Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:48]=[CH:49][C:50]=1[O:51][CH3:52])[CH2:6][O:7][CH2:8][C@@H:9]([O:22][CH2:23]/[CH:24]=[C:25](/[CH3:47])\[CH2:26][CH2:27]/[CH:28]=[CH:29]/[C:30]([CH3:46])([CH3:45])[CH2:31][CH2:32][C:33](=[CH2:44])[CH2:34]/[CH:35]=[C:36](\[CH3:43])/[CH2:37][CH2:38][CH:39]=[C:40]([CH3:42])[CH3:41])[CH2:10][O:11][Si](C(C)C)(C(C)C)C(C)C.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>O1CCCC1.[Cl-].[Na+].O>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:48]=[CH:49][C:50]=1[O:51][CH3:52])[CH2:6][O:7][CH2:8][C@@H:9]([O:22][CH2:23]/[CH:24]=[C:25](/[CH3:47])\[CH2:26][CH2:27]/[CH:28]=[CH:29]/[C:30]([CH3:46])([CH3:45])[CH2:31][CH2:32][C:33](=[CH2:44])[CH2:34]/[CH:35]=[C:36](\[CH3:43])/[CH2:37][CH2:38][CH:39]=[C:40]([CH3:41])[CH3:42])[CH2:10][OH:11]
Reactant: C=C(C/C=C(\C)CCC=C(C)C)CCC(C)(C)/C=C/CC/C(C)=C\CO[C@H](COCc1ccc(OC)c(OC)c1)CO[Si](C(C)C)(C(C)C)C(C)C
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [Cl-]
Agent: [F-]
Solvent: C1CCOC1
Solvent: O
Product: C=C(C/C=C(\C)CCC=C(C)C)CCC(C)(C)/C=C/CC/C(C)=C\CO[C@@H](CO)COCc1ccc(OC)c(OC)c1
Reaction time: 1 h
Yield: 96.7 %

Procedure:
To a solution of (R)-3-(3,4-dimethoxybenzyloxy)-1-triisopropylsiloxy-2-[(2Z,6E,13E)-3,8,8,14,18-pentamethyl-11-methylene-nonadeca-2,6,13,17-tetraen-1-yloxy]-propane (8) (20.0 mg, 27.3 μmol, 1.00 eq.) in dry tetrahydrofuran (0.55 mL) was added 1 M tetrabutylammonium fluoride solution in tetrahydrofuran (41 μL, 40.9 μmol, 1.50 eq.) at 0° C. After being stirred at the same temperature for 1 h, the reaction mixture was poured into brine. The aqueous layer was extracted with two portions of ethyl acetate. The combined extract was washed with brine, dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by silica gel chromatography (hexane:ethyl acetate=55:45) to give (S)-3-(3,4-dimethoxybenzyloxy)-2-[(2Z,6E,13E)-3,8,8,14,18-pentamethyl-11-methylene-nonadeca-2,6,13,17-tetraen-1-yloxy]-1-propanol (9) (15.4 mg, 26.4 μmol, 97%) as a colorless oil.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([NH:15][N:16]=[C:17]([C:22](=[O:26])[CH2:23][O:24][CH3:25])[C:18]([O:20][CH3:21])=[O:19])=[C:11]([F:27])[CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:28]OC(OC)N(C)C>>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([N:15]2[CH:28]=[C:23]([O:24][CH3:25])[C:22](=[O:26])[C:17]([C:18]([O:20][CH3:21])=[O:19])=[N:16]2)=[C:11]([F:27])[CH:10]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: COCC(=O)C(=NNc1ccc(OCc2ccccc2)cc1F)C(=O)OC
Reactant: COC(OC)N(C)C
Product: COC(=O)c1nn(-c2ccc(OCc3ccccc3)cc2F)cc(OC)c1=O
Temperature: 25 °C
Yield: 93 %

Procedure:
A solution of methyl 2-{[4-(benzyloxy)-2-fluorophenyl]hydrazono}-4-methoxy-3-oxobutanoate (8.46 g, 22.6 mmol) in N,N-dimethylformamide dimethyl acetal (80 mL) was refluxed for 3 h. After cooling to room temperature, the reaction mixture was concentrated under reduced pressure. The residue was diluted with AcOEt, washed with water and brine, dried over MgSO4, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography eluting with THF and recrystallized from hexane/THF to give the title compound (8.12 g, 93% yield) as a white solid: mp 143-144° C.; 1H NMR (300 MHz, CDCl3): δ ppm 3.89 (3H, s), 3.96 (3H, s), 5.12 (2H, s), 6.83-6.91 (2H, m), 7.33-7.44 (5H, m), 7.48-7.54 (1H, m), 7.69 (1H, d, J=2.3 Hz). Anal. Calcd for C20H17FN2O5: C, 62.50; H, 4.46; N, 7.29. Found: C, 62.40; H, 4.59; N, 7.26.
Reaction SMILES: [CH:1]12[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH:2]1[NH:11][C:12](=[O:31])[C:13]([CH3:30])([N:15]([CH3:29])[S:16]([CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=1[N+:26]([O-:28])=[O:27])(=[O:18])=[O:17])[CH3:14])[CH2:8]2.[C:32](=O)=O.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.CI.[Cl-].[NH4+]>C1COCC1.CC(C)=O>[CH:1]12[CH2:8][CH:7]3[CH2:6][CH:5]([CH2:4][CH:3]([CH2:9]3)[CH:2]1[NH:11][C:12](=[O:31])[C:13]([CH3:14])([N:15]([CH3:29])[S:16]([CH:19]([C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=1[N+:26]([O-:28])=[O:27])[CH3:32])(=[O:18])=[O:17])[CH3:30])[CH2:10]2
Reactant: O=C=O
Reactant: CN(C(C)(C)C(=O)NC1C2CC3CC(C2)CC1C3)S(=O)(=O)Cc1ccccc1[N+](=O)[O-]
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Cl-]
Agent: [Li+]
Solvent: CI
Solvent: CC(C)=O
Solvent: C1CCOC1
Product: CC(c1ccccc1[N+](=O)[O-])S(=O)(=O)N(C)C(C)(C)C(=O)NC1C2CC3CC(C2)CC1C3
Temperature: -70 °C
Reaction time: 1 h
Yield: 19 %

Procedure:
N-(adamantane-2-yl)-2-methyl-2-(N-methyl-1-(2-nitrophenyl)methylsulfonamido)propanamide (100 mg, 0.23 mmol) was dissolved in THF (2 ml), and cooled to −70° C. by using Dry ice and acetone. 1M LiHMDS (0.46 ml, 0.46 mmol) in THF was added thereto, followed by stirring for 1 hour at −70° C. Then, the temperature was raised up to −40° C., and MeI (0.143 ml, 2.3 mmol) was added thereto, followed by stirring at room temperature for 4 hours. After the stirring for 4 hours, ammonium chloride solution (4 ml) was added thereto to quench the reaction. The organic layer was washed with ammonium chloride solution (4 ml) twice, and separated. The separated organic layer was dried with MgSO4, and filtered. Through vacuum distillation, the solvent was removed, and through column chromatography, N-(adamantane-2-yl)-2-methyl-2-(N-methyl-1-(2-nitrophenyl)ethylsulfonamido)propanamide (21 mg, 0.11 mmol, 19%) was obtained.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:14]=[C:13](I)[CH:12]=[CH:11][C:10]=1[N:16]1[S:20](=[O:22])(=[O:21])[N:19]([CH2:23][CH2:24][Si:25]([CH3:28])([CH3:27])[CH3:26])[C:18](=[O:29])[CH2:17]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:30]([Sn](CCCC)(CCCC)C=C)[CH2:31]CC.C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.[F-].[K+]>C(#N)C.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]>[CH2:1]([O:8][C:9]1[CH:14]=[C:13]([CH:30]=[CH2:31])[CH:12]=[CH:11][C:10]=1[N:16]1[S:20](=[O:22])(=[O:21])[N:19]([CH2:23][CH2:24][Si:25]([CH3:28])([CH3:27])[CH3:26])[C:18](=[O:29])[CH2:17]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: C[Si](C)(C)CCN1C(=O)CN(c2ccc(I)cc2OCc2ccccc2)S1(=O)=O
Reactant: C=C[Sn](CCCC)(CCCC)CCCC
Agent: [Pd]
Agent: Cc1ccccc1P(c1ccccc1C)c1ccccc1C
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Solvent: CC#N
Product: C=Cc1ccc(N2CC(=O)N(CC[Si](C)(C)C)S2(=O)=O)c(OCc2ccccc2)c1
Temperature: 80 °C
Reaction time: 18 h

Procedure:
To a solution of 5-(2-benzyloxy-4-iodophenyl)-1,1-dioxo-2-(2-trimethylsilanylethyl)-1,2,5-thiadiazolidin-3-one (2.24 g, 4.1 mmol) in acetonitrile (41 mL), in a pressure vessel, is added tributyl(vinyl)tin (1.43 mL, 4.9 mmol), Pd2(dba)3 (73 mg, 0.16 mmol), and tri-o-tolylphosphine. The vessel is sealed and the mixture is stirred at 80° C. for 18 h. The reaction is allowed to cool to RT, then stirred vigorously with saturated KF (10 mL) for 15 min. The mixture is filtered through Celite, washing several times with acetonitrile. The solvent is removed under reduced pressure and the crude residue is purified via silica gel chromatography using a gradient of 0-40% EtOAc/hexanes to give the title compound as a colorless oil: (M+NH4)+=462.
Reaction SMILES: [Br:1][C:2]1[CH:11]=[C:10]([NH2:12])[C:9]([NH2:13])=[C:8]2[C:3]=1[CH2:4][CH2:5][N:6]([CH2:14][CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[CH2:7]2.[C:22](O)(=[O:26])[C:23](O)=[O:24]>Cl>[Br:1][C:2]1[C:3]2[CH2:4][CH2:5][N:6]([CH2:14][CH2:15][C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[CH2:7][C:8]=2[C:9]2[NH:13][C:22](=[O:26])[C:23](=[O:24])[NH:12][C:10]=2[CH:11]=1
Reactant: Nc1cc(Br)c2c(c1N)CN(CCc1ccccc1)CC2
Reactant: O=C(O)C(=O)O
Agent: Cl
Product: O=c1[nH]c2cc(Br)c3c(c2[nH]c1=O)CN(CCc1ccccc1)CC3
Temperature: 25 °C
Yield: 59.3 %

Procedure:
A solution of the product from Example 10 (0.54 g, 1.56 mmol) in 3N HCl (20 mL) was treated with oxalic acid (0.3 g, 2.34 mmol) and refluxed for four hours. When cool to room temperature the precipitate was filtered, suspended in water (70 mL) and basifyed to pH 10. The solids were filtered, and dried to give the title compound (0.37 g, 60%) as a brown solid, mp=290-295° C.
Reaction SMILES: F[C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[N+:9]([O-:11])=[O:10].C(N(CC)CC)C.[CH2:19]([NH2:22])[C:20]#[CH:21].O>O1CCOCC1>[CH2:19]([NH:22][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[N+:9]([O-:11])=[O:10])[C:20]#[CH:21]
Reactant: C#CCN
Reactant: O=[N+]([O-])c1cc(F)ccc1F
Solvent: CCN(CC)CC
Solvent: C1COCCO1
Solvent: O
Product: C#CCNc1ccc(F)cc1[N+](=O)[O-]
Temperature: 25 °C
Reaction time: 4 h
Yield: 54.8 %

Procedure:
To a stirred solution of 15.0 grams (0.094 mole) of 2,5-difluoronitrobenzene in 250 mL of dioxane was added 100 mL of triethylamine, followed by 7.3 grams (0.132 mole) of 2-propyn-1-ylamine. The reaction mixture was then warmed to reflux, where it was stirred for about four hours, then cooled to ambient temperature and poured into cold water. The resultant solid precipitate was collected by filtration and dried, yielding 10.0 grams of N-(2-propyn-1-yl)-4-fluoro-2-nitroaniline. The NMR spectrum was consistent with the proposed structure.
Reaction SMILES: [CH2:1]([NH:3][C:4]([C:6]1[C:10](I)=[C:9]([C:12]2[CH:17]=[C:16]([CH2:18][CH:19]([CH3:21])[CH3:20])[C:15]([O:22][CH2:23][C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)=[CH:14][C:13]=2[O:30][CH2:31][C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[O:8][N:7]=1)=[O:5])[CH3:2].C([O-])([O-])=O.[Na+].[Na+].[CH:44]([C:46]1[CH:51]=[CH:50][C:49](B(O)O)=[CH:48][CH:47]=1)=[O:45]>CN(C=O)C.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>[CH2:1]([NH:3][C:4]([C:6]1[C:10]([C:49]2[CH:50]=[CH:51][C:46]([CH:44]=[O:45])=[CH:47][CH:48]=2)=[C:9]([C:12]2[CH:17]=[C:16]([CH2:18][CH:19]([CH3:21])[CH3:20])[C:15]([O:22][CH2:23][C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)=[CH:14][C:13]=2[O:30][CH2:31][C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[O:8][N:7]=1)=[O:5])[CH3:2]
Reactant: O=Cc1ccc(B(O)O)cc1
Reactant: CCNC(=O)c1noc(-c2cc(CC(C)C)c(OCc3ccccc3)cc2OCc2ccccc2)c1I
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CCNC(=O)c1noc(-c2cc(CC(C)C)c(OCc3ccccc3)cc2OCc2ccccc2)c1-c1ccc(C=O)cc1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
5-(2,4-Bis-benzyloxy-5-isobutyl-phenyl)-4-iodo-isoxazole-3-carboxylic acid ethylamide (1 eq) was dissolved in DMF and 1M Na2CO3 (aq) (3 eq) was added, followed by 4-formylphenylboronic acid (2 eq) and catalytic PdCl2(PPh3)2. Nitrogen was bubbled through the solution for ten minutes at ambient temperature, after which time, the temperature was elevated to 80° C. under a nitrogen atmosphere, for 2 hours. The reaction mixture was allowed to cool to room temperature and the reaction mixture was diluted with ethyl acetate. This solution was washed with brine, then dried over magnesium sulfate, filtered and concentrated in vacuo to give an oil which was purified by column chromatography, eluting with 10% EtOAc in hexane, to give 5-(2,4-bis-benzyloxy-5-isobutyl-phenyl)-4-(4-formyl-phenyl)-isoxazole-3-carboxylic acid ethylamide as a white solid.
Reaction SMILES: Cl[C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[CH3:11])=[C:4]([NH:12][C:13]2[CH:18]=[CH:17][C:16]([Cl:19])=[CH:15][CH:14]=2)[N:3]=1.[Cl:20][C:21]1[C:22]([CH3:26])=[N:23][NH:24][CH:25]=1>>[Cl:20][C:21]1[C:22]([CH3:26])=[N:23][N:24]([C:2]2[N:10]=[C:9]3[C:5]([N:6]=[CH:7][N:8]3[CH3:11])=[C:4]([NH:12][C:13]3[CH:18]=[CH:17][C:16]([Cl:19])=[CH:15][CH:14]=3)[N:3]=2)[CH:25]=1
Reactant: Cn1cnc2c(Nc3ccc(Cl)cc3)nc(Cl)nc21
Reactant: Cc1n[nH]cc1Cl
Product: Cc1nn(-c2nc(Nc3ccc(Cl)cc3)c3ncn(C)c3n2)cc1Cl

Procedure:
Was prepared according to Example 6 from (2-chloro-9-methyl-9H-purin-6-yl)-(4-chloro-phenyl)-amine and 4-chloro-3-methyl-1H-pyrazole.
Reaction SMILES: [CH3:1][O:2][CH2:3][CH2:4][O:5][CH2:6][O:7][C:8]1[CH:13]=[CH:12][C:11]([N+:14]([O-])=O)=[CH:10][CH:9]=1>CO.[Pd]>[CH3:1][O:2][CH2:3][CH2:4][O:5][CH2:6][O:7][C:8]1[CH:9]=[CH:10][C:11]([NH2:14])=[CH:12][CH:13]=1
Reactant: COCCOCOc1ccc([N+](=O)[O-])cc1
Agent: [Pd]
Solvent: CO
Product: COCCOCOc1ccc(N)cc1
Yield: 98 %

Procedure:
To a suspension of Pd/C (0.5 g) in methanol (25 mL), 1-[(2-methoxyethoxy)methoxy]-4-nitrobenzene (2.35 g) was added to a 50 mL 3-neck RBF at room temperature under nitrogen atmosphere. Hydrogen gas was bubbled through the reaction mixture for 1-2 hr at room temperature and the reaction was monitored on TLC using chloroform:methanol (9.8:0.2) as mobile phase. After completion, the reaction mixture was filtered using Celite and washed with methanol. The combined filtrate was concentrated under reduced pressure at 40° C. to give 2.0 g of 4-[(2-methoxyethoxy)methoxy]aniline as a dark brown liquid.
Reaction SMILES: Cl[CH2:2][CH2:3][CH2:4][S:5]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[C:22]3[C:17](=[C:18]([C:29]([NH2:31])=[O:30])[CH:19]=[C:20]([C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=4)[CH:21]=3)[NH:16][N:15]=2)[CH2:10][CH2:9]1)(=[O:7])=[O:6].C([O-])([O-])=O.[K+].[K+].[NH:38]1[CH2:43][CH2:42][NH:41][CH2:40][CH2:39]1.[I-].[Na+]>C(#N)C>[C:23]1([C:20]2[CH:21]=[C:22]3[C:17](=[C:18]([C:29]([NH2:31])=[O:30])[CH:19]=2)[NH:16][N:15]=[C:14]3[CH:11]2[CH2:12][CH2:13][N:8]([S:5]([CH2:4][CH2:3][CH2:2][N:38]3[CH2:43][CH2:42][NH:41][CH2:40][CH2:39]3)(=[O:7])=[O:6])[CH2:9][CH2:10]2)[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1
Reactant: C1CNCCN1
Reactant: NC(=O)c1cc(-c2ccccc2)cc2c(C3CCN(S(=O)(=O)CCCCl)CC3)n[nH]c12
Agent: O=C([O-])[O-]
Agent: [I-]
Agent: [K+]
Solvent: CC#N
Product: NC(=O)c1cc(-c2ccccc2)cc2c(C3CCN(S(=O)(=O)CCCN4CCNCC4)CC3)n[nH]c12
Temperature: 60 °C
Reaction time: 0 h
Yield: 49.5 %

Procedure:
To a solution of 3-{1-[(3-chloropropyl)sulfonyl]-4-piperidinyl}-5-phenyl-1H-indazole-7-carboxamide (Intermediate 22) (20 mg, 0.0435 mmol) in acetonitrile (1 mL) was added K2CO3 (27 mg, 0.174 mmol), piperazine (18.9 mg, 0.219 mmol) and sodium iodide (0.8 mg, 0.00435 mmol). The reaction mixture was heated to 60° C. for 14 hrs. The solution was filtered and concentrated. The residue was purified by using a Gilson semi-preparative HPLC system with a YMC ODS-A (C-18) column 50 mm by 20 mm ID, eluting with 10% B to 80% B in 10 min, hold for 0.1 min where A=H2O (0.1% trifluoroacetic acid) and B=CH3CN (0.1% trifluoroacetic acid) pumped at 25 mL/min to afford the title compound (11.0 mg, 49%).
Reaction SMILES: [NH2:1][C:2]1[C:11](/[CH:12]=[CH:13]/[C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])=[CH:10][C:9]2[CH2:8][CH2:7][CH2:6][CH2:5][C:4]=2[C:3]=1[C:21]([O:23][CH3:24])=[O:22].[C:25]1([S:31](Cl)(=[O:33])=[O:32])[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1>N1C=CC=CC=1>[C:17]([O:16][C:14](=[O:15])/[CH:13]=[CH:12]/[C:11]1[C:2]([NH:1][S:31]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)(=[O:33])=[O:32])=[C:3]([C:21]([O:23][CH3:24])=[O:22])[C:4]2[CH2:5][CH2:6][CH2:7][CH2:8][C:9]=2[CH:10]=1)([CH3:20])([CH3:19])[CH3:18]
Reactant: O=S(=O)(Cl)c1ccccc1
Reactant: COC(=O)c1c(N)c(/C=C/C(=O)OC(C)(C)C)cc2c1CCCC2
Solvent: c1ccncc1
Product: COC(=O)c1c2c(cc(/C=C/C(=O)OC(C)(C)C)c1NS(=O)(=O)c1ccccc1)CCCC2
Temperature: 25 °C
Reaction time: 16 h
Yield: 70.7 %

Procedure:
A solution of Example 476B (0.12 g, 0.36 mmol) in pyridine (1 mL) was treated with benzenesulfonyl chloride (0.071 g, 0.40 mmol), and stirred for 16 hours at ambient temperature. The mixture was concentrated, diluted with 1M NaHSO4 and extracted with dichloromethane. The extract was dried (MgSO4), filtered, and concentrated. The concentrate was purified by flash chromatography eluting with 30% ethyl acetate/hexanes gave the desired product (0.12 g). MS (DCI) m/e 472 (M+H)+.
Reaction SMILES: [Cl:1][C:2]1[C:7]([Cl:8])=[CH:6][C:5]([NH2:9])=[C:4]([NH2:10])[CH:3]=1.C([O:15][C:16](=O)[CH2:17][C:18]([C:20]1[CH:25]=[CH:24][CH:23]=[C:22]([C:26]2[C:31]([CH2:32][CH3:33])=[CH:30][N:29]=[C:28]([CH3:34])[CH:27]=2)[CH:21]=1)=O)(C)(C)C>C1(C)C(C)=CC=CC=1>[Cl:1][C:2]1[C:7]([Cl:8])=[CH:6][C:5]2[NH:9][C:16](=[O:15])[CH2:17][C:18]([C:20]3[CH:25]=[CH:24][CH:23]=[C:22]([C:26]4[C:31]([CH2:32][CH3:33])=[CH:30][N:29]=[C:28]([CH3:34])[CH:27]=4)[CH:21]=3)=[N:10][C:4]=2[CH:3]=1
Reactant: Nc1cc(Cl)c(Cl)cc1N
Reactant: CCc1cnc(C)cc1-c1cccc(C(=O)CC(=O)OC(C)(C)C)c1
Solvent: Cc1ccccc1C
Product: CCc1cnc(C)cc1-c1cccc(C2=Nc3cc(Cl)c(Cl)cc3NC(=O)C2)c1

Procedure:
The title compound was prepared from commercially available 4,5-dichloro-1,2-phenylendiamine (133 mg, 0.75 mmol) and 3-[3-(5-ethyl-2-methyl-pyridin-4-yl)-phenyl]-3-oxo-propionic acid tert-butyl ester (Example K19) (255 mg, 0.75 mmol) in xylene (15 ml) under reflux conditions for 2 h according to the general procedure M. Obtained as a light brown solid (230 mg, 72%).
Reaction SMILES: [NH2:1][C:2]1[N:3]=[C:4]([C:11]([C:13]2[S:14][CH:15]=[CH:16][CH:17]=2)=[O:12])[C:5]2[S:10][CH:9]=[CH:8][C:6]=2[N:7]=1.N1C=CC=CC=1.[C:24](Cl)(=[O:26])[CH3:25]>O>[S:14]1[CH:15]=[CH:16][CH:17]=[C:13]1[C:11]([C:4]1[C:5]2[S:10][CH:9]=[CH:8][C:6]=2[N:7]=[C:2]([NH:1][C:24](=[O:26])[CH3:25])[N:3]=1)=[O:12]
Reactant: CC(=O)Cl
Reactant: Nc1nc(C(=O)c2cccs2)c2sccc2n1
Solvent: c1ccncc1
Solvent: O
Product: CC(=O)Nc1nc(C(=O)c2cccs2)c2sccc2n1
Temperature: 25 °C
Yield: 61 %

Procedure:
A mixture of 2-aminothieno[3,2-d]pyrimidin-4-yl 2-thienylmethanone (0.07 g, 0.27 mmol), anhydrous pyridine (3 mL) and acetyl chloride (0.15 g, 1.88 mmol) was refluxed for 24 h, cooled to room temperature, poured into water (30 mL) and extracted with EtOAc (2×30 mL). The organic phase was washed with 1-M HCl (2×25 mL) and saturated brine (25 mL), dried (MgSO4) and concentrated in vacuo to give a yellow solid which was purified by chromatography (SiO2; heptane-EtOAc (2:1)] to give the title compound (50 mg, 58%) as a yellow solid.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5](/[CH:8]=[CH:9]/[C:10](O)=[O:11])=[CH:4][C:3]=1[O:13][CH3:14].C(N(CC)CC)C.C1C=CC(P([N:36]=[N+:37]=[N-:38])(C2C=CC=CC=2)=O)=CC=1>C1C=CC=CC=1>[F:1][C:2]1[CH:7]=[CH:6][C:5](/[CH:8]=[CH:9]/[C:10]([N:36]=[N+:37]=[N-:38])=[O:11])=[CH:4][C:3]=1[O:13][CH3:14]
Reactant: COc1cc(/C=C/C(=O)O)ccc1F
Reactant: [N-]=[N+]=NP(=O)(c1ccccc1)c1ccccc1
Solvent: c1ccccc1
Solvent: CCN(CC)CC
Product: COc1cc(/C=C/C(=O)N=[N+]=[N-])ccc1F
Reaction time: 18 h
Yield: 70.9 %

Procedure:
To a solution of (E)-3-(4-fluoro-3-methoxyphenyl)acrylic acid (5 g, 25.5 mmol) in benzene (30 ml) was added triethylamine (5.16 g, 51 mmol) followed by DPPA (7.01 g, 25.5 mmol) at room temperature. The reaction mass was stirred at the same temperature for 18 h. The solvent was evaporated under reduced pressure and the residue was diluted with water and extracted with dichloromethane. The organic layer was dried over anhydrous sodium sulfate, filtered and evaporated to get crude compound. The crude compound was purified by conventional column chromatography (Silica gel, 60-120 mesh) using 10% ethyl acetate in pet ether as mobile phase to get the desire compound as white solid (4 g, 71%). 1H NMR (400 MHz, CDCl3): δ ppm 7.70-7.66 (d, J=16 Hz, 1H), 7.12-7.07 (m, 3H), 6.35-6.31 (d, J=16 Hz, 1H), 3.92 (s, 3H).
Reaction SMILES: [C:1]1([C:7]2[CH:12]=[C:11]([NH2:13])[CH:10]=[CH:9][N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C([O-])(=O)C.[Na+].[I:19]Cl.S([O-])([O-])(=O)=S.[Na+].[Na+].[OH-].[Na+]>C(O)(=O)C>[I:19][C:10]1[C:11]([NH2:13])=[CH:12][C:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)=[N:8][CH:9]=1
Reactant: Nc1ccnc(-c2ccccc2)c1
Reactant: ClI
Agent: CC(=O)[O-]
Agent: O=S([O-])([O-])=S
Agent: [Na+]
Solvent: CC(=O)O
Product: Nc1cc(-c2ccccc2)ncc1I
Temperature: 15 °C
Reaction time: 48 h
Yield: 56.9 %

Procedure:
To a stirred solution of 10.0 g (58.8 mmol) 2-phenyl-pyridin-4-ylamine in 300 ml glacial acetic acid was added 28.9 g (352 mmol) sodium acetate and the mixture was then cooled to 15° C. in an ice-bath and 19.1 g (118 mmol) iodine monochloride added in small portions (reaction slightly exothermic). The reaction mixture was stirred for 48 h at room temperature before being poured onto 500 ml 20% aq. sodium thiosulfate solution. The mixture was then made basic by addition of 5 N aq. sodium hydroxide solution and extracted three times with dichloromethane. The combined organic phases were washed with 20% aq. sodium thiosulfate solution, then dried over sodium sulfate and concentrated in vacuo. Flash chromatography (methanol/dichloromethane 3/97) followed by trituration in ether afforded 9.90 g (57%) 5-iodo-2-phenyl-pyridin-4-ylamine as an off-white solid. ES-MS m/e (%): 297 (M+H+, 100).
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][C:7]([C:10]2[C:14]([C:15]3[CH:20]=[CH:19][N:18]=[C:17]4[N:21](S(C5C=CC=CC=5)(=O)=O)[C:22]([C:24]5[CH:29]=[CH:28][CH:27]=[C:26]([CH2:30][N:31]([CH3:33])[CH3:32])[CH:25]=5)=[CH:23][C:16]=34)=[CH:13][N:12]([CH2:43][CH3:44])[N:11]=2)=[CH:6][CH:5]=1)([O-])=O>CC(O)=O.[Zn]>[NH2:1][C:4]1[CH:5]=[CH:6][C:7]([C:10]2[C:14]([C:15]3[CH:20]=[CH:19][N:18]=[C:17]4[NH:21][C:22]([C:24]5[CH:29]=[CH:28][CH:27]=[C:26]([CH2:30][N:31]([CH3:32])[CH3:33])[CH:25]=5)=[CH:23][C:16]=34)=[CH:13][N:12]([CH2:43][CH3:44])[N:11]=2)=[CH:8][CH:9]=1
Reactant: CCn1cc(-c2ccnc3c2cc(-c2cccc(CN(C)C)c2)n3S(=O)(=O)c2ccccc2)c(-c2ccc([N+](=O)[O-])cc2)n1
Agent: [Zn]
Solvent: CC(=O)O
Product: CCn1cc(-c2ccnc3[nH]c(-c4cccc(CN(C)C)c4)cc23)c(-c2ccc(N)cc2)n1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a stirred solution of 4-[3-(4-nitrophenyl)-1-ethyl-1H-pyrazol-4-yl]-2-[3-(dimethylaminomethyl)phenyl]-1-phenylsulfonyl-1H-pyrrolo[2,3-b]pyridine (1.1 mmol) in HOAc (20 mL) was added portionwise zinc dust (8.0 mmol) over 5 minutes. The reaction was stirred at room temperature for 1 h, filtered through a pad of Celite, rinsed with acetic acid, and concentrated to dryness under vacuum. The residue was re-evaporated several times from methanol/toluene to remove the excess acetic acid, taken up in methanol (35 mL) and treated with 6 N sodium hydroxide (1.5 mL). The reaction mixture was stirred and heated at 70° C. for 8 h. After cooling to room temperature the reaction was concentrated under vacuum, triturated with cold water, filtered, washed with water, and dried under vacuum to give the crude product as a pale orange solid: ESMS [M+H]+: 437.2
Reaction SMILES: [CH2:1]([O:3][C:4]([CH:6]1[CH2:19][C:9]2[NH:10][C:11]3[CH:12]=[CH:13][C:14]([O:17][CH3:18])=[CH:15][C:16]=3[C:8]=2[CH2:7]1)=[O:5])[CH3:2].[H-].[Na+].[CH3:22]I.O>CN(C)C=O>[CH2:1]([O:3][C:4]([CH:6]1[CH2:19][C:9]2[N:10]([CH3:22])[C:11]3[CH:12]=[CH:13][C:14]([O:17][CH3:18])=[CH:15][C:16]=3[C:8]=2[CH2:7]1)=[O:5])[CH3:2]
Reactant: CCOC(=O)C1Cc2[nH]c3ccc(OC)cc3c2C1
Reactant: CI
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: CCOC(=O)C1Cc2c(n(C)c3ccc(OC)cc23)C1
Temperature: 25 °C
Reaction time: 2 h
Yield: 91.5 %

Procedure:
To a solution of 1,2,3,4-tetrahydro-7-methoxycyclopent[b]indole-2-carboxylic acid ethyl ester (10 g, 0.04 mole) in 75 ml of dimethylformamide, was added sodium hydride (1.7 g, 60% in oil, 0.043 mole). After stirring at ambient temperature for two hours, a solution of methyl iodide (2.7 ml, 0.043 mole) in dimethylformamide (10 ml) was added, and the mixture was stirred at 70° C. for five hours. After cooling, the mixture was poured into 200 ml of water, stirred for five minutes, and extracted with ethyl acetate. The organic layer was washed successively with water (2×) and a saturated NaCl solution, and then dried over anhydrous MgSO4. After filtering, the solvent was evaporated to afford a dark oil (~10 g) which was eluted on a silica gel column with dichloromethane via HPLC. The desired fractions were combined and concentrated to give the product as a thick yellow oil, 6.8 g.
Reaction SMILES: [CH3:1][C:2](=[CH:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)[C:3]([N:5]1[C@@H:9]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[C@H:8]([C:16]([O:18]C)=[O:17])[O:7][CH:6]1[C:20]1[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[C:22]([O:28][CH3:29])[CH:21]=1)=[O:4].[Li+].[OH-].Cl>C1COCC1>[CH3:1][C:2](=[CH:30][C:31]1[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=1)[C:3]([N:5]1[C@@H:9]([C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=2)[C@H:8]([C:16]([OH:18])=[O:17])[O:7][CH:6]1[C:20]1[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[C:22]([O:28][CH3:29])[CH:21]=1)=[O:4]
Reactant: COC(=O)[C@@H]1OC(c2ccc(OC)c(OC)c2)N(C(=O)C(C)=Cc2ccccc2)[C@H]1c1ccccc1
Agent: Cl
Agent: [Li+]
Agent: [OH-]
Solvent: C1CCOC1
Product: COc1ccc(C2O[C@@H](C(=O)O)[C@H](c3ccccc3)N2C(=O)C(C)=Cc2ccccc2)cc1OC
Reaction time: 0.5 h

Procedure:
Compound 3 (25 g) in 125 ml of THF was added with 63 ml of 1N LiOH at room temperature. After 30 minutes, the mixture was adjusted to a pH of 2 by adding 1N HCl. After separation of the aqueous part, the organic part was washed with brine and dried over MgSO4. Removing the solvent under reduced pressure gave quantitatively Compound 4.