Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Si:1](Cl)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].N1C=CN=C1.[OH:14][CH2:15][CH2:16][CH2:17][C:18]1[CH:19]=[CH:20][C:21]2[CH:22]3[CH2:31][CH2:30][CH2:29][CH:23]3[C:24](=[O:28])[NH:25][C:26]=2[CH:27]=1>CN(C=O)C.C(OCC)(=O)C>[Si:1]([O:14][CH2:15][CH2:16][CH2:17][C:18]1[CH:19]=[CH:20][C:21]2[CH:22]3[CH2:31][CH2:30][CH2:29][CH:23]3[C:24](=[O:28])[NH:25][C:26]=2[CH:27]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]
Reactant: CC(C)(C)[Si](C)(C)Cl
Reactant: O=C1Nc2cc(CCCO)ccc2C2CCCC12
Agent: c1c[nH]cn1
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: CC(C)(C)[Si](C)(C)OCCCc1ccc2c(c1)NC(=O)C1CCCC21
Reaction time: 3 h
Yield: 105.3 %

Procedure:
At 0° C., 3.65 g (24.5 mmol) of tert-butyldimethylsilyl-chloride and 3.29 g (48.9 mol) of imidazole are added to a solution of 3.0 g (12.2 mmol) of 7-(3-hydroxypropyl)-1,2,3,3a,5,9b-hexahydrocyclopenta[c]quinolin-4-one in 50 ml of DMF. After 3 hours, the batch is diluted with ethyl acetate, washed with water, 10% citric acid and saturated NaHCO3, dried (Na2SO4) and concentrated by evaporation in a vacuum. Column chromatography with hexane-ethyl acetate on silica gel yields 4.62 g of product.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([S:9]([CH2:11][CH:12]([C:19](=[O:31])[N:20]([CH2:26][CH2:27][CH2:28][CH2:29][CH3:30])[CH2:21][CH2:22][CH2:23][CH2:24][CH3:25])[CH2:13][CH2:14][C:15]([O:17][CH3:18])=[O:16])=[O:10])[CH:5]=[CH:6][C:7]=1[Cl:8].ClC1C=CC=C(C(OO)=[O:40])C=1.S([O-])([O-])=O.[Na+].[Na+]>ClCCl>[Cl:1][C:2]1[CH:3]=[C:4]([S:9]([CH2:11][CH:12]([C:19](=[O:31])[N:20]([CH2:26][CH2:27][CH2:28][CH2:29][CH3:30])[CH2:21][CH2:22][CH2:23][CH2:24][CH3:25])[CH2:13][CH2:14][C:15]([O:17][CH3:18])=[O:16])(=[O:40])=[O:10])[CH:5]=[CH:6][C:7]=1[Cl:8]
Reactant: CCCCCN(CCCCC)C(=O)C(CCC(=O)OC)CS(=O)c1ccc(Cl)c(Cl)c1
Reactant: O=C(OO)c1cccc(Cl)c1
Agent: O=S([O-])[O-]
Agent: [Na+]
Solvent: ClCCl
Product: CCCCCN(CCCCC)C(=O)C(CCC(=O)OC)CS(=O)(=O)c1ccc(Cl)c(Cl)c1
Temperature: 0 °C
Yield: 102 %

Procedure:
Into a solution of methyl 5-(3,4-dichlorophenylsulfinyl)-4-(N,N-dipentylcarbamoyl)pentanoate (95 mg) in dry dichloromethane (10 ml) were added portions of m-chloroperbenzoic acid (80%, 51 mg) with stirring at 0° C. After stirring at room temperature for 2 hours, sodium sulfite was added. The reaction mixture was washed with a saturated sodium bicarbonate solution and water, dried over MgSO4, and concentrated in vacuo. The residue was recrystallized from hexane to give 100 mg of methyl 5-(3,4-dichlorophenylsulfonyl)-4-(N,N-dipentylcarbamoyl)pentanoate. The physical properties of this compound were identical to that of the compound which was prepared in example 1.
Reaction SMILES: Cl.Cl.[NH:3]1[CH2:8][CH2:7][CH:6]([N:9]2[C:17]3[C:12](=[N:13][CH:14]=[CH:15][CH:16]=3)[NH:11][C:10]2=[O:18])[CH2:5][CH2:4]1.Cl[C:20]1[CH:25]=[C:24]([C:26]([N:28]2[C:36]3[C:31](=[CH:32][C:33]([F:37])=[CH:34][CH:35]=3)[CH2:30][CH2:29]2)=[O:27])[CH:23]=[CH:22][N:21]=1.CCN(C(C)C)C(C)C.C(=O)([O-])[O-].[K+].[K+]>CN1CCCC1=O.O>[F:37][C:33]1[CH:32]=[C:31]2[C:36](=[CH:35][CH:34]=1)[N:28]([C:26]([C:24]1[CH:25]=[CH:20][N:21]=[C:22]([N:3]3[CH2:4][CH2:5][CH:6]([N:9]4[C:17]5[C:12](=[N:13][CH:14]=[CH:15][CH:16]=5)[NH:11][C:10]4=[O:18])[CH2:7][CH2:8]3)[CH:23]=1)=[O:27])[CH2:29][CH2:30]2
Reactant: O=C(c1ccnc(Cl)c1)N1CCc2cc(F)ccc21
Reactant: O=c1[nH]c2ncccc2n1C1CCNCC1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN1CCCC1=O
Solvent: CCN(C(C)C)C(C)C
Solvent: O
Product: O=C(c1ccnc(N2CCC(n3c(=O)[nH]c4ncccc43)CC2)c1)N1CCc2cc(F)ccc21
Temperature: 130 °C
Reaction time: 6 h

Procedure:
232 mg (0.8 mmol) 1-piperidin-4-yl-1,3-dihydro-imidazo[4,5-b]pyridin-2-one dihydrochloride were added to 220 mg (0.80 mmol) (2-chloropyridin-4-yl)-(5-fluoro-2,3-dihydro-indol-1-yl)-methanone and 0.52 mL (3.00 mmol) DIPEA in 3.0 mL N-methylpyrrolidone. The reaction mixture was stirred for 6 h at 130° C. After 4 h 400 mg potassium carbonate were added and the reaction mixture was stirred for a further 24 h at 130° C. Then the mixture was poured onto 100 mL water and extracted with EtOAc (3×100 mL). The combined organic phases were dried and evaporated down using the rotary evaporator. The residue was purified by preparative HPLC. The product fractions were combined and evaporated down i. vac. The residue was triturated with 30 mL diethyl ether. The precipitated solid was suction filtered and dried in the air.
Reaction SMILES: [N+:1]([O-:4])(O)=[O:2].[CH3:5][C:6]1([CH3:18])[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[C:9]([CH3:17])([CH3:16])[CH2:8][CH2:7]1.O>C(O)(=O)C.C(OC(=O)C)(=O)C>[N+:1]([C:13]1[CH:12]=[CH:11][C:10]2[C:9]([CH3:17])([CH3:16])[CH2:8][CH2:7][C:6]([CH3:18])([CH3:5])[C:15]=2[CH:14]=1)([O-:4])=[O:2]
Reactant: O=[N+]([O-])O
Reactant: CC1(C)CCC(C)(C)c2ccccc21
Solvent: O
Solvent: CC(=O)OC(C)=O
Solvent: CC(=O)O
Product: CC1(C)CCC(C)(C)c2cc([N+](=O)[O-])ccc21
Temperature: 25 °C
Reaction time: 8 h

Procedure:
77.2 ml of glacial acetic acid and 20.8 ml of nitric acid (98% strength) were mixed while cooling and then added dropwise within 2 hours to a solution of 65.8 g (0.35 mol) of 1,2,3,4-tetrahydro-1,1,4,4-tetramethylnaphthalene in 154 ml of glacial acetic acid and 257 ml of acetic anhydride in a salt/ice bath. After the addition was complete, the reaction mixture was warmed to room temperature and stirred overnight. The solution was then poured into water, and the precipitate was filtered off with suction, washed with water and dried. 79.7 g of crude 2-nitro-5,6,7,8-tetrahydro-5,5,8,8-tetramethylnaphthalene of melting point 46°-50° C. were obtained.
Reaction SMILES: S(C)C.[CH3:4][C:5]1[N:6]=[C:7]([NH:10][C:11]2[N:16]=[CH:15][C:14]([S:17][CH:18]([C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][N:33]=3)[CH:19]3[CH2:24][CH2:23][N:22](C(OC(C)(C)C)=O)[CH2:21][CH2:20]3)=[CH:13][C:12]=2[O:38][C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)[S:8][CH:9]=1.[F:45][C:46]([F:51])([F:50])[C:47]([OH:49])=[O:48]>>[F:45][C:46]([F:51])([F:50])[C:47]([OH:49])=[O:48].[F:45][C:46]([F:51])([F:50])[C:47]([OH:49])=[O:48].[F:45][C:46]([F:51])([F:50])[C:47]([OH:49])=[O:48].[CH3:4][C:5]1[N:6]=[C:7]([NH:10][C:11]2[C:12]([O:38][C:39]3[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=3)=[CH:13][C:14]([S:17][CH:18]([CH:19]3[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]3)[C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][N:33]=3)=[CH:15][N:16]=2)[S:8][CH:9]=1
Reactant: Cc1csc(Nc2ncc(SC(c3ccccn3)C3CCN(C(=O)OC(C)(C)C)CC3)cc2Oc2ccccc2)n1
Solvent: O=C(O)C(F)(F)F
Solvent: CSC
Product: Cc1csc(Nc2ncc(SC(c3ccccn3)C3CCNCC3)cc2Oc2ccccc2)n1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 90 %

Procedure:
Placed Me2S (0.0072 g, 0.12 mmol) in Trifluoroacetic acid (10 mL) followed by tert-butyl 4-((6-(4-methylthiazol-2-ylamino)-5-phenoxypyridin-3-ylthio)(pyridin-2-yl)methyl)piperidine-1-carboxylate (0.068 g, 0.12 mmol) stirred at ambient temperature for 30 minutes, then concentrated to give the title compound (0.086 g, 90% yield). 1H NMR (d6-DMSO) δ 8.52 (bs, 1H), 8.42 (m, 1), 8.17 (bs, 1H), 8.00 (d, 1H), 7.70 (dt, 1H), 7.41 (t, 2H), 7.25-7.16 (m, 3H), 6.92 (d, 2H), 6.90 (s, 1H), 6.63 (s, 1H), 4.22 (d, 1H), 3.32 (d, 1H), 3.17 (d, 1H), 2.9872.74 (m, 2H), 2.30 (m, 2H), 2.23 (s, 3H), 1.45 (m, 2H), 1.30 (m, 1H).
Reaction SMILES: Cl[C:2]1[N:3]=[N:4][CH:5]=[C:6]2[C:10]([CH3:11])=[C:9]([CH3:12])[N:8]([CH2:13][C:14]([F:17])([F:16])[F:15])[C:7]=12.[CH2:18]([OH:25])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1>>[CH2:18]([O:25][C:2]1[N:3]=[N:4][CH:5]=[C:6]2[C:10]([CH3:11])=[C:9]([CH3:12])[N:8]([CH2:13][C:14]([F:17])([F:16])[F:15])[C:7]=12)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1
Reactant: OCc1ccccc1
Reactant: Cc1c(C)n(CC(F)(F)F)c2c(Cl)nncc12
Product: Cc1c(C)n(CC(F)(F)F)c2c(OCc3ccccc3)nncc12
Yield: 65.2 %

Procedure:
The title compound was prepared as a white powder in 65.20% yield in a similar procedure to that described in Example 1 by using 7-chloro-2,3-dimethyl-1-(2,2,2-trifluoroethyl)pyrrolo[2,3-d]pyridazine and benzyl alcohol.
Reaction SMILES: C(=O)([O-])[O-].[K+].[K+].Cl.[C:8]1([C:14]2([NH:20][C:21](=[O:27])[O:22][C:23]([CH3:26])([CH3:25])[CH3:24])[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]2)[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.[C:28]([N:36]1[CH2:41][CH2:40][O:39][C:38]([C:54]2[CH:59]=[CH:58][C:57]([F:60])=[C:56]([F:61])[CH:55]=2)([CH2:42][CH2:43]OS(C2C=CC=CC=2)(=O)=O)[CH2:37]1)(=[O:35])[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1>O.C(#N)C>[C:28]([N:36]1[CH2:41][CH2:40][O:39][C:38]([CH2:42][CH2:43][N:17]2[CH2:18][CH2:19][C:14]([NH:20][C:21](=[O:27])[O:22][C:23]([CH3:24])([CH3:26])[CH3:25])([C:8]3[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=3)[CH2:15][CH2:16]2)([C:54]2[CH:59]=[CH:58][C:57]([F:60])=[C:56]([F:61])[CH:55]=2)[CH2:37]1)(=[O:35])[C:29]1[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=1
Reactant: CC(C)(C)OC(=O)NC1(c2ccccc2)CCNCC1
Reactant: O=C(c1ccccc1)N1CCOC(CCOS(=O)(=O)c2ccccc2)(c2ccc(F)c(F)c2)C1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Solvent: O
Product: CC(C)(C)OC(=O)NC1(c2ccccc2)CCN(CCC2(c3ccc(F)c(F)c3)CN(C(=O)c3ccccc3)CCO2)CC1
Temperature: 70 °C
Reaction time: 8 h

Procedure:
A solution of 18 g of potassium carbonate in 18 ml of water is added to a mixture of 22.6 g of tert-butyl (4-phenylpiperid-4-yl)carbamate hydrochloride (compound (IV)) and 30 g of compound of formula (III) obtained in Example 1 in 300 ml of acetonitrile, and the mixture is then heated at 70° C. for 12 hours and left overnight at room temperature. The acetonitrile is concentrated under vacuum, the residue is taken up in 300 ml of dichloromethane, the organic phase is washed successively with 150 ml of a 0.3 M solution of sodium hydroxide in water, with 150 ml of water, twice with 150 ml of pH 2 sulfate buffer, with 150 ml of water and with 150 ml of a 10% by weight solution of potassium carbonate in water, dried over magnesium sulfate and filtered, and the solvent is evaporated off under vacuum at room temperature. The expected product is obtained, which is used in Example 3.
Reaction SMILES: C([Li])CCC.C(NC(C)C)(C)C.[C:13]([O:17][C:18]([N:20]1[CH2:24][C@H:23]([O:25][Si:26]([C:29]([CH3:32])([CH3:31])[CH3:30])([CH3:28])[CH3:27])[CH2:22][C@H:21]1[CH:33]1[CH2:37][N:36]([C:38]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:39])[C:35](=[O:45])[CH2:34]1)=[O:19])([CH3:16])([CH3:15])[CH3:14].C1(C)C=CC(S([N:55]=[N+:56]=[N-:57])(=O)=O)=CC=1.C[Si](Cl)(C)C>O1CCCC1>[N:55]([CH:34]1[CH:33]([C@@H:21]2[CH2:22][C@@H:23]([O:25][Si:26]([C:29]([CH3:32])([CH3:31])[CH3:30])([CH3:28])[CH3:27])[CH2:24][N:20]2[C:18]([O:17][C:13]([CH3:14])([CH3:15])[CH3:16])=[O:19])[CH2:37][N:36]([C:38]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:39])[C:35]1=[O:45])=[N+:56]=[N-:57]
Reactant: CC(C)(C)OC(=O)N1CC([C@@H]2C[C@@H](O[Si](C)(C)C(C)(C)C)CN2C(=O)OC(C)(C)C)CC1=O
Reactant: Cc1ccc(S(=O)(=O)N=[N+]=[N-])cc1
Agent: C[Si](C)(C)Cl
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: CC(C)NC(C)C
Product: CC(C)(C)OC(=O)N1CC([C@@H]2C[C@@H](O[Si](C)(C)C(C)(C)C)CN2C(=O)OC(C)(C)C)C(N=[N+]=[N-])C1=O
Reaction time: 0.75 h
Yield: 68.5 %

Procedure:
1.6M n-butyllithium (2.5 ml, 4 mmol) was dropwise added to a solution of diisopropylamine (0.64 ml, 4.6 mmol) in tetrahydrofuran (40 ml) under a nitrogen stream at -78° C., and the reaction solution was stirred for 45 minutes. A solution of (2S,4R)-N-tert-butoxycarbonyl-4-tert-butyldimethylsiloxy-2-(N-tert-butoxycarbonyl-2-pyrrolidon-4-yl)pyrrolidine (986 mg, 2 mmol, compound of Reference Example 5-1) in tetrahydrofuran (10 ml) was dropwise added to this solution, and the mixture was stirred at the same temperature for 2 hours. Then, p-toluenesulfonyl azide (945 mg, 4.8 mmol) was added thereto, and the mixture was stirred further for 1 hour. Then, trimethylsilyl chloride (1.29 ml, 10 mmol) was added to this reaction solution, and the mixture was stirred at room temperature for 1 hour. The reaction solution was concentrated under reduced pressure. A saturated sodium hydrogen carbonate aqueous solution was added to the residue, and then the mixture was extracted with methylene chloride (50 ml). The organic layer was washed with a saturated sodium chloride aqueous solution, then dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography (Wakogel™ C-300, chloroform) to obtain (2S,4R)-2-(3-azido-N-tert-butoxycarbonyl-2-pyrrolidon-4-yl)-N-tert-butoxycarbonyl-4-(tert-butyldimethylsiloxy)pyrrolidine (720 mg, yield: 68.5%).
Reaction SMILES: C(OCC1OC1)C1OC1.OC1C=CC([C:17]([C:20]2[CH:25]=[CH:24][C:23](O)=[CH:22][CH:21]=2)(C)C)=CC=1.CC(C1C=CC(OCC2OC2)=CC=1)(C1C=CC(OCC2OC2)=CC=1)C.F[Sb-](F)(F)(F)(F)F.C([Br:66])C1C=CC=CC=1.[N:67]1[CH:72]=[CH:71][N:70]=[CH:69][CH:68]=1>N1C=CC=CC=1>[Br-:66].[CH2:17]([N+:67]1[CH:72]=[CH:71][N:70]=[CH:69][CH:68]=1)[C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1
Reactant: BrCc1ccccc1
Reactant: c1cnccn1
Reactant: CC(C)(c1ccc(O)cc1)c1ccc(O)cc1
Agent: C(OCC1CO1)C1CO1
Agent: CC(C)(c1ccc(OCC2CO2)cc1)c1ccc(OCC2CO2)cc1
Agent: F[Sb-](F)(F)(F)(F)F
Solvent: c1ccncc1
Product: [Br-]
Product: c1ccc(C[n+]2ccncc2)cc1

Procedure:
As a difunctional resin, a diglycidylether of bisphenol A (hereinafter referred to as “DGEBA”) type epoxy resin, in a greater detail, “LY 556” manufactured by Ciba-Geigy AG and “YD-128” manufactured by Kukdo Chemicals were used. As a cycloaliphatic difunctional resin (hereinafter referred to as “CAE”), an epoxy resin “ERL 4221” manuafactured by Union Carbide Company was used. As a trifunctional resin, “Tactix 742” manufactured by Dow Chemicals and “YH 300” manufactured by Kukdo chemicals were used. As a tetrafunctional epoxy resin, “MY720” manufactured by Ciba-Geigy AG, was used. The latent cationic curing agent (the latent cationic curing agent containing a hexafluoroantimonate) was synthesized by the use of benzyl bromide, pyrazine and pyridine as starting materials (Y. C. Kim, S. J. Park, and J. R. Lee, Polymer J., 29, 759 (1997)). More particularly, for example, the method for synthesizing Sb-A type curing agent was explained as follows. To a 250 ml flask equipped with a stirrer, 60 g (20 mmol) of pyrazine and 7.30 g (42.7 mmol) of benzyl bromide were charged and reacted by mixing them at room temperature for 24 hours. Subsequently, the reaction solution was filtered to obtain a benzylpyrazinium bromide in white color. This benzylpyrazinium bromide was dissolved in 30 ml of distilled water and filtered to obtain a solution in which no purity (insoluble material) was contained. To said solution 5.17 g (20 mmol) of NaSbF6 was added to obtain a white product, which was then subjected to recrystallization by the use of methyl alcohol to give 4.84 g of N-benzylpyrazinium hexafluoroantimonate (BPH; a sort of Sb-A type curing agent, cationic latent catalytic curing agent containing hexafluoroantimonate) as a white reaction product.
Reaction SMILES: [CH3:1][C:2]1[C:3]([C:12]2[CH:16]=[C:15]([NH2:17])[NH:14][N:13]=2)=[N:4][C:5]2[C:10]([N:11]=1)=[CH:9][CH:8]=[CH:7][CH:6]=2.[C:18]([O:24][CH2:25][CH3:26])(=[O:23])[CH2:19][C:20](O)=[O:21].Cl.C(N=C=NCCCN(C)C)C>N1C=CC=CC=1>[CH3:1][C:2]1[C:3]([C:12]2[CH:16]=[C:15]([NH:17][C:20](=[O:21])[CH2:19][C:18]([O:24][CH2:25][CH3:26])=[O:23])[NH:14][N:13]=2)=[N:4][C:5]2[C:10]([N:11]=1)=[CH:9][CH:8]=[CH:7][CH:6]=2
Reactant: Cc1nc2ccccc2nc1-c1cc(N)[nH]n1
Reactant: CCOC(=O)CC(=O)O
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Solvent: c1ccncc1
Product: CCOC(=O)CC(=O)Nc1cc(-c2nc3ccccc3nc2C)n[nH]1
Reaction time: 0.5 h

Procedure:
To a suspension of 3-(3-methylquinoxalin-2-yl)-1H-pyrazol-5-amine (5.00 g, 22.2 mmol) and ethyl hydrogen malonate (2.88 mL, 24.4 mmol) in pyridine (89 mL) was added N-ethyl-N′-(3-dimethylaminopropyl)carbodiimide hydrochloride (6.38 g, 33.3 mmol) at 0° C. and stirred for 30 min. The reaction mixture was stirred for 1 h at room temperature and then concentrated in vacuo. The residue was diluted with water (100 mL) and the resulting precipitate was collected and washed with water followed by diethyl ether to give ethyl 3-{[3-(3-methylquinoxalin-2-yl)-1H-pyrazol-5-yl]amino}-3-oxopropanoate. MS (APCI): m/z 340 (M+H).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:24]=[CH:23][C:6]2[N:7]=[C:8]([NH:10][CH:11]=[C:12]([C:18]([O:20]CC)=[O:19])[C:13](OCC)=[O:14])[S:9][C:5]=2[CH:4]=1.[OH-:25].[Na+].O>C(O)C>[SH:9][C:5]1[CH:4]=[C:3]([O:2][CH3:1])[CH:24]=[CH:23][C:6]=1[N:7]1[C:13](=[O:14])[C:12]([C:18]([OH:20])=[O:19])=[CH:11][NH:10][C:8]1=[O:25]
Reactant: CCOC(=O)C(=CNc1nc2ccc(OC)cc2s1)C(=O)OCC
Reactant: [OH-]
Agent: [Na+]
Solvent: CCO
Solvent: O
Product: COc1ccc(-n2c(=O)[nH]cc(C(=O)O)c2=O)c(S)c1

Procedure:
25 g. Diethyl N-(6-methoxybenzthiazol-2-yl)-aminomethylenemalonate are introduced into a solution of 36 g. sodium hydroxide, 360 ml. water and 120 ml. ethanol which has been heated to 70° C. and the reaction mixture is heated under reflux for 30 minutes. A part of the ethanol is then removed in vacuo, filtered and, after cooling, the filtrate is acidified with 2 N hydrochloric acid. 1-(2-Mercapto-4-methoxyphenyl)-5-carboxypyrimidine-2,6-dione is obtained in a yield of 14.7 g. (70% of theory). According to the melting point and the IR, UV and NMR spectra, the product is identical with the compound prepared according to Variant I.
Reaction SMILES: Cl[C:2]1[C:3](CSCCN)=[N:4]C=C[CH:7]=1.C(C=C(OC)OC)#N.[C:21]([CH:23]=[C:24](OC)[NH:25][CH2:26][CH2:27][S:28][CH2:29][C:30]1[C:35]([Cl:36])=[CH:34][CH:33]=[CH:32][N:31]=1)#[N:22].C(N)C#C>>[C:21]([CH:23]=[C:24]([NH:4][CH2:3][C:2]#[CH:7])[NH:25][CH2:26][CH2:27][S:28][CH2:29][C:30]1[C:35]([Cl:36])=[CH:34][CH:33]=[CH:32][N:31]=1)#[N:22]
Reactant: COC(=CC#N)NCCSCc1ncccc1Cl
Reactant: NCCSCc1ncccc1Cl
Agent: C#CCN
Agent: COC(=CC#N)OC
Product: C#CCNC(=CC#N)NCCSCc1ncccc1Cl

Procedure:
When 2-[(3-chloro-2-pyridyl)methylthio]ethylamine is reacted with 1-cyano-2,2-bis(methoxy)ethylene and the resultant 1-cyano-2-methoxy-2-{2-[(3-chloro-2-pyridyl)methylthio]ethylamino}ethylene is reacted with propargylamine according to the general procedure of Example 1 Step B the title compound is produced.
Reaction SMILES: [N+:1]([O-:15])([O:3][CH2:4][CH:5]([O:11][N+:12]([O-:14])=[O:13])[CH2:6][CH2:7][CH2:8][CH2:9][OH:10])=[O:2].Cl[C:17]([O:19][C:20]1[CH:25]=[CH:24][C:23]([N+:26]([O-:28])=[O:27])=[CH:22][CH:21]=1)=[O:18].N1C=CC=CC=1>C(Cl)Cl.O>[C:17](=[O:18])([O:19][C:20]1[CH:21]=[CH:22][C:23]([N+:26]([O-:28])=[O:27])=[CH:24][CH:25]=1)[O:10][CH2:9][CH2:8][CH2:7][CH2:6][CH:5]([O:11][N+:12]([O-:14])=[O:13])[CH2:4][O:3][N+:1]([O-:15])=[O:2]
Reactant: O=[N+]([O-])OCC(CCCCO)O[N+](=O)[O-]
Reactant: O=C(Cl)Oc1ccc([N+](=O)[O-])cc1
Solvent: ClCCl
Solvent: O
Solvent: c1ccncc1
Product: O=C(OCCCCC(CO[N+](=O)[O-])O[N+](=O)[O-])Oc1ccc([N+](=O)[O-])cc1
Temperature: 25 °C
Yield: 80.5 %

Procedure:
To the solution of 6-hydroxyhexane-1,2-diyl dinitrate (150 mg, 0.67 mmol) in CH2Cl2 (15 mL) at rt was added 4-nitrophenyl chloroformate (202 mg, 1.00 mmol) and followed by pyridine (159 mg, 2.01 mmol). The mixture was stirred at rt over night and diluted with H2O. The mixture was extracted with CH2Cl2 and the organic layer was washed with brine, dried over MgSO4 and concentrated. The residue was purified by flash chromatography (Biotage SP1; column 25M; TLC method: n-hexane/ethyl acetate 7/3; Rf=0.35), affording product (210 mg, yield 81%).
Reaction SMILES: C1C=C2C(C(O)(O)C(=O)C2=CC=1)=O.Cl.CO[C:17]1[CH:39]=[CH:38][C:20]([C:21]([NH:34][CH2:35][CH2:36][NH2:37])([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)=[CH:19][CH:18]=1.COC1C=CC(C(NCCN)(C2C=CC=CC=2)C2C=CC(OC)=CC=2)=CC=1>C(Cl)Cl.CO>[C:21]([NH:34][CH2:35][CH2:36][NH2:37])([C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1)([C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[C:20]1[CH:38]=[CH:39][CH:17]=[CH:18][CH:19]=1
Reactant: COc1ccc(C(NCCN)(c2ccccc2)c2ccccc2)cc1
Agent: COc1ccc(C(NCCN)(c2ccccc2)c2ccc(OC)cc2)cc1
Agent: Cl
Agent: O=C1c2ccccc2C(=O)C1(O)O
Solvent: CO
Solvent: ClCCl
Product: NCCNC(c1ccccc1)(c1ccccc1)c1ccccc1

Procedure:
C21H22N2 (288.42); RF=0.21 (DCM/MeOH 5:1, v/v); spot stains with ninhydrin spray or with HCl vapour); N-(4-monomethoxytrityl)ethylenediamine; C22H24N2O (332.45); RF=0.21 (DCM/MeOH 5:1, v/v); spot stains with ninhydrin spray or with HCl vapour); N-(4,4′-dimethoxytrityl)ethylenediamine; C23H26N2O2 (362.48); RF=0.22 (DCM/MeOH 5:1, v/v); spot stains with ninhydrin spray or with HCl vapour).
Reaction SMILES: [C:1]([C:3]1[CH:8]=[CH:7][C:6]([CH2:9][CH2:10][C:11]([O:13][CH3:14])=[O:12])=[CH:5][CH:4]=1)#[CH:2].[Cl:15][C:16]1[CH:25]=[C:24]2[C:19]([C:20](I)=[CH:21][CH:22]=[N:23]2)=[CH:18][CH:17]=1>>[Cl:15][C:16]1[CH:25]=[C:24]2[C:19]([C:20]([C:2]#[C:1][C:3]3[CH:8]=[CH:7][C:6]([CH2:9][CH2:10][C:11]([O:13][CH3:14])=[O:12])=[CH:5][CH:4]=3)=[CH:21][CH:22]=[N:23]2)=[CH:18][CH:17]=1
Reactant: C#Cc1ccc(CCC(=O)OC)cc1
Reactant: Clc1ccc2c(I)ccnc2c1
Product: COC(=O)CCc1ccc(C#Cc2ccnc3cc(Cl)ccc23)cc1

Procedure:
The title compound was prepared from methyl 3-(4-ethynylphenyl)propanoate (54 mg, 0.29 mmol) and 7-chloro-4-iodoquinoline (93 mg, 0.32 mmol) according to the general procedure IC to give 54 mg (54%) of a beige solid after purification by flash chromatography (SiO2, EtOAc:PE, 1:4). Rf=0.06 (EtOAc:PE, 1:4); 1H NMR (CDCl3) δ 8.88 (d, J=4.8 Hz, 1H), 8.27 (d, J=9.0 Hz, 1H), 8.11 (m, 1H), 7.59-7.52 (m, 4H), 7.28-7.25 (m, 2H), 3.69 (s, 3H), 3.01 (t, J=7.8 Hz, 2H), 2.67 (t, J=7.8 Hz, 2H); 13C NMR (CDCl3) δ 172.9, 150.8, 148.5, 142.4, 135.8, 132.1, 129.9, 128.8, 128.6, 128.1, 127.4, 126.1, 123.5, 119.9, 99.2, 84.4, 51.7, 35.2, 30.9; ESI-MS m/z 372.1 (M+Na+).
Reaction SMILES: C(N(CC)CC)C.[Br:8][C:9]1[CH:10]=[C:11]([F:26])[C:12]([NH2:25])=[C:13]2[C:18]=1[O:17][CH2:16][CH:15]([C:19]1[CH:20]=[N:21][CH:22]=[CH:23][CH:24]=1)[NH:14]2.Cl[C:28](Cl)([O:30]C(=O)OC(Cl)(Cl)Cl)Cl>C1COCC1.O>[Br:8][C:9]1[C:18]2[O:17][CH2:16][CH:15]([C:19]3[CH:20]=[N:21][CH:22]=[CH:23][CH:24]=3)[N:14]3[C:28](=[O:30])[NH:25][C:12]([C:13]=23)=[C:11]([F:26])[CH:10]=1
Reactant: O=C(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl
Reactant: Nc1c(F)cc(Br)c2c1NC(c1cccnc1)CO2
Solvent: O
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: O=c1[nH]c2c(F)cc(Br)c3c2n1C(c1cccnc1)CO3
Temperature: 25 °C
Reaction time: 0.17 h

Procedure:
Triethylamine (140 μL, 1.0 mmol) was added to a solution of 8-bromo-6-fluoro-3-pyridin-3-yl-3,4-dihydro-2H-1,4-benzoxazin-5-amine (160 mg, 0.50 mmol)) in THF (6.0 mL), followed by addition of triphosgene (60 mg, 0.2 mmol), and the mixture was subsequently stirred at room temperature for 10 min. The mixture was diluted with water and extracted with ethyl acetate. The organic extracts were washed with brine and concentrated. Purification on silica gel eluting ethyl acetate in hexanes afforded the title compound. LCMS calc. for C14H10BrFN3O2 (M+H)+: m/z=350.0. found: 350.0.
Reaction SMILES: [NH2:1][C:2]1[C:7]([NH2:8])=[CH:6][C:5]([CH3:9])=[CH:4][N:3]=1.[CH2:10]([O:12][C:13](=[O:19])[CH2:14][C:15]([CH2:17]Cl)=O)[CH3:11]>C(O)C>[NH2:8][C:7]1[C:2]2[N:3]([C:14]([C:13]([O:12][CH2:10][CH3:11])=[O:19])=[C:15]([CH3:17])[N:1]=2)[CH:4]=[C:5]([CH3:9])[CH:6]=1
Reactant: CCOC(=O)CC(=O)CCl
Reactant: Cc1cnc(N)c(N)c1
Solvent: CCO
Product: CCOC(=O)c1c(C)nc2c(N)cc(C)cn12
Yield: 26.4 %

Procedure:
A stirred mixture of 2,3-diamino-5-methyl-pyridine (4.0 g, 32.5 mmol) and (5.9 g, 36.0 mmol) of ethyl-chloroacetoacetate in 75 ml abs. ethanol was refluxed over night. The ethanol was evaporated under reduced pressure. The residue was dissolved in 2 M HCl and washed 3 times with diethyl ether, pH was adjusted to 9 and extracted 3 times with dichloromethane. The organic layer was dried over anhydrous sodium sulfate and evaporated. The residue was purified by column chromatography on silica gel with dichloromethane:methanol 95:5 as eluent to give the title product 2.0 g (28%).