Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl[S:2]([N:5]=[C:6]=[O:7])(=[O:4])=[O:3].[C:8]([OH:12])([CH3:11])([CH3:10])[CH3:9].CCN(C(C)C)C(C)C.[CH2:22]([O:29][C:30]1[C:34]([O:35][CH2:36][C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)=[CH:33][N:32]([C:43]2[CH:48]=[CH:47][C:46]([O:49][CH3:50])=[CH:45][CH:44]=2)[C:31]=1[C:51]([N:53]([CH3:55])[CH3:54])=[O:52])[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1>C(Cl)Cl>[CH2:36]([O:35][C:34]1[C:30]([O:29][CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)=[C:31]([C:51](=[O:52])[N:53]([CH3:55])[CH3:54])[N:32]([C:43]2[CH:44]=[CH:45][C:46]([O:49][CH3:50])=[CH:47][CH:48]=2)[C:33]=1[S:2]([NH:5][C:6](=[O:7])[O:12][C:8]([CH3:11])([CH3:10])[CH3:9])(=[O:4])=[O:3])[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1
Reactant: O=C=NS(=O)(=O)Cl
Reactant: COc1ccc(-n2cc(OCc3ccccc3)c(OCc3ccccc3)c2C(=O)N(C)C)cc1
Reactant: CC(C)(C)O
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: COc1ccc(-n2c(C(=O)N(C)C)c(OCc3ccccc3)c(OCc3ccccc3)c2S(=O)(=O)NC(=O)OC(C)(C)C)cc1
Temperature: -5 °C
Reaction time: 0.25 h
Yield: 38.4 %

Procedure:
To a solution of chlorosulfonyl isocyanate (70.9 μL, 0.82 mmol) at −5° C. in anhydrous DCM (4 mL) was added tert-butanol (solution in 0.5 mL anhydrous DCM) (81 μL, 0.85 mmol) dropwise over 5 min and the reaction stirred at −5° C. for 15 min. After this time, DIPEA (296 μL, 1.70 mmol) was added dropwise. After 15 min a solution of 3,4-bis(benzyloxy)-1-(4-methoxyphenyl)-N,N-dimethyl-1H-pyrrole-2-carboxamide (9) (310 mg, 0.68 mmol) in DCM (1 mL) was added and the reaction was allowed to warm to RT and stirred for 16 h. The reaction was partitioned between water (10 mL) and DCM (20 mL) and the organic washed with 1 M HCl (aq.) (2×20 mL), and brine (10 mL), dried (MgSO4), filtered and solvent removed in vacuo to afford crude product. The residue was purified by silica gel chromatography (40 g, 0-4% MeOH in DCM) to afford tert-butyl (3,4-bis(benzyloxy)-5-(dimethylcarbamoyl)-1-(4-methoxyphenyl)-1H-pyrrol-2-yl)sulfonylcarbamate (10) (166 mg, 35%) as a colourless oil: m/z 636 (M+H)+ (ES+); 634 (M−H)− (ES−).
Reaction SMILES: [Cl:1][C:2]1[C:7]([Cl:8])=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:9][N:10]1[C:14]2[CH:15]=[C:16]([N:23]3[CH2:28][CH2:27][O:26][CH2:25][CH2:24]3)[CH:17]=[C:18]([C:19]([O:21]C)=[O:20])[C:13]=2[N:12]=[C:11]1[CH3:29].[Li+].[OH-].Cl>C1COCC1.O>[Cl:1][C:2]1[C:7]([Cl:8])=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:9][N:10]1[C:14]2[CH:15]=[C:16]([N:23]3[CH2:24][CH2:25][O:26][CH2:27][CH2:28]3)[CH:17]=[C:18]([C:19]([OH:21])=[O:20])[C:13]=2[N:12]=[C:11]1[CH3:29]
Reactant: COC(=O)c1cc(N2CCOCC2)cc2c1nc(C)n2Cc1cccc(Cl)c1Cl
Agent: Cl
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: C1CCOC1
Product: Cc1nc2c(C(=O)O)cc(N3CCOCC3)cc2n1Cc1cccc(Cl)c1Cl
Temperature: 25 °C
Reaction time: 8 h

Procedure:
A mixture of methyl 1-[(2,3-dichlorophenyl)methyl]-2-methyl-6-(4-morpholinyl)-1H-benzimidazole-4-carboxylate (65 mg, 0.15 mmol) and LiOH (19 mg, 0.5 mmol) in THF (5 mL) and water (5 mL), was stirred overnight at rt. Then the pH of the reaction mixture was neutralized with 1N aq. HCl. Then the mixture was stirred at rt for 1 h, filtered to give the product (47 mg, 74%, with about 10% monochloride as the impurity) as a white solid. 1H NMR (300 MHz, DMSO-d6) δ ppm 2.53 (s, 3H), 3.12 (t, 4H, J=4.5 Hz), 3.73 (t, 4H, J=4.5 Hz), 5.66 (s, 2H), 6.42 (d, 1H, J=7.8 Hz), 7.26 (t, 1H, J=7.8 Hz), 7.42 (s, 1H,), 7.48 (s, 1H), 7.62 (d, 1H, J=7.8 Hz); LC-MS: m/e=420 [M+1]+
Reaction SMILES: O([C:9]1[CH:18]=[CH:17][C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[CH:10]=1)S(C(F)(F)F)(=O)=O.[CH3:19][N:20]([CH3:26])[CH2:21][CH2:22][O:23][CH:24]=[CH2:25].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CN(C=O)C>CCCCC.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:19][N:20]([CH3:26])[CH2:21][CH2:22][O:23][CH:24]=[CH:25][C:9]1[CH:18]=[CH:17][C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[CH:10]=1
Reactant: C=COCCN(C)C
Reactant: O=S(=O)(Oc1ccc2ccccc2c1)C(F)(F)F
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CN(C)C=O
Solvent: CCCCC
Product: CN(C)CCOC=Cc1ccc2ccccc2c1
Yield: 87 %

Procedure:
Table 1, Entry 7. In the reaction tube were mixed 2-naphthyl triflate (0.276 g, 1.0 mmol), [2-(dimethylamino)ethoxy]ethene (0.23 g, 2.0 mmol), palladium acetate (0.00673 g, 0.030 mmol), triphenylphosphine (0.0173 g, 0.066 mmol) triethylamine (0.202 g, 2.0 mmol) and 0.75 ml DMF.under nitrogen. The contents of the flask were irradiated for 7.00 min with an effect of 35 W. After cooling, the product mixture was diluted with 50 ml pentane, transferred to a separatory funnel and washed with 2×25 ml water. Additional extraction of the aqueous phases was performed with 25 ml pentane. The combined organic portions were then treated 5 times with 20 ml of 0.1 M HCl. The aqueous extracts were combined, poured into a flask containing excess NaOH (1.0 M) and was extracted with 2×50 ml pentane. The combined organic phases were dried (K2CO3) and concentrated by evaporation. The yield was 87% (yellow oil, trans/cis 1/1).
Reaction SMILES: Cl.[F:2][C:3]([F:22])([F:21])[O:4][C:5]1[CH:6]=[C:7]([C:11]2[CH:12]=[C:13]3[C:18](=[O:19])[NH:17][CH2:16][CH2:15][N:14]3[CH:20]=2)[CH:8]=[CH:9][CH:10]=1.[CH3:23][S:24](Cl)(=[O:26])=[O:25].CCN([CH:34]([CH3:36])[CH3:35])C(C)C.C([O-])(O)=O.[Na+]>C(Cl)Cl.C(OCC)(=O)C>[O:19]=[C:18]1[NH:17][CH2:16][C@H:15]([CH2:12][CH2:13][NH:14][S:24]([CH3:23])(=[O:26])=[O:25])[N:14]2[C:20]([C:35]3[CH:34]=[CH:36][CH:6]=[CH:5][CH:10]=3)=[C:11]([C:7]3[CH:8]=[CH:9][CH:10]=[C:5]([O:4][C:3]([F:2])([F:21])[F:22])[CH:6]=3)[CH:12]=[C:13]12
Reactant: O=C1NCCn2cc(-c3cccc(OC(F)(F)F)c3)cc21
Reactant: CS(=O)(=O)Cl
Reactant: CCN(C(C)C)C(C)C
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: ClCCl
Product: CS(=O)(=O)NCC[C@H]1CNC(=O)c2cc(-c3cccc(OC(F)(F)F)c3)c(-c3ccccc3)n21
Temperature: 25 °C
Reaction time: 2 h
Yield: 51 %

Procedure:
40 mg (0.096 mmol) of 1(4S)-4-(2-aminoethyl)-6-phenyl)-7-[3-(trifluoromethoxy)phenyl]-3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)-one hydrochloride were dissolved in 3 ml of DCM. To the obtained solution, 15 μl (0.192 mmol) of methanesulfonyl chloride, 57 μl (0.33 mmol) of DIPEA, were added. The mixture was stirred at rt for 2 hours, the solution was portioned between ethyl acetate and saturated aqueous solution of NaHCO3, the organic layer was washed with brine, dried over Na2SO4 and evaporated under vacuum. The product was purified by HPLC preparative method 2 and isolated as a off-white solid 24 mg (51%) as a white solid.
Reaction SMILES: [CH3:1][NH:2][C:3]1[CH:4]=[N:5][CH:6]=[CH:7][C:8]=1[C:9]1[C:10]([O:15][CH2:16][C:17]([F:20])([F:19])[F:18])=[N:11][CH:12]=[CH:13][CH:14]=1.[CH3:21][S:22]([C:25]1[CH:26]=[C:27]([CH:31]=[C:32]([C:34]([F:37])([F:36])[F:35])[CH:33]=1)[C:28]([OH:30])=O)(=[O:24])=[O:23].[NH4+].[Cl-]>C(Cl)Cl>[CH3:21][S:22]([C:25]1[CH:26]=[C:27]([CH:31]=[C:32]([C:34]([F:37])([F:36])[F:35])[CH:33]=1)[C:28]([N:2]([CH3:1])[C:3]1[CH:4]=[N:5][CH:6]=[CH:7][C:8]=1[C:9]1[C:10]([O:15][CH2:16][C:17]([F:20])([F:19])[F:18])=[N:11][CH:12]=[CH:13][CH:14]=1)=[O:30])(=[O:23])=[O:24]
Reactant: CNc1cnccc1-c1cccnc1OCC(F)(F)F
Reactant: CS(=O)(=O)c1cc(C(=O)O)cc(C(F)(F)F)c1
Agent: [Cl-]
Agent: [NH4+]
Solvent: ClCCl
Product: CN(C(=O)c1cc(C(F)(F)F)cc(S(C)(=O)=O)c1)c1cnccc1-c1cccnc1OCC(F)(F)F

Procedure:
The title compound was prepared in analogy to example 90, from methyl-[2-(2,2,2-trifluoro-ethoxy)-[3,4]bipyridinyl-3′-yl]-amine and 3-(methylsulfonyl)-5-(trifluoromethyl)-benzoic acid (example 114, intermediate a) after a reaction time of 18 hours. The reaction mixture was poured on saturated aqueous NH4Cl solution and CH2Cl2 and the layers were separated. The aqueous layer was extracted three times with CH2Cl2. The organic layers were dried over MgSO4, filtered, treated with silica gel and evaporated. The compound was purified by silica gel chromatography on a 20 g column using an MPLC (ISCO) system eluting with EtOAc (isocratic). Further purification by preparative HPLC (Gemini NX column) using a gradient of MeOH:water (containing 0.1% formic acid) (20:80 to 98:2). Colorless foam (41%). MS (ESI): m/z=534.09 [M+H]+.
Reaction SMILES: C([O:3][C:4]([C:6]1[C:7]2[N:8]=[CH:9][CH:10]=[N:11][C:12]=2[C:13]([C:16]2[CH:21]=[C:20]([O:22][CH3:23])[CH:19]=[C:18]([O:24][CH3:25])[C:17]=2[F:26])=[CH:14][CH:15]=1)=O)C.[CH3:27][N:28]1[CH2:33][CH2:32][N:31]([CH2:34][C:35]2[CH:36]=[CH:37][C:38]([NH2:41])=[N:39][CH:40]=2)[CH2:30][CH2:29]1>C(Cl)Cl.CO>[CH3:27][N:28]1[CH2:33][CH2:32][N:31]([CH2:34][C:35]2[CH:36]=[CH:37][C:38]([NH:41][C:4]([C:6]3[C:7]4[N:8]=[CH:9][CH:10]=[N:11][C:12]=4[C:13]([C:16]4[CH:21]=[C:20]([O:22][CH3:23])[CH:19]=[C:18]([O:24][CH3:25])[C:17]=4[F:26])=[CH:14][CH:15]=3)=[O:3])=[N:39][CH:40]=2)[CH2:30][CH2:29]1
Reactant: CCOC(=O)c1ccc(-c2cc(OC)cc(OC)c2F)c2nccnc12
Reactant: CN1CCN(Cc2ccc(N)nc2)CC1
Solvent: ClCCl
Solvent: CO
Product: COc1cc(OC)c(F)c(-c2ccc(C(=O)Nc3ccc(CN4CCN(C)CC4)cn3)c3nccnc23)c1
Reaction time: 1 h

Procedure:
The title compound was prepared in analogy to the procedure described in Example 115 but using 8-(2-fluoro-3,5-dimethoxy-phenyl)-quinoxaline-5-carboxylic acid ethyl ester (Step 143.1), 5-(4-methyl-piperazin-1-ylmethyl)-pyridin-2-ylamine (Example 31; purified by silica gel column chromatography), and stirring the reaction mixture for 1 h at reflux. Title compound: ESI-MS: 517.1 [M+H]+; tR=3.37 min (System 1); TLC: Rf=0.11 (DCM/MeOH/NH3aq, 94:5:1).
Reaction SMILES: C1CCN2C(=NCCC2)CC1.[F:12][C:13]1[CH:22]=[C:21]2[C:16]([CH2:17][CH2:18][CH2:19][C@@H:20]2O)=[CH:15][CH:14]=1.C1(P([N:38]=[N+:39]=[N-:40])(C2C=CC=CC=2)=O)C=CC=CC=1>C1(C)C=CC=CC=1.C(Cl)Cl>[N:38]([C@H:20]1[C:21]2[C:16](=[CH:15][CH:14]=[C:13]([F:12])[CH:22]=2)[CH2:17][CH2:18][CH2:19]1)=[N+:39]=[N-:40]
Reactant: [N-]=[N+]=NP(=O)(c1ccccc1)c1ccccc1
Reactant: O[C@H]1CCCc2ccc(F)cc21
Solvent: C1CCC2=NCCCN2CC1
Solvent: ClCCl
Solvent: Cc1ccccc1
Product: [N-]=[N+]=N[C@@H]1CCCc2ccc(F)cc21
Reaction time: 8 h
Yield: 68.6 %

Procedure:
DBU (27.1 mL, 180.5 mmol, 3 equiv.) was added to a solution of (S)-7-Fluoro-1,2,3,4-tetrahydronaphthalen-1-ol (10 g, 60.2 mmol, 1 equiv.) in toluene (300 mL). The resulted dark red solution was cooled in ice bath. Diphenylphosphoryl azide (38.6 mL, 180.6 mmol, 3 equiv) was added drop-wise within 30 min. The reaction solution was slowly brought to RT and stirred overnight. TLC was checked and showed no more SM. The reaction was diluted with methylene chloride (200 mL). The methylene chloride layer was washed with saturated NaHCO3, brine, water, saturated NH4Cl, and brine. The organic layer was separated and dried (Na2SO4), evaporated under reduced pressure to give a dark-red syrup which was purified on ISCO (80 g column, 0-2% EtOAc-hexane) to give a colorless oil product (7.9 g, 70%). 1H NMR (400 MHz, CDCl3) δ 7.07-7.11 (m, 1H), 7.02 (dd, 1H), 6.91-6.96 (m, 1H), 4.51 (t, 1H), 2.69-2.86 (m, 2H), 1.76-2.05 (m, 4H).
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[CH:4][C:5]2[N:10](N=C(C)C)[CH2:9][CH:8]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[O:7][C:6]=2[CH:21]=1.[CH3:22][N:23]1[CH2:28][CH2:27][CH2:26][CH2:25][C:24]1=O.OS(O)(=O)=O>O1CCOCC1>[CH3:1][C:2]1[CH:3]=[C:4]2[C:5]3=[C:6]([O:7][CH:8]([C:15]4[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=4)[CH2:9][N:10]3[C:26]3[CH2:27][CH2:28][N:23]([CH3:22])[CH2:24][C:25]2=3)[CH:21]=1
Reactant: CN1CCCCC1=O
Reactant: CC(C)=NN1CC(c2ccccc2)Oc2cc(C)ccc21
Agent: O=S(=O)(O)O
Solvent: C1COCCO1
Product: Cc1cc2c3c(c1)c1c(n3CC(c3ccccc3)O2)CCN(C)C1
Temperature: 95 °C
Yield: 5.4 %

Procedure:
7-Methyl-2-phenyl-N-(propan-2-ylidene)-2H-benzo[b][1,4]oxazin-4(3H)-amine (1.3 g) and N-methyl piperidone (0.629 g) were dissolved in dioxane (2 mL). To this mixture was added 7% H2SO4 in Dioxane (25 mL) and the resulting reaction mixture was heated at 95° C. for 2 h. Reaction was monitored by TLC. After completion of reaction, the mixture was concentrated under reduced pressure, and the residue basified with NaOH solution to pH 12. The mixture was extracted with EtOAc (3×100 mL), and the organic layer dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography using silica (100-200 mesh size) using 3% MeOH/DCM as eluent. The purified compound was further purified using preparative TLC using 5% MeOH/DCM as mobile phase to obtain pure product as a light brown solid (0.08 g). 1H NMR (CD3OD, HCl Salt): d (ppm): 7.56 (d, 2H), 7.42 (m, 3H), 6.90 (s, 1H), 6.56 (s, 1H), 5.32 (m, 1H), 4.70 (m, 1H), 4.50 (m, 1H), 4.38 (m, 1H), 4.05 (m, 1H), 3.82 (m, 1H), 3.58 (m, 1H), 3.20 (m, 2H), 3.10 (s, 3H), 2.40 (s, 3H).
Reaction SMILES: [CH3:1][N:2]1[C:14]2[CH2:13][CH2:12][CH2:11][C:10](=[O:15])[C:9]=2[C:8]2[C:3]1=[CH:4][CH:5]=[CH:6][CH:7]=2.[H-].[Na+].C1(S(OC)=O)C=CC=CC=1>O1CCCC1.O>[OH:15][C:10]1[C:9]2[C:8]3[C:3](=[CH:4][CH:5]=[CH:6][CH:7]=3)[N:2]([CH3:1])[C:14]=2[CH:13]=[CH:12][CH:11]=1
Reactant: Cn1c2c(c3ccccc31)C(=O)CCC2
Agent: COS(=O)c1ccccc1
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: O
Product: Cn1c2ccccc2c2c(O)cccc21
Temperature: 50 °C
Reaction time: 1 h

Procedure:
A suspension of 9-methyl-4-oxo-1,2,3,4-tetrahydrocarbazole (prepared by the methods described by Osuka, A.; Mori, Y.; Suzuki, H. Chem. Lett. 1982, 2031-2034; and Elz, S.; Heil, W. L. Biorg. Med. Chem. Lett. 1995, 5, 667). (0.20 g, 1.0 mmol) in 3 mL tetrahydrofuran was sonicated and heated to 50° C. Sodium hydride (60% dispersion in mineral oil; 0.07 g, 1.8 mmol) was added in one portion. Sonication and heating was continued for 1 hour and then methyl phenylsulfinate (0.2 g, 1.2 mmol) was added in one portion. The mixture was diluted after 3 hours with retrahydrofuran and water to give a homogenous solution. The solution was concentrated by rotary evaporation and the residue was partitioned between dichloromethane and water. The organic layer was washed with sodium bicarbonate and brine and then dried over magnesium sulfate, filtered and concentrated. The residue was Dissolved in dioxane and heated to reflux for 1 hour. The mixture was concentrated and partitioned between dichloromethane and water. The organic fraction was dried over magnesium sulfate, filtered and concentrated. The mixture was purified by silica gel chromatography (20% EtOAc, hexanes) to 0.075 g of the desired product (38%). TLC Rf=0.49 (20% ethyl acetate, hexanes); 13C NMR (CDCl3) d 151.5, 142.6, 140.1, 126.0, 124.6, 122.4, 121.5, 118.8, 110.7, 107.7, 104.6, 101.0, 28.9; mass spectrum, m/z (FD, M+1) 198.
Reaction SMILES: [C:1]1([C:7]2[C:16]3[C:11](=[CH:12][C:13]([O:17][CH2:18][C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=4)=[CH:14][CH:15]=3)[CH:10]=C(C(=O)CCl)[CH:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C([O-])([O-])=O.[Cs+].[Cs+].[C:35](O)(=[S:37])[CH3:36].[CH3:39][CH2:40]O>CCOCC>[C:1]1([C:7]2[C:16]3[C:11](=[CH:12][C:13]([O:17][CH2:18][C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=4)=[CH:14][CH:15]=3)[CH:10]=[C:36]([C:35](=[S:37])[CH2:39][CH3:40])[CH:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: O=C(CCl)c1cc(-c2ccccc2)c2ccc(OCc3ccccc3)cc2c1
Reactant: CC(O)=S
Reactant: CCO
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CCOCC
Product: CCC(=S)c1cc(-c2ccccc2)c2ccc(OCc3ccccc3)cc2c1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
A mixture of chloroacetyl derivative from Step 3 (150 mg), Cs2CO3 (75 mg), thioacetic acid (30 μL) in EtOH (10 mL) was stirred at r.t. for 1 hr. The reaction mixture was diluted with Et2O, washed with pH 7 buffer solution, brine and the solvent evaporated. The residue was dissolved in MeOH, NaOMe (1M, 3 drops) and MeI (50 μL) was added. The mixture was stirred at r.t. for 3 hr. and diluted with a saturated NH4Cl solution and Et2O. The organic phase was separated, washed with H2O, brine, dried over MgSO4 and the solvent evaporated. The residue was flash chromatographed, eluting with hexane:EtOAc (85:15) to afford the title compound as a foam.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][C:3]=1[SH:9].Cl[CH2:11][C:12]([CH3:17])([CH3:16])[C:13]([OH:15])=[O:14].CC(C)=O.C(=O)([O-])[O-].[K+].[K+]>O>[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][C:3]=1[S:9][CH2:11][C:12]([CH3:17])([CH3:16])[C:13]([OH:15])=[O:14]
Reactant: CC(C)(CCl)C(=O)O
Reactant: Cc1ccc(C)c(S)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CC(C)=O
Product: Cc1ccc(C)c(SCC(C)(C)C(=O)O)c1
Temperature: 25 °C
Yield: 79.7 %

Procedure:
A 100-ml round-bottomed flask was charged with 1.38 g (10.00 mmol) of 2,5-dimethylthiophenol, 1.40 g (10.26 mmol) of 3-chloropivalic acid and 15 ml of acetone. Then, 2.07 g (15.0 mmol) of potassium carbonate was added, and the mixture was refluxed under heat for 30 minutes. The reaction mixture was allowed to cool to room temperature, and then about 100 ml of water was added. An aqueous layer was washed with n-hexane once, and neutralized and acidified with a 5 wt % hydrochloric acid aqueous solution. A precipitated solid was extracted with ethyl acetate, and an organic layer was washed with diluted hydrochloric acid and with a saturated sodium chloride aqueous solution and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure to give 1.90 g (yield 80%) of 3-(2,5-dimethylphenylthio)pivalic acid.
Reaction SMILES: [CH:1]([B:5]([O:10][CH:11]([CH3:13])[CH3:12])OC(C)C)([CH2:3][CH3:4])[CH3:2].[C:14]([Li])#[C:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH3:21].Cl.[B].C=C(C)C>C(OCC)C>[CH:1]([B:5]([C:14]#[C:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH3:21])[O:10][CH:11]([CH3:12])[CH3:13])([CH2:3][CH3:4])[CH3:2]
Reactant: [Li]C#CCCCCCC
Reactant: CCC(C)B(OC(C)C)OC(C)C
Agent: C=C(C)C
Agent: Cl
Agent: [B]
Solvent: CCOCC
Product: CCCCCCC#CB(OC(C)C)C(C)CC

Procedure:
sec-Butyl(1-octynyl)isopropoxyborane was prepared following the method of Example 12 with sec-butyldiisopropoxyborane (10.79 g, 58 mmol) in ethyl ether (58 mL) and added to a solution of 1-octynyllithium (64 mmol in 64 mL, THF) and quenched with HCl in ethyl ether (18.82 mL, 64 mmol). Yield: 10.1 g (74%), bp 68°-70° C. (0.1 mm Hg); n20D 1.4366; proton NMR (CDCl3)δ4.60 (septet, =18 Hz, 1H), 2.23 (triplet, 2H), 1.17 (d, J=18 Hz, 6H), 0.87 (m, 9H); boron NMR (CDCl3)δ+41.6 ppm(s); mass spectrum (chemical ionization, isobutene) m/e 237 M+H, 15%); IR (thin film) 2183, 1324 cm-1. Anal Calcd. for C15H29BO: C, 76.77; H, 12.38; B, 4.58. Found: C, 76.30; H, 12.39; B, 4.63.
Reaction SMILES: [I-].ClC1C=CC=C[N+]=1C.CCN(C(C)C)C(C)C.[C:19]1([CH3:31])[CH:24]=[CH:23][C:22]([C:25]2[S:29][C:28]([NH2:30])=[N:27][CH:26]=2)=[CH:21][CH:20]=1.[Br:32][C:33]1[S:34][C:35]([C:38](O)=[O:39])=[CH:36][N:37]=1>CN(C=O)C.CCOC(C)=O>[Br:32][C:33]1[S:34][C:35]([C:38]([NH:30][C:28]2[S:29][C:25]([C:22]3[CH:21]=[CH:20][C:19]([CH3:31])=[CH:24][CH:23]=3)=[CH:26][N:27]=2)=[O:39])=[CH:36][N:37]=1
Reactant: O=C(O)c1cnc(Br)s1
Reactant: Cc1ccc(-c2cnc(N)s2)cc1
Agent: C[n+]1ccccc1Cl
Agent: [I-]
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Solvent: CCOC(C)=O
Product: Cc1ccc(-c2cnc(NC(=O)c3cnc(Br)s3)s2)cc1
Temperature: 25 °C
Yield: 45.7 %

Procedure:
2-Chloro-1-methylpyridinium iodide (0.55 g, 2.2 mmol), DIEA (0.37 g, 2.9 mmol) and 5-p-tolylthiazol-2-amine (0.27 g, 1.44 mmol) were added to a suspension of 2-bromothiazole-5-carboxylic acid (0.30 g, 1.44 mmol) in DMF (5 mL). The resulting solution was stirred at RT till completion of the reaction. The mixture was then diluted with AcOEt, washed with water, dried with Na2SO4 and concentrated. The crude product was purified by column (30% AcOEt/PE), yielding 2-bromo-N-(5-p-tolylthiazol-2-yl)thiazole-5-carboxamide (250 mg, 46%) as a solid.
Reaction SMILES: [C:1]([NH:4][C:5]1[CH:14]=[CH:13][C:8]([S:9](Cl)(=[O:11])=[O:10])=[CH:7][CH:6]=1)(=[O:3])[CH3:2].[CH3:15][C:16]1[CH:17]=[C:18]([CH:20]=[C:21]([CH3:30])[C:22]=1[S:23]([CH2:26][N+:27]([O-:29])=[O:28])(=[O:25])=[O:24])[NH2:19].C(=O)([O-])[O-].[Ca+2].O>O1CCCC1>[CH3:30][C:21]1[CH:20]=[C:18]([NH:19][S:9]([C:8]2[CH:13]=[CH:14][C:5]([NH:4][C:1](=[O:3])[CH3:2])=[CH:6][CH:7]=2)(=[O:11])=[O:10])[CH:17]=[C:16]([CH3:15])[C:22]=1[S:23]([CH2:26][N+:27]([O-:29])=[O:28])(=[O:25])=[O:24]
Reactant: Cc1cc(N)cc(C)c1S(=O)(=O)C[N+](=O)[O-]
Reactant: CC(=O)Nc1ccc(S(=O)(=O)Cl)cc1
Agent: O=C([O-])[O-]
Agent: [Ca+2]
Solvent: C1CCOC1
Solvent: O
Product: CC(=O)Nc1ccc(S(=O)(=O)Nc2cc(C)c(S(=O)(=O)C[N+](=O)[O-])c(C)c2)cc1
Temperature: 25 °C
Reaction time: 6 h
Yield: 7.2 %

Procedure:
2.9 g (12.4 mmol) of N-acetylsulphanilyl chloride are added portionwise to a mixture, maintained under a nitrogen atmosphere, of 2.0 g (8.19 mmol) of 3,5-dimethyl-4-[(nitromethyl)sulphonyl]aniline and 1.6 g (16.0 mmol) of calcium carbonate in 40 ml of anhydrous tetrahydrofuran. The reaction medium is stirred for 6 h at room temperature and is then refluxed for 2 h, after which it is poured into 200 ml of water. The mixture is extracted 3 times with methylene chloride. The combined organic extracts are washed with water, dried over sodium sulphate and concentrated to dryness under reduced pressure. The oily residue obtained is crystallized by trituration from a mixture of hexane and ethyl acetate. These crystals are washed with a mixture of methylene chloride and methanol at room temperature and then with a mixture of hexane and ethyl acetate at reflux, and finally with ethanol at room temperature, to give 0.26 g (7.2%) of N-[4-[3,5-dimethyl-4-[(nitromethyl)sulphonyl]phenylsulphamoyl]phenyl]acetamide.
Reaction SMILES: [CH3:1][C:2]1[C:6]([C:7]([N:9]2[C:13]3([C:22]4[CH:23]=[N:24][CH:25]=[CH:26][CH:27]=4)[CH2:14][N:15]4[CH:21]=[CH:20][CH:19]=[C:16]4[C:17](=[O:18])[N:12]3[CH2:11][CH2:10]2)=[O:8])=[CH:5][O:4][N:3]=1.[OH:28]O.O>C(Cl)Cl.C[Re](=O)(=O)=O>[CH3:1][C:2]1[C:6]([C:7]([N:9]2[C:13]3([C:22]4[CH:23]=[N+:24]([O-:28])[CH:25]=[CH:26][CH:27]=4)[CH2:14][N:15]4[CH:21]=[CH:20][CH:19]=[C:16]4[C:17](=[O:18])[N:12]3[CH2:11][CH2:10]2)=[O:8])=[CH:5][O:4][N:3]=1
Reactant: OO
Reactant: Cc1nocc1C(=O)N1CCN2C(=O)c3cccn3CC12c1cccnc1
Agent: C[Re](=O)(=O)=O
Solvent: O
Solvent: ClCCl
Product: Cc1nocc1C(=O)N1CCN2C(=O)c3cccn3CC12c1ccc[n+]([O-])c1
Temperature: 25 °C
Reaction time: 4.5 h

Procedure:
To a solution of 1-[(3-methyl-1,2-oxazol-4-yl)carbonyl]-10a-(pyridin-3-yl)-2,3,10,10a-tetrahydro-1H,5H-imidazo[1,2-a]pyrrolo[1,2-d]pyrazin-5-one (15 mg, 0.041 mmol) in CH2Cl2 (0.5 mL) was added methyltrioxorhenium (VII) (1 mg, 0.004 mmol) followed by hydrogen peroxide (30% aqueous solution, 70 μL, 0.62 mmol). The resulting solution was stirred vigorously at room temperature. After 4.5 hours the reaction was complete (monitored by LCMS). Water (2 mL) was then added and the mixture extracted with CH2Cl2 (3×1 mL). The extracts were combined, dried (MgSO4), filtered and concentrated in vacuo to give an oil that was purified by flash chromatography (Biotage SP4, 4 g cartridge, gradient 0 to 10% methanol in CH2Cl2). The compound 1-[(3-methyl-1,2-oxazol-4-yl)carbonyl]-10a-(1-oxidopyridin-3-yl)-2,3,10,10a-tetrahydro-1H,5H-imidazo[1,2-a]pyrrolo[1,2-d]pyrazin-5-one (78) was isolated as a colourless oil (2 mg, yield 12%).
Reaction SMILES: [Cl:1][C:2]1[CH:23]=[CH:22][C:5]2[C:6](=O)[C:7](=[CH:17]N(C)C)[CH2:8][N:9]=[C:10]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=3)[C:4]=2[CH:3]=1.C(=O)(O)O.[NH2:28][C:29]([NH2:31])=[NH:30].C[O-].[Na+]>CO.C(Cl)Cl>[NH2:30][C:29]1[N:31]=[CH:17][C:7]2[CH2:8][N:9]=[C:10]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=3)[C:4]3[CH:3]=[C:2]([Cl:1])[CH:23]=[CH:22][C:5]=3[C:6]=2[N:28]=1
Reactant: N=C(N)N
Reactant: CN(C)C=C1CN=C(c2ccccc2)c2cc(Cl)ccc2C1=O
Agent: C[O-]
Agent: O=C(O)O
Agent: [Na+]
Solvent: CO
Solvent: ClCCl
Product: Nc1ncc2c(n1)-c1ccc(Cl)cc1C(c1ccccc1)=NC2
Reaction time: 8 h

Procedure:
A stirred suspension of 10 g (0.032 mol) of 8-chloro-3,4-dihydro-4-(dimethylaminomethylene)-1-phenyl-5H-2-benzazepin-5-one and 8.5 g (0.047 mol) of guanidine carbonate in 250 ml of methanol was treated at room temperature, under argon, with 5.1 g (0.094 mol) of sodium methylate in one portion. Methylene chloride (150 ml) was added after 10 min and stirring was continued. The same quantities of sodium methylate and guanidine carbonate were added two more times at 2 hr intervals and stirring was continued overnight. After diluting with 250 ml of methylene chloride, the mixture was washed with water, dried over sodium sulfate and evaporated at reduced pressure. Crystallization of the residue from ethanol gave light tan crystals: mp 209°-210° C. Recrystallization of a sample from methylene chloride/ethyl acetate gave off-white prisms: mp 210°-211° C.