Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH:1]1([O:7][CH2:8][C:9]2[NH:14][C:13](=[S:15])[NH:12][C:11](=[O:16])[CH:10]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.IC.[C:19](=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1>[CH:1]1([O:7][CH2:8][C:9]2[N:14]=[C:13]([S:15][CH3:19])[NH:12][C:11](=[O:16])[CH:10]=2)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1
Reactant: O=c1cc(COC2CCCCC2)[nH]c(=S)[nH]1
Reactant: O=C([O-])[O-]
Agent: [K+]
Solvent: CI
Solvent: Cc1ccccc1
Product: CSc1nc(COC2CCCCC2)cc(=O)[nH]1
Temperature: 90 °C
Yield: 42.5 %

Procedure:
A mixture of 6-cyclohexyloxymethyl-2-thioxo-2,3-dihydro-1H-pyrimidin-4-one (0.2 g), toluene (5.5 mL), iodomethane (0.48 g) and potassium carbonate (0.57 g) was heated at 90° C. in a sealed tube for 16 h. The mixture was partitioned in water and ethyl acetate. The ethyl acetate layer was dried over magnesium sulfate, filtered, and evaporated. The residue was purified by column chromatography (40% ethyl acetate in hexanes) to afford 6-cyclohexyloxymethyl-2-methylsulfanyl-3H-pyrimidin-4-one (90 mg).
Reaction SMILES: [N+:1]([C:4]1[CH:21]=[CH:20][C:7]([CH2:8][O:9][C:10]([NH:12][CH2:13][CH2:14][C@H:15]([OH:19])[C:16]([OH:18])=O)=[O:11])=[CH:6][CH:5]=1)([O-:3])=[O:2].C1(N=C=NC2CCCCC2)CCCCC1.COC1C=CC(COC([N:47]2[CH2:52][CH2:51][NH:50][CH2:49][CH2:48]2)=O)=CC=1.C(N(CC)CC)C>O1CCCC1>[N+:1]([C:4]1[CH:5]=[CH:6][C:7]([CH2:8][O:9][C:10]([NH:12][CH2:13][CH2:14][C@H:15]([OH:19])[C:16]([N:47]2[CH2:52][CH2:51][NH:50][CH2:49][CH2:48]2)=[O:18])=[O:11])=[CH:20][CH:21]=1)([O-:3])=[O:2]
Reactant: COc1ccc(COC(=O)N2CCNCC2)cc1
Reactant: O=C(NCC[C@H](O)C(=O)O)OCc1ccc([N+](=O)[O-])cc1
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: O=C(NCC[C@H](O)C(=O)N1CCNCC1)OCc1ccc([N+](=O)[O-])cc1

Procedure:
To 0.9 g of (2S)-4-(p-nitrobenzyloxycarbonyl)amino-2-hydroxybutyric acid dissolved in tetrahydrofuran were added, with cooling on an ice bath, 0.36 g of N-hydroxysuccunimide and 0.65 g of dicyclohexylcarbodiimide, followed by overnight reaction with stirring. To the solution were added 0.75 g of 1-(p-methoxybenzyloxycarbonyl)piperazine and 0.31 g of triethylamine, followed by 2 hours of reaction. After removal of insoluble material from the reaction mixture by filtration and subsequent concentration of the filtrate, a residue was mixed with ethyl acetate, washed with sodium bicarbonate aqueous solution, citric acid aqueous solution and sodium chloride aqueous solution in that order and then dried over sodium sulfate, followed by evaporation of the solvent under a reduced pressure. Thereafter, the resulting residue was subjected to a silica gel column chromatography to yield 1.33 g of 1-(p-methoxybenzyloxycarbonyl)-4-((2S)-(4-(p-nitrobenzyloxycarbonyl) amino-2-hydroxybutyryl)piperazine.
Reaction SMILES: [CH3:1][CH:2]([O:5][C:6]1[CH:19]=[CH:18][C:9]([O:10][CH:11]([CH2:16]C)[CH:12]([OH:15])[CH2:13][OH:14])=[CH:8][CH:7]=1)[CH2:3][CH3:4].[CH:20](=O)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1>CC(C)=O>[C:21]1([CH:20]2[O:15][CH:12]([CH:11]([O:10][C:9]3[CH:8]=[CH:7][C:6]([O:5][CH:2]([CH3:1])[CH2:3][CH3:4])=[CH:19][CH:18]=3)[CH3:16])[CH2:13][O:14]2)[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1
Reactant: O=Cc1ccccc1
Reactant: CCC(C)Oc1ccc(OC(CC)C(O)CO)cc1
Solvent: CC(C)=O
Product: CCC(C)Oc1ccc(OC(C)C2COC(c3ccccc3)O2)cc1

Procedure:
In the same manner, 3-[4-(1-methylpropoxy)phenoxy]-1,2-pentanediol is reacted with each of acetone and benzaldehyde to give, respectively,
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][N:3]=1.[C:9]1([CH3:19])[CH:14]=[CH:13][C:12]([S:15](Cl)(=[O:17])=[O:16])=[CH:11][CH:10]=1>N1C=CC=CC=1>[F:8][C:5]1[CH:6]=[CH:7][C:2]([NH:1][S:15]([C:12]2[CH:13]=[CH:14][C:9]([CH3:19])=[CH:10][CH:11]=2)(=[O:17])=[O:16])=[N:3][CH:4]=1
Reactant: Nc1ccc(F)cn1
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Solvent: c1ccncc1
Product: Cc1ccc(S(=O)(=O)Nc2ccc(F)cn2)cc1
Temperature: 80 °C
Yield: 100.7 %

Procedure:
2-amino-5-fluoropyridine (25 g, 0.22 mol) in pyridine (100 mL) was treated portion wise with p-toluenesulfonyl chloride (47.5 g, 0.25 mol) and heated at 80° C. for 2 hours. The cooled material was concentrated to remove the majority of pyridine. The resulting viscous solution was diluted with 200 ml of ethyl acetate then 200 ml of water. The resulting suspension was stirred for about an hour to break up the solids then filtered. The filter cake was washed with water then cold ethyl acetate, dried to afford 59 g of a light brown solid. Rf 0.43, 50% ethyl acetate/hexanes; MS m/z 266 (M+H).
Reaction SMILES: C(N([C:12]1[S:13][C:14](B2OC(C)(C)C(C)(C)O2)=[CH:15][N:16]=1)C(=O)OC(C)(C)C)(C)C.Br[C:27]1[CH:28]=[C:29]([C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=2)[C:30]2[N:31]([CH:33]=[C:34]([CH2:36][C:37]([O:39][CH3:40])=[O:38])[N:35]=2)[CH:32]=1>>[CH:34]([NH:35][C:14]1[S:13][C:12]([C:27]2[CH:28]=[C:29]([C:41]3[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=3)[C:30]3[N:31]([CH:33]=[C:34]([CH2:36][C:37]([O:39][CH3:40])=[O:38])[N:35]=3)[CH:32]=2)=[N:16][CH:15]=1)([CH3:36])[CH3:33]
Reactant: CC(C)N(C(=O)OC(C)(C)C)c1ncc(B2OC(C)(C)C(C)(C)O2)s1
Reactant: COC(=O)Cc1cn2cc(Br)cc(-c3ccccc3)c2n1
Product: COC(=O)Cc1cn2cc(-c3ncc(NC(C)C)s3)cc(-c3ccccc3)c2n1

Procedure:
Prepared in an similar fashion as Example 34, step #4 from tert-butyl isopropyl(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)thiazol-2-yl)carbamate and Methyl 2-(6-bromo-8-phenylimidazo[1,2-a]pyridin-2-yl)acetate. LCMS 407.4, HPLC Tr 2.02 min (Conditions C).
Reaction SMILES: [NH:1]1[C:5]2[CH2:6][CH2:7][CH2:8][CH2:9][C:4]=2[N:3]=[C:2]1[CH2:10][N:11]([CH:27]1[C:36]2[N:35]=[CH:34][CH:33]=[CH:32][C:31]=2[CH2:30][CH2:29][CH2:28]1)[CH2:12][CH2:13][CH2:14][CH2:15][N:16]1C(=O)C2C(=CC=CC=2)C1=O.O.NN>C(O)C>[NH:1]1[C:5]2[CH2:6][CH2:7][CH2:8][CH2:9][C:4]=2[N:3]=[C:2]1[CH2:10][N:11]([CH:27]1[C:36]2[N:35]=[CH:34][CH:33]=[CH:32][C:31]=2[CH2:30][CH2:29][CH2:28]1)[CH2:12][CH2:13][CH2:14][CH2:15][NH2:16]
Reactant: O=C1c2ccccc2C(=O)N1CCCCN(Cc1nc2c([nH]1)CCCC2)C1CCCc2cccnc21
Agent: NN
Solvent: O
Solvent: CCO
Product: NCCCCN(Cc1nc2c([nH]1)CCCC2)C1CCCc2cccnc21
Temperature: 25 °C
Reaction time: 18 h

Procedure:
To a solution of 2-{4-[(4,5,6,7-tetrahydro-1H-benzoimidazol-2-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-butyl}-isoindole-1,3-dione (0.2466 g, 0.51 mmol) in ethanol (5 mL) was added hydrazine hydrate (0.3 mL, 2.5 mmol), and stirred at room temperature for 18 hours. The reaction mixture was concentrated, and purification of the crude material by column chromatography on silica gel (20:1:1 CH2Cl2-MeOH—NH4OH) provided 0.1031 g (58%) of
Reaction SMILES: [CH2:1]([O:3]/[N:4]=[C:5](/[C:36]1[N:37]=[C:38]([NH:41]C(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[S:39][CH:40]=1)\[C:6]([NH:8][CH:9]1[C:34](=[O:35])[N:11]2[C:12]([C:18]([O:20]C(C3C=CC=CC=3)C3C=CC=CC=3)=[O:19])=[C:13]([CH2:16]I)[CH2:14][S:15][C@H:10]12)=[O:7])[CH3:2].[CH3:61][S:62][C:63]1[S:64][CH:65]=[CH:66][N:67]=1>C(Cl)Cl.C(Cl)(Cl)Cl.[B-](F)(F)(F)F.[Ag+]>[NH2:41][C:38]1[S:39][CH:40]=[C:36](/[C:5](=[N:4]/[O:3][CH2:1][CH3:2])/[C:6]([NH:8][CH:9]2[C:34](=[O:35])[N:11]3[C:12]([C:18]([O-:20])=[O:19])=[C:13]([CH2:16][N+:67]4[CH:66]=[CH:65][S:64][C:63]=4[S:62][CH3:61])[CH2:14][S:15][C@H:10]23)=[O:7])[N:37]=1
Reactant: CSc1nccs1
Reactant: CCO/N=C(\C(=O)NC1C(=O)N2C(C(=O)OC(c3ccccc3)c3ccccc3)=C(CI)CS[C@H]12)c1csc(NC(c2ccccc2)(c2ccccc2)c2ccccc2)n1
Agent: [Ag+]
Agent: F[B-](F)(F)F
Solvent: ClC(Cl)Cl
Solvent: ClCCl
Product: CCO/N=C(\C(=O)NC1C(=O)N2C(C(=O)[O-])=C(C[n+]3ccsc3SC)CS[C@H]12)c1csc(N)n1
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 145.6 %

Procedure:
To an ice-cooled solution of diphenylmethyl 7-[(Z)-2-(ethoxyimino)-2-(2-tritylaminothiazol-4-yl)acetamido]-3-iodomethyl-3-cephem-4-carboxylate [VII-2] (517 mg, 0.55 mmole) and 2-methylthiothiazole (85.3 mg, 0.65 mmole) in CH2Cl2 (10 ml) was added AgBF4 (117 mg, 0.60 mmole) and the mixture was stirred for 1.5 hours at room temperature. The reaction mixture was diluted with CHCl3 (100 mL), and the resulting precipitate was recovered by filtration and washed with CHCl3 (100 mL). The filtrate and the washings were combined and washed with water, dried over MgSO4 and evaporated. The residue was triturated with ether (50 mL) to give an amorphous solid (433 mg), which was dissolved in 90% TFA. The mixture was allowed to stand for 45 minutes at room temperature and then evaporated in vacuo at 10° C. The residue was triturated with ether to give crude Id (291 mg) which was dissolved in a small amount of methanol and passed through an HP-20 (20 mL) column by eluting with 30% aqueous methanol, to give 63.3 mg (29%) of the title compound [Id]. Estimated purity 70%.
Reaction SMILES: [I:1]Cl.[Cl:3][C:4]1[CH:5]=[C:6]([CH:8]=[CH:9][C:10]=1[Cl:11])[NH2:7]>C(O)(=O)C>[Cl:11][C:10]1[C:4]([Cl:3])=[CH:5][C:6]([NH2:7])=[C:8]([I:1])[CH:9]=1
Reactant: Nc1ccc(Cl)c(Cl)c1
Reactant: ClI
Solvent: CC(=O)O
Product: Nc1cc(Cl)c(Cl)cc1I
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 43.3 %

Procedure:
Iodine monochloride (1.39 mL; 27.77 mmol) was added to a solution of 3,4-dichloroaniline (4.50 g; 27.77 mmol) in acetic acid (15 mL) and the resulting mixture was stirred 30 minutes at room temperature. The solution was concentrated to dryness, neutralized with sodium bicarbonate and extracted with dichloromethane. The combined organic layers were washed with a saturated solution of sodium thiosulphate, dried over magnesium sulphate and concentrated under reduced pressure. The crude material was purified by flash chromatography on silica gel (eluent 2 to 20% ethyl acetate in heptane) to afford 3.46 g (43%) of 4,5-dichloro-2-iodoaniline as a brown solid.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9](=[O:14])[C:10]([CH3:13])([CH3:12])[CH3:11])=[C:4](I)[C:3]=1[C:16]([F:19])([F:18])[F:17].[Si:20]([C:24]#[CH:25])([CH3:23])([CH3:22])[CH3:21]>[Cu](I)I.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C(N(CC)CC)C>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9](=[O:14])[C:10]([CH3:13])([CH3:12])[CH3:11])=[C:4]([C:25]#[C:24][Si:20]([CH3:23])([CH3:22])[CH3:21])[C:3]=1[C:16]([F:19])([F:18])[F:17]
Reactant: C#C[Si](C)(C)C
Reactant: CC(C)(C)C(=O)Nc1ccc(Cl)c(C(F)(F)F)c1I
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: I[Cu]I
Solvent: CCN(CC)CC
Product: CC(C)(C)C(=O)Nc1ccc(Cl)c(C(F)(F)F)c1C#C[Si](C)(C)C
Temperature: 50 °C

Procedure:
A triethylamine (2.2 mL) solution of N-[4-chloro-2-iodo-3-(trifluoromethyl)phenyl]-2,2-dimethylpropanamide (0.413 g, 1.02 mmol) was treated with TMS acetylene (0.158 mL, 1.12 mmol) followed by copper iodide (0.019 g, 0.102 mmol) and PdCl2(PPh3)2 (0.021 g, 0.031 mmol). The reaction vessel was purged with N2, sealed and heated to 50° C. for 14 h. TLC at this time showed excellent conversion to the desired product. The cooled mixture was filtered through a plug of celite and partitioned between EtOAc (10 mL) and H2O (10 mL). The organic portion was dried (Na2SO4), filtered, and concentrated. Column chromatography (SiO2, EtOAc/hexanes) affored the title compound as a light brown solid: 1H NMR (CDCl3) δ 8.72 (bs, 1H), 8.64 (d, J=6.0 Hz, 1H), 7.41 (d, J=6.0 Hz, 1H), 1.34 (s, 9H), 0.29 (s, 9H).
Reaction SMILES: [CH3:1][S:2][C:3]1[CH:4]=[C:5]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][N:11]=2)[N+:6]([O-])=[CH:7][CH:8]=1.P([C:24]#[N:25])(=O)(OCC)OCC.C(N(CC)CC)C>C(#N)C>[CH3:1][S:2][C:3]1[CH:8]=[C:7]([C:24]#[N:25])[N:6]=[C:5]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][N:11]=2)[CH:4]=1
Reactant: CSc1cc[n+]([O-])c(-c2ccccn2)c1
Reactant: CCOP(=O)(C#N)OCC
Solvent: CCN(CC)CC
Solvent: CC#N
Product: CSc1cc(C#N)nc(-c2ccccn2)c1
Yield: 72 %

Procedure:
4-Methylsulfanyl-[2,2′]bipyridinyl 1-oxide (480 mg, 2.20 mmol) was treated under nitrogen with diethyl phosphorocyanidate and triethylamine in dry acetonitrile following a described procedure (I. Antonioni; G. Cristalli; P. Franchetti; M. Grifantini; S. Martelli, Il Farmaco, 1986, 41, 346-354). Crystallization in ethyl acetate afforded 4-methylsulfanyl-[2,2′]bipyridinyl-6-carbonitrile as a white solid (360 mg, 72% yield)
Reaction SMILES: [O:1]1[CH:5]=[CH:4][C:3]([N:6](CC2C=CC(OC)=CC=2)[S:7]([C:10]2[CH:11]=[C:12]3[C:17](=[CH:18][CH:19]=2)[N:16]([C:20]2[C:25]([OH:26])=[CH:24][C:23]([C:27]4[CH:32]=[C:31]([F:33])[CH:30]=[C:29]([F:34])[CH:28]=4)=[C:22]([F:35])[CH:21]=2)[C:15](=[O:36])[CH:14]=[CH:13]3)(=[O:9])=[O:8])=[N:2]1.C(=O)([O-])[O-].[K+].[K+].Br[CH:53]([CH3:56])[C:54]#[N:55].O>CN(C=O)C>[C:54]([CH:53]([O:26][C:25]1[C:20]([N:16]2[C:17]3[C:12](=[CH:11][C:10]([S:7]([NH:6][C:3]4[CH:4]=[CH:5][O:1][N:2]=4)(=[O:8])=[O:9])=[CH:19][CH:18]=3)[CH:13]=[CH:14][C:15]2=[O:36])=[CH:21][C:22]([F:35])=[C:23]([C:27]2[CH:32]=[C:31]([F:33])[CH:30]=[C:29]([F:34])[CH:28]=2)[CH:24]=1)[CH3:56])#[N:55]
Reactant: COc1ccc(CN(c2ccon2)S(=O)(=O)c2ccc3c(ccc(=O)n3-c3cc(F)c(-c4cc(F)cc(F)c4)cc3O)c2)cc1
Reactant: CC(Br)C#N
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: CC(C#N)Oc1cc(-c2cc(F)cc(F)c2)c(F)cc1-n1c(=O)ccc2cc(S(=O)(=O)Nc3ccon3)ccc21
Reaction time: 16 h

Procedure:
To a solution of N-(isoxazol-3-yl)-N-(4-methoxybenzyl)-2-oxo-1-(2,3′,5′-trifluoro-5-hydroxy-[1,1′-biphenyl]-4-yl)-1,2-dihydroquinoline-6-sulfonamide (0.066 g, 0.104 mmol) in DMF (0.208 ml) at room temperature was added potassium carbonate (0.016 g, 0.115 mmol) followed by 2-bromopropanenitrile (0.014 ml, 0.156 mmol). The reaction mixture was stirred 16 hr. The resulting mixture was transferred to a sep.funnel containing water and the aqueous layer was washed 3× with DCM. The organic layers were combined, dried with MgSO4, filtered and concentrated to an oil. The crude material was taken onward to the next step without further purification, assuming quantitative yield. m/z (ESI) 687.1 (M+H)+.
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[N:6]([CH2:25][C:26]2[CH:31]=[CH:30][C:29]([S:32]([CH3:35])(=[O:34])=[O:33])=[CH:28][CH:27]=2)[C:7](=[O:24])[C:8]2[C:13]([C:14]=1OS(C(F)(F)F)(=O)=O)=[CH:12][C:11]([Cl:23])=[CH:10][CH:9]=2)=[O:4].[CH:36]([C:38]1[CH:39]=[C:40](B(O)O)[CH:41]=[CH:42][CH:43]=1)=[O:37]>>[CH3:1][O:2][C:3]([C:5]1[N:6]([CH2:25][C:26]2[CH:31]=[CH:30][C:29]([S:32]([CH3:35])(=[O:33])=[O:34])=[CH:28][CH:27]=2)[C:7](=[O:24])[C:8]2[C:13]([C:14]=1[C:42]1[CH:41]=[CH:40][CH:39]=[C:38]([CH:36]=[O:37])[CH:43]=1)=[CH:12][C:11]([Cl:23])=[CH:10][CH:9]=2)=[O:4]
Reactant: COC(=O)c1c(OS(=O)(=O)C(F)(F)F)c2cc(Cl)ccc2c(=O)n1Cc1ccc(S(C)(=O)=O)cc1
Reactant: O=Cc1cccc(B(O)O)c1
Product: COC(=O)c1c(-c2cccc(C=O)c2)c2cc(Cl)ccc2c(=O)n1Cc1ccc(S(C)(=O)=O)cc1

Procedure:
The present compound was synthesized by a method similar to that in Example 272 and using 6-chloro-2-(4-methanesulfonylbenzyl)-1-oxo-4-trifluoromethanesulfonyloxy-1,2-dihydroisoquinoline-3-carboxylic acid methyl ester and 3-formylphenylboronic acid.
Reaction SMILES: CON(C)[C:4]([C:6]1[C:7]([NH2:15])=[N:8][C:9]([S:12][CH2:13]C)=[N:10][CH:11]=1)=[O:5].Br[C:18]1[CH:23]=[CH:22][C:21]([C:24]([F:27])([F:26])[F:25])=[CH:20][C:19]=1[O:28][CH3:29]>>[NH2:15][C:7]1[C:6]([C:4]([C:18]2[CH:23]=[CH:22][C:21]([C:24]([F:27])([F:26])[F:25])=[CH:20][C:19]=2[O:28][CH3:29])=[O:5])=[CH:11][N:10]=[C:9]([S:12][CH3:13])[N:8]=1
Reactant: COc1cc(C(F)(F)F)ccc1Br
Reactant: CCSc1ncc(C(=O)N(C)OC)c(N)n1
Product: COc1cc(C(F)(F)F)ccc1C(=O)c1cnc(SC)nc1N

Procedure:
The compound was prepared from 4-amino-2-ethylsulfanyl-pyrimidine-5-carboxylic acid methoxy-methyl-amide, Example 1, and 1-bromo-2-methoxy-4-trifluoromethyl-benzene (prepared from 3-(trifluoromethyl)-anisole, Aldrich) in an analogous manner as described in Example 169.
Reaction SMILES: [CH2:1]([NH:8][NH2:9])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Cl:10][C:11]1[CH:16]=[CH:15][C:14]([S:17]([N:20]2[CH:25]3[CH2:26][CH2:27][CH2:28][CH:21]2[C:22](=[CH:30]O)[C:23](=O)[CH2:24]3)(=[O:19])=[O:18])=[CH:13][CH:12]=1>>[CH2:1]([N:8]1[C:23]2[CH2:24][CH:25]3[N:20]([S:17]([C:14]4[CH:15]=[CH:16][C:11]([Cl:10])=[CH:12][CH:13]=4)(=[O:19])=[O:18])[CH:21]([CH2:28][CH2:27][CH2:26]3)[C:22]=2[CH:30]=[N:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: NNCc1ccccc1
Reactant: O=C1CC2CCCC(C1=CO)N2S(=O)(=O)c1ccc(Cl)cc1
Product: O=S(=O)(c1ccc(Cl)cc1)N1C2CCCC1c1cnn(Cc3ccccc3)c1C2

Procedure:
Prepared as described in Example 5 using benzylhydrazine and 9-(4-chlorophenylsulfonyl)-2-(hydroxymethylene)-9-azabicyclo[3.3.1]nonan-3-one which was prepared as described in Example 34.
Reaction SMILES: [CH2:1]([NH:9][S:10]([C:13]1[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[C:15]([O:21][CH3:22])[CH:14]=1)(=[O:12])=[O:11])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8].[H-].[Na+].[C:25](Cl)(=[O:32])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1>CN(C=O)C>[CH3:22][O:21][C:15]1[CH:14]=[C:13]([S:10]([N:9]([CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8])[C:25](=[O:32])[C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)(=[O:12])=[O:11])[CH:18]=[CH:17][C:16]=1[O:19][CH3:20]
Reactant: CCCCCCCCNS(=O)(=O)c1ccc(OC)c(OC)c1
Reactant: O=C(Cl)c1ccccc1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CCCCCCCCN(C(=O)c1ccccc1)S(=O)(=O)c1ccc(OC)c(OC)c1
Reaction time: 0.5 h
Yield: 14.3 %

Procedure:
To a stirring solution of N-octyl-3,4-dimethoxybenzenesulfonamide (0.213 g, 0.646 mmol) in 2.00 mL of DMF, NaH (0.028 g, 0.711 mmol; 60% in oil dispersion) was added. After 30 min, benzoyl chloride (0.085 g, 0.731 mmol) was added. After a further 1 hr, the reaction mixture was diluted with 4:1 EtOAc/hexanes and washed with water (2×). The organic layer was dried over MgSO4 and concentrated in vacuo to yield a yellow solid. Purification by flash chromatography (28% ethyl acetate/hexanes) gave 0.040 g (18%) of the title compound as a clear oil.
Reaction SMILES: [CH:1]1([CH2:7][C:8]([OH:10])=O)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C(Cl)(=O)C([Cl:14])=O>C(Cl)Cl.CN(C=O)C>[CH:1]1([CH2:7][C:8]([Cl:14])=[O:10])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: O=C(Cl)C(=O)Cl
Reactant: O=C(O)CC1CCCCC1
Solvent: ClCCl
Solvent: CN(C)C=O
Product: O=C(Cl)CC1CCCCC1
Temperature: 25 °C
Reaction time: 8 h
Yield: 66.8 %

Procedure:
To a 0° C. solution of cyclohexaneacetic acid (2.12 g, 14.9 mmol) in 30 mL of CH2Cl2 was added two drops of DMF followed by oxalyl chloride (1.3 mL, 14.9 mmol). The solution was warmed to r.t. and stirred overnight. The solvent was remove in vacuo to give 1.60 g of the title compound as a colourless liquid.
Reaction SMILES: [N-:1]=[N+:2]=[N-:3].[Na+].Cl.C(N(CC)CC)C.[N+:13]([C:16]1[CH:21]=[CH:20][C:19]([C:22]2[O:23][C:24]3[CH:25]=[C:26]4[C:32](=[O:33])[N:31]([CH2:34][CH2:35][CH2:36][C:37]#[N:38])[C:30](=[S:39])[N:27]4[C:28]=3[CH:29]=2)=[CH:18][CH:17]=1)([O-:15])=[O:14]>COCCOC>[N+:13]([C:16]1[CH:17]=[CH:18][C:19]([C:22]2[O:23][C:24]3[CH:25]=[C:26]4[C:32](=[O:33])[N:31]([CH2:34][CH2:35][CH2:36][C:37]5[N:1]=[N:2][NH:3][N:38]=5)[C:30](=[S:39])[N:27]4[C:28]=3[CH:29]=2)=[CH:20][CH:21]=1)([O-:15])=[O:14]
Reactant: N#CCCCN1C(=O)c2cc3oc(-c4ccc([N+](=O)[O-])cc4)cc3n2C1=S
Reactant: [N-]=[N+]=[N-]
Agent: Cl
Agent: [Na+]
Solvent: CCN(CC)CC
Solvent: COCCOC
Product: O=C1c2cc3oc(-c4ccc([N+](=O)[O-])cc4)cc3n2C(=S)N1CCCc1nn[nH]n1
Temperature: 25 °C

Procedure:
Sodium azide (76 mg, 1.17 mmol) and triethylamine hydrochloride (161 mg, 1.17 mmol) are added to a solution of Compound 35 (462.5 mg, 1.25 mmol) dissolved in DME (15 ml) and the suspension is refluxed for 48 hours. The mixture is then cooled to room temperature and the solvent is removed under reduced pressure. Water (30 ml) and ethyl acetate (30 ml) are added thereto and the aqueous phase is extracted three more times with ethyl acetate. The combined organic extracts are dried over Na2SO4 and the solvent is evaporated under reduced pressure. The crude product is recrystallized from ethanol to give Compound 36.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]([N:16]2[C:20]([CH2:21]O)=[C:19]([CH3:23])[N:18]=[C:17]2[CH2:24][N:25]([CH3:27])[CH3:26])=[C:6]([CH:15]=1)[C:7]([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)=[O:8].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[C:47]1(=[O:57])[NH:51][C:50](=[O:52])[C:49]2=[CH:53][CH:54]=[CH:55][CH:56]=[C:48]12.N(C(OCC)=O)=NC(OCC)=O>>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([N:16]2[C:20]([CH2:21][N:51]3[C:47](=[O:57])[C:48]4=[CH:56][CH:55]=[CH:54][CH:53]=[C:49]4[C:50]3=[O:52])=[C:19]([CH3:23])[N:18]=[C:17]2[CH2:24][N:25]([CH3:27])[CH3:26])=[C:6]([C:7](=[O:8])[C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH:15]=1
Reactant: Cc1nc(CN(C)C)n(-c2ccc(Cl)cc2C(=O)c2ccccc2)c1CO
Reactant: O=C1NC(=O)c2ccccc21
Agent: CCOC(=O)N=NC(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Product: Cc1nc(CN(C)C)n(-c2ccc(Cl)cc2C(=O)c2ccccc2)c1CN1C(=O)c2ccccc2C1=O

Procedure:
In the manner given in Example 3, 5-chloro-2-[2-[(dimethylamino)methyl]-4-methyl-5-hydroxymethylimidazo1-yl]benzophenone, triphenylphosphine, phthalimide and thereafter diethyl azodicarboxylate are reacted together to give N-[[1-[4-chloro-2-(benzoyl)phenyl]-2-[(dimethylamino)methyl]-4-methylimidazol-5-yl]methyl]phthalimide.
Reaction SMILES: [I:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][CH:10]=1)[C:5]([OH:7])=O.[CH2:11]([NH2:14])[CH2:12][CH3:13]>>[CH2:11]([NH:14][C:5](=[O:7])[C:4]1[CH:8]=[CH:9][CH:10]=[C:2]([I:1])[CH:3]=1)[CH2:12][CH3:13]
Reactant: O=C(O)c1cccc(I)c1
Reactant: CCCN
Product: CCCNC(=O)c1cccc(I)c1
Yield: 82 %

Procedure:
Using Preparation Method 1, 3-iodobenzoic acid was reacted with n-propylamine. The resulting reaction mixture was purified using SiO2 with CH2Cl2/petroleum ether 95:5 to CH2Cl2/AcOEt 95:5 to give N-n-propyl-3-iodobenzamide as an off-white solid (82%). NMR 1H (ppm, CDCl3): 8.07 (t, J4=1.6 Hz, 1H), 7.80 (d. t., J3=7.9 Hz, J4=1.1 Hz, 1H), 7.69 (d. t., J3=7.8 Hz, J4=1.1 Hz, 1H), 7.15 (t, J3=7.8 Hz, 1H), 6.06 (br. s., 1H), 3.43-3.36 (m, 2H), 1.62 (sext., J3=7.3 Hz, 2H), 0.97 (t, J3=7.4 Hz, 3H).
Reaction SMILES: C1(C(C2C=CC=CC=2)N2C3C(=CC=CC=3)C(C3C(O)=CC4C[CH2:22][O:23]C=4C=3)C2=O)C=CC=CC=1.[C:34]1([CH:40]([C:63]2[CH:68]=[CH:67][CH:66]=[CH:65][CH:64]=2)[N:41]2[C:49]3[C:44](=[CH:45][CH:46]=[CH:47][CH:48]=3)[CH:43]([C:50]3[C:51]([OH:61])=[CH:52][C:53]4[O:57][CH2:56][C:55]([CH3:59])([CH3:58])[C:54]=4[CH:60]=3)[C:42]2=[O:62])[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1>>[C:63]1([CH:40]([C:34]2[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=2)[N:41]2[C:49]3[C:44](=[CH:45][CH:46]=[CH:47][CH:48]=3)[C:43]([C:50]3[C:51]([OH:61])=[CH:52][C:53]4[O:57][CH2:56][C:55]([CH3:58])([CH3:59])[C:54]=4[CH:60]=3)([CH2:22][OH:23])[C:42]2=[O:62])[CH:68]=[CH:67][CH:66]=[CH:65][CH:64]=1
Reactant: CC1(C)COc2cc(O)c(C3C(=O)N(C(c4ccccc4)c4ccccc4)c4ccccc43)cc21
Reactant: O=C1C(c2cc3c(cc2O)CCO3)c2ccccc2N1C(c1ccccc1)c1ccccc1
Product: CC1(C)COc2cc(O)c(C3(CO)C(=O)N(C(c4ccccc4)c4ccccc4)c4ccccc43)cc21

Procedure:
Following the procedure as described in PREPARATION 26C, and making non-critical variations to replace 1-(diphenylmethyl)-3-(5-hydroxy-2,3-dihydro-1-benzofuran-6-yl)-1,3-dihydro-2H-indol-2-one with 1-(diphenylmethyl)-3-(6-hydroxy-3,3-dimethyl-2,3-dihydro-1-benzofuran-5-yl)-1,3-dihydro-2H-indol-2-one, the title compound was obtained: MS (ES+) m/z 492.5 (M+1)
Reaction SMILES: [C:1]1([C:16]2[NH:15][C:14]3[C:7](=[CH:8][CH:9]=[C:10]([CH:13]=3)[O:11][CH3:12])[C:6]=2[CH:5]=[CH:4][N:3]=1)[CH3:2].CN(C=O)C.[H-].[Na+].[CH2:24](Br)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1>C1COCC1>[CH2:24]([N:15]1[C:16]2[C:1]([CH3:2])=[N:3][CH:4]=[CH:5][C:6]=2[C:7]2[C:14]1=[CH:13][C:10]([O:11][CH3:12])=[CH:9][CH:8]=2)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1
Reactant: BrCc1ccccc1
Reactant: COc1ccc2c(c1)[nH]c1c(C)nccc12
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: C1CCOC1
Product: COc1ccc2c3ccnc(C)c3n(Cc3ccccc3)c2c1
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 67 %

Procedure:
Harmine 1 (2.1 g, 10 mmol), DMF (50 ml) and THF (50 ml) were respectively added in a 250 ml round-bottom flask, and were stirred at room temperature for 10 minutes followed by the addition of 60% NaH (1.2 g, 30 mmol). The mixture was stirred until there were no bubbles formed. Benzyl bromide (3 ml) was added dropwise. The mixture was then refluxed by heating for 8 h. THF was evaporated in reduced pressure, and the residues were poured into cold water. The mixture was adjusted to pH 3.0 with concentrated HCl, and extracted with ethyl ether. The aqueous phase was neutralized (pH8) with saturated NaHCO3 solution and extracted with ethyl acetate. The organic phases were combined, washed with water and brine, dried over anhydrous sodium sulfate, filtered, evaporated in reduced pressure and then recrystallized with ethyl acetate to afford gray crystals (2.2 g, 67%). mp 131-133° C.