Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][CH:2]1[CH2:6][CH2:5][N:4]([C:7]2[CH:12]=[C:11]([CH3:13])[CH:10]=[CH:9][N:8]=2)[CH2:3]1.[C:14]([O:18][C:19]([NH:21][C:22]([NH:24][C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])=S)=[O:20])([CH3:17])([CH3:16])[CH3:15].C(N(C(C)C)CC)(C)C.[I-].C[N+]1C=CC=CC=1Cl>ClCCl.C(OCC)(=O)C>[C:28]([O:27][C:25]([NH:24][C:22]([NH:21][C:19]([O:18][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:20])=[N:1][CH:2]1[CH2:6][CH2:5][N:4]([C:7]2[CH:12]=[C:11]([CH3:13])[CH:10]=[CH:9][N:8]=2)[CH2:3]1)=[O:26])([CH3:31])([CH3:30])[CH3:29]
Reactant: CC(C)(C)OC(=O)NC(=S)NC(=O)OC(C)(C)C
Reactant: Cc1ccnc(N2CCC(N)C2)c1
Agent: C[n+]1ccccc1Cl
Agent: [I-]
Solvent: ClCCl
Solvent: CCOC(C)=O
Solvent: CCN(C(C)C)C(C)C
Product: Cc1ccnc(N2CCC(N=C(NC(=O)OC(C)(C)C)NC(=O)OC(C)(C)C)C2)c1
Reaction time: 16 h
Yield: 69.2 %

Procedure:
To a suspension of 3-amino-1-(4-methylpyridin-2-yl)pyrrolidine (177 mg) and N,N′-bis(tert-butoxycarbonyl)thiourea (331 mg) and diisopropylethylamine (0.4 ml) in dichloromethane (10 ml) was added 1-methyl-2-chloropyridinium iodide (332 mg), and the mixture was stirred for 16 hours. The mixture was diluted with ethyl acetate, washed with water and brine, dried over magnesium sulfate and evaporated under reduced pressure. The residue was purified by column chromatography (silica gel 25 g, n-hexane:ethyl acetate=4:1) and crystallized from diisopropyl ether to give N,N′-bis(tert-butoxycarbonyl)-N″-(1-(4-methylpyridin-2-yl)pyrrolidin-3-yl)guanidine (290 mg).
Reaction SMILES: Cl[C:2]1[N:7]2[N:8]=[C:9](C)[CH:10]=[C:6]2[N:5]=[C:4]([NH:12][C:13](=[O:24])[C:14]2[CH:19]=[CH:18][C:17]([C:20]([OH:23])([CH3:22])[CH3:21])=[CH:16][CH:15]=2)[CH:3]=1.[O:25]1[C:29]2[CH:30]=[CH:31][CH:32]=[C:33](B(O)O)[C:28]=2[O:27][CH2:26]1.O1CCOCC1>CO.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[O:25]1[C:29]2[CH:30]=[CH:31][CH:32]=[C:33]([C:2]3[N:7]4[N:8]=[CH:9][CH:10]=[C:6]4[N:5]=[C:4]([NH:12][C:13](=[O:24])[C:14]4[CH:19]=[CH:18][C:17]([C:20]([OH:23])([CH3:21])[CH3:22])=[CH:16][CH:15]=4)[CH:3]=3)[C:28]=2[O:27][CH2:26]1
Reactant: Cc1cc2nc(NC(=O)c3ccc(C(C)(C)O)cc3)cc(Cl)n2n1
Reactant: OB(O)c1cccc2c1OCO2
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: c1ccc(P(c2ccccc2)[c-]2cccc2)cc1
Solvent: CO
Solvent: C1COCCO1
Product: CC(C)(O)c1ccc(C(=O)Nc2cc(-c3cccc4c3OCO4)n3nccc3n2)cc1
Temperature: 110 °C
Yield: 4.5 %

Procedure:
A suspension of N-(7-chloro-2-methylpyrazolo[1,5-a]pyrimidin-5-yl)-4-(2-hydroxypropan-2-yl)benzamide (2D, 50 mg, 0.151 mmol), benzo[d][1,3]dioxol-4-ylboronic acid (50 mg, 0.302 mmol), and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (9 mg, 12 μmol) in 2:1 1,4-dioxane/saturated aqueous NaHCO3 (330 microliters of 1,4-dioxane and 670 microliters of saturated aqueous NaHCO3) was prepared in a 2 mL microwave reaction vessel and the sealed reaction vessel warmed to 110° C. for 20 minutes. The reaction mixture was cooled to rt, diluted with methanol, filtered, and purified via preparative HPLC, 5-95% (MeCN/H2O gradient+0.01% TFA). Lyophilization of the combined fractions gave the titled compound as a yellow solid (2.8 mg, 4%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.46 (s, 6 H) 5.20 (s, 1 H) 6.18 (s, 2 H) 6.57 (d, J=2.27 Hz, 1 H) 7.17 (d, J=8.34 Hz, 1 H) 7.56-7.69 (m, 3 H) 7.72 (d, J=1.77 Hz, 1 H) 7.98-8.10 (m, 3 H) 8.19 (d, J=2.27 Hz, 1 H) 11.23 (s, 1 H). ESI-MS: m/z 417.0 (M+H)+.
Reaction SMILES: [C:1]([C:3]1[CH:8]=[CH:7][C:6]([N:9]2[CH2:14][CH2:13][N:12]([C:15]3[C:16]([NH2:25])=[N:17][C:18]([NH2:24])=[N:19][C:20]=3[CH2:21][CH2:22][CH3:23])[CH2:11][CH2:10]2)=[CH:5][CH:4]=1)#N.S(=O)(=O)(O)[OH:27].[CH2:31]([OH:33])[CH3:32]>>[NH2:24][C:18]1[N:17]=[C:16]([NH2:25])[C:15]([N:12]2[CH2:11][CH2:10][N:9]([C:6]3[CH:7]=[CH:8][C:3]([C:1]([O:33][CH2:31][CH3:32])=[O:27])=[CH:4][CH:5]=3)[CH2:14][CH2:13]2)=[C:20]([CH2:21][CH2:22][CH3:23])[N:19]=1
Reactant: CCO
Reactant: O=S(=O)(O)O
Reactant: CCCc1nc(N)nc(N)c1N1CCN(c2ccc(C#N)cc2)CC1
Product: CCCc1nc(N)nc(N)c1N1CCN(c2ccc(C(=O)OCC)cc2)CC1
Temperature: 100 °C

Procedure:
A mixture of 1.0 g (2.96 mmole) of 5-[4-(4-cyanophenyl)-1-piperazinyl]-6-propyl-2,4-pyrimidinediamine, 15 ml of 95% ethanol and 15 ml of sulfuric acid was heated under reflux at 100° C. for four hours and cooled. The solution was poured into 200 ml of ice water and filtered. The filtrate was kept cool and neutralized with 50% aqueous sodium hydroxide solution to pH 7. The solid was collected and washed with 50 ml of water. Recrystallization from N,N-dimethylformamide and drying in vacuo at 78° C. for 16 hours gave 0.7 g of the product as a white solid, mp 215°-216° C.
Reaction SMILES: [NH2:1][C@@H:2]([CH2:8][C:9]1[CH:14]=[C:13]([O:15][CH3:16])[C:12]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[C:11]([O:23][CH3:24])[CH:10]=1)[C:3]([O:5][CH2:6][CH3:7])=[O:4].[OH:25][C:26]1[C:29]([CH3:31])([CH3:30])[C:28](=O)[CH:27]=1>C(Cl)Cl>[CH3:30][C:29]1([CH3:31])[C:28]([NH:1][C@@H:2]([CH2:8][C:9]2[CH:10]=[C:11]([O:23][CH3:24])[C:12]([C:17]3[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=3)=[C:13]([O:15][CH3:16])[CH:14]=2)[C:3]([O:5][CH2:6][CH3:7])=[O:4])=[CH:27][C:26]1=[O:25]
Reactant: CC1(C)C(=O)C=C1O
Reactant: CCOC(=O)[C@@H](N)Cc1cc(OC)c(-c2ccccc2)c(OC)c1
Solvent: ClCCl
Product: CCOC(=O)[C@H](Cc1cc(OC)c(-c2ccccc2)c(OC)c1)NC1=CC(=O)C1(C)C

Procedure:
The title compound was prepared in a similar manner to that of the compound of Example 41 from ethyl (2S)-2-amino-3-(2,6-dimethoxy[1,1′-biphenyl]-4-yl)propanoate (1.5 g, 4.5 mol), and 3-hydroxy-4,4-dimethyl-2-cyclobutenone (0.5 g, 4.5 mmol) in DCM (15 ml) as a white foam (1.8 g, 93%). δH (300 MHz, DMSO d6) 8.68 (1H, d, J 8.6 Hz), 7.22–7.37 (3H, m), 7.18 (2H, d, J 8.3 Hz), 6.78 (2H, d, J 8.4 Hz), 4.46 (1H, s), 4.32 (1H, m), 4.21 (2H, q, J 7.1 Hz), 3.69 (6H, s), 3.24 (1H, dd, J 13.8, 5.9 Hz), 3.09 (1H, dd, J 13.8, 9.1 Hz), 1.24 (3H, t, J 7.1 Hz), 1.16 (3H, s), 1.08 (3H, s); m/z (ES+, 70V) 424 (MH+).
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([SH:8])=[CH:4][CH:3]=1.[N-:9]=[N+:10]=[N-:11].[Na+].[CH:13](OCC)(OCC)OCC>C(O)(=O)C>[N:1]1([C:2]2[CH:7]=[CH:6][C:5]([SH:8])=[CH:4][CH:3]=2)[CH:13]=[N:11][N:10]=[N:9]1
Reactant: CCOC(OCC)OCC
Reactant: Nc1ccc(S)cc1
Reactant: [N-]=[N+]=[N-]
Agent: [Na+]
Solvent: CC(=O)O
Product: Sc1ccc(-n2cnnn2)cc1
Temperature: 85 °C

Procedure:
Alternatively a mixture of p-aminothiophenol (9.0 g.), sodium azide (7.0 g.), triethyl orthoformate (30 ml.), and acetic acid (30 ml.) was stirred and heated at 85° C. for 30 minutes. The reaction mixture was evaporated at reduced pressure and diluted with water to give a crystalline product which was collected and recrystallized from chloroform:hexane.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([CH:8]=[C:9]([N+:11]([O-:13])=[O:12])[CH:10]=1)[NH2:7])([O-:3])=[O:2].CO[CH:16]1[CH2:20][CH2:19][CH:18](OC)O1>C(O)(=O)C>[N+:1]([C:4]1[CH:5]=[C:6]([N:7]2[CH:16]=[CH:20][CH:19]=[CH:18]2)[CH:8]=[C:9]([N+:11]([O-:13])=[O:12])[CH:10]=1)([O-:3])=[O:2]
Reactant: COC1CCC(OC)O1
Reactant: Nc1cc([N+](=O)[O-])cc([N+](=O)[O-])c1
Solvent: CC(=O)O
Product: O=[N+]([O-])c1cc(-n2cccc2)cc([N+](=O)[O-])c1
Yield: 54 %

Procedure:
A solution of 3,5-dinitroaniline (10 g, 54.644 mmol) and 2,5-dimethoxytetrahydrofuran (18.05 g, 136.61 mmol, 2.5 eq.) in acetic acid (122 ml) was heated to 100° C. for 16 h. Completion of reaction was monitored by TLC. Then the mixture was brought to RT and poured into ice-cold water. The precipitate was filtered, washed with water (150 ml) and dried to give the product in 54% yield (8.2 g). LC-MS (ESI): Calculated mass: 233.18; Observed mass: 233.04 [M+H]+ (rt: 1.667 min).
Reaction SMILES: [Si:1]([O:8][CH2:9][C@H:10]1[CH2:15][NH:14][CH2:13][C@@H:12]([NH:16][C:17](=[O:23])[O:18][C:19]([CH3:22])([CH3:21])[CH3:20])[CH2:11]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].Cl[C:25]1[CH:30]=[CH:29][N:28]=[CH:27][C:26]=1[N+:31]([O-:33])=[O:32]>>[Si:1]([O:8][CH2:9][C@H:10]1[CH2:15][N:14]([C:25]2[CH:30]=[CH:29][N:28]=[CH:27][C:26]=2[N+:31]([O-:33])=[O:32])[CH2:13][C@@H:12]([NH:16][C:17](=[O:23])[O:18][C:19]([CH3:22])([CH3:21])[CH3:20])[CH2:11]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]
Reactant: O=[N+]([O-])c1cnccc1Cl
Reactant: CC(C)(C)OC(=O)N[C@@H]1CNC[C@H](CO[Si](C)(C)C(C)(C)C)C1
Product: CC(C)(C)OC(=O)N[C@H]1C[C@@H](CO[Si](C)(C)C(C)(C)C)CN(c2ccncc2[N+](=O)[O-])C1

Procedure:
Method 1 was followed using cis(+/−)-tert-butyl 5-((tert-butyldimethylsilyloxy)methyl)piperidin-3-ylcarbamate and 4-chloro-3-nitropyridine yielding cis(+/−)-tert-butyl 5-((tert-butyldimethylsilyloxy)methyl)-1-(3-nitropyridin-4-yl)-piperidin-3-ylcarbamate. LCMS (m/z): 467.0 (MH+); LC Rt=4.02 min.
Reaction SMILES: [N:1]1[C:9]2[C:4](=[N:5][CH:6]=[CH:7][CH:8]=2)[N:3]([C:10]2[CH:15]=[CH:14][C:13]([CH2:16][C:17]([OH:19])=O)=[C:12]([CH3:20])[CH:11]=2)[CH:2]=1.[F:21][C:22]([F:31])([F:30])[C:23]1[CH:24]=[C:25]([CH:27]=[CH:28][CH:29]=1)[NH2:26]>C(Cl)Cl.CO>[N:1]1[C:9]2[C:4](=[N:5][CH:6]=[CH:7][CH:8]=2)[N:3]([C:10]2[CH:15]=[CH:14][C:13]([CH2:16][C:17]([NH:26][C:25]3[CH:27]=[CH:28][CH:29]=[C:23]([C:22]([F:21])([F:30])[F:31])[CH:24]=3)=[O:19])=[C:12]([CH3:20])[CH:11]=2)[CH:2]=1
Reactant: Cc1cc(-n2cnc3cccnc32)ccc1CC(=O)O
Reactant: Nc1cccc(C(F)(F)F)c1
Solvent: CO
Solvent: ClCCl
Product: Cc1cc(-n2cnc3cccnc32)ccc1CC(=O)Nc1cccc(C(F)(F)F)c1

Procedure:
The title compound is prepared as described in Example 7 but using (4-imidazo[4,5-b]pyridin-3-yl-2-methyl-phenyl)-acetic acid (Step 60.1) and 3-(trifluoromethyl)aniline. Title compound: ES-MS: 411.1 [M+H]+; tR=4.19 min (System 1); Rf=0.28 (CH2Cl2/MeOH, 95:5+0.1% NH3aq).
Reaction SMILES: C(N(CC)CC)C.[NH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13]O.Cl[C:16]1[C:25]2[C:20](=[CH:21][C:22]([NH:29][CH2:30][CH3:31])=[C:23]([N+:26]([O-:28])=[O:27])[CH:24]=2)[N:19]=[CH:18][N:17]=1.S(Cl)([Cl:34])=O>ClCCCl.O1CCOCC1>[Cl:34][CH2:13][CH2:12][CH2:11][CH2:10][CH2:9][NH:8][C:16]1[C:25]2[C:20](=[CH:21][C:22]([NH:29][CH2:30][CH3:31])=[C:23]([N+:26]([O-:28])=[O:27])[CH:24]=2)[N:19]=[CH:18][N:17]=1
Reactant: O=S(Cl)Cl
Reactant: NCCCCCO
Reactant: CCNc1cc2ncnc(Cl)c2cc1[N+](=O)[O-]
Solvent: ClCCCl
Solvent: C1COCCO1
Solvent: CCN(CC)CC
Product: CCNc1cc2ncnc(NCCCCCCl)c2cc1[N+](=O)[O-]
Temperature: 25 °C
Reaction time: 19 h
Yield: 93.2 %

Procedure:
Triethylamine (14.9 ml, 106.9 mmol) and 5-amino-1-pentanol (2.47 ml, 22.7 mmol) were added to a 1,4-dioxane solution (100 ml) of 4-chloro-7-ethylamino-6-nitroquinazoline (5.74 g, 22.7 mmol) obtained in Reference Example 13 under ice-cooling and the mixture was stirred at room temperature for 19 hours. The precipitated solid was filtered off, washed successively with water and ether and dried. To a solution of the resulting solid in 1,2-dichloroethane (40 ml), thionyl chloride (4.80 ml, 65.8 mmol) was added and the mixture was heated under reflux for 3 hours. After the solvent was distilled off, ice and a saturated aqueous solution of sodium bicarbonate were added and the mixture was extracted with chloroform. The organic layer was dried over a drying agent (magnesium sulfate), the drying agent was filtered off and the filtrate was concentrated under reduced pressure to give 7.15 g (93.3%) of the title compound as a crude product.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][NH:9][CH2:10][CH2:11][NH2:12])=[CH:4][CH:3]=1.[N:13]#[C:14]Br>CO>[ClH:1].[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:8][N:9]2[CH2:10][CH2:11][N:12]=[C:14]2[NH2:13])=[CH:6][CH:7]=1
Reactant: NCCNCc1ccc(Cl)cc1
Reactant: N#CBr
Solvent: CO
Product: Cl
Product: NC1=NCCN1Cc1ccc(Cl)cc1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
The amine produced in Procedure 90, 14.5 g. (0.079 mole) was dissolved in 50 ml. of methanol and treated with a solution 9.1 g. (0.086 mole) of cyanogen bromide in 30 ml. of methanol in dropwise fashion. The warm solution was cooled to room temperature which resulted in the formation of a precipitate. The mixture was kept with stirring for 1/2 hr. and then a portion of the solvent was removed by distillation in vacuo. The solid product which separated was collected on a filter, washed with Et2O, and air dried, yield 16 g., m.p. 270°-272°.
Reaction SMILES: [I-].C([N:9]1[CH2:14][CH2:13][N:12]([C:15]2[CH:16]=[C:17]([CH2:36][CH3:37])[C:18]3[C:27]([CH:28]=2)=[S+:26][C:25]2[C:20](=[C:21]([CH3:35])[CH:22]=[C:23]([N:29]4[CH2:34][CH2:33][O:32][CH2:31][CH2:30]4)[CH:24]=2)[N:19]=3)[CH2:11][CH2:10]1)(OC(C)(C)C)=O.[F:38][C:39]([F:44])([F:43])[C:40]([OH:42])=[O:41]>ClCCl>[F:38][C:39]([F:44])([F:43])[C:40]([O-:42])=[O:41].[CH2:36]([C:17]1[C:18]2[C:27](=[S+:26][C:25]3[C:20]([N:19]=2)=[C:21]([CH3:35])[CH:22]=[C:23]([N:29]2[CH2:34][CH2:33][O:32][CH2:31][CH2:30]2)[CH:24]=3)[CH:28]=[C:15]([N:12]2[CH2:13][CH2:14][NH:9][CH2:10][CH2:11]2)[CH:16]=1)[CH3:37]
Reactant: O=C(O)C(F)(F)F
Reactant: CCc1cc(N2CCN(C(=O)OC(C)(C)C)CC2)cc2[s+]c3cc(N4CCOCC4)cc(C)c3nc12
Agent: [I-]
Solvent: ClCCl
Product: CCc1cc(N2CCNCC2)cc2[s+]c3cc(N4CCOCC4)cc(C)c3nc12
Product: O=C([O-])C(F)(F)F

Procedure:
A solution of 3-(4-Boc-piperazin-1-yl)-1-ethyl-9-methyl-7-morpholinophenothiazin-5-ium iodide (65 mg, 0.01 mmol) in dichloromethane (10 mL) and trifluoroacetic acid (1.0 mL) was stirred for 1 h at 50° C. The resulting mixture was washed by toluene (2×5 mL), pentane (2×5 mL) and concentrated to dryness.
Reaction SMILES: [F:1][C:2]([F:44])([F:43])[O:3][C:4]1[CH:5]=[C:6]([C@@H:10]([NH:12][C:13]([C:15]2[C:23]3[C:18](=[N:19][CH:20]=[C:21]([C:24]4[C:32]5[C:27](=[CH:28][C:29]([F:33])=[CH:30][CH:31]=5)[N:26]([CH3:34])[N:25]=4)[N:22]=3)[N:17](COCC[Si](C)(C)C)[CH:16]=2)=[O:14])[CH3:11])[CH:7]=[CH:8][CH:9]=1.FC(F)(F)C(O)=O.C(N)CN>ClCCl>[F:44][C:2]([F:1])([F:43])[O:3][C:4]1[CH:5]=[C:6]([C@@H:10]([NH:12][C:13]([C:15]2[C:23]3[C:18](=[N:19][CH:20]=[C:21]([C:24]4[C:32]5[C:27](=[CH:28][C:29]([F:33])=[CH:30][CH:31]=5)[N:26]([CH3:34])[N:25]=4)[N:22]=3)[NH:17][CH:16]=2)=[O:14])[CH3:11])[CH:7]=[CH:8][CH:9]=1
Reactant: C[C@H](NC(=O)c1cn(COCC[Si](C)(C)C)c2ncc(-c3nn(C)c4cc(F)ccc34)nc12)c1cccc(OC(F)(F)F)c1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Solvent: NCCN
Product: C[C@H](NC(=O)c1c[nH]c2ncc(-c3nn(C)c4cc(F)ccc34)nc12)c1cccc(OC(F)(F)F)c1
Temperature: 25 °C
Reaction time: 2 h
Yield: 57.3 %

Procedure:
In a 10 ml round-bottomed flask, 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(S)-1-(3-trifluoromethoxy-phenyl)-ethyl]-amide (123 mg, 0.196 mmol) was dissolved in dichloromethane (1 ml) and trifluoroacetic acid (0.6 ml, 7.9 mmol) was added. The light yellow reaction was stirred at room temperature for 2 h then concentrated. The residue was dissolved in dichloromethane (1 ml) and ethylenediamine (0.80 ml, 11.8 mmol) was added. The yellow reaction mixture was stirred at room temperature for 1 h then quenched with water and diluted with ethyl acetate. The resulting suspension was filtered and washed with hot water and ethyl acetate and the solid collected was dried under high vacuum to provide 56 mg (57%) of 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(S)-1-(3-trifluoromethoxy-phenyl)-ethyl]-amide as a light yellow powder. MS: (M+Na)+=521; 1H NMR (DMSO-d6, 400 MHz): δ (ppm) 12.85 (br. s., 1H), 9.11 (s, 1H), 8.53 (d, J=7.8 Hz, 1H), 8.45 (s, 1H), 8.36 (dd, J=9.2, 5.2 Hz, 1H), 7.67 (dd, J=9.7, 1.9 Hz, 1H), 7.39-7.54 (m, 3H), 7.24 (d, J=7.1 Hz, 1H), 6.98 (td, J=9.0, 2.1 Hz, 1H), 5.27-5.43 (m, 1H), 4.14 (s, 3H), 1.65 (d, J=7.1 Hz, 3H).
Reaction SMILES: Br[C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[CH:4][C:3]=1N.C(O[C:13]([SH:15])=[S:14])C.[K].C[N:18](C=O)C>>[SH:15][C:13]1[S:14][C:2]2[CH:3]=[CH:4][CH:5]=[C:6]([CH3:8])[C:7]=2[N:18]=1
Reactant: Cc1ccc(N)c(Br)c1
Reactant: CCOC(=S)S
Reactant: CN(C)C=O
Agent: [K]
Product: Cc1cccc2sc(S)nc12

Procedure:
The title compound was prepared using the method of example 239, starting with 2-bromo-4-methyl-phenylamine (Acros) (27.9 g), O-ethylxanthic acid, potassium salt (Lancaster, 54 g) in DMF (250 mL). The mercaptobenzothiazole 340 was obtained as an pale brown solid (27 g). Recrystalization from CHCl3 gave pinkish white crystals (20 g).
Reaction SMILES: Br[C:2]1[C:3]2[C:8]([C:9]3[CH:10]=[CH:11][CH:12]=[CH:13][C:14]=3[CH:15]=1)=[CH:7][CH:6]=[CH:5][CH:4]=2.[Li]C(C)(C)C.[CH3:21][O:22][C:23]1[CH:36]=[CH:35][CH:34]=[CH:33][C:24]=1/[N:25]=[CH:26]/[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1.O>C1COCC1.CCCCC>[CH3:21][O:22][C:23]1[CH:36]=[CH:35][CH:34]=[CH:33][C:24]=1[NH:25][CH:26]([C:2]1[C:3]2[C:8]([C:9]3[CH:10]=[CH:11][CH:12]=[CH:13][C:14]=3[CH:15]=1)=[CH:7][CH:6]=[CH:5][CH:4]=2)[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1
Reactant: COc1ccccc1/N=C/c1ccccc1
Reactant: Brc1cc2ccccc2c2ccccc12
Agent: [Li]C(C)(C)C
Solvent: C1CCOC1
Solvent: O
Solvent: CCCCC
Product: COc1ccccc1NC(c1ccccc1)c1cc2ccccc2c2ccccc12
Temperature: -80 °C

Procedure:
To a solution of 5.14 g (20.0 mmol) of 9-bromophenanthrene in 80 mL of THF, 26.7 mL (40.1 mmol) of 1.5 M tBuLi in pentane was added with vigorous stirring at −80° C. This mixture was additionally stirred for 1 hr at this temperature and then slowly warmed to room temperature. The resulting mixture was stirred for 30 min at ambient temperature and then cooled to −80° C. A solution of 4.22 g (20.0 mol) of 9 in 50 mL of THF was added. To the resulting mixture, 5 mL of water was added, and then this mixture was evaporated to dryness. The title product was isolated by flash chromatography on silica gel 60 (40-63 um, eluent: from hexanes to hexanes-diethyl ether=40:1, vol.). Yield 7.32 g (94%).
Reaction SMILES: [F:1][C:2]([F:18])([F:17])[C:3]1[CH:4]=[CH:5][C:6]([O:9][C:10]2[CH:11]=[CH:12][C:13]([OH:16])=[N:14][CH:15]=2)=[N:7][CH:8]=1.[I-].C([Si](C)(C)[O:25][CH:26]1[CH2:31][CH2:30][N:29]([C:32](N2C=C[N+](C)=C2)=[O:33])[CH2:28][CH2:27]1)(C)(C)C.C(N(CC)CC)C>C(#N)C>[F:18][C:2]([F:1])([F:17])[C:3]1[CH:4]=[CH:5][C:6]([O:9][C:10]2[CH:11]=[CH:12][C:13]([O:16][C:32]([N:29]3[CH2:30][CH2:31][CH:26]([OH:25])[CH2:27][CH2:28]3)=[O:33])=[N:14][CH:15]=2)=[N:7][CH:8]=1
Reactant: C[n+]1ccn(C(=O)N2CCC(O[Si](C)(C)C(C)(C)C)CC2)c1
Reactant: Oc1ccc(Oc2ccc(C(F)(F)F)cn2)cn1
Agent: [I-]
Solvent: CCN(CC)CC
Solvent: CC#N
Product: O=C(Oc1ccc(Oc2ccc(C(F)(F)F)cn2)cn1)N1CCC(O)CC1
Temperature: 25 °C
Reaction time: 1 h
Yield: 64.8 %

Procedure:
A solution of 5-(5-trifluoromethyl-pyridin-2-yloxy)-pyridin-2-ol (180 mg, 0.70 mmol), 3-[4-(tert-butyl-dimethyl-silanyloxy)-piperidine-1-carbonyl]-1-methyl-3H-imidazol-1-ium iodide (317 mg, 0.70 mmol) and triethylamine (98 μL) in acetonitrile (10 mL) was stirred at room temperature overnight. The solvent was evaporated in vacuo. The residue was redissolved in some dichloromethane, filtered over a short pad of silicagel and washed with ethyl acetate:heptane 50:50. The solvent was evaporated in vacuo and the residue was dissolved in 3.2N HCl in ether (10 mL). After stirring for 1 hour at room temperature the solvent was evaporated in vacuo and the residue was dissolved in dichloromethane. Triethylamine (0.5 mL) was added and the solution was extracted with water. The organic layer was dried over sodium sulphate, filtered and evaporated in vacuo to yield the title compound (174 mg, 65% yield) as a thick oil.
Reaction SMILES: [N+:1]([C:4]1[CH:11]=[CH:10][C:7]([CH:8]=O)=[CH:6][CH:5]=1)([O-:3])=[O:2].[CH3:12][C:13]1[CH:18]=[CH:17][N:16]=[CH:15][N:14]=1.C(OC(=O)C)(=O)C>O>[N+:1]([C:4]1[CH:11]=[CH:10][C:7]([CH:8]=[CH:12][C:13]2[CH:18]=[CH:17][N:16]=[CH:15][N:14]=2)=[CH:6][CH:5]=1)([O-:3])=[O:2]
Reactant: Cc1ccncn1
Reactant: O=Cc1ccc([N+](=O)[O-])cc1
Solvent: CC(=O)OC(C)=O
Solvent: O
Product: O=[N+]([O-])c1ccc(C=Cc2ccncn2)cc1
Temperature: 120 °C
Yield: 77 %

Procedure:
The starting compound is prepared as follows. p-Nitrobenzaldehyde (24.2 g), 4-methyl-pyrimidine (15.5 g) and acetic anhydride (16.7 g) are mixed at room temperature, and the mixture is heated at 120° C. for 5 hours. After cooling, the mixture is poured into water (500 ml), and the aqueous mixture is extracted several times with chloroform. The combined chloroform extracts are dried over magnesium sulfate and concentrated until crystals separated. Addition of ether gives 4-[2-(p-nitrophenyl) ethenyl]pyrimidine (28 g), m.p. 213°-215° C.
Reaction SMILES: [H-].[Na+].[CH:3]1([OH:10])[CH2:8][CH2:7]C(O)C=C1.[CH3:11]I.[CH2:13]1[CH2:17][O:16][CH2:15][CH2:14]1>>[CH3:15][O:16][CH:17]1[CH2:13][CH2:14][CH:3]([O:10][CH3:11])[CH:8]=[CH:7]1
Reactant: C1CCOC1
Reactant: OC1C=CC(O)CC1
Reactant: CI
Agent: [H-]
Agent: [Na+]
Product: COC1C=CC(OC)CC1
Reaction time: 48 h
Yield: 91 %

Procedure:
Lit., J. Org. Chem., 53:5695 (1988). To 14.3 g (328 mmol) sodium hydride (55% dispersion in oil) was added dropwise at 0° C. with stirring a solution of 10.1 g (88.5 mmol) (1RS,4RS)-cyclohex-2-ene-1,4-diol in 100 ml THF. 34 ml (546 mmol) methyl iodide was then added and stirring continued for an additional 48 h at room temperature. The reaction was quenched with saturated ammonium chloride solution and extracted with ether. The combined organic extracts were washed successively with saturated ammonium chloride solution and saturated brine, dried over sodium sulphate, and concentrated in vacuo to afford 11.5 g (91%) of the title compound as a yellow oil. 1H NMR d (250 MHz, CDCl3) 5.90 (2H, s), 3.82 (2H, br t), 3.37 (6H, s), 2.10 (2H, m), 1.51 (2H, m).
Reaction SMILES: [F:1][C:2]([F:26])([F:25])[C:3]1[N:8]2[N:9]=[CH:10][C:11]([C:12](O)=[O:13])=[C:7]2[N:6]=[C:5]([C:15]2[CH:20]=[CH:19][C:18]([C:21]([F:24])([F:23])[F:22])=[CH:17][CH:16]=2)[CH:4]=1.[Cl:27][C:28]1[S:32][C:31]([S:33]([N:36]2[CH2:40][CH2:39][CH:38]([OH:41])[CH2:37]2)(=[O:35])=[O:34])=[CH:30][C:29]=1[N+:42]([O-])=O>>[Cl:27][C:28]1[S:32][C:31]([S:33]([N:36]2[CH2:40][CH2:39][CH:38]([OH:41])[CH2:37]2)(=[O:35])=[O:34])=[CH:30][C:29]=1[NH:42][C:12]([C:11]1[CH:10]=[N:9][N:8]2[C:3]([C:2]([F:26])([F:25])[F:1])=[CH:4][C:5]([C:15]3[CH:20]=[CH:19][C:18]([C:21]([F:24])([F:22])[F:23])=[CH:17][CH:16]=3)=[N:6][C:7]=12)=[O:13]
Reactant: O=C(O)c1cnn2c(C(F)(F)F)cc(-c3ccc(C(F)(F)F)cc3)nc12
Reactant: O=[N+]([O-])c1cc(S(=O)(=O)N2CCC(O)C2)sc1Cl
Product: O=C(Nc1cc(S(=O)(=O)N2CCC(O)C2)sc1Cl)c1cnn2c(C(F)(F)F)cc(-c3ccc(C(F)(F)F)cc3)nc12

Procedure:
The title compound was prepared from 7-trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-carboxylic acid (example C.1) and (RS)-1-(4-amino-5-chloro-thiophene-2-sulfonyl)-pyrrolidin-3-ol-(example B.18) according to general procedure II. Yellow solid. MS (ISP) 640.2 [(M+H)+]; mp 270° C.
Reaction SMILES: [C:1]1([CH:7]2[S:12][CH2:11][CH2:10][CH2:9][S:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Li:13]CCCC.C=CC=C.C=CC=C.C=CC1C=CC=CC=1>C1COCC1.C1CCCCC1>[Li:13][C:7]1([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[S:8][CH2:9][CH2:10][CH2:11][S:12]1
Reactant: [Li]CCCC
Reactant: c1ccc(C2SCCCS2)cc1
Agent: C=CC=C
Solvent: C1CCCCC1
Solvent: C1CCOC1
Solvent: C=Cc1ccccc1
Product: [Li]C1(c2ccccc2)SCCCS1
Temperature: 0 °C
Reaction time: 3 h

Procedure:
To a solution of 2-phenyl-1,3-dithiane (2.1 g, 10.69 mmol) in THF (5 mL) and cyclohexane (10 mL) was added n-BuLi (6.37 mL, 1.68 M in hexane) dropwise via a syringe at −78° C. The solution was stirred for an additional 3 hours at 0° C. The resulting 0.5 M 2-litho-2-phenyl-1,3-dithiane (abbreviated as PDT-Li) was used for anionic initiator for polymerizing butadiene and/or butadiene/styrene and stored in an inert atmosphere of nitrogen in a refrigerator.
Reaction SMILES: [NH2:1][C:2]1[CH:11]=[CH:10][C:9]([Br:12])=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5].C(N(CC)CC)C.[C:20]1([CH2:26][CH2:27][C:28](Cl)=[O:29])[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1>ClCCl>[Br:12][C:9]1[CH:10]=[CH:11][C:2]([NH:1][C:28](=[O:29])[CH2:27][CH2:26][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)=[C:3]([CH:8]=1)[C:4]([O:6][CH3:7])=[O:5]
Reactant: COC(=O)c1cc(Br)ccc1N
Reactant: O=C(Cl)CCc1ccccc1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: COC(=O)c1cc(Br)ccc1NC(=O)CCc1ccccc1
Temperature: 25 °C
Reaction time: 12 h

Procedure:
Into a 100-mL round-bottom flask, was placed a solution of methyl 2-amino-5-bromobenzoate (5.0 g, 21.73 mmol), triethylamine (4.39 g, 43.38 mmol) and 3-phenylpropanoyl chloride (3.67 g, 21.76 mmol) in dichloromethane (50 mL). The resulting mixture was stirred for 12 hours at room temperature. The reaction was then quenched by the addition of 50 mL of water. The resulting mixture was extracted with 3×50 mL of dichloromethane. The combined organic layers were dried over anhydrous sodium sulfate, filtered and concentrated under vacuum. The residue was purified by chromatography over a silica gel column with ethyl acetate/petroleum ether (2:1) to provide the title compound as a white solid.