Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][C@H:12]([CH2:14][OH:15])[N:11]([CH2:16][C:17]([N:19]2[C:27]3[C:22](=[CH:23][CH:24]=[C:25]([Cl:28])[CH:26]=3)[C:21]([CH3:30])([CH3:29])[CH2:20]2)=[O:18])[CH2:10][C@H:9]1[CH3:31])=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[CH3:34]I>CN(C=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][C@H:12]([CH2:14][O:15][CH3:34])[N:11]([CH2:16][C:17]([N:19]2[C:27]3[C:22](=[CH:23][CH:24]=[C:25]([Cl:28])[CH:26]=3)[C:21]([CH3:30])([CH3:29])[CH2:20]2)=[O:18])[CH2:10][C@H:9]1[CH3:31])=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: CI
Reactant: C[C@@H]1CN(CC(=O)N2CC(C)(C)c3ccc(Cl)cc32)[C@@H](CO)CN1C(=O)OC(C)(C)C
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: COC[C@H]1CN(C(=O)OC(C)(C)C)[C@H](C)CN1CC(=O)N1CC(C)(C)c2ccc(Cl)cc21
Temperature: 25 °C
Reaction time: 1 h
Yield: 19.5 %

Procedure:
To a cooled solution of (2R,5R)-4-[2-(6-chloro-3,3-dimethyl-2,3-dihydro-indol-1-yl)-2-oxo-ethyl]-5-hydroxymethyl-2-methyl-piperazine-1-carboxylic acid tert-butyl ester (100 mg, 0.22 mmol) in DMF (1.1 mL) at 0° C. (ice bath) was added sodium hydride (60%, 10 mg, 0.24 mmol). After stirring for 1 h, methyl iodide (15 μL, 0.24 mmol) was added and the reaction stirred for 30 mins. Reaction was allowed to warm gently to ambient temperature over 18 h. The solvent was removed in vacuo and residue was purified by column chromatography on silica gel (gradient elution, 0-100% EtOAc/petrol), to give the title compound (20 mg, 19%) as a colourless oil. 1H NMR (Me-d3-OD): 8.14 (1H, s), 7.27-7.13 (1H, m), 7.09 (1H, dd), 4.19 (1H, dd), 4.13-3.84 (3H, m), 3.78-3.44 (3H, m), 3.44-3.38 (1H, m), 3.36 (3H, s), 3.29 (1H, d), 3.07-2.94 (1H, m), 2.94-2.81 (1H, m), 2.66 (1H, dd), 1.48 (9H, s), 1.37 (6H, s), 1.34-1.20 (3H, m).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([NH:16][C:17]2[C:18]3[CH:26]=[C:25](F)[N:24]=[CH:23][C:19]=3[N:20]=[CH:21][N:22]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][N:11]=1.[CH3:28][O:29][C:30]1[CH:37]=[CH:36][C:33]([CH2:34][NH2:35])=[CH:32][CH:31]=1>CS(C)=O>[Cl:1][C:2]1[CH:3]=[C:4]([NH:16][C:17]2[C:18]3[CH:26]=[C:25]([NH:35][CH2:34][C:33]4[CH:36]=[CH:37][C:30]([O:29][CH3:28])=[CH:31][CH:32]=4)[N:24]=[CH:23][C:19]=3[N:20]=[CH:21][N:22]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][N:11]=1
Reactant: Fc1cc2c(Nc3ccc(OCc4ccccn4)c(Cl)c3)ncnc2cn1
Reactant: COc1ccc(CN)cc1
Solvent: CS(C)=O
Product: COc1ccc(CNc2cc3c(Nc4ccc(OCc5ccccn5)c(Cl)c4)ncnc3cn2)cc1
Temperature: 70 °C
Reaction time: 118 h
Yield: 76.8 %

Procedure:
A mixture of compound 203 (3.07 g, 8.04 mmol) and 4-methoxybenzylamine (10.6 mL, 80.4 mmol) in dry DMSO (20 mL) was stirred under a nitrogen atmosphere at 70° C. (bath temperature) for 118 h. The mixture was then cooled and petroleum ether (200 mL) was added. It was stirred at room temperature for 15 min. The layers were allowed to separate and the petroleum ether layer was decanted. This procedure was repeated with more petroleum ether (200 ml). Water (200 mL) was added and the mixture was stirred at room temperature overnight (22 h). It was filtered and washed solid with water (5×30 mL), then with petroleum ether (3×30 mL). The sticky yellow/orange solid was stirred with acetone (150 mL) at room temperature for 20 min. Water (150 mL) was added slowly and stirred further at room temperature for 45 min. The fine solid was collected by suction-filtration, washed with water/acetone (1:1) (4×20 mL), petroleum ether (3×20 mL) and dried in vacuum over silica-gel/KOH to give pure N4-(3-chloro-4-(pyridin-2-ylmethoxy)phenyl)-N6-(4-methoxybenzyl)pyrido[3,4-d]pyrimidine-4,6-diamine (212) (3.08 g, 77%) as a yellow/orange solid, mp 182-184° C.; 1HNMR δ [(CD3)2SO] 9.60 (s, 1H), 8.72 (s, 1H), 8.64-8.56 (m, 1H), 8.33 (s, 1H), 8.01 (d, J=2.6 Hz, 1H), 7.88 (td, J=7.7, 1.8 Hz, 1H), 7.71 (dd, J=9.0, 2.6 Hz, 1H), 7.58 (d, J=7.7 Hz), 7.42-7.19 (m, 5H), 7.15 (s, 1H), 6.93-6.84 (m, 2H), 5.25 (s, 2H), 4.48 (d, J=6.3 Hz, 2H), 3.71 (s, 3H). Anal. Calcd for C27H23ClN6O2.0.6aCet011e: C, 64.80; H, 5.02; N, 15.74%. Found C, 64.47; H, 5.00; N, 15.95%.
Reaction SMILES: [F:1][C:2]1[C:11]2[O:10][CH2:9][CH:8]=[CH:7][C:6]=2[C:5]([C:12]([NH2:14])=[O:13])=[CH:4][CH:3]=1.[N:15]([O-:17])=[O:16].[Na+].II.C(OCC)(=O)C>O>[F:1][C:2]1[C:11]2[O:10][CH2:9][C:8]([N+:15]([O-:17])=[O:16])=[CH:7][C:6]=2[C:5]([C:12]([NH2:14])=[O:13])=[CH:4][CH:3]=1
Reactant: NC(=O)c1ccc(F)c2c1C=CCO2
Reactant: O=N[O-]
Agent: II
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: O
Product: NC(=O)c1ccc(F)c2c1C=C([N+](=O)[O-])CO2
Temperature: 40 °C
Yield: 70 %

Procedure:
Into a reactor, equipped with a mechanic stirrer and a reflux condenser, 8-fluoro-2H-chromene-5-carboxylic acid amide (120 g;0.609 moles), sodium nitrite (96.6 g; 1.4 moles), iodine (31.2 g; 0.123 moles) and ethyl acetate (720 ml) were charged at room temperature and under inert gas. The mixture was heated under stirring at 40° C., then Oxistrong 15® (173.4 g) was added in 4 hours. At the end of the addition the reaction mixture was kept under stirring for 1 hour, then cooled at 20° C. Water (480 ml) was added and the mixture was kept under stirring for 1 hour. After filtration and wash of the panel with isopropyl acetate pre-cooled at 0° C. (2×120 ml) and then with water (150 ml), the solid was dried in oven under vacuum at 50° C. overnight obtaining 8-fluoro-3-nitro-2H-chromene-5-carboxylic acid amide (112.7 g; titre 91%; 70% yield).
Reaction SMILES: N([O-])=O.[Na+].N[C:6]1[C:14]([CH3:15])=[CH:13][CH:12]=[CH:11][C:7]=1[C:8]([OH:10])=[O:9].[ClH:16]>O.[OH-].[Na+].Cl[Cu]>[Cl:16][C:6]1[C:14]([CH3:15])=[CH:13][CH:12]=[CH:11][C:7]=1[C:8]([OH:10])=[O:9]
Reactant: Cc1cccc(C(=O)O)c1N
Reactant: Cl
Agent: Cl[Cu]
Agent: O=N[O-]
Agent: [Na+]
Solvent: O
Product: Cc1cccc(C(=O)O)c1Cl
Temperature: 0 °C

Procedure:
Sodium nitrite (14.0 g; 0.2 mol) was added to a solution of 2-amino-3-methylbenzoic acid (30.2 g; 0.2 mol) in a mixture of water (200 mL) and NaOH/aq (30%; 24 mL). The solution was cooled to 0° C. and was added dropwise, with stirring, to a mixture of HCl (conc.; 87.6 mL) and ice (100 g). After stirring for a few minutes, the resultant solution was added to an ice cold mixture of HCl/aq (23%; 100 g), CuCl (20 g; 0.2 mol) and water (40 mL). The solution was stirred at room temperature for 30 minutes and at 100° C. for 30 minutes, cooled, and the resultant precipitate was isolated by filtration, was washed with water, and was dried overnight, yielding 27.4 g (80.3%) of a white crystalline material.
Reaction SMILES: [C:1]([NH:4][CH2:5][CH2:6][NH:7][C:8](=[O:34])[C:9]1[CH:14]=[CH:13][C:12]([CH:15]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=2[CH3:33])[CH2:16][C:17]([C:19]2[CH:24]=[CH:23][C:22](=[O:25])[N:21]([CH3:26])[CH:20]=2)=O)=[CH:11][CH:10]=1)(=[O:3])[CH3:2].Cl.[NH2:36][OH:37].C([O-])(O)=O.[Na+]>>[C:1]([NH:4][CH2:5][CH2:6][NH:7][C:8](=[O:34])[C:9]1[CH:14]=[CH:13][C:12]([CH:15]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=2[CH3:33])[CH2:16]/[C:17](=[N:36]\[OH:37])/[C:19]2[CH:24]=[CH:23][C:22](=[O:25])[N:21]([CH3:26])[CH:20]=2)=[CH:11][CH:10]=1)(=[O:3])[CH3:2]
Reactant: NO
Reactant: CC(=O)NCCNC(=O)c1ccc(C(CC(=O)c2ccc(=O)n(C)c2)c2ccccc2C)cc1
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Product: CC(=O)NCCNC(=O)c1ccc(C(C/C(=N\O)c2ccc(=O)n(C)c2)c2ccccc2C)cc1

Procedure:
In analogy to example 151, step 3, N-(2-acetylamino-ethyl)-4-[3-(1-methyl-6-oxo-1,6-dihydro-pyridin-3-yl)-3-oxo-1-o-tolyl-propyl]-benzamide was reacted with hydroxylamine hydrochloride in the presence of NaHCO3 to give the title compound containing less than 10% of the corresponding Z isomer as a colorless solid, MS (ESI+): m/z=475.2 [M+H]+.
Reaction SMILES: [Cl:1][C:2]1[C:7]([C:8]2[NH:9][CH:10]=[C:11]([C:13]3[N:14]([CH:19]([CH3:21])[CH3:20])[N:15]=[C:16]([CH3:18])[N:17]=3)[N:12]=2)=[CH:6][N:5]=[C:4]([O:22][CH3:23])[CH:3]=1.C1(=O)O[CH2:27][CH2:26][O:25]1>C1(C)C=CC=CC=1>[Cl:1][C:2]1[CH:3]=[C:4]([O:22][CH3:23])[N:5]=[CH:6][C:7]=1[C:8]1[N:9]([CH2:27][CH2:26][OH:25])[CH:10]=[C:11]([C:13]2[N:14]([CH:19]([CH3:21])[CH3:20])[N:15]=[C:16]([CH3:18])[N:17]=2)[N:12]=1
Reactant: COc1cc(Cl)c(-c2nc(-c3nc(C)nn3C(C)C)c[nH]2)cn1
Reactant: O=C1OCCO1
Solvent: Cc1ccccc1
Product: COc1cc(Cl)c(-c2nc(-c3nc(C)nn3C(C)C)cn2CCO)cn1
Temperature: 130 °C
Yield: 34 %

Procedure:
A suspension of 4-chloro-5-[4-(2-isopropyl-5-methyl-2H-[1,2,4]triazol-3-yl)-1H-imidazol-2-yl]-2-methoxy-pyridine (5.9 g, 17.7 mmol) in toluene (20 mL) was treated with ethylene carbonate (50 mL) and heated at 130° C. for 2.5 h. The cooled reaction mixture was concentrated in vacuo then diluted with DCM and passed through a pad of silica eluting with DCM then 20% methanol in DCM. Methanolic fractions were combined and concentrated in vacuo and the resultant residue subjected to recrystallisation from acetonitrile to give the title compound as a pale tan solid (2.27 g, 34%). LCMS: RT=2.53 min [M+H]+=377/379. 1H NMR 400 MHz (CDCl3) δ: 8.25 (1H, s), 8.05 (1H, s), 6.92 (1H, s), 5.82-5.80 (1H, m), 4.00 (3H, s), 3.97 (2H, t, J=4.92 Hz), 3.88 (2H, t, J=4.92 Hz), 2.38 (3H, s), 1.48 (6H, d, J=6.63 Hz).
Reaction SMILES: [Cl-:1].[CH3:2][N:3]([CH3:29])[C:4]1[CH:28]=[CH:27][C:7]([CH:8]=[N:9][N+:10]2[CH:14]=[CH:13][N:12]([N:15]=[CH:16][C:17]3[CH:22]=[CH:21][C:20]([N:23]([CH3:25])[CH3:24])=[CH:19][CH:18]=3)[C:11]=2[CH3:26])=[CH:6][CH:5]=1.[CH3:30][N:31]([CH3:40])[C:32]1[CH:39]=[CH:38][C:35]([CH:36]=O)=[CH:34][CH:33]=1.N1CCCCC1>C(O)C>[Cl-:1].[CH3:25][N:23]([CH3:24])[C:20]1[CH:21]=[CH:22][C:17]([CH:16]=[N:15][N+:12]2[CH:13]=[CH:14][N:10]([N:9]=[CH:8][C:7]3[CH:6]=[CH:5][C:4]([N:3]([CH3:2])[CH3:29])=[CH:28][CH:27]=3)[C:11]=2[CH:26]=[CH:36][C:35]2[CH:38]=[CH:39][C:32]([N:31]([CH3:40])[CH3:30])=[CH:33][CH:34]=2)=[CH:18][CH:19]=1
Reactant: Cc1n(N=Cc2ccc(N(C)C)cc2)cc[n+]1N=Cc1ccc(N(C)C)cc1
Reactant: CN(C)c1ccc(C=O)cc1
Agent: [Cl-]
Solvent: C1CCNCC1
Solvent: CCO
Product: CN(C)c1ccc(C=Cc2n(N=Cc3ccc(N(C)C)cc3)cc[n+]2N=Cc2ccc(N(C)C)cc2)cc1
Reaction time: 20 h

Procedure:
0.82 g of 1,3-bis[[p-(dimethylamino)-benzylidene]amino]-2-methylimidazolium chloride is suspended in 30 ml of ethanol, whereupon the suspension is treated with 0.3 g of 4-dimethylaminobenzaldehyde and 0.17 g of piperidine and heated to boiling under reflux. A deep red solution results. After 20 hours it is left to cool. The precipitated product is removed by filtration and re-precipitated from methylene chloride/ether. After recrystallization from toluene there is obtained 1.3-bis[[p-(dimethyl-amino)benzylidene]amino]-2-[p-(dimethylamino)styryl]imidazolium chloride as a red solid of melting point 238°-240°.
Reaction SMILES: CON(C)[C:4]([C:6]1[CH:14]=[C:13]2[C:9]([C:10]([CH3:24])=[CH:11][N:12]2[CH2:15][C:16]2[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][CH:17]=2)=[CH:8][CH:7]=1)=[O:5].[C:26]1([Mg]Cl)[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.Cl>O1CCCC1>[CH3:23][O:22][C:19]1[CH:20]=[CH:21][C:16]([CH2:15][N:12]2[C:13]3[C:9](=[CH:8][CH:7]=[C:6]([C:4]([C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=4)=[O:5])[CH:14]=3)[C:10]([CH3:24])=[CH:11]2)=[CH:17][CH:18]=1
Reactant: COc1ccc(Cn2cc(C)c3ccc(C(=O)N(C)OC)cc32)cc1
Reactant: Cl[Mg]c1ccccc1
Agent: Cl
Solvent: C1CCOC1
Product: COc1ccc(Cn2cc(C)c3ccc(C(=O)c4ccccc4)cc32)cc1
Temperature: 0 °C
Reaction time: 2 h

Procedure:
A stirred solution of N-methoxy-1-(4-methoxybenzyl)-3-methyl-N-methyl-1H-indole-6-carboxamide (2.215 g, Example 25) in tetrahydrofuran (55 ml) was treated with a solution of phenylmagnesium chloride in tetrahydrofuran (9.83 ml, 2M). The solution was stirred at 0° C. for 2 hours then poured into a mixture of ice and 1N hydrochloric acid (10 ml) and then partitioned between ethyl acetate (50 ml) and water (50 ml). The organic layer was dried over sodium sulphate then evaporated. The residue was subjected to flash chromatography on silica eluting with a mixture of ethyl acetate and hexane (1:2, v/v) to yield the title compound (2.05 g) as a yellow solid, m.p. 146-147° C. [Elemental analysis:— C, 80.80; H, 6.00; N, 3.80%. Calculated for C24H21NO2:— C, 81.10; H, 5.96; N, 3.94%].
Reaction SMILES: [C:1]([O:5][CH3:6])(=[O:4])[CH:2]=[CH2:3].I[CH2:8][C:9]12[CH2:16][CH2:15][C:12]([C:17]3[S:21][C:20]([CH3:22])=[N:19][C:18]=3[C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)([CH2:13][CH2:14]1)[O:11][CH2:10]2>N1C=CC=CC=1.CCOC(C)=O.[Zn]>[CH3:22][C:20]1[S:21][C:17]([C:12]23[CH2:13][CH2:14][C:9]([CH2:8][CH2:3][CH2:2][C:1]([O:5][CH3:6])=[O:4])([CH2:16][CH2:15]2)[CH2:10][O:11]3)=[C:18]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[N:19]=1
Reactant: C=CC(=O)OC
Reactant: Cc1nc(-c2ccccc2)c(C23CCC(CI)(CC2)CO3)s1
Agent: [Zn]
Solvent: c1ccncc1
Solvent: CCOC(C)=O
Product: COC(=O)CCCC12CCC(c3sc(C)nc3-c3ccccc3)(CC1)OC2
Temperature: 75 °C
Reaction time: 2 h
Yield: 85 %

Procedure:
To a mixture of zinc powder (154 mg, 2.351 mmol), anhydrous pyridine (5 mL) and methyl acrylate (0.212 ml, 2.351 mmol) at 50° C. was added NiCl2.6H2O (56 mg, 0.235 mmol). The resulting mixture was warmed to 75° C. and stirred for 2 h until its green color turned to reddish brown. After cooling to 0° C., a solution of 5-(4-(iodomethyl)-2-oxabicyclo[2.2.2]octan-1-yl)-2-methyl-4-phenylthiazole (100 mg, 0.235 mmol) in anhydrous pyridine (3 mL) was added and the reaction mixture was stirred for 2 h at room temperature. The mixture was diluted with EtOAc (10 mL) and the resulting precipitate was filtered off through a pad of CELITE®. The filtrate was washed with 1 N aqueous HCl and brine, dried (Na2SO4), and concentrated in vacuo to afford the title compound (77 mg, 85% yield) as a clear oil. LCMS, [M+H]+=386.0. 1H NMR (500 MHz, CDCl3) δ 7.46-7.40 (m, 2H), 7.40-7.32 (m, 3H), 3.72 (s, 2H), 3.65 (s, 3H), 2.64 (s, 3H), 2.24 (t, J=7.4 Hz, 2H), 2.07-1.97 (m, 2H), 1.87-1.77 (m, 2H), 1.57-1.45 (m, 6H), 1.12-1.02 (m, 2H).
Reaction SMILES: C(OC([N:8]1[CH2:12][CH2:11][CH2:10][C@@H:9]1[CH2:13][O:14][C:15]1[CH:20]=[CH:19][C:18]([O:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)=[CH:17][CH:16]=1)=O)(C)(C)C.Cl>O1CCOCC1>[O:21]([C:18]1[CH:19]=[CH:20][C:15]([O:14][CH2:13][C@H:9]2[CH2:10][CH2:11][CH2:12][NH:8]2)=[CH:16][CH:17]=1)[C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1
Reactant: CC(C)(C)OC(=O)N1CCC[C@@H]1COc1ccc(Oc2ccccc2)cc1
Agent: Cl
Solvent: C1COCCO1
Product: c1ccc(Oc2ccc(OC[C@H]3CCCN3)cc2)cc1
Temperature: 25 °C
Reaction time: 3 h
Yield: 95.1 %

Procedure:
To the product from step 1 (91 mg, 0.246 mmol) was added 4M HCl in dioxane (6 mL) and the resulting mixture was stirred at rt for 3 h. The solvent was removed in vacuo to obtain the product as a oil (63 mg, 95%); MS; m/z 270 (M+H): LCMS (UV) 99%; 1H NMR (400 MHz, DMSO-d6) δ 1.71-1.78 (m, 1H), 1.89-2.0 (m, 2H), 2.1-2.15 (m, 1H), 3.16-3.24 (m, 2H), 3.88-3.93 (m, 1H), 4.11-4.15 (dd, 1H J1=8.4 Hz, J2=10.8 Hz), 4.22-4.26 (dd, 1H J1=3.6 Hz, J2=10.8 Hz), 6.91-6.94 (m, 2H), 7.03 (s, 3H), 7.06-7.1 (m, 1H), 7.34-7.38 (m, 2H)
Reaction SMILES: BrC1C2[C:10](=CC=CC=2)[C:9]([C:16]2[CH:17]=[C:18]([C:22]3[N:26]([C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=4)[C:25]4[CH:33]=[CH:34][CH:35]=[CH:36][C:24]=4N=3)C=CC=2)=C2C=1C=CC=C2.[Br:37][C:38]1[C:39]2[C:44]([C:45](Br)=[C:46]3[C:51]=1[CH:50]=[CH:49][CH:48]=[CH:47]3)=[CH:43][CH:42]=[CH:41][CH:40]=2.C([O-])([O-])=O.[Na+].[Na+].O>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.C1COCC1>[Br:37][C:38]1[C:39]2[C:44](=[CH:43][CH:42]=[CH:41][CH:40]=2)[C:45]([C:29]2[CH:28]=[C:27]([N:26]3[C:25]4[CH:24]=[CH:36][CH:35]=[CH:34][C:33]=4[C:10]4[C:22]3=[CH:18][CH:17]=[CH:16][CH:9]=4)[CH:32]=[CH:31][CH:30]=2)=[C:46]2[C:51]=1[CH:50]=[CH:49][CH:48]=[CH:47]2
Reactant: Brc1c2ccccc2c(Br)c2ccccc12
Reactant: Brc1c2ccccc2c(-c2cccc(-c3nc4ccccc4n3-c3ccccc3)c2)c2ccccc12
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: O
Solvent: C1CCOC1
Product: Brc1c2ccccc2c(-c2cccc(-n3c4ccccc4c4ccccc43)c2)c2ccccc12
Yield: 68 %

Procedure:
Following the procedure as outlined above for synthesizing Compound 5, Compound (2.686 g, 7.274 mmol), 9,10-dibromoanthracene (7.333 g, 21.82 mmol), tetrakis(triphenylphosphine)palladium(0) (0.420 g, 0.364 mmol), Na2CO3 (9.539 g, 90.00 mmol), H2O (90 mL) and THF (150 mL) yielded Compound 8 (2.45 g, 68%) as a light yellow solid after flash chromatography (SiO2, 19:1 to 9:1 hexanes-dichloromethane).
Reaction SMILES: [Na].C[O:3][C:4](=O)[CH2:5][C:6]1=[N:7][N:8]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=2[Cl:34])[C:9](=[O:27])/[C:10]/1=[C:11](\[NH:19][CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)/[CH2:12][N:13]1[CH2:18][CH2:17][O:16][CH2:15][CH2:14]1.Cl>CC(O)C>[CH2:20]([N:19]1[C:4](=[O:3])[CH:5]=[C:6]2[NH:7][N:8]([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=3[Cl:34])[C:9](=[O:27])[C:10]2=[C:11]1[CH2:12][N:13]1[CH2:14][CH2:15][O:16][CH2:17][CH2:18]1)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1
Reactant: COC(=O)CC1=NN(c2ccccc2Cl)C(=O)/C1=C(/CN1CCOCC1)NCc1ccccc1
Agent: Cl
Agent: [Na]
Solvent: CC(C)O
Product: O=c1c2c(CN3CCOCC3)n(Cc3ccccc3)c(=O)cc2[nH]n1-c1ccccc1Cl
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 12 %

Procedure:
An isopropanolic solution of i-PrONa, obtained by dissolving of sodium (0.017 g, 0.75 mmol, 2 equiv) in i-PrOH (2 ml), was treated with methyl[(4Z)-4-[1-(benzylamino)-2-morpholin-4-ylethylidene]-1-(2-chlorophenyl)-5-oxo-4,5-dihydro-1H-pyrazol-3-yl]acetate tate (Compound of Formula (XIV) (170 mg, 0.75 mmol, 1 equiv.). The reaction mixture was stirred at room temperature for 0.5 h, then cooled and neutralized to pH 6 by addition 1M HCl solution. i-PrOH were removed in vacuo and the crude was purified by flash chromatography to yield 9 mg of pure product 5-benzyl-2-(2-chlorophenyl)-4-(morpholin-4-ylmethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione. Yield 12%. 1HNMR (500 MHz, DMSO-d6): 2.37-2.41 (m, 4H); 3.94-4.00 (m, 2H); 5.52-5.55 (m, 2H), 5.84 (s, 1H); 7.07-7.09 (m, 2H), 7.22-7.28 (m, 2H); 7.30-7.33 (m, 2H); 7.48-7.51 (m, 2H); 7.59-7.61 (m, 1H); 7.63-7.67 (m, 1H). MS (ESI+): 451.9; MS (ESI−): 449.7.
Reaction SMILES: [C:1]1(=[O:12])[O:7][C:5](=O)[C:4]2=[CH:8][CH:9]=[CH:10][CH:11]=[C:3]2[CH2:2]1.[CH3:13][C:14]1[CH:20]=[CH:19][CH:18]=[C:17]([CH3:21])[C:15]=1[NH2:16]>C(OCC)(=O)C>[CH3:13][C:14]1[CH:20]=[CH:19][CH:18]=[C:17]([CH3:21])[C:15]=1[N:16]1[C:5](=[O:7])[C:4]2=[CH:8][CH:9]=[CH:10][CH:11]=[C:3]2[CH2:2][C:1]1=[O:12]
Reactant: O=C1Cc2ccccc2C(=O)O1
Reactant: Cc1cccc(C)c1N
Solvent: CCOC(C)=O
Product: Cc1cccc(C)c1N1C(=O)Cc2ccccc2C1=O
Reaction time: 1 h
Yield: 68 %

Procedure:
0.67 g (4.13 mmol) of homophthalic anhydride and 0.4 g (3.30 mmol) of 2,6-dimethylaniline were mixed, and melted at a temperature of 200° C. for 1 hour. The reactant was dissolved in ethyl acetate, washed with aqueous NaHCO3 solution, with water and then with saturated aqueous sodium chloride, dried over anhydrous MgSO4, and subjected to filtration with a folded filter paper. The filtrate was concentrated and evaporated to dryness. The residue was recrystallized by using a mixture of CH2Cl2 and hexane, to obtain 0.565 g (yield 68%) of the specified substance as light yellow granulated crystals. It showed the following physical properties and analyzed values.
Reaction SMILES: Cl.[NH2:2][C:3]1[CH:31]=[CH:30][C:6]2[NH:7][C:8]([C:13]3[C:14](=[O:29])[C:15]([CH2:25][CH2:26][CH2:27][CH3:28])([CH3:24])[C:16]4[C:21]([C:22]=3[OH:23])=[CH:20][CH:19]=[CH:18][CH:17]=4)=[N:9][S:10](=[O:12])(=[O:11])[C:5]=2[CH:4]=1.[S:32](Cl)([CH3:35])(=[O:34])=[O:33].N1C=CC=CC=1>CC(C)=O>[CH2:25]([C:15]1([CH3:24])[C:16]2[C:21](=[CH:20][CH:19]=[CH:18][CH:17]=2)[C:22]([OH:23])=[C:13]([C:8]2[NH:7][C:6]3[CH:30]=[CH:31][C:3]([NH:2][S:32]([CH3:35])(=[O:34])=[O:33])=[CH:4][C:5]=3[S:10](=[O:12])(=[O:11])[N:9]=2)[C:14]1=[O:29])[CH2:26][CH2:27][CH3:28]
Reactant: CCCCC1(C)C(=O)C(C2=NS(=O)(=O)c3cc(N)ccc3N2)=C(O)c2ccccc21
Reactant: CS(=O)(=O)Cl
Agent: Cl
Solvent: c1ccncc1
Solvent: CC(C)=O
Product: CCCCC1(C)C(=O)C(C2=NS(=O)(=O)c3cc(NS(C)(=O)=O)ccc3N2)=C(O)c2ccccc21
Yield: 95.7 %

Procedure:
A solution of Example 33B (0.052 g, 0.112 mmol), mesyl chloride (0.035 mL, 0.447 mmol), and pyridine (0.073 mL, 0.893 mmol) in acetone (1.5 mL) was stirred at 25° C. for 18 hours. The solution was partitioned between ethyl acetate and dilute citric acid and the layers were separated. The ethyl acetate layer was dried with sodium sulfate, filtered, and concentrated in vacuo. The residue was chromatographed on silica gel eluting with methylene chloride and 2.5% methanol in methylene chloride to give the desired product (0.054 g, 96%).
Reaction SMILES: [F:1][CH:2]([F:27])[O:3][C:4]1[CH:5]=[C:6]([C:11]2[O:12][CH:13]=[C:14]([CH2:16][CH2:17][C:18]([C:20]3[C:25]([CH3:26])=[CH:24][CH:23]=[CH:22][N:21]=3)=[O:19])[N:15]=2)[CH:7]=[CH:8][C:9]=1[OH:10].[CH2:28](Br)[CH:29]=[CH2:30]>>[CH2:30]([O:10][C:9]1[CH:8]=[CH:7][C:6]([C:11]2[O:12][CH:13]=[C:14]([CH2:16][CH2:17][C:18]([C:20]3[C:25]([CH3:26])=[CH:24][CH:23]=[CH:22][N:21]=3)=[O:19])[N:15]=2)=[CH:5][C:4]=1[O:3][CH:2]([F:1])[F:27])[CH:29]=[CH2:28]
Reactant: C=CCBr
Reactant: Cc1cccnc1C(=O)CCc1coc(-c2ccc(O)c(OC(F)F)c2)n1
Product: C=CCOc1ccc(-c2nc(CCC(=O)c3ncccc3C)co2)cc1OC(F)F

Procedure:
Using the compound obtained in Example 356 and allyl bromide, white powdery 3-[2-(4-allyloxy-3-difluoromethoxy phenyl)oxazol-4-yl]-1-(3-methylpyridin-2-yl)propan-1-one was obtained following the procedure of Example 3.
Reaction SMILES: O[C:2]1[C:3]2[CH2:17][C:16]3[CH:18]=[CH:19][CH:20]=[CH:21][C:15]=3[O:14][C:4]=2[N:5]=[C:6]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[N:7]=1.P(Cl)(Cl)(Cl)(Cl)[Cl:23].P(Cl)(Cl)(Cl)=O>>[Cl:23][C:2]1[C:3]2[CH2:17][C:16]3[CH:18]=[CH:19][CH:20]=[CH:21][C:15]=3[O:14][C:4]=2[N:5]=[C:6]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[N:7]=1
Reactant: ClP(Cl)(Cl)(Cl)Cl
Reactant: Oc1nc(-c2ccccc2)nc2c1Cc1ccccc1O2
Solvent: O=P(Cl)(Cl)Cl
Product: Clc1nc(-c2ccccc2)nc2c1Cc1ccccc1O2

Procedure:
Eight and one tenth (8.1) gram 4-hydroxy-2-phenyl[1]benzopyrano[2,3-d]pyrimidine, 9.0 g phosphoruspentachloride and 36 ml phosphorusoxychloride are heated for two hours under reflux. Excess phosphorusoxychloride is then distilled off under a vacuum and the residue is partitioned to chloroform and water, a pH 6 value being adjusted by the addition of 10% sodium hydroxide. The organic phase is separated and the chloroform removed by distillation in a rotary evaporator. The residue obtained is separated by chromatography using cyclohexane/chloroform 1:1 as an eluting agent. There are obtained 4.0 g 4-chloro-2-phenyl[1]benzopyrano[2,3-d]pyrimidine, mp 168°-170° C. as colorless crystals. Thereafter 0.05 g sodium are dissolved in 10 ml anhydrous ethanol and 0.25 g 3-dimethylamino-1-propane-thiol added to the solution. The mixture obtained is added dropwise to a solution of 0.6 g 4-chloro-2-phenyl[1]benzopyrano[2,3-d]pyrimidine at reflux temperature. The reaction mixture is then kept under reflux for another two hours. After cooling the reaction mixture is filtered and the filtrate is evaporated to dryness and the residue partitioned to chloroform and water. The organic phase is separated off, the chloroform is evaporated and the residue recrystallized from ethanol. There are obtained 0.4 g colorless crystals, mp 93° C.