Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[N:3]=[C:4](Cl)[C:5]2[O:10][CH:9]=[CH:8][C:6]=2[N:7]=1.O1CCOCC1.[CH:18]1([NH2:21])[CH2:20][CH2:19]1>CO>[Cl:1][C:2]1[N:3]=[C:4]([NH:21][CH:18]2[CH2:20][CH2:19]2)[C:5]2[O:10][CH:9]=[CH:8][C:6]=2[N:7]=1
Reactant: NC1CC1
Reactant: Clc1nc(Cl)c2occc2n1
Solvent: C1COCCO1
Solvent: CO
Product: Clc1nc(NC2CC2)c2occc2n1
Temperature: 25 °C
Reaction time: 5 h
Yield: 91.7 %

Procedure:
A vial was charged with 2,4-dichlorofuro[3,2-d]pyrimidine (0.50 g, 2.6 mmol, Ark Pharm), TEA (0.369 mL, 2.65 mmol), 1,4-dioxane (20 mL) and cyclopropylamine (0.186 mL, 2.65 mmol). The mixture was stirred at rt for about 5 h and then passed through a 5.0 g SiCO3 SPE cartridge, (MeOH eluent) and concentrated under reduced pressure. The residue was purified by silica gel chromatography with a gradient of 0 to 50% EtOAc/hexanes to give 2-chloro-N-cyclopropylfuro[3,2-d]pyrimidin-4-amine (0.5 g, 90%). 1H NMR (CDCl3): δ 7.77 (s, 1H); 6.80 (s, 1H), 5.51 (s, 1H) 3.07 (m, 1H) 0.96 (q, J=5 Hz, 15 Hz, 2H) 0.70, (q, J=5 Hz, 15 Hz, 2H).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:30]=[CH:29][C:6]([CH2:7][NH:8][C:9]([C:11]2([CH2:24][CH2:25][CH2:26][CH2:27]Br)[C:23]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[C:17]3[C:12]2=[CH:13][CH:14]=[CH:15][CH:16]=3)=[O:10])=[CH:5][CH:4]=1.[CH3:31][N:32]1[C:36]2[CH:37]=[CH:38][CH:39]=[CH:40][C:35]=2[N:34]=[C:33]1[N:41]1[CH2:46][CH2:45][NH:44][CH2:43][CH2:42]1>>[CH3:1][O:2][C:3]1[CH:30]=[CH:29][C:6]([CH2:7][NH:8][C:9]([C:11]2([CH2:24][CH2:25][CH2:26][CH2:27][N:44]3[CH2:45][CH2:46][N:41]([C:33]4[N:32]([CH3:31])[C:36]5[CH:37]=[CH:38][CH:39]=[CH:40][C:35]=5[N:34]=4)[CH2:42][CH2:43]3)[C:23]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[C:17]3[C:12]2=[CH:13][CH:14]=[CH:15][CH:16]=3)=[O:10])=[CH:5][CH:4]=1
Reactant: Cn1c(N2CCNCC2)nc2ccccc21
Reactant: COc1ccc(CNC(=O)C2(CCCCBr)c3ccccc3-c3ccccc32)cc1
Product: COc1ccc(CNC(=O)C2(CCCCN3CCN(c4nc5ccccc5n4C)CC3)c3ccccc3-c3ccccc32)cc1

Procedure:
Prepared analogously to Example 1e from 9-(4-bromo-butyl)-9H-fluorene-9-carboxylic acid-4-methoxy-benzylamide and 1-methyl-2-piperazin-1-yl-1H-benzimidazole.
Reaction SMILES: [CH:1]1[C:6]([CH:7]=O)=[CH:5][C:4]2[O:9][CH2:10][O:11][C:3]=2[CH:2]=1.[C:12]([N:17]1[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]1)(=[O:16])/[CH:13]=[CH:14]/[CH3:15].[OH-]>>[CH:7](=[CH:15]/[CH:14]=[CH:13]/[C:12]([N:17]1[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]1)=[O:16])[C:6]1[CH:1]=[CH:2][C:3]2[O:11][CH2:10][O:9][C:4]=2[CH:5]=1
Reactant: C/C=C/C(=O)N1CCCCC1
Reactant: O=Cc1ccc2c(c1)OCO2
Agent: [OH-]
Product: O=C(/C=C/C=Cc1ccc2c(c1)OCO2)N1CCCCC1

Procedure:
1 mol of piperonal is reacted with 1.1 mols of crotonic acid piperidide in the presence of 0.09 mol of a hydroxide, indicated in Table 2 below, under the reaction conditions described in Example 1 to give piperonylidenecrotonic acid piperidide. The yields obtained are likewise indicated in Table 2.
Reaction SMILES: [OH:1][C@@H:2]1[C@H:6]2[N:7](C(OCC3C=CC=CC=3)=O)[CH2:8][C@@H:9]([CH3:10])[C@H:5]2[O:4][CH2:3]1.[H][H]>[Pd].CO>[CH3:10][C@H:9]1[CH2:8][NH:7][C@@H:6]2[C@@H:2]([OH:1])[CH2:3][O:4][C@H:5]12
Reactant: [H][H]
Reactant: C[C@@H]1CN(C(=O)OCc2ccccc2)[C@H]2[C@@H]1OC[C@@H]2O
Agent: [Pd]
Solvent: CO
Product: C[C@H]1CN[C@H]2[C@@H]1OC[C@@H]2O
Reaction time: 1 h

Procedure:
Methanol (1.25 mL) was added dropwise to a mixture of 10% palladium on charcoal (20 mg) and bicyclic alcohol (108) (49 mg, 0.177 mmol) under an atmosphere of argon. The argon was replaced by hydrogen then the suspension was stirred for 1 hour then filtered through celite in vacuo. The filter cake was washed with ethanol (10 mL) then the solvents removed in vacuo from the filtrate. The residue was azeotroped with diethyl ether (3×3 mL) to obtain the crude (3R,3aR,6S,6aR)-6-methylhexahydro-2H-furo[3,2-b]pyrrol-3-ol (107) which was used without further purification.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]([CH2:12][CH2:13]Cl)[CH:10]([CH2:15]Cl)[CH2:9][N:8]=[C:7]([C:17]3[O:18][CH:19]=[CH:20][CH:21]=3)[C:6]=2[CH:22]=1.[CH3:23][NH2:24]>CO>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]3[CH2:12][CH2:13][N:24]([CH3:23])[CH2:15][CH:10]3[CH2:9][N:8]=[C:7]([C:17]3[O:18][CH:19]=[CH:20][CH:21]=3)[C:6]=2[CH:22]=1
Reactant: ClCCN1c2ccc(Cl)cc2C(c2ccco2)=NCC1CCl
Reactant: CN
Solvent: CO
Product: CN1CCN2c3ccc(Cl)cc3C(c3ccco3)=NCC2C1
Yield: 45.3 %

Procedure:
1 g of 7-chloro-1-(β-chloroethyl)-2-chloromethyl-5-(2-furyl)-2,3-dihydro-1H-1,4-benzodiazepine in 40 ml of methanol is left to react with 0.8 g of methylamine at 50° C. for 3 hours. The reaction mixture is then worked up as described in Example 7. On purification by chromatography, the fractions containing the more highly polar title compound are separated off. 0.4 g of 1,2,3,4,4a,5-hexahydro-9-chloro-3-methyl-7-(2-furyl)-pyrazino[1,2-a][1,4]benzodiazepine is obtained therefrom.
Reaction SMILES: C([O:4][CH2:5][C:6]1[C:7]([N:35]2[CH2:46][CH2:45][N:44]3[C:37](=[CH:38][C:39]4[CH2:40][C:41]([CH3:48])([CH3:47])[CH2:42][C:43]=43)[C:36]2=[O:49])=[N:8][CH:9]=[CH:10][C:11]=1[C:12]1[CH:17]=[C:16]([NH:18][C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([O:25][CH2:26][CH2:27][NH:28][C:29](=[O:32])[CH:30]=[CH2:31])[N:20]=2)[C:15](=[O:33])[N:14]([CH3:34])[CH:13]=1)(=O)C.[Li+].[OH-]>C1COCC1.CC(O)C.O.O>[CH3:47][C:41]1([CH3:48])[CH2:40][C:39]2[CH:38]=[C:37]3[N:44]([CH2:45][CH2:46][N:35]([C:7]4[C:6]([CH2:5][OH:4])=[C:11]([C:12]5[CH:17]=[C:16]([NH:18][C:19]6[N:20]=[C:21]([O:25][CH2:26][CH2:27][NH:28][C:29](=[O:32])[CH:30]=[CH2:31])[CH:22]=[CH:23][CH:24]=6)[C:15](=[O:33])[N:14]([CH3:34])[CH:13]=5)[CH:10]=[CH:9][N:8]=4)[C:36]3=[O:49])[C:43]=2[CH2:42]1
Reactant: C=CC(=O)NCCOc1cccc(Nc2cc(-c3ccnc(N4CCn5c(cc6c5CC(C)(C)C6)C4=O)c3COC(C)=O)cn(C)c2=O)n1
Agent: [Li+]
Agent: [OH-]
Solvent: CC(C)O
Solvent: C1CCOC1
Solvent: O
Product: C=CC(=O)NCCOc1cccc(Nc2cc(-c3ccnc(N4CCn5c(cc6c5CC(C)(C)C6)C4=O)c3CO)cn(C)c2=O)n1
Reaction time: 1 h
Yield: 39.4 %

Procedure:
—Step 6: To a solution of 101f (257 mg, 0.387 mmol) in THF/i-PrOH/H2O (5.0/3.0/2.0 mL) was added LiOH (46 mg, 1.95 mmol) at room temperature. The reaction was stirred for 1 h. The mixture was diluted with water (15 mL) and extracted with DCM (15 mL×3). The combined organic layer was washed with brine (10 mL), dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue solid was purified by reverse-phase prep-HPLC to afford 101 (95 mg, 39% two steps) as a white solid. MS-ESI: [M+H]+ 624.2. 1H NMR (500 MHz, CDCl3) δ 8.74 (d, J=2.0 Hz, 1H), 8.53 (d, J=5.0 Hz, 1H), 9.70 (s, 1H), 7.73 (d, J=2.0 Hz, 1H), 7.50-7.48 (m, 1H), 7.29-7.27 (m, 1H), 6.85 (s, 1H), 6.46-6.44 (m, 2H), 6.27-6.23 (m, 2H), 6.05-6.00 (m, 1H), 5.61-5.59 (m, 1H), 4.98-4.96 (m, 1H), 4.72-4.70 (m, 1H), 4.55-4.53 (m, 1H), 4.39-4.29 (m, 3H), 4.19-4.16 (m, 2H), 3.96-3.94 (m, 1H), 375-3.73 (m, 4H, overlap), 3.64-3.60 (m, 1H), 2.61-2.59 (m, 2H), 2.53-2.51 (m, 2H), 1.30 (s, 6H).
Reaction SMILES: [H-].[Na+].[F:3][C:4]1[CH:9]=[C:8]([F:10])[CH:7]=[CH:6][C:5]=1[C:11]([OH:28])([C:18]([CH3:27])([CH3:26])[CH:19](OS(C)(=O)=O)[CH3:20])[CH2:12][N:13]1[CH:17]=[N:16][CH:15]=[N:14]1.CO>O1CCCC1.O>[F:3][C:4]1[CH:9]=[C:8]([F:10])[CH:7]=[CH:6][C:5]=1[C:11]1([CH2:12][N:13]2[CH:17]=[N:16][CH:15]=[N:14]2)[C:18]([CH3:26])([CH3:27])[CH:19]([CH3:20])[O:28]1
Reactant: CC(OS(C)(=O)=O)C(C)(C)C(O)(Cn1cncn1)c1ccc(F)cc1F
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CO
Solvent: O
Product: CC1OC(Cn2cncn2)(c2ccc(F)cc2F)C1(C)C
Reaction time: 0.17 h

Procedure:
10 mg of sodium hydride were added to a solution of 77 mg of this 2-(2,4-difluorophenyl)-3,3-dimethyl-4-(methanesulfonyloxy)-1-(1H-1,2,4-triazol-1-yl)-2-pentanol in 1.5 ml of tetrahydrofuran, whilst ice-cooling and stirring, after which 0.1 ml of methanol was added. After 10 minutes, the reaction mixture was diluted with water and extracted with ethyl acetate. The resulting crude product was purified by column chromatography through silica gel, using a 3:2 by volume mixture of ethyl acetate and hexane as the eluent. The resulting compound was recrystallized from cyclohexane to afford 39 mg of a pure specimen of the title compound, melting at 112°-113° C.
Reaction SMILES: [NH2:1][C@H:2]([C:4]1[N:9]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[C:8](=[O:16])[C:7]2=[C:17]([CH3:20])[CH:18]=[CH:19][N:6]2[N:5]=1)[CH3:3].Cl[C:22]1[C:23]2[CH:31]=[CH:30][S:29][C:24]=2[N:25]=[C:26]([CH3:28])[N:27]=1.C(N(CC)C(C)C)(C)C>>[CH3:20][C:17]1[CH:18]=[CH:19][N:6]2[C:7]=1[C:8](=[O:16])[N:9]([C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)[C:4]([C@@H:2]([NH:1][C:22]1[C:23]3[CH:31]=[CH:30][S:29][C:24]=3[N:25]=[C:26]([CH3:28])[N:27]=1)[CH3:3])=[N:5]2
Reactant: Cc1nc(Cl)c2ccsc2n1
Reactant: Cc1ccn2nc([C@H](C)N)n(-c3ccccc3)c(=O)c12
Solvent: CCN(C(C)C)C(C)C
Product: Cc1nc(N[C@@H](C)c2nn3ccc(C)c3c(=O)n2-c2ccccc2)c2ccsc2n1
Yield: 40.5 %

Procedure:
(S)-2-(1-Aminoethyl)-5-methyl-3-phenylpyrrolo[2,1-f][1,2,4]triazin-4(3H)-one (50 mg, 0.16 mmol) was treated with 4-chloro-2-methylthieno[2,3-d]pyrimidine (45 mg, 0.25 mmol), N,N-diisopropylethylamine (257 μl, 1.48 mmol) according to the method described in Example 17. The crude was purified using SP1® Purification System by reverse phase to give 27 mg (40% yield) of the title compound as a white solid. Purity 100%.
Reaction SMILES: [NH2:1][CH2:2][CH2:3][N:4]1[C:8]([Cl:9])=[C:7]([C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([C:16]#[N:17])[CH:11]=2)[C:6]([C:18]([O:20][CH3:21])=[O:19])=[CH:5]1.Cl.[CH2:23]=O.N>CO.O>[Cl:9][C:8]1[N:4]2[CH2:3][CH2:2][NH:1][CH2:23][C:5]2=[C:6]([C:18]([O:20][CH3:21])=[O:19])[C:7]=1[C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([C:16]#[N:17])[CH:11]=1
Reactant: C=O
Reactant: COC(=O)c1cn(CCN)c(Cl)c1-c1cccc(C#N)c1
Agent: Cl
Agent: N
Solvent: O
Solvent: CO
Product: COC(=O)c1c(-c2cccc(C#N)c2)c(Cl)n2c1CNCC2
Temperature: 90 °C
Reaction time: 4 h
Yield: 224.9 %

Procedure:
To a solution of 8.41 g (27.7 mmol) of methyl 1-(2-aminoethyl)-5-chloro-4-(3-cyanophenyl)-1H-pyrrole-3-carboxylate in 20 ml of methanol are added 84 ml (340 mmol) of aqueous 4N hydrochloric acid solution. The formation of a white precipitate is rapidly observed and the medium then becomes clear, while the mixture is heated to 90° C. and 0.92 g (10 mmol) of paraformaldehyde is added. Heating is continued at 90° C. for 4 hours. After cooling, the reaction medium is poured into 200 ml of water and the solution is basified by adding aqueous ammonia. The product is extracted with ethyl acetate, the organic phase is dried over sodium sulfate and the solvent is evaporated off under reduced pressure to give an orange-coloured oil, which is chromatographed on a column of 80 g of silica gel, eluting with a mixture of 2% methanol in dichloromethane, to give 7.1 g of methyl 6-chloro-7-(3-cyanophenyl)-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazine-8-carboxylate in the form of a yellow oil.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=1.Br[C:9]1[CH:10]=[CH:11][C:12]([O:29][CH2:30][CH3:31])=[C:13]([C:15]2[NH:16][C:17](=[O:28])[C:18]3[N:23]([CH3:24])[N:22]=[C:21]([CH2:25][CH2:26][CH3:27])[C:19]=3[N:20]=2)[CH:14]=1>>[CH2:30]([O:29][C:12]1[CH:11]=[CH:10][C:9]([N:3]2[CH:4]=[CH:5][CH:6]=[CH:7][CH2:2]2)=[CH:14][C:13]=1[C:15]1[NH:16][C:17](=[O:28])[C:18]2[N:23]([CH3:24])[N:22]=[C:21]([CH2:25][CH2:26][CH3:27])[C:19]=2[N:20]=1)[CH3:31]
Reactant: Brc1ccccn1
Reactant: CCCc1nn(C)c2c(=O)[nH]c(-c3cc(Br)ccc3OCC)nc12
Product: CCCc1nn(C)c2c(=O)[nH]c(-c3cc(N4C=CC=CC4)ccc3OCC)nc12

Procedure:
The title compound was prepared from 2-bromopyridine and 5-(5-bromo-2-ethoxyphenyl)-1-methyl-3-n-propyl-1,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one, following the procedure described in Example 82, and was obtained as an off-white solid (33%), m.p. 216-218° C. Found: C,67.61; H,5.81; N,17.63. C22H23N5O2 requires C,67.85; H,5.95; N,17.98%.
Reaction SMILES: [CH3:1][CH:2]1[CH:15]2[CH:5]([CH2:6][C:7]32[CH2:9][CH:8]3[C:10]([O:12]CC)=[O:11])[CH2:4][CH2:3]1.C1(C(OCC)=O)C2(CCCCC2)C1>>[CH3:1][CH:2]1[CH:15]2[CH:5]([CH2:6][C:7]32[CH2:9][CH:8]3[C:10]([OH:12])=[O:11])[CH2:4][CH2:3]1
Reactant: CCOC(=O)C1CC12CC1CCC(C)C12
Agent: CCOC(=O)C1CC12CCCCC2
Product: CC1CCC2CC3(CC3C(=O)O)C12

Procedure:
The title compound was prepared as described in Example 1B substituting the product from Example 33B for the product from Example 1A. MS (ESI) m/z 179 (M−H)−.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:15][C@H:14]([OH:16])[CH2:13][C@H:9]1[C:10]([OH:12])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CCOC(/N=N/C(OCC)=O)=O>C1COCC1>[O:12]=[C:10]1[C@@H:9]2[CH2:13][C@@H:14]([CH2:15][N:8]2[C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[O:16]1
Reactant: CC(C)(C)OC(=O)N1C[C@H](O)C[C@H]1C(=O)O
Agent: CCOC(=O)/N=N/C(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)N1C[C@@H]2C[C@H]1C(=O)O2
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution of (4R)-1-(tert-butoxycarbonyl)-4-hydroxy-L-proline (100 g, 0.443 mol) and PPh3 (227 g, 0.866 mol) in dry THF (1 L) was added dropwise DEAD (151 g, 0.866 mol) at 0° C. under nitrogen. After the addition, the reaction was allowed to warm up to room temperature and stirred overnight. The reaction was concentrated in vacuo and the residue was purified by column chromatography (petroleum ether:ethyl acetate=20:1˜5:1) which gave the title compound Va as a yellow solid (106.5 g).
Reaction SMILES: [CH:1]1([N:6]2[C:14]3[C:9](=[CH:10][CH:11]=[C:12]([C:15]([OH:17])=O)[CH:13]=3)[C:8]([CH2:18][CH3:19])=[N:7]2)[CH2:5][CH2:4][CH2:3][CH2:2]1.Cl.[CH2:21]([O:23][C:24](=[O:28])[CH2:25][CH2:26][NH2:27])[CH3:22]>>[CH2:21]([O:23][C:24](=[O:28])[CH2:25][CH2:26][NH:27][C:15]([C:12]1[CH:13]=[C:14]2[C:9]([C:8]([CH2:18][CH3:19])=[N:7][N:6]2[CH:1]2[CH2:2][CH2:3][CH2:4][CH2:5]2)=[CH:10][CH:11]=1)=[O:17])[CH3:22]
Reactant: CCc1nn(C2CCCC2)c2cc(C(=O)O)ccc12
Reactant: CCOC(=O)CCN
Agent: Cl
Product: CCOC(=O)CCNC(=O)c1ccc2c(CC)nn(C3CCCC3)c2c1
Yield: 90.5 %

Procedure:
This compound was prepared according to the method of Example 35, using 297 mg (1.15 mmol, 1.0 equiv) 1-cyclopentyl-3-ethyl-1H-indazole-6-carboxylic acid and 177 mg (1.15 mmol, 1.0 equiv) beta-alanine ethyl ester hydrochloride as starting materials to give 372 mg (90%) of white crystals: mp 74-76° C.; Anal. calcd for C20H27N3O3: C, 67.21; H, 7.61; N, 11.76. Found: C, 67.40; H, 7.56; N, 11.99.
Reaction SMILES: [C:1](Cl)(=[O:5])[C:2]([CH3:4])=[O:3].Cl.[CH3:8][Si:9]([O:12][C:13](=[O:19])[C@H:14]([CH:16]([CH3:18])[CH3:17])[NH2:15])([CH3:11])[CH3:10]>>[CH3:11][Si:9]([O:12][C:13](=[O:19])[C@H:14]([CH:16]([CH3:17])[CH3:18])[NH:15][C:1](=[O:5])[C:2]([CH3:4])=[O:3])([CH3:8])[CH3:10]
Reactant: CC(=O)C(=O)Cl
Reactant: CC(C)[C@H](N)C(=O)O[Si](C)(C)C
Agent: Cl
Product: CC(=O)C(=O)N[C@H](C(=O)O[Si](C)(C)C)C(C)C

Procedure:
A method of synthesizing pyruvyl-valine according to the invention comprises the steps of reacting sodium pyruvate with oxalyl chloride to yield pyruvyl chloride, then reacting the pyruvyl chloride with a suspension of valine trimethylsilyl ester hydrochloride to yield pyruvyl-valine trimethylsilyl ester and then subjecting the pyruvyl-valine trimethylsilyl ester to hydrolysis to yield pyruvyl-valine. The pyruvyl-valine synthesized via the route set forth above serves as a pyruvyl-amino acid pyruvate precursor.
Reaction SMILES: [O:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6](=[O:30])[CH2:7][CH:8]([CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)[C:9]([NH:11][C@@H:12]([C:19]([O:21]C)=[O:20])[CH2:13][C:14]1[N:18]=[CH:17][NH:16][CH:15]=1)=[O:10].[OH-].[Na+]>CO>[O:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6](=[O:30])[CH2:7][CH:8]([CH2:23][C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1)[C:9]([NH:11][C@@H:12]([C:19]([OH:21])=[O:20])[CH2:13][C:14]1[N:18]=[CH:17][NH:16][CH:15]=1)=[O:10]
Reactant: COC(=O)[C@@H](Cc1c[nH]cn1)NC(=O)C(CC(=O)c1ccco1)Cc1ccccc1
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: O=C(CC(Cc1ccccc1)C(=O)N[C@H](Cc1c[nH]cn1)C(=O)O)c1ccco1
Temperature: 25 °C
Reaction time: 2 h
Yield: 0 %

Procedure:
A mixture of 0,581 g of methyl (R)-N-[4-(2-furanyl)-1,4-dioxo-2-(phenylmethyl)butyl]-L-histidinate, 1.8 ml of methanol and 1.8 ml of 1N sodium hydroxide is stirred at room temperature for 2 hours. The solvent is removed, water added and the pH adjusted to pH 4 to pH 5. The mixture is extracted with dichloromethane (5×10 ml), the extract dried (Na2SO4) and the solvent removed to give 0.26 g of product as a white foam. The aqueous layer is extracted again with ethyl acetate (3×10 ml) and with chloroform containing 1% CH3OH. The ethyl acetate and chloroform extracts are combined, dried (Na2SO4) and the solvent removed to give 0.21 g of product as a white foams [α]D26 +25°±1 (c, 0.92, CH30H).
Reaction SMILES: [Br:1][C:2]1[CH:7]=[C:6]([O:8][CH3:9])[C:5]([O:10][CH3:11])=[CH:4][C:3]=1[CH2:12]O.[ClH:14]>>[Br:1][C:2]1[CH:7]=[C:6]([O:8][CH3:9])[C:5]([O:10][CH3:11])=[CH:4][C:3]=1[CH2:12][Cl:14]
Reactant: Cl
Reactant: COc1cc(Br)c(CO)cc1OC
Product: COc1cc(Br)c(CCl)cc1OC
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
(2-Bromo-4,5-dimethoxy-phenyl)-methanol (25.09 g, 0.1015 mol) was added as a solid to a vigorously stirred solution of concentrated aqueous HCl (75 mL). The resulting white suspension was stirred at room temperature for 30 min. The resulting mixture was then extracted with CH2Cl2 (3×) and the combined extracts dried over MgSO4, filtered and concentrated in vacuo to yield 1-bromo-2-chloromethyl-4,5-dimethoxy-benzene as a white solid.
Reaction SMILES: [CH:1]([N:4]1[CH2:9][CH2:8][N:7]([C:10]([C:12]2[CH:13]=[C:14]3[C:18](=[CH:19][CH:20]=2)[NH:17][C:16]([C:21]([OH:23])=O)=[CH:15]3)=[O:11])[CH2:6][CH2:5]1)([CH3:3])[CH3:2].Cl.F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.[NH:47]1[CH2:52][CH2:51][S:50](=[O:54])(=[O:53])[CH2:49][CH2:48]1.C(N(CC)C(C)C)(C)C.C(=O)(O)[O-].[Na+]>CN(C)C=O>[O:53]=[S:50]1(=[O:54])[CH2:51][CH2:52][N:47]([C:21]([C:16]2[NH:17][C:18]3[C:14]([CH:15]=2)=[CH:13][C:12]([C:10]([N:7]2[CH2:8][CH2:9][N:4]([CH:1]([CH3:2])[CH3:3])[CH2:5][CH2:6]2)=[O:11])=[CH:20][CH:19]=3)=[O:23])[CH2:48][CH2:49]1
Reactant: CC(C)N1CCN(C(=O)c2ccc3[nH]c(C(=O)O)cc3c2)CC1
Reactant: O=S1(=O)CCNCC1
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: Cl
Agent: F[B-](F)(F)F
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: CC(C)N1CCN(C(=O)c2ccc3[nH]c(C(=O)N4CCS(=O)(=O)CC4)cc3c2)CC1
Yield: 52.7 %

Procedure:
To the solution of 0.20 g (0.57 mmol) 5-(4-isopropyl-piperazine-1-carbonyl)-1H-indole-2-carboxylic acid 1:1 hydrochloride in 2 mL N,N-dimethylformamide, 0.19 g (0.60 mmol) O-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium tetrafluoroborate (commercially available), 82 mg (0.60 mmol) thiomorpholine 1,1-dioxide (commercially available) and 0.58 mL (0.44 g, 3.4 mmol) N,N-diisopropylethylamine were added. After 1 h the solution was poured on saturated aqueous sodium bicarbonate solution, the phases were separated and the aqueous phase was extracted three times with ethyl acetate. The combined organic layers were washed three times with water followed by brine, dried over magnesium sulfate, filtered and evaporated. The residue was flash-chromatographed twice on silica gel with dichloromethane:methanol:ammonia (12:1:0.1 v/v) as eluant to give 0.13 g (64%) of the desired compound as a light brown solid.
Reaction SMILES: [C:1]1([CH:8]=[CH:7][CH:6]=[C:4]([OH:5])[CH:3]=1)[OH:2].[CH2:9]=[O:10].O.Cl>C(O)C>[C:1]1([CH:8]=[CH:7][CH:6]=[C:4]([OH:5])[C:3]=1[CH:9]=[O:10])[OH:2]
Reactant: C=O
Reactant: Oc1cccc(O)c1
Agent: Cl
Solvent: O
Solvent: CCO
Product: O=Cc1c(O)cccc1O
Temperature: 25 °C
Reaction time: 0.21 h

Procedure:
Mesoporous carbons with highly ordered structure were prepared using weight ratios of 1.1 resorcinol:1.1 F127:0.48 formaldehyde:3.55-8.2 ethanol:5.1-1.67 water:0.16-0.66 HCl. In a typical synthesis, 1.1 g of resorcinol and 1.1 g of F127 were dissolved in 4.5 ml of ethanol (EtOH), and to this was added 4.5 ml of 3.0M HCl aqueous solution and 1.3 g of 37% formaldehyde (37%) was then added. After stirring for 12-13 min. at room temperature, the clear mixture turned turbid, indicating the formation of the ordered nanocomposite and a phase separation. After stirring for a total of 40 minutes, the mixture was centrifuged at 9500 rpm for 4 minutes in order to completely separate and isolate the polymer-rich gel phase. The gel was then loaded on a large Petri dish and cured at 80° C. and subsequently 150° C. for 24 hours each. Carbonization was carried out under nitrogen atmosphere at 400° C. for 2 hours at a heating rate of 1° C./min followed by further treatment at 850° C. for 3 hours at a heating rate of 5° C./min. The produced carbon material is referred to as C-ORNL-1.
Reaction SMILES: [C:1]([NH2:4])(=[NH:3])[CH3:2].[Cl:5][C:6]1[CH:7]=[C:8]([CH:15]=[CH:16][C:17]=1[Cl:18])[CH:9]=[CH:10][S:11](Cl)(=[O:13])=[O:12]>>[Cl:5][C:6]1[CH:7]=[C:8]([CH:15]=[CH:16][C:17]=1[Cl:18])[CH:9]=[CH:10][S:11]([NH:3][C:1](=[NH:4])[CH3:2])(=[O:13])=[O:12]
Reactant: O=S(=O)(Cl)C=Cc1ccc(Cl)c(Cl)c1
Reactant: CC(=N)N
Product: CC(=N)NS(=O)(=O)C=Cc1ccc(Cl)c(Cl)c1

Procedure:
Reaction of actamidine with 3,4-dichlorostyrylsulfonyl chloride according to the above procedure affords N-[(3,4-DICHLOROSTYRYL)SULFONYL]ACETAMIDINE, m.p. 197.5°-198.5° C. (corr.), crystallized from acetone-isopropanol.
Reaction SMILES: COC1C=CC([C:9]2[S:13][C:12]3[CH:14]=[CH:15][CH:16]=[CH:17][C:11]=3[CH:10]=2)=CC=1.COC1C=C(C=C(OC)C=1OC)C(Cl)=O.[Al+3].[Cl-].[Cl-].[Cl-].O>C(Cl)Cl.CCOC(C)=O>[S:13]1[CH:9]=[CH:10][C:11]2[CH:17]=[CH:16][CH:15]=[CH:14][C:12]1=2
Reactant: COc1ccc(-c2cc3ccccc3s2)cc1
Agent: COc1cc(C(=O)Cl)cc(OC)c1OC
Agent: [Al+3]
Agent: [Cl-]
Solvent: CCOC(C)=O
Solvent: ClCCl
Solvent: O
Product: c1ccc2sccc2c1
Yield: 81.5 %

Procedure:
To a well-stirred solution of 2-(4′-methoxyphenyl)benzo[b]thiophene (0.081 g, 0.32 mmol) and 3,4,5-trimethoxybenzoyl chloride (0.148 g, 0.64 mmol) in CH2Cl2 (15 mL) was added AlCl3 (0.144 g, 1.08 mmol) portion-wise over a 5 minute period. After 3 h 20 min, water was added, and the product was isolated initially by extraction with CH2Cl2 and subsequently by extraction with EtOAc. The organic layers were separately washed with brine and then combined and dried over MgSO4. Purification by flash chromatography (silica gel, 90:10 hexane/EtOAc then with 80:20 hexane/EtOAc) afforded desired benzo[b]thiophene (0.035 g, 26%) as white solid. 1H-NMR-(CDCl3, 360 MHz) δ7.87 (m, 1H, ArH), 7.78 (m, 1H, ArH), 7.37 (m, 4H, ArH), 7.07 (s, 2H, ArH), 6.76 (d, J=6.7, 2H, ArH), 3.84 (s, 3H, —OCH3), 3.75 (s, 3H, —OCH3), 3.73 (S, 6H, —OCH3).
Reaction SMILES: [CH3:1][N:2]([C:12]1[CH:17]=[CH:16][C:15]([C:18](=[O:23])[C:19]([F:22])([F:21])[F:20])=[CH:14][CH:13]=1)[S:3]([C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)(=[O:5])=[O:4].[CH3:24][CH:25]([CH3:29])[CH2:26][C:27]#[CH:28]>>[OH:23][C:18]([C:15]1[CH:16]=[CH:17][C:12]([N:2]([CH3:1])[S:3]([C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][CH:11]=2)(=[O:5])=[O:4])=[CH:13][CH:14]=1)([C:19]([F:21])([F:22])[F:20])[C:28]#[C:27][CH2:26][CH:25]([CH3:29])[CH3:24]
Reactant: CN(c1ccc(C(=O)C(F)(F)F)cc1)S(=O)(=O)c1ccccc1
Reactant: C#CCC(C)C
Product: CC(C)CC#CC(O)(c1ccc(N(C)S(=O)(=O)c2ccccc2)cc1)C(F)(F)F

Procedure:
The compound was prepared from N-methyl-N-(4-trifluoroacetyl-phenyl)-benzenesulfonamide (Example 22, Step A) and 4-methyl-pent-1-yne following the procedure described in Example 29. 1H NMR (CDCl3) δ 1.01 (d, J=6.6 Hz, 6 H), 1.90 (sept, J=6.6 Hz, 1 H), 2.21 (d, J=7.7 Hz, 2 H), 3.17 (s, 3 H), 3.24 (br s, 1 H), 7.12-7.68 (m, 9 H). Mass Spectrum (CI+) m/e=426 (M+1).