Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: FC(F)(F)C(O)=O.[CH3:8][C:9]1([CH2:20][CH2:21][C:22]([O:24]C(C)(C)C)=[O:23])[O:13][C:12]2=[N:14][C:15]([N+:17]([O-:19])=[O:18])=[CH:16][N:11]2[CH2:10]1>C(Cl)Cl>[CH3:8][C:9]1([CH2:20][CH2:21][C:22]([OH:24])=[O:23])[O:13][C:12]2=[N:14][C:15]([N+:17]([O-:19])=[O:18])=[CH:16][N:11]2[CH2:10]1
Reactant: CC(C)(C)OC(=O)CCC1(C)Cn2cc([N+](=O)[O-])nc2O1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: CC1(CCC(=O)O)Cn2cc([N+](=O)[O-])nc2O1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 51.4 %

Procedure:
Trifluoroacetic acid (2 ml) was added to a solution of tert-butyl 3-(2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazol-2-yl) propionate prepared in Example 44 (0.72 g, 2.42 mmol) in methylene chloride (14 ml) followed by stirring at room temperature for 30 minutes. The reaction mixture was concentrated under reduced pressure. The residue was crystallized from ethanol-methylene chloride to afford 3-(2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazol-2-yl)propionic acid (0.30 g, 51%) as a light yellow solid.
Reaction SMILES: [O:1]1[C:5]2([CH2:10][CH2:9][CH:8]([NH:11][C:12]3[NH:16][N:15]=[CH:14][CH:13]=3)[CH2:7][CH2:6]2)[O:4][CH2:3][CH2:2]1.N12CCCN=C1CCCCC2.[C:28]([C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=1[C:36]1[CH:41]=[CH:40][C:39]([CH2:42][CH:43]([C:48](=O)[CH2:49][CH2:50][CH2:51][CH3:52])[C:44](OC)=[O:45])=[CH:38][C:37]=1[F:54])#[N:29].C(OCC)(=O)C>CCN(C1C=CC=CC=1)CC.O>[CH2:49]([C:48]1[N:16]2[N:15]=[CH:14][CH:13]=[C:12]2[N:11]([CH:8]2[CH2:7][CH2:6][C:5]3([O:4][CH2:3][CH2:2][O:1]3)[CH2:10][CH2:9]2)[C:44](=[O:45])[C:43]=1[CH2:42][C:39]1[CH:40]=[CH:41][C:36]([C:31]2[C:30]([C:28]#[N:29])=[CH:35][CH:34]=[CH:33][CH:32]=2)=[C:37]([F:54])[CH:38]=1)[CH2:50][CH2:51][CH3:52]
Reactant: c1cc(NC2CCC3(CC2)OCCO3)[nH]n1
Reactant: CCCCC(=O)C(Cc1ccc(-c2ccccc2C#N)c(F)c1)C(=O)OC
Solvent: C1CCC2=NCCCN2CC1
Solvent: O
Solvent: CCOC(C)=O
Product: CCCCc1c(Cc2ccc(-c3ccccc3C#N)c(F)c2)c(=O)n(C2CCC3(CC2)OCCO3)c2ccnn12
Yield: 88.2 %

Procedure:
A solution of N-(1,4-dioxaspiro[4.5]dec-8-yl)-1H-pyrazol-5-amine (2.2 g), 1,8-diazabicyclo[5.4.0]undec-7-ene (0.30 mL) and methyl 2-[(2′-cyano-2-fluorobiphenyl-4-yl)methyl]-3-oxoheptanoate (6.4 g) in diethylaniline (10 mL) was stirred at 180° C. for 2 hr. The mixture was allowed to cool, ethyl acetate and water were added, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine, dried over anhydrous magnesium sulfate, and concentrated. The residue was purified by silica gel column chromatography to give the title compound as a pale-yellow amorphous solid (4.7 g, 87%).
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([Cl:8])=[CH:4][C:3]=1[F:9].[Li+].CC([N-]C(C)C)C.Br[CH2:19][O:20][CH3:21]>C1COCC1>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([Cl:8])=[C:4]([CH2:19][O:20][CH3:21])[C:3]=1[F:9]
Reactant: Fc1cc(Cl)ccc1Br
Reactant: COCBr
Agent: CC(C)[N-]C(C)C
Agent: [Li+]
Solvent: C1CCOC1
Product: COCc1c(Cl)ccc(Br)c1F
Temperature: -20 °C
Yield: 71 %

Procedure:
A solution of 1-bromo-4-chloro-2-fluorobenzene (20.4 g, 0.100 mol) in THF (50 mL) was slowly added to LDA (0.125 mol) in THF (600 mL) at −50° C. After addition the solution was warmed to −20° C. and then cooled to −50° C. a solution of bromomethoxymethane (25 g, 0.200 mol) in THF (25 mL) was slowly added and the reaction mixture was warmed to ambient temperature. The reaction was quenched with water (400 mL) and extracted with diethyl ether (2×150 mL). The combined organic phases were dried (sodium sulfate) and concentrated. The residual oil was distilled (70°-75° C./0.5 mm) to give 1-bromo-4-chloro-2-fluoro-3-methoxymethylbenzene (18.0 g, 0.071 mol): 1H NMR (CDCl3): δ 7.50 (m, 1H), 7.15 (dd, 1H), 4.65 (s, 1H), 3.40 (s, 1H).
Reaction SMILES: [Cl:1][CH2:2][CH2:3][CH2:4][N:5]1[CH2:10][CH2:9][CH:8]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[CH2:7][CH2:6]1.BrCCCCl.C1(C2CCNCC=2)C=CC=CC=1.C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[Cl:1][CH2:2][CH2:3][CH2:4][N:5]1[CH2:6][CH:7]=[C:8]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[CH2:9][CH2:10]1
Reactant: ClCCCN1CCC(c2ccccc2)CC1
Agent: C1=C(c2ccccc2)CCNC1
Agent: ClCCCBr
Agent: O=C([O-])[O-]
Solvent: CC#N
Product: ClCCCN1CC=C(c2ccccc2)CC1

Procedure:
1-(3-Chloropropyl)-4-phenyl-1,2,4,6-tetrahydropyridine can be prepared as follows: a solution of 1-bromo-3-chloropropane (6 cc) and 4-phenyl-1,2,3,6-tetrahydropyridine (5.1 g) in acetonitrile (60 cc) is stirred at 25° C. for 20 hours with potassium carbonate (97 g). The mixture is filtered and then concentrated to dryness under reduced pressure (2.7 kPa). The residue is chromatographed on a column of silica gel (0.2-0.063-mm particle size, 4-cm diameter, 40-cm height) and eluted with a mixture of cyclohexane and ethyl acetate (50--50 by volume), 250-cc fractions being collected. Fractions 7 to 13 are combined and concentrated to dryness under reduced pressure (2.7 kPa) to give 1-(3-chloropropyl)-4-phenyl-1,2,3,6-tetrahydropyridine (5 g) in the form of a yellow oil.
Reaction SMILES: C([O:8][C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][CH:18]=1)[N:15]=[CH:14][CH:13]=[C:12]2Cl)C1C=CC=CC=1.N1C2C(=CC=CC=2)C=NC1=O.C1(O)C=CC=CC=1.NC1C=CC=CC=1>ClC1C=CC=CC=1Cl>[OH:8][C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][CH:18]=1)[N:15]=[CH:14][CH:13]=[CH:12]2
Reactant: Clc1ccnc2ccc(OCc3ccccc3)cc12
Agent: O=c1ncc2ccccc2[nH]1
Solvent: Oc1ccccc1
Solvent: Clc1ccccc1Cl
Solvent: Nc1ccccc1
Product: Oc1ccc2ncccc2c1

Procedure:
A 6-benzyloxy-4-chloroquinoline derivative or a corresponding quinazolone derivative is reacted with a phenol derivative or a corresponding aniline derivative in a suitable solvent, for example, o-dichlorobenzene, or in the absence of a solvent, for example, at 120 to 180° C. (step (i) above). Next, a 6-hydroxyquinoline derivative may be produced by reacting the resultant compound with a suitable acid, for example, methanesulfonic acid/trifluoroacetic acid (step (ii) above). The contemplated compound may be produced by reacting the 6-hydroxyquinoline derivative with an alkylating agent, for example, 1-bromo-2-chloroethane (step (iii) above).
Reaction SMILES: [CH2:1]([O:8][C:9](=[O:19])[CH2:10][C:11]1([C:16]([OH:18])=O)[CH2:15][CH2:14][CH2:13][CH2:12]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:20][C@@H:21]([C:35]1[N:39]([CH2:40][CH2:41][C:42]#[N:43])[N:38]=[N:37][N:36]=1)[CH2:22][C:23]1[CH:28]=[CH:27][C:26]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)=[CH:25][CH:24]=1.CCN=C=NCCCN(C)C.Cl.C1C=NC2N(O)N=NC=2C=1.C(N(CC)CC)C>CN(C=O)C.CCOC(C)=O>[C:26]1([C:29]2[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=2)[CH:25]=[CH:24][C:23]([CH2:22][C@@H:21]([NH:20][C:16]([C:11]2([CH2:10][C:9]([O:8][CH2:1][C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=3)=[O:19])[CH2:12][CH2:13][CH2:14][CH2:15]2)=[O:18])[C:35]2[N:39]([CH2:40][CH2:41][C:42]#[N:43])[N:38]=[N:37][N:36]=2)=[CH:28][CH:27]=1
Reactant: O=C(CC1(C(=O)O)CCCC1)OCc1ccccc1
Reactant: N#CCCn1nnnc1[C@H](N)Cc1ccc(-c2ccccc2)cc1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2cccnc21
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Solvent: CCN(CC)CC
Product: N#CCCn1nnnc1[C@@H](Cc1ccc(-c2ccccc2)cc1)NC(=O)C1(CC(=O)OCc2ccccc2)CCCC1
Reaction time: 2 h
Yield: 44.1 %

Procedure:
To a solution of 1-(2-(benzyloxy)-2-oxoethyl)cyclopentanecarboxylic acid (49.4 mg, 0.188 mmol) and (R)-3-(5-(1-amino-2-(biphenyl-4-yl)ethyl)-1H-tetrazol-1-yl)propanenitrile (50 mg, 0.157 mmol) in DMF (1.5 mL) were added EDC.HCl (36 mg, 0.188 mmol), HOAt (26 mg, 0.188 mmol) and triethylamine (0.033 mL, 0.236 mmol). After being stirred for 2 hours, the reaction mixture was diluted with EtOAc. The mixture was washed with H2O2O and brine, dried over Na2SO4 and concentrated. The residue was purified by silica gel flash column chromatography (eluent; EtOAc/heptane) to give (R)-benzyl 2-(1-(2-(biphenyl-4-yl)-1-(1-(2-cyanoethyl)-1H-tetrazol-5-yl)ethylcarbamoyl)cyclopentyl)acetate (39 mg). LCMS (condition A) δ 563 (M+1); retention time=1.85 min.
Reaction SMILES: [CH3:1][C:2]1[C:8]([N+:9]([O-:11])=[O:10])=[CH:7][CH:6]=[CH:5][C:3]=1[NH2:4].O.[As+3]=O.S(=O)(=O)(O)O.[OH-].[NH4+].O[CH2:23][CH:24]([CH2:26]O)O>O.C(OCC)(=O)C>[CH3:1][C:2]1[C:8]([N+:9]([O-:11])=[O:10])=[CH:7][CH:6]=[C:5]2[C:3]=1[N:4]=[CH:26][CH:24]=[CH:23]2
Reactant: OCC(O)CO
Reactant: Cc1c(N)cccc1[N+](=O)[O-]
Agent: O=S(=O)(O)O
Agent: O=[As+3]
Agent: [NH4+]
Solvent: O
Solvent: CCOC(C)=O
Product: Cc1c([N+](=O)[O-])ccc2cccnc12
Temperature: 150 °C
Reaction time: 4 h

Procedure:
To a suspension of 2 g of 2-methyl-3-nitroaniline and 1.02 g of arsenic(v) oxide hydrate are added 2.88 mL of glycerin followed by 1.09 mL of concentrated sulfuric acid. The resulting black slurry is stirred at about 150° C. for 4 hours. The black oil is cooled to room temperature, diluted with water and poured into a mixture of 25% aqueous ammonium hydroxide and ethyl acetate. The organic layer is washed with water followed by brine. The aqueous layers are extracted with ethyl acetate; the combined organic layers are dried over magnesium sulfate, filtered and rotary evaporated. The residue is purified by flash column chromatography on silica gel, eluting with 50% ethyl acetate/hexanes followed by recrystallization from hexanes/methylene chloride to provide 1.45 g of 8-methyl-7-nitroquinoline as a pale brown solid.
Reaction SMILES: [C:1]([NH:4][C:5]1[NH:6][C:7]([CH3:16])=[C:8]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[N:9]=1)(=[O:3])[CH3:2].[N+:17]([O-])([O-:19])=[O:18].[NH4+]>S(=O)(=O)(O)O>[C:1]([NH:4][C:5]1[NH:6][C:7]([CH3:16])=[C:8]([C:10]2[CH:15]=[CH:14][C:13]([N+:17]([O-:19])=[O:18])=[CH:12][CH:11]=2)[N:9]=1)(=[O:3])[CH3:2]
Reactant: CC(=O)Nc1nc(-c2ccccc2)c(C)[nH]1
Reactant: O=[N+]([O-])[O-]
Agent: O=S(=O)(O)O
Agent: [NH4+]
Product: CC(=O)Nc1nc(-c2ccc([N+](=O)[O-])cc2)c(C)[nH]1

Procedure:
Prepared analogously to Example D by reacting 2-acetylamino-5-methyl-4-phenyl-imidazole with ammonium nitrate in concentrated sulphuric acid.
Reaction SMILES: Cl[C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[N:5]=[C:4]([C:12]([O:14][CH3:15])=[O:13])[CH:3]=1.[N-:16]=[N+]=[N-].[Na+].O.[BH4-].[Na+]>CN(C=O)C.CO>[NH2:16][C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[N:5]=[C:4]([C:12]([O:14][CH3:15])=[O:13])[CH:3]=1
Reactant: [N-]=[N+]=[N-]
Reactant: COC(=O)c1cc(Cl)cc(C(F)(F)F)n1
Agent: [BH4-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Solvent: CO
Product: COC(=O)c1cc(N)cc(C(F)(F)F)n1
Temperature: 70 °C
Reaction time: 0.5 h

Procedure:
To a solution of methyl 4-chloro-6-trifluoromethylpyridine-2-carboxylate (2.44 g, 10.2 mmol) in aqueous DMF was added NaN3 (0.7 g, 10.8 mmol). The resulting mixture was heated at 70° C. for 18 hr, added to H2O and extracted (3×) with Et2O. The organic layer was concentrated to yield a white solid that was dissolved in 10 mL of MeOH. Excess NaBH4 was added and the reaction mixture stirred at RT for 0.5 hr. This material was added to H2O, extracted (3×) with Et2O. The extract was dried over MgSO4 and concentrated. The resulting residue was purified via flash column chromatography to give 0.95 of product as a white solid; mp 114° C.
Reaction SMILES: [F:1][C:2]([F:38])([C:25]1[CH:30]=[CH:29][C:28]([CH:31]([CH3:37])[C:32]([O:34]CC)=[O:33])=[CH:27][CH:26]=1)[C:3]([F:24])([F:23])[C:4]([F:22])([F:21])[C:5]([F:20])([F:19])[C:6]([F:18])([F:17])[C:7]([F:16])([F:15])[C:8]([F:14])([F:13])[C:9]([F:12])([F:11])[F:10].Cl>C(O)C.[OH-].[Na+]>[F:1][C:2]([F:38])([C:25]1[CH:26]=[CH:27][C:28]([CH:31]([CH3:37])[C:32]([OH:34])=[O:33])=[CH:29][CH:30]=1)[C:3]([F:23])([F:24])[C:4]([F:21])([F:22])[C:5]([F:19])([F:20])[C:6]([F:17])([F:18])[C:7]([F:16])([F:15])[C:8]([F:14])([F:13])[C:9]([F:12])([F:11])[F:10]
Reactant: CCOC(=O)C(C)c1ccc(C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F)cc1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: CC(C(=O)O)c1ccc(C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F)cc1
Temperature: 25 °C
Yield: 97.6 %

Procedure:
Ethyl 2-(4-[perfluorooctyl]phenyl)propionate (68 mg, 0.11 mmol) was dissolved in 5 mL of ethanol and 5 mL of 1N NaOH. The solution was heated to reflux for 1 hour, cooled to room temperature, poured into 30 mL of 1N HCl and extracted with three 10-mL portions of dichloromethane. Combination, drying (MgSO4), and concentration of the organic layers gave a residue which wa purified by PTLC (one 2 mm silica gel plate eluted with 15% methanol-85% dichloromethane) to give 61 mg (94% yield) of 2-(4-[perfluorooctyl]phenyl)propionic acid as a brown oil. The oil was recrystallized from dichloromethane to give brown crystals.
Reaction SMILES: [Cl:1][C:2]1[C:7]([N+:8]([O-])=O)=[CH:6][CH:5]=[C:4]([Cl:11])[C:3]=1[CH3:12].[OH-].[Na+]>Cl.C(O)C>[Cl:1][C:2]1[C:3]([CH3:12])=[C:4]([Cl:11])[CH:5]=[CH:6][C:7]=1[NH2:8]
Reactant: Cc1c(Cl)ccc([N+](=O)[O-])c1Cl
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: Cc1c(Cl)ccc(N)c1Cl
Temperature: 25 °C
Reaction time: 16 h
Yield: 78.3 %

Procedure:
A stirred solution of 50.0 g (0.243 mole) of 2,6-dichloro-3-nitrotoluene and 225 g (1.0 mole) of stannous chloride in 250 ml of concentrated hydrochloric acid and 125 ml of ethanol was heated under reflux for 1 hour. The reaction mixture was allowed to cool to ambient temperature and was stirred for 16 hours, made basic with sodium hydroxide, and concentrated under reduced pressure. The residue was slurried with water and the insolubles were collected by filtration and allowed to air dry. The solid was digested with 500 ml of chloroform and 100 ml of ethanol. The mixture was filtered and the filtrate concentrated under reduced pressure to give 33.5 g of 2,4-dichloro-3-methylaniline, m.p. 56°-57.5° C. The nmr spectrum was consistent with the proposed structure.
Reaction SMILES: C(NC(C)C)(C)C.C([Li])CCC.[CH3:13][C:14]1[C:22]2[C:21](=[O:23])[CH2:20][CH2:19][CH2:18][C:17]=2[NH:16][N:15]=1.[CH:24](OCC)=[O:25]>O1CCCC1.CCCCCC>[OH:25][CH:24]=[C:20]1[CH2:19][CH2:18][C:17]2[NH:16][N:15]=[C:14]([CH3:13])[C:22]=2[C:21]1=[O:23]
Reactant: Cc1n[nH]c2c1C(=O)CCC2
Reactant: CCOC=O
Agent: [Li]CCCC
Solvent: CCCCCC
Solvent: CC(C)NC(C)C
Solvent: C1CCOC1
Product: Cc1n[nH]c2c1C(=O)C(=CO)CC2
Temperature: -78 °C
Reaction time: 0.5 h

Procedure:
To an ice-cold solution of 13.9 ml of diisopropylamine in 50 ml of anhydrous tetrahydrofuran there was added, by syringe, 38 ml of 2.6 N butyllithium in hexane. The mixture was cooled to -78° C. and a solution of 4.5 grams of 1,5,6,7-tetrahydro-3-methyl-4H-indazol-4-one was added dropwise. The mixture was stirred at -78° C. for 30 minutes and a solution of 10 ml of ethyl formate in 30 ml of anhydrous tetrahydrofuran was added dropwise. When the addition was complete, the reaction was allowed to warm to 0° C. and it was quenched by the dropwise addition of water (200 ml). After the mixture was stirred vigorously for a few minutes, the two layers which formed were separated. The aqueous layer was washed with ethyl ether and then acidified to a pH of about 4 with 5 N hydrochloric acid. The slurry which formed was extracted several times with dichloromethane and the combined extracts were dried and concentrated under reduced pressure to give 1,5,6,7-tetrahydro-5-hydroxymethylene-3-methyl-4H-indazol-4-one as a clammy yellow semi-solid.
Reaction SMILES: [N:1]1([C:7]2[CH:20]=[CH:19][CH:18]=[CH:17][C:8]=2[CH:9]([NH2:16])[CH2:10][CH:11]2[CH2:15][CH2:14][CH2:13][O:12]2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[CH2:21]([O:23][C:24]1[CH:25]=[C:26]([CH2:35][C:36](O)=[O:37])[CH:27]=[CH:28][C:29]=1[C:30]([O:32][CH2:33][CH3:34])=[O:31])[CH3:22]>>[CH2:21]([O:23][C:24]1[CH:25]=[C:26]([CH2:35][C:36]([NH:16][CH:9]([CH2:10][CH:11]2[CH2:15][CH2:14][CH2:13][O:12]2)[C:8]2[CH:17]=[CH:18][CH:19]=[CH:20][C:7]=2[N:1]2[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]2)=[O:37])[CH:27]=[CH:28][C:29]=1[C:30]([O:32][CH2:33][CH3:34])=[O:31])[CH3:22]
Reactant: NC(CC1CCCO1)c1ccccc1N1CCCCC1
Reactant: CCOC(=O)c1ccc(CC(=O)O)cc1OCC
Product: CCOC(=O)c1ccc(CC(=O)NC(CC2CCCO2)c2ccccc2N2CCCCC2)cc1OCC

Procedure:
Prepared analogously to Example 47 from 2-piperidino-α-(tetrahydrofuran-2-yl-methyl)-benzylamine and 3-ethoxy-4-ethoxycarbonyl-phenylacetic acid.
Reaction SMILES: [CH3:1][N:2]1[C:6]2=[N:7][CH:8]=[CH:9][CH:10]=[C:5]2[CH:4]=[CH:3]1.C1COCC1.C([Li])CCC.C(O[B:25]1[O:29][C:28]([CH3:31])([CH3:30])[C:27]([CH3:33])([CH3:32])[O:26]1)(C)C>C(Cl)Cl>[CH3:1][N:2]1[C:6]2=[N:7][CH:8]=[CH:9][CH:10]=[C:5]2[CH:4]=[C:3]1[B:25]1[O:29][C:28]([CH3:31])([CH3:30])[C:27]([CH3:33])([CH3:32])[O:26]1
Reactant: Cn1ccc2cccnc21
Reactant: CC(C)OB1OC(C)(C)C(C)(C)O1
Agent: [Li]CCCC
Solvent: ClCCl
Solvent: C1CCOC1
Product: Cn1c(B2OC(C)(C)C(C)(C)O2)cc2cccnc21
Temperature: 25 °C
Reaction time: 1 h
Yield: 11 %

Procedure:
To a −78° C. solution of 1-methyl-1H-pyrrolo[2,3-b]pyridine (example Rupp-28) (1.17 g, 8.85 mmol) and THF (12 mL) is added 1.6M n-Bu—Li (6.6 mL, 10.62 mmol). The solution is heated to a reflux for 1 hour, cooled to ambient temperature, and 2-isopropoxy-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane (3.60 mL, 17.70 mmol) is added. After 1 hour, the solution is diluted with CH2Cl2 (100 mL), washed with water (2×100 mL), brine (75 mL), dried over MgSO4, filtered and concentrated. The residue is purified by ISCO (5%-15% EtOAc gradient) to furnish the title compound (0.25 g, 0.97 mmol, 11%). 1H NMR (CDCl3), δ 1.38 (s, 12H), 4.07 (s, 3H), 7.02 (dd, J=7.9, 4.7 Hz, 1H), 7.07 (s, 1H), 7.92 (d, J=7.9, 1.8 Hz, 1H), 8.39 (d, J=4.7, 1.8 Hz, 1H) ppm. LC/MS (m/z): calcd. for C14H19BN2O2 (M+H)+: 259.2. found: 258.7.
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=O.[CH:11]1([CH2:14][C:15]([CH3:28])([C:18]2[CH:19]=[N:20][C:21]([C:24]([F:27])([F:26])[F:25])=[N:22][CH:23]=2)[CH2:16][NH2:17])[CH2:13][CH2:12]1>>[Cl:1][C:2]1[CH:10]=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([NH:17][CH2:16][C:15]([CH3:28])([C:18]1[CH:19]=[N:20][C:21]([C:24]([F:27])([F:26])[F:25])=[N:22][CH:23]=1)[CH2:14][CH:11]1[CH2:13][CH2:12]1)=[O:6]
Reactant: CC(CN)(CC1CC1)c1cnc(C(F)(F)F)nc1
Reactant: O=C(O)c1ccccc1Cl
Product: CC(CNC(=O)c1ccccc1Cl)(CC1CC1)c1cnc(C(F)(F)F)nc1

Procedure:
From 2-chlorobenzoic acid and 3-cyclopropyl-2-methyl-2-(2-(trifluoromethyl)pyrimidin-5-yl)propan-1-amine. LCMS (MH+): m/z=398.1, tR (minutes, Method F)=2.62
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[F:12])[NH:8][CH2:7][CH2:6][CH2:5]2.[Cl:13][C:14]1[CH:38]=[CH:37][C:36]([Cl:39])=[CH:35][C:15]=1[O:16][C:17]1[CH:22]=[CH:21][N:20]=[CH:19][C:18]=1[C:23](N1C2C(=CC=CC=2)CCC1)=[O:24]>>[Cl:13][C:14]1[CH:38]=[CH:37][C:36]([Cl:39])=[CH:35][C:15]=1[O:16][C:17]1[CH:22]=[CH:21][N:20]=[CH:19][C:18]=1[C:23]([N:8]1[C:9]2[C:4](=[CH:3][C:2]([F:1])=[C:11]([F:12])[CH:10]=2)[CH2:5][CH2:6][CH2:7]1)=[O:24]
Reactant: O=C(c1cnccc1Oc1cc(Cl)ccc1Cl)N1CCCc2ccccc21
Reactant: Fc1cc2c(cc1F)NCCC2
Product: O=C(c1cnccc1Oc1cc(Cl)ccc1Cl)N1CCCc2cc(F)c(F)cc21

Procedure:
The title compound was prepared in analogy to Example 1, from 6,7-difluoro-1,2,3,4-tetrahydro-quinoline (commercially available; CAS RN 953717-64-1) and 4-(2,5-dichloro-phenoxy)-nicotinic acid (Example 1, intermediate). Light brown gum (28%). MS (ESI): m/z=435.04 [M+H]+.
Reaction SMILES: Cl.[N+:2]([C:5]1[CH:11]=[CH:10][CH:9]=[CH:8][C:6]=1[NH2:7])([O-:4])=[O:3].[CH3:12][C:13]([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=[CH2:14].[OH-].[Na+]>[Cl-].[Zn+2].[Cl-].CCOCC.O>[C:13]([C:10]1[CH:9]=[CH:8][C:6]([NH2:7])=[C:5]([N+:2]([O-:4])=[O:3])[CH:11]=1)([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)([CH3:14])[CH3:12]
Reactant: C=C(C)c1ccccc1
Reactant: Nc1ccccc1[N+](=O)[O-]
Agent: Cl
Agent: [Cl-]
Agent: [Na+]
Solvent: O
Solvent: CCOCC
Product: CC(C)(c1ccccc1)c1ccc(N)c([N+](=O)[O-])c1

Procedure:
To 510 parts of 36% w/w hydrochloric acid containing 170 parts of anhydrous zinc chloride, are added 690 parts of o-nitroaniline. This mixture is heated to reflux temperature and, over the next hour, 708 parts of α-methylstyrene are added with stirring. On completing the addition, the reaction mixture is maintained at reflux for a further one and a half hours before being poured, whilst still hot, into a solution of 600 g sodium hydroxide in 1400 parts of water. The mixture is stirred until cool and then 1500 parts of ether are added and the resulting two phases are passed through a fibre filter to remove a small quantity of suspended solids. The filtrate is transferred to a separator and the lower aqueous phase is run off and discarded. The organic phase is washed with 2×500 parts of water, dried over magnesium sulphate, treated with decolouring charcoal and filtered. The filtrate is concentrated on a steam-bath until the residue weighed approximately 2000 parts. It is diluted with 2000 parts of 40°-60° C. petroleum-ether and set aside to crystallise overnight. The product following filtration is suspended in 1500 parts of 40°-60° petroleum-ether, stirred for 1 hour, and filtered to yield 4-cumyl-2-nitroaniline as an orange crystalline solid with a m.p. 92°-3° C. and a purity of 100% by G.L.C. analysis.
Reaction SMILES: [NH2:1][C:2]1[C:7]([N+:8]([O-:10])=[O:9])=[C:6]([N:11]2[CH2:16][CH2:15][N:14]([CH2:17][C:18](NC3SC=CN=3)=O)[CH2:13][CH2:12]2)[C:5](Br)=[CH:4][N:3]=1.[Cl:27]C1C(Cl)=CN=C(N)C=1[N+]([O-])=O.CCN(C(C)C)C(C)C.C(N1CCNCC1)C>CC(O)C>[Cl:27][C:5]1[C:6]([N:11]2[CH2:16][CH2:15][N:14]([CH2:17][CH3:18])[CH2:13][CH2:12]2)=[C:7]([N+:8]([O-:10])=[O:9])[C:2]([NH2:1])=[N:3][CH:4]=1
Reactant: Nc1ncc(Br)c(N2CCN(CC(=O)Nc3nccs3)CC2)c1[N+](=O)[O-]
Reactant: Nc1ncc(Cl)c(Cl)c1[N+](=O)[O-]
Agent: CCN1CCNCC1
Solvent: CC(C)O
Solvent: CCN(C(C)C)C(C)C
Product: CCN1CCN(c2c(Cl)cnc(N)c2[N+](=O)[O-])CC1
Yield: 31 %

Procedure:
This was prepared using the same procedure as for 2-(4-(2-amino-5-bromo-3-nitropyridin-4-yl)piperazin-1-yl)-N-(thiazol-2-yl)acetamide, but here using 4,5-dichloro-3-nitropyridin-2-amine (75 mg, 0.36 mmol), iPrOH (2 mL), DIPEA (3.5 eq, 1.26 mmol, 0.22 mL) and 1-ethylpiperazine (1.2 eq, 0.43 mmol, 0.05 mL). Concentration in vacuo and purification by preparative tlc (CH2Cl2-MeOH, 95:5) gave the product (32 mg, 31%) as a yellow solid;
Reaction SMILES: [OH:1][C:2]1[CH:9]=[CH:8][CH:7]=[CH:6][C:3]=1[CH:4]=O.C([NH:29][CH2:30][CH2:31][N:32]1[C:36](=[O:37])[CH2:35][S:34][C:33]1=[O:38])(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.N1CCCCC1.NCCN1C(=O)/C(=C/C2C=CC=CC=2)/SC1=O>>[NH2:29][CH2:30][CH2:31][N:32]1[C:36](=[O:37])/[C:35](=[CH:4]/[C:3]2[CH:6]=[CH:7][CH:8]=[CH:9][C:2]=2[OH:1])/[S:34][C:33]1=[O:38]
Reactant: O=Cc1ccccc1O
Reactant: O=C1CSC(=O)N1CCNC(c1ccccc1)(c1ccccc1)c1ccccc1
Agent: NCCN1C(=O)S/C(=C\c2ccccc2)C1=O
Solvent: C1CCNCC1
Product: NCCN1C(=O)S/C(=C\c2ccccc2O)C1=O

Procedure:
The title compound 30i was prepared from 2-hydroxybenzaldehyde (76 mg, 0.62 mmol), compound 29 (250 mg, 0.62 mmol) and piperidine (20.0 μL, 0.19 mmol) in a manner similar to that described for 30a in 50.0% (117 mg) yield as a yellow solid.
Reaction SMILES: [I:1][C:2]1[C:3]2[C:4]3[C:8](=[CH:9][CH:10]=1)[NH:7][C:6](=O)[C:5]=3[CH:12]=[CH:13][CH:14]=2.Cl.[CH2:16]([NH2:23])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>C[Si](C)(C)N[Si](C)(C)C>[CH2:16]([N:23]=[C:6]1[C:5]2[CH:12]=[CH:13][CH:14]=[C:3]3[C:4]=2[C:8](=[CH:9][CH:10]=[C:2]3[I:1])[NH:7]1)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1
Reactant: O=C1Nc2ccc(I)c3cccc1c23
Reactant: NCc1ccccc1
Agent: C[Si](C)(C)N[Si](C)(C)C
Agent: Cc1ccc(S(=O)(=O)O)cc1
Agent: Cl
Solvent: O
Product: Ic1ccc2c3c(cccc13)C(=NCc1ccccc1)N2
Yield: 65.8 %

Procedure:
The product of the example was also prepared using the procedures of Method B as described in Example 21. 6-Iodo-1H-benzo[cd]indol-2-one (0.2 g, 0.68 mmol), benzylamine hydrochloride (0.195 g, 1.36 mmol) and p-toluenesulfonic acid monohydrate (0.01 g, 0.052 mmol) were stirred in hexamethyldisilazane (0.45 ml) for 3 h at 130°. Workup as before provided the crude product. Crystallization from EtOAc-ether gave 0.172 g (66%) of a dark yellow solid: mp 160-163°; NMR (CDCl3) δ 4.90 (s, 2H), 6.99 (d, J=7.3, 1H), 7.36 (m, 3H), 7.46 (m, 2H), 7.62 (m, 1H), 7.78 (m, 1H), 7.87 (m, 2H). MS (EI) m/z 385 (M+H calcd. for C18H14IN2 385).