Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C([Sn](CCCC)(CCCC)[C:6]1[S:7][CH:8]=[CH:9][C:10]=1[CH:11]1[O:15][CH2:14][CH2:13][O:12]1)CCC.[N+:24]([C:27]1[CH:34]=[CH:33][CH:32]=[CH:31][C:28]=1[CH2:29]Br)([O-:26])=[O:25].CCCCCC>C1(C)C=CC=CC=1.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[N+:24]([C:27]1[CH:34]=[CH:33][CH:32]=[CH:31][C:28]=1[CH2:29][C:6]1[S:7][CH:8]=[CH:9][C:10]=1[CH:11]1[O:12][CH2:13][CH2:14][O:15]1)([O-:26])=[O:25]
Reactant: CCCC[Sn](CCCC)(CCCC)c1sccc1C1OCCO1
Reactant: O=[N+]([O-])c1ccccc1CBr
Agent: [Pd]
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CCCCCC
Solvent: Cc1ccccc1
Product: O=[N+]([O-])c1ccccc1Cc1sccc1C1OCCO1
Temperature: 25 °C

Procedure:
A mixture of 2-[2-(tributylstannyl)-3-thienyl]-1,3-dioxolane (8.8 gms, 20 mmols), 2-nitrobenzyl bromide (4.5 gms, 22 mmol) and tetrakis (triphenylphosphine)-palladium (0) (200 mg) is refluxed in degassed toluene for 16 hours under nitrogen atmosphere. At the end, the reaction mixture is cooled to room temperature and filtered through diatomaceous earth. The toluene is removed by concentrating at reduced pressure and the product isolated by silica gel column chromatography by elution with 30% ethyl acetate:hexane to give 4.5 gms. of the desired product as a viscous liquid. Mass Spectrum; M+ 292.
Reaction SMILES: [C:1]1([CH:7]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[N:8]2[CH2:13][CH2:12][N:11]([CH2:14][CH:15]3[O:17][CH2:16]3)[CH2:10][CH2:9]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH3:24][O:25][C:26]1[CH:27]=[C:28]([CH2:34][CH2:35][NH2:36])[CH:29]=[CH:30][C:31]=1[O:32][CH3:33].C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[CH3:24][O:25][C:26]1[CH:27]=[C:28]([CH2:34][CH2:35][NH:36][CH2:16][CH:15]([OH:17])[CH2:14][N:11]2[CH2:12][CH2:13][N:8]([CH:7]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)[CH2:9][CH2:10]2)[CH:29]=[CH:30][C:31]=1[O:32][CH3:33]
Reactant: COc1ccc(CCN)cc1OC
Reactant: c1ccc(C(c2ccccc2)N2CCN(CC3CO3)CC2)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: COc1ccc(CCNCC(O)CN2CCN(C(c3ccccc3)c3ccccc3)CC2)cc1OC
Yield: 24.5 %

Procedure:
3.08 g (0.01 mol) of 1-(diphenylmethyl)-4-(2,3-epoxypropyl)piperazine and 2 g (0.01 mol) of 2-(3,4-dimethoxyphenyl)ethylamine were refluxed with heating together with 200 ml of DMF for 24 hours in the presence of a catalytic amount of an alkali such as potassium carbonate. DMF was distilled off under reduced pressure, and a residue was extracted with ethyl acetate, and after washing with water and drying, the ethyl acetate was distilled off under reduced pressure to obtain 5.1 g of a crude subject compound of a viscous liquid. The obtained compound was refined by flush chromatography and fractional thin-layer chromatography with solvent mixtures of ethyl acetate--methanol and methylene chloride--methanol respectively to obtain 1.2 g of the subject compound in a viscous liquid state.
Reaction SMILES: [CH3:1][C:2]1[N:3]=[C:4]([N:12]2[CH2:16][CH2:15][NH:14][C:13]2=[O:17])[S:5][C:6]=1[C:7]([O:9][CH2:10][CH3:11])=[O:8].[F:18][CH:19]([F:27])[C:20]1[O:24][C:23]([CH2:25]O)=[CH:22][CH:21]=1.C(P(CCCC)CCCC)CCC.N(C(N(C)C)=O)=NC(N(C)C)=O>O1CCCC1>[F:18][CH:19]([F:27])[C:20]1[O:24][C:23]([CH2:25][N:14]2[CH2:15][CH2:16][N:12]([C:4]3[S:5][C:6]([C:7]([O:9][CH2:10][CH3:11])=[O:8])=[C:2]([CH3:1])[N:3]=3)[C:13]2=[O:17])=[CH:22][CH:21]=1
Reactant: OCc1ccc(C(F)F)o1
Reactant: CCOC(=O)c1sc(N2CCNC2=O)nc1C
Agent: CCCCP(CCCC)CCCC
Agent: CN(C)C(=O)N=NC(=O)N(C)C
Solvent: C1CCOC1
Product: CCOC(=O)c1sc(N2CCN(Cc3ccc(C(F)F)o3)C2=O)nc1C
Temperature: 0 °C
Reaction time: 0.17 h
Yield: 53 %

Procedure:
To the solution of ethyl 4-methyl-2-(2-oxoimidazolidin-1-yl)thiazole-5-carboxylate (0.35 g, 1.37 mmol) and (5-(difluoromethyl)furan-2-yl)methanol (0.20 g, 1.37 mmol) in anhydrous tetrahydrofuran (10 mL) was added dropwise tributylphosphine (0.51 mL, 2.06 mmol) at 0° C. The reaction mixture was stirred at 0° C. for 10 minutes and followed by the addition of 1,1′-azobis(N,N-dimethylformamide) (0.35 g, 2.06 mmol). The reaction mixture was stirred at ambient temperature for 18 hours, quenched with saturated aqueous ammonium chloride solution and extracted with ethyl acetate (4×20 mL). The organic solutions were combined, dried over anhydrous sodium sulphate, filtered and concentrated in vacuo. The residue was purified by column chromatography eluted with ethyl acetate/hexane (1/4) to afford the title compound as a white solid in 53% yield (0.25 g): 1H NMR (300 MHz, CDCl3) δ 6.60-6.50 (m, 1H), 6.52 (t, JH-F=54.2 Hz, 1H), 6.37-6.29 (m, 1H), 4.45 (s, 2H), 4.21 (q, J=7.1 Hz, 2H), 4.09-3.98 (m, 2H), 3.60-3.49 (m, 2H), 2.54 (s, 3H), 1.27 (t, J=7.1 Hz, 3H); MS (ES+) m/z 386.3 (M+1).
Reaction SMILES: C(N(CC)CC)C.Br[CH2:9][C:10]([C:12]1[CH:17]=[CH:16][C:15]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[CH:14][CH:13]=1)=O.[C:24]([NH:27][N:28]=[CH:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)(=[NH:26])[NH2:25]>C(O)C>[NH2:26][C:24]1[N:27]([N:28]=[CH:29][C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[CH:9]=[C:10]([C:12]2[CH:17]=[CH:16][C:15]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)=[CH:14][CH:13]=2)[N:25]=1
Reactant: O=C(CBr)c1ccc(-c2ccccc2)cc1
Reactant: N=C(N)NN=Cc1ccccc1
Solvent: CCN(CC)CC
Solvent: CCO
Product: Nc1nc(-c2ccc(-c3ccccc3)cc2)cn1N=Cc1ccccc1
Temperature: 20 °C
Reaction time: 15 h

Procedure:
7 ml (0.0507 mol) of triethylamine and 13.75 g (0.050 mol) of 2-bromo-4'-phenylaceto-phenone (Aldrich, Buchs, Switzerland; tech., Cat. no. 10,108-7) are added to a solution of 8.11 g (0.05 mol) of benzaldehyde guanylhydrazone in 40 ml of ethanol. The reaction mixture is stirred at 20° C. for 15 hours and is filtered, and the crystallizate is taken up in methylene chloride and acidified to pH 1 with 1N hydrochloric acid. After filtration, the filtration product is taken up in methanol, and 2N sodium hydroxide solution is added until a basic reaction is obtained (pH 11). Filtration is carried out and the crystalline product is washed with methanol/water (1:1). The title compound so obtained melts at 254°-255° C. (decomp.), 1H-NMR (DMSO): δ=8.60 (s, 1H); 8.10 (s, 1H); 7.93-7.98 (m, 2H); 7.67-7.83 (m, 6H); 7.32-7.55 (m, 6H); 6.24 (s, 2H).
Reaction SMILES: [C:1]([C:3]1[CH:8]=[C:7]([CH2:9][CH2:10][C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH:6]=[C:5]([CH3:18])[N:4]=1)#[N:2].[Cl:19][C:20]1[CH:21]=[C:22]([SH:29])[C:23](=[CH:27][CH:28]=1)[C:24](O)=[O:25]>N1C=CC=CC=1>[Cl:19][C:20]1[CH:28]=[CH:27][C:23]2[C:24](=[O:25])[N:2]=[C:1]([C:3]3[CH:8]=[C:7]([CH2:9][CH2:10][C:11]([O:13][C:14]([CH3:15])([CH3:17])[CH3:16])=[O:12])[CH:6]=[C:5]([CH3:18])[N:4]=3)[S:29][C:22]=2[CH:21]=1
Reactant: O=C(O)c1ccc(Cl)cc1S
Reactant: Cc1cc(CCC(=O)OC(C)(C)C)cc(C#N)n1
Solvent: c1ccncc1
Product: Cc1cc(CCC(=O)OC(C)(C)C)cc(-c2nc(=O)c3ccc(Cl)cc3s2)n1
Yield: 44.3 %

Procedure:
tert-Butyl 3-(2-cyano-6-methyl-4-pyridyl)propanoate (1.6 g, 6.5 mmol) and 4-chlorothiosalicylic acid (2.4 g, 13.1 mmol) were dissolved in pyridine (20 ml). The mixture was refluxed for 24 hrs. The solvent was evaporated, and residue was subjected to a silica gel column chromatography. The fractions eluted with hexane-ethyl acetate (2:1, v/v) were collected, concentrated and recrystallized from hexane-ethyl acetate to give the titled compound (1.2 g, 46%) as pale yellow crystals.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][C:11]([CH:14]([N:22]([CH3:39])[C:23](=[O:38])[CH2:24][N:25]3[C:30]4[CH:31]=[C:32]([Cl:36])[C:33]([Cl:35])=[CH:34][C:29]=4[O:28][CH2:27][C:26]3=[O:37])[CH2:15][N:16]3[CH2:21][CH2:20][O:19][CH2:18][CH2:17]3)=[CH:10][CH:9]=2)=[CH:4][CH:3]=1.[N:40]([CH2:43][CH3:44])=[C:41]=[O:42].C(N(CC)CC)C>ClCCl>[Cl:36][C:32]1[C:33]([Cl:35])=[CH:34][C:29]2[O:28][CH2:27][C:26](=[O:37])[N:25]([CH2:24][C:23]([N:22]([CH:14]([C:11]3[CH:12]=[CH:13][C:8]([C:5]4[CH:4]=[CH:3][C:2]([NH:1][C:41]([NH:40][CH2:43][CH3:44])=[O:42])=[CH:7][CH:6]=4)=[CH:9][CH:10]=3)[CH2:15][N:16]3[CH2:17][CH2:18][O:19][CH2:20][CH2:21]3)[CH3:39])=[O:38])[C:30]=2[CH:31]=1
Reactant: CN(C(=O)CN1C(=O)COc2cc(Cl)c(Cl)cc21)C(CN1CCOCC1)c1ccc(-c2ccc(N)cc2)cc1
Reactant: CCN=C=O
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CCNC(=O)Nc1ccc(-c2ccc(C(CN3CCOCC3)N(C)C(=O)CN3C(=O)COc4cc(Cl)c(Cl)cc43)cc2)cc1
Reaction time: 0.25 h
Yield: 69.6 %

Procedure:
To a solution of N-[1-(4′-amino-4-biphenylyl)-2-(4-morpholinyl)ethyl]-2-(6,7-dichloro-3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl)-N-methylacetamide (68 mg, 0.12 mmol) in dichloromethane (2 mL) was added isocyanatoethane (36.5 mg, 0.51 mmol). Triethylamine (36 mg, 0.36 mmol) was added, and the resultant mixture was stirred at room temperature for 18 h. The mixture was concentrated under reduced pressure, and the residue was purified by Gilson preparative HPLC (Xterra Prep RP, 30×100 mm, 45 mL/min, A: acetonitrile with 0.1% TFA B: water with 0.1% TFA, A: 20 to 50% over 15 min, UV detection at 214 nm) to give 53.5 mg (70%) of the title compound as an off white solid. MS (ES) m/e 640.2 [M+H]+.
Reaction SMILES: [F:1][C:2]([F:23])([F:22])[CH:3]([C:5]1[CH:10]=[CH:9][C:8]([N:11]2[CH2:15][CH2:14][C:13]3([CH2:20][CH2:19][NH:18][CH2:17][CH2:16]3)[C:12]2=[O:21])=[CH:7][CH:6]=1)[OH:4].[F:24][C:25]([F:38])([F:37])[O:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=1[S:33](Cl)(=[O:35])=[O:34]>N1C=CC=CC=1>[F:23][C:2]([F:1])([F:22])[CH:3]([C:5]1[CH:10]=[CH:9][C:8]([N:11]2[CH2:15][CH2:14][C:13]3([CH2:16][CH2:17][N:18]([S:33]([C:28]4[CH:29]=[CH:30][CH:31]=[CH:32][C:27]=4[O:26][C:25]([F:24])([F:37])[F:38])(=[O:35])=[O:34])[CH2:19][CH2:20]3)[C:12]2=[O:21])=[CH:7][CH:6]=1)[OH:4]
Reactant: O=S(=O)(Cl)c1ccccc1OC(F)(F)F
Reactant: O=C1N(c2ccc(C(O)C(F)(F)F)cc2)CCC12CCNCC2
Solvent: c1ccncc1
Product: O=C1N(c2ccc(C(O)C(F)(F)F)cc2)CCC12CCN(S(=O)(=O)c1ccccc1OC(F)(F)F)CC2
Temperature: 25 °C

Procedure:
Crude 2-[4-(2,2,2-trifluoro-1-hydroxy-ethyl)-phenyl]-2,8-diaza-spiro[4.5]decan-1-one from step A) (0.327 g) dissolved in pyridine at RT and under an argon atmosphere was treated with 2-trifluoromethoxy-benzenesulfonyl chloride (0.286 g) and the mixture was then stirred at RT over night. Then the most of pyridine was evaporated off in vacuo, the residue was dissolved in AcOEt which was then washed with 1M aqueous HCl and brine, dried over magnesium sulphate and concentrated in vacuo. The crude product was chromatographed over silica gel (eluent: AcOEt/Heptane, gradient from 0 to 30%) to give the desired product as a light brown solid. MS (ESI): 553.12 (MH+).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:17]=[CH:16][CH:15]=[C:14]3[C:10]=2[CH2:11][C:12](=[O:18])[NH:13]3)=[CH:5][CH:4]=1.[CH3:19][C@H:20]1[NH:25][C@@H:24]([CH3:26])[CH2:23][N:22]([C:27]([C:29]2[C:30]([CH3:36])=[C:31]([CH:34]=O)[NH:32][CH:33]=2)=[O:28])[CH2:21]1>C(O)C.N1CCCCC1>[CH3:26][C@H:24]1[NH:25][C@@H:20]([CH3:19])[CH2:21][N:22]([C:27]([C:29]2[C:30]([CH3:36])=[C:31]([CH:34]=[C:11]3[C:10]4[C:14](=[CH:15][CH:16]=[CH:17][C:9]=4[C:6]4[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=4)[NH:13][C:12]3=[O:18])[NH:32][CH:33]=2)=[O:28])[CH2:23]1
Reactant: COc1ccc(-c2cccc3c2CC(=O)N3)cc1
Reactant: Cc1c(C(=O)N2C[C@@H](C)N[C@@H](C)C2)c[nH]c1C=O
Solvent: C1CCNCC1
Solvent: CCO
Product: COc1ccc(-c2cccc3c2C(=Cc2[nH]cc(C(=O)N4C[C@@H](C)N[C@@H](C)C4)c2C)C(=O)N3)cc1
Temperature: 25 °C
Reaction time: 72 h
Yield: 62.9 %

Procedure:
To a solution of 4-(4-methoxy-phenyl)-1,3-dihydro-indol-2-one (59.8 mg, 0.25 mmol) and 4-[(cis)-3,5-dimethyl-piperazine-1-carbonyl]-3-methyl-1H-pyrrole-2-carbaldehyde (64.8 mg, 0.26 mmol) in ethanol (2 mL) was added piperidine (3 drops). The reaction mixture was stirred at room temperature for three days. A yellow solid product was precipitated out, filtered, washed by ethanol for three times, and dried under high vacuum to provide pure product 3-{4-((cis)-3,5-dimethyl-piperazine-1-carbonyl]-3-methyl-1H-pyrrol-2-ylmethylene}-4-(4-methoxy-phenyl)-1,3-dihydro-indol-2-one as a yellow solid (74 mg, 63%).
Reaction SMILES: [NH2:1][C@@H:2]([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[C@@H:3]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)[OH:4].Br[CH2:18][C:19]([O:21][CH2:22][CH3:23])=[O:20].C(N(CC)CC)C>ClCCl>[CH2:22]([O:21][C:19]([CH2:18][NH:1][C@@H:2]([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[C@@H:3]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)[OH:4])=[O:20])[CH3:23]
Reactant: N[C@@H](c1ccccc1)[C@H](O)c1ccccc1
Reactant: CCOC(=O)CBr
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CCOC(=O)CN[C@@H](c1ccccc1)[C@H](O)c1ccccc1
Temperature: 25 °C

Procedure:
(1R,2S)-2-amino-1,2-diphenylethanol (2.10 g) was dissolved in dichloromethane (30 ml) and stirred at room temperature. Ethyl bromoacetate (2.00 g), dissolved in dichloromethane (15 ml), was added to the solution. The mixture was stirred at room temperature for 7 days, and then triethylamine (1.5 ml) was added and stirred at room temperature for an additional day. After the spot of the starting material in TLC disappeared, dichloromethane was evaporated under reduced pressure. Benzene (100 ml) was added to the remaining residue, and the triethylamine hydrobromide salt was washed out with water. The organic layer was washed with brine and dried over anhydrous sodium sulfate. The solution was filtered and evaporated. The residue (2.60 g, 88%) was recrystallized from hexane (ca. 300 ml). The crystals deposited were collected and dried under reduced pressure. Yield 2.20 g (75%); mp 123°-125° C.; [α]D18 +2.4° (c 1.00, EtOH). IR (KBr): 3180, 1745, 765, 705 cm -1. 1H-NMR (CDCl3): 1.17 (t, 3H, J=7 Hz), 2.35 (bs, 2H), 3.16 (pseudo s, 2H), 3.98 (q, 2H, J=7 Hz), 4.15 (d, 1H, J=6 Hz), 4.76 (d, 1H, J=6 Hz), 7.20 (s, 10H) ppm.
Reaction SMILES: C[O:2][C:3](=[O:31])[C@H:4]([NH:12][C:13]([O:15][CH2:16][C:17]1[CH:22]=[CH:21][C:20]([CH2:23][O:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)=[CH:19][CH:18]=1)=[O:14])[CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.[Li+].[OH-]>CO.O>[O:24]([CH2:23][C:20]1[CH:21]=[CH:22][C:17]([CH2:16][O:15][C:13]([NH:12][C@H:4]([CH2:5][C:6]2[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=2)[C:3]([OH:31])=[O:2])=[O:14])=[CH:18][CH:19]=1)[C:25]1[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=1
Reactant: COC(=O)[C@@H](Cc1ccccc1)NC(=O)OCc1ccc(COc2ccccc2)cc1
Agent: [Li+]
Agent: [OH-]
Solvent: CO
Solvent: O
Product: O=C(N[C@H](Cc1ccccc1)C(=O)O)OCc1ccc(COc2ccccc2)cc1
Reaction time: 8 h
Yield: 77.3 %

Procedure:
(R)-2-(4-Phenoxymethyl-benzyloxycarbonylamino)-3-phenyl-propionic acid methyl ester 6 (1.605 g, 3.83 mmol) was dissolved in methanol (40 ml) at room temperature. A solution of LiOH (177 mgs, 4.21 mmol) in 15 ml of H2O was then added and the mixture was stirred overnight. The mixture was diluted with H2O (50 ml). The methanol was then removed in vacuo. The aqueous residue was acidified with 4.5N HCl forming a precipitate that was filtered and dried. Recrystallization gave about 1.2 g of (R)-2-(4-phenoxymethyl-benzyloxycarbonylamino)-3-phenyl-propionic acid 7, mp. 115.9-116.7° C.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:29])[CH2:4][CH2:5][C:6]#[C:7][C:8]1[C:16]([N+:17]([O-])=O)=[CH:15][CH:14]=[C:13]2[C:9]=1/[C:10](=[CH:21]/[C:22]1[NH:23][CH:24]=[CH:25][C:26]=1[O:27][CH3:28])/[C:11](=[O:20])[NH:12]2.[Cl-].[NH4+]>O.CO.[Zn]>[CH3:1][O:2][C:3](=[O:29])[CH2:4][CH2:5][C:6]#[C:7][C:8]1[C:16]([NH2:17])=[CH:15][CH:14]=[C:13]2[C:9]=1/[C:10](=[CH:21]/[C:22]1[NH:23][CH:24]=[CH:25][C:26]=1[O:27][CH3:28])/[C:11](=[O:20])[NH:12]2
Reactant: COC(=O)CCC#Cc1c([N+](=O)[O-])ccc2c1/C(=C/c1[nH]ccc1OC)C(=O)N2
Agent: [Cl-]
Agent: [NH4+]
Agent: [Zn]
Solvent: CO
Solvent: O
Product: COC(=O)CCC#Cc1c(N)ccc2c1/C(=C/c1[nH]ccc1OC)C(=O)N2
Yield: 48 %

Procedure:
Using Method L above, (Z)-5-[2,3-dihydro-3-[(3-methoxy-1H-pyrrol-2-yl)methylene]-5-nitro-2-oxo-1H-indol-4-yl]-4-pentynoic acid methyl ester (0.22 g, 0.57 mmol) (from Example 35 above) was reduced with zinc (0.33 g, 5.1 mmol) and ammonium chloride (67.1 mg, 1.25 mmol) in 10% water in methanol (20 mL) with heating at reflux for 4 h to give (Z)-5-[5-amino-2,3-dihydro-3-[(3-methoxy-1H-pyrrol-2-yl)methylene]-2-oxo-1H-indol-4-yl]-4-pentynoic acid methyl ester (Yield 0.1 g, 48%).
Reaction SMILES: [N:1]([C:4]1[CH:5]=[C:6]([CH:8]=[C:9]([I:11])[CH:10]=1)[NH2:7])=[N+:2]=[N-:3].[CH:12]1[CH:17]=[CH:16][C:15]([O:18][C:19](OC2C=CC=CC=2)=[N:20][C:21]#[N:22])=[CH:14][CH:13]=1>C(Cl)(Cl)Cl>[N:1]([C:4]1[CH:5]=[C:6]([NH:7][C:19](=[N:20][C:21]#[N:22])[O:18][C:15]2[CH:16]=[CH:17][CH:12]=[CH:13][CH:14]=2)[CH:8]=[C:9]([I:11])[CH:10]=1)=[N+:2]=[N-:3]
Reactant: [N-]=[N+]=Nc1cc(N)cc(I)c1
Reactant: N#CN=C(Oc1ccccc1)Oc1ccccc1
Solvent: ClC(Cl)Cl
Product: N#CN=C(Nc1cc(I)cc(N=[N+]=[N-])c1)Oc1ccccc1
Yield: 94.6 %

Procedure:
CHART B, Step B-1. To a solution of 3-azido-5-iodoaniline (A-4, 2.42 g, 9.31 mmol) in chloroform (8 mL) is added diphenyl cyanocarbonimidate (2.21g, 9.31 mmol). The solvent is allowed to evaporate at a temperature of 70° C. overnight. The resulting solid is washed with ether, filtered and dried to afford 3.558 g of N-(3-azido-5-iodophenyl)-N'-cyanocarbamimidic acid, phenyl ester (B-1) which is used without further purification. A small analytical sample is recrystallized from ethyl acetate in hexane. Mp=195° C. (dec). IR (mull) 3094, 3078, 2954, 2925, 2867, 2854, 2208, 2121, 2106, 1652, 1600, 1590, 1565, 1504, 1491, 1446, 1433, 1401, 1302, 1219, 1195, 833 cm -1 ; 1H NMR (DMSO) δ10.57 (bs (1 H), 7.50 (t, 1 H, J=2 Hz), 7.28 (m, 2 H), 7.10 (m, 5 H); 13C NMR (DMSO) δ151.4, 141.3, 138.6, 129.9, 128.2, 126.4, 124.6, 120.8, 113.6, 95.0; Mass Spec (70eV, EI) m/z 404 (parent), 376, 249 (base), 222, 207, 194, 155, 145, 128, 118, 103, 94, 77, 65, 51; Exact mass calculated for C14H9IN6O: 403.9884. Found: 403.9877. Melt solvate: 3.6% ethyl acetate; Analysis calculated for C14H9IN6O plus 3.6% C4H8O2 : C, 42.07; H, 2.49; N, 20.04; Found; C, 41.95; H, 2.25; N, 19.76.
Reaction SMILES: [CH:1]1([CH2:4][S:5]([C:8]([CH3:13])([CH3:12])[C:9]([OH:11])=O)(=[O:7])=[O:6])[CH2:3][CH2:2]1.S(Cl)(Cl)=O.C(N(CC)C(C)C)(C)C.[CH3:27][O:28][C:29]1[CH:30]=[C:31]([C:35]2[NH:36][C:37]([NH2:40])=[N:38][N:39]=2)[CH:32]=[CH:33][CH:34]=1>>[CH:1]1([CH2:4][S:5]([C:8]([CH3:13])([CH3:12])[C:9]([NH:40][C:37]2[NH:36][C:35]([C:31]3[CH:32]=[CH:33][CH:34]=[C:29]([O:28][CH3:27])[CH:30]=3)=[N:39][N:38]=2)=[O:11])(=[O:6])=[O:7])[CH2:2][CH2:3]1
Reactant: CC(C)(C(=O)O)S(=O)(=O)CC1CC1
Reactant: COc1cccc(-c2nnc(N)[nH]2)c1
Solvent: CCN(C(C)C)C(C)C
Solvent: O=S(Cl)Cl
Product: COc1cccc(-c2nnc(NC(=O)C(C)(C)S(=O)(=O)CC3CC3)[nH]2)c1
Temperature: 25 °C
Yield: 47.2 %

Procedure:
Activation of 0.46 g (2.23 mmol) of 2-cyclopropylmethanesulfonyl-2-methyl-propionic acid as the corresponding acid chloride is achieved by treatment with thionyl chloride (5 mL, 69 mmol) at 70° C. for 2 h. The reaction is cooled to room temperature and excess thionyl chloride is removed under reduced pressure. The crude acid chloride is dissolved in THF (5 mL) and N,N-diisopropylethylamine (0.54 mL, 5.64 mmol) is added followed by 0.3 g (2.6 mmol) of 5-(3-methoxy-phenyl)-4H-[1,2,4]triazol-3-ylamine. After complete addition the reaction is heated to 70° C. for 36 h. The reaction is cooled to room temperature and the solvent is removed under reduced pressure. The residue is dissolved in DCM (20 mL) and washed with saturated aqueous NaHCO3 solution (20 mL). The aqueous layer is back-extracted with DCM (2×20 mL). The combined organic layers are dried over Na2SO4, filtered and the filtrate is concentrated under reduced pressure. The residue is slurried in DCM/ether (1/1, 10 mL) to yield 0.398 g of 2-cyclopropylmethanesulfonyl-N-[5-(3-methoxy-phenyl)-4H-[1,2,4]triazol-3-yl]-2-methyl-propionamide. Yield: 46%; ES-MS: m/z 379 [M+H]
Reaction SMILES: [C:1]([N:4]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:6](=O)[C:5]1=[CH:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1[N+:21]([O-])=O)(=[O:3])[CH3:2]>[Pd].CCO>[C:1]([N:4]1[C:5]2[CH:14]=[C:15]3[C:16]([CH:17]=[CH:18][CH:19]=[CH:20]3)=[N:21][C:6]=2[C:7]2[C:12]1=[CH:11][CH:10]=[CH:9][CH:8]=2)(=[O:3])[CH3:2]
Reactant: CC(=O)N1C(=Cc2ccccc2[N+](=O)[O-])C(=O)c2ccccc21
Agent: [Pd]
Solvent: CCO
Product: CC(=O)n1c2ccccc2c2nc3ccccc3cc21
Reaction time: 3 h
Yield: 49.8 %

Procedure:
A suspension of 1-acetyl-2-(2-nitrophenyl methylene)-3-oxo-2,3-dihydroindole from Example 33 (220 mg, 0.71 mmol), 10% Pd/C (33 mg) and absolute EtOH (25 mL) was shaken on a Parr Shaker at 50 psi of H2 for 3 hours. The Pd catalyst was filtered off over a celite pad and the solvent was evaporated. The crude yellow product (209 mg, >100%) was purified by LPLC, eluting with hexane-EtOAc (2:1), to afford 92 mg (50%) of the title compound as a light yellow solid (90% pure by NMR), Rf 0.38 (hexane-EtOAc 1:1), mp 163.2-164.6° C. [(lit 177-178° C. (Fichter, F.; Boehringer, R. Chem. Ber. 1906, 39, 3932)]; 1H NMR (CDCl3) δ 9.04 (s, 1H), 8.52 (d, J=8.0, 1H), 8.28 (d, J=8.8, 1H), 8.16 (d, J=8.4, 1H), 8.02 (d, J=8.4, 1H), 7.77 (m, 1H), 7.68 (m, 1H), 7.61 (m, 1H), 7.52 (m, 1H), 2.99 (s, 3H); 13C NMR (CDCl3) 169.7, 147.3, 145.9, 141.5, 137.5, 131.4, 130.6, 128.8, 128.6, 128.5, 127.3, 126.1, 124.4, 122.0, 121.6, 115.8, 27.6; MS (EI, m/z) 260 (M+)
Reaction SMILES: [C:1]([N:8]1[CH2:14][CH2:13][CH2:12][C@H:9]1[CH:10]=[O:11])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[S:15]1[CH:19]=[CH:18][N:17]=[CH:16]1.[Li]CCCC>>[S:15]1[CH:19]=[CH:18][N:17]=[C:16]1[CH:10]([OH:11])[C@@H:9]1[CH2:12][CH2:13][CH2:14][N:8]1[C:1]([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2]
Reactant: c1cscn1
Reactant: CC(C)(C)OC(=O)N1CCC[C@H]1C=O
Agent: [Li]CCCC
Product: CC(C)(C)OC(=O)N1CCC[C@H]1C(O)c1nccs1

Procedure:
31 (1.0 g, 5.02 mmol), thiazole (0.39 ml, 5.52 mmol), n-BuLi (1.6 M) (3.45 ml 5.52 mmol).
Reaction SMILES: [C:1]([NH:4][C:5]1[CH:6]=[C:7]([CH:9]=[CH:10][CH:11]=1)[NH2:8])(=[O:3])[CH3:2].[CH2:12](Br)[CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH3:19].C(=O)([O-])[O-].[Na+].[Na+]>>[C:1]([NH:4][C:5]1[CH:6]=[C:7]([CH:9]=[CH:10][CH:11]=1)[NH:8][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH3:19])(=[O:3])[CH3:2]
Reactant: CC(=O)Nc1cccc(N)c1
Reactant: CCCCCCCCBr
Agent: O=C([O-])[O-]
Agent: [Na+]
Product: CCCCCCCCNc1cccc(NC(C)=O)c1

Procedure:
3-Acetylaminoaniline (15 parts) was reacted with n-octyl bromide (19.3 parts) at 100° C. for 4 hours in the presence of anhydrous sodium carbonate (5.3 parts) to obtain 3-acetylamino-N-n-octylaniline. Thereafter, reaction was further continued at 120° to 130° C. for 4 hours with addition of n-amyl bromide (15.1 parts) and anhydrous sodium carbonate (5.3 parts) to obtain 3-acetylamino-N-n-octyl-N-n-pentylaniline (coupling component). In the same manner as in Example 1, 2-cyano-4-nitro-6-chloroaniline was diazotized and coupled with the above coupling component to obtain 43.8 parts of a dye (8).
Reaction SMILES: C(O[C:4]([C:6]1[C:7]2[S:15][CH:14]=[C:13]([CH2:16][O:17][C:18]3[CH:23]=[CH:22][CH:21]=[C:20]([C:24]4[O:25][C:26]([CH3:29])=[N:27][N:28]=4)[CH:19]=3)[C:8]=2[C:9]([NH2:12])=[N:10][CH:11]=1)=[O:5])C.[CH2:30]([CH2:32][NH2:33])[OH:31]>CS(C)=O>[OH:31][CH2:30][CH2:32][NH:33][C:4]([C:6]1[C:7]2[S:15][CH:14]=[C:13]([CH2:16][O:17][C:18]3[CH:23]=[CH:22][CH:21]=[C:20]([C:24]4[O:25][C:26]([CH3:29])=[N:27][N:28]=4)[CH:19]=3)[C:8]=2[C:9]([NH2:12])=[N:10][CH:11]=1)=[O:5]
Reactant: CCOC(=O)c1cnc(N)c2c(COc3cccc(-c4nnc(C)o4)c3)csc12
Reactant: NCCO
Solvent: CS(C)=O
Product: Cc1nnc(-c2cccc(OCc3csc4c(C(=O)NCCO)cnc(N)c34)c2)o1
Temperature: 160 °C

Procedure:
A solution of 4-amino-3-[3-(5-methyl-[1,3,4]oxadiazol-2-yl)-phenoxymethyl]-thieno[3,2-c]pyridine-7-carboxylic acid ethyl ester (0.05 g, 0.12 mmol) (from Example 9 supra) in dimethylsulfoxide (0.5 mL) was treated with ethanolamine (1.5 mL) (Aldrich) and heated at 160° C. for 2 hours in a microwave reactor. The reaction mixture was purified by reverse-phase chromatography (C18 column) eluting with acetonitrile-water to give 4-amino-3-[3-(5-methyl-[1,3,4]oxadiazol-2-yl)-phenoxymethyl]-thieno[3,2-c]pyridine-7-carboxylic acid (2-hydroxy-ethyl)-amide as a white powder. (Yield 15.0 mg, 29%).