Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][NH:2][S:3]([C:6]1[S:7][C:8]([Br:11])=[CH:9][CH:10]=1)(=[O:5])=[O:4].[H-].[Na+].Br[CH2:15][C:16]([C:18]1[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=1)=[O:17].O>O1CCCC1.C(OCC)(=O)C>[F:24][C:21]1[CH:22]=[CH:23][C:18]([C:16](=[O:17])[CH2:15][N:2]([CH3:1])[S:3]([C:6]2[S:7][C:8]([Br:11])=[CH:9][CH:10]=2)(=[O:4])=[O:5])=[CH:19][CH:20]=1
Reactant: CNS(=O)(=O)c1ccc(Br)s1
Reactant: O=C(CBr)c1ccc(F)cc1
Agent: [H-]
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: O
Solvent: C1CCOC1
Product: CN(CC(=O)c1ccc(F)cc1)S(=O)(=O)c1ccc(Br)s1
Reaction time: 0.33 h
Yield: 49.8 %

Procedure:
To a solution of 5-bromothiophene-2-sulfonic acid methyl-amide (608 mg) in tetrahydrofuran (5 mL) was added 60% sodium hydride (115 mg). After stirring for 20 minutes, 2-bromo-1-(4-fluorophenyl)ethanone (630 mg) was added. After adding water and ethyl acetate, and washing the organic layer with saturated sodium chloride water, this solution was dried with anhydrous sodium sulfate. The residue that was obtained upon removing the solvent by evaporation was purified by silica gel column chromatography (hexane/ethyl acetate) and the title compound (464 mg) was obtained as a yellow oily substance.
Reaction SMILES: [C:1]([OH:24])(=O)[CH2:2][CH2:3]/[CH:4]=[CH:5]\[CH2:6]/[CH:7]=[CH:8]\[CH2:9]/[CH:10]=[CH:11]\[CH2:12]/[CH:13]=[CH:14]\[CH2:15]/[CH:16]=[CH:17]\[CH2:18]/[CH:19]=[CH:20]\[CH2:21][CH3:22].[CH2:25]([CH2:27][NH2:28])[OH:26].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CC#N.CCOC(C)=O>[OH:26][CH2:25][CH2:27][NH:28][C:1](=[O:24])[CH2:2][CH2:3]/[CH:4]=[CH:5]\[CH2:6]/[CH:7]=[CH:8]\[CH2:9]/[CH:10]=[CH:11]\[CH2:12]/[CH:13]=[CH:14]\[CH2:15]/[CH:16]=[CH:17]\[CH2:18]/[CH:19]=[CH:20]\[CH2:21][CH3:22]
Reactant: CC/C=C\C/C=C\C/C=C\C/C=C\C/C=C\C/C=C\CCC(=O)O
Reactant: NCCO
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: CCOC(C)=O
Solvent: CC#N
Product: CC/C=C\C/C=C\C/C=C\C/C=C\C/C=C\C/C=C\CCC(=O)NCCO
Temperature: 25 °C
Reaction time: 2 h

Procedure:
(4Z,7Z,10Z,13Z,16Z,19Z)-Docosa-4,7,10,13,16,19-hexaenoic acid (DHA, 1.2 g, 3.66 mmol) was taken up in 20 mL of CH3CN along with ethanolamine (220 μL, 3.66 mmol), HATU (1.5 g, 4.0 mmol) and DIEA (950 μL, 5.49 mmol). The resulting reaction mixture was stirred at room temperature for 2 h and then diluted with EtOAc. The organic layer was washed with saturated aqueous NaHCO3, brine, dried (Na2SO4) and concentrated under reduced pressure to afford crude (4Z,7Z,10Z,13Z,16Z,19Z)—N-(2-hydroxyethyl)docosa-4,7,10,13,16,19-hexaenamide. This material was taken up in 15 mL of CH2Cl2 along with (E)-methyl 4-chloro-4-oxobut-2-enoate (3.66 mmol) and triethylamine (765 μL, 5.49 mmol). The resulting reaction mixture was stirred at room temperature for 18 h. It was then diluted with CH2Cl2 and washed with brine. The organic layer was dried (Na2SO4) and concentrated under reduced pressure. Purification by chromatography (60% EtOAc, 40% pentane) afforded 380 mg of 2-(4Z,7Z,10Z,13Z,16Z,19Z)-docosa-4,7,10,13,16,19-hexaenamidoethyl methyl fumarate (21% yield). MS (EI) calcd for C29H41NO5: 483.3. found: 484 (M+1).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:21]=[CH:20][C:6]([C:7]([C:9]2[O:10][C:11]3[C:16]([C:17](=O)[CH:18]=2)=[CH:15][CH:14]=[CH:13][CH:12]=3)=[O:8])=[CH:5][CH:4]=1.[C:22]1([S:28]([N:31]=C=O)(=[O:30])=[O:29])[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1>C(#N)C>[CH3:1][O:2][C:3]1[CH:21]=[CH:20][C:6]([C:7]([C:9]2[O:10][C:11]3[C:16]([C:17](=[N:31][S:28]([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=4)(=[O:30])=[O:29])[CH:18]=2)=[CH:15][CH:14]=[CH:13][CH:12]=3)=[O:8])=[CH:5][CH:4]=1
Reactant: COc1ccc(C(=O)c2cc(=O)c3ccccc3o2)cc1
Reactant: O=C=NS(=O)(=O)c1ccccc1
Solvent: CC#N
Product: COc1ccc(C(=O)c2cc(=NS(=O)(=O)c3ccccc3)c3ccccc3o2)cc1

Procedure:
Combine 2-(4-methoxybenzoyl)-chromone (1 mmol) and benzenesulfonyl isocyanate (1.2 mmol) in acetonitrile (7.0 mL). Heat at reflux for 48 hours. Add methanol (5 mL) to quench the reaction. Evaporate in vacuo. Recrystallize to give the title compound.
Reaction SMILES: ClS([N:5]=C=O)(=O)=O.[CH3:8][O:9][C:10]1[CH:11]=[C:12]([CH:16]=[CH:17][C:18]=1[CH3:19])[C:13](O)=O.CN(C)C=O>ClCCl>[CH3:8][O:9][C:10]1[CH:11]=[C:12]([CH:16]=[CH:17][C:18]=1[CH3:19])[C:13]#[N:5]
Reactant: COc1cc(C(=O)O)ccc1C
Reactant: O=C=NS(=O)(=O)Cl
Solvent: CN(C)C=O
Solvent: ClCCl
Product: COc1cc(C#N)ccc1C
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 60 %

Procedure:
A solution of chlorosulphonyl isocyanate (5.35 m].) in dichloromethane (3 ml.) was added over 45 minutes to a stirred suspension of 3-methoxy-4-methylbenzoic acid (9.97 g.) in dichloromethane (18 ml.) at reflux under an atmosphere of nitrogen. The resulting bright-red homogeneous solution was heated under reflux for 45 minutes, chilled in an ice-bath, and treated dropwise with N,N-dimethylformamide (9.5 ml.), over 15 minutes after stirring for 30 minutes at 0° C., the orange solution was poured onto ice. The organic layer was separated, washed with water (5×20 ml.), dried (MgSO4) and evaporated. The residue was purified by preparative HPLC (SiO2, 10:90 v/v hexane: toluene) to give 3-methoxy-4-methylbenzonitrile (5.28 g., 60%) as a white solid, m.p. 51°-52.5° C.
Reaction SMILES: C[O:2][C:3](=[O:28])[C:4](=[O:27])[C:5]1[CH:10]=[C:9]([F:11])[C:8]([O:12][CH2:13][CH2:14][O:15][C:16]2[CH:25]=[CH:24][C:23]3[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=3)[CH:17]=2)=[C:7]([F:26])[CH:6]=1.[OH-].[Na+]>CO.O1CCCC1.O>[F:11][C:9]1[CH:10]=[C:5]([C:4](=[O:27])[C:3]([OH:28])=[O:2])[CH:6]=[C:7]([F:26])[C:8]=1[O:12][CH2:13][CH2:14][O:15][C:16]1[CH:25]=[CH:24][C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[CH:17]=1
Reactant: COC(=O)C(=O)c1cc(F)c(OCCOc2ccc3ccccc3c2)c(F)c1
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: O
Solvent: CO
Product: O=C(O)C(=O)c1cc(F)c(OCCOc2ccc3ccccc3c2)c(F)c1
Yield: 90.8 %

Procedure:
A solution of 3,5-difluoro-4-[2-(2-naphthalenyloxy)ethoxy]-alpha-oxobenzeneacetic acid methyl ester (0.6 g) in warm methanol (10 mL) and tetrahydrofuran (10 mL) was treated with 1N sodium hydroxide (2 mL) and after 10 minutes the mixture was diluted with water and concentrated to remove the organic solvents. The residue was acidified with excess hydrochloric acid and extracted with dichloromethane containing a little tetrahydrofuran. The organic layer was washed with water, dried (Na2SO4), filtered and evaporated. Crystallization of the residue from dichloromethane-hexane provided 0.525 g of purified 3,5-difluoro-4-[2-(2-naphthalenyloxy)ethoxy]-alpha-oxobenzeneacetic acid as a yellow solid, mp 129°-130 ° C.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:6]=[CH:5][C:4]=1B(O)O.Cl[C:17]1[C:26]2[C:21](=[CH:22][C:23]([S:28]([N:31](CC3C=CC(OC)=CC=3)[C:32]3[S:33][CH:34]=[CH:35][N:36]=3)(=[O:30])=[O:29])=[CH:24][C:25]=2[CH3:27])[N:20]=[CH:19][CH:18]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].O1CCOCC1>C(C1C(C(C)(C)C)=C([Pd]Cl)C=CC=1NC)(C)(C)C.O>[CH3:1][O:2][C:3]1[CH:8]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:6]=[CH:5][C:4]=1[C:17]1[C:26]2[C:21](=[CH:22][C:23]([S:28]([NH:31][C:32]3[S:33][CH:34]=[CH:35][N:36]=3)(=[O:29])=[O:30])=[CH:24][C:25]=2[CH3:27])[N:20]=[CH:19][CH:18]=1
Reactant: COc1ccc(CN(c2nccs2)S(=O)(=O)c2cc(C)c3c(Cl)ccnc3c2)cc1
Reactant: COc1cc(C(F)(F)F)ccc1B(O)O
Agent: CNc1ccc([Pd]Cl)c(C(C)(C)C)c1C(C)(C)C
Agent: O=P([O-])([O-])[O-]
Agent: [K+]
Solvent: C1COCCO1
Solvent: O
Product: COc1cc(C(F)(F)F)ccc1-c1ccnc2cc(S(=O)(=O)Nc3nccs3)cc(C)c12

Procedure:
To a microwave vial charged with (2-methoxy-4-(trifluoromethyl)phenyl)boronic acid (3.16 mg, 0.014 mmol), 4-chloro-N-(4-methoxybenzyl)-5-methyl-N-(thiazol-2-yl)quinoline-7-sulfonamide (6 mg, 0.013 mmol), potassium phosphate tribasic (3.24 μl, 0.039 mmol) and 1,1-bis[(di-t-butyl-p-methylaminophenyl]palladium(ii) chloride (0.924 mg, 1.304 μmol) was added dioxane (52.3 μl) and water (17.44 μl). The mixture was irradiated at 100° C. for 30 min affording conversion to desired product according to LC-MS, 4-(2-methoxy-4-(trifluoromethyl)phenyl)-N-(4-methoxybenzyl)-5-methyl-N-(thiazol-2-yl)quinoline-7-sulfonamide. m/z (ESI) 600.2 (M+H)+. The mixture was dried under reduced pressure. To the crude oil was added DCM (0.9 ml) and TFA (0.3 ml) was added at room temperature. After 1 hr of stirring, LC/MS indicated complete PMB cleavage. The mixture was dried under reduced pressure and purified with a 25 g (15 μm spherical silica) column ramping EtOAc in heptane (0 to 100%, 10% DCM throughout) providing product, obtained as a film. The material was lyophilized from MeOH/H2O providing 4-(2-methoxy-4-(trifluoromethyl)phenyl)-5-methyl-N-(thiazol-2-yl)quinoline-7-sulfonamide (2 mg, 4.17 μmol, 32.0% yield) as a yellow film. 1H NMR (500 MHz, DMSO-d6) δ ppm 3.75 (s, 3H) 6.86 (d, J=4.59 Hz, 1H) 7.28 (d, J=4.59 Hz, 1H) 7.38 (d, J=4.27 Hz, 1H) 7.41-7.48 (m, 2H) 7.49 (s, 1H) 7.63 (s, 1H) 8.32-8.39 (m, 1H) 8.99 (d, J=4.27 Hz, 1H). m/z (ESI) 480.2 (M+H)+.
Reaction SMILES: [Cl:1][C:2]1[S:6][C:5]([C:7]([O:9][CH3:10])=[O:8])=[CH:4][C:3]=1/[C:11](/[N:14]([CH2:17][CH3:18])[N:15]=[CH2:16])=[CH:12]/C.[Cl:19]N1C(=O)CCC1=O>C1COCC1>[Cl:1][C:2]1[S:6][C:5]([C:7]([O:9][CH3:10])=[O:8])=[CH:4][C:3]=1[C:11]1[N:14]([CH2:17][CH3:18])[N:15]=[CH:16][C:12]=1[Cl:19]
Reactant: C=NN(CC)/C(=C\C)c1cc(C(=O)OC)sc1Cl
Reactant: O=C1CCC(=O)N1Cl
Solvent: C1CCOC1
Product: CCn1ncc(Cl)c1-c1cc(C(=O)OC)sc1Cl
Yield: 95.9 %

Procedure:
Methyl 5-chloro-4-[(1Z)-1-(1-ethyl-2-methylidenehydrazino)-1-propen-1-yl]-2-thiophenecarboxylate (260 mg, 0.96 mmol) and 1-chloro-2,5-pyrrolidinedione (154 mg, 1.15 mmol) in THF (4 mL) were heated at 70° C. under N2 for 2 h, concentrated and purified on silica (EtOAc/Hex, 10-30%) to afford the title compound (0.281 g, 83%) as a syrup: LC-MS (ES) m/z=305 (M+H)+.
Reaction SMILES: Cl[Si:2]([CH3:10])([CH3:9])[CH2:3][CH2:4][Si:5](Cl)([CH3:7])[CH3:6].[NH2:11][CH:12]1[C:33](=[O:34])[N:14]2[C:15]([C:20]([O:22][CH2:23][C:24]3[CH:29]=[CH:28][C:27]([N+:30]([O-:32])=[O:31])=[CH:26][CH:25]=3)=[O:21])=[C:16]([Cl:19])[CH2:17][S:18][C@H:13]12.C(N(CC)CC)C>C(Cl)Cl>[Cl:19][C:16]1[CH2:17][S:18][C@@H:13]2[CH:12]([N:11]3[Si:5]([CH3:7])([CH3:6])[CH2:4][CH2:3][Si:2]3([CH3:10])[CH3:9])[C:33](=[O:34])[N:14]2[C:15]=1[C:20]([O:22][CH2:23][C:24]1[CH:29]=[CH:28][C:27]([N+:30]([O-:32])=[O:31])=[CH:26][CH:25]=1)=[O:21]
Reactant: C[Si](C)(Cl)CC[Si](C)(C)Cl
Reactant: NC1C(=O)N2C(C(=O)OCc3ccc([N+](=O)[O-])cc3)=C(Cl)CS[C@H]12
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: C[Si]1(C)CC[Si](C)(C)N1C1C(=O)N2C(C(=O)OCc3ccc([N+](=O)[O-])cc3)=C(Cl)CS[C@H]12
Temperature: 25 °C

Procedure:
A solution of 1,2-bis(chlorodimethylsilyl)ethane (3.2 g) in methylene chloride (20 ml) was added to a stirred mixture of p-nitrobenzyl 7-amino-3-chloro-3-cephem-4-carboxylate (5.0 g) and triethylamine (4.9 ml) in methylene chloride (25 ml) under a nitrogen atmosphere. The mixture was stirred at reflux for 16 hours, then allowed to cool to room temperature, and washed with 8% aqueous sodium hydrogen phosphate solution. The organic layer was separated, dried with magnesium sulphate, and evaporated under reduced pressure to give the title compound as a gum, nmr (CDCl3) δ0.17 (s, 12H), 0.78 (s, 4H), 3.38+3.82 (ABq, J=18 Hz, 2H), 4.76 (d, J=4 Hz, 1H), 4.93 (d, J=4 Hz, 1H), 5.28 (s, 2H), 7.3-8.1 (m, 4H).
Reaction SMILES: [Cl:1][C:2]1[C:3]([C:22]2[S:26][C:25]([C:27]3([O:31][CH2:32][O:33][CH3:34])[CH2:30][CH2:29][CH2:28]3)=[N:24][CH:23]=2)=[C:4]2[CH:10]=[C:9](I)[N:8]([S:12]([C:15]3[CH:21]=[CH:20][C:18]([CH3:19])=[CH:17][CH:16]=3)(=[O:14])=[O:13])[C:5]2=[N:6][CH:7]=1.[C:35]([O:39][C:40]([N:42]1[CH2:51][CH2:50][C:49]2[C:44](=[CH:45][C:46](B(O)O)=[CH:47][CH:48]=2)[CH2:43]1)=[O:41])([CH3:38])([CH3:37])[CH3:36].C(=O)(O)[O-].[Na+].C(OCC)(=O)C>CN(C)C=O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O>[Cl:1][C:2]1[C:3]([C:22]2[S:26][C:25]([C:27]3([O:31][CH2:32][O:33][CH3:34])[CH2:30][CH2:29][CH2:28]3)=[N:24][CH:23]=2)=[C:4]2[CH:10]=[C:9]([C:46]3[CH:45]=[C:44]4[C:49]([CH2:50][CH2:51][N:42]([C:40]([O:39][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:41])[CH2:43]4)=[CH:48][CH:47]=3)[N:8]([S:12]([C:15]3[CH:21]=[CH:20][C:18]([CH3:19])=[CH:17][CH:16]=3)(=[O:14])=[O:13])[C:5]2=[N:6][CH:7]=1
Reactant: CC(C)(C)OC(=O)N1CCc2ccc(B(O)O)cc2C1
Reactant: COCOC1(c2ncc(-c3c(Cl)cnc4c3cc(I)n4S(=O)(=O)c3ccc(C)cc3)s2)CCC1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: COCOC1(c2ncc(-c3c(Cl)cnc4c3cc(-c3ccc5c(c3)CN(C(=O)OC(C)(C)C)CC5)n4S(=O)(=O)c3ccc(C)cc3)s2)CCC1
Temperature: 65 °C

Procedure:
A stirring solution of Example 1F (0.1 g, 0.159 mmol) and 2-(tert-butoxycarbonyl)-1,2,3,4-tetrahydroisoquinolin-7-ylboronic acid (0.053 g, 0.191 mmol) in N,N-dimethylformamide (1.4 mL) was treated with saturated aqueous sodium bicarbonate (0.35 mL) followed by bis(triphenylphosphine)palladium(II) chloride (0.008 g, 0.012 mmol). The suspension was heated at 65° C. for 4 hours. The reaction was cooled to ambient temperature, and ethyl acetate and water were added. The layers were separated, and the aqueous layer was extracted with additional ethyl acetate. The combined organic layers were washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated. The concentrate was purified by flash chromatography on silica gel, eluting with a gradient of from 0% to 25% ethyl acetate in hexane, to provide the title compound. MS ESI(+) m/z 735.2 [M+H]+.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([NH:15][C:16]2[C:25]3[C:20](=[CH:21][CH:22]=[C:23](Br)[CH:24]=3)[N:19]=[CH:18][N:17]=2)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[O:27]1[CH2:31][CH2:30][O:29][CH:28]1[C:32]1[O:36][C:35]([Sn](CCCC)(CCCC)CCCC)=[CH:34][CH:33]=1>O1CCOCC1>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([NH:15][C:16]2[C:25]3[C:20](=[CH:21][CH:22]=[C:23]([C:35]4[O:36][C:32]([CH:28]5[O:29][CH2:30][CH2:31][O:27]5)=[CH:33][CH:34]=4)[CH:24]=3)[N:19]=[CH:18][N:17]=2)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CCCC[Sn](CCCC)(CCCC)c1ccc(C2OCCO2)o1
Reactant: Brc1ccc2ncnc(Nc3ccc(OCc4ccccc4)cc3)c2c1
Solvent: C1COCCO1
Product: c1ccc(COc2ccc(Nc3ncnc4ccc(-c5ccc(C6OCCO6)o5)cc34)cc2)cc1
Yield: 62.1 %

Procedure:
Prepared according to Procedure B from (4-benzyloxy-phenyl)-(6-bromoquinazolin-4-yl)-amine (1.5 g, 3.7 mmol) and 5-(1,3-dioxolan-2-yl)-2-(tributylstannyl)-furan (1.9 g, 4.42 mmol) dissolved in dioxan (30 ml) and heated at reflux under nitrogen for 6 hr. The solvent was removed from the cooled reaction under vacuum, and the residual oil was triturated with iso-hexane/ethyl acetate to give the product (1.07 g, 62%) as a pale yellow solid; δ H [2H6]-DMSO 9.96 (1H, b, NH), 8.80 (1H, s, 5-H), 8.51 (1H, s, 2-H), 8.18 (1H, d, 7-H), 7.80 (1H, d, 8-H), 7.70 (2H, d, 2′-H, 6′-H), 7.58-7.30 (5H, m, 5×Ph-H), 7.10 (3H, m, 3′-H, 5′-H, furan 3-H), 6.78 (1H, d, furan 4-H), 6.12 (1H, s, CH02), 5.18 (2H, s, PhCH2), 4.22-3.94 (4H, m, 2×CH2); m/z 466 (M+1)+.
Reaction SMILES: [F:1][C:2]([F:20])([F:19])[C:3]([C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][CH:13]([CH3:18])[CH2:12]2)([OH:8])[C:4]([F:7])([F:6])[F:5].[CH2:21]([C:28]1[O:29][C:30]([CH3:35])=[C:31]([CH2:33]Cl)[N:32]=1)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.FC(F)(F)C(C1C=C2C(=CC=1)N(CC1N=C(C=CC3C=CC=CC=3)OC=1C)C(C)C2)(O)C(F)(F)F>>[CH2:21]([C:28]1[O:29][C:30]([CH3:35])=[C:31]([CH2:33][N:14]2[C:15]3[C:11](=[CH:10][C:9]([C:3]([OH:8])([C:2]([F:1])([F:19])[F:20])[C:4]([F:7])([F:6])[F:5])=[CH:17][CH:16]=3)[CH2:12][CH:13]2[CH3:18])[N:32]=1)[C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1
Reactant: CC1Cc2cc(C(O)(C(F)(F)F)C(F)(F)F)ccc2N1
Reactant: Cc1oc(Cc2ccccc2)nc1CCl
Agent: Cc1oc(C=Cc2ccccc2)nc1CN1c2ccc(C(O)(C(F)(F)F)C(F)(F)F)cc2CC1C
Product: Cc1oc(Cc2ccccc2)nc1CN1c2ccc(C(O)(C(F)(F)F)C(F)(F)F)cc2CC1C

Procedure:
In analogy to example 75.2, from 1,1,1,3,3,3-hexafluoro-2-(2-methyl-2,3-dihydro-1H-indol-5-yl)-propan-2-ol (example 51.1) and 2-benzyl-4-chloromethyl-5-methyl-oxazole was prepared 1,1,1,3,3,3-hexafluoro-2-[2-methyl-1-(5-methyl-2-styryl-oxazol-4-ylmethyl)-2,3-dihydro-1H-indol-5-yl]-propan-2-ol, red oil, MS: 485 (MH+).
Reaction SMILES: [N:1]1([CH2:7][CH2:8][CH2:9][O:10][C:11]2[CH:16]=[CH:15][C:14]([C:17]3([C:23]#[N:24])[CH2:22][CH2:21][O:20][CH2:19][CH2:18]3)=[CH:13][CH:12]=2)[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.C1C=[CH:27][C:28]2[N:33](O)N=N[C:29]=2C=1.CCN=C=NCCCN(C)C.Cl.Cl.N1CCCCC1.[OH2:54]>C(Cl)Cl>[NH2:33][CH:28]([CH3:29])[C:27]([N:4]1[CH2:5][CH2:6][N:1]([CH2:7][CH2:8][CH2:9][O:10][C:11]2[CH:12]=[CH:13][C:14]([C:17]3([C:23]#[N:24])[CH2:22][CH2:21][O:20][CH2:19][CH2:18]3)=[CH:15][CH:16]=2)[CH2:2][CH2:3]1)=[O:54]
Reactant: On1nnc2ccccc21
Reactant: O
Reactant: N#CC1(c2ccc(OCCCN3CCNCC3)cc2)CCOCC1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Solvent: ClCCl
Solvent: C1CCNCC1
Product: CC(N)C(=O)N1CCN(CCCOc2ccc(C3(C#N)CCOCC3)cc2)CC1
Reaction time: 1 h
Yield: 42 %

Procedure:
4-[4-(3-piperazin-1-ylpropoxy)phenyl]tetrahydropyran-4-carbonitrile (265 mg, 0.81 mmol), DCM (10.6 ml), HOBT (120 mg, 0.89 mmol), FMoc (L)-aniline (277 mg, 0.89 mmol) and EDCl.HCl (171 mg, 0.89 mmol) were stirred at ambient temperature overnight. Water (10 ml) was added and stirred for one hour, the mixture was filtered and the organic phase separated and washed with water (10 ml), the organic phase was dried over MgSO4, filtered and concentrated in vacuo at 35° C. The residue was dissolved in DCM (9 ml) and piperidine (86 mg, 10 mmol) was added, the mixture was stirred at ambient temperature for one hour. To the reaction mixture, water (5 ml) was added and the organic phase separated, dried over MgSO4, filtered and concentrated in vacuo at 35° C. The crude material was subjected to chromatography on silica eluting with 2% MeOH in DCM to provide title compound (136 mg, 42%). 1H NMR (400 MHz, CDCl3), δ 7.38 (d, 2H), 6.93 (d, 2H), 4.11-4.05 (m, 2H), 4.03 (t, 2H), 3.89 (td, 2H), 3.77 (q, 1H), 3.65 (br s, 2H), 3.49 (br s, 2H), 2.55 (t, 2H), 2.45 (br s, 4H), 2.14-2.00 (m, 4H), 1.97 (m, 2H), 1.58 (br s, 2H), 1.25 (d, 3H).
Reaction SMILES: [CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[OH:11].C1C=CC2C(=CC=CC=2O)C=1.[Cl:23]Cl.C(N(CC)CC)C.[NH:32]1[CH2:37][CH2:36][O:35][CH2:34][CH2:33]1>C1(C)C=CC=CC=1>[Cl:23][C:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4]([N:32]2[CH2:37][CH2:36][O:35][CH2:34][CH2:33]2)=[CH:3][C:2]=1[OH:11]
Reactant: Oc1ccc2ccccc2c1
Reactant: ClCl
Reactant: C1COCCN1
Agent: Oc1cccc2ccccc12
Solvent: Cc1ccccc1
Solvent: CCN(CC)CC
Product: Oc1cc(N2CCOCC2)c2ccccc2c1Cl
Yield: 109.5 %

Procedure:
2-Naphthol (28.8 g; 0.200 mol) was dissolved in toluene (200 ml) by warming. The pale brown solution was cooled and vigorously stirred until the naphthol began to precipitate and chlorine (31.29 g;0.442 mol) was then passed through the solution at approximately 2.5-3.0 g/min followed immediately by nitrogen gas. The resulting amber solution was treated firstly with triethylamine (24.68 g;0.244 mol) in one portion and then with a solution of morpholine (17.40 g;0.20 mol) in toluene (180 ml) dropwise over 1.5 hours keeping the temperature at 15°-20° C. The resulting brown mixture was filtered to remove triethylamine hydrochloride as a white amorphous solid. The toluene filtrate was washed with water, dried and evaporated to give 1-chloro-4-morpholino-2-naphthol as a brown viscous oil (57.76 g). Purification by chromatography over silica (eluent: 15% ethyl acetate in toluene) gave the product as an off-white solid (34.37 g;65%). Further purification by crystallisation from toluene gave the product as a white solid, m.pt. 163°-65° C. ##STR18## (b) 4-Morpholino-2-naphthol
Reaction SMILES: Cl.[NH2:2][CH:3]([C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)[C:4]#[N:5].[C:12]([N:29]=[C:30]=[S:31])([O:14][CH2:15][CH:16]1[C:28]2[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=2)[C:22]2[C:17]1=[CH:18][CH:19]=[CH:20][CH:21]=2)=[O:13].C(N(C(C)C)C(C)C)C.C(=O)(O)[O-].[Na+]>C(Cl)Cl>[NH2:5][C:4]1[S:31][C:30]([NH:29][C:12]([O:14][CH2:15][CH:16]2[C:17]3[C:22](=[CH:21][CH:20]=[CH:19][CH:18]=3)[C:23]3[C:28]2=[CH:27][CH:26]=[CH:25][CH:24]=3)=[O:13])=[N:2][C:3]=1[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1
Reactant: N#CC(N)c1ccccc1
Reactant: O=C(N=C=S)OCC1c2ccccc2-c2ccccc21
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: Nc1sc(NC(=O)OCC2c3ccccc3-c3ccccc32)nc1-c1ccccc1
Reaction time: 3 h
Yield: 48 %

Procedure:
A suspension of α-aminophenylacetonitrile hydrochloride (3.19 g, 18.9 mmol) and Fmoc-isothiocyanate (5.31 g, 18.9 mmol) in DCM was treated with ethyldiisopropylamine (3.62 ml, 20.8 mmol) at 0° C. for 1 hr and then at ambient temperature for 3 hr. The mixture was poured into saturated aqueous sodium bicarbonate and extracted three times into ethyl acetate. The combined organic phases were washed with water and brine, and dried over sodium sulfate and concentrated in vacuo. Flash chromatography on silica gel (ethyl acetate/hexanes) yielded 5-amino-2-(Fmoc-amino)-4-phenylthiazole (3.75 g, 48%).
Reaction SMILES: [O:1]=[C:2]1[CH2:6][N:5]([CH2:7][C:8]([O-:10])=[O:9])[C:4](=[O:11])[NH:3]1.[N+:12]([C:15]1[CH:16]=[C:17]([CH:31]=[CH:32][CH:33]=1)[CH2:18]N1C(=O)C(=O)N(CC(O)=O)C1=C)([O-:14])=[O:13].[H-].[Na+].[N+]([C:39]1C=C(C=C[CH:46]=1)CBr)([O-])=O.Cl>CN(C)C=O>[N+:12]([C:15]1[CH:16]=[C:17]([CH:31]=[CH:32][CH:33]=1)[CH2:18][N:3]1[C:2](=[O:1])[CH2:6][N:5]([CH2:7][C:8]([O:10][CH2:39][CH3:46])=[O:9])[C:4]1=[O:11])([O-:14])=[O:13]
Reactant: C=C1N(CC(=O)O)C(=O)C(=O)N1Cc1cccc([N+](=O)[O-])c1
Reactant: O=[N+]([O-])c1cccc(CBr)c1
Reactant: O=C([O-])CN1CC(=O)NC1=O
Agent: Cl
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CCOC(=O)CN1CC(=O)N(Cc2cccc([N+](=O)[O-])c2)C1=O
Temperature: 0 °C
Reaction time: 1 h

Procedure:
A solution of 815 mg of the above-prepared dioxoimidazolidine-l-acetate product of paragraph (1) dissolved in 30 mL of dimethylformamide was dropped into a suspension of 221 mg of sodium hydride in 20 mL of dimethylformamide at not higher than 0° C. The mixture was stirred for one hour more at the same temperature condition and then a solution of 1.3 g of 3-nitrobenzyl bromide dissolved in 30 mL of dimethylformamide was dropped thereinto at 0° C. The reaction mixture was stirred for two hours and added to an ice-cooled 2N hydrochloric acid with vigorous stirring. The resulting reaction mixture was extracted with ethyl acetate several times and the combined extract was washed with a saturated physiological saline solution and concentrated to give a residue. This residue was purified by a silica gel column to give 1.32 g of ethyl 3-(3-nitrobenzyl)-2,4-dioxoimidazolidine-1-acetate.
Reaction SMILES: Br[CH2:2][CH2:3][CH2:4][N:5]1[C:10](=[O:11])[NH:9][C:8]2[CH:12]=[CH:13][C:14]([O:16][CH3:17])=[CH:15][C:7]=2[S:6]1(=[O:19])=[O:18].[N:20]1[CH:25]=[CH:24][CH:23]=[N:22][C:21]=1[N:26]1[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]1.C(N(CC)CC)C.O>CN(C=O)C>[N:20]1[CH:25]=[CH:24][CH:23]=[N:22][C:21]=1[N:26]1[CH2:31][CH2:30][N:29]([CH2:2][CH2:3][CH2:4][N:5]2[C:10](=[O:11])[NH:9][C:8]3[CH:12]=[CH:13][C:14]([O:16][CH3:17])=[CH:15][C:7]=3[S:6]2(=[O:19])=[O:18])[CH2:28][CH2:27]1
Reactant: c1cnc(N2CCNCC2)nc1
Reactant: COc1ccc2c(c1)S(=O)(=O)N(CCCBr)C(=O)N2
Solvent: CN(C)C=O
Solvent: O
Solvent: CCN(CC)CC
Product: COc1ccc2c(c1)S(=O)(=O)N(CCCN1CCN(c3ncccn3)CC1)C(=O)N2
Temperature: 60 °C
Reaction time: 1.5 h
Yield: 53 %

Procedure:
0.01 mol of 2-(3-bromopropyl)-7-methoxy-1,2,4-benzothiadiazin-3(4H)one 1,1-dioxide, 0.012 mol of 1-(2-pyrimidinyl)piperazine and 0.01 mol of triethylamine are dissolved in 30 ml of DMF and the solution is heated at 60° C., with stirring, for 1.5 hours. Then 15 ml of water are added and the reaction mixture is cooled to 0° C. The substance which crystallises out during this is filtered off with suction, stirred with isopropanol, again filtered off with suction and dried in vacuo. Yield: 53% of theory; melting point: 178° C.