Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([S:20](Cl)(=[O:22])=[O:21])[CH:5]=[C:6]([Cl:19])[C:7]=1[O:8][C:9]1[CH:14]=[CH:13][C:12]([N+:15]([O-:17])=[O:16])=[CH:11][C:10]=1[Cl:18].CCN(C(C)C)C(C)C.[CH:33]([O:36][C:37]1[CH:43]=[CH:42][C:40]([NH2:41])=[CH:39][CH:38]=1)([CH3:35])[CH3:34]>ClCCl>[Cl:1][C:2]1[CH:3]=[C:4]([S:20]([NH:41][C:40]2[CH:39]=[CH:38][C:37]([O:36][CH:33]([CH3:35])[CH3:34])=[CH:43][CH:42]=2)(=[O:22])=[O:21])[CH:5]=[C:6]([Cl:19])[C:7]=1[O:8][C:9]1[CH:14]=[CH:13][C:12]([N+:15]([O-:17])=[O:16])=[CH:11][C:10]=1[Cl:18]
Reactant: O=[N+]([O-])c1ccc(Oc2c(Cl)cc(S(=O)(=O)Cl)cc2Cl)c(Cl)c1
Reactant: CC(C)Oc1ccc(N)cc1
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: CC(C)Oc1ccc(NS(=O)(=O)c2cc(Cl)c(Oc3ccc([N+](=O)[O-])cc3Cl)c(Cl)c2)cc1
Temperature: 40 °C
Yield: 63 %

Procedure:
To 100 mg of 3,5-Dichloro-4-(2-Chloro-4-Nitrophenoxy)Benzene-1-Sulfonyl Chloride (0.23 m.mol) was added 0.2 ml of DIEA, 5 ml of dichloromethane and 150 mg of 4-isopropoxyaniline. The mixture was maintained at 40° C. for 4 hours. The solvent was evaporated and the residue dissolved in ethyl acetate and washed with water and brine. The organic layer was dried over anhydrous Na2SO4 and the solvent evaporated. The residue as purified using radial silica-gel chromatography using 1:4 ethyl acetate:hexane as solvent. The purity of the product by LC/MS was 97.19%. M−1 (530) was seen in the mass spectrum. The yield of the product was 80.3 mg or 63% yield.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[N:4][C:5]([N:11]2[CH2:14][CH:13]([O:15][C:16]3[CH:21]=[CH:20][C:19]([F:22])=[C:18]([F:23])[CH:17]=3)[CH2:12]2)=[C:6]([CH:10]=1)[C:7]([OH:9])=O.Cl.[NH2:25][C:26]1([C:29]2[CH:38]=[CH:37][C:32]([C:33]([O:35][CH3:36])=[O:34])=[CH:31][CH:30]=2)[CH2:28][CH2:27]1>>[Cl:1][C:2]1[CH:3]=[N:4][C:5]([N:11]2[CH2:12][CH:13]([O:15][C:16]3[CH:21]=[CH:20][C:19]([F:22])=[C:18]([F:23])[CH:17]=3)[CH2:14]2)=[C:6]([CH:10]=1)[C:7]([NH:25][C:26]1([C:29]2[CH:38]=[CH:37][C:32]([C:33]([O:35][CH3:36])=[O:34])=[CH:31][CH:30]=2)[CH2:28][CH2:27]1)=[O:9]
Reactant: O=C(O)c1cc(Cl)cnc1N1CC(Oc2ccc(F)c(F)c2)C1
Reactant: COC(=O)c1ccc(C2(N)CC2)cc1
Agent: Cl
Product: COC(=O)c1ccc(C2(NC(=O)c3cc(Cl)cnc3N3CC(Oc4ccc(F)c(F)c4)C3)CC2)cc1
Yield: 38.2 %

Procedure:
The title compound (D155) (50 mg) was prepared according to the experimental procedure described in Description 144 starting from 5-chloro-2-(3-(3,4-difluorophenoxy)azetidin-1-yl)nicotinic acid (D109) (87 mg, 0.255 mmol) and methyl 4-(1-aminocyclopropyl)benzoate (D7) (58.14 mg, 0.255 mmol).
Reaction SMILES: OC1C([N+]([O-])=O)([N+]([O-])=O)C(O)=[N:5][C:4](=[C:15]([N+:19]([O-:21])=[O:20])[N+:16]([O-:18])=[O:17])[N:3]=1.OC1C=C(O)N=C(C)N=1>>[NH2:3][C:4]([NH2:5])=[C:15]([N+:19]([O-:21])=[O:20])[N+:16]([O-:18])=[O:17]
Reactant: O=[N+]([O-])C(=C1N=C(O)C([N+](=O)[O-])([N+](=O)[O-])C(O)=N1)[N+](=O)[O-]
Agent: Cc1nc(O)cc(O)n1
Product: NC(N)=C([N+](=O)[O-])[N+](=O)[O-]
Yield: 50 %

Procedure:
The 4,6-dihydroxy-5,5-dinitro-2-(dinitromethylene)-2,5-dihydropyrimidine produced by the nitration reaction of 4,6-dihydroxy-2-methylpyrimidine in this comparative example, was hydrolyzed to give 1,1-diamino-2,2-dinitroethylene with the combined yield of 50%.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:21]=[CH:20][C:6]([CH2:7][N:8]2[CH:12]=[C:11]([C:13]3[N:14]=[C:15]([OH:18])[S:16][CH:17]=3)[C:10]([CH3:19])=[N:9]2)=[CH:5][CH:4]=1.Cl[C:23]1[N:28]=[CH:27][CH:26]=[CH:25][N:24]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C.CCOC(C)=O.[Cu]>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([CH2:7][N:8]2[CH:12]=[C:11]([C:13]3[N:14]=[C:15]([O:18][C:23]4[N:28]=[CH:27][CH:26]=[CH:25][N:24]=4)[S:16][CH:17]=3)[C:10]([CH3:19])=[N:9]2)=[CH:20][CH:21]=1
Reactant: COc1ccc(Cn2cc(-c3csc(O)n3)c(C)n2)cc1
Reactant: Clc1ncccn1
Agent: [Cu]
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: COc1ccc(Cn2cc(-c3csc(Oc4ncccn4)n3)c(C)n2)cc1
Temperature: 160 °C
Reaction time: 0.75 h
Yield: 18.2 %

Procedure:
According to Scheme 2, Step 5: A mixture of 4-(1-(4-methoxybenzyl)-3-methyl-1H-pyrazol-4-yl)thiazol-2-ol (0.99 mmol, 300 mg), 2-chloropyrimidine (0.99 mmol, 114 mg), copper (0.20 mmol, 12.6 mg) and cesium carbonate (2.99 mmol, 973 mg) in DMF (3.3 mL) was stirred at 160° C. under microwave conditions for 45 minutes. Then, the reaction mixture was diluted with EtOAc and was washed with water. The organic phase was dried over MgSO4, was filtered and was evaporated. The crude mixture was purified by flash chromatography over silica gel using cyclohexane/EtOAc (80:20 to 60:40) as eluent to yield 4-(1-(4-methoxybenzyl)-3-methyl-1H-pyrazol-4-yl)-2-(pyrimidin-2-yloxy)thiazole (0.18 mmol, 67 mg, 18%) as a yellow oil.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[CH:6][CH:7]=[C:8]2[C:13]=1[CH:12]=[C:11]([C:14]1[CH:23]=[CH:22][C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[N:15]=1)[CH:10]=[CH:9]2)([O-])=O.[BH4-].[Na+].Cl>CO.[Pd]>[NH2:1][C:4]1[CH:5]=[CH:6][CH:7]=[C:8]2[C:13]=1[CH:12]=[C:11]([C:14]1[CH:23]=[CH:22][C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[N:15]=1)[CH:10]=[CH:9]2
Reactant: O=[N+]([O-])c1cccc2ccc(-c3ccc4ccccc4n3)cc12
Agent: [Pd]
Agent: Cl
Agent: [BH4-]
Solvent: CO
Product: Nc1cccc2ccc(-c3ccc4ccccc4n3)cc12
Temperature: 0 °C
Yield: 135.5 %

Procedure:
12.6 g (42 mmol) of 8-nitro-2-naphthylquinoline and 1.99 g of Pd/C (10%) are suspended in 200 ml of methanol. 8.4 g (222 mmol) of sodium borohydride are added in portions with stirring at 0° C. After stirring for 2 h, the clear solution is neutralised using dilute HCl. The solvent is then removed, and the resultant residue is washed vigorously with water and recrystallised from dioxane. The precipitate is filtered and dried in vacuo, giving 9.9 g (56.9 mmol) of crystalline solid. The overall yield is 88%.
Reaction SMILES: [F:1][C:2]1[C:7]([F:8])=[CH:6][C:5]([C:9](=[O:14])[CH2:10]S(C)=O)=[C:4]([NH:15][CH3:16])[CH:3]=1>C(O)(=O)C.C(O)C.[Zn]>[F:1][C:2]1[C:7]([F:8])=[CH:6][C:5]([C:9](=[O:14])[CH3:10])=[C:4]([NH:15][CH3:16])[CH:3]=1
Reactant: CNc1cc(F)c(F)cc1C(=O)CS(C)=O
Agent: [Zn]
Solvent: CC(=O)O
Solvent: CCO
Product: CNc1cc(F)c(F)cc1C(C)=O
Temperature: 25 °C
Reaction time: 8 h

Procedure:
A solution of 1-[4,5-difluoro-2-(methylamino)phenyl]-2-methylsulphinylethanone (32.4 g) in acetic acid (90 ml) and ethanol (90 ml) was added over a period of 20 minutes to a stirred suspension of zinc dust (50 g) in acetic acid (45 ml) and ethanol (80 ml) at 0° under nitrogen. The mixture was stirred at ambient temperature overnight and then filtered through diatomaceous earth (sold under the trade name CELITE). The filter bed was washed with acetic acid (3×50 ml). The combined filtrate and washings were poured into water (1200 ml) and the mixture was extracted with dichloromethane (3×400 ml). The combined extracts were washed with aqueous sodium carbonate (1M, 2×500 ml) and dried over magnesium sulphate. The solvent was removed by distillation to give the novel compound 4',5'-difluoro-2'-(methylamino)acetophenone, m.p 51°-52°.
Reaction SMILES: [CH:1]1([CH2:4][OH:5])[CH2:3][CH2:2]1.[H-].[Na+].F[C:9]1[CH:17]=[C:16]([CH3:18])[C:12]([C:13]([OH:15])=[O:14])=[CH:11][N:10]=1.Cl>C1COCC1>[CH:1]1([CH2:4][O:5][C:9]2[CH:17]=[C:16]([CH3:18])[C:12]([C:13]([OH:15])=[O:14])=[CH:11][N:10]=2)[CH2:3][CH2:2]1
Reactant: Cc1cc(F)ncc1C(=O)O
Reactant: OCC1CC1
Agent: Cl
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: Cc1cc(OCC2CC2)ncc1C(=O)O
Temperature: 25 °C
Reaction time: 1 h

Procedure:
Cyclopropylmethanol (3.92 mL) was added to a suspension of sodium hydride (60% oil, 1.93 g) in THF (30 mL) by small portions at 0° C., and the obtained mixture was stirred at room temperature for 1 hr. To the reaction mixture was added 6-fluoro-4-methylnicotinic acid, and the mixture was stirred at room temperature for 20 hr. The reaction mixture was neutralized with 1 M hydrochloric acid, and the mixture was extracted with ethyl acetate. The obtained organic layer was washed with saturated brine, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The obtained solid was recrystallized (hexane/ethyl acetate) to give the title compound (1.14 g).
Reaction SMILES: [Sn](Cl)Cl.[N+](=[CH:6][C:7]([O:9][CH2:10][CH3:11])=[O:8])=[N-].[N+:12]([C:15]1[CH:16]=[C:17]([CH:20]=[CH:21][CH:22]=1)[CH:18]=[O:19])([O-:14])=[O:13]>C(Cl)Cl>[N+:12]([C:15]1[CH:16]=[C:17]([C:18](=[O:19])[CH2:6][C:7]([O:9][CH2:10][CH3:11])=[O:8])[CH:20]=[CH:21][CH:22]=1)([O-:14])=[O:13]
Reactant: O=Cc1cccc([N+](=O)[O-])c1
Reactant: CCOC(=O)C=[N+]=[N-]
Agent: Cl[Sn]Cl
Solvent: ClCCl
Product: CCOC(=O)CC(=O)c1cccc([N+](=O)[O-])c1
Temperature: 25 °C
Reaction time: 24 h
Yield: 31.8 %

Procedure:
To a suspension of anhydrous tin (II) chloride (2.5 g, 13.2 mmol) in 150 mL of methylene chloride was added ethyl diazoacetate (8.3 g, 72.8 mmol). Then 3-nitrobenzaldehyde (10.0 g, 66.2 mmol) was added as a solid in small portions over 30 min. The resulting suspension was stirred at room temperature for 24 h. Additional tin (II) chloride (2.5 g) was added and the reaction was stirred an additional 24 h. The reaction was concentrated in vacuo, diluted with ethyl acetate, washed with water (2 times) and brine, dried (MgSO4) and concentrated. The residue was purified by flash chromatography (elution with 4:1 hexanes/ethyl acetate) to afford 5 g (32%) of the title compound. 1H NMR (CDCl3) (approximately 12:1 mixture of enol and keto tautomers, data for enol only) δ: 12.6 (s, 1H); 8.60 (t, 1H, J=1.8 Hz); 8.3 (m, 1H); 8.1 (m, 1H); 7.62 (t, 1H, J=7.9 Hz) 5.77 (s, 1H); 4.30 (q, 2H, J=7.2 Hz); 1.35 (t, 3H, J=7.2 Hz).
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([NH:14][C:15](=[O:17])[CH3:16])[CH:5]=[C:6]([N:8]2[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)[CH:7]=1.Cl[C:19]1[C:28]2[C:23](=[N:24][CH:25]=[CH:26][CH:27]=2)[N:22]=[C:21]([C:29]2[CH:34]=[C:33]([F:35])[CH:32]=[C:31]([F:36])[CH:30]=2)[C:20]=1[CH3:37].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.C(=O)([O-])[O-].[K+].[K+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(O)(C)(C)C>[F:36][C:31]1[CH:30]=[C:29]([C:21]2[C:20]([CH3:37])=[C:19]([NH:1][C:2]3[CH:3]=[C:4]([NH:14][C:15](=[O:17])[CH3:16])[CH:5]=[C:6]([N:8]4[CH2:13][CH2:12][O:11][CH2:10][CH2:9]4)[CH:7]=3)[C:28]3[C:23](=[N:24][CH:25]=[CH:26][CH:27]=3)[N:22]=2)[CH:34]=[C:33]([F:35])[CH:32]=1
Reactant: CC(=O)Nc1cc(N)cc(N2CCOCC2)c1
Reactant: Cc1c(-c2cc(F)cc(F)c2)nc2ncccc2c1Cl
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: CC(C)c1cc(C(C)C)c(-c2ccccc2P(C2CCCCC2)C2CCCCC2)c(C(C)C)c1
Solvent: CC(C)(C)O
Product: CC(=O)Nc1cc(Nc2c(C)c(-c3cc(F)cc(F)c3)nc3ncccc23)cc(N2CCOCC2)c1

Procedure:
Prepared according to Procedure X by stirring N-(3-amino-5-morpholinophenyl)-acetamide (48.6 mg, 0.206 mmol), 4-chloro-2-(3,5-difluorophenyl)-3-methyl-1,8-naphthyridine (50 mg, 0.172 mmol), palladium (II) acetate (3.9 mg, 0.017 mmol), XPhos (16.4 mg, 0.034 mmol), potassium carbonate (60 mg, 0.43 mmol), and 1 mL tert-butanol at 85° C. for 24 h. Purification by reverse-phase HPLC afforded N-(3-((2-(3,5-difluorophenyl)-3-methyl-1,8-naphthyridin-4-yl)amino)-5-(4-morpholinyl)phenyl)acetamide. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 8.84 (1H, dd, J=4.1, 2.0 Hz), 8.21-8.28 (2H, m), 7.23-7.27 (1H, m), 7.10-7.14 (1H, m), 7.04-7.10 (2H, m), 6.85-6.91 (1H, m), 6.45-6.50 (1H, m), 6.14-6.21 (2H, m), 3.77-3.86 (4H, m), 3.09-3.15 (4H, m), 2.33 (3H, s), 1.99 (3H, s). Mass Spectrum (ESI) m/e=490.0 (M+1).
Reaction SMILES: [NH2:1][CH:2]1[C:19](=[O:20])[N:4]2[C:5]([C:16]([OH:18])=[O:17])=[C:6]([CH2:9][S:10][C:11]3[S:12][CH:13]=[N:14][N:15]=3)[CH2:7][S:8][C@H:3]12.[F:21][C:22]([F:30])([F:29])[S:23]([CH2:25][C:26](Cl)=[O:27])=[O:24].[OH-].[Na+]>C(=O)(O)[O-].[Na+].CC(C)=O>[F:21][C:22]([F:30])([F:29])[S:23]([CH2:25][C:26]([NH:1][CH:2]1[C:19](=[O:20])[N:4]2[C:5]([C:16]([OH:18])=[O:17])=[C:6]([CH2:9][S:10][C:11]3[S:12][CH:13]=[N:14][N:15]=3)[CH2:7][S:8][C@H:3]12)=[O:27])=[O:24]
Reactant: NC1C(=O)N2C(C(=O)O)=C(CSc3nncs3)CS[C@H]12
Reactant: O=C(Cl)CS(=O)C(F)(F)F
Agent: O=C([O-])O
Agent: [Na+]
Agent: [OH-]
Solvent: CC(C)=O
Product: O=C(CS(=O)C(F)(F)F)NC1C(=O)N2C(C(=O)O)=C(CSc3nncs3)CS[C@H]12
Reaction time: 0.5 h

Procedure:
To a solution of 3.1 g (0.009 mol) of 7-amino-3-(1,3,4-thiadiazol-2-ylthiomethyl)-3-cephem-4-carboxylic acid in 60 ml of 3 percent aqueous sodium bicarbonate is added 60 ml of acetone. The solution is cooled to -15° and 1.94 g (0.010 mol) of trifluoromethylsulfinylacetyl chloride in 20 ml of acetone is added over a 10-minute period. The reaction mixture is stirred at -15° for 30 minutes while maintaining the pH at 7.6-8.0 by addition of 10 percent sodium hydroxide, then at 25° for one hour. The reaction mixture is extracted once with ether and the aqueous phase is acidified to pH 2.5 with dilute hydrochloric acid and extracted with ethyl acetate. The organic extracts are dried (MgSO4) and concentrated in vacuo to give the title compound.
Reaction SMILES: [C:1]1([CH2:7][CH2:8][CH:9]2[CH2:14][CH2:13][CH:12]([C:15]([O:17]CC)=[O:16])[CH2:11][CH2:10]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Li+].[OH-]>CO.O>[C:1]1([CH2:7][CH2:8][CH:9]2[CH2:14][CH2:13][CH:12]([C:15]([OH:17])=[O:16])[CH2:11][CH2:10]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: CCOC(=O)C1CCC(CCc2ccccc2)CC1
Agent: [Li+]
Agent: [OH-]
Solvent: CO
Solvent: O
Product: O=C(O)C1CCC(CCc2ccccc2)CC1
Temperature: 25 °C
Reaction time: 8 h
Yield: 94.3 %

Procedure:
To a solution of the product of STEP 2 (1.26 g) in MeOH (20 mL), add water (5 mL) and LiOH (0.61 g) and stir overnight at ambient temperature. Dilute the reaction mixture with water and extract with Et2O. Acidify the aqueous layer with conc.HCl and extract with EtOAc. Separate the organic layer, wash with water and brine, and concentrate to obtain the title compound (1.06 g).
Reaction SMILES: [Si]([O:8][C@H:9]([CH3:38])[C@@H:10]([NH:24][C:25]1[CH:32]=[CH:31][C:28]([C:29]#[N:30])=[C:27]([C:33]([F:36])([F:35])[F:34])[C:26]=1[CH3:37])[C:11]1[O:12][C:13]([C:16]2[CH:21]=[CH:20][C:19]([C:22]#[N:23])=[CH:18][CH:17]=2)=[N:14][N:15]=1)(C(C)(C)C)(C)C.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1>[C:22]([C:19]1[CH:18]=[CH:17][C:16]([C:13]2[O:12][C:11]([C@H:10]([NH:24][C:25]3[CH:32]=[CH:31][C:28]([C:29]#[N:30])=[C:27]([C:33]([F:34])([F:36])[F:35])[C:26]=3[CH3:37])[C@H:9]([OH:8])[CH3:38])=[N:15][N:14]=2)=[CH:21][CH:20]=1)#[N:23]
Reactant: Cc1c(N[C@@H](c2nnc(-c3ccc(C#N)cc3)o2)[C@@H](C)O[Si](C)(C)C(C)(C)C)ccc(C#N)c1C(F)(F)F
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: C1CCOC1
Product: Cc1c(N[C@@H](c2nnc(-c3ccc(C#N)cc3)o2)[C@@H](C)O)ccc(C#N)c1C(F)(F)F
Temperature: -55 °C
Yield: 68.7 %

Procedure:
4-((1R,2R)-2-(tert-butyldimethylsilyloxy)-1-(5-(4-cyanophenyl)-1,3,4-oxadiazol-2-yl)propylamino)-3-methyl-2-(trifluoromethyl)benzonitrile (500 mg, 0.92 mmol) was dissolved in THF and cooled to −55° C. under N2 atmosphere. TBAF (1.0M solution in 1.10 mL, 1.11 mmol) was added to the precooled solution slowly and the temperature was allowed to rise. The progress of the reaction was monitored by TLC. After the reaction was complete, it was quenched with a saturated solution of NR4Cl and extracted with EtOAc. Purification with column chromatography provided the desired product (270 mg, 68%). 1H NMR (400 MHz, acetone-d6, δ in ppm): 8.17 (d, J=9 Hz, 2H), 7.96 (d, J=9 Hz, 2H), 7.60 (d, J=9 Hz, 1H), 7.15 (d, J=9 Hz, 1H), 6.01 (d, J=9 Hz, 1H), 5.13 (m, 1H), 4.69 (d, J=6 Hz, 1H), 4.53 (m, 1H), 2.35 (m, 3H), 1.39 (d, J=6 Hz, 3H).
Reaction SMILES: C(OP([CH2:9][C:10]#[N:11])(=O)OCC)C.[H-].[Na+].[CH3:14][S:15]([N:18]1[C:22]2=[N:23][CH:24]=[CH:25][CH:26]=[C:21]2[C:20](=O)[CH2:19]1)(=[O:17])=[O:16]>O1CCCC1.O.Cl>[CH3:14][S:15]([N:18]1[C:22]2=[N:23][CH:24]=[CH:25][CH:26]=[C:21]2[C:20]([CH2:9][C:10]#[N:11])=[CH:19]1)(=[O:16])=[O:17]
Reactant: CS(=O)(=O)N1CC(=O)c2cccnc21
Reactant: CCOP(=O)(CC#N)OCC
Agent: Cl
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: O
Product: CS(=O)(=O)n1cc(CC#N)c2cccnc21
Temperature: 0 °C
Reaction time: 0.17 h
Yield: 81.2 %

Procedure:
Diethyl(cyanomethyl)phosphonate (0.47 ml, 3.1 mmol) was dissolved in tetrahydrofuran (5 ml) and cooled to 0° C. Sodium hydride (0.12 g, 3.1 mmol) was added portionwise and the reaction was stirred for 10 min. 1-Methanesulfonyl-1,2-dihydro-pyrrolo[2,3-b]pyridin-3-one (0.332 g, 1.57 mmoles) suspended in tetrahydrofuran (3 ml) was added dropwise, whereupon it immediately dissolved. The reaction was stirred at room temperature for 2 h. The reaction mixture was diluted with water and neutralized with 1M hydrochloric acid The aqueous solution was extracted with ethyl acetate. The organic extract was washed with brine, dried (sodium sulfate) and concentrated under reduced pressure. The crude product was chromatographed over silica gel eluting with 50% ethyl acetate in hexane to provide pure (1-methanesulfonyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-acetonitrile (0.30 g, 45%). 1H NMR (CDCl3) δ: 3.61 (3H, s), 3.81 (2H, s), 7.34 (1H, dd, J=4.8 Hz, 7.9 Hz), 8.02 (1H, dd, J=1.6 Hz, 7.9 Hz), 8.54 (1H, dd, J=1.6 Hz, 4.8 Hz).
Reaction SMILES: [CH:1]1([NH:4][CH:5]2[CH2:10][CH2:9][N:8]([C:11]3[C:16]([F:17])=[CH:15][C:14]([C:18]([F:21])([F:20])[F:19])=[CH:13][N:12]=3)[CH2:7][CH2:6]2)[CH2:3][CH2:2]1.[N:22]1([C:27]2[CH:35]=[CH:34][C:30]([C:31](O)=[O:32])=[CH:29][CH:28]=2)[CH:26]=[N:25][CH:24]=[N:23]1>>[CH:1]1([N:4]([CH:5]2[CH2:10][CH2:9][N:8]([C:11]3[C:16]([F:17])=[CH:15][C:14]([C:18]([F:20])([F:19])[F:21])=[CH:13][N:12]=3)[CH2:7][CH2:6]2)[C:31](=[O:32])[C:30]2[CH:29]=[CH:28][C:27]([N:22]3[CH:26]=[N:25][CH:24]=[N:23]3)=[CH:35][CH:34]=2)[CH2:2][CH2:3]1
Reactant: Fc1cc(C(F)(F)F)cnc1N1CCC(NC2CC2)CC1
Reactant: O=C(O)c1ccc(-n2cncn2)cc1
Product: O=C(c1ccc(-n2cncn2)cc1)N(C1CC1)C1CCN(c2ncc(C(F)(F)F)cc2F)CC1

Procedure:
The title compound is prepared from cyclopropyl-(3′-fluoro-5′-trifluoromethyl-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-4-yl)-amine and 4-[1,2,4]triazol-1-yl-benzoic acid following a procedure analogous to that described in Example 90. LC (method 19): tR=4.61 min; Mass spectrum (ESI+): m/z=475 [M+H]+.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=O)/[CH:9]=[CH:10]/[N:11](C)C)=[C:4]([N+:15]([O-:17])=[O:16])[CH:3]=1.Cl.[CH:19]1([NH:24]N)[CH2:23][CH2:22][CH2:21][CH2:20]1.O.C(OCC)(=O)C.[OH-].[Na+]>C(O)(=O)C>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:24]([CH:19]3[CH2:23][CH2:22][CH2:21][CH2:20]3)[N:11]=[CH:10][CH:9]=2)=[C:4]([N+:15]([O-:17])=[O:16])[CH:3]=1
Reactant: CN(C)/C=C/C(=O)c1ccc(Br)cc1[N+](=O)[O-]
Reactant: NNC1CCCC1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CCOC(C)=O
Solvent: O
Solvent: CC(=O)O
Product: O=[N+]([O-])c1cc(Br)ccc1-c1ccnn1C1CCCC1
Temperature: 25 °C
Reaction time: 60 h
Yield: 72.7 %

Procedure:
Under a nitrogen atmosphere, to a solution of 1.15 g of (2E)-1-(4-bromo-2-nitrophenyl)-3-(dimethylamino)prop-2-en-1-one in 9.2 mL of acetic acid was added 1.05 g of cyclopentylhydrazine hydrochloride, followed by stirring at room temperature for 60 hours. The reaction mixture was poured into a mixture of water/ethyl acetate, followed by adjusting to pH 10 with a 6 M aqueous sodium hydroxide solution. The aqueous layer was separated, and then the organic layer was washed with water and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and then the residue was purified by silica gel column chromatography (n-hexane/ethyl acetate) to obtain 940 mg of 5-(4-bromo-2-nitrophenyl)-1-cyclopentyl-1H-pyrazole.
Reaction SMILES: [CH3:1][C:2]1[NH:3][C:4]2[C:9]([CH:10]=1)=[CH:8][C:7]([NH2:11])=[CH:6][CH:5]=2.[N:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[CH2:18][CH2:19][NH:20][C:21]([C:23]1[S:31][C:30]2[C:25](=[N:26][CH:27]=[CH:28][C:29]=2Cl)[CH:24]=1)=[O:22]>>[N:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[CH2:18][CH2:19][NH:20][C:21]([C:23]1[S:31][C:30]2[C:25](=[N:26][CH:27]=[CH:28][C:29]=2[NH:11][C:7]2[CH:8]=[C:9]3[C:4](=[CH:5][CH:6]=2)[NH:3][C:2]([CH3:1])=[CH:10]3)[CH:24]=1)=[O:22]
Reactant: Cc1cc2cc(N)ccc2[nH]1
Reactant: O=C(NCCc1ccccn1)c1cc2nccc(Cl)c2s1
Product: Cc1cc2cc(Nc3ccnc4cc(C(=O)NCCc5ccccn5)sc34)ccc2[nH]1

Procedure:
The title compound was prepared from 2-methyl-1H-indol-5-ylamine and 7-chloro-thieno[3,2-b]pyridine-2-carboxylic acid (2-pyridin-2-yl-ethyl)-amide by a procedure analogous to Example 1C. MS: 428 (MH+), HPLC Rf: 4.33 min; HPLC purity 99%.
Reaction SMILES: C1([OH:7])C=CC=CC=1.[CH:8](Cl)(Cl)[CH:9](Cl)Cl.[CH:14]1[CH:19]=[C:18]([C:20]2[CH:25]=[CH:24][CH:23]=[C:22]([OH:26])[CH:21]=2)[C:17]([OH:27])=[CH:16][CH:15]=1>>[CH:14]1[CH:19]=[C:18]([C:20]2[CH:25]=[CH:24][CH:23]=[C:22]([OH:26])[CH:21]=2)[C:17]([OH:27])=[CH:16][CH:15]=1.[OH:7][C:23]1[CH:22]=[CH:21][C:20]([CH2:18][CH2:19][C:14]2[CH:15]=[CH:16][C:17]([OH:27])=[CH:9][CH:8]=2)=[CH:25][CH:24]=1
Reactant: ClC(Cl)C(Cl)Cl
Reactant: Oc1ccccc1
Agent: Oc1cccc(-c2ccccc2O)c1
Product: Oc1ccc(CCc2ccc(O)cc2)cc1

Procedure:
The inherent viscosity of the polyesters determined at 30° C., in a solvent combination of 60 parts by weight phenol and 40 parts by weight sym-tetrachloroethane at a concentration of 0.5 g per dl., is at least about 0.5 and is preferably at least about 0.7. The selection of acid and diphenol components is made so that the polyester preferably has a glass transition temperature of at least 100° C., a viscosity at 320° C. determined in a capillary rheometer at a shear rate of 100 sec-1 of less than 105 poise and a melting point less than about 350° C. An especially preferred group of polyarylene esters comprises those polyesters obtained by condensation of a diphenol comprising at least 90 mol percent 1,2-bis(4-hydroxyphenyl)ethane and a dicarboxylic acid comprising at least 67 mol percent isophthalic acid. Of this preferred group, one of the more preferred combinations is obtained from 1,2-bis(4-hydroxyphenyl)ethane and isophthalic acid without additional components. The preferences are based on the availability and cost of the acid as well as on the desirable glass transition and melting points of the resulting polyesters. Since molding cycles are preferably rapid, it is desirable that a crystalline polyester crystallize in the short period during which the polymer is cooling in the mold. Thus a molding material for uses where high temperature dimensional stability is important, needs to have a rapid rate of crystallization. The glass transition temperature, the melting point and the rate of crystallization can be determined by means of differential scanning calorimetry as described in copending application Ser. No. 709,469, filed July 28, 1976, now U.S. Pat. No. 4,102,864, which methods are hereby incorporated by reference.
Reaction SMILES: [SH:1][C:2]1[N:6]([CH2:7][C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[C:5]2[CH:15]=[CH:16][CH:17]=[CH:18][C:4]=2[N:3]=1.[CH2:19]([O:21][C:22](=[O:29])[CH2:23][CH2:24][CH2:25][CH2:26][CH2:27]Br)[CH3:20].C([O-])([O-])=O.[K+].[K+]>CC(C)=O>[C:11]([O:10][C:8](=[O:9])[CH2:7][N:6]1[C:5]2[CH:15]=[CH:16][CH:17]=[CH:18][C:4]=2[N:3]=[C:2]1[S:1][CH2:27][CH2:26][CH2:25][CH2:24][CH2:23][C:22]([O:21][CH2:19][CH3:20])=[O:29])([CH3:13])([CH3:14])[CH3:12]
Reactant: CC(C)(C)OC(=O)Cn1c(S)nc2ccccc21
Reactant: CCOC(=O)CCCCCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: CCOC(=O)CCCCCSc1nc2ccccc2n1CC(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 8 h
Yield: 67.6 %

Procedure:
A mixture of tert-butyl (2-mercapto-benzoimidazol-1-yl)-acetate (Intermediate 3-I, 52 mg, 0.2 mmol), 6-bromo-hexanoic acid ethyl ester (49 mg, 39 μl, 0.22 mmol) and K2CO3 (55 mg, 0.4 mmol) is refluxed in acetone (2 ml) for 5 h and stirred at rt overnight. Evaporation of the solvent in vacuo affords a residue that is purified by flash-chromatography on silica-gel (AcOEt/heptane, 25:75), yielding the title compound (55 mg) in 68% as a colourless oil: tR=7.24 min (LC-1), ESI-MS (pos.): m/z 407.23 [M+H]+, ESI-MS (neg.) 405.22 [M−H]+; 1H-NMR (CDCl3): δ (ppm) 1.25 (t, 3H CH3), 1.44 (s, 9H, tBu), 1.48 (m, 2H), 1.66 (quint., 2H), 1.79 (quint., 2H), 2.30 (t, 2H, CH2C═O), 3.38 (t, 2H, SCH2), 4.10 (q, 2H, OCH2), 4.73 (s, 2H, CH2CO2), 7.17-7.25 (m, 3Harom), 7.69 (m, 1Harom).