Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C[Si]([C:5]#[C:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[C:13]1([C:16]([NH2:18])=[O:17])[CH2:15][CH2:14]1)(C)C.C(O)(=O)C.CCCC[N+](CCCC)(CCCC)CCCC.[F-].C1COCC1>C(Cl)Cl.O>[C:6]([C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[C:13]1([C:16]([NH2:18])=[O:17])[CH2:15][CH2:14]1)#[CH:5]
Reactant: C[Si](C)(C)C#Cc1ccccc1C1(C(N)=O)CC1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: ClCCl
Solvent: CC(=O)O
Solvent: O
Product: C#Cc1ccccc1C1(C(N)=O)CC1
Temperature: 25 °C
Reaction time: 2 h
Yield: 99.6 %

Procedure:
A cooled (5° C. water/ice bath) solution of 1-(2-((trimethylsilyl)ethynyl)phenyl)cyclopropanecarboxamide (I12) (1.09 g, 4.23 mmol) in DCM (20 mL) containing acetic acid (0.315 mL, 5.50 mmol) was slowly treated with a 1 M solution of TBAF in THF (5.08 mL, 5.08 mmol). The resulting mixture was stirred at room temperature for 2 hours then water (30 mL) was added. The aqueous layer was extracted with DCM (2×15 mL), then the combined organic extracts were washed with water, brine, dried (MgSO4), filtered and evaporated in vacuo to give the title compound as a tan solid (0.780 g, 99%); 1H NMR (300 MHz, CDCl3) δ 7.57 (d, J=6.7 Hz, 1H), 7.31-7.45 (m, 3H), 5.46 (brs, 1H), 5.27 (brs, 1H), 3.38 (s, 1H), 1.75 (dq, J=4.0 Hz, 2H) 1.18 (dq, J=3.7 Hz, 2H). LCMS-B: rt 5.489 min; m/z 186 [M+H]+.
Reaction SMILES: [CH3:1][N:2]1[C:7]([NH:8][CH2:9][CH2:10][CH2:11]Cl)=[C:6]([CH3:13])[C:5](=[O:14])[N:4]([CH3:15])[C:3]1=[O:16].[CH3:17][O:18][C:19]1[CH:24]=[C:23]([N+:25]([O-:27])=[O:26])[CH:22]=[CH:21][C:20]=1[N:28]1[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]1.C(N(CCC)CCC)CC>COCCOCCOC>[CH3:1][N:2]1[C:7]([NH:8][CH2:9][CH2:10][CH2:11][N:31]2[CH2:32][CH2:33][N:28]([C:20]3[CH:21]=[CH:22][C:23]([N+:25]([O-:27])=[O:26])=[CH:24][C:19]=3[O:18][CH3:17])[CH2:29][CH2:30]2)=[C:6]([CH3:13])[C:5](=[O:14])[N:4]([CH3:15])[C:3]1=[O:16]
Reactant: COc1cc([N+](=O)[O-])ccc1N1CCNCC1
Reactant: Cc1c(NCCCCl)n(C)c(=O)n(C)c1=O
Agent: CCCN(CCC)CCC
Solvent: COCCOCCOC
Product: COc1cc([N+](=O)[O-])ccc1N1CCN(CCCNc2c(C)c(=O)n(C)c(=O)n2C)CC1
Yield: 79 %

Procedure:
Analogously to Example 13, 1,3,5-trimethyl-6-(3-chloropropylamino)-2,4(1H,3H)-pyrimidinedione (130 mmol) is refluxed for 14 h with 1-(2-methoxy-4-nitrophenyl)piperazine (100 mmol) and tripropylamine (75 ml) in 300 ml of diglyme. After removing the solvent in vacuo, the mixture is worked up in the customary manner, and after purification by column chromatography, the title compound is obtained in 79% yield (m.p. 131-133° C.).
Reaction SMILES: [N:1]1([CH:6]([CH3:9])[CH2:7][OH:8])[CH:5]=[CH:4][N:3]=[CH:2]1.N1(CCO[C:18]2[CH:19]=[C:20]3[C:25](=[CH:26][CH:27]=2)[C:24](=[O:28])[CH2:23][CH2:22][CH2:21]3)C=CN=C1>>[N:1]1([CH:6]([CH3:9])[CH2:7][O:8][C:18]2[CH:19]=[C:20]3[C:25](=[CH:26][CH:27]=2)[C:24](=[O:28])[CH2:23][CH2:22][CH2:21]3)[CH:5]=[CH:4][N:3]=[CH:2]1
Reactant: O=C1CCCc2cc(OCCn3ccnc3)ccc21
Reactant: CC(CO)n1ccnc1
Product: CC(COc1ccc2c(c1)CCCC2=O)n1ccnc1
Yield: 49 %

Procedure:
Following the procedure of Example 76, but using 1.79 g (14.2 mmol) of 2-(1H-1-imidazolyl)-1-propanol and 2.0 g (12.3 mmol) of 6-[2-(1H-1-imidazolyl)ethoxy]-1,2,3,4-tetrahydro-1-naphthalenone, there was obtained 1.63 g (49% yield) of the product as a white solid, mp 132-135° C. The structure was confirmed by NMR and mass spectroscopy. MS m/z 271 (M+H+).
Reaction SMILES: [O:1]=[C:2]1[CH2:11][CH2:10][C:9]2([O:12][Si](C)(C)C)[C:4]3([CH3:20])[CH:5]=[CH:6][CH:7]([CH2:19][CH:3]13)[C:8]2([CH3:18])[CH3:17].C([O-])(O)=O.[Na+]>C(O)(=O)C.O1CCCC1.O>[O:1]=[C:2]1[CH2:11][CH2:10][C:9]2([OH:12])[C:4]3([CH3:20])[CH:5]=[CH:6][CH:7]([CH2:19][CH:3]13)[C:8]2([CH3:17])[CH3:18]
Reactant: CC1(C)C2C=CC3(C)C(C2)C(=O)CCC13O[Si](C)(C)C
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O
Solvent: CC(=O)O
Solvent: C1CCOC1
Product: CC1(C)C2C=CC3(C)C(C2)C(=O)CCC13O
Yield: 94.8 %

Procedure:
A solution of 21 mg of 1,2,3,4,4a,5,6,8a-octahydro-2-oxo-4a-trimethylsilyloxy-5,5,8a-trimethyl-1,6-methanonaphthalene in 4 ml of acetic acid/tetrahydrofuran/water (3:1:1) was stirred under argon at 25° C. over 10 hours, then poured into saturated aqueous NaHCO3 solution and extracted with CH2Cl2. After chromatography (SiO2, ethyl acetate/CH2Cl2) and sublimation, there were obtained 15 mg of 1,2,3,4,4a,5,6,8a-octahydro-2-oxo-4a-hydroxy-5,5,8a-trimethyl-1,6-methanonaphthalene (m.p. 112°-115° C., 95 o/o yield).
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([O:11][CH2:12][CH3:13])=[O:10])=[CH:4][CH:3]=1.[Cl:14][C:15]1[CH:16]=[CH:17][C:18]([O:24][CH3:25])=[C:19]([CH:23]=1)[C:20](Cl)=[O:21].Cl.C(=O)(O)[O-].[Na+]>C1(C)C=CC=CC=1.O.N1C=CC=CC=1>[Cl:14][C:15]1[CH:16]=[CH:17][C:18]([O:24][CH3:25])=[C:19]([CH:23]=1)[C:20]([NH:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:8][C:9]([O:11][CH2:12][CH3:13])=[O:10])=[CH:6][CH:7]=1)=[O:21]
Reactant: CCOC(=O)Cc1ccc(N)cc1
Reactant: COc1ccc(Cl)cc1C(=O)Cl
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: c1ccncc1
Solvent: Cc1ccccc1
Solvent: O
Product: CCOC(=O)Cc1ccc(NC(=O)c2cc(Cl)ccc2OC)cc1
Yield: 70.6 %

Procedure:
8.9 g Ethyl 4-aminophenylacetate are suspended in 200 ml. toluene. After the addition of 4 ml pyridine, a solution of 10.2 g 5-chloro-2-methoxybenzoyl chloride in 10 ml toluene is added dropwise thereto and the reaction mixture heated under reflux for 2 hours. After cooling, the toluene phase is successively shaken out with dilute hydrochloric acid, aqueous sodium bicarbonate solution and water and thereafter dried and evaporated. The evaporation residue is then recrystallized twice from ethanol to give 12.2 g (70% of theory) ethyl 4-(5-chloro-2-methoxybenzamido)-phenylacetate; m.p. 104° C.
Reaction SMILES: B(O)(O)[C:2]1[CH:3]=[CH:4][C:5]([O:8][CH3:9])=[CH:6][CH:7]=1.[CH3:12][O:13][C:14](=[O:34])[CH2:15][CH:16]([C:25]1[CH:33]=[C:32]2[C:28]([CH:29]=[CH:30][NH:31]2)=[CH:27][CH:26]=1)C1C=CC=C(OC)C=1>>[CH3:12][O:13][C:14](=[O:34])[CH2:15][CH:16]([C:25]1[CH:33]=[C:32]2[C:28]([CH:29]=[CH:30][NH:31]2)=[CH:27][CH:26]=1)[C:2]1[CH:3]=[CH:4][C:5]([O:8][CH3:9])=[CH:6][CH:7]=1
Reactant: COc1ccc(B(O)O)cc1
Reactant: COC(=O)CC(c1cccc(OC)c1)c1ccc2cc[nH]c2c1
Product: COC(=O)CC(c1ccc(OC)cc1)c1ccc2cc[nH]c2c1
Yield: 66 %

Procedure:
3-(1H-Indol-6-yl)-3-(4-methoxy-phenyl)-propionic acid methyl ester XXXIV (0.51 g, 66% yield) was prepared from 4-methoxy boronic acid using the procedure described for preparation of 3-(1H-indol-6-yl)-3-(3-methoxy-phenyl)-propionic acid methyl ester XXXI (see Example 7).
Reaction SMILES: F[C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[C:4]([O:9][CH3:10])[C:3]=1[N+:11]([O-:13])=[O:12].[Br:14][C:15]1[NH:16][CH:17]=[C:18]([CH3:20])[N:19]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.C(OCC)(=O)C.ClCCl>[Br:14][C:15]1[N:16]([C:2]2[CH:7]=[C:6]([F:8])[CH:5]=[C:4]([O:9][CH3:10])[C:3]=2[N+:11]([O-:13])=[O:12])[CH:17]=[C:18]([CH3:20])[N:19]=1
Reactant: COc1cc(F)cc(F)c1[N+](=O)[O-]
Reactant: Cc1c[nH]c(Br)n1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Solvent: ClCCl
Product: COc1cc(F)cc(-n2cc(C)nc2Br)c1[N+](=O)[O-]
Temperature: 25 °C
Reaction time: 8 h
Yield: 30.5 %

Procedure:
A mixture of 1,5-difluoro-3-methoxy-2-nitrobenzene (9 g, 47.6 mmol), 2-bromo-4-methylimidazole (7.7 g, 47.6 mmol) and potassium carbonate (14.5 g, 104.7 mmol) in 240 mL DMF was stirred at room temperature overnight. The majority of solvent was removed by rotavap and the residue was diluted with ethyl acetate and washed with water. The aqueous phase was extracted with ethyl acetate and the combined organic phase was washed with water, brined, dried over magnesium sulfate. Condensation and purification using 5-10% ethyl acetate in dichloromethane as eluent provided 4.8 g (31% yield) of 2-bromo-1-(5-fluoro-3-methoxy-2-nitrophenyl)-4-methyl-1H-imidazole as a yellow solid. 1H NMR (400 MHz, DMSO) δ ppm 7.60 (dd, 1H), 7.38 (dd, 1H), 7.21 (s, 1H), 3.98 (s, 3H), 2.09 (s, 3H). EIMS 330.0 [M+H]+.
Reaction SMILES: [NH2:1][C:2]1[C:10]([Cl:11])=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[C:4]([O:12][CH3:13])[CH:3]=1.C(N1C=CN=C1)(N1C=CN=C1)=O.[N:26]12[CH2:33][C:30]([CH2:34]O)([CH2:31][CH2:32]1)[CH2:29][CH2:28][CH2:27]2.C([Li])CCC.CCCCCC>O1CCCC1>[N:26]12[CH2:33][C:30]([CH2:34][O:7][C:6](=[O:8])[C:5]3[CH:9]=[C:10]([Cl:11])[C:2]([NH2:1])=[CH:3][C:4]=3[O:12][CH3:13])([CH2:31][CH2:32]1)[CH2:29][CH2:28][CH2:27]2
Reactant: COc1cc(N)c(Cl)cc1C(=O)O
Reactant: OCC12CCCN(CC1)C2
Agent: O=C(n1ccnc1)n1ccnc1
Agent: [Li]CCCC
Solvent: CCCCCC
Solvent: C1CCOC1
Product: COc1cc(N)c(Cl)cc1C(=O)OCC12CCCN(CC1)C2
Reaction time: 1 h
Yield: 47.3 %

Procedure:
A solution of 4-amino-5-chloro-2-methoxybenzoic acid (1.62 g, 8.0 mmol) in anhydrous tetrahydrofuran (10 mL) under nitrogen was treated with 1,1'-carbonyldiimidazole (1.38 g, 8.5 mmol), stirred one hour, and degassed under a stream of nitrogen over 10 minutes. Meanwhile, a cooled (-10° C.) solution of 1-azabicyclo[3.2.1]octane-5-methanol (1.20 g, 8.5 mmol) in anhydrous tetrahydrofuran (10 mL) under nitrogen was treated (via syringe) with 2.50 N n-butyllithium/hexane (8.25 mmol), stirred for 30 minutes, concentrated in vacuo, and taken up in anhydrous tetrahydrofuran (10 mL) under nitrogen. The above degassed solution was transferred into this solution by syringe, and the mixture was stirred at room temperature for 65 hours and at 50° C. for one hour, then concentrated in vacuo. The residue was partitioned between toluene (100 mL) containing a little 2-propanol and saturated aqueous sodium carbonate (50 mL), and the organic layer was separated. The aqueous solution was extracted with toluene (2×50 mL) containing a little 2-propanol, and the combined organic solution was dried (Na2SO4) and concentrated in vacuo. The residue was filtered through alumina (eluted with 2% methanol/tetrahydrofuran, then with 35% methanol/tetrahydrofuran to collect product),and the filtrate was concentrated in vacuo and triturated from cold ether. Recrystallization from ethyl acetate/hexane afforded 1.23 g (47%) of a colorless solid; mp 131°-133° C.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][N+:5]([O-])=[C:4]([CH3:9])[C:3]=1[CH3:10].C(OC(=O)C)(=[O:13])C>>[Cl:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]([CH2:9][OH:13])[C:3]=1[CH3:10]
Reactant: CC(=O)OC(C)=O
Reactant: Cc1c(Cl)cc[n+]([O-])c1C
Product: Cc1c(Cl)ccnc1CO
Temperature: 110 °C

Procedure:
50 ml of acetic anhydride was added to 5.63 g of 4-chloro-2,3-dimethylpyridine-N-oxide (VI) and the resulting mixture was heated at 110° C. for 1 hour. The solvent was distilled off under reduced pressure and water was added thereto and the resulting mixture was extracted with ether. The resulting organic layer was washed with water and dried over anhydrous sodium sulfate and the solvent was distilled off under reduced pressure. The resulting residue was dissolved in 90% ethanol, and 2.10 g of sodium hydroxide was added thereto, and the resulting mixture was heated at 80° C. for 3 hours. The solvent was distilled off under reduced pressure, and thereafter, water was added thereto and the resulting mixture was extracted with chloroform. The resulting organic layer was washed with saturated salt water, and then dried over anhydrous sodium sulfate and the solvent was distilled off under reduced pressure. The resulting residue was purified by silica gel column chromatography (eluent; chloroform) to obtain 1.69 g of 4-chloro-2-hydroxymethyl-3-methylpyridine (VII).
Reaction SMILES: [CH3:1][C:2]1[O:6][N:5]=[C:4]([NH2:7])[CH:3]=1.[CH:8]1([CH2:12][N:13]([CH2:26][CH3:27])[C:14]2[C:23]([CH:24]=O)=[CH:22][C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[N:15]=2)[CH2:11][CH2:10][CH2:9]1.C([BH3-])#N.[Na+]>CO.C(O)(=O)C>[CH:8]1([CH2:12][N:13]([CH2:26][CH3:27])[C:14]2[C:23]([CH2:24][NH:7][C:4]3[CH:3]=[C:2]([CH3:1])[O:6][N:5]=3)=[CH:22][C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[N:15]=2)[CH2:9][CH2:10][CH2:11]1
Reactant: Cc1cc(N)no1
Reactant: CCN(CC1CCC1)c1nc2ccccc2cc1C=O
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: CC(=O)O
Solvent: CO
Product: CCN(CC1CCC1)c1nc2ccccc2cc1CNc1cc(C)on1
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 42.8 %

Procedure:
5-Methyl-isoxazol-3-ylamine (0.098 g, 1 mmol) was added to a solution of 2-(cyclobutylmethyl-ethyl-amino)-quinoline-3-carbaldehyde (0.268 g, 1 mmol) in anhydrous methanol (5 mL) and acetic acid (0.15 mL) under nitrogen. After being stirred for 15 minutes at ambient temperature, sodium cyanoborohydride (0.19 g, 3 mmol) was added slowly, and the reaction mixture was stirred overnight. Afterwards, the solvent was evaporated in vacuo, and water (30 mL) and ethyl acetate (30 mL) were added to the residue. The organic layer was separated, washed with brine, dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by chromatography on silica gel, eluting with 1-5% methanol in dichloromethane, to afford the title compound (0.150 g), yield: 43%.
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[CH:4][C:5]2[CH:9]=[CH:8][S:7][C:6]=2[CH:10]=1.[CH:11](=[O:18])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1>>[CH3:1][C:2]1[CH:3]=[CH:4][C:5]2[CH:9]=[C:8]([CH:11]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)[OH:18])[S:7][C:6]=2[CH:10]=1
Reactant: Cc1ccc2ccsc2c1
Reactant: O=Cc1ccccc1
Product: Cc1ccc2cc(C(O)c3ccccc3)sc2c1

Procedure:
Using general procedure B, 6-methyl-benzo[b]thiophene was reacted with benzaldehyde to give (6-methyl-benzo[b]thiophen-2-yl)-phenyl-methanol as an off-white solid. MS: 236.9 ([M+H—H2O]+).
Reaction SMILES: [C:1]([C:3]1[CH:8]=[CH:7][C:6]([NH:9][C:10](=[O:33])[NH:11][C:12]2[CH:17]=[CH:16][C:15]([S:18]([NH:21][CH2:22][C:23]3[CH:28]=[CH:27][C:26]([S:29](=[O:32])(=[O:31])[NH2:30])=[CH:25][CH:24]=3)(=[O:20])=[O:19])=[CH:14][CH:13]=2)=[CH:5][CH:4]=1)#[N:2].[CH2:34]([N:38]1[CH2:43][CH2:42][NH:41][CH2:40][CH2:39]1)[CH2:35][CH2:36][CH3:37]>>[CH2:34]([N:38]1[CH2:43][CH2:42][N:41]([C:1](=[NH:2])[C:3]2[CH:4]=[CH:5][C:6]([NH:9][C:10](=[O:33])[NH:11][C:12]3[CH:13]=[CH:14][C:15]([S:18]([NH:21][CH2:22][C:23]4[CH:28]=[CH:27][C:26]([S:29](=[O:31])(=[O:32])[NH2:30])=[CH:25][CH:24]=4)(=[O:20])=[O:19])=[CH:16][CH:17]=3)=[CH:7][CH:8]=2)[CH2:40][CH2:39]1)[CH2:35][CH2:36][CH3:37]
Reactant: N#Cc1ccc(NC(=O)Nc2ccc(S(=O)(=O)NCc3ccc(S(N)(=O)=O)cc3)cc2)cc1
Reactant: CCCCN1CCNCC1
Product: CCCCN1CCN(C(=N)c2ccc(NC(=O)Nc3ccc(S(=O)(=O)NCc4ccc(S(N)(=O)=O)cc4)cc3)cc2)CC1
Yield: 2.4 %

Procedure:
The title compound was prepared from 4-(3-(4-cyanophenyl)ureido)-N-(4-sulfamoylbenzyl)benzenesulfonamide following procedure C and using 3 equivalents of n-butylpiperazine as secondary amine. The product was purified by preparative HPLC.
Reaction SMILES: CC1CCCC(C)(C)C=1/C=C/C(C)=O.[CH3:15][C:16]1[C:21](=[O:22])[CH2:20][CH2:19][C:18]([CH3:24])([CH3:23])[C:17]=1/[CH:25]=[CH:26]/[C:27]([CH3:29])=[O:28]>>[O:28]=[C:27]([CH3:29])[CH:26]=[CH:25][C:17]1[C:18]([CH3:23])([CH3:24])[CH2:19][CH2:20][C:21](=[O:22])[C:16]=1[CH3:15]
Reactant: CC(=O)/C=C/C1=C(C)C(=O)CCC1(C)C
Agent: CC(=O)/C=C/C1=C(C)CCCC1(C)C
Product: CC(=O)C=CC1=C(C)C(=O)CCC1(C)C

Procedure:
To a 50-mL 2-neck reaction flask fitted with an additional funnel and a reflux condenser connected to an apparatus similar to that described by Johnson and Schneider [Org. Synth., 30, 18 (1950)] so that the mixture in the flask could be protected from atmospheric moisture, et al. throughout the course of the reaction were added a Teflon-coated spin bar and 1.0 mL of dimethyl sulfoxide (HPLC-grade). After sweeping the system briefly with a stream of nitrogen gas, the flask was heated to a temperature of approximately 100° C. (external oil bath temperature: 100-102° C.). At that point, a solution of 3.81 g (17.7 mmoles) of pyridinium chlorochromate and 1.00 mL (4.91 mmoles) of beta-ionone (both of which reactants were purchased from Aldrich Chemical Co., Milwaukee, Wis.) in 7.0 mL of HPLC-grade dimethyl sulfoxide was added dropwise to the reaction flask over a period of 30 minutes. This mixture was subsequently stirred at 100° C. for 12 hours. After cooling the mixture to room temperature, it was diluted with 50 mL of 2:2:1 (v/v/v) ether:hexane:dichloromethane, 50 g of crushed ice, and 125 mL of ice-cold 1 M aqueous sodium hydroxide. After swirling this mixture for several minutes, it was diluted with 150 mL of 15% (w/v) aqueous sodium chloride and the layers were separated. The organic layer was subsequently washed in successive order with 100 mL of 1:1 (v/v) 1 M aqueous NaOH: 15% (w/v) aqueous NaCl, two times with 50 mL portions of 1:1 (v/v) 2 M aqueous HCl: 15% (w/v) aqueous NaCl, 50 mL of 15% (w/v) aqueous NaCl, and 50 mL of saturated brine. The washed organic layer was then dried over anhydrous magnesium sulfate and subsequently filtered. Removal of the volatile organic solvents by evaporation at reduced pressure afforded 618 mg (61% yield) of the named diketone. The identity and purity of this compound were ascertained by comparison of its IR and proton NMR spectral properties with those previously reported for the same structure by E. Becher, et al., Helv. Chim. Acta, 64, 2419 (1981). For a more economical route to convert beta-ionone to the named diketone (the common name of which is 4-oxo-beta-ionone), see: Japanese patent 81,161,370 (Dec. 11, 1981), which is cited in Chem. Abstracts, 96, 199941t (1982).
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]([NH:8][C:9]2[C:10]3[N:18]=[C:17]([N:19]4[CH2:24][CH2:23][CH:22]([NH2:25])[CH2:21][CH2:20]4)[N:16]=[CH:15][C:11]=3[N:12]=[CH:13][N:14]=2)[CH:5]=[CH:6][CH:7]=1.[N:26]#[C:27]Br>>[CH3:1][C:2]1[CH:3]=[C:4]([NH:8][C:9]2[C:10]3[N:18]=[C:17]([N:19]4[CH2:20][CH2:21][CH:22]([NH:25][C:27]#[N:26])[CH2:23][CH2:24]4)[N:16]=[CH:15][C:11]=3[N:12]=[CH:13][N:14]=2)[CH:5]=[CH:6][CH:7]=1
Reactant: N#CBr
Reactant: Cc1cccc(Nc2ncnc3cnc(N4CCC(N)CC4)nc23)c1
Product: Cc1cccc(Nc2ncnc3cnc(N4CCC(NC#N)CC4)nc23)c1

Procedure:
Prepared from compound 61 of Example 1 by reaction with cyanogen bromide.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[NH:9][C:10]1[N:14]([CH3:15])[C:13]2[CH:16]=[CH:17][C:18]([C:20](O)=[O:21])=[CH:19][C:12]=2[N:11]=1.Cl.[F:24][C:25]([F:34])([F:33])[C@H:26]1[CH2:31][CH2:30][C@H:29]([NH2:32])[CH2:28][CH2:27]1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F>CN(C=O)C>[F:24][C:25]([F:33])([F:34])[C@H:26]1[CH2:27][CH2:28][C@H:29]([NH:32][C:20]([C:18]2[CH:17]=[CH:16][C:13]3[N:14]([CH3:15])[C:10]([NH:9][C:3]4[C:4]([F:8])=[CH:5][CH:6]=[CH:7][C:2]=4[F:1])=[N:11][C:12]=3[CH:19]=2)=[O:21])[CH2:30][CH2:31]1
Reactant: Cn1c(Nc2c(F)cccc2F)nc2cc(C(=O)O)ccc21
Reactant: N[C@H]1CC[C@H](C(F)(F)F)CC1
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: Cl
Agent: F[B-](F)(F)F
Solvent: CN(C)C=O
Product: Cn1c(Nc2c(F)cccc2F)nc2cc(C(=O)N[C@H]3CC[C@H](C(F)(F)F)CC3)ccc21

Procedure:
Prepared analogously to example 3c from 2-(2,6-difluoro-phenylamino)-1-methyl-1H-benzimidazole-5-carboxylic acid and trans-4-trifluoromethyl-cyclohexylamine hydrochloride with TBTU in DMF.
Reaction SMILES: Cl[C:2]([O:4][CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)=[O:3].[F:12][C:13]1[C:21]2[N:20]([CH3:22])[C:19]3[CH2:23][CH2:24][N:25]([CH2:28][C:29]4[N:30]=[CH:31][NH:32][C:33]=4[CH3:34])[C:26](=[O:27])[C:18]=3[C:17]=2[CH:16]=[CH:15][CH:14]=1.C(N(CC)CC)C.[OH-].[Na+]>ClCCl>[F:12][C:13]1[C:21]2[N:20]([CH3:22])[C:19]3[CH2:23][CH2:24][N:25]([CH2:28][C:29]4[N:30]=[CH:31][N:32]([C:2]([O:4][CH2:5][C:6]5[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=5)=[O:3])[C:33]=4[CH3:34])[C:26](=[O:27])[C:18]=3[C:17]=2[CH:16]=[CH:15][CH:14]=1
Reactant: O=C(Cl)OCc1ccccc1
Reactant: Cc1[nH]cnc1CN1CCc2c(c3cccc(F)c3n2C)C1=O
Agent: [Na+]
Agent: [OH-]
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: Cc1c(CN2CCc3c(c4cccc(F)c4n3C)C2=O)ncn1C(=O)OCc1ccccc1
Reaction time: 8 h

Procedure:
A solution of benzyl chloroformate (0.47 ml) in dichloromethane (1 ml) was added to a stirred solution of 6-fluoro-2,3,4,5-tetrahydro-5-methyl-2-[(5-methyl -1H-imidazol-4-yl)methyl]-1H-pyrido[4,3-b]indol-1-one (496 mg) and triethylamine (0.67 ml) in dry dichloromethane (50 ml) at 20° under nitrogen, and the mixture was stirred overnight. The cooled reaction mixture was then added to 2N sodium hydroxide (100 ml) and extracted with dichloromethane (2×100 ml). The combined, dried organic extracts were adsorbed onto silica and purified by FCC eluting with System A (200:8:1) to give the title compound (442 mg) as a solid. A sample was recrystallised from hot ethyl acetate, and the resultant solid was triturated with ether to give a crystalline solid, m.p. 126°-128°.
Reaction SMILES: [N+]([O-])(O)=O.[F:5][C:6]([F:21])([O:10][C:11]1[CH:12]=[C:13]([NH:17][C:18]([NH2:20])=[NH:19])[CH:14]=[CH:15][CH:16]=1)[CH:7]([F:9])[F:8].CN(C)[CH:24]=[CH:25][C:26]([C:28]1[CH:33]=[CH:32][C:31]([Cl:34])=[CH:30][CH:29]=1)=O.[OH-].[Na+]>CC(O)C>[F:5][C:6]([F:21])([O:10][C:11]1[CH:12]=[C:13]([NH:17][C:18]2[N:20]=[C:26]([C:28]3[CH:33]=[CH:32][C:31]([Cl:34])=[CH:30][CH:29]=3)[CH:25]=[CH:24][N:19]=2)[CH:14]=[CH:15][CH:16]=1)[CH:7]([F:8])[F:9]
Reactant: N=C(N)Nc1cccc(OC(F)(F)C(F)F)c1
Reactant: CN(C)C=CC(=O)c1ccc(Cl)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: O=[N+]([O-])O
Solvent: CC(C)O
Product: FC(F)C(F)(F)Oc1cccc(Nc2nccc(-c3ccc(Cl)cc3)n2)c1
Temperature: 25 °C

Procedure:
539 mg (2.15 mmol) of 3-(1,1,2,2-tetrafluoro-ethoxy)-phenyl-guanidine nitrate are added to a solution of 450 mg (2.15 mmol) of 3-dimethylamino-1-(4-chloro-phenyl)-2-propen-1-one in 5.5 ml of 2-propanol. After the addition of 94.5 mg (2.36 mmol) of sodium hydroxide, the reaction mixture is boiled under reflux for 29 h. After cooling to RT, the product is isolated by filtration and washed with 1-propanol and water. After drying at 60° under HV, N-[3-(1,1,2,2-tetrafluoro-ethoxy)-phenyl]-4-(4-chloro-phenyl)-2-pyrimidineamine is obtained; Rf =0.45 (methylene chloride:methanol =98:2), MS: 397 (M+), m.p. 133°-135°.
Reaction SMILES: [Cl:1][C:2]1[N:7]=[C:6]([Cl:8])[C:5]([Cl:9])=[C:4](Cl)[C:3]=1[Cl:11].COP(C)(=O)O>CC(C)P([O-])(=O)[O-].O.[Zn]>[Cl:8][C:6]1[C:5]([Cl:9])=[CH:4][C:3]([Cl:11])=[C:2]([Cl:1])[N:7]=1
Reactant: Clc1nc(Cl)c(Cl)c(Cl)c1Cl
Agent: CC(C)P(=O)([O-])[O-]
Agent: COP(C)(=O)O
Agent: [Zn]
Solvent: O
Product: Clc1cc(Cl)c(Cl)nc1Cl
Yield: 80.4 %

Procedure:
4.6 g (0.07 gram atom) of zinc dust is introduced into a solution, heated to 90° C., of 12.57 g (0.05 mol) of pentachloropyridine in 150 ml of dimethylmethanephosphonate, and there is then added dropwise in the course of 25 minutes, with stirring, a solution of 9.52 g (0.075 mol) of the ammonium salt of methanephosphonic acid monomethyl ester in 44 ml of water. After the addition of the ammonium salt has been completed, the reaction mixture is firstly stirred for 30 minutes, subsequently filtered hot, and the filter residue is washed with 10 ml of dimethylmethanephosphonate. The filtrate is poured into 500 ml of ice water; 12.5 ml of concentrated hydrochloric acid is then added and the mixture is stirred for 2 hours. The crystals which have precipitated are afterwards filtered off, washed with 150 ml of water and dried to yield 8.72 g (80.4% of theory) of crude 2,3,5,6-tetrachloropyridine, m.p. 88° to 89° C., which contains, according to gas-chromatographical analysis, 94.1% of 2,3,5,6-tetrachloropyridine, 2.5% of 2,3,5-trichloropyridine, 1.9% of 2,3,6-trichloropyridine and 0.17% of pentachloropyridine.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]2[N:12]([CH2:13][O:14][CH2:15][CH2:16][Si:17]([CH3:20])([CH3:19])[CH3:18])[CH:11]=[CH:10][C:5]2=[N:6][C:7]=1[C:8]#[N:9]>[Ni].N.CO>[F:1][C:2]1[CH:3]=[C:4]2[N:12]([CH2:13][O:14][CH2:15][CH2:16][Si:17]([CH3:20])([CH3:19])[CH3:18])[CH:11]=[CH:10][C:5]2=[N:6][C:7]=1[CH2:8][NH2:9]
Reactant: C[Si](C)(C)CCOCn1ccc2nc(C#N)c(F)cc21
Agent: [Ni]
Agent: N
Solvent: CO
Product: C[Si](C)(C)CCOCn1ccc2nc(CN)c(F)cc21
Reaction time: 8 h
Yield: 89.8 %

Procedure:
To a solution of 6-fluoro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[3,2-b]pyridine-5-carbonitrile (1096 mg, 3.77 mmol) in a solution of NH3/MeOH (7 N, 100 mL) was added Raney nickel (1000 mg), followed by stirring under a hydrogen atmosphere overnight. The reaction mixture was filtered and the filtrate concentrated under reduced pressure to afford (6-fluoro-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[3,2-b]pyridin-5-yl)methanamine (1000 mg, 90%). MS (ESI): m/z=296.1 [M+1]+.