Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([NH:8][CH2:9][C:10]1[CH:14]=[CH:13][O:12][CH:11]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Br[CH2:16][CH2:17][OH:18].C(=O)([O-])[O-].[K+].[K+].O>CN(C)C=O>[CH2:1]([N:8]([CH2:9][C:10]1[CH:14]=[CH:13][O:12][CH:11]=1)[CH2:16][CH2:17][OH:18])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: c1ccc(CNCc2ccoc2)cc1
Reactant: OCCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: OCCN(Cc1ccccc1)Cc1ccoc1
Temperature: 80 °C
Reaction time: 2 h

Procedure:
To a solution of 0.641 g (3.423 mmol) of N-benzyl-3-furylmethylamine and 0.64 g (5.1 mmol) of 2-bromoethanol in 30 ml of N,N-dimethylformamide, 0.95 g of potassium carbonate was added, followed by stirring at 80° C. for 2 hours. 0.64 g (5.1 mmol) of 2-bromoethanol was further added, followed by overnight stirring at 80° C. The reaction mixture was poured into water and extracted with dichloromethane 3 times. The combined organic layer was dried over anhydrous magnesium sulfate; the solvent was distilled off under reduced pressure. The resulting crude product was purified by silica gel column chromatography (hexane/ethyl acetate=3/1) to yield 2-[benzyl-(3-furylmethyl)amino]ethanol.
Reaction SMILES: C1(C[O:8][C:9]([CH2:11][N:12]([CH:17]2[C:50]3[C:45](=[CH:46][CH:47]=[CH:48][CH:49]=3)[C:19]3([CH2:24][CH2:23][N:22]([C:25]([C@H:27]([NH:38][C:39](=[O:44])[C:40]([NH2:43])([CH3:42])[CH3:41])[CH2:28][C:29]4[C:37]5[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=5)[NH:31][CH:30]=4)=[O:26])[CH2:21][CH2:20]3)[CH2:18]2)[S:13]([CH3:16])(=[O:15])=[O:14])=[O:10])C=CC=CC=1.[H][H]>CO.[Pd]>[C:9]([CH2:11][N:12]([CH:17]1[C:50]2[C:45](=[CH:46][CH:47]=[CH:48][CH:49]=2)[C:19]2([CH2:24][CH2:23][N:22]([C:25]([C@H:27]([NH:38][C:39](=[O:44])[C:40]([NH2:43])([CH3:42])[CH3:41])[CH2:28][C:29]3[C:37]4[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=4)[NH:31][CH:30]=3)=[O:26])[CH2:21][CH2:20]2)[CH2:18]1)[S:13]([CH3:16])(=[O:14])=[O:15])([OH:10])=[O:8]
Reactant: CC(C)(N)C(=O)N[C@H](Cc1c[nH]c2ccccc12)C(=O)N1CCC2(CC1)CC(N(CC(=O)OCc1ccccc1)S(C)(=O)=O)c1ccccc12
Reactant: [H][H]
Agent: [Pd]
Solvent: CO
Product: CC(C)(N)C(=O)N[C@H](Cc1c[nH]c2ccccc12)C(=O)N1CCC2(CC1)CC(N(CC(=O)O)S(C)(=O)=O)c1ccccc12

Procedure:
A solution of ca. 25 mg of N-[1(R)-[[3-[N-[[[phenylmethoxy]carbonyl]methyl]-N-(methylsulfonyl)amino]-2,3-dihydrospiro[1H-indene-1,4'-piperidin]-1'-yl]carbonyl]-2-(indole-3-yl)ethyl]-2-amino-2-methylpropanamide from Example 149, Step D, in 0.5 mL of methanol containing 25 mg of 10% Pd/C, is shaken under a 50 psi atmosphere of hydrogen over night. After filtration and taking the filtrate to dryness under reduced pressure, the title compound is obtained.
Reaction SMILES: Br[CH2:2][C:3]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][N:6]=1)=O.[I:11][C:12]1[CH:13]=[C:14]([CH:18]=[CH:19][CH:20]=1)[C:15]([NH2:17])=[S:16]>C(O)C>[I:11][C:12]1[CH:13]=[C:14]([C:15]2[S:16][CH:2]=[C:3]([C:5]3[CH:10]=[CH:9][CH:8]=[CH:7][N:6]=3)[N:17]=2)[CH:18]=[CH:19][CH:20]=1
Reactant: NC(=S)c1cccc(I)c1
Reactant: O=C(CBr)c1ccccn1
Solvent: CCO
Product: Ic1cccc(-c2nc(-c3ccccn3)cs2)c1
Yield: 41.5 %

Procedure:
A solution of 2-bromoacetylpyridine (400 mg, 2.0 mmol) in ethanol (5 mL) was treated with 3-iodothiobenzamide (1.2g, 6 mmol) and the mixture heated at reflux for 16 hours. After cooling the mixture was concentrated in vacuo. Silica gel chromatography of the residue using a gradient of hexane to ethyl acetate afforded 302 mg (55%) of 2-(3-iodophenyl)-4-(pyridin-2-yl)-1,3-thiazole, as a white solid.
Reaction SMILES: [CH2:1]([O:3][C@@H:4]([CH2:9][C:10]1[CH:15]=[CH:14][C:13]([C:16]2[N:17]([CH3:33])[N:18]=[C:19]([N:21]([CH3:32])[C:22]([NH:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH3:31])=[O:23])[N:20]=2)=[CH:12][CH:11]=1)[C:5]([O:7]C)=[O:6])[CH3:2].[OH-].[Li+]>O1CCCC1>[CH2:1]([O:3][C@@H:4]([CH2:9][C:10]1[CH:15]=[CH:14][C:13]([C:16]2[N:17]([CH3:33])[N:18]=[C:19]([N:21]([CH3:32])[C:22]([NH:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH3:31])=[O:23])[N:20]=2)=[CH:12][CH:11]=1)[C:5]([OH:7])=[O:6])[CH3:2]
Reactant: CCCCCCCNC(=O)N(C)c1nc(-c2ccc(C[C@H](OCC)C(=O)OC)cc2)n(C)n1
Agent: [Li+]
Agent: [OH-]
Solvent: C1CCOC1
Product: CCCCCCCNC(=O)N(C)c1nc(-c2ccc(C[C@H](OCC)C(=O)O)cc2)n(C)n1
Yield: 84.2 %

Procedure:
37 mg (80 μmol) of methyl 2(S)-ethoxy-3-{4-[5-(3-heptyl-1-methylureido)-2-methyl-2H-[1,2,4]triazol-3-yl]phenyl}propanoate placed in 2 ml of tetrahydrofuran and 0.1 ml (0.1 mmol) of aqueous 1M lithium hydroxide solution are stirred at room temperature overnight. The reaction medium is acidified to pH 4 and extracted with ethyl acetate. The organic phase is washed with water, with saturated sodium chloride solution, dried over magnesium sulfate, filtered and evaporated. 30 mg (83%) of 2(S)-ethoxy-3-{4-[5-(3-heptyl-1-methylureido)-2-methyl-2H-[1,2,4]triazol-3-yl]phenyl}propanoic acid are obtained in the form of a white solid.
Reaction SMILES: [CH2:1]1[N:9]2[CH:4]([NH:5][S:6](=[O:16])(=[O:15])[C:7]3[CH:13]=[C:12]([OH:14])[CH:11]=[CH:10][C:8]=32)[CH2:3][CH2:2]1.[C:17]([CH2:19][C:20]1[CH:25]=[CH:24][C:23](B(O)O)=[CH:22][CH:21]=1)#[N:18].N1C=CC=CC=1>C(Cl)Cl.C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[O:16]=[S:6]1(=[O:15])[C:7]2[CH:13]=[C:12]([O:14][C:23]3[CH:24]=[CH:25][C:20]([CH2:19][C:17]#[N:18])=[CH:21][CH:22]=3)[CH:11]=[CH:10][C:8]=2[N:9]2[CH2:1][CH2:2][CH2:3][CH:4]2[NH:5]1
Reactant: N#CCc1ccc(B(O)O)cc1
Reactant: O=S1(=O)NC2CCCN2c2ccc(O)cc21
Agent: [Cu+2]
Agent: CC(=O)[O-]
Solvent: ClCCl
Solvent: c1ccncc1
Product: N#CCc1ccc(Oc2ccc3c(c2)S(=O)(=O)NC2CCCN32)cc1
Reaction time: 8 h

Procedure:
A suspension composed of 1.15 g (4.77 mmol) of 2,3,3a,4-tetrahydro-1H-pyrrolo[2,1-c]-[1,2,4]benzothiadiazin-7-ol 5,5-dioxide, 1.00 g (6.21 mmol) of [4-(cyanomethyl)phenyl]-boronic acid, 1.3 g (7.15 mmol) of copper(II) acetate, 1.16 ml (14.31 mmol) of pyridine and about 500 mg of 4 Å molecular sieve in 200 ml of methylene chloride is stirred overnight. The reaction mixture is diluted by adding a further 100 ml of methylene chloride and the suspension is filtered. The filtrate is concentrated and then directly placed on a silica column which is eluted with a methylene chloride/methanol 99/1 system. The fractions containing the expected product are combined and evaporated, and the residue is taken up in a small amount of ethyl ether. After filtering off the solid, the title product is obtained in the form of beige powder.
Reaction SMILES: [F:1][C:2]([F:50])([F:49])[C:3]1[CH:48]=[CH:47][C:6]2[NH:7][C:8]([C:10]3[CH:15]=[CH:14][C:13]([S:16]([CH:19]4[CH2:25][CH2:24][CH2:23][CH2:22][N:21]([O:26]C(C5C=CC=CC=5)(C5C=CC=CC=5)C5C=CC=CC=5)[C:20]4=[O:46])(=[O:18])=[O:17])=[CH:12][CH:11]=3)=[N:9][C:5]=2[CH:4]=1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[OH:26][N:21]1[CH2:22][CH2:23][CH2:24][CH2:25][CH:19]([S:16]([C:13]2[CH:12]=[CH:11][C:10]([C:8]3[NH:7][C:6]4[CH:47]=[CH:48][C:3]([C:2]([F:50])([F:49])[F:1])=[CH:4][C:5]=4[N:9]=3)=[CH:15][CH:14]=2)(=[O:18])=[O:17])[C:20]1=[O:46]
Reactant: O=C1C(S(=O)(=O)c2ccc(-c3nc4cc(C(F)(F)F)ccc4[nH]3)cc2)CCCCN1OC(c1ccccc1)(c1ccccc1)c1ccccc1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: O=C1C(S(=O)(=O)c2ccc(-c3nc4cc(C(F)(F)F)ccc4[nH]3)cc2)CCCCN1O
Reaction time: 0.5 h

Procedure:
3-[4-(5-trifluoromethyl-1H-benzoimidazol-2-yl)-benzenesulfonyl]-1-trityloxy-azepan-2-one prepared from step H (8.2 mg, 0.0117 mmol) in 0.75 ml of anhydrous CH2Cl2 was added 0.75 ml of TFA and the resulting solution was stirred for 30 min. After TLC indicated the completion of the reaction (<30 min), the reaction mixture was concentrated under reduced pressure to gave a crude material, which was then purified by a column chromatography (0˜5% MeOH in EtOAc and CH2Cl2 1:1). MS: 454.0 (M+H)+, 476.0 (M+Na)+.
Reaction SMILES: [CH2:1]([O:4][C@H:5]1[C@@H:20]([OH:21])[C@@H:19]([CH2:22][OH:23])[O:18][C@@H:7]([O:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][C:14]([O:16][CH3:17])=[O:15])[C@@H:6]1[OH:24])[CH:2]=[CH2:3].N1C=CN=C1.[Si:30](Cl)([C:33]([CH3:36])([CH3:35])[CH3:34])([CH3:32])[CH3:31].CO>CN(C)C=O>[CH2:1]([O:4][C@H:5]1[C@@H:20]([OH:21])[C@@H:19]([CH:22]([Si:30]([C:33]([CH3:36])([CH3:35])[CH3:34])([CH3:32])[CH3:31])[OH:23])[O:18][C@@H:7]([O:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][C:14]([O:16][CH3:17])=[O:15])[C@@H:6]1[OH:24])[CH:2]=[CH2:3]
Reactant: CC(C)(C)[Si](C)(C)Cl
Reactant: C=CCO[C@H]1[C@@H](O)[C@@H](CO)O[C@@H](OCCCCCC(=O)OC)[C@@H]1O
Agent: c1c[nH]cn1
Solvent: CO
Solvent: CN(C)C=O
Product: C=CCO[C@H]1[C@@H](O)[C@@H](C(O)[Si](C)(C)C(C)(C)C)O[C@@H](OCCCCCC(=O)OC)[C@@H]1O
Temperature: 0 °C
Reaction time: 0.17 h

Procedure:
Compound 2 of Example 2 (10.85 g) was dissolved in dry dimethylformamide (DMF, 120 mL) containing imidazole (1.63 g) and 4 Å molecular sieves and cooled in an ice bath. To this, t-butyldimethylsilyl chloride (tBDMS chloride, 3.6 g) was added and stirred at this temperature for 10 min and then at room temperature 1 h. Another portion of imidazole (1.05 g) and tBDMS chloride (2.34 g) were added to the ice cold solution and stirred for 1 h. Methanol (1 mL) was added and the reaction mixture was evaporated to dryness. The residue was dissolved in CH2Cl2 and washed with water, 1M ice cold HCl and saturated NaHCO3 solution. The solution was dried over anhydrous magnesium sulfate, filtered and evaporated. 1H n.m.r. of the crude product (12.0 g of colorless solid) showed it to be essentially pure titled compound. [α]D25 -3.2±2° (c 1.03, CHCl3). 1H n.m.r.(CDCl3 +D2O<5 %) ∂: 5.95 (m, 1 H, --CH=C), 5.33 and 5.23 (m, 2 H, C=CH2), 4.24 (m, 3 H, H-1, J1,2 =Hz, O--CH2 --C=), 4.06 (d, H-4), 3.9-3.8 (m, 3 H, H-6a,b, OCH2 --C), 3.73 (dd, H-2), 3.67 (s, COOCH3), 3.52 (m, OCH2 --C), 3.44 (m, H-5), 3.35 (dd, H-3),2.32 (t, CH2COO), 1.65 and 1.40 (6 H, hydrogens of pentyl group), 0.89 (s, t-butyl group), 0.09 (d, CH3 --Si--CH3). 13C n.m.r. (CDCl3) ∂: 173.9, 134.8, 117.4, 103.2, 80.7, 75.0, 71.2, 71.0, 69.3, 66.3, 62.2, 51.3, 33.9, 29.2, 25.9, 25.6, 24.6, 18.3, -5.34, -5.39. Anal. Calcd for C22H2842O8Si: C, 57.14; H, 9.09. Found: C, 56.30; H 9.06.
Reaction SMILES: B.N1C=CC=CC=1.[CH3:8][O:9][C:10]1[CH:15]=[CH:14][C:13]([CH:16]=[N:17][N:18]2[C:26](=[O:27])[C:25]3[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=3)[C:19]2=[O:28])=[CH:12][C:11]=1[CH3:29]>C(O)(=O)C>[CH3:8][O:9][C:10]1[CH:15]=[CH:14][C:13]([CH2:16][NH:17][N:18]2[C:26](=[O:27])[C:25]3[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=3)[C:19]2=[O:28])=[CH:12][C:11]=1[CH3:29]
Reactant: COc1ccc(C=NN2C(=O)c3ccccc3C2=O)cc1C
Agent: B
Solvent: c1ccncc1
Solvent: CC(=O)O
Product: COc1ccc(CNN2C(=O)c3ccccc3C2=O)cc1C
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 67.9 %

Procedure:
Acetic acid (40 ml) and pyridine-borane (4.3 ml) were added to 2-{[1-(4-methoxy-3-methylphenyl)-methylidene]amino}isoindole-1,3-dione (2.50 g) prepared in the Step 15-1-1, and the mixture was stirred under a room temperature for 0.5 hours. The mixture was concentrated under a reduced pressure, and under an ice cooling 10% hydrochloric acid (10 ml) was added to the resulting residue. Sodium hydroxide (1.1 g) was added thereto, and the resulting mixture was subjected to extraction with ethyl acetate. The organic layer was washed with a saturated saline solution, and then dried over sodium sulfate and concentrated under a reduced pressure. To the resulting residue, ethanol (10 ml) was added, and the mixture was stirred at a room temperature. The precipitate was separated by filtration, washed with ethanol, and concentrated under a reduced pressure to give the title compound (1.71 g, 68%).
Reaction SMILES: [C:1]1(=[O:11])[O:6][C:4](=[O:5])[C:3]2=[CH:7][CH:8]=[CH:9][CH:10]=[C:2]12.[CH3:12][N:13]1[CH:17]=[CH:16][CH:15]=[CH:14]1.[Cl-].[Al+3].[Cl-].[Cl-]>ClC1C=CC=CC=1>[C:12]1([N:13]2[CH:17]=[CH:16][CH:15]=[C:14]2[C:4]([C:3]2[CH:7]=[CH:8][CH:9]=[CH:10][C:2]=2[C:1]([OH:6])=[O:11])=[O:5])[CH:4]=[CH:3][CH:2]=[CH:10][CH:9]=1
Reactant: O=C1OC(=O)c2ccccc21
Reactant: Cn1cccc1
Agent: [Al+3]
Agent: [Cl-]
Solvent: Clc1ccccc1
Product: O=C(O)c1ccccc1C(=O)c1cccn1-c1ccccc1

Procedure:
Proceeding in a manner similar to that described in part A of Example 16, 14.8 g (0.1 mole) of phthalic anhydride, 16.2 g (0.2 mole) of N-methylpyrrole and 39.0 g (0.3 mole) of aluminum chloride were interacted in 50 ml of chlorobenzene to obtain 2-[(1-methyl-2-pyrrolyl)carbonyl]benzoic acid (Formula IX: R°=R1 =R2 =R3 =H; R7 =CH3) melting at 165°-167° C. A significant infrared absorption maximum appeared at 1710 cm-1 (C=O; s).
Reaction SMILES: C([N-]C(C)C)(C)C.[Li+].[Br:9][C:10]1[CH:15]=[CH:14][C:13]([F:16])=[CH:12][C:11]=1[F:17].[CH3:18][C:19]([CH3:21])=[O:20].Cl>O1CCCC1>[Br:9][C:10]1[C:11]([F:17])=[C:12]([C:19]([OH:20])([CH3:21])[CH3:18])[C:13]([F:16])=[CH:14][CH:15]=1
Reactant: CC(C)=O
Reactant: Fc1ccc(Br)c(F)c1
Agent: CC(C)[N-]C(C)C
Agent: Cl
Agent: [Li+]
Solvent: C1CCOC1
Product: CC(C)(O)c1c(F)ccc(Br)c1F
Temperature: -78 °C
Reaction time: 0.5 h

Procedure:
6.3 ml of a 2M solution of lithium diisopropylamide in tetrahydrofuran (standardized beforehand at 0.86M) are introduced under a stream of argon into 5 ml of tetrahydrofuran in a round-bottomed flask. The mixture is cooled to −78° C. and 0.59 ml of 1-bromo-2,4-difluorobenzene is added dropwise thereto. The mixture is stirred at −78° C. for 30 min and acetone is added via four fractions of 0.5 ml. The reaction medium is run into 20 ml of 1N hydrochloric acid after returning to ambient temperature. The organic phase, extracted with diethyl ether, is subsequently washed twice with 20 ml of water, separated, dried over magnesium sulphate and concentrated under reduced pressure. The oil obtained is purified by chromatography on silica gel, elution being carried out with a heptane/ethyl acetate mixture. 0.50 g of compound is obtained.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:10]=[C:11]([CH:14]=[C:15]([CH3:17])[CH:16]=1)[CH2:12]Br)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[ClH:18].[CH3:19][NH:20][CH2:21]/[CH:22]=[CH:23]/[C:24]#[C:25][C:26]([CH3:29])([CH3:28])[CH3:27].C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[ClH:18].[CH3:27][C:26]([CH3:29])([CH3:28])[C:25]#[C:24]/[CH:23]=[CH:22]/[CH2:21][N:20]([CH2:12][C:11]1[CH:14]=[C:15]([CH3:17])[CH:16]=[C:9]([O:8][CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[CH:10]=1)[CH3:19]
Reactant: CNC/C=C/C#CC(C)(C)C
Reactant: Cc1cc(CBr)cc(OCc2ccccc2)c1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: Cc1cc(CN(C)C/C=C/C#CC(C)(C)C)cc(OCc2ccccc2)c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 63.3 %

Procedure:
3-Benzyloxy-5-methylbenzyl bromide (118 mg) and 76 mg of (E)-N-methyl-6,6-dimethyl-2-hepten-4-ynylamine hydrochloride were dissolved in 25 ml of dimethylformamide, and 67 mg of potassium carbonate was added. The mixture was stirred overnight at room temperature. The reaction mixture was evaporated under reduced pressure, and the residue was purified by preparative thin-layer chromatography [thin layer plate: Kieselgel 60F254, Art. 5715 (a product of E. Merck Co.); developing solvent: hexane/ethyl acetate=4/1]. The purified compound was then converted into a hydrochloride using HCl methanol solution. Treatment with a mixture of tetrahydrofuran and hexane gave 102 mg (yield 60.9%) of the captioned compound as a colorless crystalline powder having a melting point of 180° to 186° C.
Reaction SMILES: [CH2:1]([NH:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1)[CH3:2].C([O:12][C:13]([C:15]1[C:16](=[O:30])[N:17]([CH3:29])[C:18]2[C:23]([C:24]=1[OH:25])=[C:22]([N:26]([CH3:28])[CH3:27])[CH:21]=[CH:20][CH:19]=2)=O)C.C(O)C>C1(C)C=CC=CC=1>[CH2:1]([N:3]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1)[C:13]([C:15]1[C:16](=[O:30])[N:17]([CH3:29])[C:18]2[C:23]([C:24]=1[OH:25])=[C:22]([N:26]([CH3:27])[CH3:28])[CH:21]=[CH:20][CH:19]=2)=[O:12])[CH3:2]
Reactant: CCOC(=O)c1c(O)c2c(N(C)C)cccc2n(C)c1=O
Reactant: CCNc1ccccc1
Solvent: CCO
Solvent: Cc1ccccc1
Product: CCN(C(=O)c1c(O)c2c(N(C)C)cccc2n(C)c1=O)c1ccccc1
Temperature: 25 °C
Yield: 70.7 %

Procedure:
N-Ethylaniline (4.4 g, 0.036 mol) was dissolved in 80 ml of toluene. About 30 ml of the solvent was distilled off in order to obtain a dry solution. 1,2-Dihydro-4-hydroxy-5-dimethylamino-1-methyl-2-oxo-quinoline-3-carboxylic acid ethyl ester (3.5 g, 0.012 mol) was added to the boiling solution. The ethanol formed during the reaction was distilled off together with some toluene for about 10 hours. The mixture was cooled to room temperature. The precipitate was collected, washed with cold toluene and hexane and dried to give the title compound (3.1 g), yield 71%.
Reaction SMILES: [CH3:1][C:2]1[C:11]2[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=2[N:5]=[C:4]2[CH2:12][CH2:13][NH:14][CH2:15][CH2:16][C:3]=12.[C:17](Cl)(=[O:21])[CH:18]([CH3:20])[CH3:19]>>[C:17]([N:14]1[CH2:15][CH2:16][C:3]2[C:4](=[N:5][C:6]3[CH:7]=[CH:8][CH:9]=[CH:10][C:11]=3[C:2]=2[CH3:1])[CH2:12][CH2:13]1)(=[O:21])[CH:18]([CH3:20])[CH3:19]
Reactant: CC(C)C(=O)Cl
Reactant: Cc1c2c(nc3ccccc13)CCNCC2
Product: Cc1c2c(nc3ccccc13)CCN(C(=O)C(C)C)CC2
Yield: 50 %

Procedure:
3-Isobutyryl-1,2,4,5-tetrahydro-11-methyl-3H-azepino[4,5-b]quinoline was prepared by acylation of 1,2,4,5-tetrahydro-11-methyl-3H-azepino[4,5-b]quinoline with isobutyryl chloride in pryidine.
Reaction SMILES: Cl[CH2:2][C:3](=[O:13])[CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([F:11])[C:6]=1[CH3:12].[Br-:14].[Li+]>CC(C)=O>[Br:14][CH2:2][C:3](=[O:13])[CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([F:11])[C:6]=1[CH3:12]
Reactant: [Br-]
Reactant: Cc1c(F)cccc1CC(=O)CCl
Agent: [Li+]
Solvent: CC(C)=O
Product: Cc1c(F)cccc1CC(=O)CBr
Reaction time: 8 h
Yield: 93.6 %

Procedure:
The compound of step 1 (3.20 g, 15.95 mmol) was dissolved in acetone (70 ml), and lithium bromide (11.08 g, 127.59 mmol) was added. The mixture was stirred overnight. The solvent was evaporated, the resulting solid was dissolved in EA and the solution washed twice with water followed by a saturated solution of sodium chloride, dried over sodium sulfate, filtered and evaporated to dryness. 3.66 g of the title compound were obtained as a white powder.
Reaction SMILES: C([O:3][C:4](=[O:31])[CH2:5][CH2:6][NH:7][C:8](=[O:30])[C:9]1[CH:14]=[CH:13][C:12]([CH:15]([CH2:19][O:20][C:21]2[CH:26]=[C:25]([CH3:27])[C:24](Br)=[C:23]([CH3:29])[CH:22]=2)[CH:16]([CH3:18])[CH3:17])=[CH:11][CH:10]=1)C.[C:32]([C:36]1[CH:41]=[CH:40][C:39](B(O)O)=[CH:38][CH:37]=1)([CH3:35])([CH3:34])[CH3:33]>>[C:32]([C:36]1[CH:41]=[CH:40][C:39]([C:24]2[C:23]([CH3:29])=[CH:22][C:21]([O:20][CH2:19][CH:15]([C:12]3[CH:11]=[CH:10][C:9]([C:8]([NH:7][CH2:6][CH2:5][C:4]([OH:31])=[O:3])=[O:30])=[CH:14][CH:13]=3)[CH:16]([CH3:18])[CH3:17])=[CH:26][C:25]=2[CH3:27])=[CH:38][CH:37]=1)([CH3:35])([CH3:34])[CH3:33]
Reactant: CC(C)(C)c1ccc(B(O)O)cc1
Reactant: CCOC(=O)CCNC(=O)c1ccc(C(COc2cc(C)c(Br)c(C)c2)C(C)C)cc1
Product: Cc1cc(OCC(c2ccc(C(=O)NCCC(=O)O)cc2)C(C)C)cc(C)c1-c1ccc(C(C)(C)C)cc1

Procedure:
The title compound is prepared by essentially following the procedures as described in Example 21, using 3-{4-[1-(4-bromo-3,5-dimethyl-phenoxymethyl)-2-methyl-propyl]-benzoylamino}-propionic acid ethyl ester and 4-tert-butyl phenyl boronic acid as starting materials. MS (ES): 514.2 [M+H]−.
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[C:9]2[CH:10]=[CH:11][C:12]([OH:14])=[CH:13][C:8]=2[O:7][CH:6]=1)=[O:4].C([O-])([O-])=O.[Cs+].[Cs+].Cl.Cl[C:23]1[S:24][C:25]2[C:26]([N:31]=1)=[N:27][CH:28]=[CH:29][CH:30]=2.O>CN(C=O)C>[CH3:1][O:2][C:3]([C:5]1[C:9]2[CH:10]=[CH:11][C:12]([O:14][C:23]3[S:24][C:25]4[C:26]([N:31]=3)=[N:27][CH:28]=[CH:29][CH:30]=4)=[CH:13][C:8]=2[O:7][CH:6]=1)=[O:4]
Reactant: Clc1nc2ncccc2s1
Reactant: COC(=O)c1coc2cc(O)ccc12
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Solvent: O
Product: COC(=O)c1coc2cc(Oc3nc4ncccc4s3)ccc12
Temperature: 25 °C
Reaction time: 3 h
Yield: 87.1 %

Procedure:
To a solution of 6-hydroxy-benzofuran-3-carboxylic acid methyl ester (1.7 g, 8.8 mmol) in DMF (88 mL) was added Cs2CO3 (8.6 g, 1.8 mmol) followed by 2-chloro-thiazolo[4,5-b]pyridine hydrochloride (1.8 g, 8.8 mmol) and the reaction mixture was stirred (rt, 3 h). The reaction mixture was treated with water (50 mL) to form a solid. The solid was filtered to provide the title compound as a white solid (2.5 g, 87%). MS (ESI): mass calcd. for C16H10N2O4S, 326.0; m/z found, 327.0 [M+H]+. 1H NMR (400 MHz, CDCl3): 8.57 (dd, J=4.8, 1.6, 1H), 8.30 (s, 1H), 8.11 (d, J=8.6, 1H), 8.03 (dd, J=7.9, 1.6, 1H), 7.75 (d, J=2.1, 1H), 7.41 (dd, J=8.6, 2.1, 1H), 7.22 (dd, J=7.9, 4.8, 1H), 3.97 (s, 3H).
Reaction SMILES: Cl[CH2:2][C:3]([C:5]1[CH:10]=[CH:9][C:8]([NH:11][C:12](=[O:14])[CH3:13])=[C:7]([CH:15]([CH3:17])[CH3:16])[CH:6]=1)=[O:4].Cl.[N:19]1([C:25]2[C:29]3[CH:30]=[CH:31][CH:32]=[CH:33][C:28]=3[S:27][N:26]=2)[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]1>>[S:27]1[C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=2[C:25]([N:19]2[CH2:20][CH2:21][N:22]([CH2:2][C:3]([C:5]3[CH:10]=[CH:9][C:8]([NH:11][C:12](=[O:14])[CH3:13])=[C:7]([CH:15]([CH3:17])[CH3:16])[CH:6]=3)=[O:4])[CH2:23][CH2:24]2)=[N:26]1
Reactant: c1ccc2c(N3CCNCC3)nsc2c1
Reactant: CC(=O)Nc1ccc(C(=O)CCl)cc1C(C)C
Agent: Cl
Product: CC(=O)Nc1ccc(C(=O)CN2CCN(c3nsc4ccccc34)CC2)cc1C(C)C
Yield: 55.1 %

Procedure:
Starting with N-[4-(2-Chloro-acetyl)-2-isopropyl-phenyl]-acetamide (0.380 g, 1.498 mmole), and 3-piperazin-1-yl-benzo[d]isothiazole hydrochloride (0.383 g, 1.498 mmole, 1.0 eq) and following the procedure as outlined in Example 17, N-{4-[2-(4-Benzo[d]isothiazol-3-yl-piperazin-1-yl)-acetyl]-2-isopropyl-phenyl}-acetamide (0.360 g, 0.825 mmole) was obtained as its hydrochloride salt from treatment with dioxane/HCl(gas).
Reaction SMILES: [CH3:1][C:2]([C:5]([NH:7][C:8]1[N:17]=[C:16]([NH:18][C:19]([C:21]([CH3:24])([CH3:23])[CH3:22])=[O:20])[C:15]2[CH2:14][C:13](=O)[CH2:12][CH2:11][C:10]=2[N:9]=1)=[O:6])([CH3:4])[CH3:3].Cl.[F:27][C:28]([F:39])([F:38])[C:29]1[CH:30]=[C:31]([CH2:35][O:36][NH2:37])[CH:32]=[CH:33][CH:34]=1.C(N(CC)CC)C>C(O)C>[CH3:3][C:2]([C:5]([NH:7][C:8]1[N:17]=[C:16]([NH:18][C:19]([C:21]([CH3:22])([CH3:23])[CH3:24])=[O:20])[C:15]2[CH2:14][C:13](=[N:37][O:36][CH2:35][C:31]3[CH:32]=[CH:33][CH:34]=[C:29]([C:28]([F:27])([F:39])[F:38])[CH:30]=3)[CH2:12][CH2:11][C:10]=2[N:9]=1)=[O:6])([CH3:4])[CH3:1]
Reactant: CC(C)(C)C(=O)Nc1nc2c(c(NC(=O)C(C)(C)C)n1)CC(=O)CC2
Reactant: NOCc1cccc(C(F)(F)F)c1
Agent: Cl
Solvent: CCO
Solvent: CCN(CC)CC
Product: CC(C)(C)C(=O)Nc1nc2c(c(NC(=O)C(C)(C)C)n1)CC(=NOCc1cccc(C(F)(F)F)c1)CC2

Procedure:
This compound is prepared in a manner analogous to that of Step E of Example 12, using 3.5 grams (0.010 mole) of 2,4-di[(1,1-dimethylethyl)carbonylamino]-5,6,7,8-tetrahydro-6-quinazolinone (prepared in Step C of Example 12) and 2.7 grams (0.012 mole) of O-(3-trifluoromethylphenylmethyl)hydroxylamine hydrochloride in about 45 mL of ethanol. This preparation differs from Step E of Example 12 in that prior to heating at reflux for four hours, 1.5 grams (0.01 5 mole) of triethylamine is added as an acid acceptor, yielding 2,4-di[(1,1-dimethylethyl)carbonylamino]-6-(3-trifluoromethylphenylmethoxyimino)-5,6,7,8-tetrahydroquinazoline.
Reaction SMILES: [OH2:1].[O:2]=[CH:3][C:4]1[CH:12]=[CH:11][C:9]([OH:10])=[C:6]([O:7][CH3:8])[CH:5]=1.OO>C(O)(C)C>[CH3:8][O:7][C:6]1[CH:5]=[C:4]([CH:3]=[O:2])[CH:12]=[C:11]([C:11]2[C:9]([OH:1])=[C:6]([O:7][CH3:8])[CH:5]=[C:4]([CH:3]=[O:2])[CH:12]=2)[C:9]=1[OH:10]
Reactant: O
Reactant: COc1cc(C=O)ccc1O
Agent: OO
Solvent: CC(C)O
Product: COc1cc(C=O)cc(-c2cc(C=O)cc(OC)c2O)c1O
Reaction time: 21 h
Yield: 82 %

Procedure:
A 2 liter, round bottom flask was charged with 261.7 milligrams (13085 units) of medium purity, soybean peroxidase, 600 mL water, 900 mL isopropanol, and 157.36 grams (1.0342 moles) vanillin. The mixture was heated to 45°-50° C. Over 18-24 hours, 120 mL of 30% hydrogen peroxide was then metered into the reaction mixture. The product precipitated out of solution during peroxide addition affording 127.63 grams (82% theory) of dehydrodivanillin (CAS Registry No. 2092-49-1) which has the following chemical formula: ##STR10##