Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([C:5]1[CH:9]=[C:8]([NH:10][C:11]([NH:13][C:14]2[CH:19]=[CH:18][C:17]([CH3:20])=[C:16]([NH:21][C:22]3[N:27]=[C:26]([C:28]4[CH:29]=[N:30][CH:31]=[CH:32][CH:33]=4)[CH:25]=[CH:24][N:23]=3)[CH:15]=2)=[O:12])[N:7]([C:34]2[CH:35]=[C:36]([CH2:40][C:41](OCC)=[O:42])[CH:37]=[CH:38][CH:39]=2)[N:6]=1)([CH3:4])([CH3:3])[CH3:2].[NH2:46][CH2:47][CH:48]([OH:51])[CH2:49][OH:50]>>[C:1]([C:5]1[CH:9]=[C:8]([NH:10][C:11]([NH:13][C:14]2[CH:19]=[CH:18][C:17]([CH3:20])=[C:16]([NH:21][C:22]3[N:27]=[C:26]([C:28]4[CH:29]=[N:30][CH:31]=[CH:32][CH:33]=4)[CH:25]=[CH:24][N:23]=3)[CH:15]=2)=[O:12])[N:7]([C:34]2[CH:39]=[CH:38][CH:37]=[C:36]([CH2:40][C:41]([NH:46][CH2:47][CH:48]([OH:51])[CH2:49][OH:50])=[O:42])[CH:35]=2)[N:6]=1)([CH3:2])([CH3:3])[CH3:4]
Reactant: NCC(O)CO
Reactant: CCOC(=O)Cc1cccc(-n2nc(C(C)(C)C)cc2NC(=O)Nc2ccc(C)c(Nc3nccc(-c4cccnc4)n3)c2)c1
Product: Cc1ccc(NC(=O)Nc2cc(C(C)(C)C)nn2-c2cccc(CC(=O)NCC(O)CO)c2)cc1Nc1nccc(-c2cccnc2)n1
Yield: 54.2 %

Procedure:
Using the same method as for Example 21, ethyl 2-(3-(3-t-butyl-5-(3-(4-methyl-3-(4-(pyridin-3-yl)pyrimidin-2-ylamino)phenyl)ureido)-1H-pyrazol-1-yl)phenyl)acetate (137 mg, 0.23 mmol) and 1-amino-2,3-dihydroxypropane (49 mg, 0.54 mmol) were combined to yield 1-(3-t-butyl-1-(3-(2-(2,3-dihydroxypropylamino)-2-oxoethyl)phenyl)-1H-pyrazol-5-yl)-3-(4-methyl-3-(4-(pyridin-3-yl)pyrimidin-2-ylamino)phenyl)urea (81 mg, 69% yield). 1H NMR (400 MHz, DMSO-d6): δ 9.29 (dd, J=2.2, and 0.8 Hz, 1H), 8.95 (s, 1H), 8.86 (s, 1H), 8.69 (dd, J=4.8, and 1.6 Hz, 1H), 8.51-8.47 (m, 2H), 8.38 (s, 1H), 8.10 (brt, J=5.8 Hz, 1H), 7.83 (d, J=1.6 Hz, 1H), 7.51 (ddd, J=8.4, 4.7, and 0.8 Hz, 1H), 7.47-7.42 (m, 3H), 7.36 (m, 1H), 7.31 (brd, J=7.6 Hz, 1H), 7.11 (d, J=8.5 Hz, 1H), 7.05 (dd, J=8.5, and 2.1 Hz, 1H), 6.41 (s, 1H), 4.76 (d, J=4.8 Hz, 1H), 4.51 (t, J=5.8 Hz, 1H), 3.53 (s, 2H), 3.48 (m, 1H), 3.30-3.18 (m, 3H), 2.96 (m, 1H), 2.19 (s, 3H), 1.27 (s, 9H); MS (ESI) m/z: 650.3 (M+H+).
Reaction SMILES: [CH2:1]1[O:9][C:8]2[C:3](=[CH:4][CH:5]=[C:6]([OH:10])[CH:7]=2)[O:2]1.[OH-].[Na+].S(Cl)([Cl:16])(=O)=O>C(OCC)C>[Cl:16][C:5]1[CH:4]=[C:3]2[O:2][CH2:1][O:9][C:8]2=[CH:7][C:6]=1[OH:10]
Reactant: O=S(=O)(Cl)Cl
Reactant: Oc1ccc2c(c1)OCO2
Agent: [Na+]
Agent: [OH-]
Solvent: CCOCC
Product: Oc1cc2c(cc1Cl)OCO2

Procedure:
To a solution of 0.18 mol (25 g) of 4,5-methylenedioxyphenol in 125 ml of ethyl ether, 17 ml of sulphuryl chloride are added at a temperature below 35° C. As soon as the addition is complete, the ethyl ether is evaporated off at room temperature. The dry residue thereby obtained is taken up with 2N sodium hydroxide. The mixture is filtered to remove a resin. The filtrate is acidified with 2N hydrochloric acid; the expected product precipitates. After being washed with water and dried under vacuum in the presence of phosphorus pentoxide, it is recrystallized from a cyclohexane/benzene mixture. It melts at 95° C.
Reaction SMILES: [OH:1][C:2]1[C:3]([CH3:18])=[C:4]2[C:12](=[CH:13][C:14]=1[CH3:15])[O:11][C:7]1([CH2:10][CH2:9][CH2:8]1)[C:6]([CH:16]=[O:17])=[CH:5]2.S([CH2:29][N+:30]#[C-:31])(C1C=CC(C)=CC=1)(=O)=O.C(=O)([O-])[O-].[K+].[K+]>CO>[CH3:18][C:3]1[C:2]([OH:1])=[C:14]([CH3:15])[CH:13]=[C:12]2[C:4]=1[CH:5]=[C:6]([C:16]1[O:17][CH:31]=[N:30][CH:29]=1)[C:7]1([O:11]2)[CH2:8][CH2:9][CH2:10]1
Reactant: Cc1cc2c(c(C)c1O)C=C(C=O)C1(CCC1)O2
Reactant: [C-]#[N+]CS(=O)(=O)c1ccc(C)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CO
Product: Cc1cc2c(c(C)c1O)C=C(c1cnco1)C1(CCC1)O2
Temperature: 80 °C
Yield: 37.6 %

Procedure:
To a solution of 6-hydroxy-5,7-dimethylspiro[chromene-2,1′-cyclobutane]-3-carbaldehyde (315 mg), prepared as described herein, in 4 mL of MeOH was added tosylmethyl isocyanide (TosMIC) reagent (218 mg) and potassium carbonate (310 mg). The reaction mixture was allowed to heat at 80° C. for 20 min. The mixture was quenched with water and extracted with ethyl acetate. After concentrated in vacuo, the residue was purified by flash chromatography eluted with 30% ethyl acetate in hexane to give 118.8 mg of 5,7-dimethyl-3-(1,3-oxazol-5-yl)spiro[chromene-2,1′-cyclobutan]-6-ol as a yellow solid.
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][CH2:13][CH3:14])=[CH:4][N:3]=1.[F-:15].[Cs+]>CS(C)=O.O>[F:15][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([O:12][CH2:13][CH3:14])=[CH:4][N:3]=1
Reactant: [F-]
Reactant: CCOc1cnc(Cl)c2ccccc12
Agent: [Cs+]
Solvent: O
Solvent: CS(C)=O
Product: CCOc1cnc(F)c2ccccc12
Temperature: 145 °C
Yield: 58.8 %

Procedure:
To a solution of 1-chloro-4-ethoxyisoquinolin (4.8 g, 23.12 mmol) in DMSO was added cesium fluoride (6.9 g, 46.24 mmol) at room temperature. The reaction vessel (Pressure tube) was sealed and heated at 145° C. for 18 h. The reaction mass was diluted with water and extracted with ethyl acetate. The organic layer was dried over anhydrous Na2SO4 and evaporated under reduced pressure to get crude compound. The crude compound was purified by silica gel chromatography to get desired compound (2.6 g, 58.8%) as white solid. MS: MS m/z 192.3 (M++1).
Reaction SMILES: [F:1][C:2]([F:30])([F:29])[C:3]1[CH:4]=[C:5]([CH:22]=[C:23]([C:25]([F:28])([F:27])[F:26])[CH:24]=1)[CH2:6][O:7][CH2:8][CH:9]([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[CH2:10][C:11]([O:13]CC)=[O:12].[OH-].[Na+]>C(O)C>[F:1][C:2]([F:29])([F:30])[C:3]1[CH:4]=[C:5]([CH:22]=[C:23]([C:25]([F:27])([F:26])[F:28])[CH:24]=1)[CH2:6][O:7][CH2:8][CH:9]([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[CH2:10][C:11]([OH:13])=[O:12]
Reactant: CCOC(=O)CC(COCc1cc(C(F)(F)F)cc(C(F)(F)F)c1)c1ccccc1
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: O=C(O)CC(COCc1cc(C(F)(F)F)cc(C(F)(F)F)c1)c1ccccc1
Temperature: 25 °C
Reaction time: 20 h
Yield: 109.1 %

Procedure:
Ethyl 4-(3,5-bis(trifluoromethyl)benzyloxy)-3-phenylbutanoate (26.06 g, 60 mmol) was dissolved in ethanol (300 mL), a 2 mol/L aqueous solution of sodium hydroxide was added thereto and the mixture was stirred for 20 hours at room temperature. The solvent was evaporated in vacuo and the resulting residue was dissolved in water and acidified with 6 mol/L hydrochloric acid. The oily product separated out therefrom was extracted with chloroform and the organic layers were combined and washed with water and a saturated saline solution. After it was dried over anhydrous sodium sulfate, the solvent was evaporated in vacuo to give 4-(3,5-bis(trifluoromethyl)benzyloxy)-3-phenylbutanoic acid (26.60 g, 90%) as an oily product. 1H-NMR (DMSO-d6) δ: 2.56 (dd, J=8.4, 16.0 Hz, 1H), 2.73 (dd, J=6.4, 16.0 Hz, 1H), 3.35-3.40 (m, 1H), 3.63-3.66 (m, 2H), 4.64 and 4.66 (ABq, J=13.4 Hz, 2H), 7.19-7.25 (m, 1H), 7.27-7.31 (m, 4H), 7.88 (s, 2H), 7.98 (s, 1H), 12.09 (brs, 1H).
Reaction SMILES: [Br-:1].[Br-:2].[Br-].[Al+3].BrBr.[F:7][C:8]1[CH:13]=[CH:12][C:11]([CH3:14])=[CH:10][CH:9]=1>O>[Br:1][C:9]1[C:10]([Br:2])=[C:11]([CH3:14])[CH:12]=[CH:13][C:8]=1[F:7]
Reactant: [Br-]
Reactant: Cc1ccc(F)cc1
Agent: BrBr
Agent: [Al+3]
Solvent: O
Product: Cc1ccc(F)c(Br)c1Br
Temperature: -15 °C
Yield: 4 %

Procedure:
2.67 g of aluminum tribromide and 16.0 g of bromine were added to 110 g of 4-fluorotoluene, which had been cooled to -15° C. After increasing the temperature to +10° C., hydrolysis was carried out with water, the mixture was extracted by shaking with methylene chloride and the methylene chloride phase was washed and dried. After distilling off the solvent and the excess 4-fluorotoluene, 5.5 g of a mixture consisting of 88% of 2-bromo-4-fluorotoluene, 8% of 3-bromo-4-fluorotoluene and 4% of dibromo-4-fluorotoluene were obtained at a boiling point of 172° to 184° C. (normal pressure). Relative to the 4-fluorotoluene reacted, the yield of 3-bromo-4-fluorotoluene was 2.3%.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([N:8]2[CH2:16][CH:15]3[CH2:17][N:11]4[CH2:12][CH:13]([CH2:18][CH:9]2[CH2:10]4)[CH2:14]3)[CH:5]=[N:6][CH:7]=1.[CH3:19][O:20][C:21]1[C:26](B(O)O)=[CH:25][CH:24]=[CH:23][N:22]=1>>[CH3:19][O:20][C:21]1[C:26]([C:2]2[CH:7]=[N:6][CH:5]=[C:4]([N:8]3[CH2:16][CH:15]4[CH2:17][N:11]5[CH2:12][CH:13]([CH2:18][CH:9]3[CH2:10]5)[CH2:14]4)[CH:3]=2)=[CH:25][CH:24]=[CH:23][N:22]=1
Reactant: Brc1cncc(N2CC3CC4CC2CN(C4)C3)c1
Reactant: COc1ncccc1B(O)O
Product: COc1ncccc1-c1cncc(N2CC3CC4CC2CN(C4)C3)c1

Procedure:
The title compound was prepared from the product of Example 65A and 2-methoxypyridin-3-ylboronic acid according to General Method B: LC-MS Method D (ESI+) m/z 337.0 (M+H)+, retention time 1.24 minutes.
Reaction SMILES: [CH:1]1([C:4]2([F:26])[CH2:7][N:6]([C:8]3[N:13]=[C:12]([S:14]([CH3:17])(=O)=O)[N:11]=[C:10]([NH:18][C:19]4[NH:23][N:22]=[C:21]([CH3:24])[CH:20]=4)[C:9]=3[F:25])[CH2:5]2)[CH2:3][CH2:2]1.[F:27][C:28]([F:41])([F:40])[CH2:29][C:30]([NH:32][C:33]1[CH:38]=[CH:37]C(S)=[CH:35][CH:34]=1)=[O:31]>CN(C=O)C.C(OC(=O)C)C.C([O-])(O)=O.[Na+]>[CH3:24][C:21]1[CH:20]=[C:19]([NH:18][C:10]2[C:9]([F:25])=[C:8]([N:6]3[CH2:7][C:4]([CH:1]4[CH2:3][CH2:2]4)([F:26])[CH2:5]3)[N:13]=[C:12]([S:14][C:17]3[CH:35]=[CH:34][C:33]([NH:32][C:30](=[O:31])[CH2:29][C:28]([F:41])([F:27])[F:40])=[CH:38][CH:37]=3)[N:11]=2)[NH:23][N:22]=1
Reactant: O=C(CC(F)(F)F)Nc1ccc(S)cc1
Reactant: Cc1cc(Nc2nc(S(C)(=O)=O)nc(N3CC(F)(C4CC4)C3)c2F)[nH]n1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: Cc1cc(Nc2nc(Sc3ccc(NC(=O)CC(F)(F)F)cc3)nc(N3CC(F)(C4CC4)C3)c2F)[nH]n1
Reaction time: 6 h
Yield: 44.9 %

Procedure:
A solution of 6-(3-cyclopropyl-3-fluoroazetidin-1-yl)-5-fluoro-N-(3-methyl-1H-pyrazol-5-yl)-2-(methylsulfonyl)pyrimidin-4-amine (64 mg, 0.17 mmol) and 3,3,3-trifluoro-N-(4-mercaptophenyl)propanamide (47 mg, 0.20 mmol) in DMF (3 ml) was heated to 80° C. and stirred for 6 hrs. The reaction was diluted with ethylacetate (20 ml) and Sat. NaHCO3 (20 ml) and the organic layer washed with brine (20 ml), dried (Na2SO4) and concentrated to give an oil. Compound was purified by mass directed preparative HPLC, eluted with acetonitrile/water/TFA to give the title compound as a white solid (TFA salt, 41.2 mg, 37%). 1H NMR (DMSO, 400 MHz) 0.46-0.50 (2H, m), 0.61-0.64 (2H, m), 1.38-1.45 (1H, m), 1.93 (3H, s), 3.55 (2H, q), 4.00-4.18 (4H, m), 5.27 (1H, s), 7.54 (2H, d), 7.71 (2H, d), 9.39 (1H, s), 10.57 (1H, s). ES+ 540.
Reaction SMILES: C(N(CC)CC)C.[NH2:8][CH2:9][CH:10]1[CH2:15][CH2:14][N:13]([CH2:16][C@@H:17]2[O:22][C:21]3[CH:23]=[C:24]([Cl:27])[CH:25]=[CH:26][C:20]=3[O:19][CH2:18]2)[CH2:12][CH2:11]1.[Cl:28][C:29]1[CH:34]=[CH:33][C:32]([S:35](Cl)(=[O:37])=[O:36])=[CH:31][CH:30]=1>ClCCl>[Cl:27][C:24]1[CH:25]=[CH:26][C:20]2[O:19][CH2:18][C@H:17]([CH2:16][N:13]3[CH2:14][CH2:15][CH:10]([CH2:9][NH:8][S:35]([C:32]4[CH:33]=[CH:34][C:29]([Cl:28])=[CH:30][CH:31]=4)(=[O:37])=[O:36])[CH2:11][CH2:12]3)[O:22][C:21]=2[CH:23]=1
Reactant: O=S(=O)(Cl)c1ccc(Cl)cc1
Reactant: NCC1CCN(C[C@H]2COc3ccc(Cl)cc3O2)CC1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: O=S(=O)(NCC1CCN(C[C@H]2COc3ccc(Cl)cc3O2)CC1)c1ccc(Cl)cc1
Reaction time: 20 h
Yield: 42.9 %

Procedure:
Triethylamine (0.62 ml) was added to a solution of (S)-4-(aminomethyl)-1-(7-chloro-1,4-benzodioxan-2-ylmethyl)piperidine (0.44 g) and 4-chlorobenzene-sulphonyl chloride (0.62 g) in dichloromethane (22 ml), under nitrogen, and stirred for 20 hours. The reaction was diluted with dichloromethane (100 ml), washed with water (100 ml) and brine (100 ml), dried over anhydrous magnesium sulphate and concentrated under reduced pressure. Purification by flash chromatography on silica gel eluting with a 20:1 mixture of dichloromethane and methanol gave (S)-(-)-N-{[1-(7-chloro-1,4-benzodioxan-2-ylmethyl)-4-piperidyl]methyl}-4-chlorobenzene-sulphonamide as a white solid (0.30 g); m.p. 152-154° C., [α]D22.5 -23.8° (c=0.97, CH2Cl2).
Reaction SMILES: S(=O)(=O)(O)O.C([O:9][C:10]1[CH:15]=[CH:14][C:13]([N:16]2[C:21](=[O:22])[N:20]([CH3:23])[C:19](=[O:24])[CH:18]=[N:17]2)=[C:12]([F:25])[CH:11]=1)(C)C>>[OH:9][C:10]1[CH:15]=[CH:14][C:13]([N:16]2[C:21](=[O:22])[N:20]([CH3:23])[C:19](=[O:24])[CH:18]=[N:17]2)=[C:12]([F:25])[CH:11]=1
Reactant: CC(C)Oc1ccc(-n2ncc(=O)n(C)c2=O)c(F)c1
Agent: O=S(=O)(O)O
Product: Cn1c(=O)cnn(-c2ccc(O)cc2F)c1=O
Temperature: 0 °C

Procedure:
Concentrated sulfuric acid (5 mL) that had been cooled to 0°-5° C. was mixed with 2.80 g (0.010 mole) of 2-(4-isopropoxy-2-fluorophenyl)-4-methyl-1,2,4-triazine-3,5-dione that had been cooled to 0° C. The mixture was maintained at 9° C. for ten minutes, during which time it became homogeneous. The mixture was then poured into ice-water, and the resulting mixture was extracted with ethyl acetate. The extract was washed in succession with a saturated aqueous solution of sodium bicarbonate and a saturated aqueous solution of sodium chloride. The extract was dried over anhydrous magnesium sulfate and filtered. The solvent was evaporated from the filtrate under reduced pressure, leaving a residue. This residue was placed on a column of silica gel and eluted with ethyl acetate/hexane (1:1). After the product-containing fractions were combined and the solvents evaporated under reduced pressure, 1.38 g of 2-(4-hydroxy-2-fluorophenyl)-4-methyl-1,2,4-triazine-3,5-dione was recovered as a stiff syrup. The NMR was consistent with the proposed structure.
Reaction SMILES: [CH2:1]([N:8]1[CH2:12][CH:11]=[C:10]([CH2:13][OH:14])[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Br:15][C:16]1[CH:21]=[CH:20][C:19]([C:22]([F:25])([F:24])[F:23])=[CH:18][C:17]=1O.CCOC(/N=N/C(OCC)=O)=O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>O1CCCC1>[CH2:1]([N:8]1[CH2:12][CH:11]=[C:10]([CH2:13][O:14][C:17]2[CH:18]=[C:19]([C:22]([F:24])([F:25])[F:23])[CH:20]=[CH:21][C:16]=2[Br:15])[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: OCC1=CCN(Cc2ccccc2)C1
Reactant: Oc1cc(C(F)(F)F)ccc1Br
Agent: CCOC(=O)/N=N/C(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: FC(F)(F)c1ccc(Br)c(OCC2=CCN(Cc3ccccc3)C2)c1
Temperature: 50 °C
Reaction time: 8 h
Yield: 49.4 %

Procedure:
(1-Benzyl-2,5-dihydro-1H-pyrrol-3-yl)methanol (11.44 g) obtained in Example 50(2), 2-bromo-5-trifluoromethylphenol (16.04 g), DEAD (40% toluene solution, 11.06 mL) and triphenylphosphine (18.95 g) were dissolved in tetrahydrofuran (450 mL). The reaction solution was stirred at 50° C. overnight. Tetrahydrofuran was evaporated under reduced pressure, and the residue was purified by silica gel column (10% ethyl acetate/petroleum ether to 20% ethyl acetate/petroleum ether) to give the object product as a white solid (12.3 g, 49%).
Reaction SMILES: [CH3:1][Si]([N-][Si](C)(C)C)(C)C.[Na+].[O:11]1[C:15]2([CH2:20][CH2:19][O:18][CH2:17][CH:16]2[CH2:21][CH2:22][CH2:23][CH:24]=O)[O:14][CH2:13][CH2:12]1>[Br-].C[P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH2:21]([CH:16]1[CH2:17][O:18][CH2:19][CH2:20][C:15]21[O:11][CH2:12][CH2:13][O:14]2)[CH2:22][CH2:23][CH:24]=[CH2:1]
Reactant: C[Si](C)(C)[N-][Si](C)(C)C
Reactant: O=CCCCC1COCCC12OCCO2
Agent: C[P+](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Br-]
Agent: [Na+]
Product: C=CCCCC1COCCC12OCCO2
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a mixture of methyltriphenylphosphonium bromide (0.920 g, 2.58 mmol) in TI IF (10 mL) under N2 at it was added NaHMDS (2M in THF, 1.30 mL, 2.58 mmol). The mixture was stirred at rt for 1 hr. 4-(1,4,8-trioxaspiro[4.5]dec-6-yl)butanal (0.276 g, 1.29 mmol) was then added and the reaction was stirred at it for 1 hr. It was quenched with sat'd. aq. NH4Cl and extracted 3× with Et2O. The combined organics were dried (anhd. Na2SO4), filtered, and concentrated. The residue was purified by column chromatography to give the title compound. 1H NMR (500 MHz, CDCl3) δ 5.75-5.86 (m, 1H), 4.91-5.03 (m, 2H), 3.91-4.05 (m, 4H), 3.78-3.90 (m, 2H), 3.62-3.71 (m, 1H), 3.43 (dd, 1H, J=9.0 Hz, 11.2 Hz), 1.98-2.12 (m, 2H), 1.11-1.81 (m, 7H).
Reaction SMILES: [C:1]([O:4][C@@H:5]1[C@@H:10]([O:11][C:12](=[O:14])[CH3:13])[C@H:9]([O:15][C:16](=[O:18])[CH3:17])[CH2:8][S:7][CH:6]1Br)(=[O:3])[CH3:2].[OH:20][C:21]1[C:26]2[N:27]=[CH:28][O:29][C:25]=2[CH:24]=[CH:23][CH:22]=1>>[C:1]([O:4][C@@H:5]1[C@@H:10]([O:11][C:12](=[O:14])[CH3:13])[C@H:9]([O:15][C:16](=[O:18])[CH3:17])[CH2:8][S:7][C@H:6]1[O:20][C:21]1[C:26]2[N:27]=[CH:28][O:29][C:25]=2[CH:24]=[CH:23][CH:22]=1)(=[O:3])[CH3:2]
Reactant: CC(=O)O[C@H]1[C@H](OC(C)=O)CSC(Br)[C@@H]1OC(C)=O
Reactant: Oc1cccc2ocnc12
Product: CC(=O)O[C@@H]1[C@@H](OC(C)=O)[C@H](OC(C)=O)CS[C@H]1Oc1cccc2ocnc12
Yield: 41 %

Procedure:
By carrying out the process in a manner similar to example 7, starting from 2,3,4-tri-O-acetyl-5-thio-D-xylopyranosyl bromide and 4-hydroxybenzoxazole, the desired product is obtained in the form of a white solid with a yield of 41%.
Reaction SMILES: Cl[CH2:2][C:3]1[CH:12]=[CH:11][CH:10]=[C:9]2[C:4]=1[CH:5]=[CH:6][C:7]([NH:13][CH2:14][C:15]1[O:16][C:17]([CH3:20])=[CH:18][CH:19]=1)=[N:8]2.[Na+].[Cl:22][C:23]1[CH:28]=[CH:27][C:26]([S:29]([O-:31])=[O:30])=[CH:25][CH:24]=1.O>CN(C)C=O>[Cl:22][C:23]1[CH:28]=[CH:27][C:26]([S:29]([CH2:2][C:3]2[CH:12]=[CH:11][CH:10]=[C:9]3[C:4]=2[CH:5]=[CH:6][C:7]([NH:13][CH2:14][C:15]2[O:16][C:17]([CH3:20])=[CH:18][CH:19]=2)=[N:8]3)(=[O:31])=[O:30])=[CH:25][CH:24]=1
Reactant: O=S([O-])c1ccc(Cl)cc1
Reactant: Cc1ccc(CNc2ccc3c(CCl)cccc3n2)o1
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: Cc1ccc(CNc2ccc3c(CS(=O)(=O)c4ccc(Cl)cc4)cccc3n2)o1
Temperature: 60 °C
Reaction time: 3 h

Procedure:
(5-Chloromethyl-quinolin-2-yl)-(5-methyl-furan-2-ylmethyl)-amine (55 mg, 0.192 mmol) were dissolved in 1 mL dimethylformamide and 4-chlorobenzenesulphinic acid sodium salt (47 mg, 0.237 mmol) was added. The reaction mixture was stirred at 60° C. for 3 h. Water was added until a suspension was formed and the mixture was stirred for 15 min. The solid was filtered off and dried. The title compound was obtained as a brown solid (53 mg, 65%), MS: m/e=427.4 (M+H+).
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:20])[C:5]1[CH:10]=[CH:9][C:8]([N:11]=[CH:12][C:13]2[CH:14]=[N:15][CH:16]=[C:17]([Br:19])[CH:18]=2)=[CH:7][CH:6]=1)[CH3:2].[CH:21](=[O:25])[CH:22]([CH3:24])[CH3:23].O>O1CCCC1.O.[O-]S(C(F)(F)F)(=O)=O.[Yb+3].[O-]S(C(F)(F)F)(=O)=O.[O-]S(C(F)(F)F)(=O)=O>[CH2:1]([O:3][C:4]([C:5]1[CH:10]=[C:9]2[C:8](=[CH:7][CH:6]=1)[NH:11][CH:12]([C:13]1[CH:14]=[N:15][CH:16]=[C:17]([Br:19])[CH:18]=1)[C:22]([CH3:24])([CH3:23])[CH:21]2[OH:25])=[O:20])[CH3:2]
Reactant: CC(C)C=O
Reactant: CCOC(=O)c1ccc(N=Cc2cncc(Br)c2)cc1
Agent: O=S(=O)([O-])C(F)(F)F
Agent: [Yb+3]
Solvent: C1CCOC1
Solvent: O
Product: CCOC(=O)c1ccc2c(c1)C(O)C(C)(C)C(c1cncc(Br)c1)N2
Temperature: 25 °C
Reaction time: 16 h
Yield: 104.1 %

Procedure:
To a mixture of 4-[(5-bromo-pyridin-3-ylmethylene)-amino]-benzoic acid ethyl ester (33.8 g, 100 mmol) and Ytterbium(III) triflate hydrate (6.2 g, 10 mmol) in dry tetrahydrofuran (100 mL) at 25° C. was added isobutyraldehyde (9.2 mL, 100 mmol) and water (1.8 mL, 100 mmol) dropwise. The reaction mixture was stirred at 25° C. for 16 h. Then the reaction mixture was concentrated in vacuo and the residue was extracted with ethyl acetate (2×200 mL), washed with brine, dried over anhydrous sodium sulfate and concentrated in vacuo to afford 2-(5-bromo-pyridin-3-yl)-4-hydroxy-3,3-dimethyl-1,2,3,4-tetrahydro-quinoline-6-carboxylic acid ethyl ester (42.2 g, quant.) as a light yellow oil which was used for next step without further purification: LC/MS m/e calcd for C19H21BrN2O3 (M+H)+: 406.29, observed: 405.0 & 406.9.
Reaction SMILES: S(=O)(=O)(O)O.C([O:9][C:10]1[CH:11]=[C:12]2[C:16](=[CH:17][CH:18]=1)[C:15](=[O:19])[CH:14](C(OCC)=O)[CH:13]2[OH:25])(=O)C>O>[OH:9][C:10]1[CH:11]=[C:12]2[C:16](=[CH:17][CH:18]=1)[C:15](=[O:19])[CH2:14][C:13]2=[O:25]
Reactant: CCOC(=O)C1C(=O)c2ccc(OC(C)=O)cc2C1O
Agent: O=S(=O)(O)O
Solvent: O
Product: O=C1CC(=O)c2cc(O)ccc21

Procedure:
4 ml of 10N sulphuric acid were added to a suspension of 0.01 mol of 5-acetoxy-2-carbethoxy-3-hydroxy-1-indanone in 80 ml water. The reaction mixture was refluxed for 15 minutes. The insoluble substance was filtered when hot and the yellow precipitate formed after cooling was dried on suction pump, washed in ice water and dried.
Reaction SMILES: [CH3:1][N:2]1[C:10]2[N:9]=[C:8]([Br:11])[N:7]([CH2:12][C:13]#[C:14][CH3:15])[C:6]=2[C:5](=[O:16])[NH:4][C:3]1=[O:17].Cl[CH2:19][C:20]1[N:29]=[C:28]([CH3:30])[C:27]2[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=2)[N:21]=1.C(=O)([O-])[O-].[K+].[K+].O>CN1CCCC1=O>[CH3:30][C:28]1[C:27]2[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=2)[N:21]=[C:20]([CH2:19][N:4]2[C:5](=[O:16])[C:6]3[N:7]([CH2:12][C:13]#[C:14][CH3:15])[C:8]([Br:11])=[N:9][C:10]=3[N:2]([CH3:1])[C:3]2=[O:17])[N:29]=1
Reactant: CC#CCn1c(Br)nc2c1c(=O)[nH]c(=O)n2C
Reactant: Cc1nc(CCl)nc2ccccc12
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN1CCCC1=O
Solvent: O
Product: CC#CCn1c(Br)nc2c1c(=O)n(Cc1nc(C)c3ccccc3n1)c(=O)n2C
Temperature: 75 °C
Reaction time: 6 h

Procedure:
A mixture of 28.91 g of 3-methyl-7-(2-butyn-1-yl)-8-bromoxanthine, 20.00 g of 2-chloromethyl-4-methylquinazoline and 27.74 g of potassium carbonate in 235 ml of N-methylpyrrolidone is warmed to 75° C. and stirred at this temperature for six hours. Subsequently, the reaction mixture is slowly treated with 235 ml of water, a pale precipitate depositing. The suspension is cooled in an ice bath. The precipitate is filtered off with suction, washed with water and a little petroleum ether and dried at 50° C. in a circulating air drying oven.
Reaction SMILES: [BH4-].[Na+].[C:3]([C:8]1[C:9](=[O:17])[CH2:10][CH:11]([CH:15]=[O:16])[CH2:12][C:13]=1[OH:14])(=[O:7])[CH2:4][CH2:5][CH3:6]>O1CCCC1.O>[C:3]([C:8]1[C:13](=[O:14])[CH2:12][CH:11]([CH2:15][OH:16])[CH2:10][C:9]=1[OH:17])(=[O:7])[CH2:4][CH2:5][CH3:6]
Reactant: CCCC(=O)C1=C(O)CC(C=O)CC1=O
Agent: [BH4-]
Agent: [Na+]
Solvent: O
Solvent: C1CCOC1
Product: CCCC(=O)C1=C(O)CC(CO)CC1=O
Temperature: 25 °C
Reaction time: 2 h
Yield: 74.3 %

Procedure:
0.1 g of sodium borohydride was added to 2.0 g of 2-butyryl-5-formyl-3-hydroxycyclohex-2-en-1-one in 30 ml of aqueous tetrahydrofuran; the mixture was stirred for 2 hours at 25° C. The mixture was then diluted with water, extracted several times with diethyl ether, dried and concentrated. There was obtained 1.5 g of 2-butyryl-3-hydroxy-5-hydroxymethylcyclohex-2-en-1-one (compound no. 3).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:9]=[C:8]([O:10][CH3:11])[CH:7]=[CH:6][C:4]=1[NH2:5].C(=O)([O-])[O-].[K+].[K+].Br[CH2:19][C:20]([O:22][CH3:23])=[O:21].O>CN(C=O)C>[CH3:23][O:22][C:20](=[O:21])[CH2:19][NH:5][C:4]1[CH:6]=[CH:7][C:8]([O:10][CH3:11])=[CH:9][C:3]=1[O:2][CH3:1]
Reactant: COc1ccc(N)c(OC)c1
Reactant: COC(=O)CBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: COC(=O)CNc1ccc(OC)cc1OC
Temperature: 60 °C
Reaction time: 3 h

Procedure:
To a mixture of 1.53 g (10 mmol) of 2,4-dimethoxyaniline and 2.76 g (20 mmol) of potassium carbonate in 10 mL of DMF are added 1.53 g (10 mmol) of methyl bromoacetate. The mixture is stirred at 60° C. for 3 h, then allowed to cool to RT. The mixture is poured into water and extracted with EtOAc. The organic phase is washed with water, brine and dried over anhydrous Na2SO4. The solvent is removed under reduced pressure and the residue is chromatographed using CH2Cl2 as the eluant to give (2,4-dimethoxyphenylamino)-acetic acid methyl ester as an oil: 1H-NMR (CDCl3) δ 6.46 (d, J=2.20, 1H), 6.41-6.38 (m, 2H), 3.91 (s, 2H), 3.84 (s, 3H), 3.77 (s, 3H), 3.75 (s, 3H).