Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][N:2]([CH3:24])[C:3]1[CH:8]=[CH:7][C:6]([NH:9][C:10](=[O:23])[C:11]2[CH:16]=[CH:15][C:14]([N+:17]([O-])=O)=[C:13]([N+:20]([O-])=O)[CH:12]=2)=[CH:5][CH:4]=1.[CH3:25][N:26]([CH3:44])[C:27]1[CH:32]=[CH:31][C:30]([NH:33][C:34]([C:36]2[CH:43]=[CH:42][C:39]([CH:40]=O)=[CH:38][CH:37]=2)=[O:35])=[CH:29][CH:28]=1>>[CH3:1][N:2]([CH3:24])[C:3]1[CH:8]=[CH:7][C:6]([NH:9][C:10]([C:11]2[CH:16]=[CH:15][C:14]3[NH:17][C:40]([C:39]4[CH:38]=[CH:37][C:36]([C:34](=[O:35])[NH:33][C:30]5[CH:31]=[CH:32][C:27]([N:26]([CH3:44])[CH3:25])=[CH:28][CH:29]=5)=[CH:43][CH:42]=4)=[N:20][C:13]=3[CH:12]=2)=[O:23])=[CH:5][CH:4]=1
Reactant: CN(C)c1ccc(NC(=O)c2ccc([N+](=O)[O-])c([N+](=O)[O-])c2)cc1
Reactant: CN(C)c1ccc(NC(=O)c2ccc(C=O)cc2)cc1
Product: CN(C)c1ccc(NC(=O)c2ccc(-c3nc4cc(C(=O)Nc5ccc(N(C)C)cc5)ccc4[nH]3)cc2)cc1

Procedure:
Compound 197 was prepared according to the procedure similar to that described in Scheme III from N-(4-dimethylaminophenyl)-3,4-dinitrobenzamide and 4-(4-dimethylaminophenyl)aminocarbonylbenzaldehyde. [M+H]+ calcd for C31H30N6O2: 519.24; found: 519.04.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:18])[C:4]1[CH:9]=[CH:8][C:7]([N+:10]([O-:12])=[O:11])=[C:6](/[CH:13]=C/N(C)C)[CH:5]=1.C1C[O:22]CC1.O>>[CH3:1][O:2][C:3](=[O:18])[C:4]1[CH:9]=[CH:8][C:7]([N+:10]([O-:12])=[O:11])=[C:6]([CH:13]=[O:22])[CH:5]=1
Reactant: COC(=O)c1ccc([N+](=O)[O-])c(/C=C/N(C)C)c1
Reactant: C1CCOC1
Solvent: O
Product: COC(=O)c1ccc([N+](=O)[O-])c(C=O)c1
Temperature: 40 °C

Procedure:
Compound 3 (11.81 g 47.2 mmol) and NaIO4 (30.3 g 141.6 mmol) was dissolved in 250 mL THF/H2O 1:1 at room temperature. The dark red solution was warmed to about 40° C. while heavy precipitation occurred and the color changed to light brown. After 1 h the precipitate was removed by filtration and washed with 200 mL ethyl acetate. The organic layer was washed three times with saturated NaHCO3, once with brine and dried with Na2SO4. The solution was evaporated to dryness and the resulting oil was purified on a silicagel pad eluting with DCM-hexane gradient (30% to 60% DCM) to yield after evaporation yellow Compound 4.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1/[CH:7]=[CH:8]/[C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][N:13]=[C:12]2[C:18]1[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=1>CO>[F:24][C:21]1[CH:22]=[CH:23][C:18]([C:12]2[C:11]3[C:15](=[CH:16][CH:17]=[C:9]([CH2:8][CH2:7][C:2]4[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=4)[CH:10]=3)[NH:14][N:13]=2)=[CH:19][CH:20]=1
Reactant: Fc1ccc(-c2n[nH]c3ccc(/C=C/c4ccccn4)cc23)cc1
Solvent: CO
Product: Fc1ccc(-c2n[nH]c3ccc(CCc4ccccn4)cc23)cc1
Yield: 47 %

Procedure:
The title compound was prepared as described in Example 141 A, using 5-[(1 E)-2-pyridylvinyl]-3-(4-fluorophenyl)-1H-indazole (0.125 g, 0.4 mmol) in methanol and it was then purified by HPLC (0.060 g, 47% yield): 1H NMR (DMSO-d6) δ 13.14 (br s, 1H), 8.52 (d, 1H), 7.95 (m, 2H), 7.79 (s, 1H), 7.69 (ddd, 1H), 7.42 (dd, 1H), 7.22–7.35 (m, 5H), 3.12 (m, 4H); ES-MS (m/z) 318 [M+1]+.
Reaction SMILES: [CH:1]1([C:4]2[CH:5]=[CH:6][C:7]([C:16]([OH:18])=O)=[N:8][C:9]=2[O:10][CH2:11][C:12]([F:15])([F:14])[F:13])[CH2:3][CH2:2]1.[F:19][C:20]([F:30])([F:29])[CH:21]([C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][N:24]=1)[NH2:22]>>[F:30][C:20]([F:19])([F:29])[CH:21]([NH:22][C:16]([C:7]1[CH:6]=[CH:5][C:4]([CH:1]2[CH2:2][CH2:3]2)=[C:9]([O:10][CH2:11][C:12]([F:13])([F:14])[F:15])[N:8]=1)=[O:18])[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][N:24]=1
Reactant: O=C(O)c1ccc(C2CC2)c(OCC(F)(F)F)n1
Reactant: NC(c1ccccn1)C(F)(F)F
Product: O=C(NC(c1ccccn1)C(F)(F)F)c1ccc(C2CC2)c(OCC(F)(F)F)n1

Procedure:
The title compound was synthesized in analogy to Example 280c, using 5-cyclopropyl-6-(2,2,2-trifluoro-ethoxy)-pyridine-2-carboxylic acid (Example 301a) and 2,2,2-trifluoro-1-(pyridin-2-yl)ethanamine (CAN 35272-15-2) as starting materials, MS (EI): m/e=420.1 [M+H]+.
Reaction SMILES: [F:1][C:2]([F:25])([F:24])[C:3]1[CH:8]=[CH:7][C:6]([C:9]2[C:10]([C:15]([NH:17][CH:18]3[CH2:23][CH2:22][NH:21][CH2:20][CH2:19]3)=[O:16])=[CH:11][CH:12]=[CH:13][CH:14]=2)=[CH:5][CH:4]=1.C(=O)([O-])[O-].[K+].[K+].[CH2:32]([O:34][C:35](=[O:38])[CH2:36]Br)[CH3:33]>CN(C)C=O>[CH2:32]([O:34][C:35](=[O:38])[CH2:36][N:21]1[CH2:20][CH2:19][CH:18]([NH:17][C:15]([C:10]2[C:9]([C:6]3[CH:5]=[CH:4][C:3]([C:2]([F:1])([F:24])[F:25])=[CH:8][CH:7]=3)=[CH:14][CH:13]=[CH:12][CH:11]=2)=[O:16])[CH2:23][CH2:22]1)[CH3:33]
Reactant: O=C(NC1CCNCC1)c1ccccc1-c1ccc(C(F)(F)F)cc1
Reactant: CCOC(=O)CBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CCOC(=O)CN1CCC(NC(=O)c2ccccc2-c2ccc(C(F)(F)F)cc2)CC1
Temperature: 90 °C
Reaction time: 8 h

Procedure:
To a solution of 4-(4′-trifluoromethylbiphenyl-2-carbonylamino)piperidine (1.03 g) obtained in Example 8b) in dimethylformamide (5 mL) were added potassium carbonate (276 mg) and bromoacetic acid ethyl ester (223 μL). The mixture was stirred overnight at ambient temperature of 90° C., and then concentrated in vacuo. The residue was distributed with water and chloroform, and the aqueous layer was further extracted with chloroform. The organic layers were combined, washed with saturated brine, dried over sodium sulfate, concentrated in vacuo and purified by column chromatography on silica gel with chloroform:methanol=30:1 to give the title compound (598 mg).
Reaction SMILES: [CH3:1][S:2][C:3]1[CH:10]=[C:7]([CH:8]=O)[C:6]([OH:11])=[CH:5][CH:4]=1.CN(C)C=O.C(=O)([O-])[O-].[K+].[K+].[F:23][C:24]([F:33])([F:32])/[CH:25]=[CH:26]/[C:27]([O:29][CH2:30][CH3:31])=[O:28]>O>[CH3:1][S:2][C:3]1[CH:4]=[CH:5][C:6]2[O:11][CH:25]([C:24]([F:23])([F:33])[F:32])[C:26]([C:27]([O:29][CH2:30][CH3:31])=[O:28])=[CH:8][C:7]=2[CH:10]=1
Reactant: CCOC(=O)/C=C/C(F)(F)F
Reactant: CSc1ccc(O)c(C=O)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: CCOC(=O)C1=Cc2cc(SC)ccc2OC1C(F)(F)F
Temperature: 65 °C

Procedure:
5-Methylthiosalicylaldehyde (Step 1) (2.516 g, 14.96 mmole) was added to dimethylformamide (3.5 mL), potassium carbonate (2.27 g, 16.45 mmole) and ethyl 4,4,4-trifluorocrotonate (3.3 mL, 3.8 g, 22.4 mmole). The mixture was heated to 65° C. for 3 h. The reaction was cooled to room temperature, poured into H2O (50 mL), and extracted with diethyl ether (2×75 mL). The combined ethereal phases were washed with aqueous NaHCO3 solution (3×50 mL), aqueous 2 N HCl solution (3×50 mL), and brine (3×50 mL), dried over MgSO4, filtered, diluted with isooctane and partially concentrated in vacuo causing the precipitation of the ethyl ester (2.863 g, 60%) as a yellow powder: mp 87.8–89.6° C. This ester was of suitable purity to use without further purification.
Reaction SMILES: [C:1]1([O:8][CH3:9])[C:2](=[CH:4][CH:5]=[CH:6][CH:7]=1)[OH:3].C(N(C(C)C)CC)(C)C.[CH3:19][N:20]([CH3:25])[S:21](Cl)(=[O:23])=[O:22]>C1(C)C=CC=CC=1>[CH3:9][O:8][C:1]1[CH:7]=[CH:6][CH:5]=[CH:4][C:2]=1[O:3][S:21](=[O:23])(=[O:22])[N:20]([CH3:25])[CH3:19]
Reactant: CN(C)S(=O)(=O)Cl
Reactant: COc1ccccc1O
Solvent: Cc1ccccc1
Solvent: CCN(C(C)C)C(C)C
Product: COc1ccccc1OS(=O)(=O)N(C)C
Yield: 5.4 %

Procedure:
A solution of 24.8 g (0.2 mole) of guaiacol (Aldrich) and 34.9 g (0.27 mole) of diisopropylethylamine (Hunig's base, Aldrich) in 200 ml of toluene was added to a solution of 29 ml (0.27 mole) of dimethylsulfamoyl chloride (Aldrich) in 75 ml of toluene and the stirred reaction mixture was heated at reflux for 12 hr. The reaction mixture was successively washed with four 300 ml portions of 6N hydrochloric acid solution, 400 ml of water, three 200 ml portions of 20% sodium hydroxide solution, 400 ml of water and dried (magnesium sulfate). The solvent was evaporated under reduced pressure to give a brown, viscous oil that solidfied upon standing. The solid was recrystallized from ethyl ether-petroleum ether and was collected by filtration. The filtrate was evaporated under reduced pressure and the viscous, brown oil was purified by chromatography (4.5×90 cm glass column, 5.30 g of silica gel, ethyl acetate-hexanes, 1:8). Fractions containing the desired compound were combined and the solvents evaporated under reduced pressure to yield 2.5 g (5%) of the title compound as a light yellow liquid.
Reaction SMILES: [C:1]1([CH:7](Cl)[C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH:15]1[C:28]2[C:19](=[CH:20][C:21]3[C:26](C=2CCl)=[CH:25][CH:24]=[CH:23][CH:22]=3)[CH:18]=[CH:17][CH:16]=1.O=O>>[C:1]1([C:7]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)=[C:20]([C:19]2[CH:28]=[CH:15][CH:16]=[CH:17][CH:18]=2)[C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: ClCc1c2ccccc2cc2ccccc12
Reactant: ClC(c1ccccc1)c1ccccc1
Agent: O=O
Product: c1ccc(C(=C(c2ccccc2)c2ccccc2)c2ccccc2)cc1

Procedure:
N,N'-Bisbenzyl spirodiamide 11 was obtained by diethyl ether extraction from the brine-DMSO reaction mixture in 80-93% yield. Bulkier derivatives N,N'-bis(diphenylmethyl)-spirodiamide 12 and N,N'-bis(9-anthracenylmethyl)-spirodiamide 13 have also been synthesized from diphenymethyl chloride and 9-anthracenylmethyl chloride, respectively. N,N'-bis(9-anthracenylmethyl)spirodiamide 13 was synthesized using the same method as bisbenzyl derivative 11 and isolated by column chromatography in 35% yield. The anthracenyl group in 13 is sensitive to oxygen, so analytically pure crystalline product was collected directly from fractions by cooling the chromatography fractions in a refrigerator under nitrogen. Diphenylmethyl chloride itself reacted with the basic equilibrium mixture of sodium methylsulfinylcarbanion and spirodiamide dianion in DMSO to produce a fluorescent product, tetraphenylethene. By employing a 100% excess of diphenylmethyl chloride, N,N'-bis(diphenylmethyl)-spirodiamide 12 was isolated by column chromatography in 22% yield.
Reaction SMILES: [CH3:1][NH:2][C:3]1[CH:4]=[N:5][CH:6]=[CH:7][C:8]=1[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[CH3:15].[CH3:16][C:17]1[CH:18]=[C:19]([CH:23]=[C:24]([CH3:26])[CH:25]=1)[C:20]([OH:22])=O>CCCCCCC.CCOC(C)=O>[CH3:26][C:24]1[CH:23]=[C:19]([CH:18]=[C:17]([CH3:16])[CH:25]=1)[C:20]([N:2]([CH3:1])[C:3]1[CH:4]=[N:5][CH:6]=[CH:7][C:8]=1[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[CH3:15])=[O:22]
Reactant: CNc1cnccc1-c1ccccc1C
Reactant: Cc1cc(C)cc(C(=O)O)c1
Solvent: CCCCCCC
Solvent: CCOC(C)=O
Product: Cc1cc(C)cc(C(=O)N(C)c2cnccc2-c2ccccc2C)c1

Procedure:
The title compound was prepared in analogy to example 90, from N-methyl-4-o-tolylpyridin-3-amine (example 1, intermediate a) and 3,5-dimethylbenzoic acid (CAS RN 499-06-9) and using a gradient of n-heptane:EtOAc (100:0 to 0:100) for the chromatographic purification. Brown oil (3%). MS (ESI): m/z=331.18 [M+H]+.
Reaction SMILES: [CH3:1][NH:2][C:3](=[O:5])[CH3:4].C=O.[C:8]([OH:11])(=[O:10])[CH3:9]>>[C:3]([N:2]([CH2:9][C:8]([OH:11])=[O:10])[CH3:1])(=[O:5])[CH3:4]
Reactant: CNC(C)=O
Reactant: CC(=O)O
Agent: C=O
Product: CC(=O)N(C)CC(=O)O
Temperature: 130 °C
Reaction time: 0.5 h
Yield: 92 %

Procedure:
A 1 L autoclave was charged with N-methylacetamide (IX) (160 g, 2.2 mole), Co(OAc)2-4H2O (33 g, 0.13 mole), and acetic acid (1 L). After sealing the autoclave, 2200 psi (15,172 kPa) CO:H2 (70:30) was established at a25° C. with stirring at 2000 rpm. The contents of the autoclave were heated to 130° C. and 3200 psi (22,069 kPa) CO:H2 (70:30) was established. After approximately 0.5 h, rapid gas uptake was observed. The reaction mass was cooled to 85° C. Under a constant 3200 psi (22,069 kPa), 47 Wt. % formalin (180 mL, 2.97 mole) was delivered at 6 mL/min. The reaction was stirred at 85° C. for 30 min. after the formalin addition was complete. Then the reaction was cooled to 25° C., removed from the autoclave, and assayed for N-acetylsarcosine. This resulted in a 92% yield of (XX)
Reaction SMILES: [Cl:1][C:2]1[C:7]2[O:8][CH2:9][CH2:10][CH2:11][O:12][C:6]=2[CH:5]=[C:4]([CH:13]=O)[CH:3]=1.[CH2:15]([NH2:19])[CH:16]([CH3:18])[CH3:17].C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[Cl:1][C:2]1[C:7]2[O:8][CH2:9][CH2:10][CH2:11][O:12][C:6]=2[CH:5]=[C:4]([CH2:13][NH:19][CH2:15][CH:16]([CH3:18])[CH3:17])[CH:3]=1
Reactant: O=Cc1cc(Cl)c2c(c1)OCCCO2
Reactant: CC(C)CN
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: ClCCCl
Solvent: CC(=O)O
Product: CC(C)CNCc1cc(Cl)c2c(c1)OCCCO2
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To an ice cold mixture of 9-chloro-3,4-dihydro-2H-1,5-benzodioxepine-7-carbaldehyde (2.07 g) and of isobutylamine (7.5 ml 8 eq.) were combined in 1,2-dichloroethane (75 ml) and cooled in ice water bath. Acetic acid (5.68 ml) was then added and followed by sodium triacetoxyborohydride (2.75 g, 1.4 eq.). The mixture was allowed to stir at room temperature overnight. It was partitioned with aqueous K2CO3 (75 mL, 1.5M). The aqueous layer was extracted with of dichloromethane (75 ml×2). The organic layers were combined, washed with brine, dried over sodium sulfate, and concentrated. The residue was purified by flash column chromatography (10-100% ethyl acetate in hexanes) gave the desired amine as a light yellow oil: MS (m+1)=270.2.
Reaction SMILES: CS(O[CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][O:11][C:12]1[CH:21]=[CH:20][C:15]([C:16]([O:18][CH3:19])=[O:17])=[CH:14][CH:13]=1)(=O)=O.[CH2:22]([NH:25][CH2:26][CH2:27][CH3:28])[CH2:23][CH3:24].O.C(=O)(O)[O-].[Na+]>C(O)(C)C>[CH2:22]([N:25]([CH2:26][CH2:27][CH3:28])[CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][O:11][C:12]1[CH:21]=[CH:20][C:15]([C:16]([O:18][CH3:19])=[O:17])=[CH:14][CH:13]=1)[CH2:23][CH3:24]
Reactant: CCCNCCC
Reactant: COC(=O)c1ccc(OCCCCCOS(C)(=O)=O)cc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CC(C)O
Solvent: O
Product: CCCN(CCC)CCCCCOc1ccc(C(=O)OC)cc1
Temperature: 25 °C

Procedure:
A solution of the compound 25 (3.70 g) and dipropylamine (3.00 mL) in isopropyl alcohol (40 mL) was stirred at 60° C. for 16 hours. The reaction mixture was cooled to room temperature and saturated sodium bicarbonate water (40 mL) was added. The aqueous layer was extracted twice with ethyl acetate (50 mL). The combined organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate and then concentrated. The residue was purified by silica gel chromatography (ethyl acetate:methanol=10:90→0:100) to obtain the title compound (1.94 g) having the following physical properties.
Reaction SMILES: [CH2:1]([P:3]([OH:5])[OH:4])[CH3:2].[C:6](#[N:10])[C:7]([CH3:9])=[CH2:8].CC(N=NC(C#N)(C)C)(C#N)C>C(O)C>[CH2:1]([P:3]([CH2:8][CH:7]([C:6]#[N:10])[CH3:9])(=[O:5])[OH:4])[CH3:2]
Reactant: CCP(O)O
Reactant: C=C(C)C#N
Agent: CC(C)(C#N)N=NC(C)(C)C#N
Solvent: CCO
Product: CCP(=O)(O)CC(C)C#N
Yield: 85 %

Procedure:
94 g (1 mol) of ethylphosphonous acid (produced as in Example 1) and 67 g (1 mol) of methacrylonitrile are introduced into a four-neck round-bottom flask equipped with stirrer, reflux condenser, thermometer and nitrogen inlet and heated. At about 100° C., 98.4 g of a 5% strength solution of AIBN in ethanol are added dropwise over 1 h. Thereafter, the solvent was distilled off in vacuo to leave 137 g of ethyl(2-cyano-2-methylethyl)phosphinic acid.
Reaction SMILES: I.CS[N:4]1[CH2:10][C:9]2[CH:11]=[CH:12][CH:13]=[CH:14][C:8]=2[CH2:7][N:6]=[CH:5]1.[C:15]1([CH:21]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH2:22][NH2:23])[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.C(O)(C)C.[ClH:34]>CO>[ClH:34].[C:24]1([CH:21]([C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH2:22][NH:23][C:5]2[NH:4][CH2:10][C:9]3[CH:11]=[CH:12][CH:13]=[CH:14][C:8]=3[CH2:7][N:6]=2)[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1
Reactant: CSN1C=NCc2ccccc2C1
Reactant: NCC(c1ccccc1)c1ccccc1
Agent: Cl
Agent: I
Solvent: CC(C)O
Solvent: CO
Product: c1ccc(C(CNC2=NCc3ccccc3CN2)c2ccccc2)cc1
Temperature: 0 °C
Reaction time: 0.5 h

Procedure:
A flask containing 2-methylthio-2,5-dihydro-1H-2,4-benzodiazepine hydroiodide (3.20 g 1.00×10-2 mole) and 2,2-diphenylethylamine (5.91 g, 3.00×10-2 mole) was immersed in an oil bath which had been preheated to ca. 155° C. The reaction was stirred at between 150°-160° C. for ca. 30 minutes. The resulting solid mass was treated with isopropanol and that which did not dissolve was collected by filtration. This guanidine hydroiodide was dissolved in a two phase mixture of 5 molar aqueous NaOH (80 ml) and CH2Cl2 (80 ml). After stirring overnight the CH2Cl2 layer was separated. The aqueous alkaline phase was extracted with CH2Cl2 (2×). The CH2Cl2 layers were combined, washed with H2O (2×), washed with saturated aqueous NaCl, and dried over anhydrous Na2SO4. The drying agent was removed by filtration and the filtrate was evaporated at reduced pressure leaving a foam which was dissolved in methanol (35 ml). The solution was cooled to 0° C. before being treated with a methanolic solution of HCl. The solution was concentrated to ca. 10-15 ml at which point crystallization began. After standing ca. 30 minutes, isopropanol was added and the flask was refrigerated. After 1-1.5 hour the product was collected by filtration. Recrystallization from methanol/isopropanol afforded 3-(2,2-diphenylethylamino)-2,5-dihydro-1H-2,4-benzodiazepine hydrochloride as colorless crystals: 2.53 g (67%), m.p. 243°-245° C.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([CH:9]=[CH:10][CH:11]=1)[CH:7]=O)([O-:3])=[O:2].[NH:12]1[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[CH:14]=[C:13]1[C:21]1[CH:22]=[CH:23][C:24]([O:28][CH3:29])=[C:25]([NH2:27])[CH:26]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)(O)[O-].[Na+]>C(Cl)Cl.C(O)(=O)C>[NH:12]1[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[CH:14]=[C:13]1[C:21]1[CH:22]=[CH:23][C:24]([O:28][CH3:29])=[C:25]([NH:27][CH2:7][C:6]2[CH:9]=[CH:10][CH:11]=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=2)[CH:26]=1
Reactant: COc1ccc(-c2cc3ccccc3[nH]2)cc1N
Reactant: O=Cc1cccc([N+](=O)[O-])c1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CC(=O)O
Solvent: ClCCl
Product: COc1ccc(-c2cc3ccccc3[nH]2)cc1NCc1cccc([N+](=O)[O-])c1
Temperature: 25 °C
Reaction time: 1 h
Yield: 15.4 %

Procedure:
3-Nitrobenzaldehyde (0.302 g, 2.0 mmol) was added to a stirred mixture of 5-(1H-indol-2-yl)-2-methoxy-phenylamine (0.476 g, 2.0 mmol) in methylene chloride (125 mL), followed by acetic acid (0.2 g). The resulting mixture was stirred at room temperature for 1 hour. Sodium triacetoxyborohydride (0.46 g, 2.2 mmol) was added in one portion, and the resulting homogeneous solution was stirred at room temperature for 3 days. Saturated aqueous sodium bicarbonate solution (100 mL) was added and the mixture was stirred for 2 hours. The mixture was shaken, the organic layer was separated and dried over Na2SO4. The solvent was evaporated to give an orange oil. Recrystallization from ethyl acetate/hexane gave the product (115 mg), mp 160-162° C.
Reaction SMILES: [Br:1]N1C(=O)CCC1=O.[CH:9]1([CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21]O)[CH2:13][CH2:12][CH2:11][CH2:10]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>ClCCl>[Br:1][CH2:21][CH2:20][CH2:19][CH2:18][CH2:17][CH2:16][CH2:15][CH2:14][CH:9]1[CH2:13][CH2:12][CH2:11][CH2:10]1
Reactant: O=C1CCC(=O)N1Br
Reactant: OCCCCCCCCC1CCCC1
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Product: BrCCCCCCCCC1CCCC1
Reaction time: 8 h
Yield: 76.9 %

Procedure:
2.4 g of N-bromosuccinimide were added portionwise to a solution of 2.27 g of cyclopentane-octanol and 3.22 g of triphenylphosphine in 40 ml of dichloromethane in an ice bath. The reaction mixture was left to stand at room temperature overnight, filtered and the filtrate was concentrated. The residue was partitioned between 50 ml of methanol/water (vol.) 4:1 and 40 ml of hexane and the methanol phase was separated. The hexane phase was washed twice with 20 ml of methanol/water 4:1 each time and concentrated. Distillation of the residue in a bulb-tube at 130°-150° C./0.05 Torr gave 2.3 g of (8-bromooctyl)-cyclopentane as a colorless oil.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH2:8][C:7](=O)[CH2:6][CH2:5]2.[BH3-]C#[N:15].[Na+]>>[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH2:8][CH:7]([NH2:15])[CH2:6][CH2:5]2
Reactant: [BH3-]C#N
Reactant: O=C1CCc2cc(Br)ccc2C1
Agent: [Na+]
Product: NC1CCc2cc(Br)ccc2C1

Procedure:
(rac)-6-Bromo-1,2,3,4-tetrahydronaphthalen-2-ylamine is prepared from 6-Bromo-3,4-dihydro-1H-naphthalen-2-one (28) via a general procedure described previously for the reductive amination of ketones using NaBH3CN as reducing agent. (Borch, R. F.; Bernstein, M. D.; Durst, H. D. J. Am. Chem. Soc. 1971, 93, 2897-2904.). The purity of this material (brown oil) was >95%, as determined by 1H NMR spectroscopy, and was used without further purification. 1H NMR (CDCl3): δ 1.45 (br, 2H, NH2), 1.56 (m, 1H, H-3), 1.98 (m, 1H, H-3), 2.47 (dd, J=16.0 Hz, 9.5 Hz, 1H, H-1), 2.82 (m, 2H, H-4), 2.93 (dd, J=16.0 Hz, 4.5 Hz, 1H, H-1), 3.16 (m, 1H, H-2), 6.92 (d, J=8.0 Hz, 1H, H-8), 7.22 (m, 2H, overlapping H-5 and H-7). 13C NMR (CDCl3): δ 27.8 (CH2, C-4), 32.5 (CH2, C-3), 38.9 (CH2, C-1), 47.0 (CH, C-2), 119.3 (C—Br, C-6), 128.7 (CH, C-7), 130.9 (CH, C-8), 131.4 (CH, C-5), 134.3 (C-8a), 138.2 (C-4a). LCMS m/z calcd for C10H12BrN ([M]+) 225. Found 226 ([M+H]+).
Reaction SMILES: I[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([N:11]([S:19]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=3[S:28]([CH3:31])(=[O:30])=[O:29])(=[O:21])=[O:20])C(OC(C)(C)C)=O)[CH:9]=2)[N:4](C(OC(C)(C)C)=O)[N:3]=1.[N:39]1[CH:44]=[CH:43][C:42](B(O)O)=[CH:41][CH:40]=1.C(=O)([O-])O.[Na+]>CN(C)C=O>[CH3:31][S:28]([C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][C:22]=1[S:19]([NH:11][C:8]1[CH:9]=[C:10]2[C:5](=[CH:6][CH:7]=1)[NH:4][N:3]=[C:2]2[C:42]1[CH:43]=[CH:44][N:39]=[CH:40][CH:41]=1)(=[O:21])=[O:20])(=[O:29])=[O:30]
Reactant: OB(O)c1ccncc1
Reactant: CC(C)(C)OC(=O)N(c1ccc2c(c1)c(I)nn2C(=O)OC(C)(C)C)S(=O)(=O)c1ccccc1S(C)(=O)=O
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CN(C)C=O
Product: CS(=O)(=O)c1ccccc1S(=O)(=O)Nc1ccc2[nH]nc(-c3ccncc3)c2c1
Yield: 15.8 %

Procedure:
2-Methylsulfonyl-N-(3-pyridin-4-yl-1H-indazol-5-yl)benzenesulfonamide can be obtained as described in Example 47 from 1 g of tert-butyl 3-iodo-5-(N-tert-butoxycarbonyl-2-methylsulfonylbenzenesulfonylamino)indazole-1-carboxylate, of 380 mg 4-pyridylboronic acid, 40 ml of dimethylformamide, 3.2 ml of a saturated aqueous sodium hydrogencarbonate solution and 42.7 mg of tetrakis(triphenylphosphine)palladium[0]. 100 mg of 2-methylsulfonyl-N-(3-pyridin-4-yl-1H-indazol-5-yl)benzenesulfonamide are thus obtained in the form of a white solid melting at 265° C. (analysis C19H16N4O4S2 % calculated C, 53.26; H, 3.76; N, 13.08; O, 14.94; S, 14.97. % found C, 52.59; H, 3.30; N, 12.89; S, 15.14).
Reaction SMILES: Cl[C:2]1[C:3]2[C:10]([C:11]3[CH:16]=[CH:15][C:14]([NH:17][S:18]([C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=4)(=[O:20])=[O:19])=[CH:13][CH:12]=3)=[CH:9][N:8]([CH:27]([CH3:29])[CH3:28])[C:4]=2[N:5]=[CH:6][N:7]=1.[NH3:30]>O1CCOCC1>[NH2:30][C:2]1[C:3]2[C:10]([C:11]3[CH:16]=[CH:15][C:14]([NH:17][S:18]([C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=4)(=[O:20])=[O:19])=[CH:13][CH:12]=3)=[CH:9][N:8]([CH:27]([CH3:29])[CH3:28])[C:4]=2[N:5]=[CH:6][N:7]=1
Reactant: CC(C)n1cc(-c2ccc(NS(=O)(=O)c3ccccc3)cc2)c2c(Cl)ncnc21
Reactant: N
Solvent: C1COCCO1
Product: CC(C)n1cc(-c2ccc(NS(=O)(=O)c3ccccc3)cc2)c2c(N)ncnc21
Temperature: 120 °C
Reaction time: 16 h

Procedure:
A mixture of N-[4-(4-chloro-7-isopropylpyrrolo[2,3-d]pyrimidin-5-yl)phenyl]-benzenesulphonamide (0.34 g), concentrated ammonia (30 ml, SG 0.880) and 1,4-dioxane (30 ml) was heated with stirring at 120° C. in a pressure vessel for 16 hours. The mixture was allowed to cool to ambient temperature and the solvent was removed under reduced pressure to give a residue which was partitioned between water (40 ml) and ethyl acetate (40 ml). The organic layer was separated and the aqueous layer was further extracted with ethyl acetate (2×40 ml). The combined ethyl acetate extracts were washed, dried, filtered and evaporated to give a solid which was purified by flash column chromatography on silica using ethyl acetate/cyclohexane (8:2) as the mobile phase. Appropriate fractions were collected, combined and concentrated to give N-[4-(4-amino-7-isopropyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)phenyl]benzenesulphonamide, m.p. 238-240° C.