Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl.C[O:3][C:4](=[O:8])[CH:5]([CH3:7])[NH2:6].[C:9](Cl)(=[O:16])[CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH3:15].O.[OH-].[Na+]>C(Cl)Cl>[C:9]([NH:6][CH:5]([CH3:7])[C:4]([OH:3])=[O:8])(=[O:16])[CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH3:15]
Reactant: CCCCCCC(=O)Cl
Reactant: COC(=O)C(C)N
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: ClCCl
Product: CCCCCCC(=O)NC(C)C(=O)O
Temperature: 25 °C
Reaction time: 2 h

Procedure:
30 g (291 mmol) of D,L-alanine methyl ester hydrochloride and 64.77 g (640 mmol) of triethyl)amine are initially charged in 300 ml of dry methylene chloride at 0° C. 43.24 g (291 mmol) of heptanoyl chloride in 50 ml of methylene chloride are added dropwise. The mixture is allowed to warm to RT and stirred at this temperature for 2 h. The precipitate is filtered off and the methylene chloride phase is extracted with saturated sodium bicarbonate solution and wraith saturated sodium chloride solution and dried over sodium sulfate. The solvent is removed under reduced pressure and the residue is dissolved in 300 ml of methanol. 300 ml of water, in which 46.55 g (1164 mmol) sodium hydroxide are dissolved, are added to this solution, and the mixture is stirred at RT for 2 h. The mixture is filtered, the methanol is evaporated using a rotary evaporator and the aqueous phase that remains is acidified to pH 1–2 using conc. Hcl. The precipitated product is filtered off and dried. Extraction of the aqueous phase with ethyl acetate gives a second product fraction.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH2:8][N:9]2[C:13](=[O:14])[CH2:12][CH2:11][CH:10]2[C:15]([OH:17])=O)[CH:5]=[CH:6][CH:7]=1.S(Cl)(Cl)=O.[Cl-].[Al+3].[Cl-].[Cl-]>ClCCl>[F:1][C:2]1[CH:7]=[CH:6][C:5]2[C:15](=[O:17])[CH:10]3[CH2:11][CH2:12][C:13](=[O:14])[N:9]3[CH2:8][C:4]=2[CH:3]=1
Reactant: O=C(O)C1CCC(=O)N1Cc1cccc(F)c1
Agent: [Al+3]
Agent: [Cl-]
Solvent: ClCCl
Solvent: O=S(Cl)Cl
Product: O=C1c2ccc(F)cc2CN2C(=O)CCC12
Temperature: 5 °C
Reaction time: 8 h

Procedure:
To a solution of 50.00 g of (±)-1-[(3-fluorophenyl)methyl]-5-oxo-2-pyrrolidine carboxylic acid in sieve dried dichloromethane (450 ml), 27.48 g of thionyl chloride was added, and the resultant solution was stirred and refluxed for 5 hours. An infrared spectrum of the solution indicated the presence of the acid chloride. After standing overnight at ambient temperature, the solution was chilled to 5° C. and 84 g of aluminum chloride was added in portions with vigorous stirring. The reaction was exothermic and there was a slow evolution of gas. The mixture was stirred at ambient temperature for 3 hours. The reaction was quenched by the addition of ice chips and water. The two phases of the mixture were separated and the aqueous phase was extracted with dichloromethane (4×150 ml). The combined organic phase was dried (Na2SO4) and concentrated to a solid (69.73 g).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[O:9][C:8]([C:10]3[CH:19]=[CH:18][C:17]4[C:12](=[CH:13][CH:14]=[C:15]([O:20]C)[CH:16]=4)[CH:11]=3)=[C:7]([C:22](=[O:27])[CH2:23][CH2:24][CH2:25][CH3:26])[C:6]=2[CH:28]=1.B(Br)(Br)Br.CO>C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[O:9][C:8]([C:10]3[CH:19]=[CH:18][C:17]4[C:12](=[CH:13][CH:14]=[C:15]([OH:20])[CH:16]=4)[CH:11]=3)=[C:7]([C:22](=[O:27])[CH2:23][CH2:24][CH2:25][CH3:26])[C:6]=2[CH:28]=1
Reactant: CCCCC(=O)c1c(-c2ccc3cc(OC)ccc3c2)oc2ccc(Cl)cc12
Agent: BrB(Br)Br
Solvent: ClCCl
Solvent: CO
Product: CCCCC(=O)c1c(-c2ccc3cc(O)ccc3c2)oc2ccc(Cl)cc12

Procedure:
Following the procedure described in Step 3 of Example 1,1-[5-chloro-2-(6-hydroxy-naphthalen-2-yl)-benzofuran-3-yl]-pentan-1-one was prepared 1-[5-chloro-2-(6-methoxy-naphthalen-2-yl)-benzofuran-3-yl]-pentan-1-one (5.6 g, 14.25 mmol), and boron tribromide (1M solution, 45 mL, 45 mmol) in methylene chloride (200 mL). After work-up, stirring of the solid residue with methanol and filtering afforded the title compound as a solid. (3.2 g), A sample was dissolved in chloroform and filtered through a plug of celite. The solvent was evaporated and the residue was crystallized from methanol to give white crystals, mp 156-157° C. Mass spectrum (+APCl, [M+H]+) m/z 379. 1HNMR (400 MHz, DMSO-d6): δ10.15 (br s,1H), 8.29 (d, 1H, J=1.2 Hz), 8.01 (d, 1H, J=2.2 Hz), 7.93 (d, 1H, J=8.8 Hz), 7.86 (d, 1H, J=8.6 Hz), 7.77-7.72 (m, 2H), 7.46 (dd, 1H, J=8.8, 2.2 Hz), 7.22 (d, 1H, J=2.2 Hz), 7.18 (dd, 1H, J=8.8, 2.4 Hz), 2.69 (t, 2H, J=7.3 Hz), 1.55-1.47 (m, 2H), 1.15-1.05 (m, 2H), and 0.68 ppm (t, 3H, J=7.3 Hz). Elemental Analysis for C23H19ClO3: Calculated: C, 72.92; H, 5.05; N, 0.00. Found: C, 72.73; H, 4.99; N, 0.08.
Reaction SMILES: [N:1]1([C:7]2[CH:8]=[CH:9][C:10]3[C@H:15]([CH2:16][CH2:17][OH:18])[O:14][CH2:13][CH2:12][C:11]=3[CH:19]=2)[CH2:6][CH2:5][S:4][CH2:3][CH2:2]1.[CH3:20][S:21](Cl)(=[O:23])=[O:22].CS(OCC[C@H]1C2C=CC(C(N)=O)=CC=2CCO1)(=O)=O>>[CH3:20][S:21]([O:18][CH2:17][CH2:16][C@H:15]1[C:10]2[CH:9]=[CH:8][C:7]([N:1]3[CH2:2][CH2:3][S:4][CH2:5][CH2:6]3)=[CH:19][C:11]=2[CH2:12][CH2:13][O:14]1)(=[O:23])=[O:22]
Reactant: CS(=O)(=O)Cl
Reactant: OCC[C@@H]1OCCc2cc(N3CCSCC3)ccc21
Agent: CS(=O)(=O)OCC[C@@H]1OCCc2cc(C(N)=O)ccc21
Product: CS(=O)(=O)OCC[C@@H]1OCCc2cc(N3CCSCC3)ccc21

Procedure:
Prepared from 2-[(1S)-6-(4-thiomorpholinyl)-3,4-dihydro-1H-2-benzopyran-1-yl]ethanol and methanesulfonyl chloride, as described for the preparation of 2-[(1S)-6-(aminocarbonyl)-3,4-dihydro-1H-2-benzopyran-1-yl]ethyl methanesulfonate.
Reaction SMILES: FC1C=CC(CNC)=CC=1.[CH3:11][O:12][C:13]1[CH:23]=[CH:22][C:16]([O:17][CH2:18][CH2:19][NH:20][CH3:21])=[CH:15][CH:14]=1.[F:24][C:25]1[CH:47]=[CH:46][C:28]([CH2:29][NH:30][C:31]([C:33]2[S:37][C:36]([C:38]3[CH:43]=[N:42][CH:41]=[C:40](I)[N:39]=3)=[N:35][C:34]=2[CH3:45])=[O:32])=[CH:27][CH:26]=1>>[F:24][C:25]1[CH:47]=[CH:46][C:28]([CH2:29][NH:30][C:31]([C:33]2[S:37][C:36]([C:38]3[CH:43]=[N:42][CH:41]=[C:40]([N:20]([CH2:19][CH2:18][O:17][C:16]4[CH:22]=[CH:23][C:13]([O:12][CH3:11])=[CH:14][CH:15]=4)[CH3:21])[N:39]=3)=[N:35][C:34]=2[CH3:45])=[O:32])=[CH:27][CH:26]=1
Reactant: Cc1nc(-c2cncc(I)n2)sc1C(=O)NCc1ccc(F)cc1
Reactant: CNCCOc1ccc(OC)cc1
Agent: CNCc1ccc(F)cc1
Product: COc1ccc(OCCN(C)c2cncc(-c3nc(C)c(C(=O)NCc4ccc(F)cc4)s3)n2)cc1
Yield: 80 %

Procedure:
Following the procedure described in Example 14, making variations as required to replace 4-fluoro-N-methyl-benzylamine with [2-(4-methoxy-phenoxy)-ethyl]-methyl-amine to react with 2-(6-iodo-pyrazin-2-yl)-4-methyl-thiazole-5-carboxylic acid 4-fluoro-benzylamide, the title compound was obtained in 80% yield. 1H NMR (400 MHz, CD2Cl2) δ 8.50 (s, 1H), 8.04 (s, 1H), 7.31-7.38 (m, 2H), 7.02-7.09 (m, 2H), 6.72-6.82 (m, 4H), 6.25 (bs, 1H), 4.55-4.59 (m, 2H), 4.18-4.23 (m, 2H), 4.01-4.08 (m, 2H), 3.69 (s, 3H), 3.31 (s, 3H), 2.71 (s, 3H); MS (ES+) m/z 508.2 (M+1), Rt=1.57 min.
Reaction SMILES: [C:1]([CH:6]1[C:11](=[O:12])[CH2:10][CH:9]([C:13]2[O:17][C:16]3[CH:18]=[CH:19][CH:20]=[CH:21][C:15]=3[CH:14]=2)[CH2:8][C:7]1=[O:22])(=O)[CH2:2][CH2:3][CH3:4].[CH2:23]([O:26][NH2:27])[CH:24]=[CH2:25]>C(O)C>[CH2:23]([O:26][NH:27][C:1](=[C:6]1[C:11](=[O:12])[CH2:10][CH:9]([C:13]2[O:17][C:16]3[CH:18]=[CH:19][CH:20]=[CH:21][C:15]=3[CH:14]=2)[CH2:8][C:7]1=[O:22])[CH2:2][CH2:3][CH3:4])[CH:24]=[CH2:25]
Reactant: C=CCON
Reactant: CCCC(=O)C1C(=O)CC(c2cc3ccccc3o2)CC1=O
Solvent: CCO
Product: C=CCONC(CCC)=C1C(=O)CC(c2cc3ccccc3o2)CC1=O
Yield: 92 %

Procedure:
4.6 parts by weight of 2-butyryl-5-(benzo[b]fur-2-yl)-cyclohexane-1,3-dione, 1.2 parts by weight of allyloxyamine and 30 parts by volume of ethanol were stirred for 12 hours at room temperature. The solvent was distilled off under reduced pressure, the residue was taken up in 50 parts of dichloromethane, the solution was washed twice with water and dried over sodium sulfate, and the solvent was distilled off under reduced pressure. 2-(1-Allyloxyaminobutylidene)-5-(benzo[b]fur-2-yl)-cyclohexane-1,3-dione was obtained as a viscous oil in a yield of 92% (compound no. 2).
Reaction SMILES: [NH:1]1[CH2:4][CH:3]([N:5]2[CH:9]=[C:8]([C:10]3[CH:32]=[CH:31][C:13]4[C:14]5[N:18]([CH2:19][CH2:20][O:21][C:12]=4[CH:11]=3)[CH:17]=[C:16]([C:22]3[N:23]([CH:28]([CH3:30])[CH3:29])[N:24]=[C:25]([CH3:27])[N:26]=3)[N:15]=5)[CH:7]=[N:6]2)[CH2:2]1.[C:33]([Si:37]([CH3:43])([CH3:42])[O:38][CH2:39][CH:40]=O)([CH3:36])([CH3:35])[CH3:34].C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl>[C:33]([Si:37]([CH3:43])([CH3:42])[O:38][CH2:39][CH2:40][N:1]1[CH2:2][CH:3]([N:5]2[CH:9]=[C:8]([C:10]3[CH:32]=[CH:31][C:13]4[C:14]5[N:18]([CH2:19][CH2:20][O:21][C:12]=4[CH:11]=3)[CH:17]=[C:16]([C:22]3[N:23]([CH:28]([CH3:30])[CH3:29])[N:24]=[C:25]([CH3:27])[N:26]=3)[N:15]=5)[CH:7]=[N:6]2)[CH2:4]1)([CH3:36])([CH3:35])[CH3:34]
Reactant: CC(C)(C)[Si](C)(C)OCC=O
Reactant: Cc1nc(-c2cn3c(n2)-c2ccc(-c4cnn(C5CNC5)c4)cc2OCC3)n(C(C)C)n1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: CC(=O)O
Solvent: ClCCl
Product: Cc1nc(-c2cn3c(n2)-c2ccc(-c4cnn(C5CN(CCO[Si](C)(C)C(C)(C)C)C5)c4)cc2OCC3)n(C(C)C)n1
Temperature: 25 °C
Reaction time: 5 h

Procedure:
To a solution of 8-(1-Azetidin-3-yl-1H-pyrazol-4-yl)-2-(2-isopropyl-5-methyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulene in methylene chloride was added (tert-butyl-dimethyl-silanyloxy)-acetaldehyde and acetic acid followed by sodium triacetoxyborohydride. The reaction was stirred at room temperature for about 5 hours and quenched with 1N NaOH. Methylene chloride was added and the mixture was extracted 3 times with methylene chloride. The organic phases were combined, dried with MgSO4 and concentrated. The mixture was purified by flash chromatography (0-10% MeOH in DCM) to afford 8-(1-{1-[2-(tert-Butyl-dimethyl-silanyloxy)-ethyl]-azetidin-3-yl}-1H-pyrazol-4-yl)-2-(2-isopropyl-5-methyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulene MS (ESI+) 589.3, which was treated with acid to give 230. 1H NMR (400 MHz, DMSO) δ 8.45 (s, 1H), 8.36 (d, J=8.4, 1H), 8.03 (s, 1H), 7.88 (s, 1H), 7.41 (d, J=8.3, 1H), 7.32 (d, J=1.6, 1H), 5.90-5.78 (m, 1H), 4.97 (quin, J=6.9, 1H), 4.52 (s, 4H), 4.47 (t, J=5.4, 1H), 3.73 (t, J=7.6, 2H), 3.47-3.37 (m, 4H), 2.58 (t, J=7.7, 2H), 2.25 (s, 3H), 1.47 (d, J=6.6, 6H)
Reaction SMILES: C(OC([N:8]1[C:12]([CH2:13][CH2:14][CH2:15][N:16]2[CH2:21][CH2:20][N:19]([S:22]([C:25]3[S:29][C:28]4[CH:30]=[C:31]([Cl:34])[CH:32]=[CH:33][C:27]=4[CH:26]=3)(=[O:24])=[O:23])[CH2:18][C:17]2=[O:35])=[CH:11][N:10]=[CH:9]1)=O)(C)(C)C.[F:36][C:37]([F:42])([F:41])[C:38]([OH:40])=[O:39]>C(Cl)Cl>[F:36][C:37]([F:42])([F:41])[C:38]([OH:40])=[O:39].[Cl:34][C:31]1[CH:32]=[CH:33][C:27]2[CH:26]=[C:25]([S:22]([N:19]3[CH2:20][CH2:21][N:16]([CH2:15][CH2:14][CH2:13][C:12]4[NH:8][CH:9]=[N:10][CH:11]=4)[C:17](=[O:35])[CH2:18]3)(=[O:24])=[O:23])[S:29][C:28]=2[CH:30]=1
Reactant: CC(C)(C)OC(=O)n1cncc1CCCN1CCN(S(=O)(=O)c2cc3ccc(Cl)cc3s2)CC1=O
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: O=C1CN(S(=O)(=O)c2cc3ccc(Cl)cc3s2)CCN1CCCc1cnc[nH]1
Reaction time: 3 h

Procedure:
5-{3-[4-(6-Chloro-benzo[b]thiophene-2-sulfonyl)-2-oxo-piperazin-1-yl]-propyl}-imidazol-1carboxylic acid tert-butyl ester (30 mg, 0.055 mmol) is stirred vigorously in a 30% solution of trifluoroacetic acid and methylene chloride (2 mL). The reaction is complete after stirring for three hours. The volatile solvents are removed on the rotovap, and the gummy solid is titurated with ether several times to afford 4-(6-chloro-benzo[b]thiophene-2-sulfonyl)-1-[3-(3H-imidazol-4-yl)-propyl]-piperazin-2-one trifluoroacetic acid salt (30 mg) as a yellow solid. C18H19ClN4O3S2 (m/z)+: 439, 441. Anal cald. for C18H19ClN4O3S2.C2HF3O2: C, 43.44; H, 3.65; N, 10.13. Found C, 42.03; H, 3.55; N, 8.26.
Reaction SMILES: [CH3:1][C:2]1([CH3:8])[CH2:6][CH2:5][C:4](=O)[CH2:3]1.[C:9]([CH2:11][C:12]([O:14][CH2:15][CH3:16])=[O:13])#[N:10].[Cl-].[NH4+].C(O)(=O)C>C1(C)C=CC=CC=1>[C:9](/[C:11](=[C:4]1\[CH2:3][C:2]([CH3:8])([CH3:1])[CH2:6][CH2:5]\1)/[C:12]([O:14][CH2:15][CH3:16])=[O:13])#[N:10]
Reactant: CC1(C)CCC(=O)C1
Reactant: CCOC(=O)CC#N
Agent: [Cl-]
Agent: [NH4+]
Solvent: Cc1ccccc1
Solvent: CC(=O)O
Product: CCOC(=O)/C(C#N)=C1\CCC(C)(C)C1
Temperature: 25 °C

Procedure:
To a round bottomed flask equipped with a stir bar, reflux condenser, and Dean Stark trap were added 3,3-dimethylcyclopentanone (3.4 g, 30 mmol), toluene (50 mL), and ethyl 2-cyanoacetate (3.4 g, 30 mmol), ammonium chloride (231 mg, 3 mmol) and acetic acid (0.36 mL, 6 mmol). The reaction mixture was refluxed for 24 h. The reaction was cooled to RT and concentrated to dryness. The residue was diluted with water (100 mL) and extracted with ethyl acetate (2×100 mL). The combined organic phases were dried with Na2SO4, concentrated to dryness subjected to FCC to afford the title compound as colorless oil.
Reaction SMILES: [CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][NH:14][C@H:13]([C:17]([OH:19])=[O:18])[CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.[C:27]1([N:33]([C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)[C:34](Cl)=[O:35])[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1>CN(C=O)C>[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][N:14]([C:34](=[O:35])[N:33]([C:37]2[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=2)[C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[C@H:13]([C:17]([OH:19])=[O:18])[CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=C(O)[C@@H]1CN(C(=O)OCc2ccccc2)CCN1
Reactant: O=C(Cl)N(c1ccccc1)c1ccccc1
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: O=C(O)[C@@H]1CN(C(=O)OCc2ccccc2)CCN1C(=O)N(c1ccccc1)c1ccccc1

Procedure:
A solution of 1.03 g (3.90 mmole) of (S)-4-(benzyloxycarbonyl)piperazine-2-carboxylic acid (from Step A) in 12 ml. of DMF was treated with 0.788 g (7.79 mmole) of triethylamine at 25° C. With stirring 0.901 g (3.89 mmole) of diphenylcarbamoyl chloride was added in portions over 2 hours. After 16 hours the mixture was concentrated in vacuo to an orange oil which was chromatographed over an 88×2.5 cm LH 20 column with 11 ml. fractions of methanol. Fractions 35-43 were combined and concentrated to 1.136 g (64%) of pale yellow oil which contained a major spot by TLC (80:18:2 chloroform-methanolammonia water, Rf =0.45).
Reaction SMILES: [OH:1]OS(O)(=O)=O.[C:7]1([S:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1>>[C:14]1([S:13]([C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=2)=[O:1])[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1
Reactant: O=S(=O)(O)OO
Reactant: c1ccc(Sc2ccccc2)cc1
Product: O=S(c1ccccc1)c1ccccc1
Yield: 39 %

Procedure:
The effectiveness of Caro's acid as an oxidizing agent is unexpected. More explicitly, diphenyl sulfide has been oxidized by Caro's acid to give diphenyl sulfoxide in 39% yield by I. P. Gragerov and A. F. Levit, Zh. Obshch. Khim., 33, 543 (1963). Diphenyl sulfide is a typical aromatic sulfide. The starting material used in this invention also is an aromatic sulfide and would be expected to behave as a typical aromatic sulfide; however, it does not. Most aromatic sulfides can be oxidized in 70% dioxane in water to the corresponding sulfoxide with an equivalent amount of N-bromosuccinimide. On the other hand, the reaction of N-bromosuccinimide with alkyl sulfides gives no sulfoxides, W. Tagaki et al., Chemistry and Industry (London), September 19, 1964, p 1624. The starting sulfide used in this invention failed to be oxidized to the sulfinyl compound under similar conditions using N-bromosuccinimide. Thus, the lack of reactivity of 1,2-diphenyl-4-[2-(phenylthio)ethyl]-3,5-pyrazolidinedione, when compared to typical aromatic sulfides, would predict that oxidation of the starting sulfide used in this invention with Caro's acid should give very low yields of the corresponding sulfinyl compound. However, the reverse was discovered, Caro's acid is an effective and safe oxidizing agent for selectivity converting 1,2-diphenyl-4-[2-(phenylthio)ethyl]-3,5-pyrazolidinedione to the corresponding sulfinyl compound.
Reaction SMILES: [CH3:1][C:2]([O-])(C)[CH3:3].[K+].[CH3:7]/[C:8](/[CH2:16][OH:17])=[CH:9]\[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.C(Cl)C=C>C1COCC1.[I-].C([N+](CCCC)(CCCC)CCCC)CCC>[CH2:3]([O:17][CH2:16]/[C:8](/[CH3:7])=[CH:9]/[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)[CH:2]=[CH2:1]
Reactant: CC(C)(C)[O-]
Reactant: C/C(=C\c1ccccc1)CO
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [I-]
Agent: [K+]
Solvent: C1CCOC1
Solvent: C=CCCl
Product: C=CCOC/C(C)=C/c1ccccc1
Temperature: 5 °C
Yield: 67.4 %

Procedure:
Solid potassium tert-butylate (110 g, 0.960 mol) was added portion-wise (1 hour) to a solution of trans-2-methyl-3-phenyl-2-propen-1-ol (100 g, 0.950 mol) in dry THF (1 liter) at room temperature under nitrogen. After 1 more hour at room temperature, the reaction was cooled to 5° C. and tetra butyl ammonium iodide (12.1 g, 0.032 mol) was added followed by allyl chloride (100 g, 1.280 mol) drop-wise. The reaction was warmed up to room temperature overnight and poured onto water (2 liters). The reaction was extracted twice with ethyl acetate. Each organic phase was washed with water and brine. Combined extracts are dried over solid anhydrous sodium sulfate. The solid was filtered off, rinsed with diethyl ether and the solvents were removed under vacuum. The product was purified by distillation through a 20-cm Widmer column. 120.5 g of the desired compound was obtained (97% pure, 0.620 mol, 97%). B.P.=70° C./0.067 mbar
Reaction SMILES: [S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6](=[S:8])[NH2:7].Br[CH2:10][C:11]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)=O>C(O)C.O>[C:13]1([C:11]2[N:7]=[C:6]([C:2]3[S:1][CH:5]=[CH:4][CH:3]=3)[S:8][CH:10]=2)[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1
Reactant: O=C(CBr)c1ccccc1
Reactant: NC(=S)c1cccs1
Solvent: CCO
Solvent: O
Product: c1ccc(-c2csc(-c3cccs3)n2)cc1
Temperature: 25 °C
Reaction time: 18 h
Yield: 93.5 %

Procedure:
To a stirred solution of 2-thiophenethiocarboxamide (1.56 g, 0.0109 mole) in ethanol (50 mL) was added 2-bromoacetophenone (2.19 g, 0.0110 mole). After complete addition the mixture was heated at reflux for two hours, then was allowed to cool to room temperature and stir for approximately 18 hours. The solvent was removed from the reaction mixture by evaporation under reduced pressure, leaving an oil which solidified. This solid was suspended in water and extracted twice with methylene chloride. The extracts were combined, dried over anhydrous magnesium sulfate and filtered. The filtrate was evaporated under reduced pressure to yield 2.48 g of 4-phenyl-2-(thien-2-yl)thiazole as a solid, mp 51°-53° C.
Reaction SMILES: [CH2:1]([O:3][C:4](Cl)=[O:5])[CH3:2].[CH3:7][N:8]([CH2:10][C:11]1[S:15][C:14]([CH2:16][S:17][CH2:18][CH2:19][NH:20][C:21]2[N:25]([CH3:26])[N:24]=[C:23]([NH2:27])[N:22]=2)=[CH:13][CH:12]=1)[CH3:9].C(=O)([O-])[O-].[Na+].[Na+].O>N1C=CC=CC=1>[CH2:1]([O:3][C:4](=[O:5])[NH:27][C:23]1[N:22]=[C:21]([NH:20][CH2:19][CH2:18][S:17][CH2:16][C:14]2[S:15][C:11]([CH2:10][N:8]([CH3:7])[CH3:9])=[CH:12][CH:13]=2)[N:25]([CH3:26])[N:24]=1)[CH3:2]
Reactant: CCOC(=O)Cl
Reactant: CN(C)Cc1ccc(CSCCNc2nc(N)nn2C)s1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O
Solvent: c1ccncc1
Product: CCOC(=O)Nc1nc(NCCSCc2ccc(CN(C)C)s2)n(C)n1
Yield: 56.2 %

Procedure:
A cooled mixture of ethylchloroformate (0.45 g) in pyridine was treated with a solution of N5 -[2-[[[5-[(dimethylamino)methyl]-2-thienyl]methyl]thio]ethyl]-1-methyl-1H-1,2,4-triazole-3,5-diamine (0.7 g) in pyridine (8 ml). Sodium carbonate (2 g) and water (10 ml) were added and the mixture evaporated in vacuo. The residue was dissolved in water (15 ml) and extracted with hot isopropanol (30 ml). The extract was evaporated and the residue purified by column chromatography (silica:methanol:0.88 ammonia; 79:1) to give the title compound (0.48 g).
Reaction SMILES: [C:1]([C:3]1[CH:23]=[CH:22][CH:21]=[CH:20][C:4]=1[O:5][C:6]1[CH:11]=[CH:10][C:9]([NH:12][CH2:13][C:14]2[CH:15]=[N:16][CH:17]=[CH:18][CH:19]=2)=[CH:8][CH:7]=1)#[N:2].[F:24][C:25]([F:32])([F:31])[CH2:26][S:27](Cl)(=[O:29])=[O:28]>>[C:1]([C:3]1[CH:23]=[CH:22][CH:21]=[CH:20][C:4]=1[O:5][C:6]1[CH:7]=[CH:8][C:9]([N:12]([CH2:13][C:14]2[CH:15]=[N:16][CH:17]=[CH:18][CH:19]=2)[S:27]([CH2:26][C:25]([F:32])([F:31])[F:24])(=[O:29])=[O:28])=[CH:10][CH:11]=1)#[N:2]
Reactant: N#Cc1ccccc1Oc1ccc(NCc2cccnc2)cc1
Reactant: O=S(=O)(Cl)CC(F)(F)F
Product: N#Cc1ccccc1Oc1ccc(N(Cc2cccnc2)S(=O)(=O)CC(F)(F)F)cc1

Procedure:
Using the method of Example 342 using N-(4-(2-cyanophenoxy)phenyl)pyridin-3-ylmethylamine and 2,2,2-trifluoroethanesulfonyl chloride (Aldrich) and purifying via preparative HPLC eluting with 90:10 to 78:22 DCM/ethyl acetate gave the title compound. Anal Calcd for C21H16F3N3O3S.0.2H2O: C, 55.92; H, 3.67; N, 9.32. Found: C, 55.77; H, 3.51; N, 9.18. MS found 447.8 [M+H]+
Reaction SMILES: CCN=C=NCCCN(C)C.C1C=NC2N(O)N=NC=2C=1.[CH3:22][C:23]1[C:24]([C:39]2[CH:44]=[CH:43][C:42]([CH3:45])=[CH:41][CH:40]=2)=[C:25]([C:36](O)=[O:37])[N:26]([CH2:28][C:29]2[CH:34]=[CH:33][C:32]([CH3:35])=[CH:31][CH:30]=2)[CH:27]=1.[CH2:46]([N:48]([CH2:57][CH3:58])[CH2:49][CH2:50][N:51]1[CH2:56][CH2:55][NH:54][CH2:53][CH2:52]1)[CH3:47]>C(Cl)Cl>[CH2:57]([N:48]([CH2:46][CH3:47])[CH2:49][CH2:50][N:51]1[CH2:52][CH2:53][N:54]([C:36]([C:25]2[N:26]([CH2:28][C:29]3[CH:34]=[CH:33][C:32]([CH3:35])=[CH:31][CH:30]=3)[CH:27]=[C:23]([CH3:22])[C:24]=2[C:39]2[CH:40]=[CH:41][C:42]([CH3:45])=[CH:43][CH:44]=2)=[O:37])[CH2:55][CH2:56]1)[CH3:58]
Reactant: Cc1ccc(Cn2cc(C)c(-c3ccc(C)cc3)c2C(=O)O)cc1
Reactant: CCN(CC)CCN1CCNCC1
Agent: CCN=C=NCCCN(C)C
Agent: On1nnc2cccnc21
Solvent: ClCCl
Product: CCN(CC)CCN1CCN(C(=O)c2c(-c3ccc(C)cc3)c(C)cn2Cc2ccc(C)cc2)CC1
Temperature: 0 °C
Reaction time: 8 h
Yield: 38.5 %

Procedure:
EDCI (166 mg, 0.87 mmol) and HOAt (11 mg, 0.08 mmol) were added at 0° C. to a reaction mixture of 4-methyl-1-(4-methylbenzyl)-3-p-tolyl-1H-pyrrole-2-carboxylic acid (252 mg, 0.79 mmol) and 1-(2-diethylaminoethyl)-piperazine (146 mg, 0.79 mmol) in DCM (5 mL) and the reaction mixture was stirred for 30 min at 0° C. and overnight at RT. After removal of the solvent, purification proceeded by means of column chromatography and the desired product [4-(2-diethylamino-ethyl)-piperazin-1-yl]-[4-methyl-1-(4-methylbenzyl)-3-p-tolyl-1H-pyrrol-2-yl]-methanone (148 mg, 38% of theoretical) was obtained.
Reaction SMILES: [Cl:1][C:2]1[C:7]([OH:8])=[C:6]([N+:9]([O-:11])=[O:10])[CH:5]=[CH:4][N:3]=1.[CH3:12][Si](C=[N+]=[N-])(C)C>C(#N)C.CO>[Cl:1][C:2]1[C:7]([O:8][CH3:12])=[C:6]([N+:9]([O-:11])=[O:10])[CH:5]=[CH:4][N:3]=1
Reactant: C[Si](C)(C)C=[N+]=[N-]
Reactant: O=[N+]([O-])c1ccnc(Cl)c1O
Solvent: CO
Solvent: CC#N
Product: COc1c([N+](=O)[O-])ccnc1Cl
Reaction time: 0.5 h
Yield: 67.8 %

Procedure:
To a solution of 2-chloro-4-nitro-pyridin-3-ol (1.05 g, 6.02 mmol) in acetonitrile (45 mL) and methanol (5 mL), trimethylsilyldiazomethane (2M in hexane, 3.9 mL, 7.8 mmol) were added slowly. After 30 minutes, mixture was concentrated and residue was purified by column chromatography on silica gel (hexane/ethyl acetate 5:1) to give 2-chloro-3-methoxy-4-nitro-pyridine as a white solid (0.77 g, 68%). 1HNMR (CDCl3, 400 MHz) δ 8.35-8.34 (d, J=5.1 Hz, 1H), 7.58-7.56 (d, J=5.2 Hz, 1H), 4.08 (s, 3H).