Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([NH:8][C:9]2[CH:14]=[CH:13][C:12]([N:15]3[CH2:20][CH2:19][O:18][CH2:17][CH2:16]3)=[CH:11][CH:10]=2)[C:5]([Cl:21])=[CH:4][N:3]=1.[CH2:22]([N:24]1[CH2:30][CH2:29][C:28]2[CH:31]=[C:32]([NH2:35])[CH:33]=[CH:34][C:27]=2[CH2:26][CH2:25]1)[CH3:23].Cl.C(=O)([O-])[O-]>COCCO.O1CCOCC1>[Cl:21][C:5]1[C:6]([NH:8][C:9]2[CH:14]=[CH:13][C:12]([N:15]3[CH2:20][CH2:19][O:18][CH2:17][CH2:16]3)=[CH:11][CH:10]=2)=[N:7][C:2]([NH:35][C:32]2[CH:33]=[CH:34][C:27]3[CH2:26][CH2:25][N:24]([CH2:22][CH3:23])[CH2:30][CH2:29][C:28]=3[CH:31]=2)=[N:3][CH:4]=1
Reactant: CCN1CCc2ccc(N)cc2CC1
Reactant: Clc1ncc(Cl)c(Nc2ccc(N3CCOCC3)cc2)n1
Agent: Cl
Agent: O=C([O-])[O-]
Solvent: C1COCCO1
Solvent: COCCO
Product: CCN1CCc2ccc(Nc3ncc(Cl)c(Nc4ccc(N5CCOCC5)cc4)n3)cc2CC1
Temperature: 120 °C
Reaction time: 6 h

Procedure:
(2,5-Dichloro-pyrimidin-4-yl)-(4-morpholin-4-yl-phenyl)-amine (96 mg, 0.29 mmol) was added into a vial, followed by a solution of 3-Ethyl-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-ylamine (52 mg, 0.27 mmol) in 2-Methoxyethanol (2.7 mL). 4 M of Hydrogen chloride in 1,4-Dioxane (0.10 mL) was added and the reaction was heated at 120° C. After 6 h, the reaction was cooled and Macroporous carbonate resin (3.16 mmol/g loading; 400 mg, 1.25 mmol) was added and the reaction was stirred overnight, then was concentrated in vacuo onto Celite, and chromatographed (24 g alumina column, DCM). 5-Chloro-N*2*-(3-ethyl-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-yl)-N*4*-(4-morpholin-4-yl-phenyl)-pyrimidine-2,4-diamine was isolated as a yellow powder (40 mg, 31%). m.p.=190-194° C.; LCMS (m/e) 479 (M+1); 1H-NMR (CDCl3, 400 MHz) δ 8.04 (s, 1H), 7.23 (m, 1H), 7.16 (d, 1H, J=7.9 Hz), 7.04 (dd, 1H, J=2.1, 2.2 Hz), 7.00 (m, 2H), 6.82 (s, 1H), 6.72 (dd, 1H, J=2.2, 8.3 Hz), 3.81 (t, 4H, J=4.8 Hz), 3.12 (t, 4H, J=4.8 Hz), 2.89 (m, 4H), 2.62 (m, 4H), 2.57 (q, 2H, J=7 Hz), 1.09 (t, 1H, J=7 Hz).
Reaction SMILES: [C:1]1([N:7]=[C:8]=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[O:10]1[CH2:15][CH2:14][NH:13][C:12]2[CH:16]=[CH:17][C:18]([C:20]3[CH:21]=[CH:22][C:23]([O:26][CH2:27][C:28]([CH3:34])([CH3:33])[C:29]([O:31][CH3:32])=[O:30])=[N:24][CH:25]=3)=[CH:19][C:11]1=2>C(Cl)Cl>[CH3:33][C:28]([CH3:34])([CH2:27][O:26][C:23]1[CH:22]=[CH:21][C:20]([C:18]2[CH:17]=[CH:16][C:12]3[N:13]([C:8](=[O:9])[NH:7][C:1]4[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=4)[CH2:14][CH2:15][O:10][C:11]=3[CH:19]=2)=[CH:25][N:24]=1)[C:29]([O:31][CH3:32])=[O:30]
Reactant: COC(=O)C(C)(C)COc1ccc(-c2ccc3c(c2)OCCN3)cn1
Reactant: O=C=Nc1ccccc1
Solvent: ClCCl
Product: COC(=O)C(C)(C)COc1ccc(-c2ccc3c(c2)OCCN3C(=O)Nc2ccccc2)cn1
Reaction time: 8 h

Procedure:
Phenyl isocyanate (16.1 μL, 0.148 mmol) was added at room temperature to a solution of methyl 3-(5-(3,4-dihydro-2H-benzo[b][1,4]oxazin-7-yl)pyridin-2-yloxy)-2,2-dimethylpropanoate B-2 (39.2 mg, 0.114 mmol) in anhydrous methylene chloride (0.57 mL) under an atmosphere of argon. The reaction mixture was stirred overnight, then concentrated to dryness under reduced pressure to give crude methyl 2,2-dimethyl-3-(5-(4-(phenylcarbamoyl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-7-yl)pyridin-2-yloxy)propanoate B-3 (62.0 mg), which was sufficiently pure to be used for the next step without additional purification. MS (ESI), [M+1]+ 462.
Reaction SMILES: [CH2:1]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[C:12]([S:17](Cl)(=[O:19])=[O:18])=[CH:13][CH:14]=[CH:15][CH:16]=2)=[CH:7][C:6]=1[N+:21]([O-:23])=[O:22])[CH:2]([CH3:4])[CH3:3].[NH2:24][C:25]1[C:30]([O:31][CH3:32])=[N:29][C:28]([CH3:33])=[CH:27][N:26]=1>N1C=CC=CC=1>[CH2:1]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[C:12]([S:17]([NH:24][C:25]3[C:30]([O:31][CH3:32])=[N:29][C:28]([CH3:33])=[CH:27][N:26]=3)(=[O:19])=[O:18])=[CH:13][CH:14]=[CH:15][CH:16]=2)=[CH:7][C:6]=1[N+:21]([O-:23])=[O:22])[CH:2]([CH3:4])[CH3:3]
Reactant: COc1nc(C)cnc1N
Reactant: CC(C)Cc1ccc(-c2ccccc2S(=O)(=O)Cl)cc1[N+](=O)[O-]
Solvent: c1ccncc1
Product: COc1nc(C)cnc1NS(=O)(=O)c1ccccc1-c1ccc(CC(C)C)c([N+](=O)[O-])c1
Temperature: 75 °C
Yield: 39.5 %

Procedure:
4'-Isobutyl-3'-nitro-2-biphenylsulphonyl chloride (0.353 g) was added to a solution of 2-amino-3-methoxy-5-methylpyrazine (0.139 g) in pyridine (10 ml) at 0° C. The solution was heated at 75° C. for 18 hours and then volatile material was removed by evaporation. The residue was purified by elution with dichloromethane through a silica gel Mega Bond Elut column and the resulting foam was triturated with ether/hexane (1:1 v/v) to give 4'-isobutyl-N-(3-methoxy-5-methyl-2-pyrazinyl)-3'-nitro-2-biphenylsulphonamide (0.18 g), m.p. 114°-115° C.; mass spectrum (+ve CI): 457 (M+H)+.
Reaction SMILES: [CH3:1][N:2]1[CH:6]=[C:5]([NH2:7])[CH:4]=[N:3]1.O=[C:9]1[CH2:14][CH2:13][CH2:12][CH2:11][CH:10]1[C:15]([O-])=[O:16]>C1(C)C=CC=CC=1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>[CH3:1][N:2]1[C:6]2[C:5](=[N:7][C:9]3[CH2:14][CH2:13][CH2:12][CH2:11][C:10]=3[C:15]=2[OH:16])[CH:4]=[N:3]1
Reactant: Cn1cc(N)cn1
Reactant: O=C([O-])C1CCCCC1=O
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: Cc1ccccc1
Solvent: O
Product: Cn1ncc2nc3c(c(O)c21)CCCC3
Temperature: 25 °C
Yield: 45.4 %

Procedure:
A solution of 1-methyl-1H-pyrazol-4-amine ((J. Catalan et al., J. Heterocycl. Chem., 1985, 22, 997), 200 mg, 2.06 mmol), 2-oxocyclohexanecarboxylate (351 mg, 2.06 mmol), and p-toluenesulfonic acid monohydrate (10 mg, 0.05 mmol) in toluene (20 ml) was stirred at 120° C. for 2.5 h. After cooling to room temperature, the solvent was removed in vacuo. Diphenyl ether (5 ml) was added to the residue (ca. 300 mg) and the resulting mixture was heated at 240° C. for 40 min. After cooling to room temperature, hexane (2 ml) was added. The precipitate was collected by filtration and washed with dichloromethane to give 190 mg (46%) of the title compound as a white solid.
Reaction SMILES: C[N:2](C)/[CH:3]=[CH:4]/[C:5]([C:7]1[C:12](=[O:13])[CH:11]=[CH:10][N:9]([C:14]2[CH:15]=[C:16]([CH:19]=[CH:20][CH:21]=2)[C:17]#[N:18])[N:8]=1)=O.[F:23][C:24]1[CH:25]=[C:26]([NH:30]N)[CH:27]=[CH:28][CH:29]=1>>[F:23][C:24]1[CH:25]=[C:26]([N:30]2[C:5]([C:7]3[C:12](=[O:13])[CH:11]=[CH:10][N:9]([C:14]4[CH:15]=[C:16]([CH:19]=[CH:20][CH:21]=4)[C:17]#[N:18])[N:8]=3)=[CH:4][CH:3]=[N:2]2)[CH:27]=[CH:28][CH:29]=1
Reactant: CN(C)/C=C/C(=O)c1nn(-c2cccc(C#N)c2)ccc1=O
Reactant: NNc1cccc(F)c1
Product: N#Cc1cccc(-n2ccc(=O)c(-c3ccnn3-c3cccc(F)c3)n2)c1

Procedure:
The product was obtained starting from 3-[3-((E)-3-Dimethylamino-acryloyl)-4-oxo-4H-pyridazin-1-yl]-benzonitrile (A-19) and 3-fluoro-phenylhydrazine according to the method described for example 91. MS: M=358.1 (M+H)+
Reaction SMILES: [C:1]([O:5][C:6]([C@@H:8]1[CH2:12][S:11][CH:10]([CH2:13][CH2:14][CH2:15][CH3:16])[N:9]1[C:17](=[O:39])[CH2:18][NH:19][C:20](=[O:38])[NH:21][C:22]1[CH:23]=[C:24]([CH:35]=[CH:36][CH:37]=1)[C:25]([O:27]CC1C=CC=CC=1)=[O:26])=[O:7])([CH3:4])([CH3:3])[CH3:2].C([O-])=O.[NH4+]>[Pd].CN(C=O)C>[C:1]([O:5][C:6]([C@@H:8]1[CH2:12][S:11][CH:10]([CH2:13][CH2:14][CH2:15][CH3:16])[N:9]1[C:17](=[O:39])[CH2:18][NH:19][C:20](=[O:38])[NH:21][C:22]1[CH:23]=[C:24]([CH:35]=[CH:36][CH:37]=1)[C:25]([OH:27])=[O:26])=[O:7])([CH3:2])([CH3:3])[CH3:4]
Reactant: CCCCC1SC[C@@H](C(=O)OC(C)(C)C)N1C(=O)CNC(=O)Nc1cccc(C(=O)OCc2ccccc2)c1
Agent: [Pd]
Agent: O=C[O-]
Agent: [NH4+]
Solvent: CN(C)C=O
Product: CCCCC1SC[C@@H](C(=O)OC(C)(C)C)N1C(=O)CNC(=O)Nc1cccc(C(=O)O)c1
Yield: 25.3 %

Procedure:
The procedure is similar to that described in Example 1, but starting with 1.18 g of benzyl (4R)-3-{3-[2-(4-tert-butoxycarbonyl-2-butyl-3-thiazolidinyl)-2-oxoethyl]ureido}benzoate (isomer A), 0.8 g of ammonium formate and 1.2 g of palladium on charcoal (10% Pd). 0.25 g of (4R) -3-{3- [2- (4-tert-butoxycarbonyl-2-butyl-3-thiazolidinyl)-2-oxoethyl]ureido}benzoic acid (isomer A) is thereby obtained in the form of an amorphous products [α]D25 =-35.4°±1.0° (C %=0.52; DMF).
Reaction SMILES: [C:1]1(=O)[N:5]([CH2:6][C:7]2[N:11]([C:12]3[CH:25]=[CH:24][CH:23]=[CH:22][C:13]=3C(C3C=CC=CC=3)=O)[C:10]([CH2:26][N:27]3C(=O)C4=CC=CC=C4C3=O)=[N:9][N:8]=2)C(=O)[C:3]2=[CH:39][CH:40]=[CH:41][CH:42]=[C:2]12.O.NN>C(O)C>[NH2:27][CH2:26][C:10]1[N:11]2[C:12]3[CH:25]=[CH:24][CH:23]=[CH:22][C:13]=3[C:1]([C:2]3[CH:3]=[CH:39][CH:40]=[CH:41][CH:42]=3)=[N:5][CH2:6][C:7]2=[N:8][N:9]=1
Reactant: O=C(c1ccccc1)c1ccccc1-n1c(CN2C(=O)c3ccccc3C2=O)nnc1CN1C(=O)c2ccccc2C1=O
Agent: NN
Solvent: CCO
Solvent: O
Product: NCc1nnc2n1-c1ccccc1C(c1ccccc1)=NC2

Procedure:
In the manner given in Example 22, 2-[3,5-bis(phthalimidomethyl)-4H-1,2,4-triazol-4-yl]benzophenone in ethanol is heated with hydrazine hydrate to give 1-(aminomethyl)6-phenyl-4H-s-triazolo[4,3-a][1,4]benzodiazepine.
Reaction SMILES: [C:1]([O:9][CH2:10][CH3:11])(=[O:8])[CH2:2][C:3]([O:5][CH2:6][CH3:7])=[O:4].[C:12](OCC)(OCC)([O:14][CH2:15][CH3:16])[CH3:13].C(OC(=O)C)(=O)C>[Cl-].[Zn+2].[Cl-]>[CH2:12]([O:14][C:15](=[C:2]([C:3]([O:5][CH2:6][CH3:7])=[O:4])[C:1]([O:9][CH2:10][CH3:11])=[O:8])[CH3:16])[CH3:13]
Reactant: CCOC(C)(OCC)OCC
Reactant: CCOC(=O)CC(=O)OCC
Agent: [Cl-]
Agent: [Zn+2]
Solvent: CC(=O)OC(C)=O
Product: CCOC(=O)C(C(=O)OCC)=C(C)OCC
Temperature: 140 °C

Procedure:
A mixture of diethyl malonate (4.8 mL), triethyl orthoacetate (17 mL), acetic anhydride (0.11 mL) and zinc chloride (1.2 g) was stirred at 140° C. To the mixture was added acetic anhydride (0.11 mL) each after 30, 90 and 120 minutes, and then stirred at the same temperature overnight. The reaction mixture was cooled to room temperature, and the insoluble material was removed by filtration. The filtrate was concentrated under reduced pressure, and the residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=4/1−7/3) to give diethyl 2-(1-ethoxyethylidene)malonate (5.02 g). To a solution of diethyl 2-(1-ethoxyethylidene)malonate (4.13 g) in ethanol (15 mL) were added formamidine hydrochloride (1.73 g) and a solution of potassium hydroxide (2.21 g) in water (7.5 mL), and the mixture was stirred at room temperature for 2 days. The reaction mixture was neutralized by adding acetic acid. To the mixture was added ethyl acetate (30 mL), and the mixture was stirred at room temperature for 30 minutes. The insoluble material was removed by filtration, and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (eluent: ethyl acetate−ethyl acetate/methanol=9/1) to give the title compound (1.5 g).
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[N:4][C:5]2[N:6]([N:8]=[C:9]([CH:11]=O)[N:10]=2)[CH:7]=1.C(C1NC(C=O)=C(C)N=1)C.[CH:23]1([C:28]2([CH2:36][CH2:37][C:38]3[CH:43]=[CH:42][C:41]([C:44]4([C:49]#[N:50])[CH2:48][CH2:47][CH2:46][CH2:45]4)=[C:40]([F:51])[CH:39]=3)[CH2:33][C:32](=[O:34])[CH2:31][C:30](=[O:35])[O:29]2)[CH2:27][CH2:26][CH2:25][CH2:24]1.C1(C2(CCC3C=CC(C(C)(C)C#N)=C(F)C=3)CC(O)=CC(=O)O2)CCCC1>>[CH:23]1([C:28]2([CH2:36][CH2:37][C:38]3[CH:43]=[CH:42][C:41]([C:44]4([C:49]#[N:50])[CH2:45][CH2:46][CH2:47][CH2:48]4)=[C:40]([F:51])[CH:39]=3)[CH2:33][C:32]([OH:34])=[C:31]([CH2:11][C:9]3[N:10]=[C:5]4[N:4]=[CH:3][C:2]([CH3:1])=[CH:7][N:6]4[N:8]=3)[C:30](=[O:35])[O:29]2)[CH2:27][CH2:26][CH2:25][CH2:24]1
Reactant: N#CC1(c2ccc(CCC3(C4CCCC4)CC(=O)CC(=O)O3)cc2F)CCCC1
Reactant: Cc1cnc2nc(C=O)nn2c1
Agent: CC(C)(C#N)c1ccc(CCC2(C3CCCC3)CC(O)=CC(=O)O2)cc1F
Agent: CCc1nc(C)c(C=O)[nH]1
Product: Cc1cnc2nc(CC3=C(O)CC(CCc4ccc(C5(C#N)CCCC5)c(F)c4)(C4CCCC4)OC3=O)nn2c1

Procedure:
The title compound was prepared analogously to Example A(97) where 6-Methyl-[1,2,4]triazolo[1,5-a]pyrimidine-2-carbaldehyde was substituted in place of 2-ethyl-4-methyl-1H-imidazole-5-carbaldehyde and 1-{4-[2-(2-Cyclopentyl-4,6-dioxo-tetrahydro-pyran-2-yl)-ethyl]-2-fluoro-phenyl}-cyclopentanecarbonitrile (Example A(189) (was substituted in place of 2-{4-[2-(2-cyclopentyl-4-hydroxy-6-oxo-3,6-dihydro-2H-pyran-2-yl)ethyl]-2-fluorophenyl}-2-methylpropanenitrile. 1H NMR (400 MHz, CDCl3) δ: 1.35-2.16 (m, 16H), 2.42-2.82 (m, 7H), 3.33 (s, 3H), 3.74 (d, J=16 Hz, 1H), 3.84 (d, J=16 Hz, 1H), 7.14-7.19 (m, 2H), 7.36-7.41 (m, 1H), 8.71 (s, 1H), 9 (s, 1H), 10.9 (s, 1H). Anal. Calcd. For C31H34FN5O3.0.75H2O: C, 66.83; H, 6.42; N, 12.57. Found: C, 66.93; H, 6.18; N, 12.45. MS (ESI): 544 (M+H)+.
Reaction SMILES: CCN(S(F)(F)[F:7])CC.[Br:10][C:11]1[CH:12]=[C:13]2[C:18]([NH:19][C@@H:20]3[CH2:24][N:23]([C:25]([O:27][CH2:28][C:29]4[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=4)=[O:26])[CH2:22][C@:21]3(O)[CH3:35])=[C:17]([C:37]#[N:38])[CH:16]=[N:15][N:14]2[CH:39]=1>ClCCl>[Br:10][C:11]1[CH:12]=[C:13]2[C:18]([NH:19][C@@H:20]3[CH2:24][N:23]([C:25]([O:27][CH2:28][C:29]4[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=4)=[O:26])[CH2:22][C@@:21]3([F:7])[CH3:35])=[C:17]([C:37]#[N:38])[CH:16]=[N:15][N:14]2[CH:39]=1
Reactant: C[C@@]1(O)CN(C(=O)OCc2ccccc2)C[C@H]1Nc1c(C#N)cnn2cc(Br)cc12
Reactant: CCN(CC)S(F)(F)F
Solvent: ClCCl
Product: C[C@]1(F)CN(C(=O)OCc2ccccc2)C[C@H]1Nc1c(C#N)cnn2cc(Br)cc12
Reaction time: 0.08 h
Yield: 38.6 %

Procedure:
DAST (0.697 mL, 5.27 mmol) was added to a solution of (3R,4R)-benzyl 4-((6-bromo-3-cyanopyrrolo[1,2-b]pyridazin-4-yl)amino)-3-hydroxy-3-methylpyrrolidine-1-carboxylate (310 mg, 0.659 mmol) in dichloromethane (10 mL) at 0° C. After 5 min at 0° C., the mixture was carefully quenched with saturated NaHCO3 (5 mL), diluted with dichloromethane (80 mL), washed with water, brine, dried (MgSO4) and concentrated. The residue was purified by silica gel chromatography, eluting with 0 to 30% ethyl acetate in hexanes, to give (3S,4R)-benzyl 4-((6-bromo-3-cyanopyrrolo[1,2-b]pyridazin-4-yl)amino)-3-fluoro-3-methylpyrrolidine-1-carboxylate (120 mg, 39% yield). 1H NMR (400 MHz, chloroform-d) δ ppm 7.84 (s, 1H), 7.69 (s, 1H), 7.48-7.31 (m, 5H), 6.77 (d, J=8.8 Hz, 1H), 5.25-5.06 (m, 2H), 4.91-4.70 (m, 1H), 4.37-4.21 (m, 1H), 3.99-3.82 (m, 1H), 3.69-3.35 (m, 2H), 1.73-1.55 (m, 3H); MS (ES+) m/z: 472.2 (M+H).
Reaction SMILES: [Li][Li].Br[C:4]1[CH:5]=[C:6]([CH:10]=[CH:11][CH:12]=1)[C:7]([OH:9])=[O:8].[Cl:13][C:14]1[CH:23]=[C:22]2[C:17]([CH:18]=[CH:19][C:20]([CH:24]=[CH:25][C:26]3[CH:27]=[C:28]([CH:31]=[CH:32][CH:33]=3)[CH:29]=[O:30])=[N:21]2)=[CH:16][CH:15]=1>C1COCC1>[Cl:13][C:14]1[CH:23]=[C:22]2[C:17]([CH:18]=[CH:19][C:20]([CH:24]=[CH:25][C:26]3[CH:27]=[C:28]([CH:29]([OH:30])[C:4]4[CH:5]=[C:6]([CH:10]=[CH:11][CH:12]=4)[C:7]([OH:9])=[O:8])[CH:31]=[CH:32][CH:33]=3)=[N:21]2)=[CH:16][CH:15]=1
Reactant: O=C(O)c1cccc(Br)c1
Reactant: O=Cc1cccc(C=Cc2ccc3ccc(Cl)cc3n2)c1
Agent: [Li][Li]
Solvent: C1CCOC1
Product: O=C(O)c1cccc(C(O)c2cccc(C=Cc3ccc4ccc(Cl)cc4n3)c2)c1
Temperature: -78 °C
Reaction time: 2 h

Procedure:
To the dilithium salt (5.92 mmol) obtained from 3-bromobenzoic acid (W. E. Parham and Y. A. Sayed, J. Org. Chem., 39, 2051 (1974)), a solution of 3-(2-(7-chloro-2-quinolinyl)ethenyl)benzaldehyde (1.503 g, 5.12 mmol) (U.S. Pat. No. 4,851,409, Jul. 25, 1989, Example 24, Step 1) in THF (25 mL) was added dropwise at -78° C. The mixture was stirred for 2 h at -78° C. and was quenched with 25% aqueous NH4OAc. The mixture was acidified to pH 5 with AcOH and extracted with EtOAc. The organic fractions were dried over Na2SO4 and evaporated. Flash chromatography of the residue on silica using EtOAc:toluene:AcOH 30:70:1 yielded the title compound.
Reaction SMILES: [N:1]1([CH2:6][C:7]([C:9]2[CH:21]=[CH:20][C:19]3[C:18]4[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=4)[CH2:12][C:11]=3[CH:10]=2)=[O:8])[CH:5]=[CH:4][N:3]=[CH:2]1.C1(C)C=CC=CC=1.[CH2:29](O)[CH2:30][OH:31].C1(C)C=CC(S(O)(=O)=O)=CC=1>O>[CH:10]1[C:11]2[CH2:12][C:13]3[C:18](=[CH:17][CH:16]=[CH:15][CH:14]=3)[C:19]=2[CH:20]=[CH:21][C:9]=1[C:7]1([CH2:6][N:1]2[CH:5]=[CH:4][N:3]=[CH:2]2)[O:31][CH2:30][CH2:29][O:8]1
Reactant: O=C(Cn1ccnc1)c1ccc2c(c1)Cc1ccccc1-2
Reactant: OCCO
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: Cc1ccccc1
Solvent: O
Product: c1ccc2c(c1)Cc1cc(C3(Cn4ccnc4)OCCO3)ccc1-2

Procedure:
To a slurry of 10.0 g. of 2-(1H-imidazol-1-yl)-1-(9H-fluoren-2-yl)ethanone in 100 ml. of toluene were added 4.53 g. of ethylene glycol and 13.9 g. of p-toluenesulfonic acid. The mixture was heated overnight at reflux with the azeotropic removal of water. The reaction was poured into water and the resulting solid was removed by filtration. The solid was basified with 50 percent sodium hydroxide and extracted with ethyl acetate. The ethyl acetate was washed with water, followed by a saturated sodium chloride solution, dried over sodium sulfate, filtered, and evaporated in vacuo. The residue was crystallized from acetone to provide 8.64 g. of the title product, m.p. 163°-166° C.
Reaction SMILES: Br[C:2]1[N:3]=[C:4]([S:11]([CH2:14][C:15]2[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][CH:16]=2)(=[O:13])=[O:12])[C:5](=[O:10])[N:6]([CH2:8][CH3:9])[CH:7]=1.[C:22]1(B(O)O)[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.C(=O)([O-])[O-].[Cs+].[Cs+].O>C1(C)C=CC=CC=1>[Cl:21][C:18]1[CH:19]=[CH:20][C:15]([CH2:14][S:11]([C:4]2[C:5](=[O:10])[N:6]([CH2:8][CH3:9])[CH:7]=[C:2]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[N:3]=2)(=[O:13])=[O:12])=[CH:16][CH:17]=1
Reactant: OB(O)c1ccccc1
Reactant: CCn1cc(Br)nc(S(=O)(=O)Cc2ccc(Cl)cc2)c1=O
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: Cc1ccccc1
Solvent: O
Product: CCn1cc(-c2ccccc2)nc(S(=O)(=O)Cc2ccc(Cl)cc2)c1=O
Yield: 26.2 %

Procedure:
200 mg (0.51 mM) of 5-bromo-3-[(4-chlorobenzyl)sulfonyl]-1-ethylpyrazin-2(1H)-one and 20 mg of tetrakis Pd(PPh3) in 4 ml of toluene were stirred for 10 min at room temperature under nitrogen atmosphere. 93.4 mg (0.77 mM) of phenyl boronic acid and 1.5 ml of a 2M cesium carbonate aqueous solution were added and the reaction mixture was refluxed under stirring for 1 h30. 10 ml of water and 10 ml of toluene were added, the organic layer was separated. The aqueous layer was extracted with toluene and the combined organic layer was separated and washed with water, dried on anhydrous sodium sulfate and concentrated under vacuum. The residue was further purified by silica gel column chromatography, using dichloromethane/dimethylketone (95/5) as eluant, to give 52 mg of 3-[(4-chlorobenzyl)sulfonyl]-1-ethyl-5-phenylpyrazin-2(1H)-one as a solid. Yield: 26%.
Reaction SMILES: [O:1]1[C:5]2[CH:6]=[CH:7][C:8]([C:10](=[O:20])[C:11](=[C:15]3[S:19][CH:18]=[CH:17][S:16]3)[C:12]([OH:14])=O)=[CH:9][C:4]=2[O:3][CH2:2]1.C(N(CC)CC)C.Cl.[NH2:29][CH2:30][C:31]([O:33][CH3:34])=[O:32].C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=O)C=CC=CC=1>CN(C)C=O>[O:1]1[C:5]2[CH:6]=[CH:7][C:8]([C:10](=[O:20])[C:11](=[C:15]3[S:19][CH:18]=[CH:17][S:16]3)[C:12]([NH:29][CH2:30][C:31]([O:33][CH3:34])=[O:32])=[O:14])=[CH:9][C:4]=2[O:3][CH2:2]1
Reactant: O=C(O)C(C(=O)c1ccc2c(c1)OCO2)=C1SC=CS1
Reactant: COC(=O)CN
Agent: Cl
Agent: [N-]=[N+]=NP(=O)(c1ccccc1)c1ccccc1
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: COC(=O)CNC(=O)C(C(=O)c1ccc2c(c1)OCO2)=C1SC=CS1
Reaction time: 3 h
Yield: 20.9 %

Procedure:
Dissolved in 15.0 ml of N,N-dimethylformamide were 959 mg of 3-(1,3-benzodioxol-5-yl)-2-(1,3-dithiol-2-ylidene)-3-oxopropionic acid and 997 μl of triethylamine, followed by the addition of 469 mg of methyl glycinate hydrochloride. The reaction mixture was ice-cooled, to which 737 μl of diphenylphosphoryl azide were added. The resulting mixture was stirred for 3 hours and, while allowing its temperature to rise to room temperature, was stirred overnight. The reaction mixture was extracted with ethyl acetate. The resulting organic layer was washed with water, shaken together with a saturated aqueous NaCl solution and then dried over anhydrous sodium sulfate. The solvent was distilled off, whereby crude oil was obtained. The oil was purified by column chromatography (silica gel: "Fuji Davidson BW-300", column: 35 mm across×190 mm long, N2 pressure: 0.3 kg/cm2, developer: ethyl acetate:n-hexane=3:2) and then recrystallized from a mixed solvent of ethyl acetate and n-hexane, whereby 247 mg of methyl N-[3-(1,3-benzodioxol-5-yl)-2-(1,3-dithiol-2-ylidene)-3-oxopropionyl]glycinate were obtained as yellow crystals (yield: 21.6%).
Reaction SMILES: [OH:1][CH2:2]/[CH:3]=[C:4](/[CH3:17])\[CH2:5][CH2:6]/[CH:7]=[C:8](\[CH3:16])/[CH2:9][CH2:10][C:11](=[O:15])[C:12]([CH3:14])=[CH2:13].[C:18]([O:22][CH3:23])(=[O:21])[CH2:19][SH:20].C(N(CC)CC)C>CO>[OH:1][CH2:2]/[CH:3]=[C:4](/[CH3:17])\[CH2:5][CH2:6]/[CH:7]=[C:8](\[CH3:16])/[CH2:9][CH2:10][C:11](=[O:15])[CH:12]([CH3:14])[CH2:13][S:20][CH2:19][C:18]([O:22][CH3:23])=[O:21]
Reactant: C=C(C)C(=O)CC/C(C)=C/CC/C(C)=C\CO
Reactant: COC(=O)CS
Solvent: CCN(CC)CC
Solvent: CO
Product: COC(=O)CSCC(C)C(=O)CC/C(C)=C/CC/C(C)=C\CO
Temperature: 25 °C
Reaction time: 18 h

Procedure:
A solution of 4 g (0.0017 mol) of (6E,10Z)-12-hydroxy-2,6,10-trimethyl-1,6,10-dodecatrien-3-one in 13 ml of methanol is treated with 4.7 ml of methyl thioglycolate and 7.1 ml of triethylamine. The solution is stirred at room temperature for 18 hours under argon. After removing the solvent the residue is worked-up with water and methylene chloride. The organic phase is dried and freed from solvent. The residue is chromatographed on silica gel with ether. There is obtained methyl [[(6E,10Z)-12-hydroxy-2,6,10-trimethyl-3-oxo-6,10-dodecadienyl]thio]acetate which has the following bands in the IR spectrum: 1736 cm-1, 1711 cm-1, 1437 cm-1, 1408 cm-1, 1281 cm-1, 1137 cm-1, 1007 cm-1.
Reaction SMILES: C(N(CC)CC)C.O[CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([O:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[N:11]=1.C1(C)C=CC(S([Cl:32])(=O)=O)=CC=1.C(OCC)C>CN(C)C1C=CN=CC=1.ClCCl>[Cl:32][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([O:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[N:11]=1
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Reactant: OCc1cccc(Oc2ccccc2)n1
Agent: CN(C)c1ccncc1
Solvent: ClCCl
Solvent: CCN(CC)CC
Solvent: CCOCC
Product: ClCc1cccc(Oc2ccccc2)n1
Temperature: 25 °C
Reaction time: 4 h
Yield: 62.6 %

Procedure:
Triethylamine (2.27 cm3) was added portionwise to a stirred solution of 2-hydroxymethyl-6-phenoxypyridine (3 g), para-toluenesulphonyl chloride (3.7 g), and 4-dimethylaminopyridine (1.17 g) in dichloromethane (30 cm3), whilst the reaction mixture was maintained at the ambient temperature (ca 22° C.) under an atmosphere of nitrogen. After a period of four hours, the reaction mixture was poured into diethyl ether, and washed sequentially with saturated aqueous sodium bicarbonate, water and brine. The organic layer was then dried, and after removal of the solvent by evaporation under reduced pressure, the crude crude product was subjected to column chromatography on silica gel using dichloromethane as eluent to give 2-chloromethyl-6-phenoxypyridine (2.05 g).
Reaction SMILES: [CH:1]1([NH:7][C:8]2[CH:13]=[CH:12][C:11]([N:14]=O)=[CH:10][CH:9]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[OH-].[Na+].C(O)CCCCC>>[CH:1]1([NH:7][C:8]2[CH:9]=[CH:10][C:11]([NH2:14])=[CH:12][CH:13]=2)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1
Reactant: O=Nc1ccc(NC2CCCCC2)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: CCCCCCO
Product: Nc1ccc(NC2CCCCC2)cc1
Temperature: 95 °C

Procedure:
51.0 g (0.25 mole) N-cyclohexyl-4-nitrosoaniline, 20.0 g (50%) NaOH and 135 g n-hexanol were charged to a 0.5 liter three-necked round bottom flask equipped with stirrer, condenser and thermometer, and heated while stirring to 95° C. until the development of an exotherm was observed. Heating was discontinued, the reaction temperature continued to rise to 115° C. and then dropped, within 10 minutes, to 100° C. With the application of heat, a temperature of 90°-95° C. was maintained for 30 minutes. The reaction mixture contained no unreacted nitroso compound. The yield of the product was 64 wt. %; m.p. 59°-61° C.