Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [H-].[Na+].[C:3]([O:7][C:8]([N:10]1[CH2:15][CH2:14][NH:13][C:12](=[O:16])[CH2:11]1)=[O:9])([CH3:6])([CH3:5])[CH3:4].Cl[CH2:18][CH2:19][N:20]1[CH2:24][CH2:23][CH2:22][CH2:21]1.Cl.ClCCN1CCCC1>CN(C)C(=O)C.C1(C)C=CC=CC=1>[C:3]([O:7][C:8]([N:10]1[CH2:15][CH2:14][N:13]([CH2:18][CH2:19][N:20]2[CH2:24][CH2:23][CH2:22][CH2:21]2)[C:12](=[O:16])[CH2:11]1)=[O:9])([CH3:6])([CH3:4])[CH3:5]
Reactant: CC(C)(C)OC(=O)N1CCNC(=O)C1
Reactant: ClCCN1CCCC1
Agent: Cl
Agent: [H-]
Agent: [Na+]
Solvent: CC(=O)N(C)C
Solvent: Cc1ccccc1
Product: CC(C)(C)OC(=O)N1CCN(CCN2CCCC2)C(=O)C1
Temperature: 25 °C
Reaction time: 16 h
Yield: 42 %

Procedure:
Sodium hydride (55% dispersion in mineral oil, 1.96 g, 45 mmol) was added portionwise at room temperature to a solution of 3-oxo-piperazine-1-carboxylic acid tert-butyl ester (6.01 g, 30.0 mmol) in N,N-dimethylacetamide (150 ml), then a solution of 1-(2-chloroethyl)-pyrrolidine in toluene [prepared from commercially available 1-(2-chloroethyl)-pyrrolidine hydrochloride (16.1 g, 94.5 mmol) by partitioning between toluene (70 ml) and 1 M aq. sodium hydroxide solution (70 ml) and drying of the organic layer with Na2SO4] was added dropwise. The reaction mixture was stirred at room temperature for 16 h, then heated at 75° C. for 80 min. After cooling, the reaction mixture was partitioned between diethyl ether and sat. aq. sodium hydrogen-carbonate solution. The organic layer was dried (Na2SO4) and evaporated. Crystallization of the residue from diethyl ether afforded the title compound (3.74 g, 42%). White solid, MS (ISP)=298.2 (M+H)+.
Reaction SMILES: [Si]([O:8][CH2:9][C:10]1[CH:25]=[CH:24][C:13]2=[C:14]3[C:19](=[C:20]([NH2:22])[N:21]=[C:12]2[CH:11]=1)[N:18]=[C:17](Cl)[CH:16]=[CH:15]3)(C(C)(C)C)(C)C.ClC1C(C#N)=NC=C([CH2:33][CH2:34][C:35]2[CH:40]=[CH:39][C:38]([O:41][CH2:42][CH2:43][CH3:44])=[CH:37][CH:36]=2)C=1>>[NH2:22][C:20]1[C:19]2[N:18]=[CH:17][C:16]([CH2:33][CH2:34][C:35]3[CH:40]=[CH:39][C:38]([O:41][CH2:42][CH2:43][CH3:44])=[CH:37][CH:36]=3)=[CH:15][C:14]=2[C:13]2[CH:24]=[CH:25][C:10]([CH2:9][OH:8])=[CH:11][C:12]=2[N:21]=1
Reactant: CC(C)(C)[Si](C)(C)OCc1ccc2c(c1)nc(N)c1nc(Cl)ccc12
Reactant: CCCOc1ccc(CCc2cnc(C#N)c(Cl)c2)cc1
Product: CCCOc1ccc(CCc2cnc3c(N)nc4cc(CO)ccc4c3c2)cc1

Procedure:
(5-Amino-2-(4-propoxyphenethyl)benzo[f][1,7]naphthyridin-8-yl)methanol was prepared from 8-((tert-butyldimethylsilyloxy)methyl)-3-chlorobenzo[f][1,7]naphthyridin-5-amine (from Example 99/step 1) and 3-chloro-5-(4-propoxyphenethyl)picolinonitrile (from Example 79/step 2) following the procedures described for Example 44/Step 4 and Example 99/step 3 (deprotection of TBS). 1H NMR (acetone-d6): δ 8.79 (d, 1H), 8.70 (d, 1H), 8.35 (d, 1H), 7.61 (d, 1H), 7.33 (dd, 1H), 7.17 (d, 2H), 6.83 (d, 2H), 6.57 (br s, 2H), 4.77 (d, 2H), 4.34 (t, 1H), 3.89 (t, 2H), 3.22 (t, 2H), 3.06 (t, 2H), 1.83-1.70 (m, 2H), 1.00 (t, 3H). LRMS [M+H]=388.2.
Reaction SMILES: [C:1]([C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:14]=[CH:13][C:12]([O:15][CH2:16][CH2:17][CH2:18][C:19]([OH:21])=[O:20])=[CH:11][CH:10]=2)=[CH:5][CH:4]=1)#[N:2].C([O-])([O-])=O.[K+].[K+].Cl.[NH2:29][OH:30].Cl>O.C1COCC1.CCO>[OH:30][NH:29][C:1]([C:3]1[CH:4]=[CH:5][C:6]([C:9]2[CH:14]=[CH:13][C:12]([O:15][CH2:16][CH2:17][CH2:18][C:19]([OH:21])=[O:20])=[CH:11][CH:10]=2)=[CH:7][CH:8]=1)=[NH:2]
Reactant: N#Cc1ccc(-c2ccc(OCCCC(=O)O)cc2)cc1
Reactant: NO
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: C1CCOC1
Solvent: CCO
Solvent: O
Product: N=C(NO)c1ccc(-c2ccc(OCCCC(=O)O)cc2)cc1
Temperature: 25 °C
Reaction time: 84 h
Yield: 107 %

Procedure:
A mixture of 4-(4′-cyanobiphenyl-4-yloxy)butyric acid (2.70 g, 9.60 mmol), EtOH (10 ml), THF (15 ml), K2CO3 (3.35 g, 24.2 mmol), and hydroxylamine hydrochloride (1.50 g, 21.6 mmol) was stirred at room temperature for 3.5 d, and then at 80° C. for 24 h. Water (100 ml) and 1N HCl (50 ml) were added, and the product was isolated by filtration and washed with water. The solid was suspended in MeCN (70 ml), heated to reflux, kept at room temp overnight, filtrated off, and dried under reduced pressure to yield 3.23 g (100%) of 4-(4′-(N-hydroxycarbamimidoyl)biphenyl-4-yloxy)butyric acid.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:24]=[CH:25][C:26]=1[F:27])[CH2:5][N:6]1[CH2:15][CH2:14][C:13]2[C:8](=[C:9]([OH:22])[C:10](=[O:21])[N:11]([CH3:20])[C:12]=2[C:16]([O:18][CH3:19])=[O:17])[C:7]1=[O:23].[C:28](=O)([O-])[O-].[Cs+].[Cs+].IC>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([CH:24]=[CH:25][C:26]=1[F:27])[CH2:5][N:6]1[CH2:15][CH2:14][C:13]2[C:8](=[C:9]([O:22][CH3:28])[C:10](=[O:21])[N:11]([CH3:20])[C:12]=2[C:16]([O:18][CH3:19])=[O:17])[C:7]1=[O:23]
Reactant: COC(=O)c1c2c(c(O)c(=O)n1C)C(=O)N(Cc1ccc(F)c(Cl)c1)CC2
Reactant: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CI
Solvent: CN(C)C=O
Product: COC(=O)c1c2c(c(OC)c(=O)n1C)C(=O)N(Cc1ccc(F)c(Cl)c1)CC2
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution of methyl 6-(3-chloro-4-fluorobenzyl)-4-hydroxy-2-methyl-3,5-dioxo-2,3,5,6,7,8-hexahydro-2,6-naphthyridine-1-carboxylate (7.25 g, 18 mmol) in anhydrous DMF (75 mL) was added cesium carbonate (5.98 g, 18 mmol) and iodomethane (2.86 mL, 46 mmol). The reaction was stirred at room temperature overnight, and LCMS showed 70% completion. The reaction was heated to 50° C. for 7 hours and then allowed to stir at room temperature again overnight. LCMS indicated completion. The reaction was concentrated to dryness, and the resulting residue was dissolved in chloroform. The solution was extracted twice with saturated Na2SO3 solution, dried over sodium sulfate, filtered, and evaporated to afford a dark brown oil.
Reaction SMILES: [C:1](O)(=[O:23])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH3:22].C(O)(=O)C>CCOCC>[CH2:1]([OH:23])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH3:22]
Reactant: CCCCCCCCCCCCCCCCCCCCCC(=O)O
Solvent: CCOCC
Solvent: CC(=O)O
Product: CCCCCCCCCCCCCCCCCCCCCCO
Yield: 26.1 %

Procedure:
4 g of docosanoic acid are dissolved in 150 ml of anhydrous ether. LeAlH4 is progressively introduced. On completion of the reaction, 150 ml of an aqueous solution of 1 N acetic acid are introduced. The ethereal phase is then separated off, decanted and dried. Rectification in vacuo gives approximately 1 g of 1-docosanol.
Reaction SMILES: [N:1]([CH2:4][C:5]1[CH2:6][S:7][C@@H:8]2[CH:15]([NH:16][C:17](=[O:28])/[C:18](/[C:22]3[N:23]=[C:24]([NH2:27])[S:25][CH:26]=3)=[N:19]\[O:20][CH3:21])[C:14](=[O:29])[N:9]2[C:10]=1[C:11]([OH:13])=[O:12])=[N+]=[N-].CO.[C:32]([OH:38])([C:34]([F:37])([F:36])[F:35])=[O:33]>[Ni].CO>[F:35][C:34]([F:37])([F:36])[C:32]([OH:38])=[O:33].[NH2:1][CH2:4][C:5]1[CH2:6][S:7][C@@H:8]2[CH:15]([NH:16][C:17](=[O:28])/[C:18](/[C:22]3[N:23]=[C:24]([NH2:27])[S:25][CH:26]=3)=[N:19]\[O:20][CH3:21])[C:14](=[O:29])[N:9]2[C:10]=1[C:11]([OH:13])=[O:12]
Reactant: CO/N=C(\C(=O)NC1C(=O)N2C(C(=O)O)=C(CN=[N+]=[N-])CS[C@H]12)c1csc(N)n1
Agent: [Ni]
Solvent: O=C(O)C(F)(F)F
Solvent: CO
Product: CO/N=C(\C(=O)NC1C(=O)N2C(C(=O)O)=C(CN)CS[C@H]12)c1csc(N)n1
Yield: 45 %

Procedure:
To a stirred suspension of Raney nickel (16 g.) in MeOH (13 ml.) at 0° was added a solution of 3-azidomethyl-7-[2-(2-aminothiazol-4-yl)-2-((Z)-methoxyimino)acetamido]ceph-3-em-4-carboxylic acid (2.96 g.) in MeOH/TFA (14 ml., 1.13 ml.). After effervescence ceased the mixture was diluted with MeOH and filtered through paper. The filtrate was evaporated, the residue purified by HPLC using water/HOAc/MeOH 79:1:20 v/v/v as eluant and the product dried over P2O5 to give 3-aminomethyl-7-[2-(2-aminothiazol-4-yl)-2-((Z)-methoxyimino)acetamido]ceph-3-em-4-carboxylic acid trifluoroacetate (yield 45%) having the following n.m.r. in solvent A: 3.5-4.2 (m, 4H); 3.9 (s, 3H); 5.15 (d, 1H); 5.85 (d, 1H); 6.75 (s, 1H).
Reaction SMILES: [C:1](Cl)(=[O:10])[C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][CH:3]=1.C(Cl)Cl.[CH2:15]([N:17]([CH2:37][CH3:38])[CH2:18][CH2:19][CH2:20][O:21][C:22]1[CH:27]=[CH:26][C:25]([C:28]2[O:29][C:30]3[CH:36]=[CH:35][CH:34]=[CH:33][C:31]=3[CH:32]=2)=[CH:24][CH:23]=1)[CH3:16]>O>[C:1]([C:32]1[C:31]2[CH:33]=[CH:34][CH:35]=[CH:36][C:30]=2[O:29][C:28]=1[C:25]1[CH:26]=[CH:27][C:22]([O:21][CH2:20][CH2:19][CH2:18][N:17]([CH2:15][CH3:16])[CH2:37][CH3:38])=[CH:23][CH:24]=1)(=[O:10])[C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][CH:3]=1
Reactant: COc1ccc(C(=O)Cl)cc1
Reactant: CCN(CC)CCCOc1ccc(-c2cc3ccccc3o2)cc1
Solvent: O
Solvent: ClCCl
Product: CCN(CC)CCCOc1ccc(-c2oc3ccccc3c2C(=O)c2ccc(OC)cc2)cc1
Reaction time: 0.17 h

Procedure:
To a solution of 1.02 g. (0.006 mol.) of p-anisoyl chloride in 75 ml. of methylene chloride was added 2.0 g. (6.2 mmol.) of the hydrochloride salt of 2-[4'-(3-diethylaminopropoxy)phenyl]benzofuran. The reaction mixture was cooled to 0°, 3.3 ml. (0.024 mol.) of stannic chloride was added and the resulting mixture was stirred for 10 minutes at 0° then for 2.75 hours at 25°. The mixture was then poured into water and stirred vigorously. The layers were separated and the organic phase was washed with 10% aqueous sodium carbonate solution and water, dried (MgSO4) and concentrated to give the title compound as an oil.
Reaction SMILES: [C:1]1([C:7]2[N:8]=[C:9]([C@@H:18]3[CH2:22][CH2:21][CH2:20][C@H:19]3[CH2:23][C:24]3[CH:25]=[C:26]([CH:30]=[CH:31][CH:32]=3)[C:27]([OH:29])=O)[O:10][C:11]=2[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:33]1([CH2:39][CH2:40][NH2:41])[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1.Cl.C(N=C=NCCCN(C)C)C>CN(C=O)C.CCOC(C)=O>[C:33]1([CH2:39][CH2:40][NH:41][C:27](=[O:29])[C:26]2[CH:30]=[CH:31][CH:32]=[C:24]([CH2:23][C@@H:19]3[CH2:20][CH2:21][CH2:22][C@H:18]3[C:9]3[O:10][C:11]([C:12]4[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=4)=[C:7]([C:1]4[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=4)[N:8]=3)[CH:25]=2)[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1
Reactant: O=C(O)c1cccc(C[C@@H]2CCC[C@H]2c2nc(-c3ccccc3)c(-c3ccccc3)o2)c1
Reactant: NCCc1ccccc1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: O=C(NCCc1ccccc1)c1cccc(C[C@@H]2CCC[C@H]2c2nc(-c3ccccc3)c(-c3ccccc3)o2)c1
Temperature: 25 °C
Reaction time: 2.5 h
Yield: 98.7 %

Procedure:
To a mixture of 3-{[(1S,2R)-2-(4,5-diphenyloxazol-2-yl)-1-cyclopentyl]methyl}benzoic acid (140 mg, 0.331 mmol) and 2-phenylethylamine (0.046 ml, 0.364 mmol) in DMF (5 ml) was added 1-hydroxybenzotrioxazole (49 mg, 0.364 mmol) and 1-ethyl-3-(3′-dimethylaminopropyl)carbodiimide hydrochloride (95 mg, 0.495 mmol). After stirring the mixture at room temperature for 2.5 hours, the reaction mixture was diluted with EtOAc (30 ml), washed with water, saturated sodium hydrogencarbonate solution, water, and brine. The resultant mixture was dried over magnesium sulfate, and evaporated in vacuo. The resultant residue was purified by silica gel column chromatography (hexane:EtOAc, 2:1 elution) to give N-(2-phenylethyl)-3-{[(1S,2R)-2-(4,5-diphenyloxazol-2-yl)-1-cyclopentyl]methyl}benzamide (172.1 mg, 99%).
Reaction SMILES: [F:1][C:2]1[CH:20]=[C:19]([N+:21]([O-])=O)[CH:18]=[CH:17][C:3]=1[CH2:4][NH:5][S:6]([NH:9][C:10](=[O:16])[O:11][C:12]([CH3:15])([CH3:14])[CH3:13])(=[O:8])=[O:7]>C(O)C.O1CCCC1.[Pd]>[NH2:21][C:19]1[CH:18]=[CH:17][C:3]([CH2:4][NH:5][S:6]([NH:9][C:10](=[O:16])[O:11][C:12]([CH3:15])([CH3:14])[CH3:13])(=[O:8])=[O:7])=[C:2]([F:1])[CH:20]=1
Reactant: CC(C)(C)OC(=O)NS(=O)(=O)NCc1ccc([N+](=O)[O-])cc1F
Agent: [Pd]
Solvent: C1CCOC1
Solvent: CCO
Product: CC(C)(C)OC(=O)NS(=O)(=O)NCc1ccc(N)cc1F
Reaction time: 6 h
Yield: 102.9 %

Procedure:
10% Pd/C (42 mg) was added to a solution of tert-butyl N-(2-fluoro-4-nitrobenzyl)sulfamoylcarbamate (135 mg) in ethanol and tetrahydrofuran. The mixture was charged with H2 and stirred for 6 h. The reaction mixture was filtered using celite and evaporated in vacuo to obtain tert-butyl N-(4-amino-2-fluorobenzyl)sulfamoylcarbamate (127 mg, 99%).
Reaction SMILES: [Br:1][C:2]1[CH:12]=[C:11]([F:13])[CH:10]=[C:9]([F:14])[C:3]=1[O:4][CH2:5][C:6]([OH:8])=O.[CH:15]([NH:18][NH:19][C:20](=[O:27])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)([CH3:17])[CH3:16].C(N(C(C)C)CC)(C)C.C1CN([P+](Br)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F>CN(C=O)C>[Br:1][C:2]1[CH:12]=[C:11]([F:13])[CH:10]=[C:9]([F:14])[C:3]=1[O:4][CH2:5][C:6]([N:18]([CH:15]([CH3:17])[CH3:16])[NH:19][C:20](=[O:27])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)=[O:8]
Reactant: CC(C)NNC(=O)c1ccccc1
Reactant: O=C(O)COc1c(F)cc(F)cc1Br
Agent: Br[P+](N1CCCC1)(N1CCCC1)N1CCCC1
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: CC(C)N(NC(=O)c1ccccc1)C(=O)COc1c(F)cc(F)cc1Br
Yield: 32.5 %

Procedure:
A solution of (2-bromo-4,6-difluoro-phenoxy)-acetic acid (0.92 g, 3.45 mmol) and benzoic acid N′-isopropyl-hydrazide (738 mg, 4.14 mmol) in DMF (20 ml) was treated with diisopropylethyl amine (1.5 ml, 8.625 mmol) and PyBroP (2.41 g, 5.175 mmol) at room temperature overnight. The reaction mixture was partitioned between 1N HCl and ethyl acetate. The organic layer was successively washed with saturated sodium bicarbonate and brine, then dried over sodium sulfate, filtered and concentrated. The crude was absorbed on silica and purified on a silica gel column with a 20-30% ethyl acetate/hexanes gradient to afford the product as a white solid (478 mg, 1.12 mmol, 32%).
Reaction SMILES: Cl.[F:2][C:3]1[CH:4]=[C:5]([CH:7]=[CH:8][C:9]=1[O:10][C:11]1[CH:16]=[CH:15][N:14]=[C:13]2[NH:17][CH:18]=[CH:19][C:12]=12)[NH2:6].C(N(CC)CC)C.[C:27](Cl)(=[O:29])[CH3:28].C(=O)(O)[O-].[Na+].C[O-].[Na+]>ClCCl>[F:2][C:3]1[CH:4]=[C:5]([NH:6][C:27](=[O:29])[CH3:28])[CH:7]=[CH:8][C:9]=1[O:10][C:11]1[CH:16]=[CH:15][N:14]=[C:13]2[NH:17][CH:18]=[CH:19][C:12]=12
Reactant: CC(=O)Cl
Reactant: Nc1ccc(Oc2ccnc3[nH]ccc23)c(F)c1
Agent: C[O-]
Agent: Cl
Agent: O=C([O-])O
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CC(=O)Nc1ccc(Oc2ccnc3[nH]ccc23)c(F)c1
Temperature: 0 °C
Reaction time: 2 h

Procedure:
5.00 g (17.9 mmol) of 3-fluoro-4-(1H-pyrrolo[2,3-b]pyridin-4-yloxy)aniline hydrochloride are suspended in 100 ml of dichloromethane and cooled to 0° C. 9.97 ml (71.5 mmol) of triethylamine and 3.81 ml (53.6 mmol) of acetyl chloride are added dropwise, and the mixture is stirred at 0° C. for another 2 hours. Saturated sodium bicarbonate solution is added, and the mixture is stirred at RT for 10 min. The mixture is then extracted twice with dichloromethane. Insoluble components are dissolved using a little acetone, and the mixture is diluted with dichloromethane and washed with saturated sodium chloride solution. The combined organic phases are dried over magnesium sulfate and the solvent is removed under reduced pressure. The crude product is taken up in 100 ml of ethanol. 3.31 ml (17.9 mmol) of 5.4 M sodium methoxide solution are added, and the mixture is stirred at RT for 30 min. The mixture is concentrated and the product is purified by chromatography on silica gel (mobile phase: dichloromethane/methanol (7N ammonia) 100:1 to 100:5).
Reaction SMILES: [Cl:1][C:2]1[CH:24]=[CH:23][C:5]([CH2:6][N:7]2[C:15]3[C:10](=[CH:11][C:12]([OH:16])=[CH:13][CH:14]=3)[C:9]([CH3:17])=[C:8]2[CH2:18][CH2:19][C:20]([OH:22])=[O:21])=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].[CH2:31](Br)[CH:32]=[CH2:33]>CC(C)=O.O>[Cl:1][C:2]1[CH:24]=[CH:23][C:5]([CH2:6][N:7]2[C:15]3[C:10](=[CH:11][C:12]([O:16][CH2:33][CH:32]=[CH2:31])=[CH:13][CH:14]=3)[C:9]([CH3:17])=[C:8]2[CH2:18][CH2:19][C:20]([OH:22])=[O:21])=[CH:4][CH:3]=1
Reactant: C=CCBr
Reactant: Cc1c(CCC(=O)O)n(Cc2ccc(Cl)cc2)c2ccc(O)cc12
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Solvent: O
Product: C=CCOc1ccc2c(c1)c(C)c(CCC(=O)O)n2Cc1ccc(Cl)cc1

Procedure:
Using 845 mg of the product of Example 23 as starting material, diluted in 23 ml of dimethyl ketone, 476 mg of potassium carbonate and 225 μl of allyl bromine was added. The reaction was refluxed overnight. The reaction was then diluted with water and the acetone removed in vacuo. Then the reaction was extracted with CH3CO2Et and the organic phase was dried and concentrated to yield after flash chromatography (hexane 8, ethyl acetate 2) 790 mg of the compound, which was then hydrolyzed following the procedure of Example 2.
Reaction SMILES: C(OC([N:8]1[CH2:13][CH2:12][C@@H:11]([C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([CH3:20])[CH:15]=2)[C@H:10]([O:21][CH3:22])[CH2:9]1)=O)(C)(C)C.[ClH:23]>CCOC(C)=O>[ClH:23].[CH3:20][C:16]1[CH:15]=[C:14]([C@@H:11]2[CH2:12][CH2:13][NH:8][CH2:9][C@H:10]2[O:21][CH3:22])[CH:19]=[CH:18][CH:17]=1
Reactant: CO[C@@H]1CN(C(=O)OC(C)(C)C)CC[C@H]1c1cccc(C)c1
Agent: Cl
Solvent: CCOC(C)=O
Product: CO[C@@H]1CNCC[C@H]1c1cccc(C)c1
Temperature: 0 °C
Reaction time: 0.17 h

Procedure:
To a solution of trans-N-t-butoxycarbonyl-4-(3-methylphenyl)-3 methoxy piperidine, (0.20 g, 0.65 mmol) in EtOAc (50 ml) at 0° C. was bubbled HCl gas until saturated. The reaction was stirred at 0° C. for 10 min and then the solvent evaporated in vacuo to afford the product as a white foam.
Reaction SMILES: Cl[C:2]1[N:7]2[N:8]=[C:9]([S:21][CH3:22])[C:10]([S:11]([C:14]3[CH:19]=[CH:18][C:17]([CH3:20])=[CH:16][CH:15]=3)(=[O:13])=[O:12])=[C:6]2[N:5]=[C:4]([CH3:23])[CH:3]=1.[CH3:24][NH:25][CH3:26]>CCO>[CH3:24][N:25]([CH3:26])[C:2]1[N:7]2[N:8]=[C:9]([S:21][CH3:22])[C:10]([S:11]([C:14]3[CH:19]=[CH:18][C:17]([CH3:20])=[CH:16][CH:15]=3)(=[O:13])=[O:12])=[C:6]2[N:5]=[C:4]([CH3:23])[CH:3]=1
Reactant: CSc1nn2c(Cl)cc(C)nc2c1S(=O)(=O)c1ccc(C)cc1
Reactant: CNC
Solvent: CCO
Product: CSc1nn2c(N(C)C)cc(C)nc2c1S(=O)(=O)c1ccc(C)cc1

Procedure:
In an analogous manner to that described in Example 5, from 7-chloro-5-methyl-2-methylsulphanyl-3-(toluene-4-sulphonyl) -pyrazolo[1,5-a]pyrimidine and dimethylamine in EtOH there was obtained dimethyl-[5-methyl-2-methylsulphanyl-3-(toluene-4-sulphonyl)-pyrazolo[1,5-a]pyrimidin-7-yl]-amine as colorless crystals, m.p. >230°.
Reaction SMILES: [OH:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH2:4][CH2:5][C:6]2=O.C([BH3-])#N.[Na+]>ClC(Cl)C.[I-].[Zn+2].[I-]>[CH2:6]1[C:7]2[CH:8]=[CH:9][CH:10]=[C:2]([OH:1])[C:3]=2[CH2:4][CH2:5]1
Reactant: O=C1CCc2c(O)cccc21
Agent: [BH3-]C#N
Agent: [I-]
Agent: [Na+]
Solvent: CC(Cl)Cl
Product: Oc1cccc2c1CCC2
Yield: 92.9 %

Procedure:
A mixture of 4-hydroxy-indan-1-one (5.0 g, 33.7 mmol), sodium cyanoborohydride (6.4 g, 101.1 mmol), and zinc iodide (32.3 g, 101.1 mmol) in dichloroethane, was heated at reflux for two hours. The reaction mixture was then filtered through 50 g SiO2 while still warm, eluting further with dichloroethane. The filtrate was collected and concentrated under vacuum. The residue was added to diethyl ether and the resulting white precipitate was filtered off. The filtrate was collected and concentrated in vacuo to give 4.2 g of the title compound with purity high enough for subsequent use. 400 MHz 1H NMR (DMSO-d6) δ 9.06 (s, 1H), 6.86 (t, 1H, J=7.8 Hz), 6.59 (d, 1H, J=7.8 Hz), 6.48 (d, 1H, J=7.8 Hz), 2.75 (t, 2H, J=7.3 Hz), 2.67 (t, 2H, J=7.3 Hz), 1.92 (m, 2H).
Reaction SMILES: [F:1][C:2]1[CH:3]=[CH:4][C:5]([CH3:32])=[C:6]([CH:31]=1)[O:7][CH2:8][C:9]1[C:18]([C:19]2[CH:24]=[CH:23][C:22]([OH:25])=[CH:21][C:20]=2[O:26][CH3:27])=[CH:17][CH:16]=[C:15]2[C:10]=1[C:11]([CH3:30])=[CH:12][C:13]([CH3:29])([CH3:28])[NH:14]2.C(=O)([O-])[O-].[K+].[K+].[CH2:39](Br)[C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1.C(OCC)(=O)C>CN(C)C=O>[CH2:39]([O:25][C:22]1[CH:23]=[CH:24][C:19]([C:18]2[C:9]([CH2:8][O:7][C:6]3[CH:31]=[C:2]([F:1])[CH:3]=[CH:4][C:5]=3[CH3:32])=[C:10]3[C:15](=[CH:16][CH:17]=2)[NH:14][C:13]([CH3:28])([CH3:29])[CH:12]=[C:11]3[CH3:30])=[C:20]([O:26][CH3:27])[CH:21]=1)[C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1
Reactant: COc1cc(O)ccc1-c1ccc2c(c1COc1cc(F)ccc1C)C(C)=CC(C)(C)N2
Reactant: BrCc1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: COc1cc(OCc2ccccc2)ccc1-c1ccc2c(c1COc1cc(F)ccc1C)C(C)=CC(C)(C)N2
Temperature: 60 °C
Reaction time: 0.67 h
Yield: 19 %

Procedure:
5-(5-Fluoro-2-methylphenoxymethyl)-6-(4-hydroxy-2-methoxyphenyl)-2,2,4-tri methyl-1,2-dihydroquinoline (Reference Compound No. 5-3, 20.1 mg, 0.046 mmol), potassium carbonate (16.7 mg, 0.12 mmol) and benzyl bromide (6.6 μL, 0.055 mmol) were dissolved in anhydrous N,N-dimethylformamide (0.5 mL), and the mixture was stirred at 60° C. for 40 minutes. Ethyl acetate (50 mL) was added to the reaction mixture, and the whole was washed with water (50 mL) and saturated brine (30 mL), dried over anhydrous magnesium sulfate, and then the solvent was removed under reduced pressure. The residue was purified by silica gel column chromatography (hexane-ethyl acetate) to give the titled compound (5.1 mg) as a colorless oil. (Yield 19%)
Reaction SMILES: Cl[CH2:2][CH2:3][NH:4][C:5](=[O:15])[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=1[N+:12]([O-:14])=[O:13].[F-].[K+]>C(#N)C>[C:5]1([C:6]2[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=2[N+:12]([O-:14])=[O:13])[O:15][CH2:2][CH2:3][N:4]=1
Reactant: O=C(NCCCl)c1ccccc1[N+](=O)[O-]
Agent: [F-]
Agent: [K+]
Solvent: CC#N
Product: O=[N+]([O-])c1ccccc1C1=NCCO1
Temperature: 25 °C
Reaction time: 24 h
Yield: 98.3 %

Procedure:
To a solution of N-(2-chloroethyl)-2-nitrobenzamide (3.63 g) in acetonitrile (100 ml) was slowly added 40% potassium fluoride on alumina (10 g). This slurry was stirred at ambient temperature for 24 hours. The potassium fluoride on alumina was filtered through a bed of celite, washed with ethyl acetate. The solvent was evaporated to give 2-(2,5-oxazolinyl)nitrobenzene (3.0 g).
Reaction SMILES: [CH3:1][O:2][C:3](=[O:16])[C:4]1[CH:13]=[C:12]([Br:14])[C:11]([OH:15])=[C:6]([C:7]([O:9][CH3:10])=[O:8])[CH:5]=1.C(N(C(C)C)CC)(C)C.[CH3:26][O:27][CH2:28]Cl>C(Cl)(Cl)Cl>[CH3:1][O:2][C:3](=[O:16])[C:4]1[CH:13]=[C:12]([Br:14])[C:11]([O:15][CH2:26][O:27][CH3:28])=[C:6]([C:7]([O:9][CH3:10])=[O:8])[CH:5]=1
Reactant: COC(=O)c1cc(Br)c(O)c(C(=O)OC)c1
Reactant: COCCl
Solvent: ClC(Cl)Cl
Solvent: CCN(C(C)C)C(C)C
Product: COCOc1c(Br)cc(C(=O)OC)cc1C(=O)OC
Temperature: 25 °C
Reaction time: 8 h
Yield: 60.1 %

Procedure:
To a solution of 5-bromo-4-hydroxyisophthalic acid dimethyl ester (12.3 g) in chloroform (130 mL) were successively added diisopropylethylamine (8.24 g) and methoxymethyl chloride (4.11 g) under ice-cooling, and the mixture was stirred at room temperature overnight. The reaction solution was washed successively with 1N hydrochloric acid, water, and saturated brine, dried over anhydrous sodium sulfate, and concentrated. The residue was purified by column chromatography on silica gel (hexane:ethyl acetate=5:1, v/v) to give the title compound (8.52 g).
Reaction SMILES: [Cl-].[NH4+].O.[CH3:4][O:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2[CH2:16][CH:15]([C:17]3[CH:22]=[CH:21][C:20]([N+:23]([O-])=O)=[CH:19][CH:18]=3)[N:14]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[N:13]=2)=[CH:8][CH:7]=1>[Fe].C(O)(=O)C>[NH2:23][C:20]1[CH:21]=[CH:22][C:17]([CH:15]2[N:14]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[N:13]=[C:12]([C:9]3[CH:8]=[CH:7][C:6]([O:5][CH3:4])=[CH:11][CH:10]=3)[CH2:16]2)=[CH:18][CH:19]=1
Reactant: COc1ccc(C2=NN(c3ccccc3)C(c3ccc([N+](=O)[O-])cc3)C2)cc1
Agent: [Fe]
Agent: [Cl-]
Agent: [NH4+]
Solvent: CC(=O)O
Solvent: O
Product: COc1ccc(C2=NN(c3ccccc3)C(c3ccc(N)cc3)C2)cc1
Reaction time: 0.5 h
Yield: 80.5 %

Procedure:
15.8 g of metallic iron powder and 1.6 g of ammonium chloride were dispersed in a mixed solution of 140 ml of iospropyl alcohol and 14 ml of water, and, while stirring and refluxing under heating, 13.1 g of 3-(4-methoxyphenyl)-5-(4-nitrophenyl)-1-phenyl-2-pyrazoline was added thereto. After refluxing for 2 hours, 10 ml of acetic acid was added thereto, and the reaction was thereafter continued for 30 minutes under refluxing. Solids were removed by filtration using sellaite, and 150 ml of water was added to the filtrate. Crystals precipitated were collected by filtration to obtain 9.7 g of 5-(4-aminophenyl)-3-(4-methoxyphenyl)-1-phenyl-2-pyrazoline. m.p. 164°-166° C.