Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [O:1]([C:8]1[CH:14]=[CH:13][C:11]([NH2:12])=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:15]([O:19][C:20]([N:22]1[CH2:28][CH2:27][CH2:26][C@@H:23]1[CH:24]=O)=[O:21])([CH3:18])([CH3:17])[CH3:16].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(O)(=O)C>ClC(Cl)C.C([O-])(O)=O.[Na+]>[C:15]([O:19][C:20]([N:22]1[CH2:28][CH2:27][CH2:26][C@@H:23]1[CH2:24][NH:12][C:11]1[CH:10]=[CH:9][C:8]([O:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)=[CH:14][CH:13]=1)=[O:21])([CH3:18])([CH3:16])[CH3:17]
Reactant: Nc1ccc(Oc2ccccc2)cc1
Reactant: CC(C)(C)OC(=O)N1CCC[C@@H]1C=O
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CC(Cl)Cl
Solvent: CC(=O)O
Product: CC(C)(C)OC(=O)N1CCC[C@@H]1CNc1ccc(Oc2ccccc2)cc1
Temperature: 5 °C
Reaction time: 3 h
Yield: 77.9 %

Procedure:
To a solution of 4-phenoxy aniline (100 mg, 0.54 mmol) in dichloroethane (1.5 mL) was added a solution of N-(t-butoxycarbonyl)-D-prolinal (118 mg, 0.594 mmol) in dichloroethane (1.5 mL) at 0-5° C. Sodium triacetoxyborohydride (194 mg, 0.92 mmol) was added to the above solution. Acetic acid (32 mg, 0.54 mmol) in dichloroethane (1 mL) was added dropwise, over a period of 5 min at 0-5° C. The reaction mixture was stirred at 0-10° C. for 3 h. The mixture was diluted with saturated aq NaHCO3 and extracted with dichoromethane. Organic layer was dried over anhy. MgSO4 and the solvent was removed in vacuo to obtain the crude mixture, which was purified by silica gel flash chromatography to obtain the title product (155 mg, 78%); MS; m/z 369 (M+H).
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:22]([CH3:23])=[CH:21][C:19]([NH2:20])=[C:18]([CH3:24])[CH:17]=1.Cl[C:26](Cl)([O:28][C:29](=[O:35])OC(Cl)(Cl)Cl)Cl.O[C:38]1[CH:39]=[C:40]([CH:43]=C[CH:45]=1)[C:41]#[N:42].C(=O)(O)[O-].[Na+]>C(Cl)Cl.C(N(CC)CC)C.C1(C)C=CC=CC=1>[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:22]([CH3:23])=[CH:21][C:19]([NH:20][C:29](=[O:35])[O:28][C:26]2[CH:45]=[CH:38][CH:39]=[C:40]([C:41]#[N:42])[CH:43]=2)=[C:18]([CH3:24])[CH:17]=1
Reactant: O=C(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl
Reactant: N#Cc1cccc(O)c1
Reactant: COc1cc2nccc(Oc3cc(C)c(N)cc3C)c2cc1OC
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Solvent: CCN(CC)CC
Solvent: Cc1ccccc1
Product: COc1cc2nccc(Oc3cc(C)c(NC(=O)Oc4cccc(C#N)c4)cc3C)c2cc1OC
Yield: 55.3 %

Procedure:
4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (50 mg) was added to toluene (5 ml) and triethylamine (0.5 ml), and the mixture was heated under reflux to prepare a solution. A solution of triphosgene (68 mg) in methylene chloride was then added thereto, and the mixture was heated under reflux for 10 min. Next, 3-hydroxybenzonitrile (27 mg) was added thereto, and the mixture was further stirred with heating under reflux for 3 hr. A saturated aqueous sodium bicarbonate solution was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by washing with a 1 N aqueous hydrochloric acid solution, water, and saturated brine in that order. The extract was dried over sodium sulfate and was then concentrated. The residue was purified on a column using chloroform/methanol to give the title compound (40 mg, yield 53%).
Reaction SMILES: [NH:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]1=O.CN1C=C([N+:15]([O-:17])=[O:16])C=C([N+]([O-])=O)C1=O.N>>[N+:15]([C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=1)([O-:17])=[O:16]
Reactant: O=c1cccc[nH]1
Reactant: Cn1cc([N+](=O)[O-])cc([N+](=O)[O-])c1=O
Agent: N
Product: O=[N+]([O-])c1ccccn1

Procedure:
In addition, compounds referred to hereinbelow as 7e and 7f were synthesized by modifying the method described by Tohda et al, Nucleophilic Reaction upon Electron-Deficient Pyridone Derivatives X. One-Pot Synthesis of 3-Nitropyridines by Ring Transformation of 1-Methyl-3,5-dinitro-2-pyridone with Ketones or Aldehydes in the Presence of Ammonia, Bull. Chem. Soc. Jpn. 1990, 63, 2820-2827, for producing nitropyridine by using 3,5 dinitro-1-methyl-2-pyridone which produced the nitro compound 7e which was reduced to the amine 7f.
Reaction SMILES: C(O)C.[Cl:4][C:5]1[CH:6]=[C:7]([CH2:12][N:13]2C(=O)C3C(=CC=CC=3)C2=O)[C:8]([CH3:11])=[N:9][CH:10]=1.O.NN>C(OCC)C>[Cl:4][C:5]1[CH:6]=[C:7]([CH2:12][NH2:13])[C:8]([CH3:11])=[N:9][CH:10]=1
Reactant: Cc1ncc(Cl)cc1CN1C(=O)c2ccccc2C1=O
Agent: NN
Solvent: CCO
Solvent: CCOCC
Solvent: O
Product: Cc1ncc(Cl)cc1CN
Temperature: 25 °C
Reaction time: 2 h
Yield: 119 %

Procedure:
To an ethanol (10 mL) solution of 2-((5-chloro-2-methyl-pyridine-3-yl)methyl)isoindole-1,3-dione (0.20 g), hydrazine monohydrate (0.50 mL) was added, and heat-refluxing of the reaction solution was carried out for 2 hours. The reaction solution was allowed to be cooled to room temperature, diethyl ether (50 mL) was added to the reaction solution, and the reaction solution was agitated for 30 minutes at room temperature. C-(5-chloro-2-methylpyridin-3-yl)methylamine (0.13 g) was obtained by filtering off insoluble matters in the reaction solution and condensing the obtained filtrate under reduced pressure.
Reaction SMILES: Cl[CH2:2][C:3]([NH:5][C:6]1[CH:15]=[CH:14][CH:13]=[C:12]2[C:7]=1[C:8](=[O:17])[NH:9][NH:10][C:11]2=[O:16])=[O:4].[OH-].[NH4+:19]>>[NH2:19][CH2:2][C:3]([NH:5][C:6]1[CH:15]=[CH:14][CH:13]=[C:12]2[C:7]=1[C:8](=[O:17])[NH:9][NH:10][C:11]2=[O:16])=[O:4]
Reactant: [NH4+]
Reactant: O=C(CCl)Nc1cccc2c(=O)[nH][nH]c(=O)c12
Agent: [OH-]
Product: NCC(=O)Nc1cccc2c(=O)[nH][nH]c(=O)c12

Procedure:
forming a second reaction mixture comprising the 2-Chloro-N-(1,4-dioxo-1,2,3,4-tetrahydrophthalazine-5-yl)acetamide and ammonium hydroxide, to yield 2-Amino-N-(1,4-dioxo-1,2,3,4-tetrahydrophthalazine-5-yl)acetamide; and
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]1[N:11]=[C:10]([C:12]2[CH:17]=[C:16]([OH:18])[CH:15]=[C:14]([C:19]#[N:20])[CH:13]=2)[O:9][N:8]=1.C(=O)([O-])[O-].[K+].[K+].Cl.[CH3:28][N:29]([CH3:33])[CH2:30][CH2:31]Cl>CN(C)C=O.ClCCl>[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]1[N:11]=[C:10]([C:12]2[CH:17]=[C:16]([O:18][CH2:31][CH2:30][N:29]([CH3:33])[CH3:28])[CH:15]=[C:14]([C:19]#[N:20])[CH:13]=2)[O:9][N:8]=1
Reactant: CN(C)CCCl
Reactant: N#Cc1cc(O)cc(-c2nc(-c3ccccn3)no2)c1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: ClCCl
Solvent: CN(C)C=O
Product: CN(C)CCOc1cc(C#N)cc(-c2nc(-c3ccccn3)no2)c1
Temperature: 150 °C
Yield: 65.1 %

Procedure:
A mixture of 3-(2-pyridyl)-5-(3-cyano-5-hydroxyphenyl)-1,2,4-oxadiazole (30 mg, 0.11 mmol), potassium carbonate (374mg, 2.7 mmol) and 2-dimethylaminoethyl chloride hydrochloride (46 mg, 0.32 mmol) in N,N-dimethylformamide (1 mL) were heated in a sealed vial at 150° C. for 5 minutes. The reaction was cooled, diluted with dichloromethane, washed with water (3×) and saturated brine, filtered and concentrated. Silica gel chromatography using a gradient of 1% methanol in dichloromethane to 5% methanol in dichloromethane afforded 24 mg (53%) of 3-(2-pyridyl)-5-(3-cyano-5-(2-dimethylaminoethoxy)phenyl) -1,2,4-oxadiazole: 1H NMR (CDCl3): δ-8.86 (d, 1H), 8.23 (d, 1H), 8.15 (s, 1H), 8.04 (s, 1H), 7.91 (t, 1H), 7.49 (m, 1H), 7.43 (s, 1H), 4.20 (t, 2H), 2.80 (t, 2H), 2.37 (s, 6H).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[CH:4][C:5](I)=[C:6]([CH2:8][NH2:9])[CH:7]=1.C(N(CC)C(C)C)(C)C.[C:20](#[N:24])[CH2:21][C:22]#[N:23].N>CN(C)C=O.CCOCC>[NH2:24][C:20]1[N:9]=[CH:8][C:6]2[C:5]([C:21]=1[C:22]#[N:23])=[CH:4][CH:3]=[C:2]([Br:1])[CH:7]=2
Reactant: N#CCC#N
Reactant: NCc1cc(Br)ccc1I
Agent: N
Solvent: CCOCC
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: N#Cc1c(N)ncc2cc(Br)ccc12
Temperature: 25 °C
Reaction time: 8 h
Yield: 62.5 %

Procedure:
To a stirred solution of (5-bromo-2-iodophenyl)methanamine (40 g, 0.129 mol) in N,N-dimethylformamide (500 mL) was sequentially added N,N-diisopropylethylamine (33.3 g, 0.257 mol), malononitrile (16.9 g, 0.257 mol) and CuBr (36.9 g, 0.257 mol). The mixture was stirred at room temperature overnight. After that, to the reaction mixture was added ether and 10% NH3 (1 L, 1:1) and stirred at room temperature overnight open to the air. The mixture was separated and the residue was extracted with ethyl acetate three times, and the combined organic extracts were washed with brine, filtered, and evaporated to yield 20 g (62%) of 3-amino-7-bromoisoquinoline-4-carbonitrile. LCMS (ESI): M+H=247.7; 1H NMR (400 MHz, DMSO-d6) δ 9.03 (s, 1H), 8.23 (d, J=2.0 Hz, 1H), 7.81 (dd, J=2.0, 9.2 Hz, 1H), 7.56 (d, J=9.2 Hz, 1H), 7.42 (s, 2H).
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][CH2:9][CH2:10][CH2:11][C:12]([OH:14])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].CN1CCOCC1.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.[CH2:44]([O:46][C:47](=[O:70])[NH:48][C:49]1[CH:54]=[CH:53][CH:52]=[C:51]([CH2:55][N:56]2[C:61](=[O:62])[CH:60]=[CH:59][C:58]([C:63]3[CH:68]=[CH:67][CH:66]=[C:65]([NH2:69])[CH:64]=3)=[N:57]2)[CH:50]=1)[CH3:45]>CN(C=O)C>[CH2:44]([O:46][C:47](=[O:70])[NH:48][C:49]1[CH:54]=[CH:53][CH:52]=[C:51]([CH2:55][N:56]2[C:61](=[O:62])[CH:60]=[CH:59][C:58]([C:63]3[CH:68]=[CH:67][CH:66]=[C:65]([NH:69][C:12](=[O:14])[CH2:11][CH2:10][CH2:9][NH:8][C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH:64]=3)=[N:57]2)[CH:50]=1)[CH3:45]
Reactant: CC(C)(C)OC(=O)NCCCC(=O)O
Reactant: CCOC(=O)Nc1cccc(Cn2nc(-c3cccc(N)c3)ccc2=O)c1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CN(C)C=O
Solvent: CN1CCOCC1
Product: CCOC(=O)Nc1cccc(Cn2nc(-c3cccc(NC(=O)CCCNC(=O)OC(C)(C)C)c3)ccc2=O)c1
Temperature: 25 °C
Reaction time: 0.17 h

Procedure:
138 mg (0.68 mmol) of 4-(tert-butoxycarbonylamino)butyric acid are suspended in 2 ml of DMF, 138 μl (1.23 mmol) of 4-methylmorpholine, 86 mg (0.617 mmol) of 1-hydroxybenzotriazole and 239 mg (1.23 mmol) of N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride are added. The reaction mixture is stirred at room temperature for 10 min, 274 mg (0.62 mmol) of ethyl{3-[3-(3-aminophenyl)-6-oxo-6H-pyridazin-1-ylmethyl]phenyl}carbamate are subsequently added, and the mixture is stirred at room temperature for 24 h.
Reaction SMILES: [CH:1]1([S:6]([NH2:9])(=[O:8])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1.[OH-].[Na+].[Cl:12][C:13]1[CH:14]=[C:15]([N:20]=[C:21]=[O:22])[CH:16]=[CH:17][C:18]=1[Cl:19].Cl>CC(C)=O.O>[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]([NH:9][S:6]([CH:1]2[CH2:5][CH2:4][CH2:3][CH2:2]2)(=[O:8])=[O:7])=[O:22])[CH:16]=[CH:17][C:18]=1[Cl:19]
Reactant: O=C=Nc1ccc(Cl)c(Cl)c1
Reactant: NS(=O)(=O)C1CCCC1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CC(C)=O
Solvent: O
Product: O=C(Nc1ccc(Cl)c(Cl)c1)NS(=O)(=O)C1CCCC1
Reaction time: 2 h
Yield: 85.2 %

Procedure:
The general method of procedure A was followed with cyclopentanesulfonamide (3 g), acetone (200 ml), 1N sodium hydroxide (20 ml), and 3,4-dichlorophenyl isocyanate (3.6 g) dissolved in acetone (50 ml). After two hours, 1N HCl (20 ml) was added and the resulting solid diluted with water and collected. After drying at 5° C., 5.5 g of solid product were obtained.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([C:7]#[CH:8])[CH:2]=1.C[Si]([N:13]=[N+:14]=[N-:15])(C)C>O>[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([C:7]2[N:13]=[N:14][NH:15][CH:8]=2)[CH:2]=1
Reactant: C#Cc1cccnc1
Reactant: C[Si](C)(C)N=[N+]=[N-]
Solvent: O
Product: c1cncc(-c2c[nH]nn2)c1
Temperature: 150 °C

Procedure:
In a glass-coated bomb tube 6.5 g (0.063 mol) of 3-pyridyl acetylene (T. Sakamoto et al., Synthesis (1983) 312) and 8.7 g (0.075 mol) of trimethylsilyl azide were mixed and heated to 150° C. for 20 h. After cooling the mixture was poured into water. A colorless solid, 68, formed, which was isolated by filtration and dried. Yield: 4.0 g (0.028 mol, 44%).
Reaction SMILES: [CH3:1][O:2][CH2:3][CH2:4]/[CH:5]=[CH:6]/[C:7]1[N:11]2[CH:12]=[CH:13][CH:14]=[CH:15][C:10]2=[N:9][C:8]=1[C:16]([O:18][CH2:19][CH3:20])=[O:17].C1(SC2C=CC=CC=2)C=CC=CC=1.[H][H]>C(OCC)(=O)C.[C].[Pd]>[CH3:1][O:2][CH2:3][CH2:4][CH2:5][CH2:6][C:7]1[N:11]2[CH:12]=[CH:13][CH:14]=[CH:15][C:10]2=[N:9][C:8]=1[C:16]([O:18][CH2:19][CH3:20])=[O:17]
Reactant: [H][H]
Reactant: CCOC(=O)c1nc2ccccn2c1/C=C/CCOC
Agent: [Pd]
Agent: c1ccc(Sc2ccccc2)cc1
Solvent: CCOC(C)=O
Product: CCOC(=O)c1nc2ccccn2c1CCCCOC
Reaction time: 2.5 h
Yield: 48.7 %

Procedure:
Ethyl 3-[(1E)-4-methoxybut-1-en-1-yl]imidazo[1,2-a]pyridine-2-carboxylate (530 mg) and diphenyl sulfide (3.6 mg) were dissolved in ethyl acetate (13 ml), 10% palladium carbon (50% in water) (53 mg) was added and the mixture was stirred in a hydrogen stream at ambient temperature and normal pressure for 2.5 hr. The catalyst was filtered off, and the filtrate was concentrated under reduced pressure. The residue was subjected to silica gel column chromatography, and a fraction eluted with ethyl acetate was concentrated under reduced pressure to give the object product (260 mg).
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([CH:23]=[CH:24][CH:25]=1)[C:5]([N:7]1[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[C:9]([CH2:16][CH2:17][CH2:18][C:19]([OH:21])=[O:20])=[C:8]1[CH3:22])=[O:6].[CH2:26]([C:30]1[CH:35]=[CH:34][C:33]([CH:36](Cl)[C:37]2[CH:42]=[CH:41][C:40]([CH2:43][CH:44]([CH3:46])[CH3:45])=[CH:39][CH:38]=2)=[CH:32][CH:31]=1)[CH:27]([CH3:29])[CH3:28].C(N(C(C)C)CC)(C)C.Cl>ClCCl.C(OCC)(=O)C>[CH2:43]([C:40]1[CH:41]=[CH:42][C:37]([CH:36]([NH:1][C:2]2[CH:3]=[C:4]([CH:23]=[CH:24][CH:25]=2)[C:5]([N:7]2[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[C:9]([CH2:16][CH2:17][CH2:18][C:19]([OH:21])=[O:20])=[C:8]2[CH3:22])=[O:6])[C:33]2[CH:34]=[CH:35][C:30]([CH2:26][CH:27]([CH3:29])[CH3:28])=[CH:31][CH:32]=2)=[CH:38][CH:39]=1)[CH:44]([CH3:46])[CH3:45]
Reactant: Cc1c(CCCC(=O)O)c2ccccc2n1C(=O)c1cccc(N)c1
Reactant: CC(C)Cc1ccc(C(Cl)c2ccc(CC(C)C)cc2)cc1
Agent: Cl
Solvent: CCOC(C)=O
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: Cc1c(CCCC(=O)O)c2ccccc2n1C(=O)c1cccc(NC(c2ccc(CC(C)C)cc2)c2ccc(CC(C)C)cc2)c1
Temperature: 20 °C
Reaction time: 14 h
Yield: 67.1 %

Procedure:
A mixture of 4-[1-(3-aminobenzoyl)-2-methylindol-3-yl]butyric acid (587 mg), bis(4-isobutylphenyl)methyl chloride (905 mg) and diisopropylethylamine (754 mg) in dichloromethane (20 ml) was stirred at 20° C. for 14 hours. The reaction mixture was poured into a mixture of ethyl acetate and 1N hydrochloric acid. The organic layer was separated, washed with water and brine, and dried over magnesium sulfate. After evaporation of the solvent, the residue was chromatographed on a silica gel column (50 ml) eluting with a mixture of chloroform and methanol (50:1) to give 4-[1-[3-[bis(4-isobutylphenyl)methylamino]benzoyl]-2-methylindol-3-yl]butyric acid (720 mg).
Reaction SMILES: Br[CH2:2][C:3]1[N:7]([CH3:8])[N:6]=[C:5]([N+:9]([O-:11])=[O:10])[CH:4]=1.Cl.[F:13][C:14]1([F:18])[CH2:17][NH:16][CH2:15]1.CCN(C(C)C)C(C)C>CN(C=O)C>[F:13][C:14]1([F:18])[CH2:17][N:16]([CH2:2][C:3]2[N:7]([CH3:8])[N:6]=[C:5]([N+:9]([O-:11])=[O:10])[CH:4]=2)[CH2:15]1
Reactant: FC1(F)CNC1
Reactant: Cn1nc([N+](=O)[O-])cc1CBr
Agent: Cl
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: Cn1nc([N+](=O)[O-])cc1CN1CC(F)(F)C1
Temperature: 65 °C

Procedure:
A sealed tube with a magnetic stirrer was charged with DMF (5 mL), 5-(Bromomethyl)-1-methyl-3-nitro-1H-pyrazole 156d (0.39 g, 1.78 mmol), 3,3-difluoroazetidine hydrochloride (276 mg, 2.13 mmol) and DIPEA (0.8 mL, 4.45 mmol). The reaction mixture was heated at 65° C. for 3-5 h. After this time the reaction was concentrated to dryness under reduced pressure, and the resulting residue was diluted with a mixture of Ethyl Acetate (15 mL) and water (15 mL). The aqueous layer was separated and extracted with Ethyl Acetate (2×15 mL). The combined organic extracts were dried over sodium sulfate and concentrated under reduced pressure to afford a quantitative yield of 156e as yellow oil, which was used without further purification for the next step. MS (ESI+) m/z 233.0 (M+H).
Reaction SMILES: [Na].[NH2:2][C:3]1[N:8]=[C:7]([N:9]=O)[N:6]=[C:5]([NH2:11])[C:4]=1[NH2:12].[OH:13][CH2:14][CH2:15][O:16][C:17]1[CH:22]=[CH:21][C:20]([CH2:23][C:24]#[N:25])=[CH:19][CH:18]=1>C(OCCO)C>[NH2:9][C:7]1[N:6]=[C:5]([NH2:11])[C:4]2[C:3](=[N:2][C:24]([NH2:25])=[C:23]([C:20]3[CH:19]=[CH:18][C:17]([O:16][CH2:15][CH2:14][OH:13])=[CH:22][CH:21]=3)[N:12]=2)[N:8]=1
Reactant: N#CCc1ccc(OCCO)cc1
Reactant: Nc1nc(N=O)nc(N)c1N
Agent: [Na]
Solvent: CCOCCO
Product: Nc1nc(N)c2nc(-c3ccc(OCCO)cc3)c(N)nc2n1

Procedure:
460 mg of metallic sodium are dissolved with stirring in 150 ml of 2-ethoxy-ethanol. 3.1 g (0.02 mol) of triaminonitroso-pyrimidine and 3.5 g (0.02 mol) of p-(2-hydroxyethoxy)phenyl-acetonitrile are added one after the other with stirring and the mixture is heated with stirring in a water bath at 60° C. The color of the mixture changes from violet to bright brown. After stirring for 14 hours, the reaction is over. The mixture is left to cool. Unreacted 2,4,6-triamino-nitrosopyrimidine is filtered off and the clear solution is concentrated to dryness. The precipitate is taken up in hot acetone and the crude product is precipitated by admixture with petroleum ether. Purification follows first by recrystallization from butanol and then by separation on a silica gel-dry column (silica gel 60 Merck). The compound mentioned in the title is obtained as yellow-brown crystals.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:9]3[C:14](C(C4C=CC=CC=4)=[C:16]4[C:21]=2[CH:20]=[CH:19][CH:18]=[CH:17]4)=[CH:13][CH:12]=[CH:11][CH:10]=3)=[CH:4][CH:3]=1.[CH:28]1[C:44]2[C:36]3[C:37]4[CH:43]=[CH:42][CH:41]=[CH:40][C:38]=4[O:39][C:35]=3[C:34](B(O)O)=[CH:33][C:32]=2[CH:31]=[CH:30][CH:29]=1.[C:48]1([CH3:54])[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=1.C(=O)([O-])[O-].[Na+].[Na+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C(O)C>[C:48]1([C:54]2[C:16]3[C:21](=[CH:20][CH:19]=[CH:18][CH:17]=3)[C:8]([C:9]3[CH:14]=[CH:13][C:12]([C:34]4[C:35]5[O:39][C:38]6[CH:40]=[CH:41][CH:42]=[CH:43][C:37]=6[C:36]=5[C:44]5[CH:28]=[CH:29][CH:30]=[CH:31][C:32]=5[CH:33]=4)=[CH:11][CH:10]=3)=[C:5]3[C:6]=2[CH:7]=[CH:2][CH:3]=[CH:4]3)[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=1
Reactant: OB(O)c1cc2ccccc2c2c1oc1ccccc12
Reactant: Brc1ccc(-c2c3ccccc3c(-c3ccccc3)c3ccccc23)cc1
Reactant: Cc1ccccc1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CCO
Product: c1ccc(-c2c3ccccc3c(-c3ccc(-c4cc5ccccc5c5c4oc4ccccc45)cc3)c3ccccc23)cc1
Temperature: 25 °C
Yield: 31 %

Procedure:
Into a 100 mL three-neck flask were placed 1.8 g (4.5 mmol) of 9-(4-bromophenyl)-10-phenylanthracene and 1.2 g (4.5 mmol) of benzo[b]naphtho[1,2-d]furan-6-boronic acid synthesized in Step 1 of Example 1, and the air in the flask was replaced with nitrogen. To this mixture were added 15 mL of toluene, 7.0 mL of ethanol, and 5.0 mL of an aqueous solution of sodium carbonate (2.0 mol/L). While the pressure was reduced, this mixture was stirred to be degassed. To this mixture was added 0.26 g (0.22 mmol) of tetrakis(triphenylphosphine)palladium(0), and the mixture was stirred at 80° C. for 6 hours under a nitrogen stream, so that a solid was precipitated. This flask was cooled to room temperature, and this mixture was suction-filtered. The obtained solid was dissolved in about 500 mL of hot toluene, and this solution was suction-filtered through Celite (produced by Wako Pure Chemical Industries, Ltd., Catalog No. 531-16855), alumina, silica gel, and Florisil (produced by Wako Pure Chemical Industries, Ltd., Catalog No. 540-00135). A solid obtained by concentration of the obtained filtrate was recrystallized from toluene, so that 0.77 g of a white powder of the object of the synthesis was obtained in 31% yield.
Reaction SMILES: [CH:1]12[CH2:7][CH:4]([CH2:5][CH2:6]1)[CH2:3][CH:2]2[CH2:8][C:9]([OH:11])=O.C(N1C=CN=C1)([N:14]1[CH:18]=[CH:17]N=C1)=O.N1C=C[C:27]([N:30]2[CH2:35][CH2:34][CH:33]([CH2:36][NH2:37])[CH2:32][CH2:31]2)=[N:26][CH:25]=1>C(Cl)Cl>[CH:1]12[CH2:7][CH:4]([CH2:5][CH2:6]1)[CH2:3][CH:2]2[CH2:8][C:9]([NH:37][CH2:36][CH:33]1[CH2:32][CH2:31][N:30]([C:27]2[N:26]=[CH:25][CH:17]=[CH:18][N:14]=2)[CH2:35][CH2:34]1)=[O:11]
Reactant: O=C(O)CC1CC2CCC1C2
Reactant: O=C(n1ccnc1)n1ccnc1
Reactant: NCC1CCN(c2ccncn2)CC1
Solvent: ClCCl
Product: O=C(CC1CC2CCC1C2)NCC1CCN(c2ncccn2)CC1
Reaction time: 18 h
Yield: 78.9 %

Procedure:
A solution of 2-norbornaneacetic acid (1.54 g, 10 mmole) and 1,1'-carbonyldiimidazole (1.62 g, 10 mmole) in methylene chloride (35 ml) was stirred for 15 min and then 1-(4-pyrimidinyl]-4-piperidinemethaneamine (V; 1.92 g, 10 mmole) was added. After stirring for 18 hrs the solution was diluted with methylene chloride (100 ml) and extracted with water (3×30 ml) and saturated sodium carbonate (30 ml). The methylene chloride layer was dried over magnesium sulfate and concentrated in vacuo to give a white solid. The crude product was recrystallized from a mixture of ethyl acetate (15 ml) and hexane (15 ml) to give the formula I product as a white powder (2.59 g, 79%, mp: 121°-126°).
Reaction SMILES: C[O:2][C:3]1[CH:4]=[CH:5][C:6]2[S:10][C:9]([CH2:11][C:12]3(O)[CH:19]4[CH2:20][CH:15]5[CH2:16][CH:17]([CH2:21][CH:13]3[CH2:14]5)[CH2:18]4)=[N:8][C:7]=2[CH:23]=1.Cl.N1C=CC=CC=1>C(OCC)(=O)C>[CH:13]12[CH2:21][CH:17]3[CH2:16][CH:15]([CH2:20][CH:19]([CH2:18]3)[C:12]1=[CH:11][C:9]1[S:10][C:6]3[CH:5]=[CH:4][C:3]([OH:2])=[CH:23][C:7]=3[N:8]=1)[CH2:14]2
Reactant: COc1ccc2sc(CC3(O)C4CC5CC(C4)CC3C5)nc2c1
Agent: Cl
Solvent: CCOC(C)=O
Solvent: c1ccncc1
Product: Oc1ccc2sc(C=C3C4CC5CC(C4)CC3C5)nc2c1

Procedure:
300 mg 2-(5-methoxy-benzothiazol-2-ylmethyl)adamantan-2-ol (formula IX) and 527 mg pyridine hydrochloride are heated at about 200° for about 30 minutes. The melt obtained is dissolved in 100 ml of ethyl acetate, the mixture is extracted with water, 2.5 M sodium acetate solution and brine, the organic phase dried and the solvent evaporated off. The evaporation residue obtained is subjected to chromatography. The title compound is obtained (m.p. 156-158°).
Reaction SMILES: [N:1]1([CH2:6][CH:7]2[CH2:12][CH2:11][CH2:10][CH2:9][NH:8]2)[CH2:5][CH2:4][CH2:3][CH2:2]1.[Cl:13][C:14]1[CH:24]=[CH:23][C:17]([O:18][CH2:19][C:20](O)=[O:21])=[CH:16][CH:15]=1>>[ClH:13].[Cl:13][C:14]1[CH:24]=[CH:23][C:17]([O:18][CH2:19][C:20]([N:8]2[CH2:9][CH2:10][CH2:11][CH2:12][CH:7]2[CH2:6][N:1]2[CH2:5][CH2:4][CH2:3][CH2:2]2)=[O:21])=[CH:16][CH:15]=1
Reactant: C1CCC(CN2CCCC2)NC1
Reactant: O=C(O)COc1ccc(Cl)cc1
Product: Cl
Product: O=C(COc1ccc(Cl)cc1)N1CCCCC1CN1CCCC1

Procedure:
Prepared from 2-(1-pyrrolidinylmethyl)piperidine and 4-chlorophenoxyacetic acid.
Reaction SMILES: [C:1]([O:5][CH3:6])(=[O:4])[CH2:2][SH:3].[CH3:7][O:8][C:9]([C:11]1[S:15][C:14]2[CH:16]=[C:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH:18]=[CH:19][C:13]=2[C:12]=1OS(C(F)(F)F)(=O)=O)=[O:10].O>C(Cl)Cl.CCN(CC)CC>[CH3:7][O:8][C:9]([C:11]1[S:15][C:14]2[CH:16]=[C:17]([C:20]([O:22][C:23]([CH3:24])([CH3:25])[CH3:26])=[O:21])[CH:18]=[CH:19][C:13]=2[C:12]=1[S:3][CH2:2][C:1]([O:5][CH3:6])=[O:4])=[O:10]
Reactant: COC(=O)CS
Reactant: COC(=O)c1sc2cc(C(=O)OC(C)(C)C)ccc2c1OS(=O)(=O)C(F)(F)F
Solvent: O
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: COC(=O)CSc1c(C(=O)OC)sc2cc(C(=O)OC(C)(C)C)ccc12
Temperature: 25 °C
Reaction time: 24 h
Yield: 70 %

Procedure:
Methyl thioglycolate (1.1 ml, 12 mmol) was added to a solution of 3-trifluoromethanesulfonyloxy-benzo[b]thiophene-2,6-dicarboxylic acid 6-tert-butyl ester 2-methy ester in DCM (30 ml) and Et3N (15 ml) and stirred for 24 hr at RT then 24 hr at 40° C. When the starting material was absent in LC trace, water was added. Extraction with EtOAc and evaporation left an orange liquid. Purification by column chromatography yielded 2.7 g (70%) of 3-methoxycarbonylmethylsulfanyl-benzo[b]thiophene-2,6-dicarboxylic acid 6-tert-butyl ester 2-methyl ester.