solvent. 30 ml of methanol and 20 ml of 1N sodium hydroxide solution are added to the residue and the mixture is stirred at room temperature for 20 minutes. The reaction mixture is adjusted to pH 1 with an aqueous 10% hydrochloric acid solution and extracted with a mixture of chloroform and tetrahydrofuran. The extract is dried and evaporated to remove solvent. The residue is recrystallized from tetrahydrofuran-n-hexane-isopropyl ether to give 3.57 g of {2-[(4-chlorophenyl)sulfonylamino]indan-5-yl}oxyacetic acid as yellow prisms. Yield: 94% m.p. 170°-172° C.
Reaction SMILES: [CH:1]1[CH:6]=[CH:5][C:4]([C@@H:7]([OH:16])[C@@H:8]([OH:15])[C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)=[CH:3][CH:2]=1.I(C1C=CC=CC=1C(O)=O)(=O)=O>CS(C)=O.O>[C:4]1([C:7]([C:8]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)=[O:15])=[O:16])[CH:3]=[CH:2][CH:1]=[CH:6][CH:5]=1
Reactant: O[C@H](c1ccccc1)[C@@H](O)c1ccccc1
Agent: O=C(O)c1ccccc1I(=O)=O
Solvent: CS(C)=O
Solvent: O
Product: O=C(C(=O)c1ccccc1)c1ccccc1
Yield: 92.7 %

Procedure:
meso-Hydrobenzoin (mg 250, 1.17 mmol) was added to a solution of o-iodoxybenzoic acid I (820 mg, 2.93 mmol) in DMSO (15 ml). After 2 hours the solution was diluted with water, filtered and extracted with diethyl ether (3×15 ml). The combined organic layers were washed with water (2×5 ml), dried over sodium sulfate and evaporated to dryness under vacuum. The residue was triturated with n-hexane to give 228 mg (93%) of benzil, mp 91°-94° C. (lit. 94°-95° C.)
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[S:8][CH3:9].[C:10]([C:13]1[CH:18]=[CH:17][C:16](B(O)O)=[CH:15][CH:14]=1)([OH:12])=[O:11].C(=O)([O-])[O-].[K+].[K+]>O.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>[CH3:9][S:8][C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=1[C:16]1[CH:17]=[CH:18][C:13]([C:10]([OH:12])=[O:11])=[CH:14][CH:15]=1
Reactant: CSc1ccccc1Br
Reactant: O=C(O)c1ccc(B(O)O)cc1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: C1COCCO1
Solvent: O
Product: CSc1ccccc1-c1ccc(C(=O)O)cc1
Temperature: 25 °C

Procedure:
A stirred mixture containing 4.15 g (0.025 mole) of 2-bromothioanisole, 5.08 g. (0.0025 mole) of 4-carboxybenzeneboronic acid, 10.36 g (0.075 mol) of potassium carbonate and 0.45 g (0.00063 mol) of dichlorobis(triphenylphosphine)palladium(II) in 40 mL of water and 20 mL of 1,4-dioxane was heated under reflux for two hours under nitrogen. The reacton mixture was allowed to cool to room temperature and filtered. The dioxane was removed in vacuo, the residue was diluted with 100 mL of water and then acidified with 20% hydrochloric acid. The crude product (6.1 g) was recrystallized from ethanol to yield the title compound, m.p. 220-222° C.
Reaction SMILES: [CH3:1][NH2:2].CO.Cl[C:6]1[N:11]=[C:10]([O:12][CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2/[C:20](=[N:25]\[O:26][CH3:27])/[C:21]([NH:23][CH3:24])=[O:22])[CH:9]=[CH:8][C:7]=1[C:28]([F:31])([F:30])[F:29]>O>[CH3:1][NH:2][C:6]1[N:11]=[C:10]([O:12][CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2/[C:20](=[N:25]\[O:26][CH3:27])/[C:21]([NH:23][CH3:24])=[O:22])[CH:9]=[CH:8][C:7]=1[C:28]([F:31])([F:30])[F:29]
Reactant: CNC(=O)/C(=N/OC)c1ccccc1COc1ccc(C(F)(F)F)c(Cl)n1
Reactant: CN
Solvent: O
Solvent: CO
Product: CNC(=O)/C(=N/OC)c1ccccc1COc1ccc(C(F)(F)F)c(NC)n1
Temperature: 100 °C
Reaction time: 17 h

Procedure:
A 40% methylamine--methanol solution (10 ml) was added to (E)-2-[2-(6-chloro-5-trifluoromethylpyridin-2-yloxymethyl)phenyl]-2-methoxyimino-N-methylacetamide (402 mg), and the mixture was stirred at 100° C. for 17 hours. Water was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried, and then the solvent was evaporated. The resulting oil was purified by column chromatography on silica gel to give the title compound (379 mg). mp. 66°-67° C.
Reaction SMILES: [C:1]1([C:7]2[NH:11][C:10](=[O:12])[O:9][N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.O1CCCC1.[H-].[Na+].[CH3:20][C:21]1[C:25]([S:26](Cl)(=[O:28])=[O:27])=[C:24]([CH3:30])[O:23][N:22]=1>O>[CH3:20][C:21]1[C:25]([S:26]([N:11]2[C:10](=[O:12])[O:9][N:8]=[C:7]2[C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)(=[O:28])=[O:27])=[C:24]([CH3:30])[O:23][N:22]=1
Reactant: Cc1noc(C)c1S(=O)(=O)Cl
Reactant: O=c1[nH]c(-c2ccccc2)no1
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: C1CCOC1
Product: Cc1noc(C)c1S(=O)(=O)n1c(-c2ccccc2)noc1=O
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 9.3 %

Procedure:
At room temperature, a mixture of 2.0 g (15 mmol) of 3-phenyl-4H-[1,2,4]oxadiazol-5-one and 30 ml absolute tetrahydrofuran is admixed with stirring with 0.40 g (10 mmol) of a suspension of sodium hydride (60% strength) and then stirred at room temperature for 10 minutes. 1.9 g (10 mmol) of 3,5-dimethylisoxazol-4-sulphonyl chloride are subsequently added, and the mixture is stirred at room temperature for another 20 hours. For work-up, the reaction mixture is poured into 150 ml of water. The resulting mixture is extracted twice with 80 ml of ethyl acetate each time. The combined organic phases are dried over sodium sulphate and concentrated under reduced pressure. The residue that remains is chromatographed over silica gel using methylene chloride as mobile phase. In this manner, 0.3 g (9% of theory) of 4-(3,5-dimethylisoxazole-4-sulphonyl)-3-phenyl-4H-[1,2,4]oxadiazol-5-one is obtained in the form of a colourless solid of melting point 90 to 95 C.
Reaction SMILES: CS(Cl)(=O)=O.[C:6]1([CH:12]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[N:13]2[CH2:16][CH:15]([OH:17])[CH2:14]2)[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.C(N(CC)CC)C.[CH3:31][C:32]1[CH:37]=[CH:36][CH:35]=[C:34]([CH3:38])[C:33]=1O.[H-].[Na+]>C(Cl)Cl.CN(C)C=O>[CH3:31][C:32]1[CH:37]=[CH:36][CH:35]=[C:34]([CH3:38])[C:33]=1[O:17][CH:15]1[CH2:16][N:13]([CH:12]([C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=2)[CH2:14]1
Reactant: Cc1cccc(C)c1O
Reactant: OC1CN(C(c2ccccc2)c2ccccc2)C1
Agent: CS(=O)(=O)Cl
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: Cc1cccc(C)c1OC1CN(C(c2ccccc2)c2ccccc2)C1
Temperature: 0 °C
Yield: 52.2 %

Procedure:
Methanesulfonyl chloride (14.3 g, 125 mmol) was slowly added to a solution of N-diphenylmethyl azetidin-3-ol (20.0 g, 83.7 mmol) and triethylamine (15.2 g, 151 mmol) in methylene chloride (160 mL) which was maintained at 0° C. by an ice-water bath. After 1.5 hours the slurry was diluted with methylene chloride (160 mL) and ice-water (160 mL). The layers were separated and the organic layer was washed with an ice-water mixture (160 mL), dried (MgSO4), and concentrated in vacuo. A solution of the crude mesylate in dimethylformamide (100 mL) was added dropwise to a slurry of the sodium salt of 2,6-dimethylphenol in dimethylformamide prepared by adding a solution of 2,6-dimethylphenol (15.0 g, 125 mmol) in dimethylformamide to a slurry of sodium hydride (60% oil dispension, 7.20 g, 150 mmol) which had been washed (3×60 mL) with hexane and diluted with dimethylformamide (130 mL). The reaction mixture was warmed at 50° for 42 h, cooled to room temperature and added to 1400 mL of an ice-water mixture. The aqueous slurry was extracted with ethyl acetate (3×200 mL). The combined organic extracts were washed with water (100 mL), saturated aqueous sodium chloride (100 mL), dried (MgSO4) and concentrated in vacuo. The residue was chromatographed (silica gel, flash chromatography) eluting with ether/hexane (1:9) to give 15.0 g (52%) of white solid with a melting point of 99°-100° C.
Reaction SMILES: [Cl:1][CH2:2][C:3]([NH:5][NH:6][C:7]([C:9]1[NH:13][N:12]=[CH:11][CH:10]=1)=O)=O.COC1C=CC(P2(SP(C3C=CC(OC)=CC=3)(=S)S2)=[S:23])=CC=1>C1COCC1>[Cl:1][CH2:2][C:3]1[S:23][C:7]([C:9]2[NH:13][N:12]=[CH:11][CH:10]=2)=[N:6][N:5]=1
Reactant: COc1ccc(P2(=S)SP(=S)(c3ccc(OC)cc3)S2)cc1
Reactant: O=C(CCl)NNC(=O)c1ccn[nH]1
Solvent: C1CCOC1
Product: ClCc1nnc(-c2ccn[nH]2)s1
Yield: 55.8 %

Procedure:
N′-(2-chloroacetyl)-1H-pyrazole-5-carbohydrazide (110 mg, 0.54 mmol) and Lawesson's reagent (220 mg, 0.54 mmol) were suspended in THF 5.5 mL and then heated to reflux for 3 hr. The reaction mixture was concentrated and chromatographed on silica gel eluting with a gradient solvent mixture of AcOEt and hexanes to give the title compound as white solid (60.5 mg).
Reaction SMILES: [C:1]1([CH3:14])[CH:6]=[CH:5][C:4]([NH:7][CH2:8][C:9]([O:11][CH2:12][CH3:13])=[O:10])=[CH:3][CH:2]=1.ClC1C(=O)C(C#N)=C(C#N)C(=[O:23])C=1Cl>CO.O>[CH:14]([C:1]1[CH:6]=[CH:5][C:4]([NH:7][CH2:8][C:9]([O:11][CH2:12][CH3:13])=[O:10])=[CH:3][CH:2]=1)=[O:23]
Reactant: CCOC(=O)CNc1ccc(C)cc1
Reactant: N#CC1=C(C#N)C(=O)C(Cl)=C(Cl)C1=O
Solvent: O
Solvent: CO
Product: CCOC(=O)CNc1ccc(C=O)cc1
Temperature: 25 °C
Reaction time: 4 h
Yield: 25.1 %

Procedure:
To a solution of ethyl 2-(p-tolylamino)acetate (1.69 mmol) in methanol/water (20 ml/20 ml) was added the 2,3 dichloro-5,6-dicyanobenzoquinone (2.87 mmol) and the mixture was stirred for 4 hours at room temperature. The residue was chromatographed on a silica gel column (dichloromethane/ethyl acetate 8/2 as eluent) to give 88 mg of ethyl 2-(4-formylphenylamino)acetate. (yield 25%). MS (ESI): m/z 208.0 [M+H]+
Reaction SMILES: [CH3:1][N:2]1[CH:6]=[CH:5][N:4]=[C:3]1[CH:7]1[CH:16]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[C:15](=O)[C:14]2[C:13]([C:24]([O:26]C)=O)=[CH:12][CH:11]=[CH:10][C:9]=2[NH:8]1.CN1C=CN=C1C1C(C2C=CC=CC=2)C(=O)C2C(C(OCC)=O)=CC=CC=2N1.O.[NH2:57][NH2:58]>CO>[CH3:1][N:2]1[CH:6]=[CH:5][N:4]=[C:3]1[CH:7]1[NH:8][C:9]2[C:14]3[C:15](=[N:57][NH:58][C:24](=[O:26])[C:13]=3[CH:12]=[CH:11][CH:10]=2)[CH:16]1[C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1
Reactant: NN
Reactant: COC(=O)c1cccc2c1C(=O)C(c1ccccc1)C(c1nccn1C)N2
Agent: CCOC(=O)c1cccc2c1C(=O)C(c1ccccc1)C(c1nccn1C)N2
Solvent: CO
Solvent: O
Product: Cn1ccnc1C1Nc2cccc3c(=O)[nH]nc(c23)C1c1ccccc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 42 %

Procedure:
A mixture of methyl 2-(1-methyl-1H-imidazol-2-yl)-4-oxo-3-phenyl-1,2,3,4-tetrahydroquinoline-5-carboxylate and ethyl 2-(1-methyl-1H-imidazol-2-yl)-4-oxo-3-phenyl-1,2,3,4-tetrahydroquinoline-5-carboxylate (87 mg) in 85% hydrazine monohydrate (4 mL) and methanol (10 mL) was stirred at room temperature for overnight. The mixture was extracted with ethyl acetate (50 mL×3). The combined organic layers were washed with brine, dried over anhydrous sodium sulfate, and concentrated to give the crude. The crude product was purified by pre-HPLC to give 8-(1-methyl-1H-imidazol-2-yl)-9-phenyl-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one (34 mg, yield 42%) as a yellow solid. 1H-NMR (400 MHz, CD3O) δ (ppm): 3.41 (s, 3H), 4.49 (d, 1H), 5.35 (d, 1H), 7.18-7.20 (m, 2H), 7.26-7.29 (m, 1H), 7.33-7.35 (m, 3H), 7.40 (d, 1H), 7.61 (d, 1H), 7.71-7.75 (m, 2H); LC-MS (ESI) m/z: 344 (M+1)+.