Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:18]=[CH:19][C:20]=1[O:21][CH2:22][C:23]1[CH:24]=[N:25][C:26]([O:29][CH3:30])=[CH:27][CH:28]=1)[CH2:6][N:7]1[C:11]2=[N:12][CH:13]=[C:14]([C:16]#[N:17])[CH:15]=[C:10]2[N:9]=[CH:8]1.[NH2:31][OH:32]>C(O)C>[OH:32][N:31]=[C:16]([C:14]1[CH:15]=[C:10]2[N:9]=[CH:8][N:7]([CH2:6][C:5]3[CH:18]=[CH:19][C:20]([O:21][CH2:22][C:23]4[CH:24]=[N:25][C:26]([O:29][CH3:30])=[CH:27][CH:28]=4)=[C:3]([O:2][CH3:1])[CH:4]=3)[C:11]2=[N:12][CH:13]=1)[NH2:17]
Reactant: COc1ccc(COc2ccc(Cn3cnc4cc(C#N)cnc43)cc2OC)cn1
Reactant: NO
Solvent: CCO
Product: COc1ccc(COc2ccc(Cn3cnc4cc(C(N)=NO)cnc43)cc2OC)cn1
Temperature: 100 °C
Reaction time: 1 h
Yield: 100 %

Procedure:
To a stirred solution of 3-(3-methoxy-4-((6-methoxypyridin-3-yl)methoxy)benzyl)-3H-imidazo[4,5-b]pyridine-6-carbonitrile (0.53 g, 1.32 mmol) in ethanol was added hydroxylamine solution (50% weight in water, 0.1 mL). The mixture was heated to 100° C. After 1 h, the mixture was concentrated to provide 0.66 g (>100%) of N′-hydroxy-3-(3-methoxy-4-((6-methoxypyridin-3-yl)methoxy)benzyl)-3H-imidazo[4,5-b]pyridine-6-carboximidamide as a white solid.
Reaction SMILES: [C:1]([NH:5][CH3:6])([NH:3][CH3:4])=[O:2].[CH:7]([CH:9]=[O:10])=[O:8].[OH-].[Na+]>>[OH:8][CH:7]1[CH:9]([OH:10])[N:5]([CH3:6])[C:1](=[O:2])[N:3]1[CH3:4]
Reactant: CNC(=O)NC
Reactant: O=CC=O
Agent: [Na+]
Agent: [OH-]
Product: CN1C(=O)N(C)C(O)C1O
Temperature: 25 °C

Procedure:
Dimethylurea (2-moles, 176 parts) and glyoxal (2 moles, 290 parts of 40% aqueous solution) are mixed and the pH adjusted to 7 with sodium hydroxide. The reaction mixture is stirred at room temperature for several hours and the resulting white solid is filtered, washed with methanol and dried. White crystals, melting point 140° C. are obtained in fine yield.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[CH2:9][C:10]1[N:19]([CH2:20][CH2:21]Cl)[C:18](=[O:23])[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[N:11]=1.[CH2:24]([NH2:26])[CH3:25].C(=O)([O-])[O-].[K+].[K+]>C(O)C>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[CH2:9][C:10]1[N:19]([CH2:20][CH2:21][NH:26][CH2:24][CH3:25])[C:18](=[O:23])[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[N:11]=1
Reactant: COc1ccccc1Cc1nc2ccccc2c(=O)n1CCCl
Reactant: CCN
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCO
Product: CCNCCn1c(Cc2ccccc2OC)nc2ccccc2c1=O
Reaction time: 8 h
Yield: 16 %

Procedure:
A mixture of 328 mg (1 mmol) of 2-(2-methoxyphenylmethyl) -3-(2-chloroethyl)-4(3H)-quinazolinone and a 70% aqueous ethylamine solution (0.6 ml) in ethanol (10 ml) was heated at 80 ° C. W for 8 hours in a sealed tube. The solvent was distilled off under reduced pressure and to the residue thus obtained there was added a 10 % aqueous potassium carbonate solution, followed by extraction with dichloromethane. The thus obtained dichloromethane solution was dried over magnesium sulfate and then concentrated. The resulting residue was purified by silica gel column chromatography (eluent: 1% ethanol-chloroform) to obtain 55 mg (16%) of 2-(2-methoxyphenylmethyl)-3-(2-ethylaminoethyl)-4(3H)-quinazolinone as an oily substance. Subsequently, the thus obtained quinazolinone was dissolved in ether (3 ml) and to the resulting solution was added a 10% HCl/ethanol solution. The precipitated crystals were collected by filtration to obtain the hydrochride of the captioned compound.
Reaction SMILES: Cl[C:2]1[N:11]=[C:10](Cl)[C:9]2[C:4](=[CH:5][C:6](OC)=[C:7](OC)[CH:8]=2)[N:3]=1.CC(O)=[O:19]>[OH-].[Na+].C1COCC1>[CH:7]1[CH:6]=[CH:5][C:4]2[N:3]=[CH:2][NH:11][C:10](=[O:19])[C:9]=2[CH:8]=1
Reactant: COc1cc2nc(Cl)nc(Cl)c2cc1OC
Reactant: CC(=O)O
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Product: O=c1[nH]cnc2ccccc12
Temperature: 0 °C
Yield: 100 %

Procedure:
A solution of 2,4-dichloro-6,7-dimethoxy-quinazoline (2.12 g, 8.20 mmol) in 1 M NaOH (50 mL) and THF (15 mL) was stirred at room temperature under an argon blanket for 23 hours. The solution was cooled to 0° C., then acidified to pH 5 with AcOH. The resulting solids were collected by vacuum filtration and dried in a vacuum oven at 70° C. overnight to provide Intermediate 8 as a pale yellow powder (2.02 g, 100%). 1H NMR (300 MHz, DMSO-d6) δ: 7.38 (s, 1H), 7.08 (s, 1H), 3.88 (s, 3H), 3.85 (s, 3H), 3.50–3.20 (br s, 1H).
Reaction SMILES: [O:1]1[CH:5]=[CH:4][N:3]=[CH:2]1.C([Li])CCC.[CH2:11]([N:13]([CH2:27][CH2:28][CH3:29])[C:14]([C:16]1[CH:17]=[C:18]([CH:23]=[C:24](I)[CH:25]=1)[C:19]([O:21][CH3:22])=[O:20])=[O:15])[CH3:12]>O1CCCC1.C(OCC)(=O)C.[Cl-].[Zn+2].[Cl-]>[CH2:11]([N:13]([CH2:27][CH2:28][CH3:29])[C:14]([C:16]1[CH:17]=[C:18]([CH:23]=[C:24]([C:2]2[O:1][CH:5]=[CH:4][N:3]=2)[CH:25]=1)[C:19]([O:21][CH3:22])=[O:20])=[O:15])[CH3:12]
Reactant: CCCN(CC)C(=O)c1cc(I)cc(C(=O)OC)c1
Reactant: c1cocn1
Agent: [Cl-]
Agent: [Li]CCCC
Agent: [Zn+2]
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: CCCN(CC)C(=O)c1cc(C(=O)OC)cc(-c2ncco2)c1
Temperature: 0 °C
Reaction time: 0.5 h

Procedure:
To a −70° C. stirred solution of oxazole (106 mg, 1.5 mmol) in tetrahydrofuran (4 mL) is added n-butyllithium (1.6 M in hexanes, 1.0 mL, 1.7 mmol). After 30 min, zinc chloride (1 M in diethyl ether, 4.6 mL, 4.6 mmol) is added and the reaction mixture is warmed to 0° C. for 1 h. To this mixture is added a solution of methyl 3-{[ethyl(propyl)amino]carbonyl}-5-iodobenzoate (535 mg, 1.45 mmol) in anhydrous tetrahydrofuran (1.8 mL) followed by palladium(0)tetrakis(triphenylphosphine) (120 mg, 0.10 mmol). The reaction mixture is heated at reflux for 2 h. The reaction mixture is cooled, diluted with ethyl acetate, washed with water, and saturated sodium chloride, dried (sodium sulfate), filtered, and concentrated under reduced pressure. Purification by flash column chromatography (silica gel, 60% ethyl acetate/hexane) provides the title compound. ESI MS m/z 317.1 [M+H]+.
Reaction SMILES: [NH2:1][C:2]1[C:3]2[C:8]([N:9]=[C:10]3[C:15]=1[C:14](=[O:16])[CH2:13][CH2:12][CH2:11]3)=[CH:7][C:6]([C:17]([F:20])([F:19])[F:18])=[CH:5][CH:4]=2.[H-].[Al+3].[Li+].[H-].[H-].[H-]>O1CCCC1>[NH2:1][C:2]1[C:3]2[C:8]([N:9]=[C:10]3[C:15]=1[CH:14]([OH:16])[CH2:13][CH2:12][CH2:11]3)=[CH:7][C:6]([C:17]([F:20])([F:18])[F:19])=[CH:5][CH:4]=2
Reactant: Nc1c2c(nc3cc(C(F)(F)F)ccc13)CCCC2=O
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Product: Nc1c2c(nc3cc(C(F)(F)F)ccc13)CCCC2O
Reaction time: 0.5 h

Procedure:
9-Amino-3,4-dihydro-6-trifluoromethylacridin-1(2H)-one (2.4 g) was suspended in 60 ml of tetrahydrofuran. To this cooled solution was added 9 ml of 1 molar solution of lithium aluminum hydride in THF. This was stirred for 30 minutes.
Reaction SMILES: [CH3:1][S:2][C:3]1[N:4]=[CH:5][C:6]2[CH2:11][NH:10][CH2:9][C:7]=2[N:8]=1.Br[C:13]1[CH:18]=[CH:17][N:16]=[C:15]([C:19]([NH:21][C:22]2[CH:27]=[CH:26][CH:25]=[C:24]([CH:28]([CH3:30])[CH3:29])[CH:23]=2)=[O:20])[CH:14]=1>>[CH:28]([C:24]1[CH:23]=[C:22]([NH:21][C:19]([C:15]2[CH:14]=[C:13]([N:10]3[CH2:11][C:6]4[CH:5]=[N:4][C:3]([S:2][CH3:1])=[N:8][C:7]=4[CH2:9]3)[CH:18]=[CH:17][N:16]=2)=[O:20])[CH:27]=[CH:26][CH:25]=1)([CH3:30])[CH3:29]
Reactant: CSc1ncc2c(n1)CNC2
Reactant: CC(C)c1cccc(NC(=O)c2cc(Br)ccn2)c1
Product: CSc1ncc2c(n1)CN(c1ccnc(C(=O)Nc3cccc(C(C)C)c3)c1)C2

Procedure:
In a manner similar to that describe in Example 126, 2-(methylthio)-6,7-dihydro-5H-pyrrolo[3,4-d]pyrimidine and 4-bromo-N-(3-isopropylphenyl)picolinamide were converted to the title compound.
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][C:4]2([C:10]3[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=3[C:8](=[O:15])[O:7]2)[CH2:3][CH2:2]1.[CH3:16][O:17][C:18]1[CH:19]=[C:20]([CH2:26][CH2:27][N:28]2[C:36]3[C:31](=[CH:32][C:33]([O:37][CH3:38])=[CH:34][CH:35]=3)[C:30]([C:39](O)=[O:40])=[C:29]2[CH3:42])[CH:21]=[CH:22][C:23]=1[O:24][CH3:25]>>[CH3:16][O:17][C:18]1[CH:19]=[C:20]([CH2:26][CH2:27][N:28]2[C:36]3[C:31](=[CH:32][C:33]([O:37][CH3:38])=[CH:34][CH:35]=3)[C:30]([C:39]([N:1]3[CH2:6][CH2:5][C:4]4([C:10]5[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=5[C:8](=[O:15])[O:7]4)[CH2:3][CH2:2]3)=[O:40])=[C:29]2[CH3:42])[CH:21]=[CH:22][C:23]=1[O:24][CH3:25]
Reactant: O=C1OC2(CCNCC2)c2ccccc21
Reactant: COc1ccc2c(c1)c(C(=O)O)c(C)n2CCc1ccc(OC)c(OC)c1
Product: COc1ccc2c(c1)c(C(=O)N1CCC3(CC1)OC(=O)c1ccccc13)c(C)n2CCc1ccc(OC)c(OC)c1

Procedure:
Following the general procedure I as described above, the acylation of 3H-spiro[2-benzofuran-1,4′-piperidin]-3-one prepared as described in example 16 above, with commercially available 1-[2-(3,4-dimethoxy-phenyl)-ethyl]-5-methoxy-2-methyl-1H-indole-3-carboxylic acid, gave the title compound. ES-MS m/e (%): 555.3 (M+H+).
Reaction SMILES: Cl[C:2]([O:4][CH2:5][CH3:6])=[O:3].ON1C(=O)CCC1=O.C(N(CC)C(C)C)(C)C.[CH2:24]([CH2:26][NH2:27])[OH:25]>C(Cl)Cl>[OH:25][CH2:24][CH2:26][NH:27][C:2](=[O:3])[O:4][CH2:5][CH3:6]
Reactant: NCCO
Reactant: CCOC(=O)Cl
Agent: O=C1CCC(=O)N1O
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: CCOC(=O)NCCO
Temperature: 25 °C
Reaction time: 3 h

Procedure:
To a stirred solution of ethyl chloroformate (4 g, 0.037 mol.) and N-hydroxysuccinimide (6.3 g, 0.055 mol.) in 10 mL of DCM at 0° C. under nitrogen atmosphere was added N,N-Diisopropylethylamine (9.5 g, 0.055 mol) in 10 mL of DCM. The progress of the reaction was monitored by thin layer chromatography (TLC). After stirring for 3 hrs at room temperature, the reaction mixture was filtered and the precipitate was washed with 2×10 mL of dichloromethane. The combined filtrate was evaporated and dissolved in 20 mL of acetonitrile, cooled in an ice-bath and then added dropwise a solution of Ethanolamine 23 (3.3 mL, 2.5 eq). The resulting mixture was stirred at ice-bath temperature for 1 h and then overnight at room temperature. The progress of the reaction was monitored by thin layer chromatography (TLC). The reaction mixture was filtered, and the precipitate was washed with 2×10 mL DCM and dried over sodium sulfate. After removing the solvent under reduced pressure, the residue was purified by silica gel column chromatography to give ethyl (2-hydroxyethyl)carbamate.
Reaction SMILES: Cl[C:2]1[CH:7]=[C:6]([Cl:8])[N:5]=[C:4]([NH2:9])[N:3]=1.[NH:10]1[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]1>CO>[Cl:8][C:6]1[CH:7]=[C:2]([N:10]2[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]2)[N:3]=[C:4]([NH2:9])[N:5]=1
Reactant: C1CCNCC1
Reactant: Nc1nc(Cl)cc(Cl)n1
Solvent: CO
Product: Nc1nc(Cl)cc(N2CCCCC2)n1
Temperature: 50 °C
Reaction time: 4 h
Yield: 87.1 %

Procedure:
In a 25 mL sealable tube under argon were combined 4,6-dichloro-2-pyrimidinamine (0.50 g, 3.05 mmol), piperidine (0.75 mL, 7.62 mmol) and CH3OH (10 mL). The vial was sealed and the reaction mixture was stirred for 4 hours at 50° C. The reaction was cooled to room temperature and concentrated. The resulting solid was partitioned between EtOAc and water. The organic layer was separated, dried (MgSO4), filtered and concentrated to afford the title compound (565 mg, 83%) as a yellow solid. LC-MS (ES) m/z=213 [M+H]+.
Reaction SMILES: [C:1]([NH:4][C:5]1[CH:10]=[CH:9][C:8]([S:11](Cl)(=[O:13])=[O:12])=[C:7]([CH3:15])[CH:6]=1)(=[O:3])[CH3:2].[NH:16]1[CH2:20][CH2:19][CH2:18][CH2:17]1.Cl>[OH-].[Na+].CC(C)=O>[CH3:15][C:7]1[CH:6]=[C:5]([NH:4][C:1](=[O:3])[CH3:2])[CH:10]=[CH:9][C:8]=1[S:11]([N:16]1[CH2:20][CH2:19][CH2:18][CH2:17]1)(=[O:13])=[O:12]
Reactant: CC(=O)Nc1ccc(S(=O)(=O)Cl)c(C)c1
Reactant: C1CCNC1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CC(C)=O
Product: CC(=O)Nc1ccc(S(=O)(=O)N2CCCC2)c(C)c1
Temperature: 25 °C

Procedure:
1.45 g of 4-acetylamino-2-methyl-benzenesulphonyl chloride (5.85 mmol) at 0° C. are suspended in 19 ml sodium hydroxide solution (1 M) and then 0.51 ml pyrrolidine (6.47 mmol), dissolved in 9 ml acetone, are added dropwise within half an hour. The solution is heated to ambient temperature overnight and then acidified with hydrochloric acid (2 M). The suspension is extracted twice with ethyl acetate. The combined organic phases are dried over sodium sulphate and evaporated down. A brown oil remains.
Reaction SMILES: C([O:4][C@@H:5]1[C@@H:19]([O:20]C(=O)C)[C@H:18]([O:24][C@H:25]2[O:42][C@H:41]([CH2:43][O:44]C(=O)C)[C@@H:36]([O:37]C(=O)C)[C@H:31]([O:32]C(=O)C)[C@H:26]2[O:27]C(=O)C)[C@@H:17]([CH2:48][O:49]C(=O)C)[O:16][C@H:6]1[S:7][C:8]1[CH:13]=[CH:12][C:11]([O:14][CH3:15])=[CH:10][CH:9]=1)(=O)C.C(N(CC)CC)C>CO.CO.O>[C@H:25]1([O:24][C@@H:18]2[C@@H:17]([CH2:48][OH:49])[O:16][C@@H:6]([S:7][C:8]3[CH:9]=[CH:10][C:11]([O:14][CH3:15])=[CH:12][CH:13]=3)[C@H:5]([OH:4])[C@H:19]2[OH:20])[O:42][C@H:41]([CH2:43][OH:44])[C@@H:36]([OH:37])[C@H:31]([OH:32])[C@H:26]1[OH:27]
Reactant: COc1ccc(S[C@@H]2O[C@H](COC(C)=O)[C@@H](O[C@H]3O[C@H](COC(C)=O)[C@@H](OC(C)=O)[C@H](OC(C)=O)[C@H]3OC(C)=O)[C@H](OC(C)=O)[C@H]2OC(C)=O)cc1
Solvent: O
Solvent: CO
Solvent: CCN(CC)CC
Product: COc1ccc(S[C@@H]2O[C@H](CO)[C@@H](O[C@H]3O[C@H](CO)[C@@H](O)[C@H](O)[C@H]3O)[C@H](O)[C@H]2O)cc1
Reaction time: 8 h
Yield: 81.7 %

Procedure:
A mixture comprising 2.6 g of 4-methoxyphenyl 2,3,6-tri-O-acetyl-4-O-(2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl)-1-thio-β-D-glucopyranoside in 25 ml of cold methanol was combined with a cold mixture of 2N triethylamine in methanol:water (6:2). This mixture was refrigerated overnight, then evaporated in vacuo to a solid which was triturated with ether, giving 1.3 g of the desired intermediate, UV 225-245 nm.
Reaction SMILES: [ClH:1].[CH2:2]([OH:4])[CH3:3].O.[NH2:6][C@H:7]([C:19]([OH:21])=[O:20])[CH2:8][CH2:9][C:10]([NH:12][C@H:13]([C:16](O)=[O:17])[CH2:14][SH:15])=[O:11]>CCOCC>[ClH:1].[CH2:2]([O:4][C:16](=[O:17])[C@H:13]([CH2:14][SH:15])[NH:12][C:10](=[O:11])[CH2:9][CH2:8][C@@H:7]([C:19]([OH:21])=[O:20])[NH2:6])[CH3:3]
Reactant: N[C@@H](CCC(=O)N[C@@H](CS)C(=O)O)C(=O)O
Reactant: CCO
Agent: Cl
Solvent: CCOCC
Solvent: O
Product: CCOC(=O)[C@H](CS)NC(=O)CC[C@H](N)C(=O)O
Temperature: 25 °C
Reaction time: 1 h
Yield: 83 %

Procedure:
After 250 ml of hydrogen chloride-containing ethanol (7N HCl-EtOH) was added to a dehydrated ethanol suspension (750 ml) containing 50 g (about 185 mmol) of γ-L-glutamyl-L-cysteine monohydrate, the mixture was stirred at room temperature for 1 hour. Upon addition of hydrogen chloride, the suspension turned to a solution. The reaction solution was then poured into ether (7.5 l) which had been cooled to 0° C. beforehand and the mixture was kept stirring for 2 hours to make the crystals precipitate. Thus obtained product was separated by filtration to give 48.4 g (83%) of γ-L-glutamyl-L-cysteine ethyl ester hydrochloride salt.
Reaction SMILES: Cl[C:2]1[N:3]=[C:4]([N:14]2[CH2:19][CH2:18][O:17][CH2:16][C@@H:15]2[CH3:20])[C:5]2[CH2:10][S:9](=[O:12])(=[O:11])[CH:8]([CH3:13])[C:6]=2[N:7]=1.[CH:21]1([NH:24][C:25]([NH:27][C:28]2[CH:33]=[CH:32][C:31](B3OC(C)(C)C(C)(C)O3)=[CH:30][CH:29]=2)=[O:26])[CH2:23][CH2:22]1.C([O-])([O-])=O.[Na+].[Na+]>COCCOC.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH:21]1([NH:24][C:25]([NH:27][C:28]2[CH:33]=[CH:32][C:31]([C:2]3[N:3]=[C:4]([N:14]4[CH2:19][CH2:18][O:17][CH2:16][C@@H:15]4[CH3:20])[C:5]4[CH2:10][S:9](=[O:12])(=[O:11])[CH:8]([CH3:13])[C:6]=4[N:7]=3)=[CH:30][CH:29]=2)=[O:26])[CH2:23][CH2:22]1
Reactant: CC1c2nc(Cl)nc(N3CCOC[C@@H]3C)c2CS1(=O)=O
Reactant: CC1(C)OB(c2ccc(NC(=O)NC3CC3)cc2)OC1(C)C
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: O=C([O-])[O-]
Solvent: COCCOC
Solvent: O
Product: CC1c2nc(-c3ccc(NC(=O)NC4CC4)cc3)nc(N3CCOC[C@@H]3C)c2CS1(=O)=O
Temperature: 80 °C
Reaction time: 8 h
Yield: 21.9 %

Procedure:
To a solution of 2-chloro-7-methyl-4-[(3S)-3-methylmorpholin-4-yl]-5,7-dihydrothieno[3,4-d]pyrimidine 6,6-dioxide (32 mg, 0.10 mmol) in DME/H2O (4:1, 10 mL) was added 1-cyclopropyl-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)urea (45 mg, 0.15 mmol) and Na2CO3 (32 mg, 0.30 mmol) followed by PdCl2(dppf) (10 mg, 0.013 mmol). The resulting mixture was stirred overnight at 80° C. under nitrogen. The solvent was removed under vacuum to give a residue which was partitioned between ethyl acetate and water. The organic layer was separated, dried (Na2SO4), filtered and evaporated to provide the crude product which was purified by preparative TLC (DCM/MeOH=10/1) to give the desired product as a white solid (10 mg, 22%).
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([S:8][C:9]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[NH:12]/[C:11](=[C:19]3/[C:20]([CH2:25][CH2:26][CH3:27])=[N:21][NH:22][C:23]/3=[O:24])/[CH:10]=2)=[CH:4][CH:3]=1.[C:28](Cl)(=[O:31])[CH2:29][CH3:30]>C1COCC1>[O:24]=[C:23]1[NH:22][N:21]=[C:20]([CH2:25][CH2:26][CH3:27])/[C:19]/1=[C:11]1/[NH:12][C:13]2[C:18]([C:9]([S:8][C:5]3[CH:4]=[CH:3][C:2]([NH:1][C:28](=[O:31])[CH2:29][CH3:30])=[CH:7][CH:6]=3)=[CH:10]/1)=[CH:17][CH:16]=[CH:15][CH:14]=2
Reactant: CCC(=O)Cl
Reactant: CCCC1=NNC(=O)/C1=C1/C=C(Sc2ccc(N)cc2)c2ccccc2N1
Solvent: C1CCOC1
Product: CCCC1=NNC(=O)/C1=C1/C=C(Sc2ccc(NC(=O)CC)cc2)c2ccccc2N1

Procedure:
The title compound was synthesized using (Z)-4-(4-(4-aminophenylthio)quinolin-2(1H)-ylidene)-3-propyl-1H-pyrazol-5(4H)-one and propionyl chloride in THF according to the procedure described in the synthesis of Example 26. 1H NMR (400 MHz, DMSO-d6) δ ppm 0.70 (t, J=7.33 Hz, 3H) 1.11 (t, J=7.58 Hz, 3H) 1.27-1.37 (m, J=14.87, 7.41, 7.41, 7.20 Hz, 2H) 2.22 (t, J=6.95 Hz, 2H) 2.38 (q, J=7.41 Hz, 2H) 6.74 (s, 1H) 7.62 (t, J=7.58 Hz, 1H) 7.68 (d, J=8.59 Hz, 2H) 7.83-7.93 (m, 4H) 8.13 (d, J=8.34 Hz, 1H) 10.26 (s, 1H); ESI-MS: m/z calc'd for C24H24N4O2S 432.54. found 433.2 (M+H)+.
Reaction SMILES: [CH:1]([O:5][C:6]1[CH:7]=[C:8]([CH:26]=[CH:27][CH:28]=1)[CH2:9][C:10]1[C:19]2[C:14](=[CH:15][C:16]([O:22][CH3:23])=[C:17]([O:20][CH3:21])[CH:18]=2)[C:13]([CH2:24]Cl)=[CH:12][N:11]=1)([CH2:3][CH3:4])[CH3:2].[C-:29]#[N:30].[Na+].C(OCC)(=O)C.CCCCCC>CS(C)=O.C(OCC)(=O)C.O>[CH:1]([O:5][C:6]1[CH:7]=[C:8]([CH:26]=[CH:27][CH:28]=1)[CH2:9][C:10]1[C:19]2[C:14](=[CH:15][C:16]([O:22][CH3:23])=[C:17]([O:20][CH3:21])[CH:18]=2)[C:13]([CH2:24][C:29]#[N:30])=[CH:12][N:11]=1)([CH2:3][CH3:4])[CH3:2]
Reactant: [C-]#N
Reactant: CCC(C)Oc1cccc(Cc2ncc(CCl)c3cc(OC)c(OC)cc23)c1
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: O
Solvent: CS(C)=O
Product: CCC(C)Oc1cccc(Cc2ncc(CC#N)c3cc(OC)c(OC)cc23)c1
Temperature: 25 °C
Reaction time: 1 h
Yield: 91.5 %

Procedure:
To a stirred solution of 1-(3-sec-butoxy-benzyl)-4-chloromethyl-6,7-dimethoxy-isoquinoline (950 mg, 2.38 mmol) in methyl sulfoxide (10 mL) was added sodium cyanide (582, 11.9 mmol). The reaction mixture was stirred at room temperature for 1 h and diluted with ethyl acetate and water. The aqueous phase was extracted with ethyl acetate (3×25 mL). The combined extracts were washed with saturated aqueous sodium chloride solution (20 mL), dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 70–230 mesh, 40% ethyl acetate/hexane) afforded [1-(3-sec-butoxy-benzyl)-6,7-dimethoxy-isoquinolin-4-yl]-acetonitrile (850 mg, 91% yield) as a colorless oil.
Reaction SMILES: O.[NH2:2][NH2:3].[CH2:4]([N:8]1[C:12]([CH3:13])=[C:11]([CH3:14])[C:10]([CH:15]=O)=[C:9]1[C:17](Cl)=[CH:18][CH2:19][C:20]1[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=1)[CH:5]=[CH:6][CH3:7]>C(O)C>[CH2:4]([N:8]1[C:9]2=[C:17]([CH2:18][CH2:19][C:20]3[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=3)[N:2]=[N:3][CH:15]=[C:10]2[C:11]([CH3:14])=[C:12]1[CH3:13])[CH:5]=[CH:6][CH3:7]
Reactant: CC=CCn1c(C)c(C)c(C=O)c1C(Cl)=CCc1ccc(F)cc1
Reactant: NN
Solvent: O
Solvent: CCO
Product: CC=CCn1c(C)c(C)c2cnnc(CCc3ccc(F)cc3)c21
Temperature: 75 °C
Yield: 62.9 %

Procedure:
0.10 g (0.0020 mole) of hydrazine hydrate was added to a solution of 0.39 g (0.00113 mole) of 1-(2-butenyl)-2-[1-chloro-3-(4-fluorophenyl)-1-propenyl]-3-formyl-4,5-dimethylpyrrole in 7 ml of ethanol and the resulting mixture was stirred at 75° C. for an hour. After completion of the reaction, the reaction mixture was concentrated under reduced pressure and the concentrate was diluted with ice-water. The aqueous mixture was extracted twice with 30 ml of ethyl acetate. The combined extracts were washed with a saturated aqueous solution of sodium chloride and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure and the residue was purified by column chromatography through silica gel using a 50:1 mixture of chloroform and methanol as an eluent to give 0.23 g of the title compound (cis/trans=22/78) as white powdery crystals.
Reaction SMILES: O=S(Cl)Cl.[Br:5][C:6]1[C:7]([Cl:15])=[N:8][CH:9]=[C:10]([CH:14]=1)[C:11]([OH:13])=O.CCN(C(C)C)C(C)C.[F:25][C:26]([S:29][C:30]1[CH:36]=[CH:35][C:33]([NH2:34])=[CH:32][CH:31]=1)([F:28])[F:27].Cl>C1(C)C=CC=CC=1.C1COCC1.CC(OC)(C)C.CN(C=O)C>[Br:5][C:6]1[C:7]([Cl:15])=[N:8][CH:9]=[C:10]([CH:14]=1)[C:11]([NH:34][C:33]1[CH:35]=[CH:36][C:30]([S:29][C:26]([F:28])([F:25])[F:27])=[CH:31][CH:32]=1)=[O:13]
Reactant: Nc1ccc(SC(F)(F)F)cc1
Reactant: O=C(O)c1cnc(Cl)c(Br)c1
Agent: Cl
Solvent: COC(C)(C)C
Solvent: C1CCOC1
Solvent: CN(C)C=O
Product: O=C(Nc1ccc(SC(F)(F)F)cc1)c1cnc(Cl)c(Br)c1
Temperature: 80 °C
Reaction time: 1 h

Procedure:
DMF (0.12 mL) was added followed by slow addition of SOCl2 (0.73 mL, 10 mmol) to a mixture of 5-bromo-6-chloro-nicotinic acid (473 mg, 2 mmol) in toluene (5 mL), and the RM was then stirred at 80° C. for 1 h. After cooling at RT, the toluene was evaporated off under reduce pressure and the residue was dissolved in THF (0.4 mL). DIPEA (0.7 mL, 4 mmol) was added and the solution was cooled to 0° C. under nitrogen. 4-trifluoromethylsulfanyl-aniline (438 mg, 2.2 mmol) in THF (1 mL) was then added dropwise and the RM was stirred at 0° C. for 2 h. The RM was diluted with TBME (50 mL), treated with 1 M HCl and extracted with TBME. The combined extracts were washed with 1 M aq. NaOH and brine, dried over Na2SO4 and the solvent was evaporated off under reduced pressure and the product was crystallized from TBME/n-hexane to give the title compound as an off-white crystalline powder. HPLC (Condition 4) tR=6.63 min, UPLC-MS (Condition 3) tR=1.33 min, m/z=411.1 [M+H]+.
Reaction SMILES: [CH:1]12[O:7][CH:2]1[CH2:3][CH2:4][CH2:5][CH2:6]2.Cl.C[OH:10]>C(Cl)Cl>[C:1](=[O:7])=[O:10].[CH:2]12[O:7][CH:1]1[CH2:6][CH2:5][CH2:4][CH2:3]2
Reactant: CO
Agent: C1CCC2OC2C1
Agent: Cl
Solvent: ClCCl
Product: O=C=O
Reaction time: 24 h

Procedure:
All low pressure catalytic reactions were carried out in magnetically stirred Schlenk tubes, using standard Schlenk techniques. The Schlenk tubes were dried, in an oven at 140° C., for 20 h before any use. In a typical reaction cyclohexene oxide (2.5 mL, 24.7 mmol), and the catalyst were added to a Schlenk tube. The cyclohexene oxide was rapidly de-gassed, before being left stirring under 1 atm CO2 (continuously fed using a reserve cylinder), at 80° C., for 24 h. At the end of the reaction the crude reaction mixture was then taken up in CH2Cl2 and a 0.2 mL of a 5% solution of HCl/MeOH was added. The solution was evaporated in air, after which the product was dried, in vacuo, overnight. No further purification of the product was undertaken as the vacuum was sufficient to remove unreacted cyclohexene oxide. Selectivity was determined by normalisation of the integrals of the methylene protons resonances in the 1H NMR spectra, including the copolymer carbonate linkages (broad signal δ=4.65 ppm), copolymer ether linkages (broad signal δ=3.45 ppm), and cyclic carbonate (multiplets: δ=3.9 ppm (trans-CHC) or 4.63 ppm (cis-CHC)). Conversion was calculated as [(mass of the isolated product weight of the catalyst)/142.1]/moles of starting CHO. Turn-over-number (TON) was calculated as conversion/moles catalyst. Turn-over-frequency (TOF) was calculated as TON/time of reaction (in h).