Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][N:2]1[C:8]([CH3:10])([CH3:9])[CH2:7][C:6](=[O:11])[NH:5][CH2:4][C:3]1([CH3:13])[CH3:12].[CH3:14][N:15]=[C:16]=[O:17]>>[CH3:14][NH:15][C:16]([N:5]1[C:6](=[O:11])[CH2:7][C:8]([CH3:9])([CH3:10])[N:2]([CH3:1])[C:3]([CH3:13])([CH3:12])[CH2:4]1)=[O:17]
Reactant: CN1C(C)(C)CNC(=O)CC1(C)C
Reactant: CN=C=O
Product: CNC(=O)N1CC(C)(C)N(C)C(C)(C)CC1=O

Procedure:
Using the same conditions as in Example 4, 2.76 parts of 1,2,2,7,7 -pentamethyl-1,4-diazacycloheptan-5-one and 0.93 parts of methyl isocyanate afforded a colourless solid which was crystallised from petroleum ether (of boiling range 60°-80°C) to give 4-methylcarbamoyl-1,2,2,7,7-pentamethyl-1,4-diazacycloheptan-5-one. This material had a melting point of 111°-113°C and gave the following elemental analysis by weight:
Reaction SMILES: [CH3:1][CH:2]([S:4](Cl)(=[O:6])=[O:5])[CH3:3].[NH2:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[C:16]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)=[N:17][C:18]3[C:23]([N:24]=2)=[CH:22][C:21]([C:25]([O:27][CH3:28])=[O:26])=[CH:20][CH:19]=3)=[CH:11][CH:10]=1.CCN(C(C)C)C(C)C>ClCCl>[C:29]1([C:16]2[C:15]([C:12]3[CH:13]=[CH:14][C:9]([NH:8][S:4]([CH:2]([CH3:3])[CH3:1])(=[O:6])=[O:5])=[CH:10][CH:11]=3)=[N:24][C:23]3[C:18](=[CH:19][CH:20]=[C:21]([C:25]([O:27][CH3:28])=[O:26])[CH:22]=3)[N:17]=2)[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=1
Reactant: CC(C)S(=O)(=O)Cl
Reactant: COC(=O)c1ccc2nc(-c3ccccc3)c(-c3ccc(N)cc3)nc2c1
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: COC(=O)c1ccc2nc(-c3ccccc3)c(-c3ccc(NS(=O)(=O)C(C)C)cc3)nc2c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 87.7 %

Procedure:
Propane-2-sulfonyl chloride (300 mg, 2.10 mmol, 5.00 equiv) was added to a solution of methyl 3-(4-aminophenyl)-2-phenylquinoxaline-6-carboxylate (150 mg, 0.42 mmol, 1.00 equiv) and DIEA (545 mg, 4.22 mmol, 10.00 equiv) in dichloromethane (30 mL) at 0° C., and the resulting solution was stirred overnight at room temperature. The reaction mixture was concentrated under vacuum and purified via silica gel column (ethyl acetate/petroleum ether (1:10)), affording 170 mg (87%) of methyl 2-phenyl-3-(4-(propan-2-ylsulfonamido)phenyl)quinoxaline-6-carboxylate as a yellow solid.
Reaction SMILES: [CH2:1]([OH:23])[C@H:2]1[O:7][C@H:6]([O:8][C@H:9]2[C@H:14]([OH:15])[C@@H:13]([OH:16])[C@H:12]([OH:17])O[C@@H]2CO)[C@H:5]([OH:20])[C@@H:4]([OH:21])[C@@H:3]1[OH:22].P([O-])([O-])([O-])=O>>[CH2:5]([OH:20])[C@H:6]1[O:7][C@H:9]([O:8][C@H:6]2[O:7][C@H:2]([CH2:1][OH:23])[C@@H:3]([OH:22])[C@H:4]([OH:21])[C@H:5]2[OH:20])[C@H:14]([OH:15])[C@@H:13]([OH:16])[C@@H:12]1[OH:17]
Reactant: OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O
Agent: O=P([O-])([O-])[O-]
Product: OC[C@H]1O[C@H](O[C@H]2O[C@H](CO)[C@@H](O)[C@H](O)[C@H]2O)[C@H](O)[C@@H](O)[C@@H]1O

Procedure:
Five units each per 1 g of the substrates of purified extracellular trehalose phosphorylase and purified extracellular maltose phosphorylase produced in the same manners as in Examples 2 and 1 were added to 10 ml of 20% (W/V) solution of high maltose syrup (trade name; MC-95, Nihon Shokuhin Kako Co., Ltd, Sugar composition; 2.5% of glucose, 95.2% of maltose, 0.8% of maltotriose and 1.5% of maltotetraose) containing 5 mM phosphate buffer (pH 6.0) and allowed to react as in Example 6. Trehalose formed was measured by the HPLC method described above and it was found to correspond to 54.3% of the weight of the used substrates.
Reaction SMILES: [C:1]([O:5][CH:6]([C:11]1[C:12]([C:21]2[CH:22]=[C:23]3[C:28](=[CH:29][CH:30]=2)[O:27][CH2:26][CH2:25][CH2:24]3)=[C:13]2[CH:20]=[CH:19][NH:18][C:14]2=[N:15][C:16]=1[CH3:17])[C:7]([O:9]C)=[O:8])([CH3:4])([CH3:3])[CH3:2].Br[CH2:32][CH:33]1[CH2:36][CH2:35][CH2:34]1>>[C:1]([O:5][CH:6]([C:11]1[C:12]([C:21]2[CH:22]=[C:23]3[C:28](=[CH:29][CH:30]=2)[O:27][CH2:26][CH2:25][CH2:24]3)=[C:13]2[CH:20]=[CH:19][N:18]([CH2:32][CH:33]3[CH2:36][CH2:35][CH2:34]3)[C:14]2=[N:15][C:16]=1[CH3:17])[C:7]([OH:9])=[O:8])([CH3:4])([CH3:2])[CH3:3]
Reactant: BrCC1CCC1
Reactant: COC(=O)C(OC(C)(C)C)c1c(C)nc2[nH]ccc2c1-c1ccc2c(c1)CCCO2
Product: Cc1nc2c(ccn2CC2CCC2)c(-c2ccc3c(c2)CCCO3)c1C(OC(C)(C)C)C(=O)O

Procedure:
The title compound was prepared in a manner similar to that described in Example 27, Step H from methyl 2-(tert-butoxy)-2-(4-(chroman-6-yl)-6-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl)acetate and (bromomethyl)cyclobutane. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 7.49-7.43 (m, 1 H), 7.21-7.13 (m, 2 H), 6.99-6.93 (m, 1 H), 6.34 (dd, J=3.5, 7.8 Hz, 1 H), 5.51 (d, J=3.9 Hz, 1 H), 4.54-4.37 (m, 2 H), 4.30 (t, J=5.2 Hz, 2 H), 2.96-2.80 (m, 6H), 2.17-2.05 (m, 4 H), 1.99-1.79 (m, 4 H), 0.99-0.90 (s, 9 H); LC/MS (m/z) ES+=463.37 (M+1).
Reaction SMILES: [SH:1][C:2]1[S:3][C:4]2[CH:10]=[CH:9][CH:8]=[CH:7][C:5]=2[N:6]=1.CC(C)([O-])C.[K+].Cl[CH2:18][C:19]#[N:20]>O1CCCC1>[C:19]([CH2:18][S:1][C:2]1[S:3][C:4]2[CH:10]=[CH:9][CH:8]=[CH:7][C:5]=2[N:6]=1)#[N:20]
Reactant: N#CCCl
Reactant: Sc1nc2ccccc2s1
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: C1CCOC1
Product: N#CCSc1nc2ccccc2s1
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
In a 1 liter flask were combined 33.4 g. (0.2 mole) of 2-mercaptobenzothiazole and 22.4 g. (0.2 mole) of potassium t-butoxide with 300 ml. of tetrahydrofuran. The reaction mass was stirred at room temperature for 15 minutes. Chloroacetonitrile, 16 g. (0.2 mole) was added and the resulting mixture was stirred at room temperature for 1 hour. The mixture was then poured into 400 ml. of benzene and was washed with three 250 ml. portions of water. The benzene phase was dried with anhydrous magnesium sulfate. The solvent was evaporated. There was obtained a yield of 37.2 g. of the title compound, m.p. 75°-77° C.
Reaction SMILES: [CH2:1]([CH:3]([CH2:6][CH2:7][CH2:8][CH3:9])[CH2:4][OH:5])[CH3:2].N1C=CC=CC=1.[C:16]1([CH3:26])[CH:21]=[CH:20][C:19]([S:22](Cl)(=[O:24])=[O:23])=[CH:18][CH:17]=1>CCOCC>[C:16]1([CH3:26])[CH:21]=[CH:20][C:19]([S:22]([O:5][CH2:4][CH:3]([CH2:1][CH3:2])[CH2:6][CH2:7][CH2:8][CH3:9])(=[O:24])=[O:23])=[CH:18][CH:17]=1
Reactant: CCCCC(CC)CO
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Solvent: c1ccncc1
Solvent: CCOCC
Product: CCCCC(CC)COS(=O)(=O)c1ccc(C)cc1
Temperature: -5 °C
Reaction time: 3 h

Procedure:
2-Ethylhexanol (50.51 g, 0.384 tool) and pyridine (260 mL) are combined in a flask fitted with a condenser, internal thermometer, mechanical stirrer and argon inlet. The solution is cooled to -5° C. and to it is added p-toluenesulfonyl chloride (89.63 g, 0.416 mol) in portions via Gooch tubing so as to maintain the reaction temperature -5°-5° C. After 3 h, (40 mL) is added in portions so as to keep the temperature of the reaction below 5° C. The reaction mixture is warmed to room temperature and then poured into a separatory funnel containing 540 mL of ether. The layers are separated and the organic layer is washed with 5 M H2SO4 (2×140 mL), saturated CuSO4 solution (140 mL), water (2×140 mL) and saturated NaHCO3 solution (140 mL). After drying over MgSO4, the organic layer is filtered, and concentrated to leave a light yellow liquid as 2-ethyhexanyl p-toluenesulfonate. Purity of the product is determined by thin layer chromatography and the structure confirmed by 1H and 13C NMR.
Reaction SMILES: [Cl:1][C:2]1[N:7]=[CH:6][CH:5]=[C:4]([NH:8][NH2:9])[N:3]=1.C(N(CC)CC)C.C(O[CH:20]=[C:21]([C:27](=O)[C:28]([F:31])([F:30])[F:29])[C:22]([O:24][CH2:25][CH3:26])=[O:23])C>C(#N)C>[Cl:1][C:2]1[N:3]=[C:4]([N:8]2[C:27]([C:28]([F:29])([F:30])[F:31])=[C:21]([C:22]([O:24][CH2:25][CH3:26])=[O:23])[CH:20]=[N:9]2)[CH:5]=[CH:6][N:7]=1
Reactant: CCOC=C(C(=O)OCC)C(=O)C(F)(F)F
Reactant: NNc1ccnc(Cl)n1
Solvent: CCN(CC)CC
Solvent: CC#N
Product: CCOC(=O)c1cnn(-c2ccnc(Cl)n2)c1C(F)(F)F
Temperature: 25 °C
Reaction time: 0.75 h

Procedure:
To a solution 2-chloro-6-hydrazinopyrimidine (1.00 g, 6.92 mmol) and triethylamine (0.964 mL, 6.92 mmol) in acetonitrile (35 mL) was added ethyl 2-(ethoxymethylene)-4,4,4-trifluoro-3-oxobutyrate (1.35 mL, 6.97 mmol). After 45 min, the reaction mixture was placed in a 90° C. oil bath. After 1 h, the reaction mixture was allowed to cool to ambient temperature, then was concentrated in vacuo. Purification by flash chromatography on silica gel (0 to 60% EtOAc in hexanes, then 60 to 100% EtOAc in hexanes) provided the title compound: LCMS m/z 321.0 [M+H]+; 1H NMR (500 MHz, CDCl3) δ 8.80 (d, J=5.5 Hz, 1H), 8.12 (s, 1H), 7.76 (d, J=5.5 Hz, 1H), 4.39 (q, J=7.0 Hz, 2H), 1.39 (t, J=7.0 Hz, 3H).
Reaction SMILES: [Cl:1][C:2]1[CH:11]=[CH:10][C:9]2[N:8]=[C:7]3[C:12](=[O:17])[NH:13][C:14]([CH3:16])=[N:15][C:6]3=[C:5]([C:18]([F:21])([F:20])[F:19])[C:4]=2[CH:3]=1.[Li][CH2:23][CH2:24][CH2:25][CH3:26]>C1COCC1.CN(CCN(C)C)C>[CH2:23]([C:5]1([C:18]([F:19])([F:21])[F:20])[C:4]2[CH:3]=[C:2]([Cl:1])[CH:11]=[CH:10][C:9]=2[NH:8][C:7]2[C:12](=[O:17])[NH:13][C:14]([CH3:16])=[N:15][C:6]1=2)[CH2:24][CH2:25][CH3:26]
Reactant: [Li]CCCC
Reactant: Cc1nc2c(C(F)(F)F)c3cc(Cl)ccc3nc2c(=O)[nH]1
Agent: CN(C)CCN(C)C
Solvent: C1CCOC1
Product: CCCCC1(C(F)(F)F)c2cc(Cl)ccc2Nc2c1nc(C)[nH]c2=O
Temperature: -78 °C
Reaction time: 0.33 h
Yield: 17 %

Procedure:
8-Chloro-2-methyl-10-(trifluoromethyl)-pyrimido[5,4-b]quinolin-4(3H)-one (13, 82 mg, 0.261 mmol) was suspended in THF-TMEDA (10:1, 1.74 mL) and cooled to −78° C. under a N2 atmosphere. n-BuLi was added dropwise and the reaction slowly became homogeneous. The reaction mixture was stirred at −78° C. for 20 minutes, then the ice bath was removed and the reaction allowed to warm to rt. After stirring for 90 min, the reaction was quenched with sat. aq. NH4Cl and was partitioned between EtOAc and H2O. The organic layer was separated and the aqueous layer was extracted with EtOAc (3×10 mL). The combined organics were washed with brine, dried over Na2SO4 and concentrated. Chromatography (SiO2, 60% EtOAc-hexane) provided the desired material 14 (17 mg, 17%). Rf 0.39 (50% EtOAc-hexane). 1H NMR (CDCl3, 300 MHz) 6 11.63 (br s, NH), 7.53 (s, 1H), 7.22 (dd, J=2.2, 8.4 Hz, 1H), 6.87 (br s, NH), 6.82 (d, J=8.4 Hz, 1H), 2.86 (m, 1H), 2.48 (s, 3H), 2.14 (m, 1H), 1.34 (m, 2H), 1.01 (m, 2H), 0.86 (t, J=7.3 Hz, 3H); 19F NMR (CDCl3, 300 MHz) δ −75.21. ESI-HRMS 372.1099 (M++H, C17H17ClON3F3 requires 372.1091).
Reaction SMILES: [OH:1][CH:2]([C:4]1([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:8][CH2:7][C:6]([O:11][CH3:12])([O:9][CH3:10])[CH2:5]1)[CH3:3].C(N(CC)CC)C.[C:27](OC(=O)C)(=[O:29])[CH3:28]>C(Cl)Cl.CN(C1C=CN=CC=1)C>[C:27]([O:1][CH:2]([C:4]1([C:13]([O:15][C:16]([CH3:18])([CH3:17])[CH3:19])=[O:14])[CH2:8][CH2:7][C:6]([O:11][CH3:12])([O:9][CH3:10])[CH2:5]1)[CH3:3])(=[O:29])[CH3:28]
Reactant: COC1(OC)CCC(C(=O)OC(C)(C)C)(C(C)O)C1
Reactant: CC(=O)OC(C)=O
Agent: CN(C)c1ccncc1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: COC1(OC)CCC(C(=O)OC(C)(C)C)(C(C)OC(C)=O)C1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
A solution of tert-butyl 1-(1-hydroxyethyl)-3,3-dimethoxycyclopentanecarboxylate (8.64 g, 31.5 mmol) in 100 mL of DCM was treated with triethylamine (8.78 mL, 63.0 mmol) followed by acetic anhydride (5.94 mL, 63.0 mmol). Then DMAP (˜200 mg) was added and the resulting mixture was stirred at rt overnight. The reaction mixture was diluted with DCM, washed twice with 1N HCl solution, once with saturated NaHCO3 solution, and once with brine. The organic layer was dried over anhydrous MgSO4, filtered, and concentrated. Purification by flash chromatography (silica, 20% ethyl acetate/hexanes) provided tert-butyl 1-[1-(acetyloxy)ethyl]-3,3-dimethoxycyclopentanecarboxylate.
Reaction SMILES: Cl.[I:2][C:3]1([CH2:6][C@H:7]([CH2:16][O:17][Si](C)(C)C(C)(C)C)[O:8][Si](C)(C)C(C)(C)C)[CH2:5][CH2:4]1>C1COCC1>[I:2][C:3]1([CH2:6][C@@H:7]([OH:8])[CH2:16][OH:17])[CH2:5][CH2:4]1
Reactant: CC(C)(C)[Si](C)(C)OC[C@@H](CC1(I)CC1)O[Si](C)(C)C(C)(C)C
Agent: Cl
Solvent: C1CCOC1
Product: OC[C@H](O)CC1(I)CC1
Temperature: 25 °C
Reaction time: 24 h
Yield: 100 %

Procedure:
Aqueous HCl solution (0.3 mL, 1N) was added to a solution of (R)-5-(1-iodocyclopropyl)methyl)-2,2,3,3,8,8,9,9-octamethyl-4,7-dioxa-3,8-disiladecane (step E, 281 mg, 0.598 mmol) in THF (2 mL) at 0° C. The mixture was slowly warmed at room temperature and stirred for 24 hours. The reaction was quenched by addition of aqueous NaHCO3 solution and extracted with ethyl acetate. The combined organic layers were washed with brine, dried (MgSO4) and concentrated under reduced pressure to provide (R)-3-(1-iodocyclopropyl)propane-1,2-diol (0.598 mmol), which was used in the next step with no further purification.
Reaction SMILES: Br[C:2]1[N:10]=[CH:9][N:8]=[C:7]2[C:3]=1[N:4]=[CH:5][NH:6]2.[Cl:11][C:12]1[CH:20]=[C:19]([CH:21]([NH2:23])[CH3:22])[C:18]([C:24]2[CH:29]=[C:28]([F:30])[CH:27]=[C:26]([F:31])[CH:25]=2)=[C:17]2[C:13]=1[CH:14]=[N:15][N:16]2[CH3:32].C(N(CC)C(C)C)(C)C>C(O)(C)C>[Cl:11][C:12]1[CH:20]=[C:19]([CH:21]([NH:23][C:2]2[N:10]=[CH:9][N:8]=[C:7]3[C:3]=2[N:4]=[CH:5][NH:6]3)[CH3:22])[C:18]([C:24]2[CH:29]=[C:28]([F:30])[CH:27]=[C:26]([F:31])[CH:25]=2)=[C:17]2[C:13]=1[CH:14]=[N:15][N:16]2[CH3:32]
Reactant: CC(N)c1cc(Cl)c2cnn(C)c2c1-c1cc(F)cc(F)c1
Reactant: Brc1ncnc2[nH]cnc12
Solvent: CC(C)O
Solvent: CCN(C(C)C)C(C)C
Product: CC(Nc1ncnc2[nH]cnc12)c1cc(Cl)c2cnn(C)c2c1-c1cc(F)cc(F)c1
Temperature: 90 °C

Procedure:
A mixture of 6-bromo-9H-purine (0.30 g, 1.5 mmol), 1-[4-chloro-7-(3,5-difluorophenyl)-1-methyl-1H-indazol-6-yl]ethanamine (0.439 g, 1.36 mmol), and N,N-diisopropylethylamine (0.48 mL, 2.7 mmol) in isopropyl alcohol (5 mL) was heated at 90° C. under nitrogen overnight. The mixture was evaporated and the resulting mixture was purified on a RP-HPLC (XBridge C18 column, eluting with a gradient of acetonitrile in water with 0.2% ammonium hydroxide, at a flow rate of 30 mL/min) to give the desired product. LCMS calculated for C21H17ClF2N7 (M+H)+: m/z=440.1; Found: 440.1. 1H NMR (DMSO-d6, 400 MHz) δ 8.29 (1H, br s), 8.10 (1H, s), 8.05 (1H, s), 8.04 (1H, s), 7.62 (1H, s), 7.52 (1H, d, J=8.8 Hz), 7.43 (1H, m), 7.31 (1H, d, J=8.8 Hz), 5.10(1H, br s), 3.41 (3H, s), 3.35 (1H, m), 1.41 (3H, d, J=6.8 Hz) ppm. 19F NMR (DMSO-d6, 376 MHz) δ −110 ppm.
Reaction SMILES: [CH3:1][O:2][C:3]1[C:8]2[CH2:9][CH2:10][CH2:11][CH:12]([NH:14][CH2:15][CH2:16][O:17][CH3:18])[CH2:13][C:7]=2[CH:6]=[CH:5][C:4]=1[NH2:19].Cl[C:21]1[N:26]=[C:25]([NH:27][C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=2[S:34]([CH:37]([CH3:39])[CH3:38])(=[O:36])=[O:35])[C:24]([Cl:40])=[CH:23][N:22]=1>>[Cl:40][C:24]1[C:25]([NH:27][C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=2[S:34]([CH:37]([CH3:39])[CH3:38])(=[O:36])=[O:35])=[N:26][C:21]([NH:19][C:4]2[CH:5]=[CH:6][C:7]3[CH2:13][CH:12]([NH:14][CH2:15][CH2:16][O:17][CH3:18])[CH2:11][CH2:10][CH2:9][C:8]=3[C:3]=2[O:2][CH3:1])=[N:22][CH:23]=1
Reactant: CC(C)S(=O)(=O)c1ccccc1Nc1nc(Cl)ncc1Cl
Reactant: COCCNC1CCCc2c(ccc(N)c2OC)C1
Product: COCCNC1CCCc2c(ccc(Nc3ncc(Cl)c(Nc4ccccc4S(=O)(=O)C(C)C)n3)c2OC)C1

Procedure:
The title compound was prepared from 1-methoxy-N(6)-(2-methoxyethyl)-6,7,8,9-tetrahydro-5H-benzocyclohepten-2,6-diamine (60 mg, 0.2 mmol) and (2,5-dichloropyrimidin-4-yl)-[2-(propane-2-sulfonyl)-phenyl]-amine (78 mg, 0.23 mmol) in an analogous manner to Example 946 to afford a white foam (59 mg, 40%). Mp: 83-5° C. LCMS (m/e) 574 (M+1); 1H-NMR (CDCl3, 400 MHz) δ 9.58 (s, 1H), 8.60 (d, J=8 Hz, 1H), 8.18 (s, 1H), 7.94 (d, J=8 Hz, 1H), 7.69 (d, J=8 Hz, 1H), 7.52 (br s, 1H), 7.30 (m, 1H), 6.87 (d, J=8 Hz, 1H), 3.75 (s, 3H), 3.54 (m, 2H), 3.37 (s, 3H), 3.25 (m, 1H), 3.10 (m, 1H), 2.92-2.80 (m, 4H), 2.63 (m, 2H), 2.10 (m, 1H), 1.97 (m, 1H), 1.71 (m, 1H), 1.55 (m, 2H), 1.33 (d, J=7 Hz, 6H).
Reaction SMILES: [Na].[Cl:2][S:3]([OH:6])(=O)=[O:4].[OH:7][C:8]1[CH:17]=[CH:16][C:15]([N:18]=[N:19][C:20]2[CH:25]=[CH:24][C:23]([N+:26]([O-:28])=[O:27])=[CH:22][C:21]=2[S:29]([CH3:32])(=[O:31])=[O:30])=[C:14]2[C:9]=1[CH:10]=[CH:11][C:12](S([O-])(=O)=O)=[CH:13]2.[Na+]>>[OH:7][C:8]1[CH:17]=[CH:16][C:15]([N:18]=[N:19][C:20]2[CH:25]=[CH:24][C:23]([N+:26]([O-:28])=[O:27])=[CH:22][C:21]=2[S:29]([CH3:32])(=[O:30])=[O:31])=[C:14]2[C:9]=1[CH:10]=[CH:11][C:12]([S:3]([Cl:2])(=[O:6])=[O:4])=[CH:13]2
Reactant: O=S(=O)(O)Cl
Reactant: CS(=O)(=O)c1cc([N+](=O)[O-])ccc1N=Nc1ccc(O)c2ccc(S(=O)(=O)[O-])cc12
Agent: [Na+]
Agent: [Na]
Product: CS(=O)(=O)c1cc([N+](=O)[O-])ccc1N=Nc1ccc(O)c2ccc(S(=O)(=O)Cl)cc12

Procedure:
The 5-hydroxy-8-(2-methylsulfonyl-4-nitrophenylazo)-2-naphthalenesulfonyl chloride was prepared from the sodium salt of the acid with chlorosulfonic acid; 3.55 g. (0.0075 mol) of sodium 5-hydroxy-8-(2-methylsulfonyl-4-nitrophenylazo)-2-napthalenesulfonate in 35 ml. of chlorosulfonic acid was heated at 60°C. for one hour. The solution was cooled and poured onto ice. The solid was collected on a filter funnel and dried in a vaccum desiccator to yield 2.8 g. (80 percent) of the product which contained a small amount of starting material.
Reaction SMILES: [F:1][C:2]1[C:25]([N:26]2[CH2:31][CH2:30][N:29]([CH3:32])[CH2:28][CH2:27]2)=[CH:24][C:5]2[NH:6][C:7]([C:9]3[C:21]4[C:20]5[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=5)[C:14](=[N:22]O)[C:13]=4[CH:12]=[CH:11][CH:10]=3)=[N:8][C:4]=2[CH:3]=1>[Ni].C(O)C.O1CCCC1>[F:1][C:2]1[C:25]([N:26]2[CH2:31][CH2:30][N:29]([CH3:32])[CH2:28][CH2:27]2)=[CH:24][C:5]2[NH:6][C:7]([C:9]3[C:21]4[C:20]5[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=5)[CH:14]([NH2:22])[C:13]=4[CH:12]=[CH:11][CH:10]=3)=[N:8][C:4]=2[CH:3]=1
Reactant: CN1CCN(c2cc3[nH]c(-c4cccc5c4-c4ccccc4C5=NO)nc3cc2F)CC1
Agent: [Ni]
Solvent: CCO
Solvent: C1CCOC1
Product: CN1CCN(c2cc3[nH]c(-c4cccc5c4-c4ccccc4C5N)nc3cc2F)CC1
Yield: 90.1 %

Procedure:
The procedure used in Example 6 is followed, starting from 1.95 g of 4-[5-fluoro-6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-9H-fluoren-9-one oxime (Z,E), obtained in the previous stage, and 285 mg of Raney nickel in 40 ml of ethanol and 40 ml of tetrahydrofuran for 16 hours at 60° C. under an initial hydrogen pressure of one bar. After filtration of the catalyst, concentration to dryness under reduced pressure and purification by formation of a paste with diisopropyl ether, in this way we obtain 1.7 g of 4-[5-fluoro-6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-9H-fluoren-9(R,S)-ylamine, in the form of an orange powder, which is used as it is in the following stage, with the following characteristics:
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[NH:27][C:28]4[CH:33]=[CH:32][CH:31]=[C:30](Br)[N:29]=4)=[CH:17][CH:16]=3)=[CH:11][CH:10]=2)[CH2:8][CH2:7]1)=[O:5])[CH3:2].[Cl:35][C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][C:37]=1B(O)O>>[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[NH:27][C:28]4[CH:33]=[CH:32][CH:31]=[C:30]([C:37]5[CH:38]=[CH:39][CH:40]=[CH:41][C:36]=5[Cl:35])[N:29]=4)=[CH:17][CH:16]=3)=[CH:11][CH:10]=2)[CH2:8][CH2:7]1)=[O:5])[CH3:2]
Reactant: CCOC(=O)C1(c2ccc(-c3ccc(-c4onc(C)c4Nc4cccc(Br)n4)cc3)cc2)CC1
Reactant: OB(O)c1ccccc1Cl
Product: CCOC(=O)C1(c2ccc(-c3ccc(-c4onc(C)c4Nc4cccc(-c5ccccc5Cl)n4)cc3)cc2)CC1

Procedure:
Prepared according to the procedure described in Example 1, Step 10, using 1-{4′-[4-(6-bromo-pyridin-2-ylamino)-3-methyl-isoxazol-5-yl]-biphenyl-4-yl}-cyclopropanecarboxylic acid ethyl ester and 2-chlorophenylboronic acid.
Reaction SMILES: [O:1]=[C:2]1[C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=2[N:6]([C:13](=[O:30])[C:14]2[CH:19]=[CH:18][C:17]([NH:20][C:21](=[O:29])[C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=3[CH3:28])=[CH:16][CH:15]=2)[CH2:5][CH2:4][CH2:3]1.[CH3:31][Mg]Br>O1CCCC1.C(OCC)C>[CH3:31][C:2]1([OH:1])[C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=2[N:6]([C:13](=[O:30])[C:14]2[CH:19]=[CH:18][C:17]([NH:20][C:21](=[O:29])[C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=3[CH3:28])=[CH:16][CH:15]=2)[CH2:5][CH2:4][CH2:3]1
Reactant: Cc1ccccc1C(=O)Nc1ccc(C(=O)N2CCCC(=O)c3ccccc32)cc1
Reactant: C[Mg]Br
Solvent: CCOCC
Solvent: C1CCOC1
Product: Cc1ccccc1C(=O)Nc1ccc(C(=O)N2CCCC(C)(O)c3ccccc32)cc1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
5-Oxo-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine (0.50 g) is suspended in tetrahydrofuran (20 ml), and thereto is added dropwise a 3.0 M solution of methyl magnesium bromide in diethyl ether (1.5 ml) at room temperature. The mixture is stirred at room temperature for 1 hour. The reaction solution is poured into ice-water (20 ml), and extracted with ethyl acetate. The extract is dried over magnesium sulfate, and the solvent is distilled off. The resulting residue is purified by silica gel column chromatography (eluent; ethyl acetate:n-hexane=2:3→1:1), and recrystallized from ethyl acetate/n-hexane to give 5-methyl-5-hydroxy-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine (0.23 g) as white powder, m.p. 204-205° C.
Reaction SMILES: [CH3:1][C:2]1[N:3]([C:7]2[CH:12]=[CH:11][C:10]([NH:13][C:14]([NH2:16])=[NH:15])=[CH:9][CH:8]=2)[CH:4]=[CH:5][N:6]=1.[C:17]1([CH2:23][C:24]([CH:26]2[C:31](=O)[CH2:30][CH2:29][O:28][CH2:27]2)=O)[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1>>[CH2:23]([C:24]1[C:26]2[CH2:27][O:28][CH2:29][CH2:30][C:31]=2[N:15]=[C:14]([NH:13][C:10]2[CH:9]=[CH:8][C:7]([N:3]3[CH:4]=[CH:5][N:6]=[C:2]3[CH3:1])=[CH:12][CH:11]=2)[N:16]=1)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1
Reactant: O=C1CCOCC1C(=O)Cc1ccccc1
Reactant: Cc1nccn1-c1ccc(NC(=N)N)cc1
Product: Cc1nccn1-c1ccc(Nc2nc3c(c(Cc4ccccc4)n2)COCC3)cc1
Yield: 11.5 %

Procedure:
4-Benzyl-N-(4-(2-methyl-1H-imidazol-1-yl)phenyl)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-2-amine (42.0 mg, 11.5%) was obtained from 1-(4-(2-methyl-1H-imidazol-1-yl)phenyl)guanidine and 3-(2-phenylacetyl)dihydro-2H-pyran-4(3H)-one by general procedure for the preparation of pyrimidines. The crude product was purified by preparative HPLC twice. Purification using ammoniumacetate buffer was followed by purification using a 0.1% TFA. MS (ES+) m/z 398.1 (M+H)+
Reaction SMILES: [CH3:1][S:2](Cl)(=[O:4])=[O:3].[C:6]1([CH3:23])[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=1[C:12]1[C:13]2[CH:22]=[CH:21][CH:20]=[CH:19][C:14]=2[S:15][C:16]=1[CH2:17][OH:18].CCN(C(C)C)C(C)C>C(Cl)Cl>[C:6]1([CH3:23])[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=1[C:12]1[C:13]2[CH:22]=[CH:21][CH:20]=[CH:19][C:14]=2[S:15][C:16]=1[CH2:17][O:18][S:2]([CH3:1])(=[O:4])=[O:3]
Reactant: Cc1ccccc1-c1c(CO)sc2ccccc12
Reactant: CS(=O)(=O)Cl
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: Cc1ccccc1-c1c(COS(C)(=O)=O)sc2ccccc12
Temperature: 25 °C
Reaction time: 18 h
Yield: 75 %

Procedure:
Methanesulfonyl chloride (158 μL, 2.04 mmol) was added dropwise to a solution of (3-o-tolylbenzo[b]thiophen-2-yl)methanol (432 mg, 1.70 mmol) and DIPEA (385 μL, 2.21 mmol) in anhydrous DCM (10 mL) at RT. Stirring at RT was continued for 18 h then the reaction mixture was washed with water, dried (Na2SO4) and concentrated in vacuo affording the title compound as a brown oil (424 mg, 75%). 1H NMR (DMSO-d6, 400 MHz): δ 8.05 (1H, d, J=8.04 Hz), 7.45-7.40 (3H, m), 7.38-7.32 (2H, m), 7.21 (1H, d, J=7.40 Hz), 7.12 (1H, d, J=7.98 Hz), 4.82 (1H, d, J=12.41 Hz), 4.76 (1H, d, J=12.41 Hz), 3.32 (3H, s), 1.99 (3H, s)