Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [N:1]1[CH:2]=[CH:3][N:4]2[CH:9]=[CH:8][N:7]=[CH:6][C:5]=12>[Pd].Cl.CCO>[N:1]1[CH:2]=[CH:3][N:4]2[CH2:9][CH2:8][NH:7][CH2:6][C:5]=12
Reactant: c1cn2ccnc2cn1
Agent: [Pd]
Agent: Cl
Solvent: CCO
Product: c1cn2c(n1)CNCC2
Reaction time: 16 h

Procedure:
Imidazo[1,2-a]pyrazine (250 mg, 2.1 mmol) and palladium on carbon (10%) (55.8 mg, 0.53 mmol) were placed in a pressure resistant bottle and suspended under nitrogen in 0.5M HCl/EtOH. The mixture was stiffed under at 45 psi H2 for 16 hrs. LC/MS showed completion. The next day, the reaction mixture was passed through celite cake. The filtrate was concentrated under reduced pressure to afford a tan solid. This was used directly without further purification. MS: [M+H]=124.2; Calc'd for C6H9N3: 123.2.
Reaction SMILES: [H-].[Na+].[C:3]([C:6]1[CH:11]=[C:10]([C:12](=[O:14])[CH3:13])[C:9]([OH:15])=[CH:8][C:7]=1[NH:16][CH:17]=O)(=[O:5])[CH3:4].C(Br)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.O.[CH3:28]N(C)C=O>>[C:12]([C:10]1[CH:11]=[C:6]2[C:7](=[CH:8][C:9]=1[OH:15])[N:16]([CH2:17][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[CH:28]=[CH:4][C:3]2=[O:5])(=[O:14])[CH3:13]
Reactant: CN(C)C=O
Reactant: CC(=O)c1cc(C(C)=O)c(NC=O)cc1O
Reactant: BrCc1ccccc1
Agent: [H-]
Agent: [Na+]
Solvent: O
Product: CC(=O)c1cc2c(=O)ccn(Cc3ccccc3)c2cc1O
Reaction time: 0.5 h

Procedure:
A suspension of pre-washed sodium hydride (0.87 g, 0.036 mmol) was stirred at 0° in dry dimethylformamide under nitrogen while N-[2,4-diacetyl-5-hydroxyphenyl]formamide (4.0 g, 18 mmol) was added in small portions. After the addition was complete the mixture was allowed to stir at 0° for 30 minutes, then benzyl bromide (3.lg, 18 mmol) was added all at once. The mixture was stirred for 6 hours during which time the temperature was allowed to rise to 10°. The dark brown solution was poured into a large excess of water, the mixture was acidified to approximately pH 4.0, and was stirred overnight. The off-white solid was filtered off, washed well with water and was dried. The solid was crystallised as white needles 4.8 g (90%) mp 246° -7°.
Reaction SMILES: [Br:1][C:2]1[N:6]([S:7]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)(=[O:9])=[O:8])[CH:5]=[C:4]([CH:16]=O)[CH:3]=1.[Cl-].C[NH3+].[C:21]([BH3-])#[N:22].[Na+]>CO>[Br:1][C:2]1[N:6]([S:7]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)(=[O:9])=[O:8])[CH:5]=[C:4]([CH2:16][NH:22][CH3:21])[CH:3]=1
Reactant: [BH3-]C#N
Reactant: O=Cc1cc(Br)n(S(=O)(=O)c2ccccc2)c1
Agent: C[NH3+]
Agent: [Cl-]
Agent: [Na+]
Solvent: CO
Product: CNCc1cc(Br)n(S(=O)(=O)c2ccccc2)c1
Temperature: 25 °C
Reaction time: 1 h
Yield: 120 %

Procedure:
To a solution (60 mL) of 5-bromo-1-(phenylsulfonyl)-1H-pyrrole-3-carbaldehyde (3.5 g) in methanol were added methylammonium chloride (7.5 g) and sodium cyanoborohydride (2.4 g), and the mixture was stirred at room temperature for 1 hr. The reaction mixture was concentrated under reduced pressure. Saturated aqueous sodium hydrogen carbonate was added to the residue, and the mixture was extracted with ethyl acetate. The extract was washed with saturated aqueous sodium hydrogen carbonate, water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to give the title compound as a brown oil (yield 4.4 g, quantitative).
Reaction SMILES: [O:1]=[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4](=[O:11])[N:3]1[C@@H:12]([CH2:16][CH:17]=[CH2:18])[C:13]([OH:15])=O.CCN=C=NCCCN(C)C.Cl.CC1C=CN=C(N)C=1C.[CH2:40]([NH:44][C@H:45]([C:48]1[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=1)[CH:46]=[CH2:47])[CH:41]([CH3:43])[CH3:42]>C(Cl)Cl>[O:11]=[C:4]1[C:5]2[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=2)[C:2](=[O:1])[N:3]1[CH:12]([CH2:16][CH:17]=[CH2:18])[C:13]([N:44]([CH2:40][CH:41]([CH3:43])[CH3:42])[C@H:45]([C:48]1[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=1)[CH:46]=[CH2:47])=[O:15]
Reactant: C=C[C@H](NCC(C)C)c1ccccc1
Reactant: C=CC[C@@H](C(=O)O)N1C(=O)c2ccccc2C1=O
Agent: CCN=C=NCCCN(C)C
Agent: Cc1ccnc(N)c1C
Agent: Cl
Solvent: ClCCl
Product: C=CCC(C(=O)N(CC(C)C)[C@@H](C=C)c1ccccc1)N1C(=O)c2ccccc2C1=O
Temperature: -20 °C
Reaction time: 1 h

Procedure:
To a solution of (2S)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)pent-4-enoic acid (467 mg), EDAC.HCl (529 mg), and dimethyl aminopyridine (20 mg) in DCM (10 ml) at −20° C. under N2 was added a solution of (1S)-N-isobutyl-1-phenylprop-2-en-1-amine in DCM (6 ml). The mixture was allowed to stir at −20° C. for 1 hr then RT overnight. The next day the reaction was diluted with DCM and extracted with 0.1 N HCl. The aqueous layer was back extracted with DCM (×2). All organics were combined, dried (Na2SO4), filtered and evaporated. The resulting residue was purified by column chromatography (20% EtAOc/Hexane) to afford the title compound as a mixture of diastereomers in the form of a clear oil (628 mg, 82%). 1H NMR (300 MHz, d6-DMSO) δ 0.50-0.732 (m, 7H), 1.24-1.98 (m, 3H), 2.15-2.26 (m, 1H), 2.73-3.3 (m, 4H), 4.74-5.42 (m, 4H), 5.75-6.24 (m, 3H), 6.99-7.38 (m, 5H), 7.79-7.88 (m, 4H). MS APCI, m/z=417 (M+1), LC/MS, 2.93 min.
Reaction SMILES: [CH3:1][O:2][C:3]1[N:8]=[N:7][C:6]([N:9]2[CH2:14][CH2:13][CH:12]([CH2:15][CH2:16]O)[CH2:11][CH2:10]2)=[CH:5][CH:4]=1.[Cl:18]CCl.S(Cl)(Cl)=O>O>[Cl:18][CH2:16][CH2:15][CH:12]1[CH2:13][CH2:14][N:9]([C:6]2[N:7]=[N:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=2)[CH2:10][CH2:11]1
Reactant: ClCCl
Reactant: COc1ccc(N2CCC(CCO)CC2)nn1
Solvent: O
Solvent: O=S(Cl)Cl
Product: COc1ccc(N2CCC(CCCl)CC2)nn1
Reaction time: 8 h

Procedure:
A solution of 7.3 parts of 1-(6-methoxy-3-pyridazinyl)-4-piperidineethanol in 130 parts of dichloromethane was added dropwise to 7.3 parts of thionyl chloride at room temperature. Upon complete addition, stirring was continued overnight at room temperature. The residue was taken up in water and the product was extracted with dichloromethane. The extract was dried, filtered and evaporated, yielding a first fraction of 1.8 parts of 3-[4-(2-chloroethyl)-1-piperidinyl]-6-methoxypyridazine. The aqueous layer was neutralized with an ammonium hydroxide solution. The precipitated product was filtered off and taken up in dichloromethane. The organic layer was dried, filtered and evaporated, yielding a second fraction of 4.0 parts of 3-[4-(2-chloroethyl)-1-piperidinyl]-6-methoxypyridazine. Total yield: 5.8 parts (73.4%) of 3-[4-(2-chloroethyl)-1-piperidinyl]-6-methoxypyridazine as a residue (int. 96).
Reaction SMILES: [OH:1][C:2]1[CH:9]=[CH:8][CH:7]=[CH:6][C:3]=1[CH:4]=O.Cl.[NH2:11][OH:12].C(N(CC)CC)C>C(O)C>[OH:1][C:2]1[CH:9]=[CH:8][CH:7]=[CH:6][C:3]=1/[CH:4]=[N:11]/[OH:12]
Reactant: NO
Reactant: O=Cc1ccccc1O
Agent: Cl
Solvent: CCN(CC)CC
Solvent: CCO
Product: O/N=C/c1ccccc1O
Temperature: 95 °C
Reaction time: 5 h

Procedure:
Into a 500 mL round bottom flask was placed a solution of 2-hydroxybenzaldehyde (20 g, 163.93 mmol) in ethanol (200 mL). To this was added (H2NOH HCl) hydroxylamine hydrochloride (14 g, 197.18 mmol). To the mixture was added triethylamine (19.2 g, 190.10 mmol) slowly. The resulting solution was allowed to react, with stirring, for 5 hours while the temperature was maintained at 95° C. in a bath of oil. The reaction progress was monitored by TLC (ethyl acetate/petroleum ether=1:2). The mixture was concentrated by evaporation. The resulting solution was extracted two times with 150 mL of ethyl acetate and water. The resulting mixture was washed 3 times with 150 mL of water. The mixture was dried over MgSO4 and concentrated by evaporator. The residue was purified by eluting through a column with a 1:100 ethyl acetate/petroleum ether solvent system. This resulted in 10 g (43%) of (E)-2-hydroxybenzaldehyde oxime as a white solid.
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:9][C:10]3[CH:16]=[CH:15][CH:14]=[CH:13][C:11]=3[CH:12]=2)=[CH:4][CH:3]=1.C(N(CC)CC)C.O([Si:32]([CH:39]([CH3:41])[CH3:40])([CH:36]([CH3:38])[CH3:37])[CH:33]([CH3:35])[CH3:34])S(C(F)(F)F)(=O)=O>CN(C=O)C>[CH:33]([Si:32]([O:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:9][C:10]3[CH:16]=[CH:15][CH:14]=[CH:13][C:11]=3[CH:12]=2)=[CH:4][CH:3]=1)([CH:39]([CH3:41])[CH3:40])[CH:36]([CH3:38])[CH3:37])([CH3:35])[CH3:34]
Reactant: Oc1ccc(-c2cc3ccccc3s2)cc1
Reactant: CC(C)[Si](OS(=O)(=O)C(F)(F)F)(C(C)C)C(C)C
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: CC(C)[Si](Oc1ccc(-c2cc3ccccc3s2)cc1)(C(C)C)C(C)C
Temperature: 25 °C
Yield: 97.6 %

Procedure:
A mixture of 2-(4-hydroxyphenyl)benzothiophene (2.84 g, 12.6 mmol), triethylamine (2.5 g, 25.2 mmol) and 30 mL dry DMF was cooled in an ice bath and treated with triisopropylsilyl triflate (7.7 g, 25.2 mmol). The reaction was allowed to warm to room temperature, quenched with 100 mL brine then extracted twice with 50 mL EtOAc. The combined extract was washed with brine, dried over MgSO4 and concentrated to dryness. The resulting solid was purified by chromatrography (SiO2, 5% EtOAc in Hexanes) to yield 4.7 g (12.3 mmol, 98%) of a solid.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:11]=[CH:10][C:9]2[NH:8][C:7]3[CH2:12][CH2:13][N:14]([CH3:16])[CH2:15][C:6]=3[C:5]=2[CH:4]=1.[H-].[Na+].[CH3:19][C:20]1([C:23]2[CH:28]=[CH:27][N:26]=[CH:25][CH:24]=2)[CH2:22][O:21]1>CN(C=O)C>[CH3:1][O:2][C:3]1[CH:11]=[CH:10][C:9]2[N:8]([CH2:19][C:20]([C:23]3[CH:28]=[CH:27][N:26]=[CH:25][CH:24]=3)([OH:21])[CH3:22])[C:7]3[CH2:12][CH2:13][N:14]([CH3:16])[CH2:15][C:6]=3[C:5]=2[CH:4]=1
Reactant: CC1(c2ccncc2)CO1
Reactant: COc1ccc2[nH]c3c(c2c1)CN(C)CC3
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: COc1ccc2c(c1)c1c(n2CC(C)(O)c2ccncc2)CCN(C)C1
Temperature: 0 °C
Reaction time: 0.08 h

Procedure:
A flask was charged with 8-methoxy-2-methyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole (1.5 g, 6.9 mmol) in DMF (15 mL) and stirred for 5 min. To this was added NaH (60% in hexane) (828 mg, 20 mmol) and the mixture stirred at RT for 10 min. 4-(2-Methyloxiran-2-yl)pyridine (1.89 g, 13.8 mmol) was added and the mixture stirred at RT for 16 h. The progress of reaction was monitored by TLC. The reaction mixture was poured into ice water and filtered. The filtrate was washed with water and concentrated. The residue was recrystallized from ether to get pure product. 1H NMR (DMSO-d6, di-HCl salt) δ (ppm): 8.75 (m, 2H), 8.0 (dd, 2H), 7.30 (d, 1H), 6.90 (s, 1H), 6.60 (t, 1H), 6.10 (bs, 1H), 4.50 (m, 1H), 4.30 (m, 2H), 4.18 (m, 1H), 3.80 (s, 3H), 3.60 (m, 2H), 3.25 (m, 1H), 2.10 (m, 1H), 2.95 (s, 3H), 1.60 (s, 3H).
Reaction SMILES: B(F)(F)F.[CH3:5]COCC.[CH:10]1[CH2:14]C=[CH:12][CH:11]=1.[CH:15]([C:17]([CH3:21])=[CH:18][CH2:19][Cl:20])=[O:16].C(=O)([O-])[O-].[Na+].[Na+]>C(Cl)Cl>[Cl:20][CH2:19][CH:18]1[C:17]([CH3:5])([CH:15]=[O:16])[CH:21]2[CH2:12][CH:11]1[CH:10]=[CH:14]2
Reactant: CC(C=O)=CCCl
Reactant: C1=CCC=C1
Reactant: CCOCC
Agent: FB(F)F
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: ClCCl
Product: CC1(C=O)C2C=CC(C2)C1CCl
Temperature: -20 °C
Yield: 90 %

Procedure:
5 ml of boron fluoride etherate were added to 1 liter of methylene chloride and the mixture was cooled to -20° C. A solution of 452 g (6.84 moles) of cyclopentadiene and 712 g (6.0 moles) of 3-formyl-crotyl chloride were added, whilst stirring, at a rate such that the reaction temperature did not rise above -10° C. The reaction mixture was then stirred for 3 hours at -10° C. To work up the reaction mixture, it was poured onto 1 kg of ice and neutralized with sodium carbonate solution, and the methylene chloride solution was washed neutral with water. After distilling off the solvent under reduced pressure (12 mm Hg/50° C.), 1,139 g of reaction product remained. A sample distillation showed that the yield was about 90% of theory.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]=[N:9][C:10]1[NH:11][CH:12]=[CH:13][N:14]=1.C[I:16].[CH2:17]([CH2:20]OC)OC>>[I-:16].[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]=[N:9][CH:10]1[N:11]([CH3:12])[CH:20]=[CH:17][N:14]1[CH3:13]
Reactant: COCCOC
Reactant: CI
Reactant: Clc1ccccc1N=Nc1ncc[nH]1
Product: CN1C=CN(C)C1N=Nc1ccccc1Cl
Product: [I-]
Yield: 60.8 %

Procedure:
2-((2-Chlorophenyl)azo)imidazole (20.6 grams; 0.1 mole) was refluxed with 50 cc of methyl iodide in 100 milliters of glyme for 2.0 hours to give 22.0 grams (60.8 percent of theoretical) of 2-((2-chlorophenyl)azo)-1,3-dimethylimidazole iodide melting at 212°-215° C.
Reaction SMILES: CN(C)/[CH:3]=[CH:4]/[C:5]([C:7]1[S:11][C:10]([N:12]=CN(C)C)=[N:9][C:8]=1[CH3:17])=O.[Cl:19][C:20]1[CH:25]=[CH:24][CH:23]=[C:22]([Cl:26])[C:21]=1[CH2:27][C:28]([NH2:30])=[NH:29].COCCO.[OH-].[Na+]>O>[Cl:19][C:20]1[CH:25]=[CH:24][CH:23]=[C:22]([Cl:26])[C:21]=1[CH2:27][C:28]1[N:30]=[C:5]([C:7]2[S:11][C:10]([NH2:12])=[N:9][C:8]=2[CH3:17])[CH:4]=[CH:3][N:29]=1
Reactant: Cc1nc(N=CN(C)C)sc1C(=O)/C=C/N(C)C
Reactant: N=C(N)Cc1c(Cl)cccc1Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: COCCO
Product: Cc1nc(N)sc1-c1ccnc(Cc2c(Cl)cccc2Cl)n1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
A mixture of N′-[5-((E)-3-dimethylamino-acryloyl)-4-methyl-thiazol-2-yl]-N,N-dimethyl-formamidine (1 g), 2,6-dichlorophenylacetamidine (0.90 g) and 2-methoxyethanol (3.8 ml) is stirred at room temperature for 30 minutes. NaOH (0.3 g) is added and the mixture stirred at 125° C. for 1 hr. After cooling to room temperature water is added and the mixture evaporated to dryness and then purified by normal phase chromatography on silica gel eluting with a gradient from CH2Cl2 to EtOAc to give the title compound as a beige solid.
Reaction SMILES: [Cl:1][C:2]1[CH:22]=[CH:21][CH:20]=[C:19]([Cl:23])[C:3]=1[C:4]([C:6]1[C:11]([CH3:12])=[CH:10][C:9]([O:13][CH3:14])=[C:8]([O:15]C)[C:7]=1[O:17]C)=[O:5].Br.C(O)(=O)C>O>[Cl:1][C:2]1[CH:22]=[CH:21][CH:20]=[C:19]([Cl:23])[C:3]=1[C:4]([C:6]1[C:11]([CH3:12])=[CH:10][C:9]([O:13][CH3:14])=[C:8]([OH:15])[C:7]=1[OH:17])=[O:5]
Reactant: COc1cc(C)c(C(=O)c2c(Cl)cccc2Cl)c(OC)c1OC
Agent: Br
Solvent: CC(=O)O
Solvent: O
Product: COc1cc(C)c(C(=O)c2c(Cl)cccc2Cl)c(O)c1O
Temperature: 75 °C
Reaction time: 2 h

Procedure:
A mixture of 2,6-dichloro-2',3',4'-trimethoxy-6'-methyl-benzophenone (1.78 g; 5 mmol) hydrobromic acid (7.5 ml; 30% in acetic acid) and acetic acid (7.5 ml) is stirred at 75° C. for 2 hours. Water is added and the mixture extracted with methylenechloride. The extract is washed with water and shaken with 2N sodium hydroxide. The alcaline solution is acidified with hydrochloric acid, the separated compound dissolved in methylenechloride and the solution washed with water. After evaporation of the solvent purification is carried out by chromatography (flash column, filled with 36 g of silicagel; elution with 500 ml of petrolether/ethylacetate (4:1; v/v) and 250 ml of petrolether/ethylacetate (1:1; v/v)). The fraction containing the compound is concentrated, the compound crystallized. The yellow crystalls are washed with petrolether and sucked off; 0.64 g (39% y), mp. 182° C.
Reaction SMILES: [Br:1][C:2]1[C:7]2[N:8]([CH2:12][CH2:13][CH2:14][C:15]([O:17][CH2:18][CH3:19])=[O:16])[C:9](Cl)=[N:10][C:6]=2[CH:5]=[CH:4][CH:3]=1.[Cl:20][C:21]1[CH:27]=[C:26]([Cl:28])[CH:25]=[CH:24][C:22]=1[NH2:23].O.C1(C)C=CC(S(O)(=O)=O)=CC=1.C(=O)([O-])O.[Na+]>C1(C)C(C)=CC=CC=1>[Br:1][C:2]1[C:7]2[N:8]([CH2:12][CH2:13][CH2:14][C:15]([O:17][CH2:18][CH3:19])=[O:16])[C:9]([NH:23][C:22]3[CH:24]=[CH:25][C:26]([Cl:28])=[CH:27][C:21]=3[Cl:20])=[N:10][C:6]=2[CH:5]=[CH:4][CH:3]=1
Reactant: Nc1ccc(Cl)cc1Cl
Reactant: CCOC(=O)CCCn1c(Cl)nc2cccc(Br)c21
Agent: Cc1ccc(S(=O)(=O)O)cc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O
Solvent: Cc1ccccc1C
Product: CCOC(=O)CCCn1c(Nc2ccc(Cl)cc2Cl)nc2cccc(Br)c21
Temperature: 150 °C
Reaction time: 3 h
Yield: 25.1 %

Procedure:
A mixture of ethyl 4-(7-bromo-2-chloro-1H-benzimidazol-1-yl)butanoate (1.57 g, 4.54 Mmol), 2,4-di-chloroaniline (2.21 g, 13.6 mmol), p-toluenesulfonic acid monohydrate (930 mg, 4.89 mmol) and xylene (8.0 mL) was stirred at 150° C. for 3 hr. The mixture was neutralized with aqueous sodium hydrogen carbonate and extracted with ethyl acetate. The combined organic layer was washed with brine, dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel eluting with a 5-30% ethyl acetate/n-hexane gradient mixture. The filtrate was concentrated in vacuo to give the title compound as a colorless solid (1.61 g, 3.42 mmol, 75%).
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH:6]=[CH:7][C:8]=1[N:9]1[CH:13]=[CH:12][C:11]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=2)=[N:10]1)[NH2:5].C(=O)([O-])[O-].[K+].[K+].[CH:26]1[CH:31]=[CH:30][C:29]([CH2:32][O:33][C:34](Cl)=[O:35])=[CH:28][CH:27]=1.O>ClCCl>[CH2:32]([O:33][C:34](=[O:35])[NH:5][C:4]1[CH:6]=[CH:7][C:8]([N:9]2[CH:13]=[CH:12][C:11]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=3)=[N:10]2)=[C:2]([F:1])[CH:3]=1)[C:29]1[CH:30]=[CH:31][CH:26]=[CH:27][CH:28]=1
Reactant: O=C(Cl)OCc1ccccc1
Reactant: Nc1ccc(-n2ccc(-c3ccccn3)n2)c(F)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: ClCCl
Product: O=C(Nc1ccc(-n2ccc(-c3ccccn3)n2)c(F)c1)OCc1ccccc1
Yield: 81.5 %

Procedure:
The above-described product 19a (1 g, 3.9 mmol) was dissolved in dichloromethane (4 mL), and then anhydrous potassium carbonate (0.6 g) was added thereto. Then, Cbz-Cl (1.863 g, 1.537 mL) was slowly dropped, at a rate of 1-2 drops per second, into the mixture maintained in an ice-salt bath. The resultant mixture was reacted for 4 hours at room temperature. After completion of the reaction, water was added into the reaction mixture, followed by extraction with ethyl acetate. The combined ethyl acetate phase was evaporated in vacuum to get a crude product, which was recrystallized with acetone to afford the product 20a (1.235 g) as a white solid, with a yield of 80.8%.
Reaction SMILES: [Br:1][C:2]1[C:3](=[O:30])[N:4]([C:19]2[CH:28]=[CH:27][C:22]([C:23]([O:25]C)=[O:24])=[CH:21][C:20]=2[F:29])[C:5]([CH3:18])=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([F:16])=[CH:12][C:11]=1[F:17].CO.O.[OH-].[Na+]>O1CCCC1>[Br:1][C:2]1[C:3](=[O:30])[N:4]([C:19]2[CH:28]=[CH:27][C:22]([C:23]([OH:25])=[O:24])=[CH:21][C:20]=2[F:29])[C:5]([CH3:18])=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([F:16])=[CH:12][C:11]=1[F:17]
Reactant: COC(=O)c1ccc(-n2c(C)cc(OCc3ccc(F)cc3F)c(Br)c2=O)c(F)c1
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: C1CCOC1
Solvent: CO
Product: Cc1cc(OCc2ccc(F)cc2F)c(Br)c(=O)n1-c1ccc(C(=O)O)cc1F
Temperature: 25 °C
Reaction time: 2 h

Procedure:
Compound of Example 604 (4.1 g, 8.5 mmol) was suspended in tetrahydrofuran (30 mL), methanol (15 mL), water (15 mL) and 2.5 N NaOH (6.8 mL, 17 mmol)). After stirring at room temperature for 2 hour, the reaction was complete and the organics were removed. The aqueous layer was acidified to pH 1 with 3N HCl, the solids were suspended in water, filtered, and washed with diethyl ether. The title compound was obtained as a white powder and used without further purification (4.4 g). 1H NMR (400 MHz, CD3OD) δ 8.00 (dd, J=1.8 and 8.8 Hz, 1H), 7.93 (dd, J=1.48 and 10 Hz, 1H), 7.64 (q, J=8 and 14.8 Hz, 1H), 7.49 (t, J=7.6 Hz, 1H), 7.05 (t, J=10 Hz, 2H), 6.66 (s, 1H), 5.36 (s, 2H), 2.08 (s, 3H) ppm. 19F NMR (400 MHz, CD3OD) δ −111.48 (1F), −115.96 (1F), −123.35 (1F) ppm. ES-HRMS m/z 468.9987 (M+H calcd for C20H14BrF3NO4 requires 469.0086).
Reaction SMILES: CN(C)[CH:3]=[CH:4][C:5]1[C:10]([C:11](=[O:20])[C:12]2[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][CH:13]=2)=[CH:9][CH:8]=[CH:7][C:6]=1[N+:21]([O-])=O.[H][H]>C(OCC)(=O)C.[Pd]>[CH3:19][O:18][C:15]1[CH:14]=[CH:13][C:12]([C:11]([C:10]2[CH:9]=[CH:8][CH:7]=[C:6]3[C:5]=2[CH:4]=[CH:3][NH:21]3)=[O:20])=[CH:17][CH:16]=1
Reactant: COc1ccc(C(=O)c2cccc([N+](=O)[O-])c2C=CN(C)C)cc1
Reactant: [H][H]
Agent: [Pd]
Solvent: CCOC(C)=O
Product: COc1ccc(C(=O)c2cccc3[nH]ccc23)cc1
Yield: 73.5 %

Procedure:
A solution of 32 g. (0.098 mole) of 2-(2-dimethylaminoethenyl)-3-(4-methoxybenzoyl)nitrobenzene in 200 ml of ethyl acetate was treated with 5 g of 10% palladium-on-charcoal, and the starting material reduced with hydrogen under 50 p.s.i.g. The mixture was then filtered, the filtrate taken to dryness, and the residue recrystallized from ethyl acetate to give 18.1 g of 4-(4-methoxybenzoyl)indole. Another sample, similarly prepared by reduction of the starting material with Raney nickel in ethanol, afforded material having m.p. 148°-152° C.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[N+:4]([O-])[CH:5]=[CH:6][C:7]=1[CH2:8][CH3:9].ClC1C=C[N:15]=[C:14](C#N)C=1>>[Cl:1][C:2]1[C:3]([C:14]#[N:15])=[N:4][CH:5]=[CH:6][C:7]=1[CH2:8][CH3:9]
Reactant: CCc1cc[n+]([O-])cc1Cl
Reactant: N#Cc1cc(Cl)ccn1
Product: CCc1ccnc(C#N)c1Cl

Procedure:
The title compound was prepared from 3-chloro-4-ethylpyridine-N-oxide according to the procedure for preparing 4-chloro-2-pyridinecarbonitrile described in Example 33.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[C:6]([N:8]([CH3:10])[CH3:9])[CH:5]=[CH:4][C:3]=1[C:11]([C:13]1[CH:21]=[CH:20][CH:19]=[CH:18][C:14]=1[C:15]([OH:17])=[O:16])=O.[CH2:22]([O:24][CH2:25][CH2:26][N:27]1[C:35]2[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=2)[CH:29]=[C:28]1[CH3:36])[CH3:23].C(OC(=O)C)(=O)C.[OH-].[NH4+]>C1(C)C=CC=CC=1>[CH2:22]([O:24][CH2:25][CH2:26][N:27]1[C:35]2[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=2)[C:29]([C:11]2([C:3]3[CH:4]=[CH:5][C:6]([N:8]([CH3:9])[CH3:10])=[CH:7][C:2]=3[CH3:1])[C:13]3[C:14](=[CH:18][CH:19]=[CH:20][CH:21]=3)[C:15](=[O:17])[O:16]2)=[C:28]1[CH3:36])[CH3:23]
Reactant: CCOCCn1c(C)cc2ccccc21
Reactant: Cc1cc(N(C)C)ccc1C(=O)c1ccccc1C(=O)O
Agent: [NH4+]
Agent: [OH-]
Solvent: CC(=O)OC(C)=O
Solvent: Cc1ccccc1
Product: CCOCCn1c(C)c(C2(c3ccc(N(C)C)cc3C)OC(=O)c3ccccc32)c2ccccc21
Temperature: 70 °C
Yield: 37.1 %

Procedure:
A mixture of 14.5 g of 2-(2-methyl-4-dimethylaminophenyl)carbonylbenzoic acid, 11.5 g of 1-(2-ethoxyethyl)-2-methylindole and 40.0 ml acetic anhydride was maintained at approximately 70° C. for approximately four hours. The resulting solution was cooled to ambient temperature and slowly poured into a mixture of toluene and 5 percent aqueous ammonium hydroxide. The toluene layer was separated, washed with water and then with saturated sodium chloride solution. The toluene solution was evaporated to dryness. The residue which remained was recrystallized twice from a mixture of hexane and isopropyl alcohol to obtain 8.9 g of 3-[1-(2-ethoxyethyl)-2-methylindol-3-yl]-3-(2-methyl-4-dimethylaminophenyl)phthalide (Formula I: R=C2H5OC2H4 ; R1 =R2 =R3 =R4 =CH3 ; X=Y=H), a white-colored solid which melted at 170.5° to 171° C. Significant infrared maxima appeared at 1750 (C=O;s) and 1123 (C--O;s)cm-1. A toluene solution of the product spotted on an acid clay or a phenolic resin coated paper developed a cyan-colored image.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([Cl:8])=[CH:4][C:3]=1[S:9]([N:12]([CH3:16])[C:13](Cl)=[O:14])(=[O:11])=[O:10].C(N(CC)CC)C.[CH3:24][NH:25][C:26]1[N:31]=[C:30]([O:32][CH3:33])[CH:29]=[C:28]([CH3:34])[N:27]=1>O1CCCC1>[CH3:33][O:32][C:30]1[CH:29]=[C:28]([CH3:34])[N:27]=[C:26]([N:25]([CH3:24])[C:13]([N:12]([CH3:16])[S:9]([C:3]2[CH:4]=[C:5]([Cl:8])[CH:6]=[CH:7][C:2]=2[Cl:1])(=[O:11])=[O:10])=[O:14])[N:31]=1
Reactant: CN(C(=O)Cl)S(=O)(=O)c1cc(Cl)ccc1Cl
Reactant: CNc1nc(C)cc(OC)n1
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: COc1cc(C)nc(N(C)C(=O)N(C)S(=O)(=O)c2cc(Cl)ccc2Cl)n1

Procedure:
To 3.0 g of N-[(2,5-dichlorophenyl)sulfonyl]-N-methylcarbamyl chloride in 50 ml of tetrahydrofuran containing 1.0 g of triethylamine is added 1.5 g of 2-methylamino-4-methoxy-6-methylpyrimidine. After stirring at reflux for several hours, the precipitated salts are filtered off and the filtrate is concentrated to yield N-[N-(4-methoxy-6-methylpyrimidin-2-yl)-N-methylaminocarbonyl]2,5-dichloro-N-methylbenzenesulfonamide.