Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl[C:2]1[C:7]([N+:8]([O-])=O)=[CH:6][CH:5]=[CH:4][N:3]=1.[C:11]1([NH:17][C:18](=O)[CH3:19])[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1>>[CH3:19][C:18]1[N:17]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[C:2]2=[N:3][CH:4]=[CH:5][CH:6]=[C:7]2[N:8]=1
Reactant: CC(=O)Nc1ccccc1
Reactant: O=[N+]([O-])c1cccnc1Cl
Product: Cc1nc2cccnc2n1-c1ccccc1
Yield: 88.9 %

Procedure:
Method A applied to 2-chloro-3-nitropyridine (79 mg, 0.5 mmol) and N-phenylacetamide (81 mg, 0.6 mmol) afforded the title compound as pale yellow viscous oil (93 mg, 89%). 1H NMR (DMSO) δ 2.48 (s, 3H), 7.24 (dd, 1H), 7.53-7.63 (m, 5H), 8.02 (d, 1H), 8.20 (d, 1H); 13C NMR δ 14.6, 118.3, 125.9, 127.4, 128.7, 129.3, 134.1, 134.3, 143.0, 148.7, 152.9. HRMS (FAB): cal. for C13H12N3 [M+H+]: 210.1031; found: 210.1027.
Reaction SMILES: Cl[C:2]1[N:23]=[CH:22][C:5]2[C:6]3[N:7]([CH:11]=[C:12]([C:14]4[N:15]([CH:19]([CH3:21])[CH3:20])[CH:16]=[CH:17][N:18]=4)[N:13]=3)[CH2:8][CH2:9][O:10][C:4]=2[CH:3]=1.C(O)(=O)C>C(O)C.[OH-].[OH-].[Pd+2]>[CH:19]([N:15]1[CH:16]=[CH:17][N:18]=[C:14]1[C:12]1[N:13]=[C:6]2[C:5]3[CH:22]=[N:23][CH:2]=[CH:3][C:4]=3[O:10][CH2:9][CH2:8][N:7]2[CH:11]=1)([CH3:21])[CH3:20]
Reactant: CC(C)n1ccnc1-c1cn2c(n1)-c1cnc(Cl)cc1OCC2
Agent: [Pd+2]
Agent: [OH-]
Solvent: CCO
Solvent: CC(=O)O
Product: CC(C)n1ccnc1-c1cn2c(n1)-c1cnccc1OCC2
Temperature: 25 °C
Reaction time: 2 h
Yield: 33.9 %

Procedure:
9-Chloro-2-(1-isopropyl-1H-imidazol-2-yl)-5,6-dihydroimidazo[1,2-d]pyrido[3,4-f][1,4]oxazepine (0.044 g, 0.13 mmol), prepared according to Example 377, was taken up in ethanol (5 mL) and 20% palladium hydroxide on carbon (19 mg, 0.03 mmol), and glacial acetic acid (0.2 mL) were added. The mixture was subjected to evacuation under reduced pressure and recycled with an H2 atmosphere. This process was repeated twice. Finally, the reaction was placed under an H2 atmosphere and allowed to stir at ambient temperature 2 h. At the end of this period the mixture was filtered through a pad of Celite® and concentrated in vacuo. The residue was purified by rp-HPLC (0.1% NH4OH in acetonitrile) to provide 13 mg (39% yield) of 386. MS (ESI+) m/z 296.1 (M+H+), calcd. 295.3. 1H NMR (400 MHz, DMSO) δ 9.47 (s, 1H), 8.33 (d, J=5.6 Hz, 1H), 7.74 (s, 1H), 7.33 (d, J=1.1 Hz, 1H), 7.03 (d, J=5.6 Hz, 1H), 6.92 (d, J=0.9 Hz, 1H), 5.66 (dq, J=13.3, 6.6 Hz, 1H), 4.57 (td, J=7.9, 3.5 Hz, 4H), 1.38 (d, J=6.6 Hz, 6H)
Reaction SMILES: Cl[C:2]1[NH:6][C:5]2[CH:7]=[CH:8][C:9]([Cl:11])=[CH:10][C:4]=2[N:3]=1.[F:12][C:13]([F:27])([F:26])[C:14]1[C:15]([N:20]2[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]2)=[N:16][CH:17]=[CH:18][CH:19]=1>>[Cl:11][C:9]1[CH:8]=[CH:7][C:5]2[N:6]=[C:2]([N:23]3[CH2:24][CH2:25][N:20]([C:15]4[C:14]([C:13]([F:27])([F:12])[F:26])=[CH:19][CH:18]=[CH:17][N:16]=4)[CH2:21][CH2:22]3)[NH:3][C:4]=2[CH:10]=1
Reactant: FC(F)(F)c1cccnc1N1CCNCC1
Reactant: Clc1ccc2[nH]c(Cl)nc2c1
Product: FC(F)(F)c1cccnc1N1CCN(c2nc3ccc(Cl)cc3[nH]2)CC1

Procedure:
The benzoimidazole from step (b) above (0.186 g, 0.995 mmol) and 1-(3-trifluoromethylpyridin-2-yl)piperazine (0.23 g, 0.995 mmol, Maybridge) reacted under the conditions of Example 3c to give the title compound as a white solid. M.p. 228-231° C. MS (ESI, pos. ion) m/z: 382 (M+1).
Reaction SMILES: [CH3:1][S:2](Cl)(=[O:4])=[O:3].O[CH2:7][CH:8]1[CH2:13][O:12][CH2:11][CH:10]([CH3:14])[O:9]1.N1C=CC=CC=1>CN(C)C1C=CN=CC=1.ClCCl>[CH3:1][S:2]([CH2:7][CH:8]1[CH2:13][O:12][CH2:11][CH:10]([CH3:14])[O:9]1)(=[O:4])=[O:3]
Reactant: CC1COCC(CO)O1
Reactant: CS(=O)(=O)Cl
Agent: CN(C)c1ccncc1
Solvent: ClCCl
Solvent: c1ccncc1
Product: CC1COCC(CS(C)(=O)=O)O1
Temperature: 25 °C
Reaction time: 18 h

Procedure:
13.7 ml of methanesulphonic acid chloride are added dropwise, over a period of approximately 30 minutes, while stirring at 0° to 5° C., to a solution of 21.1 g of 2-hydroxymethyl-6-methyl-1,4-dioxan, 15.2 g of pyridine and 0.6 g of 4-dimethylaminopyridine in 80 ml of dichloromethane. After stirring for a further 18 hours at room temperature, the reaction mixture is extracted repeatedly with 1N hydrochloric acid and then washed with water until neutral. After the organic phase, which has been separated off, has been dried over sodium sulphate and the solvent has been distilled off completely, the title compound of formula ##STR55## is obtained. The 1H-proton resonance spectrum corresponds to this structure; nD22 =1.4607.
Reaction SMILES: Br[CH2:2][C:3]1([CH3:29])[CH:7]([C:8]([O:10][CH2:11][C:12]([Cl:15])([Cl:14])[Cl:13])=[O:9])[N:6]2[C:16](=[O:28])[CH:17]([NH:18][C:19](=[O:27])[CH2:20][C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[C@H:5]2[S:4]1.C(N(CC)CC)C.CS(C)=[O:39]>F[B-](F)(F)F.[Ag+]>[OH:39][C:3]1([CH3:2])[CH:7]([C:8]([O:10][CH2:11][C:12]([Cl:15])([Cl:14])[Cl:13])=[O:9])[N:6]2[C:16](=[O:28])[CH:17]([NH:18][C:19](=[O:27])[CH2:20][C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[C@H:5]2[S:4][CH2:29]1
Reactant: CC1(CBr)S[C@@H]2C(NC(=O)Cc3ccccc3)C(=O)N2C1C(=O)OCC(Cl)(Cl)Cl
Reactant: CS(C)=O
Agent: [Ag+]
Agent: F[B-](F)(F)F
Solvent: CCN(CC)CC
Product: CC1(O)CS[C@@H]2C(NC(=O)Cc3ccccc3)C(=O)N2C1C(=O)OCC(Cl)(Cl)Cl
Reaction time: 3 h
Yield: 58 %

Procedure:
2,2,2-Trichloroethyl 2-bromomethyl-2-methyl-6-(2-phenylacetamido)penam-3-carboxylate (0.54 g) was dissolved in absolute dimethylsulfoxide (5 ml). To this solution was added silver fluoroborate (0.20 g) and then the mixture was stirred under shielding from light for 3 hours at room temperature. To the solution was added a solution of triethylamine (0.1 g) in dimethylsulfoxide (0.5 ml) and the solution was further stirred for 5 hours and then allowed to stand overnight at room temperature. Precipitates were filtered off and the filtrate was poured into ice-water and then extracted with ethyl acetate. The extract was washed with water and dried. The residue obtained by distilling off the solvent under reduced pressure was crystallized by a small amount of ether to give colorless crystals of 2,2,2-trichloroethyl 3-hydroxy-3-methyl-7-(2-phenylacetamido)cepham-4-carboxylate (280 mg) (58%). This substance was recrystallized from a mixed solvent of benzene-n-hexane to give colorless needles melting at 169° to 171° C.
Reaction SMILES: O[CH2:2][CH2:3][S:4][CH2:5][C:6](=[O:15])[C:7](=[N:13][OH:14])[C:8]([O:10][CH2:11][CH3:12])=[O:9].C1(C)C=CC=CC=1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>O>[OH:14][N:13]=[C:7]([C:6]1[O:15][CH2:2][CH2:3][S:4][CH:5]=1)[C:8]([O:10][CH2:11][CH3:12])=[O:9]
Reactant: CCOC(=O)C(=NO)C(=O)CSCCO
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: O
Solvent: Cc1ccccc1
Product: CCOC(=O)C(=NO)C1=CSCCO1
Reaction time: 0.25 h
Yield: 92.1 %

Procedure:
Ethyl 4-(2-hydroxy-ethylthio)-2-hydroxyimino-3-oxobutyrate (321 g.) is dissolved in boiling toluene (3.2 liters) and para-toluenesulphonic acid monohydrate (26 g.) is then added. Vigorous boiling occurs, with liberation of water, which is removed in a Dean-Stark apparatus. The heating of the reaction mixture is continued for 15 minutes. After cooling, the toluene solution is filtered and washed three times with water (a total of 1.5 liters), then with a saturated sodium bicarbonate solution (200 cc.) and finally with water (500 cc.). It is dried over magnesium sulphate, treated with decolourising charcoal, filtered and concentrated to dryness under reduced pressure (20 mm Hg). Ethyl α-hydroxyimino(5,6-dihydro-1,4-oxathiin-2-yl)acetate (273 g.) is obtained in the form of an oil which slowly solidifies.
Reaction SMILES: [F:1][C:2]([F:10])([F:9])[C:3]([CH3:8])([CH3:7])[C:4]([NH2:6])=O.COC1C=CC(P2(SP(C3C=CC(OC)=CC=3)(=S)S2)=[S:20])=CC=1>C1COCC1>[F:1][C:2]([F:10])([F:9])[C:3]([CH3:8])([CH3:7])[C:4]([NH2:6])=[S:20]
Reactant: CC(C)(C(N)=O)C(F)(F)F
Reactant: COc1ccc(P2(=S)SP(=S)(c3ccc(OC)cc3)S2)cc1
Solvent: C1CCOC1
Product: CC(C)(C(N)=S)C(F)(F)F
Temperature: 25 °C
Yield: 129.3 %

Procedure:
A mixture of 1.05 g (6.77 mmol) 3,3,3-trifluoro-2,2-dimethyl-propionamide and 1.48 g (3.66 mmol) Lawesson's reagent in 32 ml dry THF was stirred at reflux temperature for 20 h. After that the reaction mixture was cooled to room temperature and concentrated in vacuo. The residue was purified by chromatography on silicagel (heptane, EtOAc) to afford 0.81 g of the title compound as pure white crystals. MS: M+H=172.
Reaction SMILES: [C:1](N1C=CN=C1)([N:3]1[CH:7]=[CH:6][N:5]=[CH:4]1)=[O:2].[N:13]1([CH2:19][CH2:20][OH:21])[CH2:18][CH2:17][O:16][CH2:15][CH2:14]1.CCOCC>C(Cl)Cl>[N:3]1([C:1]([O:21][CH2:20][CH2:19][N:13]2[CH2:18][CH2:17][O:16][CH2:15][CH2:14]2)=[O:2])[CH:7]=[CH:6][N:5]=[CH:4]1
Reactant: OCCN1CCOCC1
Reactant: O=C(n1ccnc1)n1ccnc1
Solvent: CCOCC
Solvent: ClCCl
Product: O=C(OCCN1CCOCC1)n1ccnc1
Temperature: 25 °C
Reaction time: 22 h
Yield: 69.9 %

Procedure:
A mixture of 1,1′-carbonyldiimidazole (6.5 g, 40 mmol) and 2-(4-morpholinyl)-1-ethanol (5.0 g, 38.1 mmol) in DCM (200 mL) was stirred for 22 h at rt. Ether (400 mL) was added and the mixture was washed with water. The water layer was then extracted with DCM. The combined organic layers were dried over Na2SO4 and evaporated to give 6.0 g (70%) of the tide compound.
Reaction SMILES: [OH:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][O:10][C:11]1[CH:18]=[CH:17][CH:16]=[C:15]([N+:19]([O-:21])=[O:20])[C:12]=1[C:13]#[N:14].N1C=CC=CC=1.[C:28](Cl)(=[O:30])[CH3:29]>C(Cl)Cl>[C:28]([O:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][O:10][C:11]1[CH:18]=[CH:17][CH:16]=[C:15]([N+:19]([O-:21])=[O:20])[C:12]=1[C:13]#[N:14])(=[O:30])[CH3:29]
Reactant: CC(=O)Cl
Reactant: N#Cc1c(OCCCCCCCCO)cccc1[N+](=O)[O-]
Solvent: c1ccncc1
Solvent: ClCCl
Product: CC(=O)OCCCCCCCCOc1cccc([N+](=O)[O-])c1C#N
Temperature: 0 °C
Yield: 99.7 %

Procedure:
2-(8-hydroxyoctyloxy)-6-nitrobenzonitrile (804 μmol, 235 mg) (Example 214c) was dissolved in dry DCM (10 mL), cooled to 0° C., and treated successively with pyridine (3.216 mmol, 260 μL) and acetyl chloride (1.608 mmol, 114 μL). The reaction mixture was stirred and allowed to warm slowly to room temperature. When the reaction was complete, the volatiles were removed in vacuo and the crude product purified on silica gel (10% to 50% EtOAc in hexanes) to give the desired product (268 mg, 100%). MS 335 (MH+).
Reaction SMILES: [NH2:1][C:2]1[S:3][C:4]2[N:5]=[C:6]([NH:11][C:12]3[CH:13]=[C:14]([NH:19][C:20](=[O:32])[C:21]4[CH:26]=[CH:25][CH:24]=[C:23]([C:27]([C:30]#[N:31])([CH3:29])[CH3:28])[CH:22]=4)[CH:15]=[CH:16][C:17]=3[CH3:18])[N:7]=[CH:8][C:9]=2[N:10]=1.[CH:33]1([C:36](Cl)=[O:37])[CH2:35][CH2:34]1.C(=O)([O-])O.[Na+]>N1C=CC=CC=1>[C:30]([C:27]([C:23]1[CH:22]=[C:21]([CH:26]=[CH:25][CH:24]=1)[C:20]([NH:19][C:14]1[CH:15]=[CH:16][C:17]([CH3:18])=[C:12]([NH:11][C:6]2[N:7]=[CH:8][C:9]3[N:10]=[C:2]([NH:1][C:36]([CH:33]4[CH2:35][CH2:34]4)=[O:37])[S:3][C:4]=3[N:5]=2)[CH:13]=1)=[O:32])([CH3:29])[CH3:28])#[N:31]
Reactant: Cc1ccc(NC(=O)c2cccc(C(C)(C)C#N)c2)cc1Nc1ncc2nc(N)sc2n1
Reactant: O=C(Cl)C1CC1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: c1ccncc1
Product: Cc1ccc(NC(=O)c2cccc(C(C)(C)C#N)c2)cc1Nc1ncc2nc(NC(=O)C3CC3)sc2n1
Temperature: 25 °C
Reaction time: 2 h
Yield: 35.4 %

Procedure:
To a solution of N-{3-[(2-amino[1,3]thiazolo[5,4-d]pyrimidin-5-yl)amino]-4-methylphenyl}-3-(1-cyano-1-methylethyl)benzamide (137 mg, 309 μmol) in pyridine (3 mL) was added cyclopropanecarbonyl chloride (68 μL, 742 μmol), and the mixture was stirred at room temperature for 2 hr. To the reaction mixture was added saturated aqueous sodium hydrogen carbonate solution (20 mL), and the mixture was extracted with ethyl acetate/tetrahydrofuran mixture (9:1, 20 mL, 5 mL). The combined organic layer was washed with saturated brine (5 mL), and dried over anhydrous sodium sulfate. The insoluble material was filtered off, and the filtrate was concentrated under reduced pressure. The obtained residue was recrystallized from methanol and ethyl acetate to give the title compound (56 mg, 35%) as pale-red crystals.
Reaction SMILES: Cl[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([C:8]#[N:9])[N:3]=1.[K].C(=O)([O-])[O-].[OH:15][C:16]1[CH:17]=[C:18]([C:22]([F:25])([F:24])[F:23])[CH:19]=[CH:20][CH:21]=1.O>CN(C=O)C>[F:23][C:22]([F:24])([F:25])[C:18]1[CH:17]=[C:16]([O:15][C:2]2[CH:7]=[CH:6][CH:5]=[C:4]([C:8]#[N:9])[N:3]=2)[CH:21]=[CH:20][CH:19]=1
Reactant: N#Cc1cccc(Cl)n1
Reactant: Oc1cccc(C(F)(F)F)c1
Agent: O=C([O-])[O-]
Agent: [K]
Solvent: CN(C)C=O
Solvent: O
Product: N#Cc1cccc(Oc2cccc(C(F)(F)F)c2)n1
Temperature: 90 °C
Reaction time: 10 h

Procedure:
4.00 g (28.9 mmol) of 2-chloro-6-cyanopyridine were introduced together with 9.57 g (69.3 mmol) of potassium /carbonate in 20 ml of anhydrous DMF, and 5.62 g (34.6 mmol) of 3-hydroxybenzotrifluoride were added. After 10 h of stirring at 90° C., H2O was added and the mixture was subjected to repeated extraction with ethyl acetate. The organic phase was then washed twice with water, dried over MgSO4 and concentrated.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[N:4][C:5]([N:11]2[CH2:15][CH2:14][CH:13]([O:16][C:17]3[CH:18]=[C:19]([CH3:23])[CH:20]=[CH:21][CH:22]=3)[CH2:12]2)=[C:6]([CH:10]=1)[C:7]([OH:9])=O.Cl.[NH2:25][C:26]1([C:29]2[CH:38]=[CH:37][C:32]([C:33]([O:35][CH3:36])=[O:34])=[CH:31][CH:30]=2)[CH2:28][CH2:27]1>>[Cl:1][C:2]1[CH:3]=[N:4][C:5]([N:11]2[CH2:15][CH2:14][CH:13]([O:16][C:17]3[CH:18]=[C:19]([CH3:23])[CH:20]=[CH:21][CH:22]=3)[CH2:12]2)=[C:6]([CH:10]=1)[C:7]([NH:25][C:26]1([C:29]2[CH:38]=[CH:37][C:32]([C:33]([O:35][CH3:36])=[O:34])=[CH:31][CH:30]=2)[CH2:28][CH2:27]1)=[O:9]
Reactant: COC(=O)c1ccc(C2(N)CC2)cc1
Reactant: Cc1cccc(OC2CCN(c3ncc(Cl)cc3C(=O)O)C2)c1
Agent: Cl
Product: COC(=O)c1ccc(C2(NC(=O)c3cc(Cl)cnc3N3CCC(Oc4cccc(C)c4)C3)CC2)cc1
Yield: 5 %

Procedure:
The title compound (D198) (12 mg) was prepared according to the experimental procedure described in Description 146 starting from 5-chloro-2-(3-(m-tolyloxy)pyrrolidin-1-yl)nicotinic acid (D141) (160 mg, 0.472 mmol) and methyl 4-(1-aminocyclopropyl)benzoate (D7) (107.46 mg, 0.472 mmol). The residue (50 mg) obtained from SPE-Si cartridge purification (50 mg) dissolved in a mixture of chloroform/ethanol (1/1) (1 ml) was separated by chiral HPLC [Phenomenex Lux1 column (250×20 mm, 5 μm particle size). Mobile phase: isocratic premixed mixture of (hexane 80%, ethanol 20%) containing 0.1% of diethylamine. Flow rate=10 ml/min. UV detection: 245 nm]. Collected fractions, after solvent evaporation, afforded the title compound (D198) (12 mg)
Reaction SMILES: [C:1]([C:3]1[CH:8]=[CH:7][C:6](B(O)O)=[CH:5][CH:4]=1)#[N:2].Br[C:13]1[CH:18]=[CH:17][C:16]([OH:19])=[C:15]([F:20])[CH:14]=1.O.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>CC(O)C.O>[F:20][C:15]1[CH:14]=[C:13]([C:6]2[CH:7]=[CH:8][C:3]([C:1]#[N:2])=[CH:4][CH:5]=2)[CH:18]=[CH:17][C:16]=1[OH:19]
Reactant: N#Cc1ccc(B(O)O)cc1
Reactant: Oc1ccc(Br)cc1F
Agent: O=P([O-])([O-])[O-]
Agent: [K+]
Solvent: CC(C)O
Solvent: O
Product: N#Cc1ccc(-c2ccc(O)c(F)c2)cc1
Temperature: 70 °C
Reaction time: 2 h
Yield: 55 %

Procedure:
4-Cyanophenylboronic acid (0.92 g, 6.26 mmol), 4-bromo-2-fluorophenol (1.0 g, 5.2 mmol), potassium phosphate tribasic monohydrate (3.0 g, 15.6 mmol) and Pd (Ph3P)2Cl2 (73.0 mg, 0.1 mmol) were combined in a mixture of IPA/H2O (40 mL, 3:1) and heated at 70° C. After 2 hours, the mixture was allowed to cool to room temperature and was filtered over celite. The filtrate was diluted with 150 ml of CH2Cl2 and washed with water twice. The organic phase was dried over sodium sulfate, filtered, and the filtrate concentrated under reduced pressure. The residue was chromatographed over silica gel using CH2Cl2 to provide the title compound as a white powder (0.61 g, 55% yield). 1HNMR (300 MHz, CDCl3) δ5.20 (bs, 1H), 7.15-7.78 (m, 7H); MS (DCI) m/z 214 (M+H)+.
Reaction SMILES: [CH3:1][C:2]([N:6]1[CH:10]=[C:9]([NH:11][C:12](=[O:29])[CH:13]([NH:17][C:18](=[O:28])[CH2:19][C:20]2[CH:25]=[C:24]([F:26])[CH:23]=[C:22]([F:27])[CH:21]=2)[CH2:14][CH2:15][CH3:16])[N:8]=[CH:7]1)([CH3:5])[CH:3]=O.[CH2:30]([NH2:37])[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1>>[CH2:30]([NH:37][CH2:3][C:2]([N:6]1[CH:10]=[C:9]([NH:11][C:12](=[O:29])[CH:13]([NH:17][C:18](=[O:28])[CH2:19][C:20]2[CH:21]=[C:22]([F:27])[CH:23]=[C:24]([F:26])[CH:25]=2)[CH2:14][CH2:15][CH3:16])[N:8]=[CH:7]1)([CH3:5])[CH3:1])[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1
Reactant: NCc1ccccc1
Reactant: CCCC(NC(=O)Cc1cc(F)cc(F)c1)C(=O)Nc1cn(C(C)(C)C=O)cn1
Product: CCCC(NC(=O)Cc1cc(F)cc(F)c1)C(=O)Nc1cn(C(C)(C)CNCc2ccccc2)cn1

Procedure:
2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid [1-(1,1-dimethyl-2-oxo-ethyl)-1H-imidazol-4-yl]-amide was reacted with benzylamine to afford the title compound: C13 NMR (100 MHz, CDCl3) 14.0, 18.9, 26.4, 26.5, 36.0, 43.1, 53.2, 54.1, 59.0, 59.3, 102.6, 102.9, 103.1, 105.2, 112.4, 112.6, 127.2, 128.2, 128.6, 131.7, 137.8, 138.8, 140.3, 161.9, 164.4, 164.5, 169.2; MS m/z 498.1 (M+1).
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH:6]=[CH:7][C:8]=1[O:9][CH3:10])[NH2:5].CCN(C(C)C)C(C)C.[C:20](OC(=O)C)(=[O:22])[CH3:21]>C(Cl)Cl.CN(C1C=CN=CC=1)C>[F:1][C:2]1[CH:3]=[C:4]([NH:5][C:20](=[O:22])[CH3:21])[CH:6]=[CH:7][C:8]=1[O:9][CH3:10]
Reactant: COc1ccc(N)cc1F
Reactant: CC(=O)OC(C)=O
Agent: CN(C)c1ccncc1
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: COc1ccc(NC(C)=O)cc1F
Temperature: 25 °C
Reaction time: 8 h
Yield: 72.3 %

Procedure:
To a solution of 3-fluoro-4-methoxyaniline (1.15 g, 8.15 mmol) in dry CH2Cl2 (81 mL) in a 250 mL round-bottomed flask equipped with a magnetic stirrer were added DIEA (5.4 mL, 32.7 mmol), DMAP (221 mg, 1.81 mmol) and acetic anhydride (4.4 mL, 46.5 mmol) and the mixture was stirred overnight at RT. The solution was washed with brine (10 mL), dried over Na2SO4, filtered and concentrated at 40° C. under vacuum. Purification by column chromatography (SiO2, eluent cyclohexane:EtOAc=100:0 to 50:50) gave N-(3-fluoro-4-methoxyphenyl)acetamide SMA 44032 as a brown solid (1.08 g, 72% yield).
Reaction SMILES: [CH:1]12[CH2:9][CH:5]([CH2:6][NH:7][CH2:8]1)[CH2:4][N:3]([C:10]([O:12][CH:13]([CH3:15])[CH3:14])=[O:11])[CH2:2]2.CS(O[CH2:21][CH2:22][C:23]1[CH:28]=[CH:27][C:26]([C:29]#[N:30])=[CH:25][CH:24]=1)(=O)=O.C([O-])([O-])=O.[K+].[K+].N#N>CC#N>[C:29]([C:26]1[CH:27]=[CH:28][C:23]([CH2:22][CH2:21][N:7]2[CH2:8][CH:1]3[CH2:9][CH:5]([CH2:4][N:3]([C:10]([O:12][CH:13]([CH3:15])[CH3:14])=[O:11])[CH2:2]3)[CH2:6]2)=[CH:24][CH:25]=1)#[N:30]
Reactant: CC(C)OC(=O)N1CC2CNCC(C2)C1
Reactant: CS(=O)(=O)OCCc1ccc(C#N)cc1
Agent: N#N
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: CC(C)OC(=O)N1CC2CC(CN(CCc3ccc(C#N)cc3)C2)C1
Reaction time: 10 h
Yield: 88 %

Procedure:
iso-Propyl 3,7-diazabicyclo[3.3.1]nonane-3-carboxylate (1.06 g; 5 mmol; see Example H above) was added to a stirred suspension of 4-cyanophenethyl methanesulfonate (1.13 g; 5 mmol; from step (a) above) and K2CO3 (0.96 g; 7 mmol) in MeCN (5 mL) under an inert atmosphere (N2), and the reaction mixture was stirred for 10 h. The solvent was evaporated and the residue partitioned between DCM and NaHCO3 (aq.). The organic layer was separated, dried and concentrated. Purification using column chromatography (DCM:MeOH; 19:1) gave the title compound in a 88% yield.
Reaction SMILES: [CH2:1]([O:3][C:4]1[N:8]=[C:7]([CH:9]2[CH2:14][CH:13]([C:15]3[CH:20]=[CH:19][C:18]([CH2:21][CH3:22])=[CH:17][CH:16]=3)[CH2:12][N:11]([C:23]([N:25]3[CH2:30][CH2:29][S:28][CH2:27][CH2:26]3)=[O:24])[CH2:10]2)[O:6][N:5]=1)[CH3:2].ClC1C=CC=C(C(OO)=[O:39])C=1>>[CH2:1]([O:3][C:4]1[N:8]=[C:7]([CH:9]2[CH2:14][CH:13]([C:15]3[CH:16]=[CH:17][C:18]([CH2:21][CH3:22])=[CH:19][CH:20]=3)[CH2:12][N:11]([C:23]([N:25]3[CH2:30][CH2:29][S:28](=[O:39])[CH2:27][CH2:26]3)=[O:24])[CH2:10]2)[O:6][N:5]=1)[CH3:2]
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: CCOc1noc(C2CC(c3ccc(CC)cc3)CN(C(=O)N3CCSCC3)C2)n1
Product: CCOc1noc(C2CC(c3ccc(CC)cc3)CN(C(=O)N3CCS(=O)CC3)C2)n1
Yield: 41.7 %

Procedure:
55.0 mg (0.128 mmol) of the compound from Example 55 were reacted according to General Method 2 with 39.7 mg (0.115 mmol) of meta-chloroperbenzoic acid. Enantiomer separation of 50.7 mg of the racemate according to Method 4D gave 22.1 mg of the title compound from Example 56 (enantiomer 1) and 21.4 mg of the title compound from Example 57 (enantiomer 2).
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([O:12][CH3:13])[C:6]([NH:14][C:15](=[O:19])OCC)=[N:5]2.[CH3:20][O:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=1[N:28]1[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]1>>[F:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([O:12][CH3:13])[C:6]([NH:14][C:15]([N:31]1[CH2:30][CH2:29][N:28]([C:23]3[CH:24]=[CH:25][CH:26]=[CH:27][C:22]=3[O:21][CH3:20])[CH2:33][CH2:32]1)=[O:19])=[N:5]2
Reactant: COc1ccccc1N1CCNCC1
Reactant: CCOC(=O)Nc1nc2cc(F)ccc2nc1OC
Product: COc1ccccc1N1CCN(C(=O)Nc2nc3cc(F)ccc3nc2OC)CC1
Yield: 84 %

Procedure:
Ethyl N-(6-fluoro-2-methoxyquinoxalin-3-yl)carbamate and 1-(2-methoxyphenyl)piperazine were reacted by the same way with the example 1 to obtain the titled compound (yield, 84%). 1H NMR (200 MHz, CDCl3): δ 3.15 (s, 4H), 3.79-3.87 (m, 6H), 4.11 (s, 4H), 6.86-7.02 (m, 4H), 7.18-7.22 (m, 1H), 7.39-7.50 (m, 1H), 7.65-7.72 (m, 1H).
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1([C:9]2[CH:14]=[CH:13][C:12]([C:15]3[CH:20]=[CH:19][C:18]([C:21]4[O:25][N:24]=[C:23]([CH3:26])[C:22]=4[CH2:27][NH2:28])=[CH:17][CH:16]=3)=[CH:11][CH:10]=2)[CH2:8][CH2:7]1)=[O:5])[CH3:2].[C:29]1([CH2:35][C:36](Cl)=[O:37])[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1>>[CH2:1]([O:3][C:4]([C:6]1([C:9]2[CH:10]=[CH:11][C:12]([C:15]3[CH:20]=[CH:19][C:18]([C:21]4[O:25][N:24]=[C:23]([CH3:26])[C:22]=4[CH2:27][NH:28][C:36](=[O:37])[CH2:35][C:29]4[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=4)=[CH:17][CH:16]=3)=[CH:13][CH:14]=2)[CH2:8][CH2:7]1)=[O:5])[CH3:2]
Reactant: CCOC(=O)C1(c2ccc(-c3ccc(-c4onc(C)c4CN)cc3)cc2)CC1
Reactant: O=C(Cl)Cc1ccccc1
Product: CCOC(=O)C1(c2ccc(-c3ccc(-c4onc(C)c4CNC(=O)Cc4ccccc4)cc3)cc2)CC1

Procedure:
Prepared according to the procedure described in Example 3, Step 7, using 1-[4′-(4-aminomethyl-3-methyl-isoxazol-5-yl)-biphenyl-4-yl]-cyclopropanecarboxylic acid ethyl ester and phenylacetyl chloride.
Reaction SMILES: Br[C:2]12[CH2:11][CH:6]3[CH2:7][CH:8]([CH2:10][C:4](Br)([CH2:5]3)[CH2:3]1)[CH2:9]2.[C:13]1([OH:19])[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1>CO>[OH:19][C:13]1[CH:18]=[CH:17][C:16]([C:2]23[CH2:11][CH:6]4[CH2:7][CH:8]([CH2:10][C:4]([C:16]5[CH:17]=[CH:18][C:13]([OH:19])=[CH:14][CH:15]=5)([CH2:5]4)[CH2:3]2)[CH2:9]3)=[CH:15][CH:14]=1
Reactant: BrC12CC3CC(C1)CC(Br)(C3)C2
Reactant: Oc1ccccc1
Solvent: CO
Product: Oc1ccc(C23CC4CC(C2)CC(c2ccc(O)cc2)(C4)C3)cc1
Temperature: 185 °C
Reaction time: 5 h

Procedure:
1,3-Bis(4-hydroxyphenyl)adamantane (1,3-BPA) was synthesized as an aromatic diol monomer. First, 1,3-dibromoadamantane (1.876 g, 6.38 mmol) and phenol (28.1 mL, 0.32 mol) was added to a 50 mL 3-bulb flask, slowly heated to 185° C. under nitrogen atmosphere and stirred for 5 hours. After dissolving in 10 mL methanol, followed by precipitating in water (200 mL) at 60° C., the precipitate was filtered from the hot solution and then purified with MC and water. Thus obtained 1,3-BPA was recrystallized with MC to obtain pure 1,3-BPA (yield: 75%) of the following structure. Melting temperature was 200° C.