Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C(OC([C:17]1[N:18]2[CH:21]([O:22][CH2:23][C:24]=1[CH:25]=[CH:26]N(C)C)[CH:20](NC(=O)C(=NOC)C1N=C(NC(C3C=CC=CC=3)(C3C=CC=CC=3)C3C=CC=CC=3)SC=1)[C:19]2=[O:62])=O)(C1C=CC=CC=1)C1C=CC=CC=1.Cl.C(OCC)(=[O:66])C>>[O:62]=[C:19]1[N:18]2[CH:21]([O:22][CH2:23][C:24]([CH2:25][CH:26]=[O:66])=[CH:17]2)[CH2:20]1
Reactant: CON=C(C(=O)NC1C(=O)N2C(C(=O)OC(c3ccccc3)c3ccccc3)=C(C=CN(C)C)COC12)c1csc(NC(c2ccccc2)(c2ccccc2)c2ccccc2)n1
Reactant: CCOC(C)=O
Agent: Cl
Product: O=CCC1=CN2C(=O)CC2OC1

Procedure:
A solution of the E form of the syn isomer of 2-benzhydryloxycarbonyl-3-(2-dimethylaminovinyl)-7-[2-methoxyimino-2-(2-tritylaminothiazol-4-yl)-acetamido]-8-oxo-5-oxa-1-azabicyclo[4.2.0]oct-2-ene (1.05 g) in ethyl acetate (10 cc) is stirred vigorously for 1 hour at 20° C., in the presence of a 1 N solution of hydrochloric acid (5 cc). The mixture is separated by decantation and the organic phase is washed with a saturated solution of sodium bicarbonate (10 cc), distilled water (10 cc) and a saturated solution of sodium chloride (10 cc). The ethyl acetate phase is dried over anhydrous magnesium sulphate and filtered and the filtrate is concentrated to dryness at 30° C. under reduced pressure (20 mm Hg; 2.7 kPa). This yields the syn isomer of 2-benzhydryloxycarbonyl-7-[2-methoxyimino-2-(2-tritylaminothiazol-4-yl)-acetamido[-8-oxo-3-(2-oxoethyl)-5-oxa-1-azabicyclo[4.2.0]-oct-2-ene (1.00 g) in the form of a hard yellow foam.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C:9]([F:12])([F:11])[F:10])[CH:5]=[CH:6][C:7]=1[Cl:8].C([Li])CCC.[C:18](=[O:20])=[O:19].Cl>O1CCCC1.O.CCCCCC>[Cl:1][C:2]1[C:7]([Cl:8])=[CH:6][CH:5]=[C:4]([C:9]([F:12])([F:10])[F:11])[C:3]=1[C:18]([OH:20])=[O:19]
Reactant: FC(F)(F)c1ccc(Cl)c(Cl)c1
Reactant: O=C=O
Agent: Cl
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: O
Solvent: CCCCCC
Product: O=C(O)c1c(C(F)(F)F)ccc(Cl)c1Cl
Temperature: -78 °C
Reaction time: 2 h
Yield: 88.6 %

Procedure:
83.4 g of 3,4-dichlorobenzotrifluoride was dissolved in 800 ml of dried tetrahydrofuran, and 250 ml of hexane solution of n-butyl lithium(1.6 mol/1) was added to the solution dropwise over 15 minutes at -78° C. under nitrogen atmosphere. Following to stirring the solution for 2 hours at -78° C., 50 g of dry ice was then gradually added to the solution at the same temperature. After elevating the temperature of the solution up to room temperature, 250 ml of cold water was added to the solution to separate the resulting solution, and the aqueous layer obtained was adjusted to an acidic condition of a pH value of 1 with concentrated hydrochloric acid while cooling. Then, the aqueous layer was extracted with ether, and the extract was washed with water and dried over anhydrous magnesium sulfate. The solvent was distilled out under reduced pressure, and the oily residue obtained was crystalized with n-hexane, washed, filtered, and dried to obtain 89 g of the title compound(mp. 88-89° C.).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][C:9]2[CH:14]=[CH:13][C:12]([CH2:15]O)=[CH:11][CH:10]=2)=[CH:4][C:3]=1[C:17]([F:20])([F:19])[F:18].S(Cl)([Cl:23])=O>>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][C:9]2[CH:14]=[CH:13][C:12]([CH2:15][Cl:23])=[CH:11][CH:10]=2)=[CH:4][C:3]=1[C:17]([F:20])([F:19])[F:18]
Reactant: OCc1ccc(Oc2ccc(Cl)c(C(F)(F)F)c2)cc1
Reactant: O=S(Cl)Cl
Product: FC(F)(F)c1cc(Oc2ccc(CCl)cc2)ccc1Cl
Yield: 94.2 %

Procedure:
A solution of (4-{[4-chloro-3-(trifluoromethyl)phenyl]oxy}phenyl)methanol (200 mg, 0.661 mmol) in thionyl chloride (0.5 mL, 6.85 mmol) was stirred at rt for 1 h. Then the excess thionyl chloride was removed under vacuum to afford the title product (200 mg) as a yellow oil, which was used in the next reaction without purification. LC-MS (ESI): m/z 285 [M−Cl]+; 4.17 min (ret time).
Reaction SMILES: [CH3:1][O:2][C:3]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:6]([OH:13])=[CH:5][CH:4]=1.C[C:15](OI(OC(C)=O)C1C=CC=CC=1)=[O:16].C([O-])(O)=O.[Na+]>>[CH3:1][O:2][C:3]1([O:16][CH3:15])[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:6](=[O:13])[CH:5]=[CH:4]1
Reactant: COc1ccc(O)c2ccccc12
Reactant: CC(=O)OI(OC(C)=O)c1ccccc1
Agent: O=C([O-])O
Agent: [Na+]
Product: COC1(OC)C=CC(=O)c2ccccc21

Procedure:
A solution of 4-methoxy-1-naphthol (2.76 g, 15.8 mmol) and DAIB (6.10 g, 18.9 mmol) on methanol (75 mL) was stirred at 25° C. under a nitrogen atmosphere for 1 h. The resultant dark blue solution was poured into a saturated NaHCO3 (aq) solution (75 mL), then the mixture concentrated to approx. 50 mL in vacuo. The blue oil was extracted with dichloromethane (3×75 mL) and the organic layer washed with water (2×75 mL) and brine (2×75 mL), then dried (MgSO4), filtered and concentrated in vacuo (water bath temperature <40° C.) to yield 4,4-dimethoxy-4H-naphthalen-1-one as a dark-blue semi-solid which was used without further purification; 1H NMR (CDCl3) δ 8.15 (1H, d, J 8.0 Hz, ArH), 7.40–7.85 (3H, m, ArH), 6.90 (1H, d, J 12.2 Hz, H-3), 6.55 (1H, d, J 12.2 Hz, H-2), 3.15 (6H, s, OCH3).
Reaction SMILES: [F:1][C:2](F)(F)[CH2:3][CH2:4][O:5][C:6]1[CH:14]=[C:13]2[C:9]([CH2:10][C:11]3([CH2:20][CH2:19][C:18](=[O:21])[CH2:17][CH2:16]3)[C:12]2=[O:15])=[CH:8][CH:7]=1.FCCCOC1C=C2C(CCC2=O)=CC=1.C(OC)(=O)C=C>>[F:1][CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:14]=[C:13]2[C:9]([CH2:10][C:11]3([CH2:16][CH2:17][CH:18]([OH:21])[CH2:19][CH2:20]3)[C:12]2=[O:15])=[CH:8][CH:7]=1
Reactant: O=C1CCC2(CC1)Cc1ccc(OCCC(F)(F)F)cc1C2=O
Agent: O=C1CCc2ccc(OCCCF)cc21
Solvent: C=CC(=O)OC
Product: O=C1c2cc(OCCCF)ccc2CC12CCC(O)CC2

Procedure:
The title compound was prepared following the method described for Intermediate 17 and in a subsequent step the method described for Intermediate 18, starting from 6-(3-fluoropropoxy)-2,3-dihydro-1H-inden-1-one (Intermediate 20, 3.16 g, 15.2 mmol) and methyl acrylate (3.01 mL, 33.4 mmol). The product was purified by flash chromatography (0-100% EtOAc in heptane) to afford the title compound as a 2:1 mixture of diastereomers (0.910 g, 32% yield). 1H NMR (500 MHz, CDCl3) δ ppm 1.43-1.52 (m, 3 H) 1.74-1.85 (m, 2 H) 1.95 (td, 1 H) 2.14-2.24 (m, 2 H) 2.93-3.02 (m, 2 H) 3.73-3.80 (m, 1 H) 4.10-4.16 (m, 2 H) 4.61 (t, 1 H) 4.70 (t, 1 H) 7.18-7.22 (m, 2 H) 7.31-7.38 (m, 1 H); MS (ES+) m/z 293.09 [M+H]+.
Reaction SMILES: [Cl:1][C:2]1[CH:8]=[C:6]([OH:7])[C:5]([OH:9])=[C:4]([N+:10]([O-:12])=[O:11])[CH:3]=1.[C:13]([O-])([O-])=O.[K+].[K+].C(Br)Br.O>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([N+:10]([O-:12])=[O:11])[C:5]2[O:9][CH2:13][O:7][C:6]=2[CH:8]=1
Reactant: O=C([O-])[O-]
Reactant: O=[N+]([O-])c1cc(Cl)cc(O)c1O
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Solvent: BrCBr
Product: O=[N+]([O-])c1cc(Cl)cc2c1OCO2
Temperature: 140 °C
Yield: 82 %

Procedure:
Under N2 200 g of 5-chloro-3-nitro-catechol is dissolved in 1050 ml DMF. To this solution are added 204 g anhydrous, powdered K2CO3 and 220 ml CH2Br2, while stirring the mixture. The reaction mixture is refluxed for 1 hour (140° C.) and then cooled down to 80° C. After addition of 800 ml water, the mixture is cooled down to room temp. The crystalline product is filtered off and washed successively with 2×600 ml water, 2×250 ml ethanol, and 2×300 ml n-hexane. After drying under reduced pressure at 60° C., the desired product is obtained in a yield of 82%; purity 95%. Equally successful results are obtained in toluene as the solvent instead of DMF, under phase transfer conditions.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[N:22]=[CH:21][N:20]=[C:19]3[C:15]=2[N:16]=[CH:17][N:18]3[CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=2[C:30]#[N:31])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Cl:32]N1C(=O)CCC1=O.C(OCC)(=O)C.O>CN(C)C=O>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][N:11]([C:14]2[N:22]=[CH:21][N:20]=[C:19]3[C:15]=2[N:16]=[C:17]([Cl:32])[N:18]3[CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=2[C:30]#[N:31])[CH2:12][CH2:13]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: O=C1CCC(=O)N1Cl
Reactant: CC(C)(C)OC(=O)N1CCN(c2ncnc3c2ncn3Cc2ccccc2C#N)CC1
Solvent: CN(C)C=O
Solvent: O
Solvent: CCOC(C)=O
Product: CC(C)(C)OC(=O)N1CCN(c2ncnc3c2nc(Cl)n3Cc2ccccc2C#N)CC1
Temperature: 25 °C
Reaction time: 72 h
Yield: 22.1 %

Procedure:
4-[9-(2-Cyanobenzyl)-9H-purin-6-yl]-piperazine-1-carboxylic acid t-butyl ester (0.419 g) was suspended in N,N-dimethylformamide (80 mL), and then N-chlorosuccinimide (0.160 g) was added. This was stirred at room temperature for 72 hours. N-chlorosuccinimide (0.160 g) was added again, and this was then heated at 60° C. for 18 hours. Ethyl acetate (200 mL) and water (100 mL) were then added, and the organic layer was washed twice with 50 mL of water and then once with 5 mL of saturated aqueous sodium chloride solution. This was then dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure, and then the residue was purified by silica gel chromatography. The dichloromethane:ethyl acetate 7:3 fraction gave the title compound (0.100 g).
Reaction SMILES: [Na].Cl[C:3]1[CH:4]=[N:5][CH:6]=[CH:7][C:8]=1[C:9]#[N:10].[CH2:11]([OH:13])[CH3:12]>>[CH2:11]([O:13][C:3]1[CH:4]=[N:5][CH:6]=[CH:7][C:8]=1[C:9]#[N:10])[CH3:12]
Reactant: CCO
Reactant: N#Cc1ccncc1Cl
Agent: [Na]
Product: CCOc1cnccc1C#N
Temperature: 25 °C
Reaction time: 24 h
Yield: 62 %

Procedure:
A mixture of sodium metal (1.4 g, 0.06 mol) and ethanol (10 ml) was stirred until all of the sodium metal had dissolved and the solvent was removed in vacuo. The residue was placed under argon, and DMF (50 ml), followed by 3-chloro-4-cyanopyridine (6.95 g, 0.05 mol) were added at 5° C. The mixture was warmed to room temperature and stirred for 24 hours. The solvent was removed in vacuo and the residue was treated with dichloromethane and filtered. The filtrate was removed in vacuo, the residue was treated with water and a solid was collected by filtration to afford 4.6 g (62%) of 3-ethoxy-4-cyanopyridine as a tan solid, m.p. 56°-57° C.
Reaction SMILES: [F:1][C:2]1[CH:3]=[CH:4][C:5]([NH:8][NH2:9])=[N:6][CH:7]=1.CCN(C(C)C)C(C)C.[CH3:19][C@H:20]1[CH2:25][CH2:24][CH2:23][CH2:22][N:21]1[C:26](Cl)=[O:27].O>C(Cl)Cl.CO>[F:1][C:2]1[CH:3]=[CH:4][C:5]([NH:8][NH:9][C:26]([N:21]2[CH2:22][CH2:23][CH2:24][CH2:25][C@@H:20]2[CH3:19])=[O:27])=[N:6][CH:7]=1
Reactant: NNc1ccc(F)cn1
Reactant: C[C@H]1CCCCN1C(=O)Cl
Solvent: ClCCl
Solvent: O
Solvent: CCN(C(C)C)C(C)C
Product: C[C@H]1CCCCN1C(=O)NNc1ccc(F)cn1
Temperature: 25 °C
Reaction time: 66 h
Yield: 56.9 %

Procedure:
To a solution of (5-fluoro-pyridin-2-yl)-hydrazine (582 mg, 4.58 mmol) and DIPEA (0.997 mL, 5.72 mmol) in dry DCM (20 mL) was added Intermediate 81a (740 mg, 4.58 mmol) and the resulting red solution stirred at RT for 66 h, and at reflux for 4 h. To the cooled solution was added water (20 mL) and the mixture shaken. The aqueous was extracted with DCM (20 mL), then the combined organics passed through a hydrophobic frit and concentrated in vacuo to leave a pale brown solid. FCC, using 0-5% MeOH in DCM, gave the title compound as a pale yellow solid (657 mg, 57%). 1H NMR (300 MHz, CDCl3): 1.22 (3H, d, J 6.9), 1.40-1.77 (6H, m), 2.96 (1H, td, J 13.0, 2.9), 3.85 (1H, ddd, J 13.3, 4.5, 2.2), 4.31 (1H, m), 6.50 (1H, s), 6.59 (1H, br s), 6.75 (1H, ddd, J 9.0, 3.6, 0.7), 7.27 (1H, ddd, J 9.1, 8.1, 3.1), 8.02 (1H, d, J 2.9).
Reaction SMILES: [C:1]1([NH:7][CH2:8][CH2:9][OH:10])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.N1C=CN=C1.[CH3:16][C:17]([Si:20](Cl)([CH3:22])[CH3:21])([CH3:19])[CH3:18]>C(Cl)Cl.O>[Si:20]([O:10][CH2:9][CH2:8][NH:7][C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1)([C:17]([CH3:19])([CH3:18])[CH3:16])([CH3:22])[CH3:21]
Reactant: OCCNc1ccccc1
Reactant: CC(C)(C)[Si](C)(C)Cl
Agent: c1c[nH]cn1
Solvent: O
Solvent: ClCCl
Product: CC(C)(C)[Si](C)(C)OCCNc1ccccc1
Reaction time: 2 h
Yield: 81.7 %

Procedure:
To a solution of 2-(phenylamino)ethan-1-ol (2.0 g, 14.6 mmol) and imidazole (2.9 g, 43.7 mmol) in DCM (20 mL) was added TBSCl (2.6 g, 16.0 mmol) at r.t., and the reaction was stirred for 2 h. The reaction was diluted with water (50 mL) and extracted with DCM (50 mL×3). Organics were washed with brine (50 mL), dried (Na2SO4), and concentrated. Purification by silica gel chromatography (PE:EtOAc=40:1) gave 3.0 g (82%) of the title compound as a yellow oil.
Reaction SMILES: C[O:2][C:3]([C:5]1[N:6]=[CH:7][C:8]2[C:9](=[O:27])[N:10]([CH2:16][C:17]3[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][C:18]=3[O:25][CH3:26])[CH2:11][CH2:12][C:13]=2[C:14]=1[OH:15])=O.[CH3:28][NH2:29]>CCO>[CH3:28][NH:29][C:3]([C:5]1[N:6]=[CH:7][C:8]2[C:9](=[O:27])[N:10]([CH2:16][C:17]3[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][C:18]=3[O:25][CH3:26])[CH2:11][CH2:12][C:13]=2[C:14]=1[OH:15])=[O:2]
Reactant: CN
Reactant: COC(=O)c1ncc2c(c1O)CCN(Cc1ccc(OC)cc1OC)C2=O
Solvent: CCO
Product: CNC(=O)c1ncc2c(c1O)CCN(Cc1ccc(OC)cc1OC)C2=O
Temperature: 80 °C

Procedure:
A mixture of 7-(2,4-dimethoxy-benzyl)-4-hydroxy-8-oxo-5,6,7,8-tetrahydro-[2,7]naphthyridine-3-carboxylic acid methyl ester (15 mg, 0.040 mmol) and methylamine (0.8 mL, 2M in THF) in EtOH (2 mL) was heated at 80° C. in a sealed tube for 4 h. After the mixture was cooled to r.t., solvent was evaporated in vacuo. The residue was purified by silica gel chromatography (5-80% EtOAc/hexanes+2% AcOH) to give 12 mg of the title compound as a light yellow solid. MS: (+) m/z 372.27 (M+1).
Reaction SMILES: [N+:1]([O-:4])([O-])=[O:2].[K+].[NH2:6][C:7]1[C:12]([C:13]#[N:14])=[C:11]([CH3:15])[C:10]([Br:16])=[C:9]([F:17])[CH:8]=1>S(=O)(=O)(O)O>[NH2:6][C:7]1[C:8]([N+:1]([O-:4])=[O:2])=[C:9]([F:17])[C:10]([Br:16])=[C:11]([CH3:15])[C:12]=1[C:13]#[N:14]
Reactant: Cc1c(Br)c(F)cc(N)c1C#N
Reactant: O=[N+]([O-])[O-]
Agent: O=S(=O)(O)O
Agent: [K+]
Product: Cc1c(Br)c(F)c([N+](=O)[O-])c(N)c1C#N
Reaction time: 0.17 h

Procedure:
With cooling with ice, potassium nitrate (2.43 g, 21.8 mmol) was gradually added to a concentrated sulfuric acid (20 ml) solution of 6-amino-3-bromo-4-fluoro-2-methylbenzonitrile (I-265) (5.00 g, 21.8 mmol). After stirring for 10 minutes, the reaction liquid was poured into ice and stirred.
Reaction SMILES: [NH:1]1[CH2:5][CH2:4][CH2:3][CH2:2]1.[C:6]([C:10]1[CH:14]=[C:13]([NH:15][C:16]([NH:18][C@@H:19]2[C:28]3[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=3)[C@H:22]([O:29][C:30]3[CH:31]=[CH:32][C:33]4[N:34]([C:36]([N:39]5[C@H:44]([CH3:45])[CH2:43][CH2:42][CH2:41][C@@H:40]5[CH3:46])=[N:37][N:38]=4)[CH:35]=3)[CH2:21][CH2:20]2)=[O:17])[N:12]([C:47]2[CH:48]=[C:49]([CH:58]=[CH:59][CH:60]=2)[O:50][CH2:51][CH2:52]OS(C)(=O)=O)[N:11]=1)([CH3:9])([CH3:8])[CH3:7]>C1COCC1>[C:6]([C:10]1[CH:14]=[C:13]([NH:15][C:16]([NH:18][C@@H:19]2[C:28]3[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=3)[C@H:22]([O:29][C:30]3[CH:31]=[CH:32][C:33]4[N:34]([C:36]([N:39]5[C@H:40]([CH3:46])[CH2:41][CH2:42][CH2:43][C@@H:44]5[CH3:45])=[N:37][N:38]=4)[CH:35]=3)[CH2:21][CH2:20]2)=[O:17])[N:12]([C:47]2[CH:60]=[CH:59][CH:58]=[C:49]([O:50][CH2:51][CH2:52][N:1]3[CH2:5][CH2:4][CH2:3][CH2:2]3)[CH:48]=2)[N:11]=1)([CH3:7])([CH3:8])[CH3:9]
Reactant: C1CCNC1
Reactant: C[C@@H]1CCC[C@H](C)N1c1nnc2ccc(O[C@@H]3CC[C@H](NC(=O)Nc4cc(C(C)(C)C)nn4-c4cccc(OCCOS(C)(=O)=O)c4)c4ccccc43)cn12
Solvent: C1CCOC1
Product: C[C@@H]1CCC[C@H](C)N1c1nnc2ccc(O[C@@H]3CC[C@H](NC(=O)Nc4cc(C(C)(C)C)nn4-c4cccc(OCCN5CCCC5)c4)c4ccccc43)cn12
Temperature: 60 °C
Yield: 25.9 %

Procedure:
Pyrrolidine (36 μL, 0.43 mmol) was added to a solution of Intermediate 96f (111 mg, 0.14 mmol) in THF (2 mL). The reaction was heated to 60° C. in a sealed vial overnight. The mixture was cooled, evaporated in vacuo and the residue was purified by FCC, using 0-15% MeOH in DCM, then triturated with Et2O to give the title compound (27 mg, 25%) as an off-white solid. LCMS (Method 5): Rt 3.87 min, m/z 746.6 [MH+]. 1H NMR (400 MHz, d6-DMSO): 0.55 (3H, d, J=6.0 Hz), 0.58 (3H, d, J 6.0 Hz), 1.23 (9H, s), 1.32-1.54 (3H, m), 1.53-1.78 (7H, m), 1.79-1.95 (2H, m), 1.96-2.10 (2H, m), 2.49-2.60 (2H, m), 2.68-2.94 (2H, m), 3.06-3.20 (3H, m), 3.27 (1H, m, obscured by water), 4.03-4.14 (2H, m), 4.74-4.83 (1H, m), 5.49 (1H, t, J=4.0 Hz), 6.29 (1H, s), 6.90-6.96 (1H, m), 7.01-7.09 (3H, m), 7.16 (1H, dd, J=9.7, 2.0 Hz), 7.19-7.25 (2H, m), 7.26-7.32 (2H, m), 7.33-7.39 (1H, m), 7.62 (1H, d, J=9.7 Hz), 7.84 (1H, m), 8.06 (1H, s).
Reaction SMILES: Cl[CH2:2][C:3]([O:5][CH:6]([C:14]([F:17])([F:16])[F:15])[C:7]([F:13])([F:12])[S:8]([O-:11])(=[O:10])=[O:9])=[O:4].[C:18]1([S+:24]([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.[C:37]([O-:42])(=[O:41])[C:38]([CH3:40])=[CH2:39].[Na+].[I-].[Na+].C(C1C(O)=C(C(C)(C)C)C=C(C)C=1)C1C(O)=C(C(C)(C)C)C=C(C)C=1>ClCCl.O.CN(C)C=O>[F:12][C:7]([F:13])([S:8]([O-:11])(=[O:10])=[O:9])[CH:6]([O:5][C:3](=[O:4])[CH2:2][O:42][C:37](=[O:41])[C:38]([CH3:40])=[CH2:39])[C:14]([F:17])([F:16])[F:15].[C:31]1([S+:24]([C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=2)[C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=1
Reactant: C=C(C)C(=O)[O-]
Reactant: O=C(CCl)OC(C(F)(F)F)C(F)(F)S(=O)(=O)[O-]
Agent: Cc1cc(Cc2cc(C)cc(C(C)(C)C)c2O)c(O)c(C(C)(C)C)c1
Agent: [I-]
Agent: [Na+]
Solvent: ClCCl
Solvent: CN(C)C=O
Solvent: O
Product: C=C(C)C(=O)OCC(=O)OC(C(F)(F)F)C(F)(F)S(=O)(=O)[O-]
Temperature: 80 °C
Reaction time: 13 h

Procedure:
To 250 g of dimethylformamide were added 50.0 g (0.09 mole) of triphenylsulfonium 2-(2-chloroacetoxy)-1,1,3,3,3-pentafluoropropane-1-sulfonate synthesized in Synthesis Example 1-19, 11.4 g (0.11 mole) of sodium methacrylate, 2.6 g (0.02 mole) of sodium iodide, and 50 mg of 2,2′-methylenebis(6-t-butyl-p-cresol). The mixture was heated and stirred at 80° C. for 13 hours. The reaction solution was allowed to resume room temperature, after which 500 g of water and 1 kg of dichloromethane were added. The organic layer was separated and washed with water whereupon dichloromethane was distilled off under vacuum. The residue was combined with 300 g of methyl isobutyl ketone, washed with dilute aqueous ammonia and then with water, whereupon methyl isobutyl ketone was distilled off under vacuum. The residue was purified by silica gel chromatography. Diisopropyl ether was added to the residue, followed by decantation. The target compound, triphenylsulfonium 1,1,3,3,3-pentafluoro-2-(2-methacryloyloxy-acetoxy)-propane-1-sulfonate was obtained as brown oil (39.3 g, yield 66%). The compound has the following structure.
Reaction SMILES: [NH2:1][C:2]1[N:3]=[C:4](S(C)(=O)=O)[S:5][C:6]=1[C:7]#[N:8].[NH2:13][CH2:14][CH2:15][OH:16]>CS(C)=O>[NH2:1][C:2]1[N:3]=[C:4]([NH:13][CH2:14][CH2:15][OH:16])[S:5][C:6]=1[C:7]#[N:8]
Reactant: CS(=O)(=O)c1nc(N)c(C#N)s1
Reactant: NCCO
Solvent: CS(C)=O
Product: N#Cc1sc(NCCO)nc1N
Yield: 116.8 %

Procedure:
Example 89A is prepared in analogy to Example 48A from 4-amino-2-(methylsulphonyl)-1,3-thiazole-5-carbonitrile (Example 18A) (499 mg, 2.45 mmol) and 2-aminoethanol (300 mg, 4.91 mmol) in DMSO (80° C., 20 h). Removal of the solvent results in a crude product 527 mg (50% of theory) which is employed without further purification.
Reaction SMILES: Cl[CH2:2][CH2:3][N:4]1[C:13](=[O:14])[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[NH:6][C:5]1=[O:15].[CH3:16][O:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=1[N:24]1[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]1.[I-].[Na+].C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O.O>[CH3:16][O:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=1[N:24]1[CH2:29][CH2:28][N:27]([CH2:2][CH2:3][N:4]2[C:13](=[O:14])[C:12]3[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=3)[NH:6][C:5]2=[O:15])[CH2:26][CH2:25]1
Reactant: O=c1[nH]c2ccccc2c(=O)n1CCCl
Reactant: COc1ccccc1N1CCNCC1
Agent: O=C([O-])[O-]
Agent: [I-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: COc1ccccc1N1CCN(CCn2c(=O)[nH]c3ccccc3c2=O)CC1
Temperature: 0 °C
Reaction time: 24 h
Yield: 86.7 %

Procedure:
A mixture of 3-(2-chloroethyl)-2,4-(1H,3H)-quinazolinedione (1.57 kg), 1-(2-methoxyphenyl)piperazine (1.34 kg), sodium iodide (1.05 kg) and potassium carbonate (0.49 kg) was dissolved in dimethylformamide (7,000 ml) and the solution was heated at an internal temperature of 80°-85° C. for 7 hours. After completion of the reaction, the mixture was cooled by the addition of water (25 l) and ice (5 kg). The cooled mixture was left for 24 hours and the resulting crystal was collected, washed with water and dried with heat to give 3-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-2,4-(1H,3H)quinazolinedione (2.3 kg). Its physicochemical data was the same as that of the products obtained in Example 1.
Reaction SMILES: [CH3:1][Si:2]([CH3:9])([CH3:8])[CH2:3][CH2:4][CH2:5][CH2:6][OH:7].[CH2:10]([O:18][C:19]1[CH:20]=[N:21][C:22]([C:25]2[CH:30]=[CH:29][C:28](O)=[CH:27][CH:26]=2)=[N:23][CH:24]=1)[CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH3:17].N(C(OCC)=O)=NC(OCC)=O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>O1CCCC1>[CH2:10]([O:18][C:19]1[CH:24]=[N:23][C:22]([C:25]2[CH:30]=[CH:29][C:28]([O:7][CH2:6][CH2:5][CH2:4][CH2:3][Si:2]([CH3:9])([CH3:8])[CH3:1])=[CH:27][CH:26]=2)=[N:21][CH:20]=1)[CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH3:17]
Reactant: C[Si](C)(C)CCCCO
Reactant: CCCCCCCCOc1cnc(-c2ccc(O)cc2)nc1
Agent: CCOC(=O)N=NC(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: CCCCCCCCOc1cnc(-c2ccc(OCCCC[Si](C)(C)C)cc2)nc1

Procedure:
439 mg (3 mmol) of 4-(Trimethylsilyl)butan-1-ol and 901 mg (3 mmol) of 4-(5-n-octyloxypyrimidin-2-yl)phenol are added to the solution of 0.46 ml (3 mmol) of diethyl azodicarboxylate and 790 mg (3 mmol) of triphenylphosphine in 15 ml of dry tetrahydrofuran. After a reaction time of 15 h, the solvent is distilled off and the residue is purified chromatographically (SiO2 /CH2Cl2). After recrystallization from n-hexane, 790 mg of colorless crystals are obtained.
Reaction SMILES: [NH2:1][C:2]1[C:3]([CH3:8])=[CH:4][CH:5]=[CH:6][CH:7]=1.[F:9][C:10](I)([F:15])[C:11]([F:14])([F:13])[F:12].S([O-])(O)=O.[Na+].C(=O)([O-])O.[Na+]>[Zn].O1CCCC1.O>[CH3:8][C:3]1[CH:4]=[CH:5][CH:6]=[C:7]([C:10]([F:15])([F:9])[C:11]([F:14])([F:13])[F:12])[C:2]=1[NH2:1]
Reactant: Cc1ccccc1N
Reactant: FC(F)(F)C(F)(F)I
Agent: O=C([O-])O
Agent: O=S([O-])O
Agent: [Na+]
Solvent: C1CCOC1
Solvent: O
Product: Cc1cccc(C(F)(F)C(F)(F)F)c1N
Temperature: 25 °C
Reaction time: 3 h

Procedure:
To a two-layer system liquid mixture of 10 ml of water and 10 ml of tetrahydrofuran were added 1.07 g (10 mmoles) of 2-toluidine, 2.46 g (10 mmoles) of perfluoroethyl iodide, 1.04 g (10 mmoles) of sodium hydrogen sulfite, 0.65 g (10 mmoles) of zinc and 0.84 g (10 mmoles) of sodium hydrogen carbonate, and the resulting mixture was stirred at room temperature for 3 hours. The organic layer was dried with magnesium sulfate. The gas chromatographic analysis of the organic layer showed that, in terms of area percentage, remaining starting materials were 46%; as for the products, 2-methyl-4-pentafluoroethylaniline was 41% and 2-methyl-6-pentafluoroethylaniline was 8%, the ratio being about 5:1.
Reaction SMILES: [NH3:1].CO.[Br:4][C:5]1[CH:23]=[C:22]([F:24])[CH:21]=[CH:20][C:6]=1[CH2:7][C:8]1[N:13]=[C:12]([C:14](OC)=[O:15])[C:11]([OH:18])=[C:10]([OH:19])[N:9]=1>>[Br:4][C:5]1[CH:23]=[C:22]([F:24])[CH:21]=[CH:20][C:6]=1[CH2:7][C:8]1[NH:9][C:10](=[O:19])[C:11]([OH:18])=[C:12]([C:14]([NH2:1])=[O:15])[N:13]=1
Reactant: N
Reactant: COC(=O)c1nc(Cc2ccc(F)cc2Br)nc(O)c1O
Solvent: CO
Product: NC(=O)c1nc(Cc2ccc(F)cc2Br)[nH]c(=O)c1O
Temperature: 120 °C
Yield: 67 %

Procedure:
A solution of ammonia in MeOH (1 mL, 7.00 mmol) was added to a flask containing methyl 2-(2-bromo-4-fluorobenzyl)-5,6-dihydroxypyrimidine-4-carboxylate (50 mg, 140 μmol). The mixture was heated at 120° C. for 15 minutes in a microwave oven. The resulting product was collected by filtration, suspended in MeOH with Amberlyst resin and heated. The warm mixture was filtered and evaporated to dryness. The residue was triturated with Et2O and dried under vacuum to give the title compound as a white solid (0.032 g; 67%). LCMS: m/z=343 (MH+).