Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C:2]([O:5][C:6]([NH:8][CH2:9][C:10]([OH:12])=O)=[O:7])([CH3:4])[CH3:3].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH:37]1[C:46]2[C:41](=[CH:42][CH:43]=[CH:44][CH:45]=2)[CH2:40][CH2:39][CH2:38]1.CCN(C(C)C)C(C)C>C(Cl)Cl>[N:37]1([C:10](=[O:12])[CH2:9][NH:8][C:6](=[O:7])[O:5][C:2]([CH3:1])([CH3:3])[CH3:4])[C:46]2[C:41](=[CH:42][CH:43]=[CH:44][CH:45]=2)[CH2:40][CH2:39][CH2:38]1
Reactant: CC(C)(C)OC(=O)NCC(=O)O
Reactant: c1ccc2c(c1)CCCN2
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: CC(C)(C)OC(=O)NCC(=O)N1CCCc2ccccc21
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 86.9 %

Procedure:
To a solution of Boc Gly-OH (80) (4.0 g, 22.83 mmol) in dry CH2Cl2 (50 mL) at 0° C. under N2 was added HATU (8.70 g, 22.9 mmol). After stirring for 15 min at r.t., 1,2,3,4-tetrahydroquinoline (2.9 mL, 23.0 mmol), and DIPEA (12 mL, 68.8 mmol) were added. The reaction was stirred for 36 h at room temperature. The reaction mixture was diluted with CH2Cl2 (100 mL) and washed with saturated NaHCO3, 5% HCl, water, and saturated NaCl. Dried over MgSO4, and filtered. The solvent was removed under reduced pressure and the product was purified by column chromatography (10-50% EtOAc in hexanes) to afford 81 as a solid (5.76 g, 87%). 2-Amino-1-(3,4-dihydroquinolin-1(2H)-yl)ethanone, TFA salt (82): Compound 81 (2.8 g, 9.66 mmol) was dissolved in 20 mL of TFA/CH2Cl2 (1:3) at 0° C. under N2 After stirring for 1 h, the solvents were removed under reduced pressure. 5 mL of CH2Cl2/hexanes were added and removed again under reduced pressure to afford 82 (3.0 g). This crude material was used in the next step with out further purification. 2-(Benzo[d]thiazol-2-ylamino)-1-(3,4-dihydroquinolin-1(2H)-yl)ethanone (83): To a 0° C. solution of 2-chlorobenzothiazole (1.20 mL, 9.66 mmol) in 1-butanol (25 mL) was added compound 82 (2.94 g, 9.66 mmol)) followed by dropwise addition of Et3N (4.5 mL, 32 mmol). The reaction was heated to reflux for 24 h under N2. The solvent was removed under reduced pressure and the product was purified by column chromatography (20-50% EtOAc in hexanes) to afford 83 as a white foam (2.58 g, 82%); MS m/z: 324 (M+H)+. Anal. Calcd. For, C18H17N3OS: C, 66.85; H, 5.30; N, 12.99; S, 9.91. Found: C, 67.01; H, 5.42; N, 12.78; S, 9.85. Benzo[d]thiazol-2-yl(2-(3,4-dihydroquinolin-1(2H)-yl)-2-oxoethyl)cyanamide (84): To a suspension of compound 83 (340 g, 1.05 mmol) in dry CH3CN (10 mL) were added cyanogen bromide (5M in CH3CN) (0.42 mL, 2.1 mmol) and K2CO3 (580 g, 4.2 mmol). The reaction was heated to reflux for 4 h under N2. 0.84 mL (4.2 mmol) of cyanogen bromide was added and the reflux was continued for 12 h. The reaction mixture was diluted with EtOAc (50 mL). The solids were filtered off, filtrate was concentrated, and the yellow residue was purified by column chromatography (20% EtOAc in hexanes) to afford 84 as an off-white solid (80 mg, 28%). MS m/z: 349 (M+H)+. Anal. Calcd. For, C19H16N4OS.0.6H2O: C, 63.53; H, 4.83; N, 15.60; S, 8.92. Found: C, 63.24; H, 4.67; N, 15.25; S, 8.76.
Reaction SMILES: [C:1]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(Br)(Br)(Br)Br.[CH:25]([C:28]1[CH:35]=[C:34]([CH:36]([CH3:38])[CH3:37])[CH:33]=[C:32]([CH:39]([CH3:41])[CH3:40])[C:29]=1[CH:30]=O)([CH3:27])[CH3:26]>ClCCl>[CH:25]([C:28]1[CH:35]=[C:34]([CH:36]([CH3:38])[CH3:37])[CH:33]=[C:32]([CH:39]([CH3:41])[CH3:40])[C:29]=1[C:30]#[CH:1])([CH3:27])[CH3:26]
Reactant: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Reactant: CC(C)c1cc(C(C)C)c(C=O)c(C(C)C)c1
Agent: BrC(Br)(Br)Br
Solvent: ClCCl
Product: C#Cc1c(C(C)C)cc(C(C)C)cc1C(C)C
Temperature: 25 °C
Reaction time: 8 h
Yield: 57.6 %

Procedure:
To a stirred, degassed solution of triphenylphosphine (21 g, 80 mmol) and carbon tetrabromide (13.3 g, 40 mmol) in dry dichloromethane at 0° C. was added 2,4,6-triisopropylbenzaldehyde (4.64 g, 20 mmol). The resulting mixture was stirred overnight as it was allowed to slowly warm to room temperature. Solids were filtered off, and the volatiles were evacuated under reduced pressure. Pentane was then added, and after extensive trituration the mixture was filtered on a SiO2 plug with pentane as the eluent to afford after evaporation of the solvents the crude intermediate dibromoalkene as a colorless oil that is directly taken to the next step without surther purification. The intermediate is dissolved in dry THF (50 mL), and to the stirred solution cooled to −78° C. is then added nBuLi (2.5M in hexanes, 10 mL) dropwise. The mixture is stirred for 1 hour at −78° C., and let to warm to room temperature for an additional hour. The reaction is quenched by the addition of saturated aqueous NH4Cl, extracted with pentane, and the organic fractions are dried over anhydrous MgSO4. After filtration and evaporation of the solvents, the crude alkyne is purified by filtration on a SiO2 plug with pentane as the eluent. A small crystal of hydroquinone is added to stabilize the product, and the volatiles are evaporated under reduced pressure to afford 9d as a pale pinkish oil (2.63 g, 58% over 2 steps). 1H-NMR (CDCl3, 300 MHz): δ=7.00 (s, 2H), 3.56 (sept, J=6.9 Hz), 3.43 (s, 1H), 2.91 (sept, J=6.9 Hz), 1.28 (d, J=6.9 Hz, 12H), 1.27 (d, J=6.9 Hz, 6H). 13C-NMR (CDCl3, 75 MHz): δ=151.6, 149.7, 122.3, 120.5, 84.5, 81.0, 34.7, 31.8, 24.1, 23.5. Characterization data for 9d are consistent with literature values. (See Knorr, R.; Ruhdorfer, J.; Böhrer, P.; Bronberger, H.; Räpple, E. Liebigs Ann. Chem. 1994, 433-438).
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([OH:11])=[O:10])=[CH:4][CH:3]=1.[Li+].[CH3:13][CH:14]([N-]C(C)C)C.BrCCO[Si](C(C)(C)C)(C)C.Cl>C1COCC1>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([CH:8]2[CH2:14][CH2:13][O:10][C:9]2=[O:11])=[CH:6][CH:7]=1
Reactant: CC(C)[N-]C(C)C
Reactant: O=C(O)Cc1ccc(Br)cc1
Agent: CC(C)(C)[Si](C)(C)OCCBr
Agent: Cl
Agent: [Li+]
Solvent: C1CCOC1
Product: O=C1OCCC1c1ccc(Br)cc1
Temperature: -78 °C
Reaction time: 0.33 h
Yield: 18.8 %

Procedure:
4-Bromophenylacetic acid (1.00 g, 4.65 mmol) was dissolved in 45 mls of dry THF and chilled to −78° C. To this was added LDA (9.30 mls, 18.6 mmol, 2M in THF/heptane), resulting in a dark color, and this mixture was stirred at −78° C. for 20 minutes. (2-bromoethoxy)(tert-butyl)dimethylsilane (1.20 mls, 5.58 mmol) was then added via syringe, and then the cooling bath was removed to allowed the reaction to warm to room temperature. Upon warming, the mixture became an amber color. Once at room temperature, 50 mls of 1N aqueous HCl were then added and the mixture was vigorously stirred for 16 hours, then extracted with EtOAc (2×), extracts washed with 2M aqueous sodium carbonate, dried over sodium sulfate and concentrated to an orange oil. Flash 40 Biotage (40M cartridge, 3:1 Hexane:EtOAc) afforded 211 mgs (19%) of 3-(4-bromophenyl)dihydrofuran-2(3H)-one as an orange oil.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[C:6]([O:8][C:9]2[CH:14]=[CH:13][C:12]([N+:15]([O-:17])=[O:16])=[CH:11][C:10]=2[F:18])[N:5]=[CH:4][N:3]=1.C(N(CC)CC)C.Cl[C:27](OC1C=CC=CC=1)=[O:28].[N:36]1([CH:41]2[CH2:46][CH2:45][NH:44][CH2:43][CH2:42]2)[CH2:40][CH2:39][CH2:38][CH2:37]1>O1CCCC1.CN(C)C=O>[F:18][C:10]1[CH:11]=[C:12]([N+:15]([O-:17])=[O:16])[CH:13]=[CH:14][C:9]=1[O:8][C:6]1[N:5]=[CH:4][N:3]=[C:2]([NH:1][C:27]([N:44]2[CH2:45][CH2:46][CH:41]([N:36]3[CH2:40][CH2:39][CH2:38][CH2:37]3)[CH2:42][CH2:43]2)=[O:28])[CH:7]=1
Reactant: C1CCN(C2CCNCC2)C1
Reactant: Nc1cc(Oc2ccc([N+](=O)[O-])cc2F)ncn1
Reactant: O=C(Cl)Oc1ccccc1
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: O=C(Nc1cc(Oc2ccc([N+](=O)[O-])cc2F)ncn1)N1CCC(N2CCCC2)CC1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
4-Amino-6-(2-fluoro-4-nitrophenoxy)pyrimidine (50 mg) was dissolved in tetrahydrofuran (3 ml) under a nitrogen atmosphere, and then triethylamine (0.056 ml) and phenyl chloroformate (0.050 ml) were added dropwise thereto, followed by stirring at room temperature for 30 min. The reaction mixture was concentrated under a reduced pressure to give a residue, which was then dissolved in N,N-dimethylformamide (3 ml). 4-(Pyrrolidin-1-yl)piperidine (123 mg) was added thereto, followed by stirring at room temperature for 2 hrs. The reaction mixture was partitioned between ethyl acetate and a saturated aqueous solution of sodium hydrogencarbonate. The organic layer was washed with a saturated aqueous solution of sodium hydrogencarbonate, water and brine in this order, and dried over anhydrous sodium sulfate. The solvent was evaporated under a reduced pressure to give a residue, which was then purified by silica gel column chromatography (Fuji Silysia NH, eluent; hexane:ethyl acetate=1:5). The solvent was evaporated under a reduced pressure, and dried in vacuum to provide a crude product of 4-(pyrrolidin-1-yl)piperidine-1-carboxylic acid [6-(2-fluoro-4-nitrophenoxy)pyrimidin-4-yl]amide. The crude product (86 mg) was dissolved in tetrahydrofuran (2 ml)-methanol (2 ml), and then 10% palladium carbon (43 mg) was added thereto under a nitrogen atmosphere, followed by replacing with hydrogen inside the system and stirring overnight. After replacing with nitrogen inside the system, the reaction mixture was filtered to remove the catalyst, which was washed with methanol. The filtrate was concentrated under a reduced pressure to give a residue, which was purified by silica gel column chromatography (Fuji Silysia NH, eluent; hexane:ethyl acetate=1:5, then ethyl acetate). Fractions containing the target compound were concentrated under a reduced pressure to provide the titled compound (53.5 mg, 66.8%).
Reaction SMILES: [NH2:1][C:2]1[O:15][C:14]2[C:13]3[C:8](=[CH:9][CH:10]=[C:11]([NH2:16])[N:12]=3)[CH:7]=[CH:6][C:5]=2[CH:4]([C:17]2[CH:22]=[C:21]([O:23][CH3:24])[C:20]([O:25][CH3:26])=[C:19]([Br:27])[CH:18]=2)[C:3]=1[C:28]#[N:29].[CH2:30]([S:32]N=C=O)C.[C:36](#[N:38])C>>[NH2:1][C:2]1[O:15][C:14]2[C:13]3[C:8](=[CH:9][CH:10]=[C:11]([NH:16][C:30]([NH:38][CH3:36])=[S:32])[N:12]=3)[CH:7]=[CH:6][C:5]=2[CH:4]([C:17]2[CH:22]=[C:21]([O:23][CH3:24])[C:20]([O:25][CH3:26])=[C:19]([Br:27])[CH:18]=2)[C:3]=1[C:28]#[N:29]
Reactant: CC#N
Reactant: CCSN=C=O
Reactant: COc1cc(C2C(C#N)=C(N)Oc3c2ccc2ccc(N)nc32)cc(Br)c1OC
Product: CNC(=S)Nc1ccc2ccc3c(c2n1)OC(N)=C(C#N)C3c1cc(Br)c(OC)c(OC)c1
Temperature: 60 °C
Yield: 59 %

Procedure:
3,6-Diamino-1-(3-bromo-4,5-dimethoxy-phenyl)-1H-4-oxa-5-aza-phenanthrene-2-carbonitrile (20) (45 mg, 0.1 mmol) and ethylthioisocyanate (10.4 mg, 0.12 mmol) were taken in 2 ml dry acetonitril and stirred at 60° C. monitoring the reaction with LC-MS. The solvent was evaporated after the completion of the reaction. The residue was separated on HPLC (high pressure liquid chromatography) (21 mm×250 mm, RP18, 5 mm) with a methanol/water gradient (5% MeOH to MeOH in 25 min, flow 21 ml/min) to get the title compound (32 mg, 59%).
Reaction SMILES: C(O[C:4]1[O:8][N:7]=[C:6]([C:9]2[N:13]3[N:14]=[C:15]([O:22][CH2:23][C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][N:25]=4)[C:16]4[C:21]([C:12]3=[N:11][N:10]=2)=[CH:20][CH:19]=[CH:18][CH:17]=4)[CH:5]=1)C.C(N(CC)CC)C.C=C(Cl)[Cl:39]>ClCCl>[Cl:39][C:4]1[O:8][N:7]=[C:6]([C:9]2[N:13]3[N:14]=[C:15]([O:22][CH2:23][C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][N:25]=4)[C:16]4[C:21]([C:12]3=[N:11][N:10]=2)=[CH:20][CH:19]=[CH:18][CH:17]=4)[CH:5]=1
Reactant: CCOc1cc(-c2nnc3c4ccccc4c(OCc4ccccn4)nn23)no1
Reactant: C=C(Cl)Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: Clc1cc(-c2nnc3c4ccccc4c(OCc4ccccn4)nn23)no1
Reaction time: 16 h

Procedure:
The product from Example 70, part d) (50 mg, 0.14 mmol) was suspended in vinylidine chloride (5 ml) with triethylamine (43 mg, 0.42 mmol). The reaction was stirred for 16 hours, diluted with dichloromethane and washed with 5% ammonia solution and then dried (MgSO4), filtered and evaporated to yield a solid which was purified by preparative thin layer chromatography using methanol/dichloromethane (3:97) as elutant to yield 12.5 mg of pure product, 1H NMR (360 MHz, CDCl3) 8.66-8.72 (2H, m), 8.35 (1H, d, J=7 Hz), 7.98 (1H, t, J=7 Hz), 7.85 (1H, t, J=7 Hz), 7.80-7.70 (2H, m), 7.28 (1H, m), 7.03 (1H, s), 5.76 (2H, s); MS (ES30) 379 [MH]+.
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]([OH:19])([CH:16]([SH:18])[CH3:17])[CH2:10][N:11]1[CH:15]=[N:14][CH:13]=[N:12]1.Br[CH2:21][C:22]1[O:23][C:24](=[O:28])[O:25][C:26]=1[CH3:27].C(=O)([O-])[O-].[K+].[K+].C(OCC)(=O)C>CN(C)C=O.O>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]([OH:19])([CH:16]([S:18][CH2:21][C:22]1[O:23][C:24](=[O:28])[O:25][C:26]=1[CH3:27])[CH3:17])[CH2:10][N:11]1[CH:15]=[N:14][CH:13]=[N:12]1
Reactant: Cc1oc(=O)oc1CBr
Reactant: CC(S)C(O)(Cn1cncn1)c1ccc(F)cc1F
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: Cc1oc(=O)oc1CSC(C)C(O)(Cn1cncn1)c1ccc(F)cc1F
Reaction time: 0.17 h
Yield: 77.8 %

Procedure:
To a solution of (2RS,3RS)-2-(2,4-difluorophenyl)-3-mercapto-1-(1H-1,2,4-triazol-1-yl)-2-butanol (0.060 g), 4-bromomethyl-5-methyl-2-oxo-1,3dioxol (0.049 g) in N,N-dimethylformamide (2.0 ml) was added anhydrous potassium carbonate (0.20 g) at -20° C. and the mixture was stirred for 10 minutes. To the reaction mixture were added ethyl acetate (10 ml) and water (10 ml), and organic layer was separated. The mixture was further extracted with ethyl acetate (10 ml×2). The organic layers were combined, washed with saturated aqueous sodium chloride solution (10 ml), dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was subjected to silica gel chromatography (1 cm×5 cm), and elution was carried out with ethyl acetate-hexane (1:1). The desired fraction was concentrated and the residue was crystallized from chloroform-diethyl ether to give (2RS,3RS)-2-(2,4-difluorophenyl)-3-(5-methyl-2-oxo-1,3-dioxol-4-yl)methylthio-1-(1H-1,2,4-triazol-1-yl)-2-butanol (compound 56, 0.065 g). m.p. 173°-174° C.
Reaction SMILES: [F:1][CH2:2][C:3]1[N:8]=[C:7]([C:9]#[C:10][CH2:11][CH2:12][NH:13][CH3:14])[CH:6]=[CH:5][CH:4]=1.[Cl:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1[S:22](Cl)(=[O:24])=[O:23]>>[Cl:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1[S:22]([N:13]([CH2:12][CH2:11][C:10]#[C:9][C:7]1[CH:6]=[CH:5][CH:4]=[C:3]([CH2:2][F:1])[N:8]=1)[CH3:14])(=[O:24])=[O:23]
Reactant: CNCCC#Cc1cccc(CF)n1
Reactant: O=S(=O)(Cl)c1ccccc1Cl
Product: CN(CCC#Cc1cccc(CF)n1)S(=O)(=O)c1ccccc1Cl
Yield: 31 %

Procedure:
The title compound was prepared in accordance with the general method of Example 199(D), from 4-(6-(fluoromethyl)pyridin-2-yl)-N-methylbut-3-yn-1-amine (70 mg, 0.36 mmol) and 2-chlorobenzene-1-sulfonyl chloride (92 mg, 0.44 mmol). The crude residue was purified over silicagel chromatography (prepacked 10 g silicagel column, Cyclohexane/AcOEt: 70/30 as eluent) to afford 41 mg of 2-chloro-N-(4-(6-(fluoromethyl)pyridin-2-yl)but-3-ynyl)-N-methylbenzenesulfonamide as a yellow oil (Yield: 31%).
Reaction SMILES: [CH2:1]([N:8]1[C:17]2[C:12](=[CH:13][C:14]([C:18]([F:21])([F:20])[F:19])=[CH:15][CH:16]=2)[CH2:11][CH:10]([C:22]([O:24]CC)=[O:23])[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O.[OH-].[Li+]>CO.C1COCC1.O>[CH2:1]([N:8]1[C:17]2[C:12](=[CH:13][C:14]([C:18]([F:19])([F:20])[F:21])=[CH:15][CH:16]=2)[CH2:11][CH:10]([C:22]([OH:24])=[O:23])[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CCOC(=O)C1Cc2cc(C(F)(F)F)ccc2N(Cc2ccccc2)C1
Agent: [Li+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: O
Solvent: CO
Product: O=C(O)C1Cc2cc(C(F)(F)F)ccc2N(Cc2ccccc2)C1
Temperature: 25 °C
Reaction time: 2 h
Yield: 96.6 %

Procedure:
To a solution of 149C (825 mg, 2.27 mmol) in a mixed solvent of MeOH-THF-H2O (20 mL at ratio of 2:2:1) was added lithium hydroxide monohydrate (400 mg, 11.35 mmol). The mixture was stirred at RT for 2 h, then extracted with ether (20 mL). The aqueous layer was acidified to pH 4-5 using 3N aqueous HCl, then extracted with CH2Cl2 (3×). The combined CH2Cl2 extracts were washed with water, brine, dried (Na2SO4), and concentrated in vacuo to afford compound 149D as light yellow foam (735 mg, 97%).
Reaction SMILES: [CH3:1][C:2]1[C:3](=[O:8])[NH:4][CH:5]=[CH:6][N:7]=1.[CH2:9]([NH:16][C:17]([C:19]1[S:23][C:22](Br)=[N:21][C:20]=1[CH3:25])=[O:18])[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1>>[CH2:9]([NH:16][C:17]([C:19]1[S:23][C:22]([N:4]2[CH:5]=[CH:6][N:7]=[C:2]([CH3:1])[C:3]2=[O:8])=[N:21][C:20]=1[CH3:25])=[O:18])[C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1
Reactant: Cc1ncc[nH]c1=O
Reactant: Cc1nc(Br)sc1C(=O)NCc1ccccc1
Product: Cc1nc(-n2ccnc(C)c2=O)sc1C(=O)NCc1ccccc1
Yield: 5 %

Procedure:
Following the procedure as described in Example 3, making variations only as required to use 3-methylpyrazin-2(1H)-one in place of 4-aminopyridin-2(1H)-one to react with N-benzyl-2-bromo-4-methylthiazole-5-carboxamide, the title compound was obtained as a white solid in 5% yield: mp 186-187° C.; 1H NMR (300 MHz, CDCl3) δ 8.44 (s, 1H), 7.45-7.25 (m, 6H), 6.12 (s, 1H), 4.59 (d, J=5.7 Hz, 2H), 2.69 (s, 3H), 2.55 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 161.6, 159.2, 153.4, 152.4, 152.0, 137.5, 128.8, 127.9, 127.8, 124.5, 123.5, 119.3, 44.2, 20.8, 17.3; MS (ES+) m/z 341.2 (M+1).
Reaction SMILES: [NH2:1][CH2:2][CH2:3][C:4]1[CH:9]=[CH:8][C:7]([S:10][CH:11]2[CH2:16][CH2:15][N:14]([C:17]([NH:19][C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)=[O:18])[CH2:13][CH2:12]2)=[CH:6][CH:5]=1.C([Si]([O:43][C:44]1[CH:49]=[CH:48][C:47]([O:50][CH2:51][C@@H:52]2[CH2:54][O:53]2)=[CH:46][CH:45]=1)(C1C=CC=CC=1)C1C=CC=CC=1)(C)(C)C>ClCCl.C(Cl)(Cl)Cl.CO>[C:20]1([NH:19][C:17]([N:14]2[CH2:15][CH2:16][CH:11]([S:10][C:7]3[CH:6]=[CH:5][C:4]([CH2:3][CH2:2][NH:1][CH2:54][C@H:52]([OH:53])[CH2:51][O:50][C:47]4[CH:48]=[CH:49][C:44]([OH:43])=[CH:45][CH:46]=4)=[CH:9][CH:8]=3)[CH2:12][CH2:13]2)=[O:18])[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1
Reactant: CC(C)(C)[Si](Oc1ccc(OC[C@@H]2CO2)cc1)(c1ccccc1)c1ccccc1
Reactant: NCCc1ccc(SC2CCN(C(=O)Nc3ccccc3)CC2)cc1
Solvent: ClC(Cl)Cl
Solvent: ClCCl
Solvent: CO
Product: O=C(Nc1ccccc1)N1CCC(Sc2ccc(CCNC[C@H](O)COc3ccc(O)cc3)cc2)CC1
Yield: 26 %

Procedure:
4-{[4-(2-Aminoethyl)phenyl]sulfanyl}-N-phenyl-1-piperidinecarboxamide (0.45 g, 1.27 mmol) was reacted with tert-butyl{4-[(2S)oxiranylmethoxy]phenoxy}diphenylsilane (0.512 g, 1.27 mmol) according to Procedure G (eluant: 12:3:1 dichloromethane-chloroform-methanol) to give the title compound (0.25 g, 0.33 mmol).
Reaction SMILES: [CH:1]1[C:11]2[CH2:10][C:9]3[CH:12]=[CH:13][CH:14]=[CH:15][C:8]=3[CH2:7][NH:6][C:5]=2[CH:4]=[CH:3][CH:2]=1.C(N(CC)CC)C.[F:23][C:24]1[CH:25]=[CH:26][C:27]([CH3:42])=[C:28]([CH:41]=1)[C:29]([NH:31][C:32]1[N:37]=[CH:36][C:35]([C:38](Cl)=[O:39])=[CH:34][CH:33]=1)=[O:30]>ClCCl>[CH:1]1[C:11]2[CH2:10][C:9]3[CH:12]=[CH:13][CH:14]=[CH:15][C:8]=3[CH2:7][N:6]([C:38]([C:35]3[CH:34]=[CH:33][C:32]([NH:31][C:29](=[O:30])[C:28]4[CH:41]=[C:24]([F:23])[CH:25]=[CH:26][C:27]=4[CH3:42])=[N:37][CH:36]=3)=[O:39])[C:5]=2[CH:4]=[CH:3][CH:2]=1
Reactant: Cc1ccc(F)cc1C(=O)Nc1ccc(C(=O)Cl)cn1
Reactant: c1ccc2c(c1)CNc1ccccc1C2
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: Cc1ccc(F)cc1C(=O)Nc1ccc(C(=O)N2Cc3ccccc3Cc3ccccc32)cn1

Procedure:
As described for Example 1, 6,11-dihydro-5H-dibenz[b,e]azepine is reacted in dichloromethane in the presence of triethylamine, with 6-[(5-fluoro-2-methylbenzoyl)amino]pyridine-3-carbonyl chloride to give the product as a solid.
Reaction SMILES: [NH2-:1].[Na+].C(O)(=O)CCCCCCC/C=C\CCCCCCCC.[CH3:23][CH2:24][CH2:25][CH2:26][CH:27]([C:32]1[CH:37]=[CH:36][N:35]=[CH:34][CH:33]=1)[CH2:28][CH2:29][CH2:30][CH3:31]>C1(C)C(C)=CC=CC=1>[NH2:1][C:34]1[CH:33]=[C:32]([CH:27]([CH2:26][CH2:25][CH2:24][CH3:23])[CH2:28][CH2:29][CH2:30][CH3:31])[CH:37]=[CH:36][N:35]=1
Reactant: [NH2-]
Reactant: CCCCC(CCCC)c1ccncc1
Agent: CCCCCCCC/C=C\CCCCCCCC(=O)O
Agent: [Na+]
Solvent: Cc1ccccc1C
Product: CCCCC(CCCC)c1ccnc(N)c1
Temperature: 173 °C
Reaction time: 8.7 h
Yield: 67.3 %

Procedure:
A mixture of 50.7 g (1.3 moles) of sodamide preformed in situ as in Example 1, 350 cc of xylene containing 0.1 cc of oleic acid, and 205 g (1 mole) of 4-(5-nonyl)pyridine was placed in a Magne Drive such as the one described in Example 2. The autoclave was closed and purged of air with nitrogen, pressurized to 10 psig with ammonia and 200 psig with nitrogen. The pressure relief valve was set at 350 psig. The mixture was heated to 173° C. at which temperature amination began. The temperature was reduced and the reaction was run at 158°-163° C. for 8.7 hours. Hydrogen was evolved during this time. The autoclave was cooled to room temperature, vented to atmospheric pressure and hydrolyzed with 150 cc of water. The xylene phase was separated and the bottom aqueous caustic phase was re-extracted with 25 cc of xylene. Both xylene extracts were combined and distilled to give 2-amino-4-(5 -nonyl)pyridine boiling at 197°-225° C. at 22 mm Hg. The yield was 67.3%. This result substantially increases the yield of 2-amino-4-(5-nonyl)pyridine over that reported previously by one of the applicants, McGill, U.S. Pat. No. 4,177,349 (1979) and McGill, U.S. Pat. No. 4,267,335 (1981). In this prior work, 4-(5-nonyl)pyridine was shown to prefer to couple in the presence of sodamide, giving high yields of 4,4'-di-(5-nonyl)-2,2'-bipyridyl but only low yields of 2-amino-4-(5-nonyl)pyridine. This increased yield of 2-amino-4-(5-nonyl)pyridine is of importance because the compound has valuable biocidal properties.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([N:11]2[CH:19]3[CH2:20][CH2:21][CH2:22][CH:12]2[C:13]2[CH:14]=[N:15][NH:16][C:17]=2[C:18]3=[O:23])(=[O:10])=[O:9])=[CH:4][CH:3]=1.[BH4-].[Na+]>CO.C1COCC1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([N:11]2[CH:19]3[CH2:20][CH2:21][CH2:22][CH:12]2[C:13]2[CH:14]=[N:15][NH:16][C:17]=2[CH:18]3[OH:23])(=[O:10])=[O:9])=[CH:4][CH:3]=1
Reactant: O=C1c2[nH]ncc2C2CCCC1N2S(=O)(=O)c1ccc(Cl)cc1
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Solvent: C1CCOC1
Product: O=S(=O)(c1ccc(Cl)cc1)N1C2CCCC1C(O)c1[nH]ncc12
Yield: 77.7 %

Procedure:
To a solution of 12-(4-chloro-benzenesulfonyl)-4,5,12-triaza-tricyclo[6.3.1.02,6]dodeca-2(6),3-dien-7-one (58 mg, 0.16 mmol) in 2:1 MeOH/THF (3 mL) was added NaBH4 (12 mg, 0.33 mmol) in portions. After sixteen hours the reaction was quenched with half saturated KHSO4 and then diluted with EtOAc and water. The separated organic phase was washed with water (10 mL), brine (10 mL), dried over MgSO4, filtered and concentrated to yield 12-(4-chlorobenzenesulfonyl)-4,5,12-triaza-tricyclo[6.3.1.02,6]dodeca-2(6),3-dien-7-ol (44 mg, 76%) as a white fluffy solid. MS (ES) m/e 354.0. (M+H)
Reaction SMILES: [C:1]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[N:12]([C:30](Cl)=[O:31])[C@H:13]([C:23]3[CH:28]=[CH:27][C:26]([Cl:29])=[CH:25][CH:24]=3)[C@H:14]([C:16]3[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=3)[N:15]=2)=[C:7]([O:33][CH2:34][CH3:35])[CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[CH3:36][S:37]([N:40]1[CH2:45][CH2:44][NH:43][CH2:42][CH2:41]1)(=[O:39])=[O:38]>>[C:1]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[N:12]([C:30]([N:43]3[CH2:44][CH2:45][N:40]([S:37]([CH3:36])(=[O:39])=[O:38])[CH2:41][CH2:42]3)=[O:31])[C@H:13]([C:23]3[CH:24]=[CH:25][C:26]([Cl:29])=[CH:27][CH:28]=3)[C@H:14]([C:16]3[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=3)[N:15]=2)=[C:7]([O:33][CH2:34][CH3:35])[CH:6]=1)([CH3:3])([CH3:4])[CH3:2]
Reactant: CCOc1cc(C(C)(C)C)ccc1C1=N[C@@H](c2ccc(Cl)cc2)[C@@H](c2ccc(Cl)cc2)N1C(=O)Cl
Reactant: CS(=O)(=O)N1CCNCC1
Product: CCOc1cc(C(C)(C)C)ccc1C1=N[C@@H](c2ccc(Cl)cc2)[C@@H](c2ccc(Cl)cc2)N1C(=O)N1CCN(S(C)(=O)=O)CC1

Procedure:
[(4S,5R)-2-(4-tert-Butyl-2-ethoxy-phenyl)-4,5-bis-(4-chloro-phenyl)-4,5-dihydro-imidazol-1-yl]-(4-methanesulfonyl-piperazin-1-yl)-methanone was prepared from (4S,5R)-2-(4-tert-butyl-2-ethoxy-phenyl)-4,5-bis-(4-chloro-phenyl)-4,5-dihydro-imidazole-1-carbonyl chloride (example 11) and 1-methanesulfonyl-piperazine in an analogous manner as described in example 25. LR-MS: 657.4 [(M+H)+]