Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][C@@H:2]([C:4]([OH:6])=[O:5])[CH3:3].[OH-].[Na+].[CH2:9]([O:16][C:17](Cl)=[O:18])[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1>>[CH2:9]([O:16][C:17]([NH:1][C@@H:2]([C:4]([OH:6])=[O:5])[CH3:3])=[O:18])[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1
Reactant: O=C(Cl)OCc1ccccc1
Reactant: C[C@@H](N)C(=O)O
Agent: [Na+]
Agent: [OH-]
Product: C[C@@H](NC(=O)OCc1ccccc1)C(=O)O
Temperature: 4 °C
Reaction time: 1 h

Procedure:
To a solution of 12.5 g. of D-alanine in 70 ml. of 2N sodium hydroxide, with ice cooling and stirring, is added in simultaneous dropwise addition 24 g. of benzyloxycarbonyl chloride and 35 ml. of 4N sodium hydroxide. The pH is maintained at 10 to 12 using a pH electrode in the reaction vessel. The reaction is stirred for one hour further at 4° C. and then extracted with 100 ml. of ethyl ether and acidified to pH 3 with concentrated hydrochloric acid. The product precipitates and is separated by filtration and dried in air; 23.5 g., m.p. 82°-85° C.; [α]D25 30 14.8° (c 1, 1N acetic acid). A second cup can be obtained from the filtrate by concentration and cooling.
Reaction SMILES: [CH3:1][N:2]([CH2:12][CH2:13][O:14][C:15]1[CH:28]=[CH:27][C:18]([CH:19]=[C:20]2[S:24][C:23](=[O:25])[NH:22][C:21]2=[O:26])=[CH:17][CH:16]=1)[C:3]1[O:4][C:5]2[CH:11]=[CH:10][CH:9]=[CH:8][C:6]=2[N:7]=1.[H][H]>O1CCOCC1.[Pd]>[OH2:4].[CH3:1][N:2]([CH2:12][CH2:13][O:14][C:15]1[CH:16]=[CH:17][C:18]([CH2:19][CH:20]2[S:24][C:23](=[O:25])[NH:22][C:21]2=[O:26])=[CH:27][CH:28]=1)[C:3]1[O:4][C:5]2[CH:11]=[CH:10][CH:9]=[CH:8][C:6]=2[N:7]=1.[CH3:1][N:2]([CH2:12][CH2:13][O:14][C:15]1[CH:16]=[CH:17][C:18]([CH2:19][CH:20]2[S:24][C:23](=[O:25])[NH:22][C:21]2=[O:26])=[CH:27][CH:28]=1)[C:3]1[O:4][C:5]2[CH:11]=[CH:10][CH:9]=[CH:8][C:6]=2[N:7]=1
Reactant: [H][H]
Reactant: CN(CCOc1ccc(C=C2SC(=O)NC2=O)cc1)c1nc2ccccc2o1
Agent: [Pd]
Solvent: C1COCCO1
Product: CN(CCOc1ccc(CC2SC(=O)NC2=O)cc1)c1nc2ccccc2o1
Product: O

Procedure:
5-(4-[2-(N-Methyl-N-(2-benzoxazolyl)amino)ethoxy]benzylidene)-2,4-thiazolidinedione (1.5 g) in dry 1,4-dioxan (80 ml) was reduced under hydrogen in the presence of 10% palladium on charcoal (2 g) at ambient temperature and atmospheric pressure until hydrogen uptake ceased. The solution was filtered through diatomaceous earth, the filter pad was washed exhaustively with dioxan and the combined filtrates were evaporated to dryness under vacuum. The title compound (mp 147°-9° C.) was obtained after crystallisation from methanol.
Reaction SMILES: [N:1]1([CH2:6][CH2:7][CH2:8][CH2:9][C:10]([OH:12])=O)[CH:5]=[N:4][N:3]=[N:2]1.S(Cl)([Cl:15])=O>C1C=CC=CC=1.CN(C=O)C>[N:1]1([CH2:6][CH2:7][CH2:8][CH2:9][C:10]([Cl:15])=[O:12])[CH:5]=[N:4][N:3]=[N:2]1
Reactant: O=S(Cl)Cl
Reactant: O=C(O)CCCCn1cnnn1
Solvent: c1ccccc1
Solvent: CN(C)C=O
Product: O=C(Cl)CCCCn1cnnn1

Procedure:
1 g of 5-(tetrazol-1-yl)-valeric acid is heated for 20 minutes at reflux temperature in 12 ml of absolute benzene with 0.6 ml of thionyl chloride and 2 drops of DMF. After concentration by evaporation under reduced pressure, the title compound is obtained.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[NH:7][C:8](=[S:10])[S-:9].C([NH+](CC)CC)C.[CH2:18]=[CH:19][C:20](=[O:23])[CH2:21][CH3:22]>C(#N)C.C(Cl)(Cl)Cl.C(OCC)(=O)C>[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[NH:7][C:8](=[S:9])[S:10][CH2:18][CH2:19][C:20](=[O:23])[CH2:21][CH3:22]
Reactant: S=C([S-])Nc1ccccn1
Reactant: C=CC(=O)CC
Agent: CC[NH+](CC)CC
Solvent: ClC(Cl)Cl
Solvent: CCOC(C)=O
Solvent: CC#N
Product: CCC(=O)CCSC(=S)Nc1ccccn1
Reaction time: 3 h
Yield: 31.6 %

Procedure:
The procedure of Example 2 is followed but triethylammonium pyrid-2-yldithiocarbamate (54.0 g) and pent-1-en-3-one (17.0 g) in anhydrous acetonitrile (400 cc) are used as the starting materials at a maximum temperature of 5° C. The reaction is allowed to proceed for 3 hours at between 5° and 20° C. The crude product (45.0 g) is dissolved in a mixture of chloroform (200 cc) and ethyl acetate (50 cc). The solution is chromatographed on a column of diameter 6 cm, containing silica (0.063-0.2 mm; 600 g). Elution is carried out with a mixture of chloroform (400 cc) and ethyl acetate (100 cc), this eluate being discarded, and then with a mixture of chloroform (2,800 cc) and ethyl acetate (700 cc), this eluate being collected and evaporated to dryness under reduced pressure (20 mmHg) at 45° C. The product obtained (30.0 g) is purified by recrystallisation from a mixture of acetonitrile (30 cc) and diisopropyl ether (60 cc). 3-Oxopentyl pyrid-2-yldithiocarbamate (16.0 g) (structure determined by IR spectroscopy in petroleum jelly), which melts at 80° C., is obtained.
Reaction SMILES: [F:1][C:2]([F:12])([F:11])[C:3]1[CH:8]=[CH:7][C:6]([CH2:9][NH2:10])=[CH:5][CH:4]=1.[O:13]=[C:14]1[C:18]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH2:17][CH2:16][N:15]1[CH2:31][C:32](O)=[O:33].Cl.C(N=C=NCCCN(C)C)C>ClCCl>[O:13]=[C:14]1[C:18]([C:25]2[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=2)([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH2:17][CH2:16][N:15]1[CH2:31][C:32]([NH:10][CH2:9][C:6]1[CH:5]=[CH:4][C:3]([C:2]([F:11])([F:12])[F:1])=[CH:8][CH:7]=1)=[O:33]
Reactant: O=C(O)CN1CCC(c2ccccc2)(c2ccccc2)C1=O
Reactant: NCc1ccc(C(F)(F)F)cc1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Solvent: ClCCl
Product: O=C(CN1CCC(c2ccccc2)(c2ccccc2)C1=O)NCc1ccc(C(F)(F)F)cc1
Reaction time: 8 h

Procedure:
A solution of (4-(trifluoromethyl)phenyl)methanamine (0.033 g, 0.186 mmol), 2-(2-oxo-3,3-diphenylpyrrolidin-1-yl)acetic acid (Example 1C, 0.050 g, 0.169 mmol) and N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine hydrochloride (0.049 g, 0.254 mmol) in dichloromethane (0.5 mL) was stirred at room temperature. After stirring overnight, the reaction was loaded directly onto a SF15-12 column (Analogix®, Burlington, Wis.), and the title compound was eluted using a gradient of 5% to 100% ethyl acetate/hexanes over 20 minutes (flow=30 mL/minute). 1H NMR (300 MHz, CDCl3) δ ppm 7.50-7.54 (m, 2H), 7.17-7.33 (m, 12H), 6.39 (t, J=6.1 Hz, 1H), 4.34 (d, J=6.1 Hz, 2H), 4.07 (s, 2H), 3.51 (t, J=6.5 Hz, 2H), 2.81 (t, J=6.5 Hz, 2H); MS (ESI−) m/z 451 (M−H)−.
Reaction SMILES: [NH2:1][C:2]1[N:7]=[CH:6][C:5]2[CH2:8][NH:9][CH2:10][C:4]=2[C:3]=1[C:11]#[N:12].[NH3:13].[CH3:14]O>>[NH2:1][C:2]1[N:7]=[CH:6][C:5]2[CH2:8][NH:9][CH2:10][C:4]=2[C:3]=1[C:11]#[N:12].[CH3:14][N:7]([CH3:6])[C:2]([NH2:13])=[NH:1]
Reactant: CO
Reactant: N
Agent: N#Cc1c(N)ncc2c1CNC2
Product: CN(C)C(=N)N

Procedure:
Two 6,7-dihydropyrrolo[3,4-c]pyrido[2,3-d]pyrimidines which contain a novel tricyclic ring system of potential bilogical interest were sythesized. 6-(2,5-Dimethoxphenyl)-6,7-dihydropyrrolo[3,4-c]pyrido[2,3-d]pyrido[2,3-d]pyridmidine-2,4(1H,3H)-dione (3a) [throughout the Experimental Detail section, numbers in parenthesis () refer to numbered compounds in FIGS. 1 to 4] was prepared from a pyrido[2,3-d]pyrimidine. 6-Acetoxymethyl-5-methylpyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (4) was oxidized with SeO3 to the corresponding 5-formyl derivative (5) which was condensed with 2,5-dimethoxyaniline to form the Schiff base. Reduction of the exocyclic azomethine double bond of the Schiff base with NaBH3CN to (6) followed by thermal cyclization afforded (3a). 2,4-Diamino-6-(4-methoxyphenyl)-6,7-dihydropyrrolo[3,4-c]pyrido[2,3-d]pyrimidine (3b) was synthesized by addition of a pyrimidine ring to the dihydropyrrolo[3,4-c]pyridine system. 1-(4-Methoxphenyl)pyrrolidine- 3-one (18) was condensed with malononitrile to give a Knoevenagel adduct (19). Treatment of (19) with N,N-dimethylaminomethylene chloride in the presence of LDA afforded the 4-N,N-dimethylaminomethylenepyrrolidine derivative (20) which was converted into 6-amino-7-cyano-2,3-dihydropyrrolo[3,4-c]pyridine (21) by treatment with NH3 /MeOH. Cyclization of (21) with N,N-dimethyl-guanidine afforded the desired product (3b) in high yield.
Reaction SMILES: [CH:1]1([CH2:7][C@H:8]([CH2:12][C:13]([N:15]2[CH2:20][CH2:19][O:18][CH2:17][CH2:16]2)=[O:14])[C:9]([OH:11])=O)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C(Cl)CCl.O[N:26]1[C:30]2C=CC=CC=2N=N1.[NH2:35][C:36]1(C#N)[CH2:41][CH2:40][N:39]([CH3:42])[CH2:38][CH2:37]1>CN(C=O)C>[C:30]([CH:38]1[CH2:37][CH:36]([NH:35][C:9](=[O:11])[CH:8]([CH2:7][CH:1]2[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]2)[CH2:12][C:13]([N:15]2[CH2:20][CH2:19][O:18][CH2:17][CH2:16]2)=[O:14])[CH2:41][CH2:40][N:39]1[CH3:42])#[N:26]
Reactant: CN1CCC(N)(C#N)CC1
Reactant: On1nnc2ccccc21
Reactant: O=C(O)[C@@H](CC(=O)N1CCOCC1)CC1CCCCC1
Solvent: ClCCCl
Solvent: CN(C)C=O
Product: CN1CCC(NC(=O)C(CC(=O)N2CCOCC2)CC2CCCCC2)CC1C#N
Temperature: 0 °C
Reaction time: 0.42 h

Procedure:
(R)-2-Cyclohexylmethyl-4-morpholin-4-yl-4-oxo-butyric acid (0.20 g, 0.71 mmol) (see Example 1-part a and b) was dissolved in 5 mL of DMF and cooled to 0° C. by an ice-water bath. EDC (0.18 g, 0.92 mmol) and 1-hydroxybenzotriazole (0.12 g, 0.92 mmol) were added and stirring, under argon, continued for 25 min. Then 4-amino-4-cyano-1-methylpiperidine (0.098 g, of the mixture of aminonitrile:cyanohydrin:ketone) was dissolved in 1 mL of DMF and added to the solution of the active ester. The resulting mixture was stirred at ambient temperature for 4 h. The volatiles were removed in vacuo and the resulting residue was dissolved in 100 mL of EtOAc and washed sequentially with 2×100 mL of saturated sodium bicarbonate and 1×100 mL of brine. The organic layer was dried over MgSO4, filtered, and concentrated to a thick oil. The oil was purified by column chromatography on SiO2 using as eluent 5% MeOH in CH2Cl2 to give the title compound as a clear oil (0.005 g): 1H NMR (CDCl3) 6.64 (1H, m), 3.73-3.37 (8H, m), 2.95-2.85 (1H, m), 2.75-2.55 (2H, m), 2.5-2.37 (2H, m), 2.34-2.25 (3H, m), 1.98-1.82 (2H, m), 1.80-1.58 (6H, m), 1.32-1.10 (8H, m), 0.95-0.78 (3H,m). MS: m/z=405 M+1.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C:9]2([CH2:23][O:24]C3C=CC(OC)=CC=3)[CH2:15][N:14]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:13][CH2:12][CH2:11][O:10]2)[CH:5]=[CH:6][C:7]=1[Cl:8]>C(#N)C.O>[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2([CH2:23][OH:24])[CH2:15][N:14]([C:16]([O:18][C:19]([CH3:20])([CH3:21])[CH3:22])=[O:17])[CH2:13][CH2:12][CH2:11][O:10]2)[CH:5]=[CH:6][C:7]=1[Cl:8]
Reactant: COc1ccc(OCC2(c3ccc(Cl)c(Cl)c3)CN(C(=O)OC(C)(C)C)CCCO2)cc1
Solvent: CC#N
Solvent: O
Product: CC(C)(C)OC(=O)N1CCCOC(CO)(c2ccc(Cl)c(Cl)c2)C1
Temperature: 0 °C
Reaction time: 1 h
Yield: 76.6 %

Procedure:
To a solution of tert-butyl (2RS)-2-(3,4-dichlorophenyl)-2-[(4-methoxyphenoxy)methyl]-1,4-oxazepane-4-carboxylate (3.18 g) in acetonitrile (80 ml) and water (20 mL) was added ceric ammonium nitrate (10.8 g) at 0° C., and the mixture was stirred at 0° C. for 1 hr. The reaction mixture was diluted with water, and the mixture was extracted with ethyl acetate. The obtained extract was washed with brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (NH, ethyl acetate/hexane) to give the title compound (1.9 g).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[O:11][C:10]3=[CH:12][S:13][CH:14]=[C:9]3[C:8](=O)[NH:7][C:6]=2[CH:16]=1.P(Cl)(Cl)(Cl)(Cl)[Cl:18]>C1(C)C=CC=CC=1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[O:11][C:10]3=[CH:12][S:13][CH:14]=[C:9]3[C:8]([Cl:18])=[N:7][C:6]=2[CH:16]=1
Reactant: ClP(Cl)(Cl)(Cl)Cl
Reactant: O=C1Nc2cc(Cl)ccc2Oc2cscc21
Solvent: Cc1ccccc1
Product: ClC1=Nc2cc(Cl)ccc2Oc2cscc21

Procedure:
A 4.0 g. portion of 7-chloro-thieno[3,4-b][1,5]benzoxazepin-10(9H)-one (Example 4) and 4.0 g. of phosphorus pentachloride in 100 ml. of dry toluene are refluxed for 41/2 hours concentrated and triturated with toluene, giving 7,10-dichlorothieno[3,4-b][1,5]benzoxazepine.
Reaction SMILES: [CH:1]12[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH2:2]1)[CH2:8]2.[OH:11]N1C(=O)C2=CC=CC=C2C1=O.C1(OC)C=CC=CC=1.O=O.C12(O)CC3CC(CC(C3)C1)C2>C(O)(=O)C>[CH:1]12[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[C:2]1=[O:11])[CH2:8]2
Reactant: C1C2CC3CC1CC(C2)C3
Reactant: O=C1c2ccccc2C(=O)N1O
Agent: O=O
Agent: OC12CC3CC(CC(C3)C1)C2
Solvent: CC(=O)O
Solvent: COc1ccccc1
Product: O=C1C2CC3CC(C2)CC1C3
Temperature: 85 °C
Reaction time: 3 h
Yield: 11.3 %

Procedure:
A mixture of 27 g (200 mmol) of adamantane, 3.25 g (20 mmol) of N-hydroxyphthalimide, 0.183 g (0.1 mmol) of V2O5, 240 mL of anisol and 60 mL of acetic acid was stirred for 3 hours at 85° C. and 1 atm (0.101 MPa) in an atmosphere of oxygen. After completion of reaction, the reaction mixture was analyzed by gas chromatography and high performance liquid chromatography, and, as a result, the conversion of adamantane was 13.0%, adamantanol and adamantanone were formed in yield 11.3% (selectivity 86.9%) and yield 0.9% (selectivity 6.9%), respectively. Moreover, in the reaction mixture, 2.12 g of N-hydroxyphthalimide used as a catalyst, 0.68 g of phthalimide, and 0.18 g of phthalic anhydride were contained. The reaction mixture was condensed, 400 mL of hexane was added thereto, and the mixture was stirred for 2 hours at 50° C. After cooling, an insoluble material was filtrated to recover the catalyst and the decomposed product thereof in the form of solid. The filtrate did not contain the catalyst and the decomposed product thereof.
Reaction SMILES: [N+:1]([C:4]1[CH:12]=[C:11]2[C:7]([CH:8]=[CH:9][NH:10]2)=[CH:6][CH:5]=1)([O-:3])=[O:2].ClS([N:17]=[C:18]=O)(=O)=O.C(N(CC)CC)C>C(#N)C>[N+:1]([C:4]1[CH:12]=[C:11]2[C:7]([C:8]([C:18]#[N:17])=[CH:9][NH:10]2)=[CH:6][CH:5]=1)([O-:3])=[O:2]
Reactant: O=[N+]([O-])c1ccc2cc[nH]c2c1
Reactant: O=C=NS(=O)(=O)Cl
Solvent: CCN(CC)CC
Solvent: CC#N
Product: N#Cc1c[nH]c2cc([N+](=O)[O-])ccc12
Temperature: 0 °C
Reaction time: 2 h

Procedure:
6.1 g 6-nitro-1H-indole are dissolved in 100 ml acetonitrile and cooled to 0° C. A solution of 3.2 ml chlorosulphonyl isocyanate in 25 ml acetonitrile is added dropwise and the mixture is stirred for 2 hours. Then a solution of 5 ml triethylamine in 25 ml acetonitrile is added dropwise. The mixture is stirred for 1 hour at ambient temperature and for 50 minutes at 80° C. Then the solvents are eliminated in vacuo, the residue is extracted from cold water, the solid is suction filtered and washed successively with water, saturated sodium hydrogen carbonate solution and water. The solid thus obtained is dried in the desiccator. Then the solid is taken up in 500 ml dichloromethane/methanol 95:5 and stirred with some aluminium oxide. It is suction filtered through a thin layer of aluminium oxide and washed with 400 ml dichloromethane/methanol 95:5. The filtrate is evaporated down in vacuo and the residue is dried in vacuo.
Reaction SMILES: C(OC([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:19]=[CH:18][C:17]([NH:20][C:21]([C:23]3[NH:24][C:25]4[C:30]([C:31]=3[CH3:32])=[CH:29][CH:28]=[CH:27][C:26]=4[O:33][CH3:34])=[O:22])=[CH:16][CH:15]=2)[CH2:10][CH2:9]1)=O)(C)(C)C.[C@H:35]1([C:43]([OH:45])=[O:44])[CH2:39][CH2:38][CH2:37][C@@H:36]1[C:40]([OH:42])=O>>[CH3:34][O:33][C:26]1[CH:27]=[CH:28][CH:29]=[C:30]2[C:25]=1[NH:24][C:23]([C:21]([NH:20][C:17]1[CH:16]=[CH:15][C:14]([N:11]3[CH2:10][CH2:9][N:8]([C:40]([C@H:36]4[CH2:37][CH2:38][CH2:39][C@@H:35]4[C:43]([OH:45])=[O:44])=[O:42])[CH2:13][CH2:12]3)=[CH:19][CH:18]=1)=[O:22])=[C:31]2[CH3:32]
Reactant: COc1cccc2c(C)c(C(=O)Nc3ccc(N4CCN(C(=O)OC(C)(C)C)CC4)cc3)[nH]c12
Reactant: O=C(O)[C@H]1CCC[C@@H]1C(=O)O
Product: COc1cccc2c(C)c(C(=O)Nc3ccc(N4CCN(C(=O)[C@H]5CCC[C@@H]5C(=O)O)CC4)cc3)[nH]c12

Procedure:
With a procedure similar to example above, (1S,2S)-2-(4-{4-[(7-methoxy-3-methyl-1H-indole-2-carbonyl)-amino]-phenyl}-piperazine-1-carbonyl)-cyclopentanecarboxylic acid was prepared from 4-{4-[(7-methoxy-3-methyl-1H-indole-2-carbonyl)-amino]-phenyl}-piperazine-1-carboxylic acid tert-butyl ester and (1S,2S)-cyclopentane-1,2-dicarboxylic acid. LCMS calcd for C28H32N4O5 (m/e) 504, obsd 505 (M+H).
Reaction SMILES: CC(C1C=CC(O)=CC=1)(C1C=CC([OH:10])=CC=1)C.[CH2:18]1[O:20][CH:19]1[CH2:21]Cl.[C:23]1(=O)OCCC[CH2:31][O:30][C:28](=[O:29])[C:27]2C=C[C:24]1=[CH:25][CH:26]=2>[I-].C1(C(C2C=CC=CC=2)(C2C=CC=CC=2)C[PH3+])C=CC=CC=1>[CH3:18][O:20][C:19](=[O:10])[C:21]1[C:27](=[CH:26][CH:25]=[CH:24][CH:23]=1)[C:28]([O:30][CH3:31])=[O:29]
Reactant: ClCC1CO1
Reactant: CC(C)(c1ccc(O)cc1)c1ccc(O)cc1
Reactant: O=C1OCCCCOC(=O)c2ccc1cc2
Agent: [I-]
Agent: [PH3+]CC(c1ccccc1)(c1ccccc1)c1ccccc1
Product: COC(=O)c1ccccc1C(=O)OC
Yield: 9.5 %

Procedure:
Epikote 1004 (180 g), a homopolymer of butylene terephthalate (120 g) and triphenylethyl phosphonium iodide (0.3 g) were melt blended in an extruder as described in Composition 1. A sample of the solidified resulting mixture (30 g) and dimethylphthalate (10 g) were heated in a beaker to 260° C. and poured into butyl diglycol acetate (120 g) at 125° C. The mixture was dispersed using a Silverson high speed stirrer for 3 minutes during which time the temperature rose to 140° C. The mixture was cooled using an ice bath, reaching 49° C. within one minute. The resulting dispersion had a non-volatile content of 18.7% and a particle size range of 0.5 to 10μ.
Reaction SMILES: [Cl-].O[NH3+:3].[C:4](=[O:7])([O-])[OH:5].[Na+].CS(C)=O.[O:13]1[C:17]2([CH2:22][CH2:21][CH:20]([N:23]3[C:28](=[O:29])[C:27]([CH2:30][C:31]4[CH:36]=[CH:35][C:34]([C:37]5[C:38]([C:43]#[N:44])=[CH:39][CH:40]=[CH:41][CH:42]=5)=[CH:33][CH:32]=4)=[C:26]([CH2:45][CH2:46][CH3:47])[N:25]4[N:48]=[C:49]([CH3:51])[N:50]=[C:24]34)[CH2:19][CH2:18]2)[O:16][CH2:15][CH2:14]1>O.C(OCC)(=O)C>[O:16]1[C:17]2([CH2:18][CH2:19][CH:20]([N:23]3[C:28](=[O:29])[C:27]([CH2:30][C:31]4[CH:36]=[CH:35][C:34]([C:37]5[CH:42]=[CH:41][CH:40]=[CH:39][C:38]=5[C:43]5[NH:3][C:4](=[O:7])[O:5][N:44]=5)=[CH:33][CH:32]=4)=[C:26]([CH2:45][CH2:46][CH3:47])[N:25]4[N:48]=[C:49]([CH3:51])[N:50]=[C:24]34)[CH2:21][CH2:22]2)[O:13][CH2:14][CH2:15]1
Reactant: O=C([O-])O
Reactant: CCCc1c(Cc2ccc(-c3ccccc3C#N)cc2)c(=O)n(C2CCC3(CC2)OCCO3)c2nc(C)nn12
Reactant: [NH3+]O
Agent: [Cl-]
Agent: [Na+]
Solvent: CS(C)=O
Solvent: CCOC(C)=O
Solvent: O
Product: CCCc1c(Cc2ccc(-c3ccccc3-c3noc(=O)[nH]3)cc2)c(=O)n(C2CCC3(CC2)OCCO3)c2nc(C)nn12
Temperature: 40 °C
Reaction time: 0.5 h
Yield: 74.6 %

Procedure:
A mixture of hydroxylammonium chloride (1.9 g), sodium hydrogen carbonate (3.2 g) and dimethyl sulfoxide (15 mL) was stirred at 40° C. for 30 min, 4′-{[4-(1,4-dioxaspiro[4.5]dec-8-yl)-2-methyl-5-oxo-7-propyl-4,5-dihydro[1,2,4]triazolo[1,5-a]pyrimidin-6-yl]methyl}biphenyl-2-carbonitrile (1.0 g) was added, and the mixture was stirred at 90° C. for 16 hr. Ethyl acetate and water were added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was dissolved in tetrahydrofuran (5 mL). N,N′-Carbonyldiimidazole (0.37 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.34 mL) were added, and the mixture was stirred at room temperature 19 hr. Ethyl acetate and water were added to the reaction mixture, and the mixture was acidified with 1 M hydrochloric acid and extracted with ethyl acetate. The organic layer was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography and recrystallized (ethyl acetate-hexane) to give the title compound as a colorless solid (0.83 g, 74%).
Reaction SMILES: Br[C:2]1[CH:3]=[N:4][CH:5]=[C:6]([CH:19]=1)[C:7]([N:9]=[S@@:10]([CH3:18])(=[O:17])[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)=[O:8].[Cl:20][C:21]1[CH:26]=[CH:25][C:24]([C:27]#[CH:28])=[CH:23][CH:22]=1>>[Cl:20][C:21]1[CH:26]=[CH:25][C:24]([C:27]#[C:28][C:2]2[CH:3]=[N:4][CH:5]=[C:6]([CH:19]=2)[C:7]([N:9]=[S@@:10]([CH3:18])(=[O:17])[C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[O:8])=[CH:23][CH:22]=1
Reactant: C#Cc1ccc(Cl)cc1
Reactant: C[S@@](=O)(=NC(=O)c1cncc(Br)c1)c1ccccc1
Product: C[S@@](=O)(=NC(=O)c1cncc(C#Cc2ccc(Cl)cc2)c1)c1ccccc1
Yield: 49 %

Procedure:
In a manner similar to that describe in Example 425 a mixture of (S)-5-bromo-N-[methyl(oxo)phenyl-λ6-sulfanylidene]nicotinamide and 4-chloro-1-ethynylbenzene were reacted to give the title compound as white needles (60 mg, 49%).
Reaction SMILES: [C:1]([C:3]1[CH:8]=[CH:7][C:6]([N:9]2[C:17]3[C:12](=[CH:13][C:14]([C:18]#[C:19][CH2:20][CH2:21][CH2:22][OH:23])=[CH:15][CH:16]=3)[CH:11]=[CH:10]2)=[CH:5][CH:4]=1)#[CH:2].[CH3:24][S:25](Cl)(=[O:27])=[O:26]>>[C:1]([C:3]1[CH:8]=[CH:7][C:6]([N:9]2[C:17]3[C:12](=[CH:13][C:14]([C:18]#[C:19][CH2:20][CH2:21][CH2:22][O:23][S:25]([CH3:24])(=[O:27])=[O:26])=[CH:15][CH:16]=3)[CH:11]=[CH:10]2)=[CH:5][CH:4]=1)#[CH:2]
Reactant: C#Cc1ccc(-n2ccc3cc(C#CCCCO)ccc32)cc1
Reactant: CS(=O)(=O)Cl
Product: C#Cc1ccc(-n2ccc3cc(C#CCCCOS(C)(=O)=O)ccc32)cc1

Procedure:
In analogyto example 5.4, 5-[1-(4-Ethynyl-phenyl)-1H-indol-5-yl]-pent-4-yn-1-ol and methanesulfonyl chloride were converted to yield Methanesulfonic acid 5-[1-(4-ethynyl-phenyl)-1H-indol-5-yl]-pent-4-ynyl ester as orange oil, MS: 377 (M).
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1([C:9]2[CH:14]=[CH:13][C:12]([C:15]3[CH:20]=[CH:19][C:18]([C:21]4[O:25][N:24]=[C:23]([CH3:26])[C:22]=4[NH2:27])=[CH:17][CH:16]=3)=[CH:11][CH:10]=2)[CH2:8][CH2:7]1)=[O:5])[CH3:2].Br[C:29]1[CH:34]=[CH:33][CH:32]=[C:31]([O:35][CH:36]2[CH2:39][CH2:38][CH2:37]2)[N:30]=1>>[CH2:1]([O:3][C:4]([C:6]1([C:9]2[CH:10]=[CH:11][C:12]([C:15]3[CH:20]=[CH:19][C:18]([C:21]4[O:25][N:24]=[C:23]([CH3:26])[C:22]=4[NH:27][C:29]4[CH:34]=[CH:33][CH:32]=[C:31]([O:35][CH:36]5[CH2:39][CH2:38][CH2:37]5)[N:30]=4)=[CH:17][CH:16]=3)=[CH:13][CH:14]=2)[CH2:8][CH2:7]1)=[O:5])[CH3:2]
Reactant: CCOC(=O)C1(c2ccc(-c3ccc(-c4onc(C)c4N)cc3)cc2)CC1
Reactant: Brc1cccc(OC2CCC2)n1
Product: CCOC(=O)C1(c2ccc(-c3ccc(-c4onc(C)c4Nc4cccc(OC5CCC5)n4)cc3)cc2)CC1

Procedure:
Prepared according to the procedure described in Example 134, Step 3, using 1-[4′-(4-amino-3-methyl-isoxazol-5-yl)-biphenyl-4-yl]-cyclopropanecarboxylic acid ethyl ester and 2-bromo-6-cyclobutoxy-pyridine.
Reaction SMILES: [OH:1][CH:2]([C:9]1[CH:18]=[CH:17][C:16]2[C:11](=[CH:12][CH:13]=[C:14]([CH3:19])[CH:15]=2)[CH:10]=1)[CH2:3][N:4]1[CH:8]=[CH:7][N:6]=[CH:5]1.[C:20](Cl)(=[O:27])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1>N1C=CC=CC=1>[C:20]([O:1][CH:2]([C:9]1[CH:18]=[CH:17][C:16]2[C:11](=[CH:12][CH:13]=[C:14]([CH3:19])[CH:15]=2)[CH:10]=1)[CH2:3][N:4]1[CH:8]=[CH:7][N:6]=[CH:5]1)(=[O:27])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1
Reactant: O=C(Cl)c1ccccc1
Reactant: Cc1ccc2cc(C(O)Cn3ccnc3)ccc2c1
Solvent: c1ccncc1
Product: Cc1ccc2cc(C(Cn3ccnc3)OC(=O)c3ccccc3)ccc2c1

Procedure:
A solution of 1.26 g. 1-[2-hydroxy-2-(6-methyl-2-naphthyl)ethyl]imidazole in 20 ml. pyridine is treated dropwise with stirring with 0.72 ml. of benzoyl chloride and the mixture stirred overnight. The resulting solutionis poured into 100 ml. water, extracted with ethyl acetate and the extractswashed, dried (MgSO4) and evaporated in vacuo to remove residual pyridine and afford 1-[2-benzoyloxy-2-(6-methyl-2-naphthyl)ethyl]imidazole. The residue is dissolved in ether, treated with ethereal hydrogen chloride and the resulting precipitate recrystallized from acetone/methanol to give the hydrochloride salt.