Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]([CH2:12][CH2:13][OH:14])[CH2:9][CH2:10][OH:11])=[CH:4][CH:3]=1.[H-].[Na+].CS([C:21]1[N:33]=[C:24]2[N:25]=[C:26]([CH2:31][CH3:32])[CH:27]=[C:28]([CH2:29][CH3:30])[N:23]2[N:22]=1)(=O)=O>O1CCCC1>[CH2:31]([C:26]1[CH:27]=[C:28]([CH2:29][CH3:30])[N:23]2[N:22]=[C:21]([O:11][CH2:10][CH2:9][N:8]([C:5]3[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=3)[CH2:12][CH2:13][OH:14])[N:33]=[C:24]2[N:25]=1)[CH3:32]
Reactant: CCc1cc(CC)n2nc(S(C)(=O)=O)nc2n1
Reactant: OCCN(CCO)c1ccc(F)cc1
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: CCc1cc(CC)n2nc(OCCN(CCO)c3ccc(F)cc3)nc2n1
Temperature: 25 °C
Yield: 43 %

Procedure:
A mixture of 2-[(4-fluorophenyl)(2-hydroxyethyl)amino]ethan-1-ol (200 mg, 1.01 mmol) and tetrahydrofuran (5 mL) was added to a 50 mL RBF under a nitrogen atmosphere with a magnetic stirring bar. The flask was cooled in an ice bath. Sodium hydride (60% dispersion in mineral oil) (40 mg, 1.01 mmol) was added (Effervescence). The reaction was warmed to room temperature and stirred for 10 minutes before 2-methanesulfonyl-5,7-diethyl-[1,2,4]-triazolo[1,5-a]pyrimidine (213 mg, 0.84 mmol) was added (Effervescence). Progress of the reaction was monitored by analytical HPLC with UV detection at 215 nm. The title compound eluted with a retention time of 4.1 min. After 90 minutes the reaction was concentrated then partitioned between dichloromethane (30 mL) and water (5 mL). The aqueous layer was extracted once more with dichloromethane (20 mL). The combined organic layers were dried (Na2SO4), filtered and concentrated. The title crude material was purified by silica gel column chromatography using a gradient elution of 1-10% isopropanol in dichloromethane to afford the title compound as an oil that crystallized upon standing overnight (135 mg, 43% yield). 1H NMR (DMSO-d6, 400 MHz) δ ppm: 7.09 (s, 1H), 6.99 (t, 2H), 6.78 (m, 2H), 4.69 (t, 1H), 4.48 (t, 2H), 3.77 (t, 2H), 3.53 (q, 2H), 3.43 (t, 2H), 3.01 (q, 2H), 2.82 (q, 2H), 1.32 (t, 3H), 1.26 (t, 3H). EM (calc.): 373.2; MS (ESI) m/e: 374.3 (M+H)+.
Reaction SMILES: [CH3:1][C@H:2]1[CH2:6][CH2:5][CH2:4][N:3]1[C:7]1[C:8](=O)[NH:9][C:10]2[C:15]([N:16]=1)=[CH:14][C:13]([C:17]([O:19][CH3:20])=[O:18])=[CH:12][CH:11]=2.C1(C)C=CC=CC=1.S(Cl)([Cl:31])=O>CN(C)C=O>[Cl:31][C:8]1[C:7]([N:3]2[CH2:4][CH2:5][CH2:6][C@@H:2]2[CH3:1])=[N:16][C:15]2[C:10](=[CH:11][CH:12]=[C:13]([C:17]([O:19][CH3:20])=[O:18])[CH:14]=2)[N:9]=1
Reactant: COC(=O)c1ccc2[nH]c(=O)c(N3CCC[C@@H]3C)nc2c1
Reactant: O=S(Cl)Cl
Solvent: Cc1ccccc1
Solvent: CN(C)C=O
Product: COC(=O)c1ccc2nc(Cl)c(N3CCC[C@@H]3C)nc2c1

Procedure:
Into a 100-mL round-bottom flask, was placed a solution of (S)-methyl 3-(2-methylpyrrolidin-1-yl)-2-oxo-1,2-dihydroquinoxaline-6-carboxylate (900 mg, 3.14 mmol, 1.00 equiv), toluene (20 mL), thionyl chloride (11.2 g, 94.12 mmol, 30.00 equiv), N,N-dimethylformamide (4 mL). The resulting solution was heated to reflux for 3 hr in an oil bath. The resulting mixture was concentrated under vacuum. The residue was purified by silica gel column chromatography with ethyl acetate/petroleum ether (1:50). This resulted in 143 mg (13%) of (S)-methyl 2-chloro-3-(2-methylpyrrolidin-1-yl)quinoxaline-6-carboxylate as yellow oil.
Reaction SMILES: [CH:1]1[C:6]([NH2:7])=[CH:5][CH:4]=[C:3]([OH:8])[CH:2]=1.[CH2:9]([N:27]=[C:28]=[O:29])[CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH3:26]>C(C(C)=O)C>[OH:8][C:3]1[CH:4]=[CH:5][C:6]([NH:7][C:28]([NH:27][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH3:26])=[O:29])=[CH:1][CH:2]=1
Reactant: CCCCCCCCCCCCCCCCCCN=C=O
Reactant: Nc1ccc(O)cc1
Solvent: CCC(C)=O
Product: CCCCCCCCCCCCCCCCCCNC(=O)Nc1ccc(O)cc1
Reaction time: 0.5 h
Yield: 95.3 %

Procedure:
Under a nitrogen atmosphere, p-aminophenol (109 g) was suspended in methyl ethyl ketone (2000 ml) and the suspension was heated to 70° C. n-Octadecyl isocyanate (296 g) was added dropwise to the suspension with vigorous stirring over a period of about 30 minutes. In this case, since heat of reaction was generated, n-octadecyl isocyanate was added dropwise at a rate at which the temperature of the reaction mixture was kept at 70°-75° C. After completion of the addition, the temperature of the reaction mixture was raised to 75°-80° C. and the reaction was allowed to proceed for further 30 minutes. After completion of the reaction, the reaction mixture was tooled to room temperature to precipitate a white solid. The solvent was removed by filtration and the residue was dried under reduced pressure to obtain a nearly pure desired product (385 g). Yield 95%; m.p. 144° C.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@H:10]([NH2:13])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:14]([N:21]1[CH2:31][CH2:30][C:24]2[N:25]=[CH:26][N:27]=[C:28](Cl)[C:23]=2[CH2:22]1)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.C([O-])([O-])=O.[K+].[K+]>CN1C(=O)CCC1>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@H:10]([NH:13][C:28]2[C:23]3[CH2:22][N:21]([CH2:14][C:15]4[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=4)[CH2:31][CH2:30][C:24]=3[N:25]=[CH:26][N:27]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)N1CC[C@H](N)C1
Reactant: Clc1ncnc2c1CN(Cc1ccccc1)CC2
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN1CCCC1=O
Product: CC(C)(C)OC(=O)N1CC[C@H](Nc2ncnc3c2CN(Cc2ccccc2)CC3)C1
Temperature: 120 °C
Yield: 97 %

Procedure:
(S)-tert-Butyl-3-aminopyrrolidine-1-carboxylate (50 g, 192.5 mmol) was added to 6-benzyl-4-chloro-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidine (39.440 g, 211.8 mmol) in NMP (200 mL) solution followed by the addition of K2CO3 (39.9 g, 288.8 mmol). The mixture was heated to 120° C. for 20 h. The mixture was allowed to cool, partitioned between water (300 mL) and ethylacetate (500 mL). the bottom aqueous phase was discarded and the upper organic phase was washed with brine (150 mL) and concentrated in vacuo to provide crude (S)-3-(6-benzyl-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-4-ylamino)-pyrrolidine-1-carboxylic acid tert-butyl ester as a pale yellow foam (76.44 g, 97% yield).
Reaction SMILES: [NH2:1][C:2]1[C:7]([O:8][CH2:9][CH2:10][CH2:11][CH2:12][N:13]2[C:17](=[O:18])[CH2:16][S:15][C:14]2=[O:19])=[CH:6][CH:5]=[CH:4][N:3]=1.Cl[CH2:21][CH:22]=O>C(O)C>[N:1]1[CH:21]=[CH:22][N:3]2[CH:4]=[CH:5][CH:6]=[C:7]([O:8][CH2:9][CH2:10][CH2:11][CH2:12][N:13]3[C:17](=[O:18])[CH2:16][S:15][C:14]3=[O:19])[C:2]=12
Reactant: Nc1ncccc1OCCCCN1C(=O)CSC1=O
Reactant: O=CCCl
Solvent: CCO
Product: O=C1CSC(=O)N1CCCCOc1cccn2ccnc12

Procedure:
To a solution of 14.08 g (50 mmol) of 3-[4-(2-aminopyridin-3-yloxy)butyl]thiazolidine-2,4-dione in 150 ml of ethanol, 50 ml of a 40% chloroacetaldehyde solution was added at 60° C., followed by refluxing for 2 hours. After the reaction mixture was cooled, the solvent was distilled off. The residue was dissolved in dichloromethane, washed with saturated aqueous sodium hydrogen carbonate and dried, after which the solvent was distilled off. The residue was purified by column chromatography (eluent: n-hexane/residue=1/4) to yield 10.04 g (65.8%, light yellow crystal) of the desired product.
Reaction SMILES: [CH:1]1([N:6]2[C:15]3[N:14]=[C:13]([NH:16][C:17]4[CH:25]=[CH:24][C:20]([C:21](O)=[O:22])=[CH:19][C:18]=4[Cl:26])[N:12]=[CH:11][C:10]=3[N:9]3[CH:27]=[N:28][N:29]=[C:8]3[C@H:7]2[CH2:30][CH3:31])[CH2:5][CH2:4][CH2:3][CH2:2]1.C(C1NC=CN=1)([C:34]1[NH:35]C=CN=1)=O>CN(C=O)C>[CH:1]1([N:6]2[C:15]3[N:14]=[C:13]([NH:16][C:17]4[CH:25]=[CH:24][C:20]([C:21]([NH:35][CH3:34])=[O:22])=[CH:19][C:18]=4[Cl:26])[N:12]=[CH:11][C:10]=3[N:9]3[CH:27]=[N:28][N:29]=[C:8]3[C@H:7]2[CH2:30][CH3:31])[CH2:2][CH2:3][CH2:4][CH2:5]1
Reactant: CC[C@@H]1c2nncn2-c2cnc(Nc3ccc(C(=O)O)cc3Cl)nc2N1C1CCCC1
Reactant: O=C(c1ncc[nH]1)c1ncc[nH]1
Solvent: CN(C)C=O
Product: CC[C@@H]1c2nncn2-c2cnc(Nc3ccc(C(=O)NC)cc3Cl)nc2N1C1CCCC1
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 54 %

Procedure:
4-((R)-5-cyclopentyl-4-ethyl-4,5-dihydro-[1,2,4]triazolo[4,3-f]pteridin-7-ylamino)-3-chlorobenzoic acid (1-3) (27 mg) was dissolved in DMF (0.4 ml) and treated with carbonyl diimidazole (12 mg, 0.077 mmol) and the mixture stirred at RT for 90 min. The solution was cooled in an ice bath and methylamine gas bubbled in for 2 min. The mixture was stirred at RT for 2 hours, evaporated under reduced pressure and purified by chromatography to give 4-((R)-5-cyclopentyl-4-ethyl-4,5-dihydro-[1,2,4]triazolo[4,3-f]pteridin-7-ylamino)-3-chloro-N-methylbenzamide (15 mg) as a colourless solid.
Reaction SMILES: [Br:1][C:2]1[S:3][CH:4]=[C:5]([CH2:7][C:8]2[CH:13]=[CH:12][C:11]([S:14][C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)=[CH:10][CH:9]=2)[N:6]=1.ClC1C=CC=C(C(OO)=[O:29])C=1>C(Cl)(Cl)Cl>[Br:1][C:2]1[S:3][CH:4]=[C:5]([CH2:7][C:8]2[CH:9]=[CH:10][C:11]([S:14]([C:15]3[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=3)=[O:29])=[CH:12][CH:13]=2)[N:6]=1
Reactant: Brc1nc(Cc2ccc(Sc3ccccc3)cc2)cs1
Reactant: O=C(OO)c1cccc(Cl)c1
Solvent: ClC(Cl)Cl
Product: O=S(c1ccccc1)c1ccc(Cc2csc(Br)n2)cc1

Procedure:
The starting 2-bromo-4-(4-phenylsulfinylbenzyl)thiazole was prepared by mild oxydation of 2-bromo-4-(4-phenylthiobenzyl)thiazole, M.P. 82° C., by the means of meta-chloroperbenzoic acid in chloroform.
Reaction SMILES: [OH:1][C:2]1[C:3]([CH3:19])=[C:4]2[C:9](=[C:10]([CH3:13])[C:11]=1[CH3:12])[O:8][C:7]([CH2:15][C:16]([OH:18])=[O:17])([CH3:14])[CH2:6][CH2:5]2.N1C=CC=CC=1.[C:26](OC(=O)C)(=[O:28])[CH3:27]>O1CCCC1>[C:26]([O:1][C:2]1[C:3]([CH3:19])=[C:4]2[C:9](=[C:10]([CH3:13])[C:11]=1[CH3:12])[O:8][C:7]([CH2:15][C:16]([OH:18])=[O:17])([CH3:14])[CH2:6][CH2:5]2)(=[O:28])[CH3:27]
Reactant: Cc1c(C)c2c(c(C)c1O)CCC(C)(CC(=O)O)O2
Reactant: CC(=O)OC(C)=O
Solvent: C1CCOC1
Solvent: c1ccncc1
Product: CC(=O)Oc1c(C)c(C)c2c(c1C)CCC(C)(CC(=O)O)O2
Temperature: 25 °C
Reaction time: 4 h

Procedure:
A mixture of 66.1 g. (0.25 mol.) of (±)-(6-hydroxy-2,5, 7,8-tetramethylchroman-2-yl) acetic acid and 250 ml. each of pyridine and acetic anhydride was stirred at 25° C. under N 2 for 20 hours and stripped of solvent at 40° C. to give an orangebrown oil. To a suspension of this material in 500 ml. of H 2 O and 100 ml. of tetrahydrofuran was added 166 g. (2.0 mol.) of NaHCO 3. the suspension was stirred at 25° C. for 4.0 hours, washed with ether, acidified with 2N-aqueous HCl and extracted with ether. The ether solutions were washed with saturated brine, dried over sodium sulfate and stripped of solvent to give (±)-(6-acetoxy-2,5,7,8-tetramethylchroman-2-yl) acetic acid as and orangeish resin. Crystallization from diethyl ether petroleum ether (b.p. 30°-60° C.) gave (±)-(6-acetoxy-2,5,7,8 -tetramethylchroman-2-yl) acetic acid as a granular white solid.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:12][C:11]([NH2:13])=[N:10][N:9]=2)=[CH:4][CH:3]=1.[NH2:14][S:15]([C:18]1[CH:19]=[CH:20][C:21]([Cl:27])=[C:22]([CH:26]=1)[C:23](O)=[O:24])(=[O:17])=[O:16].C(Cl)CCl.C1C=NC2N(O)N=NC=2C=1>C(Cl)Cl>[NH2:14][S:15]([C:18]1[CH:19]=[CH:20][C:21]([Cl:27])=[C:22]([CH:26]=1)[C:23]([NH:13][C:11]1[S:12][C:8]([C:5]2[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=2)=[N:9][N:10]=1)=[O:24])(=[O:17])=[O:16]
Reactant: NS(=O)(=O)c1ccc(Cl)c(C(=O)O)c1
Reactant: Nc1nnc(-c2ccc(F)cc2)s1
Agent: On1nnc2cccnc21
Solvent: ClCCl
Solvent: ClCCCl
Product: NS(=O)(=O)c1ccc(Cl)c(C(=O)Nc2nnc(-c3ccc(F)cc3)s2)c1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a 20 ml scintillation vial containing a Teflon covered magnetic stir-bar was added commercially available 5-(4-fluorophenyl)-1,3,4-thiadiazol-2-amine (25 mg, 0.128 mmol) and 5-(aminosulfonyl)-2-chlorobenzoic acid (22.3 mg, 0.128 mmol). To this mixture was added EDC (25 mg, 0.128 mmol) and HOAt (18 mg, 0.128 mmol) followed by 3 ml of DCM. The resulting mixture was stirred at room temperature overnight. The product precipitated and was collected by vacuum filtration, washed with 3 ml of MeOH and air-dried under vacuum. Yield of 5-(aminosulfonyl)-2-chloro-N-[5-(4-fluorophenyl)-1,3,4-thiadiazol-2-yl]benzamide was (7 mg) as a white powder.
Reaction SMILES: [Br:1][C:2]1[C:7]2[N:8]=[C:9]([NH:11][C:12](=[O:15])[O:13][CH3:14])[S:10][C:6]=2[CH:5]=[C:4]([O:16][C:17]2[CH:22]=[CH:21][C:20]([N+:23]([O-])=O)=[CH:19][CH:18]=2)[CH:3]=1>CC(O)=O.[Zn]>[Br:1][C:2]1[C:7]2[N:8]=[C:9]([NH:11][C:12](=[O:15])[O:13][CH3:14])[S:10][C:6]=2[CH:5]=[C:4]([O:16][C:17]2[CH:22]=[CH:21][C:20]([NH2:23])=[CH:19][CH:18]=2)[CH:3]=1
Reactant: COC(=O)Nc1nc2c(Br)cc(Oc3ccc([N+](=O)[O-])cc3)cc2s1
Agent: [Zn]
Solvent: CC(=O)O
Product: COC(=O)Nc1nc2c(Br)cc(Oc3ccc(N)cc3)cc2s1
Temperature: 25 °C
Reaction time: 2 h
Yield: 67 %

Procedure:
To a solution of methyl (4-bromo-6-(4-nitrophenoxy)benzthiazole-2-yl)carbamate (Intermediate 10F-65.3 mg, 0.15 mmol) in AcOH (2 mL) was added Zn powder (300 mg) and stirred at room temperature for 2 hrs. The insoluble materials were removed by filtration. The solvent was removed by evaporation. The residue was charged on SCX column chromatography then washed with MeOH then eluted with NH3—MeOH to give the title compound (39.6 mg, 65%): MS m/e 394, 396 (M+1).
Reaction SMILES: Cl[C:2](Cl)([O:4]C(=O)OC(Cl)(Cl)Cl)Cl.[Cl:13][C:14]1[S:18][C:17]([CH2:19][NH2:20])=[CH:16][CH:15]=1.CCN(C(C)C)C(C)C>C(Cl)Cl>[Cl:13][C:14]1[S:18][C:17]([CH2:19][N:20]=[C:2]=[O:4])=[CH:16][CH:15]=1
Reactant: NCc1ccc(Cl)s1
Reactant: O=C(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: O=C=NCc1ccc(Cl)s1
Temperature: 25 °C

Procedure:
To a solution of triphosgene (1.15 g, 3.9 mmol) in CH2Cl2 (30 mL) was added dropwise a mixture of (5-chlorothiophen-2-yl)methanamine (1.14 g, 7.8 mmol) and DIPEA (2.0 g, 15.6 mmol) in CH2Cl2 (32 mL) over 2 hours at 0 C under N2 atmosphere. After addition was complete, the mixture was refluxed for 1 hour and then cooled to ambient temperature. The mixture was washed with aq. KHSO4, brine, dried over Na2SO4, and concentrated to give 5-chlorothiophen-2-yl-methyl isocynate a yellow liquid (1.34 g, yield 100%), which was used in the next step without further purification.
Reaction SMILES: C1C2C(CO[C:16]([NH:18][C@H:19]([C:26]([NH:28][CH2:29][CH2:30][C:31]3[CH:38]=[CH:37][C:35]([OH:36])=[C:33]([OH:34])[CH:32]=3)=[O:27])[CH2:20][O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:17])C3C(=CC=CC=3)C=2C=CC=1.[OH:39][C:40]1[C:49]2[C:44](=[C:45]([OH:50])[CH:46]=[CH:47][CH:48]=2)[N:43]=[C:42](C(O)=O)[CH:41]=1>>[OH:39][C:40]1[C:49]2[C:44](=[C:45]([OH:50])[CH:46]=[CH:47][CH:48]=2)[N:43]=[C:42]([C:16]([NH:18][C@H:19]([C:26]([NH:28][CH2:29][CH2:30][C:31]2[CH:38]=[CH:37][C:35]([OH:36])=[C:33]([OH:34])[CH:32]=2)=[O:27])[CH2:20][O:21][C:22]([CH3:23])([CH3:24])[CH3:25])=[O:17])[CH:41]=1
Reactant: O=C(O)c1cc(O)c2cccc(O)c2n1
Reactant: CC(C)(C)OC[C@H](NC(=O)OCC1c2ccccc2-c2ccccc21)C(=O)NCCc1ccc(O)c(O)c1
Product: CC(C)(C)OC[C@H](NC(=O)c1cc(O)c2cccc(O)c2n1)C(=O)NCCc1ccc(O)c(O)c1

Procedure:
The title compound was prepared from N-[Nα-(9-fluorenylmethoxycarbonyl)-O-tert-butyl-L-seryl]dopamine (676 mg, 1.3 mmol, example 42, step A) as described for example 42 (step B) using 4,8-dihydroxyquinoline-2-carboxylic acid (402 mg, 1.96 mmol) instead of caffeic acid. The crude material was purified by flash chromatography using successively 30%, 40% and 70% EtOAc/CH2Cl2/1% AcOH as the eluent. The title compound was obtained as a yellow powder (130 mg, 21%).
Reaction SMILES: [C:1]1(S([O-])(=O)=O)[C:10]2[C:5](=[CH:6][CH:7]=CC=2)[CH:4]=[CH:3][CH:2]=1.[Na+].C=O.P([O-])([O-])([O-])=O.[K+].[K+].[K+].[CH3:26][CH:27]([C:29]1CC[C@H]2C(=CC[C@H]3[C@@](C(O)=O)(C)CCC[C@@]32C)[CH:30]=1)C.[OH-].[K+].S([O-])[O-].C=O.[Na+].[Na+].C=CC1C=CC=CC=1.[N:65]1([CH2:70][CH2:71][CH:72]=[CH:73][C:74]2[CH:79]=[CH:78][CH:77]=[CH:76][CH:75]=2)[CH2:69][CH2:68][CH2:67][CH2:66]1.CC(C(C(C(S)(C)C)(C)C)(C)C)C>O>[CH2:7]=[CH:6][C:5]1[CH:10]=[CH:1][CH:2]=[CH:3][CH:4]=1.[CH2:26]=[CH:27][CH:29]=[CH2:30].[N:65]1([CH2:70][CH2:71][CH:72]=[CH:73][C:74]2[CH:75]=[CH:76][CH:77]=[CH:78][CH:79]=2)[CH2:69][CH2:68][CH2:67][CH2:66]1
Reactant: CC(C)C1=CC2=CC[C@@H]3[C@](C)(CCC[C@@]3(C)C(=O)O)[C@H]2CC1
Reactant: O=S(=O)([O-])c1cccc2ccccc12
Agent: C(=Cc1ccccc1)CCN1CCCC1
Agent: C=O
Agent: CC(C)C(C)(C)C(C)(C)C(C)(C)S
Solvent: C=Cc1ccccc1
Solvent: O
Product: C=CC=C

Procedure:
In this experiment, an emulsion a styrene/butadiene/pyrrolidinoethyl styrene (PES) terpolymer was prepared. In the procedure used, 7.29 lbs. of soft water, 4.76 grams of sodium naphthalenesulfonate-formaldehyde dispersant (Daxad 14B from Hampshire Chemical Co., 47.5% active), 7.2 gms. of tripotassium phosphate, 140 grams of disproportionated rosin acid (potassium salt, 20% solution in water at pH 9.5), and 532 grams of C14-18 and C16-18 unsaturated fatty acids (potassium salt, 10% solution in water at pH 9.5) were charged into a 2-gallon stainless steel reactor. Prior to charging to the reactor, the pH of the solution was adjusted to 10.2-10.8 by the addition of a 10% aqueous potassium hydroxide solution. Then, 100 grams of soft water, 0.32 grams of ethylenediaminetetraacetic acid/ferric sodium complex (Akzo Nobel Chemicals Co.) and 1.08 grams of sodium formaldehyde sulfoxylate were added. Then, 580 grams of styrene, 22.5 grams of PES (92% purity), and 4.5 grams of tert-dodecylmercaptan were added.
Reaction SMILES: [CH3:1][N:2]([CH3:26])[CH2:3][CH2:4][O:5][C:6]1[CH:11]=[C:10]([S:12]([CH3:15])(=[O:14])=[O:13])[CH:9]=[CH:8][C:7]=1[N:16]1[C:20]2=[N:21][CH:22]=[N:23][C:24](O)=[C:19]2[CH:18]=[N:17]1.O=P(Cl)(Cl)[Cl:29].CN(C)C1C=CC=CC=1>>[Cl:29][C:24]1[N:23]=[CH:22][N:21]=[C:20]2[N:16]([C:7]3[CH:8]=[CH:9][C:10]([S:12]([CH3:15])(=[O:14])=[O:13])=[CH:11][C:6]=3[O:5][CH2:4][CH2:3][N:2]([CH3:26])[CH3:1])[N:17]=[CH:18][C:19]=12
Reactant: O=P(Cl)(Cl)Cl
Reactant: CN(C)CCOc1cc(S(C)(=O)=O)ccc1-n1ncc2c(O)ncnc21
Solvent: CN(C)c1ccccc1
Product: CN(C)CCOc1cc(S(C)(=O)=O)ccc1-n1ncc2c(Cl)ncnc21
Temperature: 100 °C
Reaction time: 1 h

Procedure:
In a reaction vial was placed a stir bar, 1-[2-(2-dimethylamino-ethoxy)-4-methanesulfonyl-phenyl]-1H-pyrazolo[3,4-d]pyrimidin-4-ol (50 mg), POCl3 (0.5 mL) and N,N-dimethylaniline (15 μl). The reaction mixture was stirred at 100° C. for 1 hour. Upon cooling the reaction mixture to the room temperature, a white precipitate formed. The mixture was left sealed over the weekend at room temperature. After concentrated under the vacuum, the residue was washed with Et2O and filtered to give {2-[2-(4-chloro-pyrazolo[3,4-d]pyrimidin-1-yl)-5-methanesulfonyl-phenoxy]-ethyl}-dimethyl-amine as a white solid. Exact mass calculated for C16H18ClN5O3S 395.08, found 396 (MH+).
Reaction SMILES: [CH3:1][C:2]([O:4][CH2:5][C:6]1[CH2:23][S:22][C@@H:9]2[C@H:10]([NH:13][C:14]([CH2:16][C:17]3[S:21][CH:20]=[CH:19][CH:18]=3)=[O:15])[C:11](=[O:12])[N:8]2[C:7]=1[C:24]([O-:26])=[O:25])=[O:3].[Na+].C[Si](C)(C)Cl.[SiH3]NC(=O)C(F)(F)F.[S:41]1[CH:45]=[CH:44][CH:43]=[C:42]1CC(Cl)=O>C(Cl)(Cl)Cl>[S:21]1[CH:20]=[CH:19][CH:18]=[C:17]1[CH:16]([C:42]1[S:41][CH:45]=[CH:44][CH:43]=1)[C:14]([NH:13][CH:10]1[C:11](=[O:12])[N:8]2[C:7]([C:24]([OH:26])=[O:25])=[C:6]([CH2:5][O:4][C:2](=[O:3])[CH3:1])[CH2:23][S:22][C@H:9]12)=[O:15]
Reactant: CC(=O)OCC1=C(C(=O)[O-])N2C(=O)[C@@H](NC(=O)Cc3cccs3)[C@H]2SC1
Reactant: O=C(Cl)Cc1cccs1
Agent: C[Si](C)(C)Cl
Agent: O=C(N[SiH3])C(F)(F)F
Agent: [Na+]
Solvent: ClC(Cl)Cl
Product: CC(=O)OCC1=C(C(=O)O)N2C(=O)C(NC(=O)C(c3cccs3)c3cccs3)[C@H]2SC1
Temperature: 45 °C
Reaction time: 0.5 h

Procedure:
A suspension of sodium cephalothin (1.18 g.) in anhydrous alcohol-free chloroform (10 ml.) is silylated by the addition of trimethylchlorosilane (1.1 ml.). After stirring for 30 minutes, monosilyltrifluoroacetamide (2.5 ml.) and 2-thienylacetyl chloride (2.0 ml.) are added to the suspension which is then heated to 45° C. The mixture is allowed to remain at this temperature for two days and then evaporated in vacuo to a residue which is dissolved in ethyl acetate (50 ml.) and washed three times with water. The ethyl acetate layer is dried over magnesium sulfate, filtered and the filtrate evaporated in vacuo to obtain a residue. The residue is dissolved in chloroform and precipitated with hexane three times, each time discarding the supernatent liquid. The 7-(di-2-thienylacetyl)amino-3-acetoxymethyl-3-cephem-4-carboxylic acid is obtained in a solvent-free form by freeze-drying from a solution in benzene.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([C:8]2[N:9]=[C:10]3[CH:15]=[C:14]([C:16]4[N:25]=[C:19]5[C:20]([CH3:24])=[N:21][CH:22]=[CH:23][N:18]5[N:17]=4)[CH:13]=[CH:12][N:11]3[CH:26]=2)[CH:5]=[CH:6][CH:7]=1.[CH:27]1(B(O)O)[CH2:29][CH2:28]1.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].[Br-]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O.C1(C)C=CC=CC=1>[CH:27]1([C:2]2[CH:3]=[C:4]([C:8]3[N:9]=[C:10]4[CH:15]=[C:14]([C:16]5[N:25]=[C:19]6[C:20]([CH3:24])=[N:21][CH:22]=[CH:23][N:18]6[N:17]=5)[CH:13]=[CH:12][N:11]4[CH:26]=3)[CH:5]=[CH:6][CH:7]=2)[CH2:29][CH2:28]1
Reactant: OB(O)C1CC1
Reactant: Cc1nccn2nc(-c3ccn4cc(-c5cccc(Br)c5)nc4c3)nc12
Agent: [Pd+2]
Agent: C1CCC(P(C2CCCCC2)C2CCCCC2)CC1
Agent: CC(=O)[O-]
Solvent: Cc1ccccc1
Solvent: O
Product: Cc1nccn2nc(-c3ccn4cc(-c5cccc(C6CC6)c5)nc4c3)nc12
Temperature: 110 °C
Yield: 75.6 %

Procedure:
To a microwave vial was added 2-(2-(3-bromophenyl)imidazo[1,2-a]pyridin-7-yl)-8-methyl-[1,2,4]triazolo[1,5-a]pyrazine (35 mg, 0.086 mmol), cyclopropylboronic acid (22.26 mg, 0.259 mmol), TRICYCLOHEXYLPHOSPHINE (12.11 mg, 0.043 mmol), Toluene (1 mL), Water (0.3 mL) and Potassium phosphate tribasic (73.3 mg, 0.345 mmol). The solution was purged with nitrogen for 5 min and then PALLADIUM(II) ACETATE (1.939 mg, 8.64 μmol) was added. The reaction vial was sealed and heated to 110° C. for 2 hours. The reaction turned black and was then checked by LC/MS. The reaction was complete as indicated by no starting bromide being present. The reaction was cooled to rt and extracted with EtOAc 4×. The organic fractions were combined, dried over Na2SO4 and evaporated in vacuo. The crude oil was purified by silica gel chromatography eluting with 1% MeOH/99% CH2Cl2. The pure fractions were combined and evaporated in vacuo affording 2-(2-(3-cyclopropylphenyl)imidazo[1,2-a]pyridin-7-yl)-8-methyl-[1,2,4]triazolo[1,5-a]pyrazine (24 mg, 0.065 mmol, 75% yield) as an off white solid. 1H NMR (400 MHz, CHLOROFORM-d) δ 8.67 (br. s., 1H), 8.43 (d, J=4.5 Hz, 1H), 8.25 (d, J=5.3 Hz, 1H), 8.06 (d, J=4.5 Hz, 1H), 7.95 (s, 1H), 7.82-7.68 (m, 3H), 7.35 (t, J=7.7 Hz, 1H), 7.08 (d, J=7.5 Hz, 1H), 3.01 (s, 3H), 2.08-1.97 (m, 1H), 1.09-0.96 (m, 2H), 0.90-0.75 (m, 2H), LC/Mass spec. (Method 1) RT=2.20 min. Mass=367.2 (MH)+.
Reaction SMILES: [Cl:1][GeH:2]([Cl:4])[Cl:3].[C:5]([OH:9])(=[O:8])[CH:6]=[CH2:7]>CCOCC>[Cl:1][Ge:2]([Cl:4])([Cl:3])[CH2:7][CH2:6][C:5]([OH:9])=[O:8]
Reactant: C=CC(=O)O
Reactant: Cl[GeH](Cl)Cl
Solvent: CCOCC
Product: O=C(O)CC[Ge](Cl)(Cl)Cl
Reaction time: 2 h
Yield: 89.3 %

Procedure:
To a magnetically stirred solution of 18 g (0.1 mole) of trichlorogermane in 30 ml of anhydrous ether was added dropwise with a solution of 7.2g (0.1 mole) of acrylic acid in 20 ml of ether at -30°. Then, the mixture was allowed to stand at room temperature for 2 hrs. Evaporation of the solvent left a solid, which was recrystallized from n-hexane to give 22.5 g (89.3% yield) of white needles, mp 84°~85°. Lit. (V. F. Mironov, E. M. Berliner, and T. K. Gar, Zh. Obshch, Khim., 37, 962 (1967) reports mp 83°~85° for this compound.