Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br[C:2]([CH3:23])([CH3:22])[C:3]([C:5]1[CH:10]=[CH:9][C:8]([CH:11]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH2:12][C:13]([O-:15])=[O:14])=[CH:7][CH:6]=1)=[O:4].[OH-:24].[Na+].O>COCCOC>[OH:24][C:2]([CH3:23])([CH3:22])[C:3]([C:5]1[CH:10]=[CH:9][C:8]([CH:11]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH2:12][C:13]([OH:15])=[O:14])=[CH:7][CH:6]=1)=[O:4]
Reactant: [OH-]
Reactant: CC(C)(Br)C(=O)c1ccc(C(CC(=O)[O-])c2ccccc2)cc1
Agent: [Na+]
Solvent: O
Solvent: COCCOC
Product: CC(C)(O)C(=O)c1ccc(C(CC(=O)O)c2ccccc2)cc1
Yield: 85.9 %

Procedure:
A mixture of 64.0 g (0.164 mol) of 3-[4-(2-bromo-2-methylpropionyl)phenyl]-3-phenylpropanoate, 13.2 g (0.328 mol) of sodium hydroxide, 70 ml of water, and 300 ml of 1,2-dimethoxyethane is heated at reflux for 16 hours. The reaction is concentrated, and then acidified with 25 ml of 1.5 N hydrochloric acid solution. Ethyl acetate (200 ml) is added, and the organic layer is washed with distilled water, dried over sodium sulfate, and concentrated. The crude product is passed through a pad of silica gel with ethyl acetate as the eluent to give 44 g (86% yield) of the title compound.
Reaction SMILES: C(=O)(O)[O-:2].[Na+].Cl.NO.[F:9][C:10]([F:27])([F:26])[C:11]([C:18]1[CH:23]=[CH:22][N:21]=[C:20]([C:24]#[N:25])[CH:19]=1)([CH3:17])[O:12][Si:13]([CH3:16])([CH3:15])[CH3:14]>C(O)C>[F:27][C:10]([F:26])([F:9])[C:11]([C:18]1[CH:23]=[CH:22][N:21]=[C:20]([C:24]([NH2:25])=[O:2])[CH:19]=1)([CH3:17])[O:12][Si:13]([CH3:14])([CH3:15])[CH3:16]
Reactant: O=C([O-])O
Reactant: CC(O[Si](C)(C)C)(c1ccnc(C#N)c1)C(F)(F)F
Agent: Cl
Agent: NO
Agent: [Na+]
Solvent: CCO
Product: CC(O[Si](C)(C)C)(c1ccnc(C(N)=O)c1)C(F)(F)F
Reaction time: 2 h
Yield: 94.1 %

Procedure:
To 4 ml of ethanol were added 0.22 g of sodium bicarbonate and 0.18 g of hydroxylamine hydrochloride, and the mixture was heated to reflux for 1 hour. After allowing to cool, 0.5 g of 4-[2,2,2-trifluoro-1-methyl-1-(trimethylsilyloxy)ethyl]pyridine-2-carbonitrile was added at 0° C., and the mixture was stirred for 2 hours, and concentrated. To the residue was added water, the resultant solution was extracted with ethyl acetate three times, and the organic layers were combined, washed with an aqueous saturated sodium chloride solution, dried with anhydrous magnesium sulfate, and concentrated. The residue was subjected to silica gel column chromatography to obtain 0.5 g of 4-[2,2,2-trifluoro-1-methyl-1-(trimethylsilyloxy)ethyl]pyridine-2-carboxamide=oxime.
Reaction SMILES: [NH:1]1[CH:5]=[CH:4][N:3]=[CH:2]1.[Cl:6][C:7]1[N:8]=[N:9][C:10](Cl)=[CH:11][CH:12]=1.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[Cl:6][C:7]1[N:8]=[N:9][C:10]([N:1]2[CH:5]=[CH:4][N:3]=[CH:2]2)=[CH:11][CH:12]=1
Reactant: Clc1ccc(Cl)nn1
Reactant: c1c[nH]cn1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: Clc1ccc(-n2ccnc2)nn1
Yield: 83.1 %

Procedure:
A mixture of imidazole (0.613 g, 8 mmol) and 3,6-dichloropyridazine (1.55 g, 10 mmol), K2CO3 (4.15 g) and DMF (15 mL) was heated at 70–80° C. overnight. After removal of DMF in vacuo, the residual solid was dissolved in CH2Cl2 (50 mL), washed with 1N Na2CO3 aq. solution, and dried (MgSO4). Separation using column chromatography (CH2Cl2/methanol 100:1) afforded 3-chloro-6-(imidazol-1-yl)pyridazine (1.2 g) as a white solid.
Reaction SMILES: [OH:1][C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][CH:3]=1.Cl.[CH3:13][N:14]([CH3:18])[CH2:15][CH2:16]Cl.C(=O)([O-])[O-].[K+].[K+].O>CN(C)C=O>[CH3:13][N:14]([CH3:18])[CH2:15][CH2:16][O:1][C:2]1[CH:3]=[CH:4][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:10][CH:11]=1
Reactant: CN(C)CCCl
Reactant: COC(=O)c1ccc(O)cc1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: COC(=O)c1ccc(OCCN(C)C)cc1
Temperature: 80 °C
Reaction time: 8 h
Yield: 30.9 %

Procedure:
1.52 g (10 mmol) of methyl 4-hydroxybenzoate was dissolved in 40 ml of N,N-dimethylformamide and 2.16 g (15 mmol) of 2-dimethylaminoethyl chloride hydrochloride and 4.15 g (30 mmol) of potassium carbonate were further added. The mixture was heated at 80° C. and stirred overnight. After cooling, water was added to the reaction mixture, the obtained mixture was extracted twice with ethyl acetate, and the extract was washed with brine. The organic phase was dried (Na2SO4) and the solvent was distilled off. The resulting residue was purified by silica gel column chromatography (chloroform:methanol=70:1 to 15:1 (v/v)) to obtain 0.69 g (3.09 mmol) of methyl 4-(2-dimethylaminoethoxy)benzoate as a pale brown oily substance. Its spectroscopic data are as follows:
Reaction SMILES: C([O:4][CH2:5][C:6]1[CH:7]=[C:8]2[C:13](=[C:14]([I:16])[CH:15]=1)[N:12]=[CH:11][C:10]([C:17]([O:19]CC)=O)=[C:9]2[OH:22])(=O)C.[Cl:23][C:24]1[CH:31]=[CH:30][C:27]([CH2:28][NH2:29])=[CH:26][CH:25]=1>CCOCC>[Cl:23][C:24]1[CH:31]=[CH:30][C:27]([CH2:28][NH:29][C:17]([C:10]2[CH:11]=[N:12][C:13]3[C:8]([C:9]=2[OH:22])=[CH:7][C:6]([CH2:5][OH:4])=[CH:15][C:14]=3[I:16])=[O:19])=[CH:26][CH:25]=1
Reactant: CCOC(=O)c1cnc2c(I)cc(COC(C)=O)cc2c1O
Reactant: NCc1ccc(Cl)cc1
Solvent: CCOCC
Product: O=C(NCc1ccc(Cl)cc1)c1cnc2c(I)cc(CO)cc2c1O
Temperature: 180 °C
Yield: 73 %

Procedure:
A suspension of ethyl 6-[(acetyloxy)methyl]-4-hydroxy-8-iodo-3-quinolinecarboxylate (0.90 g) and 4-chlorobenzylamine (2.6 mL) is heated at 180° C. for 1 h. The reaction is cooled to room temperature and diluted with Et2O. The resulting solid is filtered and triturated with acetone to yield 0.74 g (73%) of N-(4-chlorobenzyl)-4-hydroxy-6-(hydroxymethyl)-8-iodo-3-quinolinecarboxamide, m.p. 283-286° C.
Reaction SMILES: Cl[SiH2:2][SiH3:3].[CH:4]([NH:7][CH:8]([CH3:10])[CH3:9])([CH3:6])[CH3:5]>CCCCCC>[CH:4]([N:7]([SiH2:2][SiH3:3])[CH:8]([CH3:10])[CH3:9])([CH3:6])[CH3:5]
Reactant: [SiH3][SiH2]Cl
Reactant: CC(C)NC(C)C
Solvent: CCCCCC
Product: CC(C)N([SiH2][SiH3])C(C)C
Temperature: 25 °C

Procedure:
In a 3-necked round bottom flask equipped with a mechanic stirrer, a condenser, and an addition funnel, a solution of 1 equivalent monochlorodisilane in hexane was cooled to −10° C. with a cold bath. With stirring, 2 equivalent of di-iso-propylamine was added dropwise through the addition funnel. After the addition was completed, the reaction mixture was allowed to warm up to room temperature. The reaction mixture was stirred at room temperature for 2 hours, followed by filtration. A distillation removed solvent hexane from the filtrate. The product di-iso-propylaminodisilane was obtained by vacuum distillation. Gas chromatography (GC) showed that it was >99% pure di-iso-propylaminodisilane (DIPADS) (1H NMR (500 MHz, C7D8): δ=4.89 (m, SiH2), 3.31 (t, SiH3), 2.93 (m, CHMe2), 1.00 (d, CHMe2). FIG. 1 shows the TGA/DSC graph of di-iso-propylaminodisilane, wherein the TGA demonstrates that the compound is volatile and the DSC shows it has a boiling point of about 157° C.
Reaction SMILES: [NH2:1][CH:2]([C:9]1[C:14]([O:15][CH3:16])=[CH:13][CH:12]=[CH:11][C:10]=1[O:17][CH3:18])[CH2:3][CH2:4][C:5]([O:7]C)=O.[C:19]1([CH:29]=O)[C:28]2[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=2)[CH:22]=[CH:21][CH:20]=1>>[CH3:18][O:17][C:10]1[CH:11]=[CH:12][CH:13]=[C:14]([O:15][CH3:16])[C:9]=1[CH:2]1[N:1]([CH2:29][C:19]2[C:28]3[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=3)[CH:22]=[CH:21][CH:20]=2)[C:5](=[O:7])[CH2:4][CH2:3]1
Reactant: COC(=O)CCC(N)c1c(OC)cccc1OC
Reactant: O=Cc1cccc2ccccc12
Product: COc1cccc(OC)c1C1CCC(=O)N1Cc1cccc2ccccc12

Procedure:
Prepared according to the described general procedure 2 (GP2) by reaction of methyl 4-amino-4-(2,6-dimethoxyphenyl)butanoate with commercially available 1-naphthaldehyde. Subsequent purification by preparative HPLC afforded the target compound. LC-MS (conditions A): tR=0.87 min.; [M+H]+: 362.17 g/mol.
Reaction SMILES: [C:1]([CH:6]1[CH2:15][C:14](=[O:16])[C:13]2[C:8](=[C:9]([CH2:37][CH2:38][CH3:39])[C:10]([O:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][O:23][C:24]3[CH:29]=[CH:28][C:27]([C:30](=[O:32])[CH3:31])=[C:26]([OH:33])[C:25]=3[CH2:34][CH2:35][CH3:36])=[CH:11][CH:12]=2)[O:7]1)([O:3]CC)=[O:2].[OH-].[Na+]>C(O)C.O1CCCC1>[CH2:34]([C:25]1[C:26]([OH:33])=[C:27]([C:30](=[O:32])[CH3:31])[CH:28]=[CH:29][C:24]=1[O:23][CH2:22][CH2:21][CH2:20][CH2:19][CH2:18][O:17][C:10]1[C:9]([CH2:37][CH2:38][CH3:39])=[C:8]2[C:13]([C:14](=[O:16])[CH2:15][CH:6]([C:1]([OH:3])=[O:2])[O:7]2)=[CH:12][CH:11]=1)[CH2:35][CH3:36]
Reactant: CCCc1c(OCCCCCOc2ccc3c(c2CCC)OC(C(=O)OCC)CC3=O)ccc(C(C)=O)c1O
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CCO
Product: CCCc1c(OCCCCCOc2ccc3c(c2CCC)OC(C(=O)O)CC3=O)ccc(C(C)=O)c1O
Temperature: 5 °C
Reaction time: 8 h
Yield: 92.9 %

Procedure:
1.35 g (2.5 mmole) of the compound of Example 3 was dissolved in 50 ml of 50% ethanol-tetrahydrofuran in a 250 ml single neck round bottom flask equipped with a magnetic stirring bar. The contents of the flask were cooled to 5° C. in an ice bath and 25 ml of 0.2N sodium hydroxide solution was added. The reaction mixture was stirred at room temperature for eight hours. Most of the solvent was removed by rotoevaporation, 50 ml of water was added and the aqueous mixture acidified with dilute hydrochloric acid. The acidified solution was extracted three times with 150 ml portions of ethyl acetate and the combined extract washed once with brine. The ethyl acetate extract was dried over anhydrous magnesium sulfate, filtered, and the ethyl acetate removed by rotoevaporation to give 1.19 g (93%) of the title compound as a white solid, mp. 166°-168° C. Calc: C, 67.95; H, 7.08, Found: C, 67.79; H, 7.04.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:11])[C:4]1[CH:9]=[CH:8][C:7]([NH2:10])=[CH:6][CH:5]=1.S(OCC)(O[CH2:16][CH3:17])(=O)=O.C(N(C(C)C)CC)(C)C>O>[CH3:1][O:2][C:3](=[O:11])[C:4]1[CH:9]=[CH:8][C:7]([NH:10][CH2:16][CH3:17])=[CH:6][CH:5]=1
Reactant: CCOS(=O)(=O)OCC
Reactant: COC(=O)c1ccc(N)cc1
Solvent: CCN(C(C)C)C(C)C
Solvent: O
Product: CCNc1ccc(C(=O)OC)cc1
Temperature: 120 °C
Yield: 48.8 %

Procedure:
A mixture of 25.0 g (0.165 mol) 4-aminobenzoic acid methyl ester, 21.75 mL (0.165 mol) of diethyl sulfate and 30 mL (0.174 mol) of diisopropyl ethyl amine was heated to 120° C. for 1 hour. The reaction was exothermic and the temperature rose to 140° C. The mixture was allowed to cool down to room temperature and 100 mL of water was added. 4-(ethylamino)benzoic acid methyl ester crystallized over night, was isolated by filtration, washed 3 times with water and dried. The crude 4-(ethylamino)benzoic acid methyl ester was recrystallized from methanol. 14.44 g of 4-(ethylamino)benzoic acid methyl ester was isolated (m.p. 132-135° C.).
Reaction SMILES: [CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[CH2:11][O:12][CH:13]1[CH:18]([C:19]2[CH:20]=[N:21][C:22]([CH2:25][CH2:26][N:27]3[C:31]4[CH:32]=[CH:33][CH:34]=[CH:35][C:30]=4[S:29][C:28]3=[S:36])=[CH:23][CH:24]=2)[CH2:17][CH2:16][N:15](C(OC(C)(C)C)=O)[CH2:14]1>[Br-].[Zn+2].[Br-]>[CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[CH2:11][O:12][CH:13]1[CH:18]([C:19]2[CH:20]=[N:21][C:22]([CH2:25][CH2:26][N:27]3[C:31]4[CH:32]=[CH:33][CH:34]=[CH:35][C:30]=4[S:29][C:28]3=[S:36])=[CH:23][CH:24]=2)[CH2:17][CH2:16][NH:15][CH2:14]1
Reactant: CC(C)(C)OC(=O)N1CCC(c2ccc(CCn3c(=S)sc4ccccc43)nc2)C(OCc2ccc3ccccc3c2)C1
Agent: [Br-]
Agent: [Zn+2]
Product: S=c1sc2ccccc2n1CCc1ccc(C2CCNCC2OCc2ccc3ccccc3c2)cn1

Procedure:
In an analogous manner to that described in Example 125 (h), from tert-butyl (3'RS,4'RS)-3'-(naphthalen-2-ylmethoxy)-6-[2-(2-thioxo-benzothiazol-3-yl)-ethyl]-3',4',5',6'-tetrahydro-2'H-[3,4']bipyridine-1'-carboxylate by cleavage of the BOC group by means of anhydrous zinc bromide there was obtained 3-[2-[(3'RS,4'RS)-3'-(naphthalen-2-ylmethoxy)-1',2',3',4',5',6'-hexahydro-[3,4']bipyridin-6-yl]-ethyl]-3H-benzothiazole-2-thione in the form of an amorphous, colourless solid; MS: 512 (M+H)+.
Reaction SMILES: [CH3:1][N:2]1[CH:6]=[CH:5][CH:4]=[C:3]1[C:7]([CH:9]1[N:14]2[CH:15]=[C:16]([CH3:18])[CH:17]=[C:13]2[CH:12]([C:19]([O:21]C(C)C)=[O:20])[CH2:11][CH2:10]1)=[O:8].CO.C(=O)([O-])[O-].[K+].[K+]>O>[CH3:1][N:2]1[CH:6]=[CH:5][CH:4]=[C:3]1[C:7]([CH:9]1[N:14]2[CH:15]=[C:16]([CH3:18])[CH:17]=[C:13]2[CH:12]([C:19]([OH:21])=[O:20])[CH2:11][CH2:10]1)=[O:8]
Reactant: Cc1cc2n(c1)C(C(=O)c1cccn1C)CCC2C(=O)OC(C)C
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CO
Solvent: O
Product: Cc1cc2n(c1)C(C(=O)c1cccn1C)CCC2C(=O)O

Procedure:
A solution of 328 mg. of isopropyl 5-(N-methyl-2-pyrroyl)-2-methyl-5,6,7,8-tetrahydropyrrolo[1,2-a]pyridine-8-carboxylate in 5 ml. of methanol is treated with a solution of 0.28 g. of potassium carbonate in 5 ml. of water. The reaction mixture is refluxed under nitrogen atmosphere for 3 hours, cooled, and evaporated to dryness. The residue is taken up in 50 ml. of water, cooled to 0°, made acidic with 10% hydrochloric acid and the resultant mixture extracted with ethyl acetate (3×50 ml.). The combined extracts are dried over magnesium sulfate and evaporated to dryness under reduced pressure, to give 5-(N-methyl-2-pyrroyl)-2-methyl-5,6,7,8-tetrahydropyrrolo[1,2-a]pyridine-8-carboxylic acid (XIVa, R and Q=CH3, n-1).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:13]2[CH2:17][S:16][C:15](=S)[S:14]2)[CH:6]=[C:7]([O:11][CH3:12])[C:8]=1[O:9][CH3:10].[I:19][C:20]1[C:21]([OH:30])=[C:22]([O:28][CH3:29])[CH:23]=[C:24]([CH:27]=1)C=O.C1(C)C=CC(S([O-])(=O)=O)=CC=1.[NH+]1C=CC=CC=1.C1C=CC=CC=1>C1C=CC=CC=1.O>[OH:30][C:21]1[C:20]([I:19])=[CH:27][C:24]([C@H:15]2[S:14][C@H:13]([C:5]3[CH:6]=[C:7]([O:11][CH3:12])[C:8]([O:9][CH3:10])=[C:3]([O:2][CH3:1])[CH:4]=3)[CH2:17][S:16]2)=[CH:23][C:22]=1[O:28][CH3:29]
Reactant: COc1cc(C2CSC(=S)S2)cc(OC)c1OC
Reactant: COc1cc(C=O)cc(I)c1O
Agent: Cc1ccc(S(=O)(=O)[O-])cc1
Agent: c1cc[nH+]cc1
Solvent: O
Solvent: c1ccccc1
Product: COc1cc([C@@H]2SC[C@@H](c3cc(OC)c(OC)c(OC)c3)S2)cc(I)c1O

Procedure:
1-(3,4,5-trimethoxyphenyl)-1,2-ethanedithiol (32) (FIG. 26) (0.500 g, 1.92 mmole), 5-iodovanillin (0.411 g, 1.48 mmole), pyridinium para-toluenesulfonate (0.193 g, 0.769 mmole) and 50 ml dry benzene were refluxed under an argon atmosphere with Dean-Stark removal of the benzene-water azeotrope for 12 hours. The benzene was removed in vacuo, and the remaining oil redissolved in dichloromethane. The organic layer was washed with 3×30 ml H2O and was dried over MgSO4, and evaporated in vacuo to an oil which was purified by flash column chromatography with 2:1 hex/ethyl acetate as eluent. The product mixture contains a 1.0/1.3 cis/trans ratio (0.578 g, 75%) after one crystallization from methanol. The trans isomer (50 mg) was isolated after one additional crytallization from ethanol.
Reaction SMILES: O[CH:2]=[C:3]([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)[C:4]([O:6]CC)=O.[NH:15]([C:17]1[N:22]=[CH:21][CH:20]=[CH:19][N:18]=1)[NH2:16].[OH-].[Na+].Cl>C(O)C.O>[N:18]1[CH:19]=[CH:20][CH:21]=[N:22][C:17]=1[N:15]1[C:4](=[O:6])[C:3]([C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=2)=[CH:2][NH:16]1
Reactant: CCOC(=O)C(=CO)c1ccccc1
Reactant: NNc1ncccn1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Solvent: O
Product: O=c1c(-c2ccccc2)c[nH]n1-c1ncccn1
Temperature: 25 °C
Reaction time: 2 h
Yield: 63 %

Procedure:
19.2 g (0.1 mol) of ethyl α-hydroxymethylene-phenylacetate and 11 g (0.1 mol) of 2-hydrazino-pyrimidine in 150 ml of ethanol are boiled under reflux for 3 hours. The mixture is cooled to room temperature, and 9 g (0.1 mol) of concentrated sodium hydroxide solution are then added dropwise, while stirring. Stirring is then continued for 2 hours at room temperature, and the mixture is then boiled under reflux for 2 hours. The mixture is neutralized with concentrated hydrochloric acid, and diluted with 1 l of water. The precipitated crystals are filtered off under suction and dried in the air. 15 g (63% of theory) of 1-pyrimid-2-yl-4-phenyl-pyrazolin-5-one of melting point 159° to 160° C. (from ethanol) are obtained.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([CH:18]=[CH:19][CH:20]=1)[CH2:5][N:6]1[C:11]2[CH:12]=[CH:13][S:14][C:10]=2[C:9](=[O:15])[N:8]([OH:16])[C:7]1=[O:17].[NH2:21][C:22]([C:24]1[CH:29]=[CH:28][C:27](B(O)O)=[CH:26][CH:25]=1)=[O:23]>>[OH:16][N:8]1[C:9](=[O:15])[C:10]2[S:14][CH:13]=[CH:12][C:11]=2[N:6]([CH2:5][C:4]2[CH:3]=[C:2]([C:27]3[CH:28]=[CH:29][C:24]([C:22]([NH2:21])=[O:23])=[CH:25][CH:26]=3)[CH:20]=[CH:19][CH:18]=2)[C:7]1=[O:17]
Reactant: O=c1c2sccc2n(Cc2cccc(Br)c2)c(=O)n1O
Reactant: NC(=O)c1ccc(B(O)O)cc1
Product: NC(=O)c1ccc(-c2cccc(Cn3c(=O)n(O)c(=O)c4sccc43)c2)cc1

Procedure:
The title compound was prepared from 1-(3-Bromo-benzyl)-3-hydroxy-1H-thieno[3,2-d]pyrimidine-2,4-dione (from previous example) and 4-aminocarbonyl-phenyl boronic acid via general procedure C. The crude product was purified by mass-triggered preparative HPLC. 1H NMR (DMSO-d6) δ 10.87 (bs, 1H), 8.11 (d, 1H, J=5.4 Hz), 7.96 (d, 2H, J=8.4 Hz), 7.74 (s, 1H), 7.71 (d, 2H, J=7.8 Hz), 7.63 (d, 1H, J=7.8 Hz), 7.45 (t, 1H, J=7.8 Hz), 7.36 (d, 1H, J=5.4 Hz), 7.28 (d, 1H, J=7.5 Hz), 5.35 (s, 2H); Electrospray MS: 394 (M+H); retention time: 1.96 min.
Reaction SMILES: [CH2:1]([S:4]([C:6]1[C:7]([S:15]([NH:18]C(C)(C)C)(=[O:17])=[O:16])=[C:8]([C:11]([O:13][CH3:14])=[O:12])[S:9][CH:10]=1)=[O:5])[CH2:2][CH3:3].FC(F)(F)C(O)=O>C(Cl)Cl>[CH2:1]([S:4]([C:6]1[C:7]([S:15]([NH2:18])(=[O:17])=[O:16])=[C:8]([C:11]([O:13][CH3:14])=[O:12])[S:9][CH:10]=1)=[O:5])[CH2:2][CH3:3]
Reactant: CCCS(=O)c1csc(C(=O)OC)c1S(=O)(=O)NC(C)(C)C
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: CCCS(=O)c1csc(C(=O)OC)c1S(N)(=O)=O
Yield: 93.3 %

Procedure:
A solution of 2.2 g of 4-propylsulfinyl-3-(N-(1,1-dimethylethyl)aminosulfonyl)-2-thiophenecarboxylic acid, methyl ester in 15 mL methylene chloride was treated with 30 mL trifluoroacetic acid at room temperature for 24 hours. The solvent were removed in vacuo and the residue was crystallized with butyl chloride to give 1.74 g white solid; m.p. 131°-144° C.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([CH:14]2[O:23][C:17]3=[CH:18][N:19]=[C:20](Cl)[CH:21]=[C:16]3[CH2:15]2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:24][C:25]1[C:29](B(O)O)=[C:28]([CH3:33])[O:27][N:26]=1>>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([CH:14]2[O:23][C:17]3=[CH:18][N:19]=[C:20]([C:29]4[C:25]([CH3:24])=[N:26][O:27][C:28]=4[CH3:33])[CH:21]=[C:16]3[CH2:15]2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(C)(C)OC(=O)N1CCC(C2Cc3cc(Cl)ncc3O2)CC1
Reactant: Cc1noc(C)c1B(O)O
Product: Cc1noc(C)c1-c1cc2c(cn1)OC(C1CCN(C(=O)OC(C)(C)C)CC1)C2

Procedure:
The title compound is prepared from 4-(5-chloro-2,3-dihydro-furo[2,3-c]pyridin-2-yl)-piperidine-1-carboxylic acid tert-butyl ester and 3,5-dimethyl-isoxazol-4-boronic acid following a procedure analogous to that described in Example 28. LC (method 7): tR=1.33 min; Mass spectrum (ESI+): m/z=400 [M+H]+.
Reaction SMILES: C(=O)([O-])[O-].[K+].[K+].[CH2:7]([N:14]1[CH:18]=[C:17]([C:19]2[C:27]3[C:22](=[N:23][CH:24]=[CH:25][N:26]=3)[N:21](C(OC(C)(C)C)=O)[CH:20]=2)[N:16]=[N:15]1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1>CO>[CH2:7]([N:14]1[CH:18]=[C:17]([C:19]2[C:27]3[C:22](=[N:23][CH:24]=[CH:25][N:26]=3)[NH:21][CH:20]=2)[N:16]=[N:15]1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1
Reactant: CC(C)(C)OC(=O)n1cc(-c2cn(Cc3ccccc3)nn2)c2nccnc21
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CO
Product: c1ccc(Cn2cc(-c3c[nH]c4nccnc34)nn2)cc1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
1.4 141 mg (1.00 mmol) of potassium carbonate are added to a solution of 152 mg (0.40 mmol) of tert-butyl 7-(1-benzyltriazol-4-yl)pyrrolo[2,3-b]-pyrazine-5-carboxylate in 2 ml of methanol, and the mixture is stirred at room temperature for 1 hour. The reaction mixture is adsorbed onto kieselguhr and chromatographed on a silica-gel column with dichloromethane/methanol/ammonia water as eluent: 7-(1-benzyl-1H-1,2,3-triazol-4-yl)-5H-pyrrolo-[2,3-b]pyrazine (“A1”) as colourless crystals;
Reaction SMILES: [NH2:1][C:2]1[NH:6][N:5]=[C:4]([SH:7])[N:3]=1.[C:8](Cl)(=[O:15])[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1>N1C=CC=CC=1>[C:8]([NH:1][C:2]1[NH:6][N:5]=[C:4]([SH:7])[N:3]=1)(=[O:15])[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1
Reactant: O=C(Cl)c1ccccc1
Reactant: Nc1nc(S)n[nH]1
Solvent: c1ccncc1
Product: O=C(Nc1nc(S)n[nH]1)c1ccccc1
Reaction time: 0.42 h

Procedure:
To a suitably equipped reaction vessel was charged 116 g (1.0 mole) of 5-amino-3-mercapto-1,2,4-triazole and 500 ml of pyridine. A total of 147.5 g (1.05 mole) of benzoyl chloride was added with vigorous stirring over 25 minutes, during which time the temperature rose from 24° to 59° C. The mobile, pale yellow slurry obtained was heated at reflux with stirring. The solid material dissolved and then, after about 40 additional minutes, a white solid began separating. An additional 200 ml of pyridine was added to aid mixing and the reaction was continued at 117°-122° for a total of 7 hours. The thick, white slurry obtained was filtered, washed with water and with methylene chloride, and dried to obtain 186 g (84 percent of theory) of the title compound, m.p. 311°-312° (dec.).
Reaction SMILES: [Br:1][CH2:2][C:3]1[CH:11]=[CH:10][CH:9]=[C:8]([CH3:12])[C:4]=1[C:5](Br)=[O:6].[CH3:13][OH:14]>CCCCCCC>[Br:1][CH2:2][C:3]1[CH:11]=[CH:10][CH:9]=[C:8]([CH3:12])[C:4]=1[C:5]([O:14][CH3:13])=[O:6]
Reactant: Cc1cccc(CBr)c1C(=O)Br
Reactant: CO
Solvent: CCCCCCC
Product: COC(=O)c1c(C)cccc1CBr
Temperature: 25 °C
Reaction time: 1 h
Yield: 98.8 %

Procedure:
200 g (240 mmol) of 2-bromomethyl-6-methylbenzoyl bromide solution (35% solution in heptane) are added to 400 ml of methanol. After stirring at RT for one hour, 400 ml of n-heptane are added. The solution is washed successively with 600 ml of sat. sodium hydrogencarbonate solution and three times with 200 ml each time of water. Subsequently, the solvent is removed fully under reduced pressure. 98.8% of methyl 2-bromomethyl-6-methylbenzoate is obtained as a colorless oil having a purity of 80% (included in the yield) and having a molecular weight of 241.99 (C10H11BrO2); MS (ESI): 243.1 [M+H+].
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[C:7](OS(C(F)(F)F)(=O)=O)=[N:8][C:9]2[C:14]([C:15]=1[CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1[Cl:23])=[CH:13][C:12]([Cl:24])=[CH:11][C:10]=2[C:25]([F:28])([F:27])[F:26])=[O:5])[CH3:2].[CH3:37][NH:38][CH3:39]>>[CH2:1]([O:3][C:4]([C:6]1[C:7]([N:38]([CH3:39])[CH3:37])=[N:8][C:9]2[C:14]([C:15]=1[CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1[Cl:23])=[CH:13][C:12]([Cl:24])=[CH:11][C:10]=2[C:25]([F:27])([F:26])[F:28])=[O:5])[CH3:2]
Reactant: CCOC(=O)c1c(OS(=O)(=O)C(F)(F)F)nc2c(C(F)(F)F)cc(Cl)cc2c1Cc1ccccc1Cl
Reactant: CNC
Product: CCOC(=O)c1c(N(C)C)nc2c(C(F)(F)F)cc(Cl)cc2c1Cc1ccccc1Cl

Procedure:
The title compound was prepared in analogy to example 29 step D from 6-chloro-4-(2-chloro-benzyl)-2-trifluoromethanesulfonyloxy-8-trifluoromethyl-quinoline-3-carboxylic acid ethyl ester (80 mg, 0.14 mmol) and dimethylamine (3 ml, 2M solution in THF). Off white solid (45 mg, 69%). LC-MS (ESI): 471 (M+H)+
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:17])[CH:5]([NH:14][CH:15]=[O:16])[CH:6](O)[C:7](=[CH2:12])[CH2:8][CH2:9][O:10][CH3:11])[CH3:2].S(Br)([Br:20])=O.O>ClCCCl>[CH2:1]([O:3][C:4](=[O:17])[CH:5]([NH:14][CH:15]=[O:16])[CH:6]=[C:7]([CH2:12][Br:20])[CH2:8][CH2:9][O:10][CH3:11])[CH3:2]
Reactant: C=C(CCOC)C(O)C(NC=O)C(=O)OCC
Reactant: O=S(Br)Br
Solvent: ClCCCl
Solvent: O
Product: CCOC(=O)C(C=C(CBr)CCOC)NC=O
Reaction time: 0.75 h

Procedure:
19.0 g (77.5 mmol) of 2-formylamino-3-hydroxy-6-methoxy-4-methylene-hexanoic acid ethyl ester are dissolved in 190 ml of 1,2-dichloroethane, and 7.20 ml (93.0 mmol) of thionyl bromide are added dropwise at room temperature. After 45 minutes, 100 ml of water are added and the mixture is stirred vigorously for 10 minutes. The organic phase is separated off, washed in succession with water, 1N potassium hydrogen carbonate solution and again with water, dried over sodium sulfate, filtered and concentrated by evaporation. 4-bromomethyl-2-formylamino-6-methoxy-hex-3-enoic acid ethyl ester is obtained in the form of a reddish-brown oil.