Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br[C:2]1[CH:19]=[CH:18][C:5]2[C:6]([CH:15]([CH3:17])[CH3:16])=[N:7][C:8]3[CH:9]=[CH:10][NH:11][C:12](=[O:14])[C:13]=3[C:4]=2[CH:3]=1.[CH3:20][N:21]1[CH:25]=[C:24](B2OC(C)(C)C(C)(C)O2)[CH:23]=[N:22]1.C(=O)([O-])[O-].[Na+].[Na+]>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].C(Cl)Cl.CN(C=O)C>[CH:15]([C:6]1[C:5]2[CH:18]=[CH:19][C:2]([C:24]3[CH:23]=[N:22][N:21]([CH3:20])[CH:25]=3)=[CH:3][C:4]=2[C:13]2[C:12](=[O:14])[NH:11][CH:10]=[CH:9][C:8]=2[N:7]=1)([CH3:17])[CH3:16]
Reactant: CC(C)c1nc2cc[nH]c(=O)c2c2cc(Br)ccc12
Reactant: Cn1cc(B2OC(C)(C)C(C)(C)O2)cn1
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: O=C([O-])[O-]
Solvent: ClCCl
Solvent: CN(C)C=O
Product: CC(C)c1nc2cc[nH]c(=O)c2c2cc(-c3cnn(C)c3)ccc12
Temperature: 100 °C

Procedure:
9-bromo-6-isopropylbenzo[c]-1,6-naphthyridin-1(2H)-one (50 mg, 0.16 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (66 mg, 0.32 mmol), PdCl2(dppf)-CH2Cl2 adduct (26 mg, 0.032 mmol), DMF (1.7 ml), and 2 M aqueous sodium carbonate (0.16 ml, 0.32 mmol) were combined in a microwave vial and sparged with argon for 5 minutes. The reaction mixture was heated in a microwave reactor at 100° C. for 30 min. The reaction mixture was diluted with MeOH and purified directly by preparative reverse phase HPLC eluting with an acetonitrile/water (with 0.05% TFA modifier) gradient to afford 6-isopropyl-9-(1-methyl-1H-pyrazol-4-yl)benzo[c]-1,6-naphthyridin-1(2H)-one. 1H NMR (500 MHz, DMSO D-6) δ 11.69 (br d, 1H), 10.20 (d, 1H), 8.42 (d, 1H), 8.32 (s, 1H), 7.97 (s, 1H), 7.94 (dd, 1H), 7.51 (t, 1H), 6.73 (d, 1H), 4.06 (septet, 1H), 3.92 (s, 3H), 1.37 (d, 6H). LRMS (ESI) calc'd for (C19H18N4O) [M+H]+, 319.1; found 319.1.
Reaction SMILES: Cl[C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[CH:8]=[C:9]([C:11]3[S:12][C:13]([C:17]([N:19]4[CH2:24][CH2:23][N:22]([CH3:25])[CH2:21][CH2:20]4)=[O:18])=[C:14]([CH3:16])[N:15]=3)[S:10][C:3]=12.[CH3:26][C:27]1[NH:28][C:29]2[C:34]([CH:35]=1)=[CH:33][C:32]([OH:36])=[CH:31][CH:30]=2>>[CH3:16][C:14]1[N:15]=[C:11]([C:9]2[S:10][C:3]3[C:4](=[N:5][CH:6]=[CH:7][C:2]=3[O:36][C:32]3[CH:33]=[C:34]4[C:29](=[CH:30][CH:31]=3)[NH:28][C:27]([CH3:26])=[CH:35]4)[CH:8]=2)[S:12][C:13]=1[C:17]([N:19]1[CH2:24][CH2:23][N:22]([CH3:25])[CH2:21][CH2:20]1)=[O:18]
Reactant: Cc1cc2cc(O)ccc2[nH]1
Reactant: Cc1nc(-c2cc3nccc(Cl)c3s2)sc1C(=O)N1CCN(C)CC1
Product: Cc1cc2cc(Oc3ccnc4cc(-c5nc(C)c(C(=O)N6CCN(C)CC6)s5)sc34)ccc2[nH]1
Yield: 51 %

Procedure:
The title compound (77 mg, 51%) was prepared from [2-(7-Chloro-thieno[3,2-b]pyridin-2-yl)-4-methyl-thiazol-5-yl]-(4-methyl-piperazin-1-yl)-methanone and 2-methyl-1H-indol-5-ol by a procedure analogous to Example 16 as a tan colored hydrochloride salt. C26H25N5O2S2: APCI m/z 504.3 (pos.); 1H NMR (CD3OD): δ 8.46 (d, 1H, J=5.4 Hz), 7.99 (s, 1H), 7.35 (d, 1H, J=8.3 Hz), 7.26 (s, 1H), 6.87 (d, 1H, J=8.3 Hz), 6.67 (d, 1H, J=5.4 Hz), 6.17 (s, 1H), 3.8–3.0 (bm, 8H), 2.95 (s, 3H), 2.49 (s, 3H), 2.43 (s, 3H) ppm.
Reaction SMILES: C[O:2][C:3]([C:5]1[CH:10]=[CH:9][C:8]([N:11]2[C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[CH2:15][CH2:14][C:12]2=[O:13])=[CH:7][CH:6]=1)=[O:4].[OH-].[Na+]>CO>[C:3]([C:5]1[CH:6]=[CH:7][C:8]([N:11]2[C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[CH2:15][CH2:14][C:12]2=[O:13])=[CH:9][CH:10]=1)([OH:4])=[O:2]
Reactant: COC(=O)c1ccc(N2C(=O)CCc3ccccc32)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: O=C(O)c1ccc(N2C(=O)CCc3ccccc32)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 49.8 %

Procedure:
To a solution of 1-(4-methoxycarbonylphenyl)-3,4-dihydrocarbostyril (1.84 g) in methanol (40 ml) is added a 5% aqueous sodium hydroxide solution (20 ml) and the mixture is stirred at room temperature overnight. Methanol is distilled off under reduced pressure and to the residue is added water. After the solution is washed with dichloromethane, the aqueous layer is made acidic with concentrated hydrochloric acid and extracted with diethyl ether and dried over magnesium sulfate. The solvent is distilled off under reduced pressure and the resulting residue is purified by silica gel column chromatography, followed by recrystallization from ethanol to give 1-(4-carboxyphenyl)-3,4-dihydrocarbostyril (0.87 g) as pale yellow powders, m.p. 265°-270° C.
Reaction SMILES: C(OC([N:8]1[CH2:13][CH2:12][C:11]2[N:14]([CH3:42])[C:15]([C:17]3[CH:22]=[CH:21][N:20]=[C:19]([NH:23][C:24]4[CH:29]=[C:28]([N:30]5[CH2:35][CH2:34][N:33]([CH3:36])[CH2:32][CH2:31]5)[CH:27]=[CH:26][C:25]=4[O:37][C:38]([F:41])([F:40])[F:39])[N:18]=3)=[CH:16][C:10]=2[C:9]1=[O:43])=O)(C)(C)C.[ClH:44]>O1CCCC1.O1CCOCC1>[ClH:44].[CH3:42][N:14]1[C:11]2[CH2:12][CH2:13][NH:8][C:9](=[O:43])[C:10]=2[CH:16]=[C:15]1[C:17]1[CH:22]=[CH:21][N:20]=[C:19]([NH:23][C:24]2[CH:29]=[C:28]([N:30]3[CH2:31][CH2:32][N:33]([CH3:36])[CH2:34][CH2:35]3)[CH:27]=[CH:26][C:25]=2[O:37][C:38]([F:40])([F:41])[F:39])[N:18]=1
Reactant: CN1CCN(c2ccc(OC(F)(F)F)c(Nc3nccc(-c4cc5c(n4C)CCN(C(=O)OC(C)(C)C)C5=O)n3)c2)CC1
Agent: Cl
Solvent: C1COCCO1
Solvent: C1CCOC1
Product: CN1CCN(c2ccc(OC(F)(F)F)c(Nc3nccc(-c4cc5c(n4C)CCNC5=O)n3)c2)CC1
Temperature: 25 °C
Yield: 98 %

Procedure:
To a solution of methyl-2-{2-[5-(4-methyl-piperazin-1-yl)-2-trifluoromethoxy-phenylamino]-pyrimidin-4-yl}-4-oxo-1,4,6,7-tetrahydro-pyrrolo[3,2-c]pyridine-5-carboxylic acid tert-butyl ester (25 mg, 0.037 mmol) in tetrahydrofuran (1 mL), 4M HCl in dioxane (0.4 mL) were added. The solution was stirred at room temperature over night. The solvent was evaporated under vacuo to yield 22 mg (98%) of the title compound as a beige powder.
Reaction SMILES: COC1C=C(OC)C=CC=1C[N:6]1[C:11](=[O:12])[C:10]2[CH:13]=[C:14]([CH2:16][CH3:17])[S:15][C:9]=2[NH:8][C:7]1=[O:18].Br[CH2:26][C:27]1[CH:32]=[CH:31][C:30]([C:33]2[C:34]([C:39]#[N:40])=[CH:35][CH:36]=[CH:37][CH:38]=2)=[C:29]([F:41])[CH:28]=1.C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[CH2:16]([C:14]1[S:15][C:9]2[N:8]([CH2:26][C:27]3[CH:32]=[CH:31][C:30]([C:33]4[C:34]([C:39]#[N:40])=[CH:35][CH:36]=[CH:37][CH:38]=4)=[C:29]([F:41])[CH:28]=3)[C:7](=[O:18])[NH:6][C:11](=[O:12])[C:10]=2[CH:13]=1)[CH3:17]
Reactant: CCc1cc2c(=O)n(Cc3ccc(OC)cc3OC)c(=O)[nH]c2s1
Reactant: N#Cc1ccccc1-c1ccc(CBr)cc1F
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: CCc1cc2c(=O)[nH]c(=O)n(Cc3ccc(-c4ccccc4C#N)c(F)c3)c2s1
Temperature: 50 °C
Reaction time: 1.5 h
Yield: 68.3 %

Procedure:
A mixture of 3-(2,4-dimethoxybenzyl)-6-ethylthieno[2,3-d]pyrimidine-2,4(1H,3H)-dione (2 g), 4′-(bromomethyl)-2′-fluorobiphenyl-2-carbonitrile (2 g), potassium carbonate (1.6 g) and acetonitrile (40 mL) was stirred at 50° C. for 1.5 hr. Insoluble material was filtered off, and the solvent was evaporated under reduced pressure. The obtained residue was dissolved in trifluoroacetic acid (15 mL), and the mixture was stirred at 50° C. for 2 hr. The reaction mixture was concentrated under reduced pressure. To the obtained residue was added ethyl acetate, and insoluble material was filtered off. The filtrate was concentrated and recrystallized from diethyl ether to give the title compound as a colorless solid (1.6 g, 90%).
Reaction SMILES: [O:1]=[C:2]1[NH:10][CH:9]=[N:8][C:7]2[N:6]([CH2:11][CH2:12][C:13]([O:15]CC)=O)[CH:5]=[N:4][C:3]1=2.[NH2:18][CH2:19][CH2:20][C:21]1[N:22]([CH3:26])[CH:23]=[CH:24][CH:25]=1>CCOCC.CC(C)=O>[O:1]=[C:2]1[NH:10][CH:9]=[N:8][C:7]2[N:6]([CH2:11][CH2:12][C:13]([NH:18][CH2:19][CH2:20][C:21]3[N:22]([CH3:26])[CH:23]=[CH:24][CH:25]=3)=[O:15])[CH:5]=[N:4][C:3]1=2
Reactant: CCOC(=O)CCn1cnc2c(=O)[nH]cnc21
Reactant: Cn1cccc1CCN
Solvent: CC(C)=O
Solvent: CCOCC
Product: Cn1cccc1CCNC(=O)CCn1cnc2c(=O)[nH]cnc21
Reaction time: 3.5 h
Yield: 79.5 %

Procedure:
250 mg (1.06 mmol) of 3-(1,6-dihydro-6-oxo-9H-purin-9-yl)propionic acid, ethyl ester (Alt-0027) and 400 mg (3.22 mmol) of 2-(2-aminoethyl)-1-methyl-pyrrole were heated together in a 10 ml round bottom flask with stirring (no solvent) at 110°-120° C. for 3.5 hours. The dark viscous residue was treated with a 1:1 mixture of ether/acetone and stirred vigorously for 30 minutes. The precipitate was collected by filtration and was washed with ether and acetone and dried in vacuo to yield 265 mg of 3-(1,6-dihydro-6-oxo-9H-purin-9-yl)-N-[2-(1-methylpyrrol-2-yl)ethyl] propanamide (AIT-0035) as an off-white solid. Yield: 80%
Reaction SMILES: Br[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([OH:12])[CH:10]=2)[N:5]=[C:4]([C:13]2[CH:18]=[CH:17][C:16]([OH:19])=[C:15]([F:20])[CH:14]=2)[CH:3]=1.C([Sn](CCCC)(CCCC)[C:26]1[S:27][CH:28]=[CH:29][N:30]=1)CCC>>[F:20][C:15]1[CH:14]=[C:13]([C:4]2[CH:3]=[C:2]([C:26]3[S:27][CH:28]=[CH:29][N:30]=3)[C:11]3[C:6](=[CH:7][CH:8]=[C:9]([OH:12])[CH:10]=3)[N:5]=2)[CH:18]=[CH:17][C:16]=1[OH:19]
Reactant: CCCC[Sn](CCCC)(CCCC)c1nccs1
Reactant: Oc1ccc2nc(-c3ccc(O)c(F)c3)cc(Br)c2c1
Product: Oc1ccc2nc(-c3ccc(O)c(F)c3)cc(-c3nccs3)c2c1
Yield: 56 %

Procedure:
This compound was prepared from 6b and 2-tributylstannylthiazole according to method J. Yellow powder; Yield: 56%; mp>280° C. (dec.); 1H-NMR (400 MHz, DMSO-d6) δ 7.10 (t, J=8.8 Hz, 1H), 7.38 (dd, J=9.1, 2.7 Hz, 1H), 7.95–8.00 (m, 2H), 8.07–8.12 (m, 3H), 8.21 (m, 2H), 10.18 (s, 1H), 10.26 (s, 1H); MS (ESI) m/z 337 ([M−H]−), 339 ([M+H]+); Anal. Calcd for C18H11FN2O2S: C: 63.90, H: 3.28, N: 8.28. Found: C: 62.6, H: 3.43, N: 7.59.
Reaction SMILES: [Cl:1][C:2]1[N:7]=[C:6]([NH:8][C:9]2[CH:10]=[C:11]([NH:15][S:16]([C:19]3[CH:24]=[CH:23][CH:22]=[C:21]([N+:25]([O-])=O)[CH:20]=3)(=[O:18])=[O:17])[CH:12]=[CH:13][CH:14]=2)[C:5]([Cl:28])=[CH:4][N:3]=1>O.CO.C(O)(=O)C.[Fe]>[NH2:25][C:21]1[CH:20]=[C:19]([S:16]([NH:15][C:11]2[CH:12]=[CH:13][CH:14]=[C:9]([NH:8][C:6]3[C:5]([Cl:28])=[CH:4][N:3]=[C:2]([Cl:1])[N:7]=3)[CH:10]=2)(=[O:17])=[O:18])[CH:24]=[CH:23][CH:22]=1
Reactant: O=[N+]([O-])c1cccc(S(=O)(=O)Nc2cccc(Nc3nc(Cl)ncc3Cl)c2)c1
Agent: [Fe]
Solvent: CC(=O)O
Solvent: CO
Solvent: O
Product: Nc1cccc(S(=O)(=O)Nc2cccc(Nc3nc(Cl)ncc3Cl)c2)c1
Temperature: 0 °C
Reaction time: 1 h
Yield: 109.7 %

Procedure:
To a solution N-{3-[(2,5-dichloropyrimidin-4-yl)amino]phenyl}-3-nitrobenzenesulfonamide (0.5 g, 1.0 mmol) in water (0.9 mL), methanol (4.4 mL) and acetic acid (1.7 mL) was added iron (250 mg, 4.5 mmol) powder in one portion. The mixture was stirred at 0° C. for 1 h and then mixed with celite and filtered. The crude cake was washed with EtOAc. The brown filtrate was concentrated and mixed with EtOAc and NaHCO3/water. The aqueous phase was extracted once with EtOAc. The organic phases were combined and dried over Na2SO4. The volatiles were removed under vacuum to give the desired product (0.45 g, 100%). LCMS for C16H13Cl2N5O2S (M+H)+: m/z=410.0, 411.9. 1H NMR (400 MHz, DMSO-d6): δ 9.57 (s, 1H), 9.42 (s, 1H), 8.33 (s, 1H), 8.16 (s, 1H), 7.91 (s, 1H), 7.29 (dd, J=7.9, 7.6 Hz, 1H), 7.15 (d, J=7.9 Hz, 1H), 7.10-7.05 (m, 2H), 6.90 (dd, J=8.2, 0.9 Hz, 1H), 6.84-6.81 (m, 1H), 4.11 (s, 2H).
Reaction SMILES: Cl[C:2]1[C:3]2[S:10][C:9]([C:11]([NH:13][CH2:14][CH2:15][N:16]3[CH2:21][CH2:20][O:19][CH2:18][CH2:17]3)=[O:12])=[CH:8][C:4]=2[N:5]=[CH:6][N:7]=1.[F:22][C:23]1[CH:28]=[C:27]([N+:29]([O-:31])=[O:30])[CH:26]=[CH:25][C:24]=1[OH:32].C([O-])([O-])=O.[K+].[K+].CO.C(Cl)Cl>O(C1C=CC=CC=1)C1C=CC=CC=1>[F:22][C:23]1[CH:28]=[C:27]([N+:29]([O-:31])=[O:30])[CH:26]=[CH:25][C:24]=1[O:32][C:2]1[C:3]2[S:10][C:9]([C:11]([NH:13][CH2:14][CH2:15][N:16]3[CH2:21][CH2:20][O:19][CH2:18][CH2:17]3)=[O:12])=[CH:8][C:4]=2[N:5]=[CH:6][N:7]=1
Reactant: O=[N+]([O-])c1ccc(O)c(F)c1
Reactant: O=C(NCCN1CCOCC1)c1cc2ncnc(Cl)c2s1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: c1ccc(Oc2ccccc2)cc1
Solvent: CO
Solvent: ClCCl
Product: O=C(NCCN1CCOCC1)c1cc2ncnc(Oc3ccc([N+](=O)[O-])cc3F)c2s1
Temperature: 120 °C
Yield: 91 %

Procedure:
To a stirred solution of compound 23 (458 mg, 1.40 mmol) in Ph2O (6 mL) was added 2-fluoro-4-nitrophenol (242 mg, 1.54 mmol). The reaction mixture was heated at 120° C. for 2.5 hours, treated with K2CO3 (80 mg, 0.56 mmol) and heated at the same temperature for additional 18 hours. After cooling, the reaction mixture was purified by flash chromatography on a silica gel column (eluents EtOAc-hexane 5:95, 1:1, then MeOH-DCM, 5:95 and 1:9), to afford the title compound 24 (570 mg, 91% yield) as a yellow solid. NMR (400 MHz, CDCl3) δ(ppm): 9.09 (t, J=5.6 Hz, 1H), 8.77 (s, 1H), 8.41 (dd, J=2.4 and 10.4 Hz, 1H), 8.30 (s, 1H), 8.22 (dd, J=2.4 and 8.8 Hz, 1H), 7.88 (t, J=8.8 Hz, 1H), 3.60-3.52 (m, 4H), 3.45 (q, J=6.8 Hz, 2H), 2.50 (q, J=6.8 Hz, 2H), 2.46-2.40 (m, 4H).
Reaction SMILES: [CH2:1]([N:7]1[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH:9]=[CH:8]1)[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6].[Cl-].C[Al+]C.[CH3:20][O:21][C:22](=[O:29])[CH2:23][CH2:24][CH2:25][C:26](Cl)=[O:27].[Cl-].[NH4+]>C(Cl)Cl.CCCCCC.C(OCC)(=O)C>[CH3:20][O:21][C:22](=[O:29])[CH2:23][CH2:24][CH2:25][C:26]([C:9]1[C:10]2[C:15](=[CH:14][CH:13]=[CH:12][CH:11]=2)[N:7]([CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH3:6])[CH:8]=1)=[O:27]
Reactant: CCCCCCn1ccc2ccccc21
Reactant: COC(=O)CCCC(=O)Cl
Agent: C[Al+]C
Agent: [Cl-]
Agent: [NH4+]
Solvent: ClCCl
Solvent: CCCCCC
Solvent: CCOC(C)=O
Product: CCCCCCn1cc(C(=O)CCCC(=O)OC)c2ccccc21
Reaction time: 0.5 h

Procedure:
To a solution of 1-hexyl-1H-indole in methylene chloride at 0° C. was added dimethyl aluminum chloride solution in hexane. The reaction mixture was stirred for 30 minutes. To the above reaction mixture was added 4-chlorocarbonyl-butyric acid methyl ester at 0° C. and the reaction mixture was stirred for 3 hours. The reaction was treated with saturated ammonium chloride and ethyl acetate. The product was purified by column chromatography.
Reaction SMILES: ClC1C=CC(=O)N(C2C=CC(CC3N([CH2:20][C:21]4[CH:26]=[C:25]([C:27]5[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=5)[C:24]([C:33]#[N:34])=[CH:23][CH:22]=4)C=NC=3)=CN=2)C=1.[Li+].[BH4-].C1C[O:41]CC1>>[OH:41][CH2:20][C:21]1[CH:26]=[C:25]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[C:24]([C:33]#[N:34])=[CH:23][CH:22]=1
Reactant: N#Cc1ccc(Cn2cncc2Cc2ccc(-n3cc(Cl)ccc3=O)nc2)cc1-c1ccccc1
Reactant: C1CCOC1
Agent: [BH4-]
Agent: [Li+]
Product: N#Cc1ccc(CO)cc1-c1ccccc1
Temperature: 70 °C

Procedure:
6-Cyano-biphenyl-3-carboxylic acid methyl ester from step 2 (1.4 g, 5.9 mmol) was dissolved in THF (24 ml). LiBH4 in THF (2 M, 5.9 ml, 11.8 mmol) was added. The reaction mixture was heated to 70° C. for 3 hours. The reaction mixture was quenched carefully with 3N HCl and then extracted with EtOAc (3×20 mL). The organic layers were combined, washed with brine, dried (MgSO4), filtered and concentrated to yield the desired product.
Reaction SMILES: [CH3:1][C:2]1[CH:8]=[C:7]([CH3:9])[CH:6]=[C:5]([CH3:10])[C:3]=1[NH2:4].[O:11]1[CH:13]([CH3:14])[CH2:12]1>>[OH:11][CH:13]([CH3:14])[CH2:12][NH:4][C:3]1[C:5]([CH3:10])=[CH:6][C:7]([CH3:9])=[CH:8][C:2]=1[CH3:1]
Reactant: Cc1cc(C)c(N)c(C)c1
Reactant: CC1CO1
Product: Cc1cc(C)c(NCC(C)O)c(C)c1
Yield: 45.1 %

Procedure:
2,4,6-Trimethylaniline is reacted with 1,2-epoxypropane as described in Example 3, Method (b), point (a) to obtain N-(β-hydroxy-propyl)-2,4,6-trimethyl-aniline with a yield of 45.1%, b.p.: 130°-135° C./0.4 mm Hg.
Reaction SMILES: O.O.O.C([O-])(=[O:6])C.[Na+].[CH3:9][O:10][C:11]1[CH:12]=[C:13]([C:17]2[CH2:21][CH2:20][CH2:19][CH:18]=2)[CH:14]=[CH:15][CH:16]=1>C(OO)(=O)C.ClCCl>[CH3:9][O:10][C:11]1[CH:12]=[C:13]([C:17]23[O:6][CH:21]2[CH2:20][CH2:19][CH2:18]3)[CH:14]=[CH:15][CH:16]=1
Reactant: COc1cccc(C2=CCCC2)c1
Reactant: CC(=O)[O-]
Agent: CC(=O)OO
Agent: [Na+]
Solvent: ClCCl
Solvent: O
Product: COc1cccc(C23CCCC2O3)c1
Temperature: 25 °C
Reaction time: 3 h
Yield: 298 %

Procedure:
A solution of sodium acetate trihydrate (6 g) in peracetic acid (38 ml) was added dropwise to a stirred solution of 1-(3-methoxyphenyl) cyclopentene (33.5 g) in dichloromethane (200 ml), maintaining the temperature in the range 0°-10°. The solution was stirred for 3 hours at room temperature and then washed with 8% aqueous sodium bicarbonate (700 ml) and 8% sodium thiosulphate solution (400 ml). The organic phase was separated, dried and evaporated and the residue was distilled in vacuo to give the title compound as a colourless oil (25 g) b.p. 89°-92° (0.01 mm).
Reaction SMILES: [Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([N:12]2[C:16]([C:17]3[C:22]([O:23]C)=[CH:21][CH:20]=[CH:19][C:18]=3[O:25]C)=[CH:15][C:14]([C:27]([NH:29][CH:30]([CH2:34][CH2:35][CH2:36][CH3:37])[C:31]([OH:33])=[O:32])=[O:28])=[N:13]2)=[CH:4][CH:3]=1.B(Br)(Br)Br.O.[OH-].[Na+]>ClCCl>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([N:12]2[C:16]([C:17]3[C:18]([OH:25])=[CH:19][CH:20]=[CH:21][C:22]=3[OH:23])=[CH:15][C:14]([C:27]([NH:29][C@@H:30]([CH2:34][CH2:35][CH2:36][CH3:37])[C:31]([OH:33])=[O:32])=[O:28])=[N:13]2)=[CH:4][CH:3]=1
Reactant: CCCCC(NC(=O)c1cc(-c2c(OC)cccc2OC)n(-c2ccc(Cl)c3ccccc23)n1)C(=O)O
Agent: BrB(Br)Br
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: ClCCl
Product: CCCC[C@H](NC(=O)c1cc(-c2c(O)cccc2O)n(-c2ccc(Cl)c3ccccc23)n1)C(=O)O
Temperature: -70 °C

Procedure:
0.3 g of 2-{[1-(4-chloro-1-naphthyl)-5-(2,6-dimethoxyphenyl)-3-pyrazolyl]carbonylamino}hexanoic acid is dissolved in 6.7 ml of dichloromethane and the mixtureis cooled to -70° C. 5.7 ml of boron tribromide, dissolved in 20 ml of dichlormethane, are added dropwise and the reaction mixture is left for2 hours at -70° C. It is allowed to return to room temperature, and 12 ml of water are then added while cooling. Concentrated NaOH is added topH 14. The aqueous phase is washed with ether and brought to pH 2, the product is extracted with ethyl acetate and the organic phase is dried over sodium sulphate, filtered and evaporated. The residue is crystallisedfrom diisopropyl ether.
Reaction SMILES: [Cl:1][C:2]([Cl:24])([Cl:23])[CH2:3][O:4][C:5](=[O:22])[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=1[CH2:12][S:13][C:14]1[CH:19]=[CH:18][C:17]([CH2:20][OH:21])=[CH:16][CH:15]=1.[F:25][C:26]([F:38])([F:37])[C:27]1[CH:32]=[CH:31][C:30]([CH2:33][C:34](O)=[O:35])=[CH:29][CH:28]=1>CN(C1C=CN=CC=1)C.C(Cl)Cl>[Cl:24][C:2]([Cl:1])([Cl:23])[CH2:3][O:4][C:5](=[O:22])[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=1[CH2:12][S:13][C:14]1[CH:19]=[CH:18][C:17]([CH2:20][O:21][C:34](=[O:35])[CH2:33][C:30]2[CH:29]=[CH:28][C:27]([C:26]([F:37])([F:25])[F:38])=[CH:32][CH:31]=2)=[CH:16][CH:15]=1
Reactant: O=C(OCC(Cl)(Cl)Cl)c1ccccc1CSc1ccc(CO)cc1
Reactant: O=C(O)Cc1ccc(C(F)(F)F)cc1
Agent: CN(C)c1ccncc1
Solvent: ClCCl
Product: O=C(Cc1ccc(C(F)(F)F)cc1)OCc1ccc(SCc2ccccc2C(=O)OCC(Cl)(Cl)Cl)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 109.4 %

Procedure:
2-(4-Hydroxymethyl-phenylsulfanylmethyl)-benzoic acid 2,2,2-trichloro-ethyl ester (70 mg, 0.173 mmol) was added to a stirred mixture of (4-trifluoromethyl-phenyl) acetic acid (39 mg, 0.190 mmol), EDCxHCl (50 mg, 0.259 mmol), DMAP (2.1 mg, 0.017 mmol) and DCM (3 mL). The reaction mixture was stirred at rt overnight, according to LC-MS analysis the reaction was uncomplete. Additional EDCxHCl (50 mg, 0.259 mmol), DMAP (2.1 mg, 0.017 mmol) and 2-(4-hydroxymethyl-phenylsulfanylmethyl)-benzoic acid 2,2,2-trichloro-ethyl ester (70 mg, 0.173 mmol) were added and the mixture was stirred for 3 h. More DCM was added and the mixture was washed with 0.25M HCl, the organic portion was dried through a phase separator and concentrated to give the titled compound (112 mg, 100%); Mass spectrum: M−H+ 590.
Reaction SMILES: [CH3:1][C:2]1[N:3]=[C:4]2[CH:14]=[CH:13][CH:12]=[C:11]([CH3:15])[N:5]2[C:6](=[O:10])[C:7]=1[CH2:8][CH3:9]>C(O)C>[CH3:1][C:2]1[N:3]=[C:4]2[CH2:14][CH2:13][CH2:12][CH:11]([CH3:15])[N:5]2[C:6](=[O:10])[C:7]=1[CH2:8][CH3:9]
Reactant: CCc1c(C)nc2cccc(C)n2c1=O
Solvent: CCO
Product: CCc1c(C)nc2n(c1=O)C(C)CCC2
Reaction time: 7 h
Yield: 99.5 %

Procedure:
4.04 g. of 2,6-dimethyl-3-ethyl-4-oxo-4H-pyrido(1,2-a)pyrimidine are dissolved in 50 ml. of ethanol and the solution is hydrogenated in the presence of 2 g. of Raney-nickel catalyst, previously washed to anhydrous with ethanol. Hydrogenation is performed under atmospheric pressure. In about seven hours the calculated amount of hydrogen is used up and the hydrogen consumption drops rapidly to zero. The catalyst is filtered off and the ethanol solution is evaporated. 4.10 g. (99.5%) of 2,6-dimethyl-3-ethyl-4-oxo-6,7,8,9-tetrahydro-4H-pyrido(1,2-a)pyrimidine are obtained as a pale-yellow non-crystallizing oil, which can be distilled under a pressure of 25 mmHg of 190° C.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[C:4]([CH3:9])[CH:3]=1.[C:10]([O-])([O-])=O.[K+].[K+].IC>C1COCC1>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:10])=[C:4]([CH3:9])[CH:3]=1
Reactant: Cc1cc(Br)ccc1O
Reactant: O=C([O-])[O-]
Agent: [K+]
Solvent: C1CCOC1
Solvent: CI
Product: COc1ccc(Br)cc1C
Temperature: 25 °C
Yield: 67 %

Procedure:
Under nitrogen, to a stirred suspension of 38.9 g (208 mmol) of 4-bromo-2-methylphenol and 43.1 g (312 mmol) of K2CO3 powder in 300 mL of THF was added 39 mL (624 mmol) of iodomethane. The mixture was heated to reflux overnight, and cooled to ambient temperature. The inorganic salts were removed by filtration, and the organic solvent was removed in vacuo. The residue was dissolved in ethyl acetate, washed with water and brine, and dried over MgSO4. Purification by silica gel plug with ethyl acetate/hexane (5:95) gave 28 g (67%) of 4-bromo-2-methylanisole as a colorless solid: mp 65.0-66.0° C.; NMR (CDCl3) δ 2.18 (s, 3H), 3.80 (s, 3H), 6.67 (d, J=9 Hz, 1H), 7.22-7.28 (m, 2H).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][CH:7]=[C:6]2[O:15][C:16]1[C:17]([F:29])=[C:18]2[C:23](=[CH:24][CH:25]=1)[C:22]([C:26](Cl)=[O:27])=[CH:21][CH:20]=[CH:19]2.[CH2:30]([NH2:32])[CH3:31]>C1COCC1>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][CH:7]=[C:6]2[O:15][C:16]1[C:17]([F:29])=[C:18]2[C:23](=[CH:24][CH:25]=1)[C:22]([C:26]([NH:32][CH2:30][CH3:31])=[O:27])=[CH:21][CH:20]=[CH:19]2
Reactant: CCN
Reactant: COc1cc2nccc(Oc3ccc4c(C(=O)Cl)cccc4c3F)c2cc1OC
Solvent: C1CCOC1
Product: CCNC(=O)c1cccc2c(F)c(Oc3ccnc4cc(OC)c(OC)cc34)ccc12

Procedure:
6-(6,7-Dimethoxyquinolin-4-yloxy)-5-fluoro-1-naphthoyl chloride (70 mg) was stirred in a solution of 2M EtNH2 in THF (3 mL) at RT for 4 days. Solvent was evaporated and residue purified by prep plate using 5% MeOH in CH2Cl2 as the eluent. The solid obtained was rinsed with ether and dried to afford the title compound. MS (ESI pos. ion) m/z: 421.1 (M+H). Calc'd for C24H21FN2O4−420.43.
Reaction SMILES: S(Cl)(Cl)=O.C(O[CH:8]([O:13][CH2:14][CH3:15])[CH2:9][C:10]([OH:12])=O)C.[CH3:16][O:17][C:18]1[CH:19]=[C:20]([NH2:27])[CH:21]=[CH:22][C:23]=1[N+:24]([O-:26])=[O:25].N1C=CC=CC=1.Cl>ClCCl>[CH2:14]([O:13]/[CH:8]=[CH:9]/[C:10]([NH:27][C:20]1[CH:21]=[CH:22][C:23]([N+:24]([O-:26])=[O:25])=[C:18]([O:17][CH3:16])[CH:19]=1)=[O:12])[CH3:15]
Reactant: COc1cc(N)ccc1[N+](=O)[O-]
Reactant: CCOC(CC(=O)O)OCC
Agent: Cl
Solvent: ClCCl
Solvent: O=S(Cl)Cl
Solvent: c1ccncc1
Product: CCO/C=C/C(=O)Nc1ccc([N+](=O)[O-])c(OC)c1
Temperature: 80 °C
Reaction time: 8 h
Yield: 109.7 %

Procedure:
Thionyl chloride (1 mL) was added to 3,3-diethoxy-propionic acid (Eur. J. Org. Chem. 2001, 2041) (0.20 g, 1.10 mmol) and the resulting mixture was heated at 80° C. for 1 hour. The reaction mixture was then evaporated under reduced pressure and the residue was dissolved in dichloromethane (2 mL). The resulting solution was added to a mixture of 3-methoxy-4-nitro-phenylamine (0.13 g, 0.77 mmol) and pyridine (0.12 g, 1.54 mmol) in dichloromethane (5 mL) at 0° C. The reaction mixture was stirred at room temperature overnight and then the pH was then neutralized by addition of an aqueous solution of hydrochloric acid (6 M). The resulting mixture was extracted twice with ethyl acetate and the combined organic extracts were washed with water, dried over anhydrous sodium sulfate, filtered and evaporated under reduced pressure to give 225 mg of (E)-3-ethoxy-N-(3-methoxy-4-nitro-phenyl)-acrylamide as an orange solid.