Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [I-].[NH2:2][N+:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[NH2:9].[C:10]1(=O)[O:14][CH2:13][CH2:12][CH2:11]1.C(=O)([O-])[O-].[K+].[K+]>>[OH:14][CH2:13][CH2:12][CH2:11][C:10]1[N:9]=[C:4]2[CH:5]=[CH:6][CH:7]=[CH:8][N:3]2[N:2]=1
Reactant: O=C1CCCO1
Reactant: Nc1cccc[n+]1N
Agent: O=C([O-])[O-]
Agent: [I-]
Agent: [K+]
Product: OCCCc1nc2ccccn2n1
Reaction time: 8 h

Procedure:
A mixture of 24 g of 1,2-diaminopyridinium iodide, 17.2 g of γ-butyrolactone and 57 g of potassium carbonate in 100 ml of diethylcellosolve was refluxed with stirring for 8 hours. The mixture was concentrated under reduced pressure to the residue, which was extracted by hot dichloromethane. The solvent was removed to give crude 2-(3-hydroxypropyl)-s-triazolo[1,5-a]pyridine, which was recrystallized from ethyl acetate to colorless needles (16 g, 90%), mp 71.5°-73° C. Anal. Calcd. for C9H11ON3 : C, 61.00; H, 6.24; N, 23.72. Found: C, 60.82; H, 6.14; N, 23.48.
Reaction SMILES: C(O[C:6]([N:8]1[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]1)=O)(C)(C)C.ClC[C:16](Cl)=[O:17].[CH3:19][O:20][CH2:21][CH2:22][NH:23][CH2:24][CH2:25][O:26][CH3:27]>>[CH3:19][O:20][CH2:21][CH2:22][N:23]([CH2:24][CH2:25][O:26][CH3:27])[C:16](=[O:17])[CH2:6][N:8]1[CH2:9][CH2:10][NH:11][CH2:12][CH2:13]1
Reactant: O=C(Cl)CCl
Reactant: CC(C)(C)OC(=O)N1CCNCC1
Reactant: COCCNCCOC
Product: COCCN(CCOC)C(=O)CN1CCNCC1

Procedure:
The title compound was prepared from 1-tert-butyloxycarbonyl-piperazine, chloroacetylchloride and N,N-bis-(2-methoxy-ethyl)amine in an analogous manner as described in example 21.
Reaction SMILES: C([O:3][C:4](=[O:15])[C:5]([C:7]1[S:8][C:9]([Cl:14])=[C:10]([Cl:13])[C:11]=1[Cl:12])=[O:6])C.Cl>CC(C)=O.O>[Cl:12][C:11]1[C:10]([Cl:13])=[C:9]([Cl:14])[S:8][C:7]=1[C:5](=[O:6])[C:4]([OH:15])=[O:3]
Reactant: CCOC(=O)C(=O)c1sc(Cl)c(Cl)c1Cl
Agent: Cl
Solvent: O
Solvent: CC(C)=O
Product: O=C(O)C(=O)c1sc(Cl)c(Cl)c1Cl
Temperature: 25 °C

Procedure:
A solution of (3,4,5-trichlorothiophen-2-yl)-oxo-acetic acid ethyl ester (0.25 g, 0.86 mmol) in acetone (6 ml), water (2 ml), and conc. HCl (6 ml) was stirred under reflux for 1.5 hours. The reaction mixture was allowed to cool to ambient temperature then evaporation of acetone gave rise to solids which were collected, washed with water and dried. (3,4,5-trichlorothiophen-2-yl)-oxo-acetic acid was thus obtained as a light yellow solid (99 mg, 50%). MS (M−H)−: 258.74; 13C NMR (75 MHz, DMSO-d6) δ174.16, 162.74, 134.73, 130.43, 125.92, 125.26. IR (KBr) cm−1 3547.5, 2855.3, 2515.5, 1924.8, 1716.3, 1667.1, 1405.7, 1339.7, 1305.4
Reaction SMILES: [CH2:1]([O:3][C:4]1[CH:5]=[C:6](/[CH:18]=[CH:19]/[C:20]([O:22][CH3:23])=[O:21])[CH:7]=[CH:8][C:9]=1OS(C(F)(F)F)(=O)=O)[CH3:2].[CH3:24][O:25][C:26]1[CH:31]=[CH:30][C:29](OB(O)O)=[CH:28][CH:27]=1.C(=O)(O)[O-].[Na+]>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.C(COC)OC>[CH2:1]([O:3][C:4]1[CH:5]=[C:6](/[CH:18]=[CH:19]/[C:20]([O:22][CH3:23])=[O:21])[CH:7]=[CH:8][C:9]=1[C:29]1[CH:30]=[CH:31][C:26]([O:25][CH3:24])=[CH:27][CH:28]=1)[CH3:2]
Reactant: CCOc1cc(/C=C/C(=O)OC)ccc1OS(=O)(=O)C(F)(F)F
Reactant: COc1ccc(OB(O)O)cc1
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: COCCOC
Product: CCOc1cc(/C=C/C(=O)OC)ccc1-c1ccc(OC)cc1
Reaction time: 15 h

Procedure:
A mixture of 1.0 g (2.82 mmol) of methyl 3(E)-(3-ethoxy-4-trifluoromethanesulfonyloxyphenyl)acrylate, 0.47 g (3.10 mmol) of 4-methoxyphenylboric acid, 0.71 g (8.46 mmol) of sodium bicarbonate and 20 ml of dimethoxyethane is flushed three times with argon, 163 mg (0.14 mmol) of tetrakis(triphenylphosphine)palladium(0) are then added and the reaction is then allowed to continue for 15 hours at 80° C. Thereafter, the reaction mixture is cooled and is partitioned between ethyl acetate and water and the organic phase is washed with water and dried over magnesium sulfate, filtered and evaporated down. The residue is chromatographed over 100 g of silica gel using toluene/ethyl acetate (3:1). This gives methyl 3(E)-(2-ethoxy-4′-methoxybiphenyl-4-yl)acrylate.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:12])[C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([NH2:10])[C:5]=1[NH2:11].[CH3:13][C:14]([CH3:19])([CH3:18])[C:15](Cl)=[O:16]>N1C=CC=CC=1>[CH3:1][O:2][C:3](=[O:12])[C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([NH:10][C:15](=[O:16])[C:14]([CH3:19])([CH3:18])[CH3:13])[C:5]=1[NH2:11]
Reactant: CC(C)(C)C(=O)Cl
Reactant: COC(=O)c1cccc(N)c1N
Solvent: c1ccncc1
Product: COC(=O)c1cccc(NC(=O)C(C)(C)C)c1N
Reaction time: 16 h
Yield: 78.3 %

Procedure:
To a solution of 2,3-diaminobenzoic acid methyl ester (2.3 g, 13.8 mmol) in pyridine (40 mL) at room temperature was added 2,2-dimethylpropionyl chloride (1.7 g, 14.0 mmol). The solution was stirred at for 16 h, evaporated, and the residue partitioned between ethyl acetate (100 mL) and 1M aqueous hydrochloric acid (100 mL). The organic phase was separated, washed with 1M aqueous hydrochloric acid (100 mL), dried over sodium sulfate and evaporated to afford the title compound as a dark oil (2.7 g, 10.8 mmol, 78%) which was used without further purification. (m/z): [M+H]+ calcd for C13H18N2O3 251.14. found 250.8.
Reaction SMILES: [C:1]1([CH2:7][CH2:8][CH2:9][NH2:10])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CN1CCOCC1.[CH3:18][N:19]([CH3:37])[C:20]1([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][N:32]=2)[CH2:25][CH2:24][C:23]([CH2:27][C:28](O)=[O:29])(O)[CH2:22][CH2:21]1.C1(N=C=NC2CCCCC2)CCCCC1.[OH-].[Na+]>O.CN(C)C=O>[CH3:37][N:19]([CH3:18])[C:20]1([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][N:32]=2)[CH2:25][CH2:24][C:23](=[CH:27][C:28]([NH:10][CH2:9][CH2:8][CH2:7][C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)=[O:29])[CH2:22][CH2:21]1
Reactant: CN(C)C1(c2ccccn2)CCC(O)(CC(=O)O)CC1
Reactant: NCCCc1ccccc1
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CN1CCOCC1
Solvent: CN(C)C=O
Product: CN(C)C1(c2ccccn2)CCC(=CC(=O)NCCCc2ccccc2)CC1
Temperature: 0 °C
Reaction time: 120 h
Yield: 27 %

Procedure:
3-phenylpropylamine (270 mg, 2.0 mmol) and N-methylmorpholine (0.444 ml, 4.0 mmol) were added to a solution of (4-dimethylamino-1-hydroxy-4-pyridin-2-yl-cyclohexyl)acetic acid (556 mg, 2.0 mmol) in abs. dimethylformamide (30 ml) under argon. The solution was cooled to 0° C., dicyclohexylcarbodiimide (825 mg, 4.0 mmol) was added and the mixture was stirred at RT for 5 d. Working up of the mixture was carried out by separating off the urea which had precipitated out and introducing the filtrate into a mixture of saturated NaCl solution (40 ml) and saturated NaHCO3 solution (10 ml). Still further urea thereby precipitated out and was separated off. The aqueous phase was diluted with water (300 ml), 5 M sodium hydroxide solution (7 ml, 35 mmol) was added and the mixture was stored at 5° C. for 16 h. The crude product thereby precipitated out as a beige-coloured oily compound (22.8 mg, 30%). After chromatography on silica gel (40 g) with EA/methanol (4:1), the amide was obtained as a beige-coloured oil in a yield of 27% (203 mg).
Reaction SMILES: [CH2:1]([CH:8]1[CH2:12][CH2:11][N:10]([S:13]([C:16](=[CH:19]OCC)[C:17]#[N:18])(=O)=[O:14])[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH2:23].[NH2:24][NH2:25]>C(O)C>[CH2:1]([CH:8]1[CH2:12][CH2:11][N:10]([S:13]([C:16]2[CH:19]=[N:25][NH:24][C:17]=2[NH2:18])(=[O:14])=[O:23])[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: NN
Reactant: O
Reactant: CCOC=C(C#N)S(=O)(=O)N1CCC(Cc2ccccc2)C1
Solvent: CCO
Product: Nc1[nH]ncc1S(=O)(=O)N1CCC(Cc2ccccc2)C1

Procedure:
A 2 mL ethanol solution containing 0.079 g (0.247 mmol) of 3 was treated with 0.013 mL (0.27 mmol) of hydrazine monohydrate and heated to reflux for 5 h. The reaction was concentrated in vacuo to give crude 4-(3-benzylpyrrolidine-1-sulfonyl)-2H-pyrazol-3-ylamine. The crude pyrazole thus obtained was dissolved in 2 mL of 2-methoxyethanol containing 0.044 g (0.27 mmol) of 3-methyl-1-phenyl-but-2-en-1-one and 0.038 mL (0.49 mmol) of trifluoroacetic acid was added. The mixture was refluxed for three days then concentrated and purified by flash chromatography eluting with 60% hexanes/AcOEt to give 3-(3-benzylpyrrolidine-1-sulfonyl)-7,7-dimethyl-5-phenyl-4,7-dihydropyrazolo[1,5-a]pyrimidine that was found to be only 90% pure by HPLC analysis. This material was then dissolved in 1 mL of 1:1 THF:ethanol and 0.010 g of 10% palladium on carbon. The reaction vessel was capped with a rubber septum and charged with hydrogen via a balloon. After 90 min at room temperature, the catalyst was removed via filtration and the filtrate concentrated to an oil. Purification by flash chromatography eluting with 75% hexanes/AcOEt gave 0.024 g (20% from 3) of the title compound as a light yellow oil. 1H NMR (CDCl3) δ 1.55-1.66 (m, 7H), 1.94-2.03 (m, 1H), 2.08-2.16 (m, 2H), 2.37-2.50 (m, 1H), 2.58-2.70 (m, 2H), 2.90-2.97 (m, 1H), 3.18-3.27 (m, 1H), 3.31-3.42 (m, 2H), 4.53-4.60 (m, 1H), 5.71 (s, 1H), 7.11-7.14 (m, 2H), 7.19-7.23 (m, 1H), 7.26-7.40 (m, 7H), 7.53 (s, 1H). MS Calcd.: 450. Found: 451 (M+H).
Reaction SMILES: [Cl:1][C:2]1[N:3]=[C:4](Cl)[C:5]2[S:10][CH:9]=[CH:8][C:6]=2[N:7]=1.[CH2:12]([NH2:15])[CH2:13][CH3:14].C(N(C(C)C)C(C)C)C>O1CCCC1>[Cl:1][C:2]1[N:3]=[C:4]([CH2:14][CH2:13][CH2:12][NH2:15])[C:5]2[S:10][CH2:9][CH2:8][C:6]=2[N:7]=1
Reactant: Clc1nc(Cl)c2sccc2n1
Reactant: CCCN
Solvent: CCN(C(C)C)C(C)C
Solvent: C1CCOC1
Product: NCCCc1nc(Cl)nc2c1SCC2
Temperature: 25 °C
Reaction time: 20 h
Yield: 86.7 %

Procedure:
10.4 g (50.2 mmol) of 2,4-dichlorothieno[3,2-d]pyrimidine (VII), 8.2 mL (100 mmol) of N-propylamine, and 17.5 mL (100 mmol) of N-ethyldiisopropylamine are placed in 100 mL of tetrahydrofuran and stirred for 20 hours at ambient temperature. The suspension is filtered, the filtrate is concentrated by evaporation. The residue is combined with 100 mL of water and treated in the ultrasound bath. Solid substance is suction filtered, dried, and stirred with 50 mL of petroleum ether. 10.0 g of the product VIII (86%) is obtained as a powder.
Reaction SMILES: [O:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[CH:6]([N:8]1[CH2:13][CH2:12][O:11][CH2:10][CH2:9]1)[CH3:7].S([O-])([O-])(=O)=S.[Na+].[Na+].[Br:21]Br>C(Cl)Cl>[Br:21][C:5]1[O:1][C:2]([CH:6]([N:8]2[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)[CH3:7])=[CH:3][CH:4]=1
Reactant: BrBr
Reactant: CC(c1ccco1)N1CCOCC1
Agent: O=S([O-])([O-])=S
Agent: [Na+]
Solvent: ClCCl
Product: CC(c1ccc(Br)o1)N1CCOCC1
Temperature: 0 °C
Yield: 42 %

Procedure:
4-(1-furan-2-yl-ethyl)-morpholine (1.1 mmol) was taken up in DCM (5 ml) and stirred at 0° C. Nitrogen was passed through the reaction vessel and bubbled out through a Dreschel bottle containing a saturated aqueous solution of sodium thiosulphate, whilst bromine (1.54 mmol in 2 ml DCM) was added dropwise. After addition the reaction was stirred at room temperature for 2 h, then diluted with more DCM, washed twice with 2M Na2CO3 solution, dried over Na2SO4 and concentrated in-vacuo. After purification by flash chromatography (silica, 5 to 10% EtOAc in hexane), 4-[1-(5-bromo-furan-2-yl)-ethyl]-morpholine was obtained as a golden oil: m/z in MS ES+=260, 262 [M+H]+, 0.46 mmol, 42% yield.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[CH:4][C:5]([NH:11][C:12]2[C:17]([Cl:18])=[CH:16][N:15]=[C:14](Cl)[N:13]=2)=[C:6]([CH:10]=1)[C:7]([NH2:9])=[O:8].[N:20]1([CH2:25][C:26]2[CH:27]=[C:28]([CH:30]=[CH:31][CH:32]=2)[NH2:29])[CH2:24][CH2:23][CH2:22][CH2:21]1>>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([NH:11][C:12]2[C:17]([Cl:18])=[CH:16][N:15]=[C:14]([NH:29][C:28]3[CH:30]=[CH:31][CH:32]=[C:26]([CH2:25][N:20]4[CH2:21][CH2:22][CH2:23][CH2:24]4)[CH:27]=3)[N:13]=2)=[C:6]([CH:10]=1)[C:7]([NH2:9])=[O:8]
Reactant: NC(=O)c1cc(Br)ccc1Nc1nc(Cl)ncc1Cl
Reactant: Nc1cccc(CN2CCCC2)c1
Product: NC(=O)c1cc(Br)ccc1Nc1nc(Nc2cccc(CN3CCCC3)c2)ncc1Cl

Procedure:
5-Bromo-2-[(5-chloro-2-{[3-(1-pyrrolidinylmethyl)phenyl]amino}-4-pyrimidinyl)amino]benzamide was prepared by contacting 5-bromo-2-[(2,5-dichloro-4-pyrimidinyl)amino]benzamide (Intermediate 37) with 3-pyrrolidinylmethylaniline following a procedure substantially as described for the preparation of Example 1. Mass (M+H)+ 501, 503, 505
Reaction SMILES: [CH3:1][C:2](O)([C:4](=O)[CH3:5])[CH3:3].[NH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.C(O)(=O)C.C1(C)C=CC=CC=1>O>[CH3:5][C:4]1[C:2]([CH3:3])([CH3:1])[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[N:8]=1
Reactant: Nc1ccccc1
Reactant: CC(=O)C(C)(C)O
Solvent: Cc1ccccc1
Solvent: CC(=O)O
Solvent: O
Product: CC1=Nc2ccccc2C1(C)C
Temperature: 160 °C
Reaction time: 5 h

Procedure:
408 parts of 2-methyl-2-hydroxy-butan-3-one, 558 parts of aniline and 20 parts of acetic acid in 650 parts of toluene are heated, with removal of water from the system, until no more water separates off. The volatile constituents are then distilled off until the internal temperature reaches 220° C. The distillate can be re-used, without further treatment, in a subsequent batch. The residue is kept for 5 hours at 220° C. and is then cooled to 160° C., and 40 parts of concentrated hydrochloric acid are added. After heating for a further three hours, during which the water formed distils off, the reaction is complete. The product is either directly processed further or distilled. 498 parts of 2,3,3-trimethyl-indolenine are obtained, corresponding to 78.5% of theory, based on 2-methyl-2-hydroxy-butan-3-one.
Reaction SMILES: C1(OC)C=CC=CC=1.[C:9]([N:17]1[CH2:22][CH2:21][CH:20]([CH2:23][CH2:24][C:25]([OH:27])=O)[CH2:19][CH2:18]1)(=[O:16])[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.[Cl:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=1[Cl:35]>>[Cl:28][C:29]1[CH:34]=[C:33]([C:25](=[O:27])[CH2:24][CH2:23][CH:20]2[CH2:19][CH2:18][N:17]([C:9](=[O:16])[C:10]3[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=3)[CH2:22][CH2:21]2)[CH:32]=[CH:31][C:30]=1[Cl:35]
Reactant: O=C(O)CCC1CCN(C(=O)c2ccccc2)CC1
Reactant: Clc1ccccc1Cl
Solvent: COc1ccccc1
Product: O=C(CCC1CCN(C(=O)c2ccccc2)CC1)c1ccc(Cl)c(Cl)c1

Procedure:
In Example 1 the 9.9 g of anisole and the 15.7 g of 3-(1-benzoyl 4-piperidyl) propionic acid are substituted by 185 ml of 1,2 dichlorobenzene and 35 g of 3-(1-benzoyl 4-piperidyl) propionic acid respectively. The reaction is effected at 100° C. and without solvent. 51.1 g of crude 1-(3,4-dichlorophenyl) 3-(1-benzoyl 4-piperidyl) 1-propanone in the form of an oil which crystallizes slowly are obtained.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:9]([C:11]2[C:19]3[C:14](=[C:15]([C:20]([F:23])([F:22])[F:21])[CH:16]=[CH:17][CH:18]=3)[NH:13][N:12]=2)=[O:10])[CH:6]=[CH:7][CH:8]=1.[H-].[Na+].[CH:26]1(Br)[CH2:30][CH2:29][CH2:28][CH2:27]1>CN(C=O)C>[CH:26]1([N:13]2[C:14]3[C:19](=[CH:18][CH:17]=[CH:16][C:15]=3[C:20]([F:23])([F:21])[F:22])[C:11]([C:9]([C:5]3[CH:6]=[CH:7][CH:8]=[C:3]([O:2][CH3:1])[CH:4]=3)=[O:10])=[N:12]2)[CH2:30][CH2:29][CH2:28][CH2:27]1
Reactant: BrC1CCCC1
Reactant: COc1cccc(C(=O)c2n[nH]c3c(C(F)(F)F)cccc23)c1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: COc1cccc(C(=O)c2nn(C3CCCC3)c3c(C(F)(F)F)cccc23)c1
Temperature: 50 °C
Reaction time: 24 h
Yield: 75.7 %

Procedure:
To a solution of [3-(methoxy)phenyl](7-trifluoromethyl-1H-indazol-3-yl)methanone (0.27 g, 0.85 mmol) in 5 mL DMF was added in one portion sodium hydride (0.034 g, 0.85 mmol, 60% in oil). After the gas evolution ceased, cyclopentyl bromide (0.107 mL, 1.0 mmol) was added and the reaction was stirred at ambient to 50° C. for 24 hours. The cool reaction mixture was partitioned with EtOAc and 1 N HCl. The organic phase was washed with brine and dried (Na2SO4). Removal of the solvent in vacuo afforded the crude product which was purified by flash chromatography (silica gel, hexane/EtOAC, 9:1) to give the title compound (0.250 g) as an oil.
Reaction SMILES: [N:1]1([CH2:6][C@@H:7]([O:14][C:15]2[CH:24]=[CH:23][C:22]3[C:21](=[O:25])[CH2:20][CH2:19][CH2:18][C:17]=3[C:16]=2[CH2:26][S:27]([C:30]2[CH:38]=[CH:37][CH:36]=[CH:35][C:31]=2[C:32](O)=[O:33])(=[O:29])=[O:28])[C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH:5]=[CH:4][N:3]=[CH:2]1.[CH3:39][N:40]([CH3:44])[CH2:41][CH2:42][NH2:43]>>[CH3:39][N:40]([CH3:44])[CH2:41][CH2:42][NH:43][C:32](=[O:33])[C:31]1[CH:35]=[CH:36][CH:37]=[CH:38][C:30]=1[S:27]([CH2:26][C:16]1[C:17]2[CH2:18][CH2:19][CH2:20][C:21](=[O:25])[C:22]=2[CH:23]=[CH:24][C:15]=1[O:14][C@@H:7]([C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1)[CH2:6][N:1]1[CH:5]=[CH:4][N:3]=[CH:2]1)(=[O:29])=[O:28]
Reactant: O=C(O)c1ccccc1S(=O)(=O)Cc1c(O[C@H](Cn2ccnc2)c2ccccc2)ccc2c1CCCC2=O
Reactant: CN(C)CCN
Product: CN(C)CCNC(=O)c1ccccc1S(=O)(=O)Cc1c(O[C@H](Cn2ccnc2)c2ccccc2)ccc2c1CCCC2=O
Yield: 33.3 %

Procedure:
Using the method in Example 172, 2-{[(2-{[(1S)-2-(1H-imidazol-1-yl)-1-phenylethyl]oxy}-5-oxo-5,6,7,8-tetrahydro-1-naphthalenyl)methyl]sulfonyl}benzoic acid (53 mg, 0.10 mmol, 0.20M in DMF) and 2-dimethylaminoethylamine (27 mg, 0.30 mmol, 0.60M in DMF) were combined to give 20 mg of the desired compound: Low resolution mass spectrum (LC-MS, APCI) m/z 601 [M+H]+.
Reaction SMILES: [CH3:1][C:2]([C:9]1[CH:22]=[CH:21][C:12]([O:13][CH2:14][C@H:15]2[O:19][C:18]([NH2:20])=[N:17][CH2:16]2)=[CH:11][CH:10]=1)([CH3:8])[CH2:3][C:4]([CH3:7])([CH3:6])[CH3:5].C([O:25][C:26](=O)[C:27]#[C:28][CH2:29][CH3:30])C>C(Cl)(Cl)Cl>[CH2:29]([C:28]1[N:17]2[CH2:16][C@@H:15]([CH2:14][O:13][C:12]3[CH:21]=[CH:22][C:9]([C:2]([CH3:1])([CH3:8])[CH2:3][C:4]([CH3:5])([CH3:6])[CH3:7])=[CH:10][CH:11]=3)[O:19][C:18]2=[N:20][C:26](=[O:25])[CH:27]=1)[CH3:30]
Reactant: CCC#CC(=O)OCC
Reactant: CC(C)(C)CC(C)(C)c1ccc(OC[C@@H]2CN=C(N)O2)cc1
Solvent: ClC(Cl)Cl
Product: CCc1cc(=O)nc2n1C[C@@H](COc1ccc(C(C)(C)CC(C)(C)C)cc1)O2

Procedure:
The title compound was prepared from (S)-5-(4-(1,1,3,3-tetramethyl-butyl) -phenoxymethyl)-4,5-dihydro-oxazol-2-ylamine (see Example 27) and pent-2-ynoic acid ethyl ester employing the procedure described in Example 95. [α]D25 −21.00 (c 0.5, CHCl3).
Reaction SMILES: [OH-].[Na+].C([O:11][C:12]1[CH:17]=[CH:16][C:15]([C:18]2[CH:23]=[CH:22][C:21]([N+:24]([O-:26])=[O:25])=[CH:20][CH:19]=2)=[CH:14][CH:13]=1)(=O)C1C=CC=CC=1>C(O)C>[OH:11][C:12]1[CH:13]=[CH:14][C:15]([C:18]2[CH:23]=[CH:22][C:21]([N+:24]([O-:26])=[O:25])=[CH:20][CH:19]=2)=[CH:16][CH:17]=1
Reactant: O=C(Oc1ccc(-c2ccc([N+](=O)[O-])cc2)cc1)c1ccccc1
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: O=[N+]([O-])c1ccc(-c2ccc(O)cc2)cc1
Reaction time: 8 h
Yield: 80 %

Procedure:
The equivalent amount of a 40% caustic soda solution is added, by drops, to a mixture of 300 g 4-benzoyloxy-4'-nitrobiphenyl (see Example 2) and 1500 ml ethanol; after addition, the mixture is heated under reflux for 30 min and then allowed to stand at room temperature overnight. Subsequently, the sodium salt is filtered off and dried. The free base, i.e. the hydroxy compound, is released by suspension of the sodium salt in water and acidification with half-concentrated hydrochloric acid The raw product is filtered off, washed neutral with water and recrystallized from ethanol (melting point: 204° C.); yield: 80%.
Reaction SMILES: [S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[CH2:6][C:7](O)=O.C(N(CC)CC)C.[N+:17](C1C=CC(CBr)=CC=1)([O-:19])=[O:18].C1C[O:31][CH2:30][CH2:29]1.C1(C)C=CC=CC=1>C1(C)C=CC=CC=1>[CH3:29][C:30]([S:1][C:5]1[CH:4]=[CH:3][C:2]([N+:17]([O-:19])=[O:18])=[CH:6][CH:7]=1)=[O:31]
Reactant: C1CCOC1
Reactant: O=C(O)Cc1cccs1
Reactant: O=[N+]([O-])c1ccc(CBr)cc1
Solvent: Cc1ccccc1
Solvent: CCN(CC)CC
Product: CC(=O)Sc1ccc([N+](=O)[O-])cc1
Reaction time: 8 h
Yield: 96 %

Procedure:
To the solution of 5 ml (69.95 mmol) of thiolacetic acid and 12 ml of triethyl amine in 75 ml of toluene was added dropwise 7.5 g (34.71 mmol) of 4-nitrobenzyl bromide in 100 ml of 1:2 THF/Toluene for 4 hours. The mixture was continuously stirred overnight, evaporated and crystallized with EtAc/Toluene/Hexane to afford 7.1 g (96%) of the title compound. 1H NMR (CDCl3) 8.13 (ddd, 2H, J=2.5, 4.5, 9.3 Hz), 7.44 (ddd, 2H, J=2.5, 4.5, 9.3 Hz), 4.14 (s, 2H), 2.35 (S, 3H); 13C NMR 194.53, 145.73, 129.91, 124.07, 32.93, 30.50; MS M+234.34 (M+Na).
Reaction SMILES: CS(O[CH2:6][CH2:7][CH:8]([C:21]1[CH:22]=[CH:23][C:24]2[S:28][CH:27]=[CH:26][C:25]=2[CH:29]=1)[C:9]1[C:17]2[C:12](=[C:13]([CH2:18][S:19][CH3:20])[CH:14]=[CH:15][CH:16]=2)[NH:11][CH:10]=1)(=O)=O.ClC1C=CC(C(C2C3C(=C(CSC)C(F)=CC=3)NC=2)CC[C:40]#[N:41])=CC=1>>[S:28]1[C:24]2[CH:23]=[CH:22][C:21]([CH:8]([C:9]3[C:17]4[C:12](=[C:13]([CH2:18][S:19][CH3:20])[CH:14]=[CH:15][CH:16]=4)[NH:11][CH:10]=3)[CH2:7][CH2:6][C:40]#[N:41])=[CH:29][C:25]=2[CH:26]=[CH:27]1
Reactant: CSCc1cccc2c(C(CCOS(C)(=O)=O)c3ccc4sccc4c3)c[nH]c12
Reactant: CSCc1c(F)ccc2c(C(CCC#N)c3ccc(Cl)cc3)c[nH]c12
Product: CSCc1cccc2c(C(CCC#N)c3ccc4sccc4c3)c[nH]c12

Procedure:
The title compound was prepared starting from 768 mg (1.72 mmol) of the compound from Example 68A in analogy to the synthesis of the compound from Example 50. 494 mg (76% of theory) of the target compound were obtained.
Reaction SMILES: CC1CNC(C2C=CN=C(NC(=O)C3C=CC=CC=3)C=2)=N1.[CH2:22]([CH:29]1[CH2:33][NH:32][C:31]([C:34]2[CH:39]=[CH:38][N:37]=[C:36]([NH:40][C:41](=[O:48])[C:42]3[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=3)[CH:35]=2)=[N:30]1)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1>>[CH2:22]([C:29]1[N:30]=[C:31]([C:34]2[CH:39]=[CH:38][N:37]=[C:36]([NH:40][C:41](=[O:48])[C:42]3[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=3)[CH:35]=2)[NH:32][CH:33]=1)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1
Reactant: O=C(Nc1cc(C2=NC(Cc3ccccc3)CN2)ccn1)c1ccccc1
Agent: CC1CNC(c2ccnc(NC(=O)c3ccccc3)c2)=N1
Product: O=C(Nc1cc(-c2nc(Cc3ccccc3)c[nH]2)ccn1)c1ccccc1
Yield: 19 %

Procedure:
Following the procedure as described in Example 10, making variations as required to replace N-(4-(4-methyl-4,5-dihydro-1H-imidazol-2-yl)pyridin-2-yl)benzamide with N-(4-(4-benzyl-4,5-dihydro-1H-imidazol-2-yl)pyridin-2-yl)benzamide, N-(4-(4-benzyl-1H-imidazol-2-yl)pyridin-2-yl)benzamide was obtained as a colorless solid in 19% yield: mp 110-112° C.; 1H NMR (300 MHz, CDCl3) δ 8.96 (br s, 1H), 8.62 (s, 1H), 8.18 (d, J=3.7 Hz, 1H), 7.83 (d, J=7.2 Hz, 2H), 7.70 (d, J=4.8 Hz, 1H), 7.58-7.50 (m, 1H), 7.48-7.40 (m, 2H), 7.30-7.14 (m, 5H), 6.81 (br s, 1H), 3.96 (s, 2H); MS (ES+) m/z 355.3 (M+1).
Reaction SMILES: [O:1]=[S:2]1(=[O:37])[C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=2[CH2:6][N:5]([C:13]2[CH:22]=[C:21]([NH:23][C:24]3([CH2:28][NH:29]C(=O)C(F)(F)F)[CH2:27][O:26][CH2:25]3)[C:20]3[C:15](=[CH:16][CH:17]=[C:18]([CH3:36])[CH:19]=3)[N:14]=2)[CH2:4][CH2:3]1.N.C[OH:40]>>[NH2:29][CH2:28][C:24]([NH:23][C:21]1[C:20]2[C:15](=[CH:16][CH:17]=[C:18]([CH3:36])[CH:19]=2)[N:14]=[C:13]([N:5]2[CH2:6][C:7]3[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=3[S:2](=[O:37])(=[O:1])[CH2:3][CH2:4]2)[CH:22]=1)([CH2:25][OH:40])[CH2:27][OH:26]
Reactant: Cc1ccc2nc(N3CCS(=O)(=O)c4ccccc4C3)cc(NC3(CNC(=O)C(F)(F)F)COC3)c2c1
Reactant: CO
Agent: N
Product: Cc1ccc2nc(N3CCS(=O)(=O)c4ccccc4C3)cc(NC(CN)(CO)CO)c2c1
Yield: 25 %

Procedure:
A mixture of N-[(3-{[2-(1,1-dioxido-2,3-dihydro-1,4-benzothiazepin-4(5H)-yl)-6-methylquinolin-4-yl]amino}oxetan-3-yl)methyl]-2,2,2-trifluoroacetamide (269 mg, 0.503 mmol) and a solution of ammonia in methanol (7 M, 10 mL,) was stirred at room temperature overnight. The resulting mixture was concentrated in vacuo and the residue was purified by preparative HPLC to afford 58 mg of the product as a white solid (yield was 25%). MS obsd. (ESI+) [(M+H)+] 457, 1H NMR (400 MHz, CD3OD) δ ppm 8.11-8.09 (t, J=6.4, 1.2 Hz, 1 H), 8.00-7.96 (m, 1 H), 7.86 (s, 1 H), 7.76-7.73 (m, 2 H), 7.64-7.60 (m, 2 H), 6.49 (s, 1 H), 5.33 (s, 2 H), 4.55 (s, 2 H), 3.82 (s, 2 H), 3.77-3.75 (m, 6 H), 2.49 (s, 3 H).