Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][C:3](=[O:31])[CH2:4][CH:5]1[CH2:10][CH2:9][N:8]([C:11](=[O:30])[C:12]([CH3:29])([CH3:28])[CH:13]([CH2:26][CH3:27])[NH:14][C:15](=[O:25])[C:16]2[CH:21]=[CH:20][C:19]([C:22]#[N:23])=[CH:18][C:17]=2[F:24])[CH2:7][CH2:6]1.[NH:32]1[CH2:36][CH2:35][CH2:34][CH2:33]1>>[CH3:1][O:2][C:3](=[O:31])[CH2:4][CH:5]1[CH2:10][CH2:9][N:8]([C:11](=[O:30])[C:12]([CH3:28])([CH3:29])[CH:13]([CH2:26][CH3:27])[NH:14][C:15](=[O:25])[C:16]2[CH:21]=[CH:20][C:19]([C:22]([N:32]3[CH2:36][CH2:35][CH2:34][CH2:33]3)=[NH:23])=[CH:18][C:17]=2[F:24])[CH2:7][CH2:6]1
Reactant: CCC(NC(=O)c1ccc(C#N)cc1F)C(C)(C)C(=O)N1CCC(CC(=O)OC)CC1
Reactant: C1CCNC1
Product: CCC(NC(=O)c1ccc(C(=N)N2CCCC2)cc1F)C(C)(C)C(=O)N1CCC(CC(=O)OC)CC1
Yield: 21 %

Procedure:
N-Boc-β-ethyl-α,α-dimethyl-β-alanine was condensed with 4-piperidineacetic acid methyl ester in the same manner as in Example 43 to yield N-(N-β-ethyl-α,α-dimethyl-β-alanyl)-4-piperidineacetic acid methyl ester. From the resulting compound, methyl-N-(N-(4-cyano-2-fluorobenzoyl)-β-ethyl-α,α-dimethyl-β-alanyl)-4-piperidineacetate was derived in the same manner as in Example 45. The same procedure as in Example 45 was performed with this compound (1.0 g, 2.3 mmol) by using pyrrolidine (1.9 ml) as an amine to yield the titled compound (248 mg, 21%).
Reaction SMILES: [CH2:1]([C@H:8]1[CH2:12][O:11][C:10](=[O:13])[N:9]1[C:14](=[O:25])[CH2:15][C:16]([CH3:24])([C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)[CH3:17])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[K].CC(C1C=C(C(C)C)C(S([N:42]=[N+:43]=[N-:44])(=O)=O)=C(C(C)C)C=1)C>O1CCCC1.C1(C)C=CC=CC=1>[N:42]([C@@H:15]([C:16]([CH3:17])([C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)[CH3:24])[C:14]([N:9]1[C@@H:8]([CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)[CH2:12][O:11][C:10]1=[O:13])=[O:25])=[N+:43]=[N-:44]
Reactant: CC(C)(CC(=O)N1C(=O)OC[C@@H]1Cc1ccccc1)c1ccccc1
Reactant: CC(C)c1cc(C(C)C)c(S(=O)(=O)N=[N+]=[N-])c(C(C)C)c1
Agent: [K]
Solvent: Cc1ccccc1
Solvent: C1CCOC1
Product: CC(C)(c1ccccc1)[C@H](N=[N+]=[N-])C(=O)N1C(=O)OC[C@@H]1Cc1ccccc1
Reaction time: 1 h
Yield: 96.9 %

Procedure:
A solution of (4S)-4-benzyl-3-(3-methyl-3-phenylbutanoyl)-1,3-oxazolidin-2-one (1.0 g, 3.0 mmol, from Reference Example 26) in anhydrous tetrahydrofuran (16 mL) is cooled to −78° C. in a dry-ice/acetone bath while stirring under a nitrogen atmosphere. Potassium hexamethylsilazide (0.5 M solution in toluene, 6.6 mL, 3.3 mmol) is added dropwise to the solution via syringe. After stirring for 1 hour at −78° C., trisyl azide (1.2 g, 3.8 mmol) in tetrahydrofuran (8 mL) is added dropwise. The reaction mixture is stirred for 2-3 minutes at −78° C. and then quenched by the addition of glacial acetic acid (0.8 mL). Stirring is continued for 1 hour at 40° C. The reaction mixture is diluted with brine and diethyl ether. The aqueous phase is extracted thrice with diethyl ether. The combined extracts are washed with saturated aqueous sodium hydrogen carbonate and saturated aqueous sodium chloride, dried over sodium sulfate, decanted, and concentrated under reduced pressure to afford a white/yellow solid. The crude material is purified by flash chromatography (ethyl acetate/hexanes) to afford a clear, straw colored oil (1.1 g, 79%). TOF MS (ES+): (M+H)=379.2
Reaction SMILES: [CH3:1][C:2]([N:13]=[C:14]=[O:15])([CH3:12])[C:3]1[CH:8]=[CH:7][CH:6]=[C:5]([C:9]([CH3:11])=[CH2:10])[CH:4]=1.[C:16]([OH:20])([CH3:19])([CH3:18])[CH3:17]>CC(C)([O-])C.[K+].CCCCCC>[CH3:17][C:16]([O:20][C:14](=[O:15])[NH:13][C:2]([CH3:1])([C:3]1[CH:8]=[CH:7][CH:6]=[C:5]([C:9]([CH3:11])=[CH2:10])[CH:4]=1)[CH3:12])([CH3:19])[CH3:18]
Reactant: C=C(C)c1cccc(C(C)(C)N=C=O)c1
Reactant: CC(C)(C)O
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: CCCCCC
Product: C=C(C)c1cccc(C(C)(C)NC(=O)OC(C)(C)C)c1
Temperature: 25 °C
Yield: 80.5 %

Procedure:
Into a 3-neck, 10 L round bottom flask equipped with a mechanical stirrer, condenser, and a nitrogen inlet was placed α,α-dimethyl-m-isopropenylbenzyl isocyanate (1083 g, 5.38 mol), hexane (6 L), and t-butyl alcohol (398.8 g, 5.38 mol). While the mixture was stirred at room temperature, potassium t-butoxide (18.0 g, 160 mmol) was added in portions. Throughout the addition the reaction temperature increased to 50° C. The reaction was complete within an hour. The reaction mixture was washed with water (5 L), and thereafter, the organics were separated from the aqueous layer. The organics were dried over magnesium sulfate, filtered, and evaporated to yield a yellow-brown semi-solid. Recrystallization from hexane afforded essentially pure {1-methyl-1-[3-(1-methylethenyl)phenyl]ethyl}carbamic acid 1,1-dimethylethyl ester (1193 g, 81% isolated yield), as shown by proton and carbon-13 NMR spectroscopy.
Reaction SMILES: [ClH:1].[N:2]12[CH2:11][CH:6]3[CH2:7][CH:8]([CH2:10][CH:4]([C@H:5]3[NH2:12])[CH2:3]1)[CH2:9]2.[N:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[C:19]1[S:23][C:22]([C:24](O)=[O:25])=[CH:21][CH:20]=1.N>>[ClH:1].[N:2]12[CH2:11][CH:6]3[CH2:7][CH:8]([CH2:10][CH:4]([C@H:5]3[NH:12][C:24]([C:22]3[S:23][C:19]([C:14]4[CH:15]=[CH:16][CH:17]=[CH:18][N:13]=4)=[CH:20][CH:21]=3)=[O:25])[CH2:3]1)[CH2:9]2
Reactant: NC1C2CC3CC1CN(C3)C2
Reactant: O=C(O)c1ccc(-c2ccccn2)s1
Agent: Cl
Agent: N
Product: O=C(NC1C2CC3CC1CN(C3)C2)c1ccc(-c2ccccn2)s1

Procedure:
Prepared from (4r)-1-azatricyclo[3.3.1.13,7]dec-4-ylamine hydrochloride and 5-(2-pyridyl)thiophene-2-carboxylic acid (Maybridge) according to methods A and C; yield 35 mg, 0.09 mmol (43%): 1H NMR (300 MHz, methanol-d4) δ 2.07-2.29 (m, 5H), 2.48 (s, 2H), 3.49 (d, J=12 Hz, 2H), 3.56 (s, 2H), 3.83 (d, J=13 Hz, 2H), 4.26 (s, 1H), 7.29-7.39 (m, 1H), 7.71 (d, J=4 Hz, 1H), 7.83-7.91 (m, 3H), 8.50-8.56 (m, 1H); MS (DCI/NH3) m/z 340 (M+H)+; Anal. C19H21N3OS.HCl.0.5H2O: C, H, N.
Reaction SMILES: [N:1]1([CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][C:14]2[S:18][C:17]([C:19](=O)[CH2:20][CH2:21][C:22]([OH:24])=O)=[CH:16][CH:15]=2)[CH:5]=[CH:4][N:3]=[CH:2]1.O.[NH2:27][NH2:28]>O>[N:1]1([CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][C:14]2[S:18][C:17]([C:19]3[CH2:20][CH2:21][C:22](=[O:24])[NH:27][N:28]=3)=[CH:16][CH:15]=2)[CH:5]=[CH:4][N:3]=[CH:2]1
Reactant: O=C(O)CCC(=O)c1ccc(CCCCCCCCn2ccnc2)s1
Reactant: NN
Solvent: O
Product: O=C1CCC(c2ccc(CCCCCCCCn3ccnc3)s2)=NN1
Temperature: 90 °C
Reaction time: 2 h

Procedure:
1.8 g of 4-{5-[8-(1-Imidazolyl)-octyl]-thien-2-yl}-4-oxo-butyric acid are suspended in 10 ml of water, 0.26 g of hydrazine hydrate are added and the mixture is stirred at 90° C. for 2 hours. After the mixture has been cooled, the precipitate formed is filtered off with suction, washed with water and dried.
Reaction SMILES: [Cl:1][CH2:2][C:3](Cl)=[O:4].[CH3:6][CH:7]([CH2:11][CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[CH2:8][CH2:9][OH:10].N1C=CC=CC=1>ClCCl>[Cl:1][CH2:2][C:3]([O:10][CH2:9][CH2:8][CH:7]([CH3:6])[CH2:11][CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)=[O:4]
Reactant: O=C(Cl)CCl
Reactant: CC(CCO)CCc1ccccc1
Solvent: c1ccncc1
Solvent: ClCCl
Product: CC(CCOC(=O)CCl)CCc1ccccc1
Reaction time: 2 h
Yield: 84.9 %

Procedure:
A 127.05 g (1.125 mol) of chloroacetyl chloride and 200 ml of dichloromethane were put into a flask and, while stirring under ice-cooling, a mixture consisting of 199.6 g (1.12 mol) of 3-methyl-5-phenylpentanol and 88.59 g (1.12 mol) of pyridine was added dropwise thereto spending 2 hours (reaction temperature 5 to 15° C.). After completion of the dropwise addition, this was further stirred at room temperature for 3 hours, and white crystals of the thus precipitated pyridine hydrochloride were removed by filtration. The reaction mixture was washed with water (3×300 ml), the organic phase was dehydrated with anhydrous magnesium sulfate and then the solvent was evaporated under a reduced pressure. By distilling the remained yellow oil under a reduced pressure, the title compound was obtained as a light yellow transparent oil. Yield 242.25 g (0.849 mol; yield 84.9%, boiling point 148-151° C./0.2 kPa).
Reaction SMILES: [CH:1]1([N:4]([CH:18]2[CH2:23][CH2:22][N:21]([C:24](=[NH:27])[NH:25][OH:26])[CH2:20][CH2:19]2)[C:5](=[O:17])[C:6]2[CH:11]=[CH:10][C:9]([C:12]3[O:16][CH:15]=[N:14][CH:13]=3)=[CH:8][CH:7]=2)[CH2:3][CH2:2]1.[N:28]1[CH:33]=[CH:32][N:31]=[CH:30][C:29]=1[C:34](Cl)=O>>[CH:1]1([N:4]([CH:18]2[CH2:23][CH2:22][N:21]([C:24]3[N:27]=[C:34]([C:29]4[CH:30]=[N:31][CH:32]=[CH:33][N:28]=4)[O:26][N:25]=3)[CH2:20][CH2:19]2)[C:5](=[O:17])[C:6]2[CH:11]=[CH:10][C:9]([C:12]3[O:16][CH:15]=[N:14][CH:13]=3)=[CH:8][CH:7]=2)[CH2:3][CH2:2]1
Reactant: O=C(Cl)c1cnccn1
Reactant: N=C(NO)N1CCC(N(C(=O)c2ccc(-c3cnco3)cc2)C2CC2)CC1
Product: O=C(c1ccc(-c2cnco2)cc1)N(C1CC1)C1CCN(c2noc(-c3cnccn3)n2)CC1

Procedure:
The title compound is prepared from N-cyclopropyl-N-[1-(N-hydroxycarbamimidoyl)-piperidin-4-yl]-4-oxazol-5-yl-benzamide and pyrazine-2-carbonyl chloride following a procedure analogous to that described in Example 47. LC (method 2): tR=1.15 min; Mass spectrum (ESI+): m/z=458 [M+H]+.
Reaction SMILES: [Na+].[Br:2][CH2:3][CH2:4][CH2:5][CH2:6][S:7]([O-:10])(=O)=[O:8].S(Cl)([Cl:13])=O>>[Br:2][CH2:3][CH2:4][CH2:5][CH2:6][S:7]([Cl:13])(=[O:10])=[O:8]
Reactant: O=S(Cl)Cl
Reactant: O=S(=O)([O-])CCCCBr
Agent: [Na+]
Product: O=S(=O)(Cl)CCCCBr

Procedure:
4-Bromo-1-butane sulfonic acid sodium salt (1.25 g) was added to thionyl chloride (12.5 mL) with stirring under nitrogen. The reaction was heated under reflux for 3 h, cooled, and concentrated under reduced pressure. The residue was then diluted with diethyl ether, washed with water, dried, filtered and concentrated under reduced pressure to afford 760 mg of a 7:3 mixture of desired product and the 4-chloro analog (instead of the 4-bromo). 1H NMR (300 MHz, CDCl3) δ3.70 (t, 2H), 3.46 (t, 2H), 2.25 (m, 2H), 2.09 (m, 2H).
Reaction SMILES: [C:1](Cl)(=[O:3])[CH3:2].Cl.[CH3:6][N:7]1[C:16]2[NH:15][C:14]3[CH:17]=[C:18]([CH3:21])[CH:19]=[CH:20][C:13]=3[N:12]([C:22]([CH:24]3[CH2:29][CH2:28][CH:27]([CH2:30][NH:31][C:32](=[O:40])[CH2:33][CH:34]4[CH2:39][CH2:38][NH:37][CH2:36][CH2:35]4)[CH2:26][CH2:25]3)=[O:23])[CH2:11][C:10]=2[CH:9]=[N:8]1>ClCCl.C(N(CC)CC)C>[C:1]([N:37]1[CH2:38][CH2:39][CH:34]([CH2:33][C:32]([NH:31][CH2:30][CH:27]2[CH2:26][CH2:25][CH:24]([C:22]([N:12]3[CH2:11][C:10]4[CH:9]=[N:8][N:7]([CH3:6])[C:16]=4[NH:15][C:14]4[CH:17]=[C:18]([CH3:21])[CH:19]=[CH:20][C:13]3=4)=[O:23])[CH2:29][CH2:28]2)=[O:40])[CH2:35][CH2:36]1)(=[O:3])[CH3:2]
Reactant: Cc1ccc2c(c1)Nc1c(cnn1C)CN2C(=O)C1CCC(CNC(=O)CC2CCNCC2)CC1
Reactant: CC(=O)Cl
Agent: Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CC(=O)N1CCC(CC(=O)NCC2CCC(C(=O)N3Cc4cnn(C)c4Nc4cc(C)ccc43)CC2)CC1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
A solution of acetyl chloride (0.39 mg, 0.005 mmol) in dichloromethane (0.05 ml) was added to a solution of N-[4-(3,6-dimethyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-cyclohexylmethyl]-2-piperidin-4-yl-acetamide hydrochloride from Example E17 (2.57 mg, 0.005 mmol) in dichloromethane (0.05 ml) and triethylamine (0.0035 ml). The mixture was stirred at room temperature for 1 h then solvents were removed in vacuo to yield the title compound. (ESI)+: [M+H]+=521.5
Reaction SMILES: [F:1][C:2]1[C:7]([F:8])=[C:6]([F:9])[C:5]([F:10])=[C:4]([F:11])[C:3]=1[OH:12].[Cl:13][C:14]1[C:23]2[C:18](=[CH:19][C:20]([S:24](Cl)(=[O:26])=[O:25])=[CH:21][CH:22]=2)[CH:17]=[CH:16][N:15]=1.C(N(CC)CC)C>C(Cl)Cl>[Cl:13][C:14]1[C:23]2[C:18](=[CH:19][C:20]([S:24]([O:12][C:3]3[C:2]([F:1])=[C:7]([F:8])[C:6]([F:9])=[C:5]([F:10])[C:4]=3[F:11])(=[O:26])=[O:25])=[CH:21][CH:22]=2)[CH:17]=[CH:16][N:15]=1
Reactant: Oc1c(F)c(F)c(F)c(F)c1F
Reactant: O=S(=O)(Cl)c1ccc2c(Cl)nccc2c1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: O=S(=O)(Oc1c(F)c(F)c(F)c(F)c1F)c1ccc2c(Cl)nccc2c1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
2,3,4,5,6-Pentafluorophenol (2.73 g, 14.82 mmol) was dissolved in DCM (49.4 ml). 1-chloroisoquinoline-6-sulfonyl chloride (2.59 g, 9.88 mmol) was added, followed by the dropwise addition of triethylamine (2.066 ml, 14.82 mmol). The reaction was stirred overnight at room temperature. The reaction was concentrated and purified by silica gel chromatography (40 g column, gradient elution 0 to 50% Et2O:Heptane) to afford perfluorophenyl 1-chloroisoquinoline-6-sulfonate as a white solid. m/z (ESI) 410.0 (M+H)+.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([C:9]([OH:11])=O)=[N:7][CH:8]=1.CN(C=O)C.S(Cl)([Cl:19])=O>O1CCCC1>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([C:9]([Cl:19])=[O:11])=[N:7][CH:8]=1
Reactant: O=S(Cl)Cl
Reactant: COc1ccc(C(=O)O)nc1
Solvent: CN(C)C=O
Solvent: C1CCOC1
Product: COc1ccc(C(=O)Cl)nc1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
To 5-methoxy-2-pyridylcarboxylic acid (11.9 g, 77.5 mmol) and DMF (5.4 ml, 69 mmol) in 200 ml of tetrahydrofuran (THF) at 5° is added thionyl chloride (8.4 ml, 116 mmol) over 15 minutes. After addition, the slurry is allowed to warm slowly to RT. After 3 hours, the reaction is rotoevaporated to give 5-methoxy-2-pyridylcarboxylic acid chloride. This acid chloride is gradually added, with cooling, to rapidly stirring ammonium hydroxide (40 ml, 340 mmol), and the slurry is stirred for 1 hour. The reaction is filtered and the residue is dried. To this is added dry toluene, with stirring, followed by filtration. More toluene is added, followed by rotoevaporation to give 5-methoxy-2-pyridylcarboxamide.
Reaction SMILES: N#N.[Br:3][C:4]1[CH:12]=[CH:11][C:7]2[NH:8][N:9]=[N:10][C:6]=2[CH:5]=1.[O:13]1[CH:18]=[CH:17][CH2:16][CH2:15][CH2:14]1.CC1C=CC(S([O-])(=O)=O)=CC=1.C1C=C[NH+]=CC=1>ClCCl>[Br:3][C:4]1[CH:12]=[CH:11][C:7]2[N:8]([CH:14]3[CH2:15][CH2:16][CH2:17][CH2:18][O:13]3)[N:9]=[N:10][C:6]=2[CH:5]=1
Reactant: C1=COCCC1
Reactant: Brc1ccc2[nH]nnc2c1
Agent: Cc1ccc(S(=O)(=O)[O-])cc1
Agent: N#N
Agent: c1cc[nH+]cc1
Solvent: ClCCl
Product: Brc1ccc2c(c1)nnn2C1CCCCO1
Temperature: 25 °C
Reaction time: 48 h

Procedure:
A 250-mL round-bottom flask equipped with a magnetic stir bar, a rubber septum and N2 inlet was charged with 5-bromo-1H-benzo[d][1,2,3]triazole (4.5 g, 22.7 mmol) and anhydrous dichloromethane (114 mL). To this solution, 3,4-dihydro-2H-pyran (10.3 mL, 113.6 mmol) was added in one portion at room temperature followed by addition of PPTS (0.57 g, 2.27 mmol). The resulting mixture was stirred at room temperature for 48 h. The reaction was monitored by TLC. Upon completion, the reaction mixture was quenched with water and extracted with dichloromethane (3×100 mL). The combined organic layers were washed with saturated NaHCO3 (50 mL), water (100 mL), and then brine (50 mL), dried over sodium sulfate, filtered and concentrated to give the crude product that was purified on a silica gel column eluted with 0-10% ethyl acetate in hexanes affording the title compound as a clear oil (3.6 g). LCMS: 198 [(M-THP+H)+H]+.
Reaction SMILES: [CH3:1][C@H:2]1[CH2:4][C@H:3]1[C:5]1[C:13]2[C:8](=[N:9][CH:10]=[C:11]([N+:14]([O-])=O)[CH:12]=2)[NH:7][N:6]=1.[H][H]>CO.[Pd]>[CH3:1][C@H:2]1[CH2:4][C@H:3]1[C:5]1[C:13]2[C:8](=[N:9][CH:10]=[C:11]([NH2:14])[CH:12]=2)[NH:7][N:6]=1
Reactant: C[C@H]1C[C@H]1c1n[nH]c2ncc([N+](=O)[O-])cc12
Reactant: [H][H]
Agent: [Pd]
Solvent: CO
Product: C[C@H]1C[C@H]1c1n[nH]c2ncc(N)cc12
Reaction time: 0.33 h

Procedure:
3-(cis-2-Methylcyclopropyl)-5-nitro-1H-pyrazolo[3,4-b]pyridine (0.0462 g, 0.212 mmol) and Pd/C were taken up in MeOH. Hydrogen gas was passed through for 10 minutes, and the reaction mixture was stirred under a hydrogen atmosphere for 20 minutes. The solution was filtered through celite and concentrated to provide 3-(cis-2-methylcyclopropyl)-1H-pyrazolo[3,4-b]pyridin-5-amine as an oil, which was used without further purification.
Reaction SMILES: [F:1][C:2]1[C:15]2[C:14](=[O:16])[C:13]3[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=3)[S:7][C:6]=2[C:5]([OH:17])=[CH:4][CH:3]=1.C(C1C=C(C)C=C(C(C)(C)C)C=1O)(C)(C)C.FC(F)(F)C(O)=O.[CH:41]([O:43][CH2:44][CH2:45][O:46][CH2:47][CH2:48][O:49][C:50](=[O:53])[CH:51]=[CH2:52])=[CH2:42]>>[F:1][C:2]1[C:15]2[C:14](=[O:16])[C:13]3[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=3)[S:7][C:6]=2[C:5]([O:17][CH:41]([O:43][CH2:44][CH2:45][O:46][CH2:47][CH2:48][O:49][C:50](=[O:53])[CH:51]=[CH2:52])[CH3:42])=[CH:4][CH:3]=1
Reactant: O=c1c2ccccc2sc2c(O)ccc(F)c12
Reactant: C=COCCOCCOC(=O)C=C
Agent: Cc1cc(C(C)(C)C)c(O)c(C(C)(C)C)c1
Solvent: O=C(O)C(F)(F)F
Product: C=CC(=O)OCCOCCOC(C)Oc1ccc(F)c2c(=O)c3ccccc3sc12
Temperature: 70 °C
Reaction time: 4 h

Procedure:
1-fluoro-4-hydroxy-thioxanthen-9-one (2.5 g, 0.01 mol), 2,6-di-tert-butyl-4-methylphenol (0.07 g, 0.32 mmol) and trifluoroacetic acid (0.1 g=92.4 μL, 1.2 mmol) were added to 2-(2′-vinyloxyethoxy)ethylacrylate (27.6 g). The mixture was heated to 70° C. and stirred for 4 hours. After cooling down to room temperature, activated Lewatit M600 MB (10 g) was added and stirred for 1 hour. After filtration, a 15 w % solution of acrylic acid 2-{2-[1-(1-fluoro-9-oxo-9H-thioxanthen-4-yloxy)-ethoxy]-ethoxy}-ethyl ester in 2-(2′-vinyloxyethoxy)ethylacrylate was obtained, which was directly used in the radiation curable compositions according to a preferred embodiment of the present invention.
Reaction SMILES: [NH:1]1[C:9]2[CH:8]=[CH:7][CH:6]=[C:5]3[CH2:10][CH2:11][CH2:12][C:3]([C:4]=23)=[C:2]1[C:13]([O:15][CH2:16][CH3:17])=[O:14].[H-].[Na+].[CH2:20](Br)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1>CN(C)C=O>[CH2:20]([N:1]1[C:9]2[CH:8]=[CH:7][CH:6]=[C:5]3[CH2:10][CH2:11][CH2:12][C:3]([C:4]=23)=[C:2]1[C:13]([O:15][CH2:16][CH3:17])=[O:14])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1
Reactant: BrCc1ccccc1
Reactant: CCOC(=O)c1[nH]c2cccc3c2c1CCC3
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CCOC(=O)c1c2c3c(cccc3n1Cc1ccccc1)CCC2
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
Ethyl 1,3,4,5-tetrahydro-benz[cd]indole-2-carboxylate (0.40 g, 1.74 mmol) was added to a suspension of 60% sodium hydride (0.077 g, 1.92 mmol) in N,N-dimethylformamide (5 ml), followed by stirring at room temperature for 30 minutes. Then, benzyl bromide (0.36 g, 2.09 mmol) was added and the resulting mixture was stirred for 1.5 hours. Thereafter, the same after-treatment as in Reference Example 1 was carried out to obtain an oil of ethyl 1,3,4,5-tetrahydro -1benzyl-benz[cd]indole-2-carboxylate. 1 Hnmr (CDC13) δ:
Reaction SMILES: [F:1][C:2]([F:32])([F:31])[CH2:3][O:4][C:5]1[CH:6]=[C:7]([C:15]2[CH:20]=[C:19]([C:21]([F:24])([F:23])[F:22])[N:18]3[N:25]=[CH:26][C:27]([C:28](O)=O)=[C:17]3[N:16]=2)[CH:8]=[CH:9][C:10]=1[C:11]([F:14])([F:13])[F:12].[OH:33][NH:34][C:35](=[NH:46])[C:36]1[CH:41]=[CH:40][CH:39]=[C:38]([S:42](=[O:45])(=[O:44])[NH2:43])[CH:37]=1>>[F:32][C:2]([F:1])([F:31])[CH2:3][O:4][C:5]1[CH:6]=[C:7]([C:15]2[CH:20]=[C:19]([C:21]([F:22])([F:23])[F:24])[N:18]3[N:25]=[CH:26][C:27]([C:28]4[O:33][N:34]=[C:35]([C:36]5[CH:37]=[C:38]([S:42]([NH2:43])(=[O:44])=[O:45])[CH:39]=[CH:40][CH:41]=5)[N:46]=4)=[C:17]3[N:16]=2)[CH:8]=[CH:9][C:10]=1[C:11]([F:12])([F:13])[F:14]
Reactant: O=C(O)c1cnn2c(C(F)(F)F)cc(-c3ccc(C(F)(F)F)c(OCC(F)(F)F)c3)nc12
Reactant: N=C(NO)c1cccc(S(N)(=O)=O)c1
Product: NS(=O)(=O)c1cccc(-c2noc(-c3cnn4c(C(F)(F)F)cc(-c5ccc(C(F)(F)F)c(OCC(F)(F)F)c5)nc34)n2)c1

Procedure:
The title compound was prepared from 5-[3-(2,2,2-trifluoro-ethoxy)-4-trifluoromethyl-phenyl]-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidine-3-carboxylic acid (example C. 10) (237 mg, 0.5 mmol) and N-hydroxy-3-sulfamoyl-benzamidine [CAS-No. 9000-88-7] (161 mg, 0.75 mmol) according to general procedure II. Obtained after purification by flash chromatography (ethyl acetate/hexane) and crystallization (dichloromethane) as a light yellow solid (220 mg, 67%). MS (EI) 652.2 [(M)+]; mp 250° C.
Reaction SMILES: [NH2:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6](=[O:13])[NH:7][C:8](=[O:12])[NH:9]2)=[CH:4][C:3]=1[O:14][CH3:15].[Cl:16][C:17]1[CH:27]=[C:26]([F:28])[C:25]([F:29])=[CH:24][C:18]=1[C:19]([N:21]=[C:22]=[O:23])=[O:20]>C(#N)C.CN1CCCC1=O>[Cl:16][C:17]1[CH:27]=[C:26]([F:28])[C:25]([F:29])=[CH:24][C:18]=1[C:19]([NH:21][C:22]([NH:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6](=[O:13])[NH:7][C:8](=[O:12])[NH:9]2)=[CH:4][C:3]=1[O:14][CH3:15])=[O:23])=[O:20]
Reactant: COc1cc2c(=O)[nH]c(=O)[nH]c2cc1N
Reactant: O=C=NC(=O)c1cc(F)c(F)cc1Cl
Solvent: CN1CCCC1=O
Solvent: CC#N
Product: COc1cc2c(=O)[nH]c(=O)[nH]c2cc1NC(=O)NC(=O)c1cc(F)c(F)cc1Cl
Yield: 28.4 %

Procedure:
100 mg (0.53 mmol) of 7-amino-6-methoxy-1H-quinazoline-2,4-dione were suspended in 20 ml of acetonitrile and 2 ml of N-methyl-2-pyrrolidinone, and 200 mg (0.97 mmol) of 2-chloro-4,5-difluorobenzoyl isocyanate (example 1a) were added. The reaction mixture was heated to boiling and then quenched with methanol and concentrated in vacuo. The residue was stirred with acetonitrile, and the resulting precipitate was filtered off. 64 mg (30%) of the desired product were obtained.
Reaction SMILES: C([O:3][C:4](=[O:36])[CH2:5][C@@H:6]([C:29]1[CH:30]=[N:31][C:32]([CH3:35])=[N:33][CH:34]=1)[CH2:7][CH2:8][CH2:9][N:10]1[C@H:14]([CH3:15])[CH2:13][C@H:12]([NH:16][CH2:17][C:18]2[CH:27]=[CH:26][C:25]3[CH2:24][CH2:23][CH2:22][NH:21][C:20]=3[N:19]=2)[C:11]1=[O:28])C.O.[OH-].[Li+]>O1CCCC1.O>[CH3:35][C:32]1[N:33]=[CH:34][C:29]([C@@H:6]([CH2:7][CH2:8][CH2:9][N:10]2[C@H:14]([CH3:15])[CH2:13][C@H:12]([NH:16][CH2:17][C:18]3[CH:27]=[CH:26][C:25]4[CH2:24][CH2:23][CH2:22][NH:21][C:20]=4[N:19]=3)[C:11]2=[O:28])[CH2:5][C:4]([OH:36])=[O:3])=[CH:30][N:31]=1
Reactant: CCOC(=O)C[C@H](CCCN1C(=O)[C@@H](NCc2ccc3c(n2)NCCC3)C[C@H]1C)c1cnc(C)nc1
Agent: [Li+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: O
Product: Cc1ncc([C@@H](CCCN2C(=O)[C@@H](NCc3ccc4c(n3)NCCC4)C[C@H]2C)CC(=O)O)cn1
Reaction time: 16 h

Procedure:
To a stirred solution of 5-6 (110 mg) in tetrahydrofuran (4.5 mL) was added lithium hydroxide monohydrate (45 mg) in water (4.5 mL) and the mixture was stirred for 16 h. The reaction mixture was concentrated at reduced pressure and the resulting oil was purified by flash column chromatography (silica gel, 30:3:3 to 50:5:5% ethanol/ammonium hydroxide/water in ethyl acetate) to give 5-7 as a white solid.
Reaction SMILES: Br[C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[C:4]1([C:25]3=[CH:26][C:27]4[O:31][CH2:30][O:29][C:28]=4[CH:32]=[C:24]3[O:23][CH2:22]1)[C:5](=[O:21])[N:6]2[CH2:11][C:12]1[O:13][C:14]([C:17]([F:20])([F:19])[F:18])=[CH:15][CH:16]=1.BrC1C=CC=[C:39]2[C:35]=1[C:36]1([C:52]3=[CH:53][C:54]4OCO[C:55]=4[CH:59]=[C:51]3OC1)C(=O)[N:38]2CCCCC.N1C2C(=CC=CC=2)C=C(B(O)O)C=1.CN(C)C1N=CC(B(O)O)=CC=1>>[N:38]1[C:53]2[C:52](=[CH:51][CH:59]=[CH:55][CH:54]=2)[CH:36]=[C:35]([C:2]2[CH:10]=[CH:9][CH:8]=[C:7]3[C:3]=2[C:4]2([C:25]4=[CH:26][C:27]5[O:31][CH2:30][O:29][C:28]=5[CH:32]=[C:24]4[O:23][CH2:22]2)[C:5](=[O:21])[N:6]3[CH2:11][C:12]2[O:13][C:14]([C:17]([F:19])([F:20])[F:18])=[CH:15][CH:16]=2)[CH:39]=1
Reactant: O=C1N(Cc2ccc(C(F)(F)F)o2)c2cccc(Br)c2C12COc1cc3c(cc12)OCO3
Reactant: CCCCCN1C(=O)C2(COc3cc4c(cc32)OCO4)c2c(Br)cccc21
Agent: CN(C)c1ccc(B(O)O)cn1
Agent: OB(O)c1cnc2ccccc2c1
Product: O=C1N(Cc2ccc(C(F)(F)F)o2)c2cccc(-c3cnc4ccccc4c3)c2C12COc1cc3c(cc12)OCO3

Procedure:
Following the procedure as described in EXAMPLE 4, and making non-critical variations using 4′-bromo-1′-{[5-(trifluoromethyl)-2-furyl]methyl}spiro[furo[2,3-f][1,3]benzodioxole-7,3′-indol]-2′(1′H)-one to replace 4′-bromo-1′-pentylspiro[furo[2,3-f][1,3]benzodioxole-7,3′-indol]-2′(1H)-one, quinolin-3-ylboronic acid to replace [6-(dimethylamino)pyridin-3-yl]boronic acid, the title compound was obtained (50%) as a colorless solid: 1H NMR (300 MHz, CDCl3) δ 8.52 (d, 1H), 8.09 (d, 1H), 7.74-7.68 (m, 1H), 7.56-7.50 (m, 1H), 7.42-7.39 (m, 2H), 7.32 (s, 1H), 7.09 (d, 1H), 7.01 (d, 1H), 6.78-6.77 (m, 1H), 6.45 (d, 1H), 6.26 (s, 1H), 5.94 (d, 1H), 5.91 (s, 1H), 5.89 (d, 1H), 5.03 (ABq, 2H), 4.52 (ABq, 2H); 13C NMR (75 MHz, CDCl3) δ 177.4, 156.0, 151.8, 150.0, 149.3, 147.0, 142.4, 141.8, 136.8, 135.8, 131.1, 130.2, 129.9, 129.3, 129.0, 128.8, 128.0, 127.1, 127.0, 126.4, 126.0, 120. 4, 112.7, 109.5, 108.8, 102.5, 101.7, 93.7, 78.3, 58.5, 37.1; MS (ES+) m/z 557.4 (M+1).