Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C:2]1([CH3:33])[O:6][C@H:5]2[C@H:7]([NH:12][C:13]3[N:18]4[N:19]=[C:20]([C:22]5[CH:27]=[CH:26][CH:25]=[C:24]([S:28][C:29]([F:32])([F:31])[F:30])[CH:23]=5)[CH:21]=[C:17]4[N:16]=[CH:15][CH:14]=3)[CH2:8][C@H:9]([CH2:10][OH:11])[C@H:4]2[O:3]1.C1(C)C=CC(S([O-])(=O)=O)=CC=1.[NH+]1C=CC=CC=1.[N+]12([S:59]([N-:62][C:63]([O:65][C:66]([CH3:69])([CH3:68])[CH3:67])=[O:64])(=[O:61])=[O:60])CCN(CC1)CC2.N12CCN(CC1)CC2.Cl>C(#N)C.O.C(OCC)(=O)C>[C:66]([O:65][C:63](=[O:64])[NH:62][S:59]([O:11][CH2:10][C@@H:9]1[C@@H:4]2[C@@H:5]([O:6][C:2]([CH3:33])([CH3:1])[O:3]2)[CH:7]([NH:12][C:13]2[N:18]3[N:19]=[C:20]([C:22]4[CH:27]=[CH:26][CH:25]=[C:24]([S:28][C:29]([F:32])([F:30])[F:31])[CH:23]=4)[CH:21]=[C:17]3[N:16]=[CH:15][CH:14]=2)[CH2:8]1)(=[O:61])=[O:60])([CH3:69])([CH3:67])[CH3:68]
Reactant: CC1(C)O[C@@H]2[C@@H](CO)C[C@@H](Nc3ccnc4cc(-c5cccc(SC(F)(F)F)c5)nn34)[C@@H]2O1
Reactant: CC(C)(C)OC(=O)[N-]S(=O)(=O)[N+]12CCN(CC1)CC2
Agent: C1CN2CCN1CC2
Agent: Cc1ccc(S(=O)(=O)[O-])cc1
Agent: Cl
Solvent: CCOC(C)=O
Solvent: O
Solvent: CC#N
Product: CC(C)(C)OC(=O)NS(=O)(=O)OC[C@H]1CC(Nc2ccnc3cc(-c4cccc(SC(F)(F)F)c4)nn23)[C@@H]2OC(C)(C)O[C@H]12
Temperature: 25 °C
Yield: 88 %

Procedure:
{(3aR,4R,6R,6aS)-2,2-dimethyl-6-[(2-{3-(trifluoromethylthio)phenyl}pyrazolo[1,5-a]pyrimidin-7-yl)amino]tetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl}methanol (3.4 g) was dissolved in 2-methyltetrahedrafuran (32.0 mL) and to this solution was added pyridinium p-toluenesulfonate (3.34 g). This formed a precipitate and to this white slurry was added (4-aza-1-azoniabicyclo[2.2.2]oct-1-ylsulfonyl)(tert-butoxycarbonyl)azanide-1,4-diazabicyclo[2.2.2]octane (1:1) hydrochloride (8.19 g). (prepared according to Armitage, I. et. al. U.S. Patent Application Publication US2009/0036678, and Armitage, I. et. al. Org. Lett., 2012, 14 (10), 2626-2629). The mixture was stirred at ambient temperature until the HPLC showed <1% remaining starting material (about 300 minutes). To the reaction was added ethyl acetate (30 mL) and water (30 mL). After stirring for 10 minutes the phases were separated and the aqueous layer was back extracted with ethyl acetate (30 mL). The organic layers were combined and washed with 10% brine (30 mL) and the layers were separated. The organic layer was then concentrated to dryness to give an off-white solid. The solids were transferred back to the reactor with acetonitrile (35 m L) and stirred for 20 minutes. The solids were isolated by filtration and dried in a vacuum oven at full vacuum overnight (40° C., 16 hours) to give tert-butyl-[({(3aR,4R,6aS)-2,2-dimethyl-6-[(2-{3-(trifluoromethylthio)phenyl}pyrazolo[1,5-a]pyrimidin-7-yl)amino]tetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl}methoxy)sulfonyl]carbamate (3.87 g, 88%). (LCMS: (FA2) M+1 660).
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([NH2:8])[C:3]=1[NH2:9].[C:10](C1NC=CN=1)(C1NC=CN=1)=[O:11].C(Cl)(Cl)=O>>[CH3:1][C:2]1[C:3]2[C:4](=[N:8][C:10](=[O:11])[N:9]=2)[CH:5]=[CH:6][CH:7]=1
Reactant: O=C(c1ncc[nH]1)c1ncc[nH]1
Reactant: Cc1cccc(N)c1N
Agent: O=C(Cl)Cl
Product: Cc1cccc2c1=NC(=O)N=2

Procedure:
The 5-amino-5,6-dihydro-4H-imidazo(4,5,1-ij)quinolin-2-ones of the invention may also be prepared by the route shown in Scheme 6. 3-Methyl-1,2-benzenediamine is reacted with carbonyl diimidazole or phosgene to give 4-methylbenzimidazolone (XXXVI). This is refluxed with phosphorus oxychloride to give XXXVII which is protected and reacted with N-bromosuccinimine to give compound XXXIX. This is coupled with VIIb and the resulting adduct LX is hydrolyzed to LI. Reduction with lithium aluminum hydride alcohol LXII which was treated with carbon tetrabromide/triphenylphosphine to give compound 51. Compound 51 was refluxed in acetic acid to effect conversion to compound 6.
Reaction SMILES: [CH2:1]([N:8]1[CH2:17][CH2:16][C:15]2[C:10](=[CH:11][CH:12]=[N:13][C:14]=2Br)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH:19]1[C:28]2[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=2)[CH:22]=[C:21]([C:29]2[CH:30]=[C:31]([CH:33]=[CH:34][C:35]=2[CH3:36])[NH2:32])[N:20]=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O1CCOCC1>[CH2:1]([N:8]1[CH2:17][CH2:16][C:15]2[C:14]([NH:32][C:31]3[CH:33]=[CH:34][C:35]([CH3:36])=[C:29]([C:21]4[N:20]=[CH:19][C:28]5[C:23]([CH:22]=4)=[CH:24][CH:25]=[CH:26][CH:27]=5)[CH:30]=3)=[N:13][CH:12]=[CH:11][C:10]=2[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: Brc1nccc2c1CCN(Cc1ccccc1)C2
Reactant: Cc1ccc(N)cc1-c1cc2ccccc2cn1
Agent: [Pd]
Agent: CC1(C)c2cccc(P(c3ccccc3)c3ccccc3)c2Oc2c(P(c3ccccc3)c3ccccc3)cccc21
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Solvent: C1COCCO1
Product: Cc1ccc(Nc2nccc3c2CCN(Cc2ccccc2)C3)cc1-c1cc2ccccc2cn1
Temperature: 100 °C

Procedure:
To the reaction vessel containing 2-benzyl-5-bromo-1,2,3,4-tetrahydro-2,6-naphthyridine (272 mg, 0.9 mmol), 3-(isoquinolin-3-yl)-4-methylaniline (210 mg, 0.9 mmol), Pd2(dba)3 (41 mg, 0.045 mmol), Xantphos (52 mg, 0.09 mmol) and K3PO4 (477 mg, 2.25 mmol) is added anhydrous dioxane (5 mL). The vessel is flushed with nitrogen, sealed and heated to 100° C. for 18 hours. The reaction is then cooled to ambient temperature, filtered through a celite pad to remove any salts. The filtrate is concentrated and purified by silica gel flash chromatography to afford 6-benzyl-N-(3-(isoquinolin-3-yl)-4-methylphenyl)-5,6,7,8-tetrahydro-2,6-naphthyridin-1-amine as an off-white solid. MS m/z 457.2 (M+1).
Reaction SMILES: [N+:1]([C:4]1[C:5]([S:26][C:27]#[N:28])=[N:6][C:7]([NH:10][C:11]2[CH:12]=[C:13]([NH:18][C:19](=[O:25])[O:20][C:21]([CH3:24])([CH3:23])[CH3:22])[CH:14]=[CH:15][C:16]=2[CH3:17])=[N:8][CH:9]=1)([O-])=O.CN1CCCC1=O.[Cl-].[Ca+2].[Cl-]>C(O)C>[NH2:28][C:27]1[S:26][C:5]2[N:6]=[C:7]([NH:10][C:11]3[CH:12]=[C:13]([NH:18][C:19](=[O:25])[O:20][C:21]([CH3:24])([CH3:23])[CH3:22])[CH:14]=[CH:15][C:16]=3[CH3:17])[N:8]=[CH:9][C:4]=2[N:1]=1
Reactant: Cc1ccc(NC(=O)OC(C)(C)C)cc1Nc1ncc([N+](=O)[O-])c(SC#N)n1
Agent: [Ca+2]
Agent: [Cl-]
Solvent: CN1CCCC1=O
Solvent: CCO
Product: Cc1ccc(NC(=O)OC(C)(C)C)cc1Nc1ncc2nc(N)sc2n1
Temperature: 100 °C
Reaction time: 16 h
Yield: 35 %

Procedure:
To a solution of the above-mentioned crude product of tert-butyl {3-[(5-nitro-4-thiocyanatopyrimidin-2-yl)amino]-4-methylphenyl}carbamate in ethanol (120 mL)/1-methylpyrrolidin-2-one (80 mL) were added reduced iron (6.68 g, 120 mmol) and aqueous solution (20 mL) of calcium chloride (13.3 g, 120 mmol), and the mixture was stirred at 100° C. for 16 hr. The insoluble material was filtered off, and the filtrate was concentrated under reduced pressure. To the obtained residue was added water (350 mL), and the mixture was extracted with ethyl acetate (200 mL, 2×80 mL). The combined organic layer was washed with saturated brine (50 mL), filtered through a silica gel pad, and the filtrate was concentrated under reduced pressure. The obtained residue was washed with ethyl acetate to give the title compound (5.24 g, 35%) as a gray solid.
Reaction SMILES: C([BH-](C(CC)C)C(CC)C)(CC)C.[Li+].[Si:15]([O:32][C@H:33]([CH3:53])[C@H:34]([N:44]1[CH2:49][C@H:48]([CH3:50])[O:47][C:46](=[O:51])[C:45]1=[O:52])[C:35]1[CH:40]=[C:39]([F:41])[C:38]([F:42])=[C:37]([F:43])[CH:36]=1)([C:28]([CH3:31])([CH3:30])[CH3:29])([C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.[OH-].[Na+].OO.S([O-])(O)=O.[Na+]>C(OCC)(=O)C.C1COCC1>[Si:15]([O:32][C@H:33]([CH3:53])[C@H:34]([N:44]1[CH2:49][CH:48]([CH3:50])[O:47][C@H:46]([OH:51])[C:45]1=[O:52])[C:35]1[CH:40]=[C:39]([F:41])[C:38]([F:42])=[C:37]([F:43])[CH:36]=1)([C:28]([CH3:29])([CH3:31])[CH3:30])([C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1
Reactant: C[C@H]1CN([C@H](c2cc(F)c(F)c(F)c2)[C@@H](C)O[Si](c2ccccc2)(c2ccccc2)C(C)(C)C)C(=O)C(=O)O1
Agent: CCC(C)[BH-](C(C)CC)C(C)CC
Agent: O=S([O-])O
Agent: OO
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: CC1CN([C@H](c2cc(F)c(F)c(F)c2)[C@@H](C)O[Si](c2ccccc2)(c2ccccc2)C(C)(C)C)C(=O)[C@@H](O)O1
Temperature: -20 °C
Reaction time: 0.5 h
Yield: 97.5 %

Procedure:
In nitrogen atmosphere, a THF solution (0.25 mL) of 1.06 M lithium tri-sec-butyl borohydride was dropwise added at −20° C. to a THF solution (3 mL) of (S)-4-[(1R,2R)-2-tert-butyldiphenylsilanyloxy-1-(3,4,5-trifluorophenyl)propyl]-6-methylmorpholin-2,3-dione (95 mg). The resulting reaction solution was stirred at −20° C. for 30 min. To the reaction solution, a 5 N sodium hydroxide aqueous solution (0.03 mL) and a 30% hydrogen peroxide aqueous solution (0.07 mL) were added in this order. The resulting reaction solution was stirred under ice-cooling for 1 hr, and a sodium hydrogensulfite powder (20 mg) was added thereto. The resulting reaction solution was stirred at room temperature for 30 min, and then saturated saline and ethyl acetate were added thereto. The organic layer was separated, washed with saturated saline, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (heptane:ethyl acetate=1:1) to give 93 mg of the title compound. The physical property values of this compound were as follows:
Reaction SMILES: [Br:1][C:2]1[CH:7]=[C:6]([Cl:8])[C:5]([S:9](Cl)(=[O:11])=[O:10])=[C:4]([Cl:13])[CH:3]=1.[NH2:14][C:15]1[CH:16]=[N:17][N:18]([CH3:21])[C:19]=1[CH3:20]>N1C=CC=CC=1>[Br:1][C:2]1[CH:7]=[C:6]([Cl:8])[C:5]([S:9]([NH:14][C:15]2[CH:16]=[N:17][N:18]([CH3:21])[C:19]=2[CH3:20])(=[O:11])=[O:10])=[C:4]([Cl:13])[CH:3]=1
Reactant: Cc1c(N)cnn1C
Reactant: O=S(=O)(Cl)c1c(Cl)cc(Br)cc1Cl
Solvent: c1ccncc1
Product: Cc1c(NS(=O)(=O)c2c(Cl)cc(Br)cc2Cl)cnn1C
Yield: 64.3 %

Procedure:
Prepared from 4-bromo-2,6-dichlorobenzenesulfonyl chloride (500 mg, 1.54 mmol) and 4-amino-1,5-dimethyl-1H-pyrazole (172 mg, 1.55 mmol) in pyridine (3 ml) according to the method of intermediate 1, to give the title compound as a cream solid (392 mg, 0.99 mmol, 64%). δH (D-6 DMSO, 300K) 9.91 (1H, s), 7.97 (2H, s), 3.64 (3H, s), 2.04 (3H, s). m/z (ES+, 70V) 399.9 (MH+).
Reaction SMILES: I([O-])(=O)(=O)=O.[Na+].[OH:7][C@@H:8]1[C@H:12]([OH:13])[O:11][C@H:10]([CH2:14][CH2:15][C:16]2[CH:21]=[CH:20][C:19]([C:22]([F:25])([F:24])[F:23])=[CH:18][CH:17]=2)[C@@H:9]1[CH2:26][CH2:27][N:28]1[C:36](=[O:37])[C:35]2[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=2)[C:29]1=[O:38].O1CCCC1>CO>[CH:12]([O:11][C@H:10]([CH2:14][CH2:15][C:16]1[CH:21]=[CH:20][C:19]([C:22]([F:23])([F:25])[F:24])=[CH:18][CH:17]=1)[C@@H:9]([CH:8]=[O:7])[CH2:26][CH2:27][N:28]1[C:36](=[O:37])[C:35]2[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=2)[C:29]1=[O:38])=[O:13]
Reactant: O=C1c2ccccc2C(=O)N1CC[C@@H]1[C@H](O)[C@H](O)O[C@@H]1CCc1ccc(C(F)(F)F)cc1
Agent: [Na+]
Agent: [O-][I+3]([O-])([O-])[O-]
Solvent: CO
Solvent: C1CCOC1
Product: O=CO[C@H](CCc1ccc(C(F)(F)F)cc1)[C@@H](C=O)CCN1C(=O)c2ccccc2C1=O
Reaction time: 2 h

Procedure:
A solution of sodium metaperiodate (0.313 g in 1 mL of water) was added to a solution of the compound obtained from step f above (0.22 g) in methanol:tetrahydrofuran (3 mL:1 mL) at 0° C. The reaction mixture was stirred for 2 hours at same temperature. After stirring the reaction mixture for an additional 6 hours at room temperature, the reaction mixture was evaporated on a rotary evaporator, and the residue was taken into water and extracted with ethyl acetate. The organic layer was washed with water and brine solution, and dried over anhydrous sodium sulphate. The solvent was evaporated under reduced pressure to afford the title compound (0.22 g).
Reaction SMILES: [CH3:1][C:2]1([C:7]2[N:8]=[C:9]([CH2:12][N:13]3[CH:17]=[CH:16][C:15]([NH2:18])=[N:14]3)[S:10][CH:11]=2)[O:6]CCO1.[Cl:19][C:20]1[CH:21]=[C:22]([C:26]2[O:30][CH:29]=[N:28][C:27]=2[C:31](O)=[O:32])[CH:23]=[CH:24][CH:25]=1>>[C:2]([C:7]1[N:8]=[C:9]([CH2:12][N:13]2[CH:17]=[CH:16][C:15]([NH:18][C:31]([C:27]3[N:28]=[CH:29][O:30][C:26]=3[C:22]3[CH:23]=[CH:24][CH:25]=[C:20]([Cl:19])[CH:21]=3)=[O:32])=[N:14]2)[S:10][CH:11]=1)(=[O:6])[CH3:1]
Reactant: CC1(c2csc(Cn3ccc(N)n3)n2)OCCO1
Reactant: O=C(O)c1ncoc1-c1cccc(Cl)c1
Product: CC(=O)c1csc(Cn2ccc(NC(=O)c3ncoc3-c3cccc(Cl)c3)n2)n1

Procedure:
Following general procedure B followed by C, starting from 1-[4-(2-methyl-[1,3]dioxolan-2-yl)-thiazol-2-ylmethyl]-1H-pyrazol-3-ylamine and 5-(3-chloro-phenyl)-oxazole-4-carboxylic acid. LC-MS-conditions 05: tR=0.89 min; [M+H]+=428.02.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][C:3]=1[N+:10]([O-:12])=[O:11].C(=O)([O-])[O-].[Na+].[Na+].Br[CH2:20][C:21]1[O:25][C:24]([CH3:26])=[N:23][CH:22]=1>CN(C)C=O>[CH3:9][O:8][C:5]1[CH:6]=[CH:7][C:2]([NH:1][CH2:20][C:21]2[O:25][C:24]([CH3:26])=[N:23][CH:22]=2)=[C:3]([N+:10]([O-:12])=[O:11])[CH:4]=1
Reactant: Cc1ncc(CBr)o1
Reactant: COc1ccc(N)c([N+](=O)[O-])c1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: COc1ccc(NCc2cnc(C)o2)c([N+](=O)[O-])c1
Temperature: 70 °C
Reaction time: 20 h
Yield: 57 %

Procedure:
To a solution of 33.63 parts of 1-amino-4-methoxy-2-nitrobenzene in 282 parts of N,N-dimethylformamide there were added 21.2 parts of sodium carbonate and a solution of 35.2 parts of 5-bromomethyl-2-methyloxazole in 94 parts of N,N-dimethylformamide. The whole was stirred for 20 hours at 70° C. and was then evaporated. The residue was taken up in water and the product was extracted with dichloromethane. The extract was dried, filtered and evaporated. The residue was purified by column chromatography (silica gel; CH2Cl2 /CH3OH 95:5). The eluent of the desired fraction was evaporated and the residue was crystallized from petroleum ether. The product was filtered off and dried, yielding 30 parts (57.0%) of N-(4-methoxy-2-nitrophenyl)-2-methyl-5-oxazolemethanamine (interm. 14).
Reaction SMILES: [CH:1]1([N:5]2[CH2:10][CH2:9][N:8]([C:11](=[O:24])[CH2:12][N:13]3[CH2:22][CH2:21][C:20]4[C:15](=[CH:16][CH:17]=[C:18]([OH:23])[CH:19]=4)[CH2:14]3)[CH2:7][CH2:6]2)[CH2:4][CH2:3][CH2:2]1.Br[CH:26]1[CH2:30][CH2:29][CH2:28][CH2:27]1.C([O-])([O-])=O.[K+].[K+].O>CN(C=O)C>[CH:1]1([N:5]2[CH2:6][CH2:7][N:8]([C:11](=[O:24])[CH2:12][N:13]3[CH2:22][CH2:21][C:20]4[C:15](=[CH:16][CH:17]=[C:18]([O:23][CH:26]5[CH2:30][CH2:29][CH2:28][CH2:27]5)[CH:19]=4)[CH2:14]3)[CH2:9][CH2:10]2)[CH2:4][CH2:3][CH2:2]1
Reactant: O=C(CN1CCc2cc(O)ccc2C1)N1CCN(C2CCC2)CC1
Reactant: BrC1CCCC1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: O=C(CN1CCc2cc(OC3CCCC3)ccc2C1)N1CCN(C2CCC2)CC1
Temperature: 50 °C
Reaction time: 8 h

Procedure:
To a stirred solution of 2-[2-(4-cyclobutylpiperazin-1-yl)-2-oxoethyl]-1,2,3,4-tetrahydroisoquinolin-6-ol (145 mg, 0.44 mmol) in DMF (10.0 ml) is added 1-bromo-cyclopentane (72 mg, 0.48 mmol), and K2CO3 (60 mg, 0.44 mmol). The resulting mixture is stirred at 50° C. overnight. Water (10.0 ml) is added to quench the reaction, and the mixture is extracted with DCM (10 ml×3). The combined organic phase is dried over sodium sulfate, and the solvent is removed under reduced pressure to give a residue that is purified by PTLC (EtOAc/4% TEA) to give the title compound. 1H NMR (300 MHz, CDCl3) δ 6.84-6.94 (1H, m), 6.60-6.70 (2H, m), 4.68-4.74 (1H, m), 3.60-3.74 (6H, m), 3.36 (2H, s), 2.62-2.86 (5H, m), 2.22-2.34 (4H, m), 1.56˜2.10 (14H, m); MS (+VE) m/z 398.3 (M++1).
Reaction SMILES: [OH:1][CH:2]1[CH2:6][C:5](=[O:7])[C:4]([CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH:13]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[C:14]([OH:16])=[S:15])=[CH:3]1.[C:23](=O)([O-])[O-].[K+].[K+].IC>CC(C)=O>[OH:1][CH:2]1[CH2:6][C:5](=[O:7])[C:4]([CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH:13]([C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=2)[C:14]([O:16][CH3:23])=[S:15])=[CH:3]1
Reactant: O=C1CC(O)C=C1CCCCCC(C(O)=S)c1ccccc1
Reactant: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Solvent: CI
Product: COC(=S)C(CCCCCC1=CC(O)CC1=O)c1ccccc1

Procedure:
A stirred mixture of 4.38 g. of 7-(4-hydroxycyclopent-2-en-1-on-2-yl)-2-phenylthioheptanoic acid, 1.99 g. of potassium carbonate, 1.63 ml. of iodomethane and 26 ml. of acetone is refluxed for 3.5 hours. The acetone is evaporated and the residue is partitioned between water and ether. The ether layer is washed with brine, dried and concentrated, giving the product as an oily liquid, identified by PMRδ 3.67 (3, s).
Reaction SMILES: [CH:1]([C:3]1[O:9][C:6]([CH2:7][OH:8])=[CH:5][CH:4]=1)=[O:2].C1(C)C=CC(S([CH2:19][N+:20]#[C-:21])(=O)=O)=CC=1.C(=O)([O-])[O-].[K+].[K+].CCCCCC.C(OCC)(=O)C>CO>[OH:8][CH2:7][C:6]1[O:9][C:3]([C:1]2[O:2][CH:21]=[N:20][CH:19]=2)=[CH:4][CH:5]=1
Reactant: [C-]#[N+]CS(=O)(=O)c1ccc(C)cc1
Reactant: O=Cc1ccc(CO)o1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCCCCC
Solvent: CO
Solvent: CCOC(C)=O
Product: OCc1ccc(-c2cnco2)o1
Yield: 66.2 %

Procedure:
300 mg of 5-formylfurfuryl alcohol see Japanese Laid-Open Patent Publication No. 154758/1979 was dissolved in 10 ml of methanol, and 502 mg of p-toluenesulfonylmethyl isocyanide and 329 mg of potassium carbonate were added. The mixture was heated under reflux for 1 hour. The reaction mixture was concentrated under reduced pressure, and the residue was dissolved in a mixture of water and ethyl acetate. The organic layer was separated, and dried over anhydrous magnesium sulfate. The desiccant was separated by filtration, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography Wakogel C-200, 45 g; eluting solvent: hexane/ethyl acetate=3/2→1/1] to give 260 mg (yield 66%) of the captioned compound as a pale yellow crystalline powder.
Reaction SMILES: [CH3:1][C:2]1[C:3]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[N:4][CH:5]=[C:6]([N+:8]([O-])=O)[CH:7]=1>C(O)C.[Pd]>[CH3:1][C:2]1[CH:7]=[C:6]([NH2:8])[CH:5]=[N:4][C:3]=1[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1
Reactant: Cc1cc([N+](=O)[O-])cnc1-c1ccccc1
Agent: [Pd]
Solvent: CCO
Product: Cc1cc(N)cnc1-c1ccccc1
Reaction time: 16 h
Yield: 79.6 %

Procedure:
A mixture of 3-methyl-5-nitro-2-phenylpyridine (4.43 mmol, 0.95 g) and Pd/C 10% (0.1 g) in ethanol (40 ml) was stirred for 16 hours under hydrogen atmosphere. The catalyst was filtered off and the solid thoughtfully washed with warm ethanol. The filtrate was evaporated and the crude was purified by chromatography over SiO2 eluting with DCM/methanol mixtures and affording 0.65 g (yield 80%) of the expected product.
Reaction SMILES: CC1C=CC2C(=O)C3C=CC=CC=3CCC=2C=1.BrN1C(=O)CCC1=O.CC1C=CC2C(=O)C3C=CC=CC=3C=CC=2C=1.[CH2:43]([C:45]1[CH:60]=[CH:59][C:48]2[C:49](=[O:58])[C:50]3[CH:57]=[CH:56][CH:55]=[CH:54][C:51]=3[CH2:52][CH2:53][C:47]=2[CH:46]=1)[CH3:44]>C(Cl)(Cl)(Cl)Cl>[CH2:43]([C:45]1[CH:60]=[CH:59][C:48]2[C:49](=[O:58])[C:50]3[CH:57]=[CH:56][CH:55]=[CH:54][C:51]=3[CH:52]=[CH:53][C:47]=2[CH:46]=1)[CH3:44]
Reactant: CCc1ccc2c(c1)CCc1ccccc1C2=O
Agent: Cc1ccc2c(=O)c3ccccc3ccc2c1
Agent: Cc1ccc2c(c1)CCc1ccccc1C2=O
Agent: O=C1CCC(=O)N1Br
Solvent: ClC(Cl)(Cl)Cl
Product: CCc1ccc2c(=O)c3ccccc3ccc2c1
Temperature: 80 °C

Procedure:
60.5 Gm. of 2-methyl-10,11-dihydro-5H-dibenzo[a,d] cyclohepten-5-one is refluxed in 500 ml. of carbon tetrachloride with 58.2 gm. of N-bromosuccinimide for 8 hours. The solution is cooled and filtered and the solvent removed under vacuum. The residue is dissolved in 200 ml. of dimethylformamide and 44 gm. of 1,5-diazabicyclo[3.4.0]nonene-5 is added. The mixture is heated to 80°C. for 20 minutes, then cooled and added to water. The solution is extracted with ether and the extract washed, dried and evaporated. The residue is recrystallized from acetone/hexane to afford 39.7 g., 69% of 2-methyl-5H-dibenzo[a,d]cyclohepten-5-one, m.p. 78°-80°C. Use of 2-ethyl-10,11-dihydro-5H-dibenzo [a,d]cyclohepten-5-one gives a similar yield of 2-ethyl-5H-dibenzo[a,d]cyclohepten-5-one, m.p. 62°-64°C.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[N:4][C:5](=[O:8])[NH:6][CH:7]=1.Br[CH2:10][C:11]([C:13]1[CH:18]=[CH:17][C:16]([OH:19])=[CH:15][CH:14]=1)=[O:12].Cl>C(N(CC)CC)C.C(O)C>[Cl:1][C:2]1[CH:3]=[N:4][C:5](=[O:8])[N:6]([CH2:10][C:11]([C:13]2[CH:18]=[CH:17][C:16]([OH:19])=[CH:15][CH:14]=2)=[O:12])[CH:7]=1
Reactant: O=C(CBr)c1ccc(O)cc1
Reactant: O=c1ncc(Cl)c[nH]1
Agent: Cl
Solvent: CCN(CC)CC
Solvent: CCO
Product: O=C(Cn1cc(Cl)cnc1=O)c1ccc(O)cc1
Temperature: 25 °C
Yield: 85.4 %

Procedure:
A suspension of 5-chloropyrimidin-2-one (405 mg) and 2-bromo-4'-hydroxyacetophenone (646 mg) in triethylamine (1 ml) and ethanol (20 ml) was stirred at ambient temperature, giving a clear solution. A precipitate had formed after an hour. After 231/2 hours, 2N-hydrochloric acid (5 ml) was added to the suspension and the solid was collected. This was washed with ethanol to give the title pyrimidinone (679 mg,); m.p. 260° with decomposition; λmaxEtOH 224 nm (ε 17300), 282.5 nm (ε 15660), 353 nm (ε 4900).
Reaction SMILES: [CH:1]1([C:4]2[N:5]=[CH:6][C:7]([C:15]([OH:17])=O)=[N:8][C:9]=2[O:10][CH2:11][CH:12]2[CH2:14][CH2:13]2)[CH2:3][CH2:2]1.[NH2:18][C:19]([CH3:24])([CH2:22][CH3:23])[CH2:20][OH:21]>>[OH:21][CH2:20][C:19]([NH:18][C:15]([C:7]1[CH:6]=[N:5][C:4]([CH:1]2[CH2:2][CH2:3]2)=[C:9]([O:10][CH2:11][CH:12]2[CH2:13][CH2:14]2)[N:8]=1)=[O:17])([CH3:24])[CH2:22][CH3:23]
Reactant: O=C(O)c1cnc(C2CC2)c(OCC2CC2)n1
Reactant: CCC(C)(N)CO
Product: CCC(C)(CO)NC(=O)c1cnc(C2CC2)c(OCC2CC2)n1

Procedure:
The title compound was synthesized in analogy to Example 8e, using 5-cyclopropyl-6-cyclopropylmethoxy-pyrazine-2-carboxylic acid (Example 10 g, 100 mg, 0.43 mmol) and 2-amino-2-methyl-1-butanol (CAN 10196-30-2, 64.74 mg, 0.64 mmol) as starting materials, and isolated (12 mg, 8.79%) as off white solid, LC-MS (UV peak area, ESI) 100%, 320.4 (M+H).
Reaction SMILES: [C:1]1(=O)[O:6][C:4](=[O:5])[CH2:3][CH2:2]1>C(O)CO>[C:4]([OH:6])(=[O:5])[C:1]1[CH:3]=[CH:2][CH:1]=[C:3]([C:4]([OH:6])=[O:5])[CH:2]=1
Reactant: O=C1CCC(=O)O1
Solvent: OCCO
Product: O=C(O)c1cccc(C(=O)O)c1

Procedure:
Using the procedure described for copolymer 5, 300 g of copolymer was first allowed to react with 2 ml of ethylene glycol, then with 3.66 g of succinic anhydride.
Reaction SMILES: Br[C:2]1[CH:11]=[CH:10][C:9]2[N:8]=[CH:7][C:6]3[N:12]([CH3:23])[C:13](=[O:22])[N:14]([C:15]4[C:16]([CH3:21])=[N:17][N:18]([CH3:20])[CH:19]=4)[C:5]=3[C:4]=2[CH:3]=1.[CH3:24][C:25]1[CH:26]=[C:27](B(O)O)[CH:28]=[N:29][CH:30]=1>>[CH3:20][N:18]1[CH:19]=[C:15]([N:14]2[C:5]3[C:4]4[CH:3]=[C:2]([C:27]5[CH:28]=[N:29][CH:30]=[C:25]([CH3:24])[CH:26]=5)[CH:11]=[CH:10][C:9]=4[N:8]=[CH:7][C:6]=3[N:12]([CH3:23])[C:13]2=[O:22])[C:16]([CH3:21])=[N:17]1
Reactant: Cc1nn(C)cc1-n1c(=O)n(C)c2cnc3ccc(Br)cc3c21
Reactant: Cc1cncc(B(O)O)c1
Product: Cc1cncc(-c2ccc3ncc4c(c3c2)n(-c2cn(C)nc2C)c(=O)n4C)c1

Procedure:
The title compound was synthesized in a similar manner as described for Example 1.1 using 8-bromo-1-(1,3-dimethyl-1H-pyrazol-4-yl)-3-methyl-1,3-dihydro-imidazo[4,5-c]quinolin-2-one (Intermediate A, 40 mg, 0.105 mmol) and 5-methylpyridine-3-boronic acid (Combi-Blocks, San Diego, USA, 17 mg, 0.123 mmol) to give the title compound as an off-white solid. (HPLC: tR 2.07 min (Method A); M+H=385 MS-ES; 1H-NMR (d6-DMSO, 400 MHz) 8.98 (s, 1H), 8.54-8.48 (m, 1H), 8.45-8.39 (m, 1H), 8.19-8.08 (m, 2H), 7.99-7.92 (m, 1H), 7.71-7.66 (m, 1H), 7.58-7.53 (m, 1H), 3.92 (s, 3H), 3.59 (s, 3H), 2.37 (s, 3H), 1.95 (s, 3H))