Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [ClH:1].Cl[C:3]1[N:8]2[CH:9]=[CH:10][N:11]=[C:7]2[CH:6]=[CH:5][CH:4]=1.C(=O)([O-])[O-].[Na+].[Na+].O1[CH2:23][CH2:22][O:21][CH2:20]C1>C(OCC)(=O)C.O.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>[Cl:1][C:4]1[CH:5]=[CH:6][C:22]([O:21][CH3:20])=[C:23]([C:3]2[N:8]3[CH:9]=[CH:10][N:11]=[C:7]3[CH:6]=[CH:5][CH:4]=2)[CH:3]=1
Reactant: Clc1cccc2nccn12
Reactant: C1COCCO1
Reactant: Cl
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: O
Solvent: CCOC(C)=O
Product: COc1ccc(Cl)cc1-c1cccc2nccn12
Temperature: 25 °C
Yield: 70 %

Procedure:
To a stirred mixture of 5-chloroimidazo[1,2-a]pyridine hydrochloride (1.89 g, 10.0 mmol), (5-chloro-2-methoxy)benzene boronic acid (2.07 g, 12.0 mmol), 2 M aqueous sodium carbonate (20 mL, 40 mmol) and p-dioxane (50 mL) was added tetrakis(triphenylphosphine)palladium(0) (0.58 g, 0.50 mmol) at ambient temperature. The mixture was heated at reflux for 16 h, allowed to cool to ambient temperature and diluted with ethyl acetate (50 mL) and water (20 mL). The organic layer was washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue was purified by column chromatography eluting with a 50-80% gradient of ethyl acetate in hexanes to afford 5-(5-chloro-2-methoxyphenyl)imidazo[1,2-a]pyridine as a colorless solid in 70% yield (1.82 g): 1H NMR (300 MHz, DMSO-d6) δ7.72-7.48 (m, 4H), 7.37-7.23 (m, 3H), 6.89 (d, J=6.6 Hz, 1H), 3.74 (s, 3H); MS (ES+) m/z 259.0 (M+1), 261.0 (M+1).
Reaction SMILES: [Cr](Cl)([O-])(=O)=O.[NH+]1C=CC=C[CH:7]=1.[OH:12][CH2:13][C:14]1[CH:19]=[C:18]([CH2:20][O:21][CH3:22])[C:17]([CH:23]([CH3:25])[CH3:24])=[CH:16][C:15]=1[CH:26]([CH3:28])[CH3:27]>C(Cl)Cl>[CH:26]([C:15]1[CH:16]=[C:17]([CH:23]([CH3:24])[CH3:25])[C:18]([CH2:20][O:21][CH2:22][CH3:7])=[CH:19][C:14]=1[CH:13]=[O:12])([CH3:28])[CH3:27]
Reactant: c1cc[nH+]cc1
Reactant: COCc1cc(CO)c(C(C)C)cc1C(C)C
Agent: O=[Cr](=O)([O-])Cl
Solvent: ClCCl
Product: CCOCc1cc(C=O)c(C(C)C)cc1C(C)C
Temperature: 25 °C
Reaction time: 8 h

Procedure:
17.2 g (80 mmol) of pyridinium chlorochromate are added to a solution of 15.7 g (66.5 mmol) of the compound from Example 4 in 300 ml of methylene chloride, the mixture is stirred overnight at room temperature, filtered with suction through kieselgur, washed with 200 ml of methylene chloride, and dried using sodium sulphate.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([S:8][CH3:9])=[C:4]([F:10])[C:3]=1[C:11]([F:14])([F:13])[F:12].C([Li])CCC.[C:20](=[O:22])=[O:21].[OH-].[Na+]>C(OCC)C.CCCCCC.O>[F:10][C:4]1[C:3]([C:11]([F:14])([F:13])[F:12])=[C:2]([CH:7]=[CH:6][C:5]=1[S:8][CH3:9])[C:20]([OH:22])=[O:21]
Reactant: O=C=O
Reactant: CSc1ccc(Br)c(C(F)(F)F)c1F
Agent: [Li]CCCC
Agent: [Na+]
Agent: [OH-]
Solvent: CCOCC
Solvent: O
Solvent: CCCCCC
Product: CSc1ccc(C(=O)O)c(C(F)(F)F)c1F
Temperature: -78 °C
Reaction time: 1 h

Procedure:
21.0 g (72.98 mmol) of 1-bromo-3-fluoro-4-(methylsulfanyl)-2-(trifluoromethyl)benzene were dissolved in 275 ml of absolute diethyl ether and cooled to −78° C. 54.8 ml (87.59 mmol) of a 1.6M solution of n-butyllithium in hexane were slowly added dropwise, and the resulting solution was stirred at −78° C. for 60 minutes. The reaction mixture was then added to freshly ground dry ice and slowly warmed to RT. Water was added, and the reaction mixture was made alkaline using 2M NaOH solution and washed with diethyl ether. The aqueous phase was then acidified with 51M HCl solution, causing the product to precipitate. The precipitate was filtered off with suction and dried under reduced pressure.
Reaction SMILES: CCCCCCCCC[CH2:10][CH2:11][C:12]([O:14][Sn](O[C:25]([CH2:27]CCCCCCCCCC)=[O:26])(CCCC)CCCC)=[O:13].CC1(C)CC(C[N:47]=[C:48]=[O:49])(C)CC(N=C=O)C1>>[C:12]([OH:14])(=[O:13])[CH:11]=[CH2:10].[NH2:47][C:48]([O:26][CH2:25][CH3:27])=[O:49]
Reactant: CC1(C)CC(N=C=O)CC(C)(CN=C=O)C1
Reactant: CCCCCCCCCCCC(=O)O[Sn](CCCC)(CCCC)OC(=O)CCCCCCCCCCC
Product: C=CC(=O)O
Product: CCOC(N)=O

Procedure:
Into the same flask as in Production Example 1, 993 g of tri- and tetra-acrylate of pentaerythritol [ARONIX M-305 produced by Toa Gosei Co., Ltd.; hereinafter referred to as “M-305”] (containing 2 mol of triacrylate), 0.61 g of BHT and 0.36 g of DBTL are prepared, and is stirred at a liquid temperature of 70 to 75° C., while 222 g (1.0 mol) of IPDI is dropped into the flask.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[N:8]([S:12]([C:15]3[CH:21]=[CH:20][C:18]([CH3:19])=[CH:17][CH:16]=3)(=[O:14])=[O:13])[C:9](I)=[CH:10][C:3]=12.CC1(C)C(C)(C)OB([C:30]2[CH2:35][CH2:34][N:33]([C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[CH2:32][CH:31]=2)O1.C(=O)(O)[O-].[Na+]>CN(C)C=O>[Cl:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[N:8]([S:12]([C:15]3[CH:21]=[CH:20][C:18]([CH3:19])=[CH:17][CH:16]=3)(=[O:14])=[O:13])[C:9]([C:30]3[CH2:35][CH2:34][N:33]([C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[CH2:32][CH:31]=3)=[CH:10][C:3]=12
Reactant: CC(C)(C)OC(=O)N1CC=C(B2OC(C)(C)C(C)(C)O2)CC1
Reactant: Cc1ccc(S(=O)(=O)n2c(I)cc3c(Cl)ccnc32)cc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CN(C)C=O
Product: Cc1ccc(S(=O)(=O)n2c(C3=CCN(C(=O)OC(C)(C)C)CC3)cc3c(Cl)ccnc32)cc1
Temperature: 85 °C

Procedure:
A mixture of 4-chloro-2-iodo-1-tosyl-1H-pyrrolo[2,3-b]pyridine (7.50 g, 17.33 mmol), tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate (6.43 g, 20.80 mmol), tetrakis(triphenylphospine)palladium (0.801 g, 0.693 mmol) and aqueous sodium bicarbonate (40 mL) in N,N-dimethylformamide (160 mL) was flushed with nitrogen and heated at 85° C. for 24 hours. The mixture was diluted with water and brine and extracted with ethyl acetate. The organic extracts were washed with water, dried over magnesium sulfate, filtered, concentrated, and purified by flash chromatography on silica (ISCO Companion), eluting with a gradient of 8:2 to 7:3 heptanes/ethyl acetate to give the title compound. MS (ESI+) m/z 488.0 (M+H)+.
Reaction SMILES: C([O:3][C:4]([C:6]1[N:7]=[N:8][C:9]([O:12][CH2:13][C:14]2[C:15]([C:20]3[CH:25]=[CH:24][CH:23]=[C:22]([F:26])[CH:21]=3)=[N:16][O:17][C:18]=2[CH3:19])=[CH:10][CH:11]=1)=O)C.[CH:27]([NH2:30])([CH3:29])[CH3:28]>>[CH:27]([NH:30][C:4]([C:6]1[N:7]=[N:8][C:9]([O:12][CH2:13][C:14]2[C:15]([C:20]3[CH:25]=[CH:24][CH:23]=[C:22]([F:26])[CH:21]=3)=[N:16][O:17][C:18]=2[CH3:19])=[CH:10][CH:11]=1)=[O:3])([CH3:29])[CH3:28]
Reactant: CC(C)N
Reactant: CCOC(=O)c1ccc(OCc2c(-c3cccc(F)c3)noc2C)nn1
Product: Cc1onc(-c2cccc(F)c2)c1COc1ccc(C(=O)NC(C)C)nn1
Yield: 39 %

Procedure:
As described for example 52, 6-[3-(3-fluoro-phenyl)-5-methyl-isoxazol-4-ylmethoxy]-pyridazine-3-carboxylic acid ethyl ester (143 mg, 0.4 mmol) was converted, using isopropylamine instead of ethanolamine, to the title compound (58 mg, 39%) which was obtained as a white solid after recrystallisation from heptane:ethyl acetate. MS: m/e=371.0 [M+H]+.
Reaction SMILES: [CH2:1]([N:8]1[CH2:12][CH2:11][CH:10]([N:13]=[N+:14]=[N-:15])[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([C:18]#[C:19][C:20]([O-:22])=[O:21])C.[CH:23]1C=CC=C[CH:24]=1>>[CH2:1]([N:8]1[CH2:12][CH2:11][CH:10]([N:13]2[C:19]([C:20]([O:22][CH2:23][CH3:24])=[O:21])=[CH:18][N:15]=[N:14]2)[CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CCC#CC(=O)[O-]
Reactant: [N-]=[N+]=NC1CCN(Cc2ccccc2)C1
Reactant: c1ccccc1
Product: CCOC(=O)c1cnnn1C1CCN(Cc2ccccc2)C1
Yield: 20.6 %

Procedure:
A mixture of N-benzyl-3-azido-pyrrolidine (5 g, 0.024 mmol) and ethylpropiolate (5 g, 0.051 mmol) in benzene (50 ml) heated under reflux for 48 hrs. Reaction solution was evaporated to dark brown oil, purified on silica gel column using ethylacetate, CHCl3 and methanol to get N-benzyl-3-(5-ethoxycarbonyl-1,2,3-triazol-1-yl) pyrrolidine (1.5 g, 20.6%). 1H NMR (CDCl3) δ: 1.37 (t, 3H), 2.42-2.58 (m, 2H), 2.71-3.01 (m, 3H), 3.20-3.32 (m, 1H), 3.73 (S, 2H), 4.35 (q, 2H), 5.72-5.88 (m, 1H), 7.2-7.4 (m, 5H), 8.12 (S, 1H). N-benzyl-3-(4-ethoxy carbonyl -1,2,3-triazol-1-yl)pyrrolidine (5 g, 68.7%). 1H NMR (CDCl3) δ: 1.40 (t, 3H), 1.8-3.20 (m, 6H), 3.70 (S, 2H), 4.40 (q, 2H), 5.06-5.48 (m, 1H), 7.33 (S, 5H), 8.43 (S, 1H).
Reaction SMILES: BrC1C=CC(S(O[CH2:12][C@@H:13]2[O:27][C:17]3=[C:18]4[C:23](=[CH:24][CH:25]=[C:16]3[O:15][CH2:14]2)[N:22]=[C:21]([CH3:26])[CH:20]=[CH:19]4)(=O)=O)=CC=1.[Br:28][C:29]1[CH:30]=[C:31]2[C:36](=[CH:37][CH:38]=1)[N:35]=[C:34]([N:39]1[CH2:44][CH2:43][NH:42][CH2:41][CH2:40]1)[CH:33]=[CH:32]2.C(=O)(O)[O-].[Na+]>CS(C)=O>[Br:28][C:29]1[CH:30]=[C:31]2[C:36](=[CH:37][CH:38]=1)[N:35]=[C:34]([N:39]1[CH2:40][CH2:41][N:42]([CH2:12][C@@H:13]3[O:27][C:17]4=[C:18]5[C:23](=[CH:24][CH:25]=[C:16]4[O:15][CH2:14]3)[N:22]=[C:21]([CH3:26])[CH:20]=[CH:19]5)[CH2:43][CH2:44]1)[CH:33]=[CH:32]2
Reactant: Cc1ccc2c3c(ccc2n1)OC[C@H](COS(=O)(=O)c1ccc(Br)cc1)O3
Reactant: Brc1ccc2nc(N3CCNCC3)ccc2c1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CS(C)=O
Product: Cc1ccc2c3c(ccc2n1)OC[C@H](CN1CCN(c2ccc4cc(Br)ccc4n2)CC1)O3
Temperature: 75 °C
Yield: 39.3 %

Procedure:
To a solution of [(2R)-8-methyl-2,3-dihydro[1,4]dioxino[2,3-f]quinolin-2-yl]methyl 4 bromobenzene sulfonate (2.31 g, 5.13 mmol) in dimethylsulfoxide (123 mL) is added the 6-bromo-2-piperazin-1-yl-quinoline of Step B (1.5 g, 5.13 mmol) and the mixture is heated at 75° C. under nitrogen overnight. The mixture is poured into saturated aqueous sodium bicarbonate and extracted with ethyl acetate. The extracts are dried over anhydrous magnesium sulfate and evaporated to dryness. The residue is flash chromatographed on silica gel Merck-60 using a gradient of methanol (0.5–2%) in ethyl acetate-hexane (55:45) to provide the title compound as an off-white solid (1.02 g), m.p. 153–154° C.
Reaction SMILES: F[C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[CH:11]([CH3:13])[CH3:12])=[C:4]([NH:14][CH2:15][C:16]2[CH:17]=[N:18][CH:19]=[CH:20][CH:21]=2)[N:3]=1.CCN(C(C)C)C(C)C.[NH2:31][CH:32]([CH2:39][CH3:40])[CH:33]([OH:38])[C:34]([F:37])([F:36])[F:35]>CCCCO.CS(C)=O>[F:35][C:34]([F:37])([F:36])[CH:33]([OH:38])[CH:32]([NH:31][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[CH:11]([CH3:13])[CH3:12])=[C:4]([NH:14][CH2:15][C:16]2[CH:17]=[N:18][CH:19]=[CH:20][CH:21]=2)[N:3]=1)[CH2:39][CH3:40]
Reactant: CC(C)n1cnc2c(NCc3cccnc3)nc(F)nc21
Reactant: CCC(N)C(O)C(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: CS(C)=O
Solvent: CCCCO
Product: CCC(Nc1nc(NCc2cccnc2)c2ncn(C(C)C)c2n1)C(O)C(F)(F)F
Temperature: 25 °C
Reaction time: 72 h

Procedure:
To a stirred solution of (2-fluoro-9-isopropyl-9H-purin-6-yl)-pyridin-3-ylmethyl-amine (300 mg, 1.05 mmol) in n-BuOH/DMSO (5 mL, 4:1) at room temperature under an argon atmosphere was added DIEA (1.4 ml, 10 eq, 8 mmol) followed by 3-amino-1,1,1-trifluoropentan-2-ol (1 g, 6.4 mmol). The flask was fitted with a condenser and the reaction mixture was placed in a preheated oil bath at 140° C. and stirred at this temperature for 72 h. The reaction mixture was allowed to cool to room temperature and the solvent was evaporated in vacuo. The residue was partitioned between EtOAc (50 ml) and water (50 ml), the aqueous phase was extracted with more EtOAc (2×25 ml), and the combined organic phase was washed with brine (50 ml), dried (MgSO4) and evaporated in vacuo. The residue was purified by gradient flash column chromatography on silica gel eluted with CHCl3:MeOH (100:0→95:5), to afford the title compound as a colorless film (42 mg, 9.4%). δH (CDCl3, 500 MHz) 1.04 (3 H, t, J 7.5, CHCH2CH3) 1.56 (6 H, d, J 7.5, CH[CH3]2), 1.8-1.73 (2 H, m, CHCH2CH3), 4.13-4.07 (1 H, m, CHMe2), 4.22-4.2 (1 H, m, CHEt) 4.57-4.55 (1 H, m, CHOHCF3), 4.71 (2 H, s, b, NHCH2Ar), 5.08 (1 H, s, b, NH), 7.2 (1 H, dd, J 5, 10 ArH), 7.51 (1 H, s, ArH), 7.64 (1 H, d, J 10, ArH), 8.46 (1 H, d, J 5, ArH), 8.55 (1 H, s, ArH); δC (CDCl3, 500 MHz) 159.28 (C), 154.72 (C), 149.07 (CH), 148.47 (CH), 135.44 (CH), 134.83 (C), 134.48 (CH), 124.12 (C), 123.44 (CH), 114.62 (C), 73.1 (CH), 55.88 (CH), 46.70 (CH), 41.78 (CH2), 23.68 (CH2) 22.36 (2×CH3), 11.55 (CH3); 19FNMR δ −74.83; m/z 424.2 (M+H)
Reaction SMILES: C(N(C(C)C)CC)(C)C.[N:10]1[CH:11]=[C:12](/[CH:19]=[CH:20]/[C:21]([OH:23])=O)[N:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=12.[C:24]([O:28][C:29](=[O:38])[NH:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=1[NH2:37])([CH3:27])([CH3:26])[CH3:25].F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1>ClCCl>[N:10]1[CH:11]=[C:12](/[CH:19]=[CH:20]/[C:21]([NH:37][C:32]2[CH:33]=[CH:34][CH:35]=[CH:36][C:31]=2[NH:30][C:29](=[O:38])[O:28][C:24]([CH3:26])([CH3:25])[CH3:27])=[O:23])[N:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=12
Reactant: CC(C)(C)OC(=O)Nc1ccccc1N
Reactant: O=C(O)/C=C/c1cnc2ccccn12
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: CC(C)(C)OC(=O)Nc1ccccc1NC(=O)/C=C/c1cnc2ccccn12
Temperature: 25 °C
Reaction time: 8 h
Yield: 33 %

Procedure:
Diisopropylethylamine (DIPEA, 0.34 g, 2.63 mmol) was added to a solution of (E)-3-(imidazo[1,2-a]pyridin-3-yl)acrylic acid (0.17 g, 0.88 mmol) in 20 mL of dichloromethane (DCM). After addition of tert-butyl-2-aminophenylcarbamate (0.22 g, 1.65 mmol) and 2-(1H-7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HATU, 0.43 g, 1.14 mmol) the reaction mixture was stirred overnight at room temperature under a nitrogen atmosphere. After completion of the reaction as indicated by HPLC, the reaction mixture was washed with saturated sodium bicarbonate (NaHCO3) and brine. It was dried over Na2SO4, filtered and evaporated to give crude (E)-tert-butyl (2-(3-(imidazo[1,2-a]pyridin-3-yl)acrylamido)phenyl)carbamate. The solid was washed with ethyl acetate (50 mL) and saturated NaHCO3 gave pure product as a light colored solid (0.11 g). ES+(M+H)+379.
Reaction SMILES: C([O:4][C:5]1[CH:10]=[CH:9][C:8]([C:11]2[C:12](Cl)=[N:13][CH:14]=[N:15][CH:16]=2)=[CH:7][C:6]=1[O:18]C(=O)C)(=O)C.O.[SH2:23].[Na]>CO>[OH:18][C:6]1[CH:7]=[C:8]([C:11]2[C:12](=[S:23])[NH:13][CH:14]=[N:15][CH:16]=2)[CH:9]=[CH:10][C:5]=1[OH:4]
Reactant: CC(=O)Oc1ccc(-c2cncnc2Cl)cc1OC(C)=O
Reactant: S
Agent: [Na]
Solvent: O
Solvent: CO
Product: Oc1ccc(-c2cnc[nH]c2=S)cc1O
Temperature: 60 °C
Reaction time: 4.5 h
Yield: 97.1 %

Procedure:
4-(4-Chloro-5-pyrimidinyl)-o-phenylene diacetate (1.1 g) (3.6 mmol) are dissolved in 30 ml of methanol. 1.56 g of sodium hydrogen sulphide hydrate are added thereto and the mixture is stirred at 60° C. for 4.5 hours. The solvent is distilled off in a vacuum and the residue is dissolved in 20 ml of water. The solution is acidified with dilute aqueous hydrochloric acid to pH 5, the precipitated product is filtered off under suction and washed with water and diethyl ether. After drying in a high vacuum there are obtained 770 mg of 5-(3,4-dihydroxyphenyl)-4(3H)-pyrimidinethione as yellow crystals of m.p. 235° C. (dec.).
Reaction SMILES: C1CCC([O:7][C:8]([CH2:10][CH:11](S([O-])(=O)=O)[C:12]([O:14]C2CCCCC2)=[O:13])=[O:9])CC1.[Na+]>O>[C:8]([OH:9])(=[O:7])[CH:10]=[CH2:11].[C:12]([OH:14])(=[O:13])/[CH:11]=[CH:10]\[C:8]([OH:9])=[O:7]
Reactant: O=C(CC(C(=O)OC1CCCCC1)S(=O)(=O)[O-])OC1CCCCC1
Agent: [Na+]
Solvent: O
Product: C=CC(=O)O
Product: O=C(O)/C=C\C(=O)O
Temperature: 50 °C
Yield: 84 %

Procedure:
3.2 l of distilled water was put in a reactor. After displacing the atmosphere with nitrogen, the temperature was increased to 50° C. An aqueous solution consisting of 4.32 g of a compound of formula ##STR8## ("Pelex CS" produced by Kao Co., Ltd.), 0.72 g of an acrylic acid-maleic acid copolymer (produced by Kao Co., Ltd.; viscosity: 520 poise), and 0.2 (of water was added thereto.
Reaction SMILES: [C:1]([N:5]1[C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][C:8]=2[O:7][C:6]1=[O:14])(=[O:4])[CH2:2][CH3:3].[CH:15](=[O:22])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1>>[CH3:3][C@H:2]([C@H:15]([OH:22])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[C:1]([N:5]1[C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][C:8]=2[O:7][C:6]1=[O:14])=[O:4]
Reactant: O=Cc1ccccc1
Reactant: CCC(=O)n1c(=O)oc2ccccc21
Product: C[C@@H](C(=O)n1c(=O)oc2ccccc21)[C@H](O)c1ccccc1

Procedure:
Prepared according to the method of paragraph C by reaction of N-propionyl-2-benzoxazolinone with benzaldehyde; mp 155-158° C. 1H NMR (CDCl3) δ 8.10 (m, 1H), 7.45 (m, 2H), 7.35 (m, 2H), 7.26 (m, 4H), 5.30 (d, 1H), 4.26 (dq, J=3,6 Hz, 1H), 1.26 (d, 3H). 13C NMR (CDCl3) δ 175.6, 151.0, 142.2, 141.0, 128.4, 127.7, 126.0, 125.5, 124.9, 116.3, 110.0, 73.2, 46.0, 10.3.
Reaction SMILES: [CH:1]1[C:6]([CH2:7]Br)=[CH:5][CH:4]=[C:3]([N+:9]([O-:11])=[O:10])[CH:2]=1.[CH2:12]([NH:14][CH2:15][CH3:16])[CH3:13]>CO>[CH2:12]([N:14]([CH2:15][CH3:16])[CH2:7][C:6]1[CH:5]=[CH:4][C:3]([N+:9]([O-:11])=[O:10])=[CH:2][CH:1]=1)[CH3:13]
Reactant: CCNCC
Reactant: O=[N+]([O-])c1ccc(CBr)cc1
Solvent: CO
Product: CCN(CC)Cc1ccc([N+](=O)[O-])cc1
Temperature: 25 °C
Reaction time: 3 h
Yield: 99.6 %

Procedure:
P-nitrobenzyl bromide (5.0 g) was added to a methanol solution (50 mL) of diethylamine (16.9 g), and stirred at room temperature for 3 hours. Methanol was evaporated off from the reaction liquid under reduced pressure, and water was added to the resulting residue, and extracted with ethyl acetate. The organic layer was extracted with 1 N hydrochloric acid, and the aqueous layer was neutralized with aqueous ammonium solution. The aqueous layer was extracted with ethyl acetate, and the organic layer was dried with anhydrous magnesium sulfate, and then the solvent was evaporated off under reduced pressure to obtain N,N-diethyl-N-(4-nitrobenzyl)amine (4.8 g) as an orange oily substance.
Reaction SMILES: CS(O[CH2:6][CH2:7][C:8]1[CH:13]=[CH:12][C:11]([NH:14][C:15]2[N:24]=[CH:23][C:22]3[CH2:21][CH:20]([C:25]4[CH:30]=[CH:29][C:28]([Cl:31])=[C:27]([Cl:32])[CH:26]=4)[C:19]4[CH:33]=[CH:34][CH:35]=[CH:36][C:18]=4[C:17]=3[N:16]=2)=[CH:10][CH:9]=1)(=O)=O.[CH3:37][N:38]1[CH2:43][CH2:42][NH:41][CH2:40][CH2:39]1>>[Cl:32][C:27]1[CH:26]=[C:25]([CH:20]2[C:19]3[CH:33]=[CH:34][CH:35]=[CH:36][C:18]=3[C:17]3[N:16]=[C:15]([NH:14][C:11]4[CH:12]=[CH:13][C:8]([CH2:7][CH2:6][N:41]5[CH2:42][CH2:43][N:38]([CH3:37])[CH2:39][CH2:40]5)=[CH:9][CH:10]=4)[N:24]=[CH:23][C:22]=3[CH2:21]2)[CH:30]=[CH:29][C:28]=1[Cl:31]
Reactant: CS(=O)(=O)OCCc1ccc(Nc2ncc3c(n2)-c2ccccc2C(c2ccc(Cl)c(Cl)c2)C3)cc1
Reactant: CN1CCNCC1
Product: CN1CCN(CCc2ccc(Nc3ncc4c(n3)-c3ccccc3C(c3ccc(Cl)c(Cl)c3)C4)cc2)CC1

Procedure:
This product was synthesized as described in general procedure 2 except 4-(6-(3,4-dichlorophenyl)-5,6-dihydrobenzo[h]quinazolin-2-ylamino)phenethyl methanesulfonate was used instead of 4-(6-(3-bromophenyl)-5,6-dihydrobenzo[h]quinazolin-2-ylamino)phenethyl methanesulfonate and N-methyl piperazine was used instead of piperidine to afford 6-(3,4-dichlorophenyl)-N-(4-(2-(4-methylpiperazin-1-yl)ethyl)phenyl)-5,6-dihydrobenzo[h]quinazolin-2-amine M.p.=119-121° C. 1H NMR 400 MHz (CDCl3) δ 13.02 (br s, 3H), 11.07 (br s, 1H), 8.42-8.35 (m, 1H), 7.97 (s, 1H), 7.74 (d, J=8.2 Hz, 2H), 7.6-7.5 (m, 2H), 7.38-7.34 (m, 1H), 7.28-7.23 (m, 2H), 7.18 (d, J=2.0 Hz, 1H), 7.12-7.07 (m, 1H), 6.9-6.8 (m, 1H), 4.35 (t, J=6.7 Hz, 1H), 3.48 (br s, 8H), 3.3-2.96 (m, 6H), 2.83 (s, 3H). LCMS m/e 545 (M+H).
Reaction SMILES: [S:1]1[CH:5]=[CH:4][C:3]([C:6]2[CH:13]=[CH:12][C:9]([CH2:10]O)=[CH:8][CH:7]=2)=[CH:2]1.C(N(C(C)C)CC)(C)C.FC(F)(F)S(OS(C(F)(F)F)(=O)=O)(=O)=O.C([N:57]1[CH:61]=[C:60]([CH2:62][C:63]2[CH:68]=[CH:67][C:66]([C:69]#[N:70])=[CH:65][CH:64]=2)[N:59]=[CH:58]1)(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cl:71]CCl>>[ClH:71].[S:1]1[CH:5]=[CH:4][C:3]([C:6]2[CH:13]=[CH:12][C:9]([CH2:10][N:59]3[C:60]([CH2:62][C:63]4[CH:68]=[CH:67][C:66]([C:69]#[N:70])=[CH:65][CH:64]=4)=[CH:61][N:57]=[CH:58]3)=[CH:8][CH:7]=2)=[CH:2]1
Reactant: OCc1ccc(-c2ccsc2)cc1
Reactant: ClCCl
Reactant: N#Cc1ccc(Cc2cn(C(c3ccccc3)(c3ccccc3)c3ccccc3)cn2)cc1
Agent: O=S(=O)(OS(=O)(=O)C(F)(F)F)C(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Product: Cl
Product: N#Cc1ccc(Cc2cncn2Cc2ccc(-c3ccsc3)cc2)cc1
Temperature: -78 °C
Reaction time: 1 h

Procedure:
To a solution of 4-thien-3-yl-benzyl alcohol (253 mg, 1.33 mmol) and diisopropylethylamine (0.464 mL, 2.66 mmol) in dichloromethane (7 mL) at -78° C. was added trifluoromethanesulfonic anhydride (0.224 mL, 1.33 mmol) and the mixture stirred at -78° C. for 1 hour. To this mixture was added a solution of 1-trityl-4-(4-cyanobenzyl)-imidazole (566 mg , 1.33 mmol) in dichloromethane (5 mL). The mixture was allowed to warm to ambient temperature and stirred for 2 hours. The solvent was evaporated in vacuo. The residue was dissolved in methanol (50 mL), heated at reflux for 1 hour, and the solvent evaporated in vacuo. The residue was partitioned between dichloromethane and sat. aq. NaHCO3 solution. The organic layer was dried, (Na2SO4) and the solvent evaporated in vacuo. The residue was chromatographed (silica gel, 2% MeOH in CH2Cl2) and the amine was converted to the HCl salt by treatment with 1.0M HCl in aqueous acetonitrile. Evaporation of the solvent in vacuo afforded the title compound as a white solid.
Reaction SMILES: [CH2:1]([C:4]1[CH:15]=[CH:14][C:7]2[O:8][CH:9]([C:11](=[O:13])[CH3:12])[O:10][C:6]=2[CH:5]=1)[CH:2]=[CH2:3].[CH2:16]=[CH:17][CH2:18]CC>ClCCl.[Ru](Cl)Cl.C1(C(P(C2CCCCC2)(C2CCCCC2)C2CCCCC2)P(C2CCCCC2)(C2CCCCC2)C2CCCCC2)C=CC=CC=1>[CH2:1]([C:4]1[CH:15]=[CH:14][C:7]2[O:8][CH:9]([C:11](=[O:13])[CH3:12])[O:10][C:6]=2[CH:5]=1)[CH:2]=[CH:3][CH2:16][CH2:17][CH3:18]
Reactant: C=CCCC
Reactant: C=CCc1ccc2c(c1)OC(C(C)=O)O2
Agent: Cl[Ru]Cl
Agent: c1ccc(C([PH](C2CCCCC2)(C2CCCCC2)C2CCCCC2)[PH](C2CCCCC2)(C2CCCCC2)C2CCCCC2)cc1
Solvent: ClCCl
Product: CCCC=CCc1ccc2c(c1)OC(C(C)=O)O2
Reaction time: 2 h
Yield: 13.3 %

Procedure:
A solution of 1-(5-allylbenzo[d][1,3]dioxol-2-yl)ethanone (5 g), phenylmethylenebis(tricyclohexylphosphine) ruthenium dichloride (0.9 g) and pent-1-ene (5 g) in dichloromethane (40 ml) was stirred at room temperature. After 2 hours, a control by gc analysis shows 60% conversion, but three additional portions of 5 g of pent-1-ene were added during the reaction time (48 hours) to go to completion. Then, the reaction mixture was filtered on a short column of silica gel and concentrated in vacuum to remove the solvent. Finely the crude product was purified by flash chromatography on silica gel (eluant heptane/ethyl acetate 95/5) to give 0.8 g (19%) of a colorless oil, identified as a 85/15 E/Z mixture.
Reaction SMILES: [NH:1]([C:5]1[C:13]([N+:14]([O-:16])=[O:15])=[CH:12][C:8]2[O:9][CH2:10][O:11][C:7]=2[CH:6]=1)C(C)=O.C[O-].[Na+].C(O)(=O)C>CO>[NH2:1][C:5]1[C:13]([N+:14]([O-:16])=[O:15])=[CH:12][C:8]2[O:9][CH2:10][O:11][C:7]=2[CH:6]=1
Reactant: CC(=O)Nc1cc2c(cc1[N+](=O)[O-])OCO2
Agent: C[O-]
Agent: [Na+]
Solvent: CO
Solvent: CC(=O)O
Product: Nc1cc2c(cc1[N+](=O)[O-])OCO2
Yield: 95.1 %

Procedure:
40 g of 5-acetamino-6-nitro-1,3-benzodioxole were dissolved with heating in 4 l of methanol in a 10 round flask equipped with a reflux condenser. To this hot solution was added a boiling solution of 40 g of sodium methoxide in 4 l of methanol and the mixture was boiled under reflux for exactly 15 minutes. Then, the reaction was interrupted by adding 220 ml of glacial acetic acid. The methanol was removed by distillation and the last traces thereof, together with the glacial acetic acid, were removed by a two-fold evaporation with toluene. The product went into solution with 3 l of methylene chloride and could be freed from the organic residues by suction filtration. The methylene chloride solution was filtered through silicon dioxide and evaporated in vacuo. The residue, recrystallized from isopropanol, gave 30.9 g (95% of theory) of 5-amino-6-nitro-1,3-benzodioxole of melting point 203°-204° C.