Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br[C:2]1[CH:3]=[CH:4][C:5]2[N:11]([CH:12]=[O:13])[CH2:10][CH2:9][C:8]([C:14]([O:16][CH3:17])=[O:15])=[CH:7][C:6]=2[CH:18]=1.B([O-])([O-])O[C:21]1[CH:26]=[CH:25][C:24]([N:27]([CH2:30][CH2:31][O:32][CH2:33][CH3:34])[CH2:28][CH3:29])=[CH:23][CH:22]=1.C(=O)([O-])[O-].[K+].[K+].C(O)C>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1(C)C=CC=CC=1>[CH2:33]([O:32][CH2:31][CH2:30][N:27]([C:24]1[CH:23]=[CH:22][C:21]([C:2]2[CH:3]=[CH:4][C:5]3[N:11]([CH:12]=[O:13])[CH2:10][CH2:9][C:8]([C:14]([O:16][CH3:17])=[O:15])=[CH:7][C:6]=3[CH:18]=2)=[CH:26][CH:25]=1)[CH2:28][CH3:29])[CH3:34]
Reactant: CCOCCN(CC)c1ccc(OB([O-])[O-])cc1
Reactant: COC(=O)C1=Cc2cc(Br)ccc2N(C=O)CC1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCO
Solvent: Cc1ccccc1
Product: CCOCCN(CC)c1ccc(-c2ccc3c(c2)C=C(C(=O)OC)CCN3C=O)cc1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 84.4 %

Procedure:
A mixture of methyl 7-bromo-1-formyl-2,3-dihydro-1H-1-benzazepine-4-carboxylate (0.2 g), 4-[N-(2-ethoxyethyl)-N-ethylamino]phenyl borate (0.46 g), 1M potassium carbonate solution (3.2 ml), ethanol (3.2 ml) and toluene (25 ml) was stirred under argon atmosphere at room temperature for 30 minutes. To the mixture was added tetrakis(triphenylphosphine)palladium (0.03 g), and the mixture was refluxed overnight under argon atmosphere and extracted with ethyl acetate. The organic layer was washed with water and saturated brine and dried with anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified with silica gel column chromatography (ethyl acetate/hexane) to give methyl 7-[4-[N-(2-ethoxyethyl)-N-ethylamino]phenyl]-1-formyl-2,3-dihydro-1H-1-benzazepine-4-carboxylate (0.23 g) as green amorphous.
Reaction SMILES: [CH3:1][O:2][CH2:3][CH2:4][O:5][C:6]1[CH:11]=[C:10]([CH3:12])[CH:9]=[CH:8][C:7]=1[NH:13][C:14]1[O:15][CH2:16][C:17](=[O:24])[C:18]=1[C:19]([O:21][CH2:22][CH3:23])=[O:20].[NH:25]1[C:33]2[C:28](=[CH:29][CH:30]=[CH:31][N:32]=2)[C:27]([CH:34]=O)=[CH:26]1>C(O)C.Cl>[NH:25]1[C:33]2=[N:32][CH:31]=[CH:30][CH:29]=[C:28]2[C:27]([CH:34]=[C:16]2[O:15][C:14]([NH:13][C:7]3[CH:8]=[CH:9][C:10]([CH3:12])=[CH:11][C:6]=3[O:5][CH2:4][CH2:3][O:2][CH3:1])=[C:18]([C:19]([O:21][CH2:22][CH3:23])=[O:20])[C:17]2=[O:24])=[CH:26]1
Reactant: CCOC(=O)C1=C(Nc2ccc(C)cc2OCCOC)OCC1=O
Reactant: O=Cc1c[nH]c2ncccc12
Agent: Cl
Solvent: CCO
Product: CCOC(=O)C1=C(Nc2ccc(C)cc2OCCOC)OC(=Cc2c[nH]c3ncccc23)C1=O
Temperature: 25 °C
Yield: 43.2 %

Procedure:
To a solution of ethyl 2-{[2-(2-methoxyethoxy)-4-methylphenyl]amino}-4-oxo-4,5-dihydrofuran-3-carboxylate (0.015 g, 0.045 mmol) which similarly prepared according to the procedure described in the Example 29, First step and 7-azaindole-3-carboxaldehyde (0.0067 g, 0.046 mmol) in ethanol (0.2 mL), 2M hydrochloric acid in ethanol (0.023 mL, 0.045 mmol) was added at ambient temperature. The mixture was refluxed for 4 h. Cooled to ambient temperature, the solvent was removed under reduced pressure. The residue was purified by preparative HPLC to afford the titled compound as solid (0.0090 g, y. 43%).
Reaction SMILES: [NH2:1][N:2]1[CH2:6][C:5](=[O:7])[NH:4][C:3]1=[O:8].[C:9](Cl)([Cl:11])=[O:10]>O1CCCC1>[Cl:11][C:9]([NH:1][N:2]1[CH2:6][C:5](=[O:7])[NH:4][C:3]1=[O:8])=[O:10]
Reactant: NN1CC(=O)NC1=O
Reactant: O=C(Cl)Cl
Solvent: C1CCOC1
Product: O=C(Cl)NN1CC(=O)NC1=O
Temperature: 25 °C
Reaction time: 3 h

Procedure:
11.5 g. (0.1 mol.) of 1-amino-2,4-dioxoimidazolidine are thoroughly stirred into 150 ml. of absolute tetrahydrofuran. A solution of 15 g. (0.15 mol.) of phosgene in 25 ml. of absolute tetrahydrofuran is added dropwise at 0°-5° over 20 minutes. The mixture is then stirred for 3 hours at room temperature. An almost clear solution results. This is filtered and the solvent is evaporated in vacuum. The oily residue crystallizes on trituration with petroleum ether to obtain 1-(chlorocarbonylamino)-2,4-dioxoimidazolidine, yield 17.2 g., m.p. 126° (dec.).
Reaction SMILES: [N:1]1[C:10]2[C:5](=[CH:6][C:7]([CH2:11][C:12]3[N:16]4[N:17]=[C:18]([C:21](=O)[CH3:22])[CH:19]=[CH:20][C:15]4=[N:14][N:13]=3)=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1.Cl.[NH2:25][O:26][CH:27]([CH3:30])[CH2:28][OH:29]>CO>[OH:29][CH2:28][CH:27]([O:26]/[N:25]=[C:21](/[C:18]1[CH:19]=[CH:20][C:15]2[N:16]([C:12]([CH2:11][C:7]3[CH:6]=[C:5]4[C:10](=[CH:9][CH:8]=3)[N:1]=[CH:2][CH:3]=[CH:4]4)=[N:13][N:14]=2)[N:17]=1)\[CH3:22])[CH3:30]
Reactant: CC(CO)ON
Reactant: CC(=O)c1ccc2nnc(Cc3ccc4ncccc4c3)n2n1
Agent: Cl
Solvent: CO
Product: C/C(=N\OC(C)CO)c1ccc2nnc(Cc3ccc4ncccc4c3)n2n1
Yield: 44.3 %

Procedure:
A solution of 1-(3-(quinolin-6-ylmethyl)-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)ethanone (41.2) (40 mg, 0.132 mmol) and 2-(aminooxy)propan-1-ol (intermediate Q) (33.6 mg, 0.264 mmol) in 15 mL of MeOH was stirred at it overnight. Solvent was evaporated and the crude was purified by HPLC (basic with 0.05% NH4OH) to give 22 mg (44%) of the title compound as a white solid. 1H-NMR (400 MHz, MeOH-d4 δ ppm 8.82 (s, 1H), 8.33 (d, 1H), 8.12 (d, 1H), 7.98 (t, 3H), 7.84 (d, 1H), 7.55 (m, 1H), 4.84 (s, 2H), 4.50 (m, 1H), 3.72 (d, 2H), 2.32 (s, 3H), 1.33 (d, 3H). LC-MS (method B): [MH]+=377.0, tR=1.867 min.
Reaction SMILES: [CH2:1]([N:8]1[C:16]2[C:11](=[CH:12][C:13]([OH:17])=[CH:14][CH:15]=2)[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:18]1[O:26][C:25]2[CH:24]=[CH:23][C:22]([N:27]=[C:28]=[O:29])=[CH:21][C:20]=2[O:19]1>>[O:26]1[C:25]2[CH:24]=[CH:23][C:22]([NH:27][C:28](=[O:29])[O:17][C:13]3[CH:12]=[C:11]4[C:16](=[CH:15][CH:14]=3)[N:8]([CH2:1][C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=3)[CH2:9][CH2:10]4)=[CH:21][C:20]=2[O:19][CH2:18]1
Reactant: Oc1ccc2c(c1)CCN2Cc1ccccc1
Reactant: O=C=Nc1ccc2c(c1)OCO2
Product: O=C(Nc1ccc2c(c1)OCO2)Oc1ccc2c(c1)CCN2Cc1ccccc1

Procedure:
The title compound was synthesized from 1-benzylindolin-5-ol (35.0 mg, 0.155 mmol) using the same procedure employed for Example 2 (2), but with 3,4-(methylenedioxy)phenylisocyanate instead of 4-isopropylphenylisocyanate. The product was obtained as a white solid (21.6 mg, 34%) having the following characteristics.
Reaction SMILES: O=[O+][O-].[Na].[CH3:5][O:6][C:7](=[O:27])[CH:8]([C:24](=O)[CH3:25])[CH:9]([C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)[C:10](=[N+:15](O)[O-])[C:11]([O:13][CH3:14])=[O:12].O.[NH2:29]N>CO>[CH3:14][O:13][C:11]([C:10]1[CH:9]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[C:8]([C:7]([O:6][CH3:5])=[O:27])=[C:24]([CH3:25])[NH:29][N:15]=1)=[O:12]
Reactant: COC(=O)C(C(c1ccccc1)C(C(C)=O)C(=O)OC)=[N+]([O-])O
Reactant: NN
Agent: O=[O+][O-]
Agent: [Na]
Solvent: O
Solvent: CO
Product: COC(=O)C1=NNC(C)=C(C(=O)OC)C1c1ccccc1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
Dry ozone is passed, in excess, into a solution of 69.0 g (0.2 mol) of the sodium salt of 2-acetyl-4-aci-nitro-3-phenyl-glutaric acid dimethyl ester in 300 ml of absolute methanol at -78° C. until the solution becomes blue-coloured. After 30 minutes, the ozone is removed by passing dry nitrogen in and the mixture is warmed to -20°, under nitrogen. 10 g (0.2 mol) of hydrazine hydrate in 50 ml of absolute methanol are added dropwise and the mixture is stirred at room temperature for 12 hours. For working up, the methanol is distilled off in vacuo, the residue is taken up in chloroform and insoluble material is filtered off. The chloroform is distilled off from the filtrate and, after adding a little isopropanol to the residue, the product slowly crystallises out. Melting point: 187°.
Reaction SMILES: [NH2:1][C:2]1[CH:11]=[CH:10][C:5]2[NH:6][C:7](=[O:9])[O:8][C:4]=2[CH:3]=1.[IH:12].CS[C:15]1[NH:16][CH2:17][CH2:18][N:19]=1.CS.C(OCC)C>N1C=CC=CC=1>[IH:12].[NH:16]1[CH2:17][CH2:18][NH:19][C:15]1=[N:1][C:2]1[CH:11]=[CH:10][C:5]2[NH:6][C:7](=[O:9])[O:8][C:4]=2[CH:3]=1
Reactant: CSC1=NCCN1
Reactant: Nc1ccc2[nH]c(=O)oc2c1
Agent: CS
Agent: I
Solvent: c1ccncc1
Solvent: CCOCC
Product: O=c1[nH]c2ccc(N=C3NCCN3)cc2o1

Procedure:
13 g (86.7 millimols) of the compound obtained in step 3 and 22.2 g of 2-methylthio-2-imidazoline hydroiodide are heated to the reflux temperature in 100 cc of pyridine. The reflux is maintained until the evolution of methanethiol has ceased (about 2-3 hours). When the reaction has ended, the cooled mixture is poured into 1.5 liters of diethyl ether. The gummy residue is washed 3 times with 300 cc of diethyl ether and taken up in 100 cc of ethanol. The product is filtered off and recrystallised from methanol. Its melting point is 270°-272° C.
Reaction SMILES: Br[CH2:2][C:3]([C:5]1[C:10]([CH3:11])=[CH:9][C:8]([O:12][CH2:13][CH:14]([OH:17])[CH2:15][OH:16])=[CH:7][C:6]=1[CH3:18])=O.[NH2:19][C:20]([NH2:22])=[S:21]>CCO>[NH2:22][C:20]1[S:21][CH:2]=[C:3]([C:5]2[C:10]([CH3:11])=[CH:9][C:8]([O:12][CH2:13][CH:14]([OH:17])[CH2:15][OH:16])=[CH:7][C:6]=2[CH3:18])[N:19]=1
Reactant: NC(N)=S
Reactant: Cc1cc(OCC(O)CO)cc(C)c1C(=O)CBr
Solvent: CCO
Product: Cc1cc(OCC(O)CO)cc(C)c1-c1csc(N)n1
Yield: 104.3 %

Procedure:
A reaction mixture containing 2-bromo-1-(4-(2,3-dihydroxypropoxy)-2,6-dimethylphenyl)ethanone (741.9 mg, 2.3 mmol, 1.0 equiv) and thiourea (178.1 mg, 2.3 mmol, 1.0 equiv) in EtOH (10.0 mL) was heated at reflux for 16 h. The solution was concentrated under reduced pressure, and the residue was re-dissolved in EtOAc (30 mL). The solution was washed with saturated aqueous NaHCO3 (30 mL), dried over MgSO4, and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (30.0% EtOAc in hexanes as eluant) to provide 3-(4-(2-aminothiazol-4-yl)-3,5-dimethylphenoxy)propane-1,2-diol (694.1 mg, 2.4 mmol) as yellow solids in >99% yield: 1H NMR (CDCl3, 500 MHz) δ 6.76 (s, 2 H), 5.31-5.32 (m, 1 H), 3.99-4.00 (m, 1 H), 3.79-3.87 (m, 1 H), 3.78-3.79 (m, 1 H), 3.43-3.44 (m, 2 H), 3.37 (brs, 2 H), 2.15 (s, 6 H); ESI-MS: m/z 295.6 (M+H)+.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][S:10]([NH:13][C:14]2[CH:19]=[CH:18][C:17]([CH2:20][OH:21])=[CH:16][C:15]=2[S:22]([NH2:25])(=[O:24])=[O:23])(=[O:12])=[O:11])=[CH:4][CH:3]=1.[CH3:26][C:27]([CH3:31])([CH3:30])[C:28]#[CH:29]>>[CH3:26][C:27]([CH3:31])([CH3:30])[C:28]#[C:29][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][S:10]([NH:13][C:14]2[CH:19]=[CH:18][C:17]([CH2:20][OH:21])=[CH:16][C:15]=2[S:22]([NH2:25])(=[O:24])=[O:23])(=[O:12])=[O:11])=[CH:4][CH:3]=1
Reactant: C#CC(C)(C)C
Reactant: NS(=O)(=O)c1cc(CO)ccc1NS(=O)(=O)CCc1ccc(Br)cc1
Product: CC(C)(C)C#Cc1ccc(CCS(=O)(=O)Nc2ccc(CO)cc2S(N)(=O)=O)cc1
Yield: 5 %

Procedure:
The title compound was synthesized as described for Example 210 in 5% yield, starting from 2-[2-(4-bromo-phenyl)-ethanesulfonylamino]-5-hydroxymethyl-benzenesulfonamide and 3,3-dimethyl-1-butyne. Purification by preparative HPLC.
Reaction SMILES: [C:1]([C:3]1[CH:11]=[CH:10][C:6]([C:7]([OH:9])=[O:8])=[CH:5][CH:4]=1)#[CH:2].[CH2:12]([SnH:16]([CH2:21][CH2:22][CH2:23][CH3:24])[CH2:17][CH2:18][CH2:19][CH3:20])[CH2:13][CH2:14][CH3:15]>>[CH2:21]([Sn:16]([CH2:12][CH2:13][CH2:14][CH3:15])([CH2:17][CH2:18][CH2:19][CH3:20])[CH:2]=[CH:1][C:3]1[CH:11]=[CH:10][C:6]([C:7]([O:9][Sn:16]([CH2:17][CH2:18][CH2:19][CH3:20])([CH2:21][CH2:22][CH2:23][CH3:24])[CH2:12][CH2:13][CH2:14][CH3:15])=[O:8])=[CH:5][CH:4]=1)[CH2:22][CH2:23][CH3:24]
Reactant: C#Cc1ccc(C(=O)O)cc1
Reactant: CCCC[SnH](CCCC)CCCC
Product: CCCC[Sn](C=Cc1ccc(C(=O)O[Sn](CCCC)(CCCC)CCCC)cc1)(CCCC)CCCC
Temperature: 60 °C

Procedure:
A mixture of 4-ethynylbenzoic acid (1.0 equiv.) and tri-n-butyltinhydride (1.0 equiv.) (Aldrich) is warmed to 60° C. for six hours. Kugelrohr distillation of the crude product gives tri-n-butylstannyl 4-[2'-(tri-n-butylstannyl)ethenyl]benzoate.
Reaction SMILES: B(Br)(Br)Br.C[O:6][C:7]1[CH:8]=[C:9]([CH2:13][C:14]#[N:15])[CH:10]=[CH:11][CH:12]=1.C([O-])(O)=O.[Na+]>ClCCl>[OH:6][C:7]1[CH:8]=[C:9]([CH2:13][C:14]#[N:15])[CH:10]=[CH:11][CH:12]=1
Reactant: COc1cccc(CC#N)c1
Agent: BrB(Br)Br
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Product: N#CCc1cccc(O)c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 91.2 %

Procedure:
Boron tribromide (68 ml, 1M in dichloromethane, 68 mmol) was added dropwise to an ice-cooled solution of (3-methoxyphenyl)acetonitrile (5.0 g, 34 mmol) in dichloromethane (50 ml), and once addition was complete, the reaction was allowed to warm to room temperature and stirred overnight. The reaction was poured into an ice/water solution, the mixture was basified using NaHCO3 and extracted with dichloromethane. The combined organic extracts were dried over MgSO4 and evaporated under reduced pressure to give the desired product as a brown oil, (4.13 g, 91%).
Reaction SMILES: CNC.BrC1SC=C(CCl)N=1.Br[C:13]1[S:14][CH:15]=[C:16]([CH2:18][N:19]([CH3:21])[CH3:20])[N:17]=1.[CH2:22]=[O:23]>C(O)C>[CH3:20][N:19]([CH2:18][C:16]1[N:17]=[C:13]([CH2:22][OH:23])[S:14][CH:15]=1)[CH3:21]
Reactant: C=O
Reactant: CN(C)Cc1csc(Br)n1
Agent: CNC
Agent: ClCc1csc(Br)n1
Solvent: CCO
Product: CN(C)Cc1csc(CO)n1

Procedure:
An ethanol solution of dimethylamine is reacted with 2-bromo-4-chloromethylthiazole, prepared according to reference (4) above, and the resultant 2-bromo-4-dimethylaminomethylthiazole is treated with a strong base and formaldehyde according to the general procedure described in Acta. Chem. Scand., 20, 2649 (1966), to give the desired 4-dimethylaminomethyl-2-hydroxymethylthiazole.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[C:9]1[C:13]([C:14](O)=[O:15])=[C:12]([C:17]2[CH:18]=[N:19][N:20]([C:26]3[CH:31]=[CH:30][CH:29]=[C:28]([Cl:32])[CH:27]=3)[C:21]=2[C:22]([F:25])([F:24])[F:23])[O:11][N:10]=1.[Cl-].[NH4+].CC([N:38](C)C)=O.CCN(C(C)C)C(C)C>C(OC(=O)C)C>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[C:9]1[C:13]([C:14]([NH2:38])=[O:15])=[C:12]([C:17]2[CH:18]=[N:19][N:20]([C:26]3[CH:31]=[CH:30][CH:29]=[C:28]([Cl:32])[CH:27]=3)[C:21]=2[C:22]([F:23])([F:25])[F:24])[O:11][N:10]=1
Reactant: O=C(O)c1c(-c2c(F)cccc2Cl)noc1-c1cnn(-c2cccc(Cl)c2)c1C(F)(F)F
Reactant: CC(=O)N(C)C
Agent: [Cl-]
Agent: [NH4+]
Solvent: CCN(C(C)C)C(C)C
Solvent: CCOC(C)=O
Product: NC(=O)c1c(-c2c(F)cccc2Cl)noc1-c1cnn(-c2cccc(Cl)c2)c1C(F)(F)F
Temperature: 25 °C
Reaction time: 3 h
Yield: 89.7 %

Procedure:
Saponification of the ester of example 11 was achieved following the description for example 19, first step, to give 3-(2-chloro-6-fluorophenyl)-5-(1-(3-chlorophenyl)-5-(trifluoromethyl)-1H-pyrazol-4-yl)isoxazole-4-carboxylic acid in 89% yield. To a solution of 6.0 g (12.34 mmol) 3-(2-chloro-6-fluorophenyl)-5-(1-(3-chlorophenyl)-5-(trifluoromethyl)-1H-pyrazol-4-yl)isoxazole-4-carboxylic acid and 1.98 g (37.021 mmol) ammoniumchlorid in 20 mL dry DMA 9.36 g (24.681 mmol) HBTU and 6.45 mL (37.021 mmol) DIPEA were added. The mixture was stirred 3 hours at r.t. Ethylacetate was added to the reaction mixture and it was washed twice with sodium hydrogen carbonate (5%, aq) and citric acid (5%, aq). The organic layer was dried over anhydrous magnesium sulfate and the solvent was removed in the vacuum. The oily residue became solid by drying in the vacuum. The solid was washed with petroleum ether, filtrated and dried in the vacuum to yield 5.37 g (90%) of example 121. Result of LC/MS MH+: 484.83; 1H NMR (DMSO-d6; CCl4): 7.39-7.78 (7H, m, CH-arom./2H NH2), 8.43 (1H, s, CH-pyraz.)
Reaction SMILES: Cl[C:2]1[N:24]=[C:5]2[C:6]([NH:10][CH2:11][C:12]3[C:13]([N:18]([CH3:23])[S:19]([CH3:22])(=[O:21])=[O:20])=[N:14][CH:15]=[CH:16][CH:17]=3)=[CH:7][CH:8]=[CH:9][N:4]2[N:3]=1.[CH3:25][S:26]([C:29]1[CH:30]=[C:31]([NH2:35])[CH:32]=[CH:33][CH:34]=1)(=[O:28])=[O:27]>>[CH3:25][S:26]([C:29]1[CH:30]=[C:31]([NH:35][C:2]2[N:24]=[C:5]3[C:6]([NH:10][CH2:11][C:12]4[C:13]([N:18]([CH3:23])[S:19]([CH3:22])(=[O:21])=[O:20])=[N:14][CH:15]=[CH:16][CH:17]=4)=[CH:7][CH:8]=[CH:9][N:4]3[N:3]=2)[CH:32]=[CH:33][CH:34]=1)(=[O:27])=[O:28]
Reactant: CS(=O)(=O)c1cccc(N)c1
Reactant: CN(c1ncccc1CNc1cccn2nc(Cl)nc12)S(C)(=O)=O
Product: CN(c1ncccc1CNc1cccn2nc(Nc3cccc(S(C)(=O)=O)c3)nc12)S(C)(=O)=O

Procedure:
N-(3-{[2-(3-Methanesulfonyl-phenylamino)-[1,2,4]triazolo[1,5-a]pyridin-8-ylamino]-methyl}-pyridin-2-yl)-N-methyl-methanesulfonamide was prepared from N-{3-[(2-chloro-[1,2,4]triazolo[1,5-a]pyridin-8-ylamino)-methyl]-pyridin-2-yl}-N-methyl-methanesulfonamide (75.0 mg, 0.204 mmol) and 3-methanesulfonyl-phenylamine;
Reaction SMILES: [C:1]([NH:5][C:6]([C:8]1[C:16]2[C:11](=[N:12][CH:13]=[C:14]([N:17]3[C:25]4[C:20](=[CH:21][C:22]([Cl:26])=[CH:23][CH:24]=4)[CH:19]=[N:18]3)[N:15]=2)[N:10](COCC[Si](C)(C)C)[CH:9]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].FC(F)(F)C(O)=O>ClCCl>[C:1]([NH:5][C:6]([C:8]1[C:16]2[C:11](=[N:12][CH:13]=[C:14]([N:17]3[C:25]4[C:20](=[CH:21][C:22]([Cl:26])=[CH:23][CH:24]=4)[CH:19]=[N:18]3)[N:15]=2)[NH:10][CH:9]=1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)NC(=O)c1cn(COCC[Si](C)(C)C)c2ncc(-n3ncc4cc(Cl)ccc43)nc12
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: CC(C)(C)NC(=O)c1c[nH]c2ncc(-n3ncc4cc(Cl)ccc43)nc12
Reaction time: 15 h
Yield: 38.4 %

Procedure:
To a stirred solution of N-tert-butyl-2-(5-chloro-1H-indazol-1-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (144 mg, 289 μmol) in dichloromethane (3 mL) was added trifluoroacetic acid (1 mL). After 15 h then mixture was concentrated in vacuo then 25 mL Jan. 10, 1960 of a mixture of ammonium hydroxide/methanol/dichloromethane added. After 1 h the mixture was concentrated in vacuo. Purification by chromatography (silica, 24 g Analogix column, 0-5% of a solution of methanol containing 10% ammonium hydroxide in dichloromethane) gave 2-(5-chloro-indazol-1-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamide (40.9 mg, 38%). MS (M+H)+=369; 1H NMR (DMSO-d6) δ: 9.02 (s, 1H), 8.60 (s, 1H), 8.57 (s, 1H), 8.53 (s, 1H), 8.43 (s, 1H), 8.09 (s, 1H), 7.61 (s, 1H), 1.50 (s, 9H).
Reaction SMILES: [CH3:1][S:2][CH:3]([C:8]1[CH:13]=[CH:12][C:11]([N:14]2[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]2)=[C:10]([Cl:20])[CH:9]=1)[C:4]([O:6][CH3:7])=[O:5].[H-].[Na+].[CH3:23]I.[Cl-].[NH4+]>CN(C)C=O>[CH3:1][S:2][C:3]([C:8]1[CH:13]=[CH:12][C:11]([N:14]2[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]2)=[C:10]([Cl:20])[CH:9]=1)([CH3:23])[C:4]([O:6][CH3:7])=[O:5]
Reactant: COC(=O)C(SC)c1ccc(N2CCCCC2)c(Cl)c1
Reactant: CI
Agent: [Cl-]
Agent: [H-]
Agent: [NH4+]
Solvent: CN(C)C=O
Product: COC(=O)C(C)(SC)c1ccc(N2CCCCC2)c(Cl)c1
Reaction time: 0.25 h
Yield: 76.2 %

Procedure:
Methyl α-methylthio(3-chloro-4-piperidinophenyl)acetate (2.524 g) was dissolved in 15 ml of N,N-dimethylformamide, and under ice cooling, 420 mg of sodium hydride (65% content) was added. The mixture was stirred for 15 minutes, and then 3.5 ml of methyl iodide was added. The mixture was stirred for 2 minutes under ice cooling, and then for 1 hour and 15 minutes at room temperature. Then 60 ml of a saturated aqueous solution of ammonium chloride was added, and the mixture was extracted twice with 25 ml of methylene chloride. The extract was dried over anhydrous sodium sulfate, and concentrated under reduced pressure to afford a brown oily product. The oily product was chromatographed on a column of Florisil using n-hexane-benzene as an eluent to afford 2.012 g (76.2%) of methyl α-methylthio-α-(3-chloro-4-piperidinophenyl)propionate. On standing overnight, the product crystallized.
Reaction SMILES: [Cl:1][CH2:2][CH2:3][NH:4][C:5]([N:7]([CH2:19][CH2:20][O:21][CH3:22])[CH:8]1[O:16][C@H:15]([CH2:17][OH:18])[C@@H:13]([OH:14])[C@H:11]([OH:12])[C@@H:9]1[OH:10])=[O:6].C([O-])(=O)C.[Na+].[N+:28]([O-])([N+]([O-])=O)=[O:29].CCCCCC>O1CCCC1.C(O)(=O)C.CO>[Cl:1][CH2:2][CH2:3][N:4]([N:28]=[O:29])[C:5]([N:7]([CH2:19][CH2:20][O:21][CH3:22])[CH:8]1[O:16][C@H:15]([CH2:17][OH:18])[C@@H:13]([OH:14])[C@H:11]([OH:12])[C@@H:9]1[OH:10])=[O:6]
Reactant: O=[N+]([O-])[N+](=O)[O-]
Reactant: COCCN(C(=O)NCCCl)C1O[C@H](CO)[C@@H](O)[C@H](O)[C@@H]1O
Agent: CC(=O)[O-]
Agent: [Na+]
Solvent: CCCCCC
Solvent: CC(=O)O
Solvent: CO
Product: COCCN(C(=O)N(CCCl)N=O)C1O[C@H](CO)[C@@H](O)[C@H](O)[C@@H]1O
Yield: 46.1 %

Procedure:
3.4 g of 1-(2-chloroethyl)-3-(2-methoxyethyl)-3-(D-mannopyranosyl)urea are dissolved in a mixture of 40 ml of tetrahydrofuran and 10 ml of acetic acid, and 17 g of sodium acetate anhydrate are added thereto. 6 g of nitrogen tetroxide gas are introduced into the mixture for 10 minutes under ice-cooling and stirring. The mixture is further stirred at the same temperature for 10 minutes. 70 ml of hexane are added to the reaction mixture, and said mixture is filtered. The filtrate is condensed under reduced pressure. A mixture of 200 ml of hexane and 4 ml of methanol is added to the residue. After the resultant oil is washed with ether, said oil is dissolved in 50 ml of ethyl acetate. 10 ml of water are added to the ethyl acetate solution, and the mixture is shaken. Then, the ethyl acetate layer is collected therefrom, dried and evaporated under reduced pressure. 1.7 g of 1-(2-chloroethyl)-1-nitroso-3-(2-methoxyethyl)-3-(D-mannopyranosyl)urea is thereby obtained as pale yellow caramel.
Reaction SMILES: [C:1]1(=[O:7])[O:6][C:4](=[O:5])[CH2:3][CH2:2]1.C(OC1C=CC=CC=1)CCCCCC.[CH2:22]([C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)[CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH3:28]>>[CH2:22]([C:29]1[CH:30]=[CH:31][C:32]([C:1]([CH2:2][CH2:3][C:4]([OH:6])=[O:5])=[O:7])=[CH:33][CH:34]=1)[CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH3:28]
Reactant: CCCCCCCc1ccccc1
Reactant: O=C1CCC(=O)O1
Agent: CCCCCCCOc1ccccc1
Product: CCCCCCCc1ccc(C(=O)CCC(=O)O)cc1
Yield: 70.2 %

Procedure:
The first step of Example 1 was repeated except that succinic anhydride (62.4 g) was replaced by 68.1 g thereof and heptyloxybenzene (100 g) was replaced by heptylbenzene (100 g), to obtain 3-(4-heptylbenzoyl)propionic acid (110 g). m.p.: 101.0°-103.5° C.
Reaction SMILES: Cl[CH2:2][CH2:3][CH2:4][CH2:5][O:6][C:7]1[C:16]2[NH:15][C:14](=[O:17])[O:13][C:12]([CH3:19])([CH3:18])[C:11]=2[CH:10]=[CH:9][CH:8]=1.[CH3:20][O:21][C:22]1[CH:23]=[C:24]([SH:30])[CH:25]=[CH:26][C:27]=1[O:28][CH3:29]>>[CH3:20][O:21][C:22]1[CH:23]=[C:24]([S:30][CH2:2][CH2:3][CH2:4][CH2:5][O:6][C:7]2[C:16]3[NH:15][C:14](=[O:17])[O:13][C:12]([CH3:19])([CH3:18])[C:11]=3[CH:10]=[CH:9][CH:8]=2)[CH:25]=[CH:26][C:27]=1[O:28][CH3:29]
Reactant: COc1ccc(S)cc1OC
Reactant: CC1(C)OC(=O)Nc2c(OCCCCCl)cccc21
Product: COc1ccc(SCCCCOc2cccc3c2NC(=O)OC3(C)C)cc1OC

Procedure:
Prepared analogously to Example 1 from 8-(4-chlorobutoxy)-4,4-dimethyl-4H-3,1-benzoxazin-2-one and 3,4-dimethoxy-thiophenol.
Reaction SMILES: [CH3:1][C:2]1([CH3:19])[CH:4]([CH:5]=[C:6]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])[C:7]([O:9][CH3:10])=[O:8])[CH:3]1[C:16]([O-:18])=[O:17].CO.CC(C)=O.Cl>O>[CH3:1][C:2]1([CH3:19])[CH:4]([CH:5]=[C:6]([O:11][C:12]([CH3:13])([CH3:14])[CH3:15])[C:7]([O:9][CH3:10])=[O:8])[CH:3]1[C:16]([OH:18])=[O:17]
Reactant: COC(=O)C(=CC1C(C(=O)[O-])C1(C)C)OC(C)(C)C
Agent: Cl
Solvent: CO
Solvent: CC(C)=O
Solvent: O
Product: COC(=O)C(=CC1C(C(=O)O)C1(C)C)OC(C)(C)C
Temperature: 20 °C
Reaction time: 6 h

Procedure:
A mixture of 410 mg of methoxymethyl (1R,trans,ΔE) 2,2-dimethyl-3-[2-tert.-butoxy-2-methoxy carbonyl-ethenyl]cyclopropane-carboxylate, 8 ml of methanol, 8 ml of acetone and 16 ml of aqueous N hydrochloric acid was stirred at 20° C. for 6 hours and was poured into water. The mixture was extracted with ether and the organic phase was evaporated to dryness under reduced pressure to obtain 300 mg of (1R,trans,ΔE) 2,2-dimethyl-3-[2-tert.-butoxy-2-methoxy carbonyl-ethenyl]cyclopropane-carboxylic acid.