Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([O:14][CH2:15][CH:16]=[C:17]([Cl:19])[Cl:18])[CH:5]=[C:6]([Cl:13])[C:7]=1[O:8][CH2:9][CH2:10][CH2:11]Br.[Cl:20][C:21]1[CH:26]=[CH:25][C:24]([CH2:27][C:28]([OH:30])=[O:29])=[CH:23][CH:22]=1.C(=O)([O-])[O-].[K+].[K+].CN(C)C=O>O>[Cl:1][C:2]1[CH:3]=[C:4]([O:14][CH2:15][CH:16]=[C:17]([Cl:19])[Cl:18])[CH:5]=[C:6]([Cl:13])[C:7]=1[O:8][CH2:9][CH2:10][CH2:11][O:30][C:28](=[O:29])[CH2:27][C:24]1[CH:25]=[CH:26][C:21]([Cl:20])=[CH:22][CH:23]=1
Reactant: O=C(O)Cc1ccc(Cl)cc1
Reactant: ClC(Cl)=CCOc1cc(Cl)c(OCCCBr)c(Cl)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: O=C(Cc1ccc(Cl)cc1)OCCCOc1c(Cl)cc(OCC=C(Cl)Cl)cc1Cl
Temperature: 25 °C
Reaction time: 12 h
Yield: 90.2 %

Procedure:
In a reaction vessel were placed 0.20 g of 3,5-dichloro-4-(3-bromopropyloxy)-1-(3,3-dichloro-2-propenyloxy)benzene, 0.10 g of 4-chlorophenylacetic acid, 0.08 g of potassium carbonate and 5 ml of N,N-dimethylformamide, followed by stirring at room temperature for 12 hours. The reaction mixture was poured into water, and extracted twice with 30 ml of diethyl ether. The combined ether layer was washed with water, dried with anhydrous magnesium sulfate, and concentrated to obtain a crude product. The crude product was subjected to silica gel chromatography, which afforded 0.22 g of 3,5-dichloro-4-(3-(4-chlorophenylacetyloxy)propyloxy)-1-(3,3-dichloro-2-propenyloxy) benzene (90% yield), nD22.0 1.5698.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.[Cl:15][CH2:16][C:17](Cl)=[O:18]>C1COCC1>[Cl:15][CH2:16][C:17]([NH:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)=[O:18]
Reactant: O=C(Cl)CCl
Reactant: Nc1ccccc1
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: O=C(CCl)Nc1ccccc1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
A solution of aniline (9.31 g, 100 mmol) and triethylamine (15.2 g, 150 mmol) in THF (150 mL) is cooled to −40° C. before chloroacetic acid chloride (11.3 g, 100 mmol) is slowly added in portions such that the temperature does not rise above 0° C. After completion of the addition, the brown suspension is stirred at rt for 1 h. The dark purple mixture is poured onto water (300 mL) and extracted twice with EA (300 mL). The organic extracts are washed with sat. aq. NaHCO3, 0.5 N aq. HCl, followed by water, and evaporated. The brown residue is suspended in diethyl ether, filtered off, washed with additional diethyl ether and dried under high vacuum to give 2-chloro-N-phenyl-acetamide. LC-MS: tR=0.75 min, [M+1]+=170, 1H NMR (CDCl3): δ 8.22 (s br, 1H), 7.56-7.51 (m, 2H), 7.40-7.24 (m, 2H), 7.20-7.14 (m, 1H), 4.20 (s, 2H).
Reaction SMILES: [CH2:1]([SH:4])[CH2:2][CH3:3].C[O-].[Na+].Cl[C:9]1[O:10][C:11]([CH2:21][CH2:22][C:23]([O:25][CH3:26])=[O:24])=[C:12]([C:14]2[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=2)[N:13]=1>CO>[Cl:20][C:17]1[CH:16]=[CH:15][C:14]([C:12]2[N:13]=[C:9]([S:4][CH2:1][CH2:2][CH3:3])[O:10][C:11]=2[CH2:21][CH2:22][C:23]([O:25][CH3:26])=[O:24])=[CH:19][CH:18]=1
Reactant: COC(=O)CCc1oc(Cl)nc1-c1ccc(Cl)cc1
Reactant: CCCS
Agent: C[O-]
Agent: [Na+]
Solvent: CO
Product: CCCSc1nc(-c2ccc(Cl)cc2)c(CCC(=O)OC)o1

Procedure:
To a solution of 1-propylmercaptan (0.54 mL) in methanol (20 mL) was added sodium methoxide (1.1 g) and then methyl 3-[2-chloro-4-(4-chlorophenyl)-5-oxazolyl]propionate (1.5 g) was added. The mixture was stirred with heating under reflux for 30 min. The reaction mixture was concentrated, diluted with water, and extracted with ethyl acetate. The organic layer was washed successively with water and saturated brine, dried over anhydrous magnesium sulfate and concentrated. The residue was subjected to silica gel column chromatography, and methyl 3-[4-(4-chlorophenyl)-2-(1-propylsulfanyl)-5-oxazolyl]propionate was obtained from a fraction eluted with hexane-acetone (9:1, volume ratio). 2N Aqueous sodium hydroxide solution (5 mL) and methanol (15 mL) were added to this ester form, and the mixture was stirred at room temperature for 1 hr. The reaction mixture was diluted with water and acidified with 2N aqueous hydrochloric acid solution. The precipitated crystals were collected by filtration and recrystallized from isopropyl ether to give 3-[4-(4-chlorophenyl)-2-(1-propylsulfanyl)-5-oxazolyl]propionic acid (1.0 g, yield 63%) as colorless prism crystals. melting point: 128–129° C.
Reaction SMILES: Cl[C:2]([O:4][CH2:5][CH2:6][Cl:7])=[O:3].[NH2:8][C:9]1[CH:27]=[CH:26][CH:25]=[C:24]([CH3:28])[C:10]=1[CH2:11][NH:12][C:13]1[C:14]2[N:15]([C:19]([CH3:23])=[C:20]([CH3:22])[N:21]=2)[CH:16]=[CH:17][CH:18]=1>ClCCl>[Cl:7][CH2:6][CH2:5][O:4][C:2]([NH:8][C:9]1[CH:27]=[CH:26][CH:25]=[C:24]([CH3:28])[C:10]=1[CH2:11][NH:12][C:13]1[C:14]2[N:15]([C:19]([CH3:23])=[C:20]([CH3:22])[N:21]=2)[CH:16]=[CH:17][CH:18]=1)=[O:3]
Reactant: O=C(Cl)OCCCl
Reactant: Cc1cccc(N)c1CNc1cccn2c(C)c(C)nc12
Solvent: ClCCl
Product: Cc1cccc(NC(=O)OCCCl)c1CNc1cccn2c(C)c(C)nc12
Temperature: 25 °C
Reaction time: 16 h

Procedure:
2-Chloroethyl chloroformate (12.4 g, 81 mmol) dissolved in dichloromethane (40 ml) is added dropwise at RT, during the course of about 30 min, to a solution of 8-(2-amino-6-methylbenzylamino)-2,3-dimethylimidazo[1,2-a]pyridine (19.65 g, 70 mmol) in anhydrous dichloromethane (600 ml). The mixture is then stirred at RT for 16 h and then extracted with sodium hydrogen carbonate (4×200 ml). After extraction of the aqueous phases with dichloromethane (200 ml), the combined organic extracts are washed with water (2×200 ml), dried over magnesium sulfate and concentrated. The crude product which remains (33.9 g) is used directly for the further reaction in Example 1b.
Reaction SMILES: [C:1]1([S:7]([NH:10][C:11]2[C:16](I)=[CH:15][C:14]([S:18][CH3:19])=[CH:13][N:12]=2)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:20]([C:22]1[N:27]=[CH:26][CH:25]=[CH:24][N:23]=1)#[CH:21].O>C(N(CC)CC)C>[C:1]1([S:7]([N:10]2[C:11]3=[N:12][CH:13]=[C:14]([S:18][CH3:19])[CH:15]=[C:16]3[CH:21]=[C:20]2[C:22]2[N:27]=[CH:26][CH:25]=[CH:24][N:23]=2)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: C#Cc1ncccn1
Reactant: CSc1cnc(NS(=O)(=O)c2ccccc2)c(I)c1
Solvent: O
Solvent: CCN(CC)CC
Product: CSc1cnc2c(c1)cc(-c1ncccn1)n2S(=O)(=O)c1ccccc1
Temperature: 100 °C
Reaction time: 1.5 h
Yield: 84 %

Procedure:
A suspension of 2-benzenesulfonylamino-5-methylthio-3-iodo-pyridine (1.53 g), 2-ethynylpyrimidine (768 mg), bistriphenylphosphine palladium dichloride (259 mg) and cuprous iodide (70.3 mg) in triethylamine (37 ml) was stirred in a sealed tube at 100° C. for 1.5 hours. After cooling, the reaction solution was poured into water, extracted with chloroform, dried over, anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The resulting residue was separated using silica gel column chromatography (hexane:ethyl acetate=1:1) to obtain 1.21 g of the desired product as a white crystal.
Reaction SMILES: Cl[CH2:2][CH2:3][CH2:4][S:5]([O:8][CH2:9][C:10]([CH3:24])([CH3:23])[C@@H:11]([OH:22])[C:12]([O:14][CH2:15][C:16]1[CH:17]=[N:18][CH:19]=[CH:20][CH:21]=1)=[O:13])(=[O:7])=[O:6].[N-:25]=[N+:26]=[N-:27].[Na+]>CS(C)=O>[N:25]([CH2:2][CH2:3][CH2:4][S:5]([O:8][CH2:9][C:10]([CH3:24])([CH3:23])[C@@H:11]([OH:22])[C:12]([O:14][CH2:15][C:16]1[CH:17]=[N:18][CH:19]=[CH:20][CH:21]=1)=[O:13])(=[O:7])=[O:6])=[N+:26]=[N-:27]
Reactant: [N-]=[N+]=[N-]
Reactant: CC(C)(COS(=O)(=O)CCCCl)[C@@H](O)C(=O)OCc1cccnc1
Agent: [Na+]
Solvent: CS(C)=O
Product: CC(C)(COS(=O)(=O)CCCN=[N+]=[N-])[C@@H](O)C(=O)OCc1cccnc1

Procedure:
Following the general procedure for the preparation of azides of Description 16, 3-pyridylmethyl (2R)-4-[(3-chloropropyl)sulfonyloxy]-2-hydroxy-3,3-dimethylbutanoate (37b) (20 mg, 0.053 mmol) dissolved in 1 mL of anhydrous dimethyl sulfoxide (DMSO) was reacted with 10 mg (0.1 mmol) of sodium azide (NaN3). After work-up, the crude title compound (37c) was used in the next step without further purification.
Reaction SMILES: C([O:3][C:4]([C:6]1[CH:7]=[N:8][N:9]([C:11]2[N:20](COCC[Si](C)(C)C)[C:19](=[O:29])[C:18]3[C:13](=[CH:14][CH:15]=[C:16](I)[CH:17]=3)[N:12]=2)[CH:10]=1)=[O:5])C.[CH3:31][O:32][C:33]1[CH:34]=[C:35](B(O)O)[CH:36]=[CH:37][CH:38]=1>>[CH3:31][O:32][C:33]1[CH:38]=[C:37]([C:16]2[CH:17]=[C:18]3[C:13](=[CH:14][CH:15]=2)[N:12]=[C:11]([N:9]2[CH:10]=[C:6]([C:4]([OH:3])=[O:5])[CH:7]=[N:8]2)[NH:20][C:19]3=[O:29])[CH:36]=[CH:35][CH:34]=1
Reactant: CCOC(=O)c1cnn(-c2nc3ccc(I)cc3c(=O)n2COCC[Si](C)(C)C)c1
Reactant: COc1cccc(B(O)O)c1
Product: COc1cccc(-c2ccc3nc(-n4cc(C(=O)O)cn4)[nH]c(=O)c3c2)c1

Procedure:
The titled compound was prepared in a manner analogous to Example 69, steps C-E, using 1-[6-iodo-4-oxo-3-(2-trimethylsilanyl-ethoxymethyl)-3,4-dihydro-quinazolin-2-yl]-1H-pyrazole-4-carboxylic acid ethyl ester (Example 69 product from step B) and 3-methoxyphenylboronic acid in step C. MS (ESI): mass calcd. for C19H14N4O4, 362.1; m/z found, 363.1 [M+H]+. 1H NMR (600 MHz, DMSO-d6): 13.01 (br s, 1H), 12.91 (br s, 1H), 8.98 (s, 1H), 8.34 (s, 1H), 8.28 (s, 1H), 8.18 (d, J=6.7 Hz, 1H), 7.78 (s, 1H), 7.44 (t, J=7.9 Hz, 1H), 7.35 (d, J=7.8 Hz, 1H), 7.29 (s, 1H), 7.00 (dd, J=8.2, 1.8 Hz, 1H), 3.86 (s, 3H).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([N+]([O-])=O)[CH:5]=[CH:4][N:3]=1.[Cl:11][C:12]1[CH:17]=[CH:16][C:15]([C@@H:18]([OH:23])[C:19]([F:22])([F:21])[F:20])=[C:14]([N:24]2[CH:28]=[CH:27][C:26]([CH3:29])=[N:25]2)[CH:13]=1.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.O>[Cl:1][C:2]1[CH:7]=[C:6]([O:23][C@H:18]([C:15]2[CH:16]=[CH:17][C:12]([Cl:11])=[CH:13][C:14]=2[N:24]2[CH:28]=[CH:27][C:26]([CH3:29])=[N:25]2)[C:19]([F:22])([F:21])[F:20])[CH:5]=[CH:4][N:3]=1
Reactant: Cc1ccn(-c2cc(Cl)ccc2[C@@H](O)C(F)(F)F)n1
Reactant: O=[N+]([O-])c1ccnc(Cl)c1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: C1COCCO1
Solvent: O
Product: Cc1ccn(-c2cc(Cl)ccc2[C@@H](Oc2ccnc(Cl)c2)C(F)(F)F)n1
Temperature: 80 °C

Procedure:
To a solution of 2-chloro-4-nitropyridine (200 mg, 1.00 mmol) in 1,4-dioxane (6 mL) was added. (R)-1-(4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl)-2,2,2-trifluoroethanol (368 mg, 1.27 mmol), and Cs2CO3 (828 mg, 2.54 mmol). The reaction was heated to 80° C. for 12 h, then cooled to RT, diluted with water, and extracted with EtOAc. The combined organic layers were dried over Na2SO4, filtered, and concentrated in vacuo. Purification by normal phase silica gel column (EtOAc/heptane) provided (R)-2-chloro-4-(1-(4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl)-2,2,2-trifluoroethoxy)pyridine as an off-white solid.
Reaction SMILES: Cl.[CH:2]([C:5]1[CH:10]=[CH:9][C:8]([CH:11]2[C:15]3([CH2:20][CH2:19][NH:18][CH2:17][CH2:16]3)[O:14][C:13]3[C:21]([CH3:27])=[C:22]([CH3:26])[CH:23]=[C:24]([CH3:25])[C:12]2=3)=[CH:7][CH:6]=1)([CH3:4])[CH3:3].C=O.[C:30]([BH3-])#N.[Na+]>C(#N)C>[CH:2]([C:5]1[CH:10]=[CH:9][C:8]([CH:11]2[C:15]3([CH2:16][CH2:17][N:18]([CH3:30])[CH2:19][CH2:20]3)[O:14][C:13]3[C:21]([CH3:27])=[C:22]([CH3:26])[CH:23]=[C:24]([CH3:25])[C:12]2=3)=[CH:7][CH:6]=1)([CH3:4])[CH3:3]
Reactant: Cc1cc(C)c2c(c1C)OC1(CCNCC1)C2c1ccc(C(C)C)cc1
Reactant: [BH3-]C#N
Agent: C=O
Agent: Cl
Agent: [Na+]
Solvent: CC#N
Product: Cc1cc(C)c2c(c1C)OC1(CCN(C)CC1)C2c1ccc(C(C)C)cc1
Temperature: 0 °C
Reaction time: 1 h
Yield: 39.5 %

Procedure:
To a suspension of 3-(4-isopropylphenyl)-4,6,7-trimethylspiro[benzofuran-2(3H),4′-piperidine] hydrochloride (389.6 mg, 1.01 mmol) in acetonitrile (5 ml) was added 37% formalin (2.0 ml) and the mixture was cooled to 0° C. Sodium cyanoborohydride (101.8 mg, 1.62 mmol) was added into this mixture and the mixture was stirred at room temperature for 1 hour. The reaction mixture was concentrated under reduced pressure and an aqueous saturated solution of sodium hydrogen carbonate was added to the residue. The product was extracted twice with ethyl acetate. The combined extracts were washed with water, dried on magnesium sulfate, filtered, and then concentrated under reduced pressure. The residue was subjected to column chromatography (on Chromatorex NHDM1020 (trade name, manufactured by Fuji Silysia Chemical Ltd.); hexane-ethyl acetate 10:1) to obtain 145.0 mg (40% yield) of the title compound. Melting point: 63-64° C. (Petroleum ether).
Reaction SMILES: [CH:1]([O:4][C:5](=[O:14])[C:6]1[CH:11]=[C:10]([Cl:12])[C:9](Cl)=[N:8][CH:7]=1)([CH3:3])[CH3:2].[CH2:15]([NH:17][CH3:18])[CH3:16]>CC(=O)OCC>[CH:1]([O:4][C:5](=[O:14])[C:6]1[CH:11]=[C:10]([Cl:12])[C:9]([N:17]([CH2:15][CH3:16])[CH3:18])=[N:8][CH:7]=1)([CH3:3])[CH3:2]
Reactant: CCNC
Reactant: CC(C)OC(=O)c1cnc(Cl)c(Cl)c1
Solvent: CCOC(C)=O
Product: CCN(C)c1ncc(C(=O)OC(C)C)cc1Cl
Temperature: 105 °C
Reaction time: 72 h
Yield: 90.5 %

Procedure:
A mixture of 5,6-dichloro nicotinic acid isopropyl ester (4.76 g, 22.3 mmol) and ethylmethylamine (6.88 g, 116.4 mmol) is stirred in a sealed vessel at 105° C. for 72 h. The mixture is cooled to rt, diluted with EA (300 mL) and washed with sat. aq. NaHCO3-solution (3×10 mL) followed by brine (10 mL). The org. extract is dried over MgSO4, filtered, concentrated and dried to give 5-chloro-6-(ethyl-methyl-amino)-nicotinic acid isopropyl ester (5.18 g) as a yellow oil; LC-MS: tR=1.38 min, [M+1]+=257.02; 1H NMR (D6-DMSO): δ 1.19 (t, J=6.8 Hz, 3H), 1.30 (d, J=6.0 Hz, 6H), 3.08 (s, 3H), 3.55 (q, J=7.0 Hz, 2H), 5.10 (hept, J=6.3 Hz, 1H), 7.98 (s, 1H), 8.58 (s, 1H).
Reaction SMILES: Cl[C:2]1[C:7]([N+:8]([O-:10])=[O:9])=[CH:6][CH:5]=[C:4]([Cl:11])[C:3]=1[CH3:12].[C:13]([Cu])#[N:14].CN(C=O)C>C(OCC)(=O)C>[Cl:11][C:4]1[C:3]([CH3:12])=[C:2]([C:7]([N+:8]([O-:10])=[O:9])=[CH:6][CH:5]=1)[C:13]#[N:14]
Reactant: N#C[Cu]
Reactant: Cc1c(Cl)ccc([N+](=O)[O-])c1Cl
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: Cc1c(Cl)ccc([N+](=O)[O-])c1C#N
Yield: 60.2 %

Procedure:
A solution of 10 g (49 mmol) of 2,6-dichloro-3-nitrotoluene and 4.8 g (54.0 mmol) of CuCN in 100 ml of abs. DMF was stirred at 150° C. for 6 h, a further 2.4 g (27.0 mmol) of CuCN being added after 4 h. The solvent was stripped off and the residue obtained taken up in ethyl acetate. The precipitate deposited was filtered off and extracted several times with warm ethyl acetate. The combined ethyl acetate solutions were washed with H2O, dilute ammonia solution, and saturated NaCl solution, dried over Na2SO4, and concentrated to dryness. The resulting yellow, crystalline residue was purified by column chromatography on SiO2 using EA/n-heptane 1:10 as a solvent. 5.8 g of the title compound resulted in the form of yellow crystals.
Reaction SMILES: [OH-].[Na+].C([O:5][C:6](=[O:28])[CH2:7][C:8]1[CH:9]=[C:10]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH:11]=[C:12]([O:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH:13]=1)C>CCO.Cl>[CH2:15]([O:14][C:12]1[CH:13]=[C:8]([CH2:7][C:6]([OH:28])=[O:5])[CH:9]=[C:10]([C:22]2[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=2)[CH:11]=1)[C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1
Reactant: CCOC(=O)Cc1cc(OCc2ccccc2)cc(-c2ccccc2)c1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: O=C(O)Cc1cc(OCc2ccccc2)cc(-c2ccccc2)c1
Temperature: 25 °C
Reaction time: 12 h
Yield: 88.6 %

Procedure:
NaOH solution (1 ml, 1M aq) was added to a solution of (5-benzyloxy-biphenyl-3-yl)acetic acid ethyl ester (0.12 g, 0.35 mmol) in EtOH (2 ml) and the mixture was stirred at room temperature for 12 h. The reaction mixture was diluted with HCl solution (2M aq) and extracted with EtOAc (×3). The combined organic extracts were washed with water, brine, dried (MgSO4), filtered and concentrated under reduced pressure to give (5-benzyloxybiphenyl-3-yl)acetic acid (0.12 g, 0.31 mmol) as colourless solid in 90% yield. 1H NMR (CDCl3) δ 7.57-7.56 (m, 2H), 7.48-7.30 (m, 8H), 7.15-7.10 (m, 2H), 6.94-6.90 (m, 1H), 5.11 (s, 2H), 3.69 (s, 2H); LCMS method (A), RT=4.2 min.
Reaction SMILES: [F:1][C:2]1[CH:10]=[CH:9][C:5]([C:6](Cl)=[O:7])=[CH:4][C:3]=1[N+:11]([O-:13])=[O:12].[F:14][C:15]1[CH:16]=[CH:17][C:18]([NH2:21])=[N:19][CH:20]=1>>[F:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([NH:21][C:18]2[CH:17]=[CH:16][C:15]([F:14])=[CH:20][N:19]=2)=[O:7])=[CH:4][C:3]=1[N+:11]([O-:13])=[O:12]
Reactant: O=C(Cl)c1ccc(F)c([N+](=O)[O-])c1
Reactant: Nc1ccc(F)cn1
Product: O=C(Nc1ccc(F)cn1)c1ccc(F)c([N+](=O)[O-])c1
Yield: 98 %

Procedure:
The product from Example 172a was reacted with 5-Fluoro-pyridin-2-ylamine (165 mg, 1.474 mmol) according to the procedure from Example 172a to provide the title compound (404 mg, 98%).
Reaction SMILES: [OH:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][CH:7]=1.C(=O)([O-])[O-].[K+].[K+].CN(C)C=O.F[C:20]1[CH:21]=[C:22]([O:30][C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=2[O:37][CH3:38])[C:23]([N+:27]([O-:29])=[O:28])=[C:24]([CH:26]=1)[NH2:25]>C(OCC)(=O)C>[CH3:38][O:37][C:32]1[CH:33]=[CH:34][CH:35]=[CH:36][C:31]=1[O:30][C:22]1[C:23]([N+:27]([O-:29])=[O:28])=[C:24]([CH:26]=[C:20]([O:1][C:2]2[CH:3]=[N:4][CH:5]=[CH:6][CH:7]=2)[CH:21]=1)[NH2:25]
Reactant: COc1ccccc1Oc1cc(F)cc(N)c1[N+](=O)[O-]
Reactant: Oc1cccnc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: COc1ccccc1Oc1cc(Oc2cccnc2)cc(N)c1[N+](=O)[O-]
Temperature: 90 °C
Reaction time: 8 h

Procedure:
1.24 g of 3-hydroxypyridine and 5.42 g of potassium carbonate were added to a dimethylformamide (30 ml) solution of 3.03 g of 5-fluoro-3-(2-methoxyphenoxy)-2-nitroaniline, and the reaction liquid was stirred overnight at 90° C. The reaction liquid was diluted with ethyl acetate, washed with water and saturated saline in order, and then dried with anhydrous magnesium sulfate. The solvent was evaporated away under reduced pressure, and the resulting residue was purified through silica gel column chromatography (developing solvent: hexane/ethyl acetate=2/1 to 1/1 to 1/2) to obtain the entitled compound as an orange solid.
Reaction SMILES: [BH4-].[Li+].[Cl:3][C:4]1[CH:5]=[CH:6][C:7]([C:28](OC)=[O:29])=[C:8]2[C:12]=1[N:11]=[C:10]1[N:13]([C:17]3[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][C:18]=3[C:24]([F:27])([F:26])[F:25])[CH2:14][CH2:15][CH2:16][N:9]21>O1CCCC1>[Cl:3][C:4]1[C:12]2[N:11]=[C:10]3[N:13]([C:17]4[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][C:18]=4[C:24]([F:26])([F:25])[F:27])[CH2:14][CH2:15][CH2:16][N:9]3[C:8]=2[C:7]([CH2:28][OH:29])=[CH:6][CH:5]=1
Reactant: COC(=O)c1ccc(Cl)c2nc3n(c12)CCCN3c1ccc(Cl)cc1C(F)(F)F
Agent: [BH4-]
Agent: [Li+]
Solvent: C1CCOC1
Product: OCc1ccc(Cl)c2nc3n(c12)CCCN3c1ccc(Cl)cc1C(F)(F)F
Temperature: 50 °C
Reaction time: 4 h
Yield: 86.5 %

Procedure:
Lithium borohydride (2.14 g, 98.1 mmol) was added to a stirred solution of methyl 9-chloro-1-[4-chloro-2-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazole-6-carboxylate (10.9 g, 24.5 mmol) in tetrahydrofuran (80 mL) at room temperature, and the mixture was stirred at room temperature for 12 hr and at 50° C. for 4 hr. The reaction was quenched by methanol, and the mixture was diluted with aqueous saturated ammonium chloride at 0° C. and extracted with ethyl acetate. The combined organic layer was washed with brine, dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo. The residue was washed with ethyl acetate/diisopropyl ether to give the title compound as a colorless powder (8.81 g, 21.2 mmol, 87%).
Reaction SMILES: [CH3:1][O:2][C:3]1[C:4]([NH2:9])=[CH:5][CH:6]=[CH:7][CH:8]=1.[F:10][C:11]1[CH:16]=[CH:15][C:14]([S:17](Cl)(=[O:19])=[O:18])=[CH:13][CH:12]=1>>[F:10][C:11]1[CH:16]=[CH:15][C:14]([S:17]([NH:9][C:4]2[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=2[O:2][CH3:1])(=[O:19])=[O:18])=[CH:13][CH:12]=1
Reactant: COc1ccccc1N
Reactant: O=S(=O)(Cl)c1ccc(F)cc1
Product: COc1ccccc1NS(=O)(=O)c1ccc(F)cc1
Yield: 93.1 %

Procedure:
Using o-anisidine (1.0 ml, 8.55 mmol) and 4-fluorobenzenesulfonyl chloride (1.7 g, 8.55 mmol), the procedure of Reference Example 2 was repeated to obtain 2.24 g (93.1%) of the title compound in the form of colorless prism crystals.
Reaction SMILES: [C:1]1([N:7]2[C:19]3[CH:18]=[CH:17][C:16](B(O)O)=[CH:15][C:14]=3[C:13]3[C:8]2=[CH:9][CH:10]=[CH:11][CH:12]=3)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Br[C:24]1[N:29]=[CH:28][C:27]([C:30]2[CH:31]=[N:32][C:33](Br)=[CH:34][CH:35]=2)=[CH:26][CH:25]=1.C([O-])([O-])=O.[Na+].[Na+].O>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1COCC1>[C:1]1([N:7]2[C:19]3[CH:18]=[CH:17][C:16]([C:24]4[N:29]=[CH:28][C:27]([C:30]5[CH:31]=[N:32][C:33]([C:16]6[CH:17]=[CH:18][C:19]7[N:7]([C:1]8[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=8)[C:8]8[C:13]([C:14]=7[CH:15]=6)=[CH:12][CH:11]=[CH:10][CH:9]=8)=[CH:34][CH:35]=5)=[CH:26][CH:25]=4)=[CH:15][C:14]=3[C:13]3[C:8]2=[CH:9][CH:10]=[CH:11][CH:12]=3)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: OB(O)c1ccc2c(c1)c1ccccc1n2-c1ccccc1
Reactant: Brc1ccc(-c2ccc(Br)nc2)cn1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O
Solvent: C1CCOC1
Product: c1ccc(-n2c3ccccc3c3cc(-c4ccc(-c5ccc(-c6ccc7c(c6)c6ccccc6n7-c6ccccc6)nc5)cn4)ccc32)cc1
Temperature: 85 °C
Yield: 64.2 %

Procedure:
A mixture of (9-phenyl-9H-carbazol-3-yl)boronic acid (1.41 g, 4.92 mmol), 6,6′-dibromo-3,3′-bipyridine (0.750 g, 2.39 mmol), tetrakis(triphenylphosphine)palladium(0) (0.166 g, 0.143 mmol), Na2CO3 (1.59 g, 15.0 mmol), H2O (15 mL) and THF (25 mL) was degassed with argon for about 25 min while stirring. The reaction mixture was then maintained at about 85° C. under argon. Upon confirming consumption of the starting material by thin layer chromatography (TLC) (SiO2, dichloromethane), the reaction was cooled to RT and poured over CH2Cl2 (ca. 350 mL). The organics were then washed with saturated NaHCO3, H2O and brine, dried over MgSO4, filtered and concentrated in vacuo. Purification of the crude via flash chromatography (SiO2, 100% CH2Cl2 to 29:1 CH2Cl2-acetone) afforded Compound 22 (0.98 g, 64%) as an off-white solid. MS (ES+) m/z: 639 (C46H30N4 requires 639).
Reaction SMILES: [CH3:1][C:2]1[S:6][C:5]2[CH:7]=[C:8]([O:11][CH2:12][CH2:13]OS(C)(=O)=O)[CH:9]=[CH:10][C:4]=2[C:3]=1[C:19]1[CH:24]=[CH:23][C:22]([C:25]([F:28])([F:27])[F:26])=[CH:21][CH:20]=1.[CH3:29][NH2:30]>C(O)C.CN(C)C(=O)C>[CH3:29][NH:30][CH2:13][CH2:12][O:11][C:8]1[CH:9]=[CH:10][C:4]2[C:3]([C:19]3[CH:24]=[CH:23][C:22]([C:25]([F:28])([F:27])[F:26])=[CH:21][CH:20]=3)=[C:2]([CH3:1])[S:6][C:5]=2[CH:7]=1
Reactant: Cc1sc2cc(OCCOS(C)(=O)=O)ccc2c1-c1ccc(C(F)(F)F)cc1
Reactant: CN
Solvent: CC(=O)N(C)C
Solvent: CCO
Product: CNCCOc1ccc2c(-c3ccc(C(F)(F)F)cc3)c(C)sc2c1

Procedure:
In analogy to the method described in example 17.1, Methanesulfonic acid 2-[2-methyl-3-(4-trifluoromethyl-phenyl)-benzo[b]thiophen-6-yloxy]-ethyl ester (example 50.2) was treated with methylamine in ethanol and N,N-dimethylacetamide to yield Methyl-{2-[2-methyl-3-(4-trifluoromethyl-phenyl)-benzo[b]thiophen-6-yloxy]-ethyl}-amine as colorless oil, MS: 366 (MH+).
Reaction SMILES: C[C@@H]1N(S(O)(=O)=O)C(=[O:5])[C@H]1NC(/C(/C1N=C(N)SC=1)=N\OC(C(O)=O)(C)C)=O.C(N(CCCC)CCCC)CCC.OC1C2N=NNC=2C=CC=1.CN(C1C=CC=CN=1)C.[CH:61]1([N:67]=[C:68]=[N:69][CH:70]2[CH2:75][CH2:74][CH2:73][CH2:72][CH2:71]2)[CH2:66][CH2:65][CH2:64][CH2:63][CH2:62]1>CN(C)C=O>[C:68]([NH:67][CH:61]1[CH2:62][CH2:63][CH2:64][CH2:65][CH2:66]1)([NH:69][CH:70]1[CH2:75][CH2:74][CH2:73][CH2:72][CH2:71]1)=[O:5]
Reactant: C(=NC1CCCCC1)=NC1CCCCC1
Reactant: C[C@H]1[C@H](NC(=O)/C(=N\OC(C)(C)C(=O)O)c2csc(N)n2)C(=O)N1S(=O)(=O)O
Agent: CN(C)c1ccccn1
Agent: Oc1cccc2[nH]nnc12
Solvent: CN(C)C=O
Solvent: CCCCN(CCCC)CCCC
Product: O=C(NC1CCCCC1)NC1CCCCC1
Reaction time: 0.5 h
Yield: 44.8 %

Procedure:
To a solution of aztreonam (2.29 g, 5.27 mmol) in 35 ml dimethylformamide were added tributylamine (0.97 g, 5.27 mmol), hydroxybenzotriazole (0.78 g, 5.79 mmol), dimethylaminopyridine (0.064 g, 0.53 mmol) and dicyclohexylcarbodiimide (1.19 g, 5.79 mmol). After stirring for 30 minutes, the resulting dicyclohexylurea (0.47 g, 40.1%) was filtered off and solution (a) was added to the filtrate. After stirring overnight at room temperature, the mixture was filtered (yielding 0.53 g, 45% of dicyclohexylurea) and evaporated. The residue was taken up in acetone, filtered, and 9.0 ml of 10% potassium perfluorobutane sulfonic acid in acetone were added. The resulting precipitate was filtered off (1.70 g), dissolved in water and chromatographed on XAD under MPLC conditions with a water - acetonitrile gradient. The sample-containing fractions were collected and freeze-dried to give 250 mg (6.9%) of Example 3.