Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[C:28]([F:29])=[CH:27][CH:26]=[C:25]([F:30])[C:3]=1[CH2:4][N:5]1[C:10](=[O:11])[CH2:9][NH:8][C:7]2[N:12]=[CH:13][C:14]([C:16]3[CH:24]=[CH:23][C:19]([C:20]([OH:22])=O)=[CH:18][CH:17]=3)=[CH:15][C:6]1=2.[CH3:31][N:32]1[CH2:37][CH2:36][NH:35][CH2:34][CH2:33]1>>[Cl:1][C:2]1[C:28]([F:29])=[CH:27][CH:26]=[C:25]([F:30])[C:3]=1[CH2:4][N:5]1[C:10](=[O:11])[CH2:9][NH:8][C:7]2[N:12]=[CH:13][C:14]([C:16]3[CH:17]=[CH:18][C:19]([C:20]([N:35]4[CH2:36][CH2:37][N:32]([CH3:31])[CH2:33][CH2:34]4)=[O:22])=[CH:23][CH:24]=3)=[CH:15][C:6]1=2
Reactant: O=C(O)c1ccc(-c2cnc3c(c2)N(Cc2c(F)ccc(F)c2Cl)C(=O)CN3)cc1
Reactant: CN1CCNCC1
Product: CN1CCN(C(=O)c2ccc(-c3cnc4c(c3)N(Cc3c(F)ccc(F)c3Cl)C(=O)CN4)cc2)CC1
Yield: 45 %

Procedure:
4-[1-(2-Chloro-3,6-difluorobenzyl)-2-oxo-1,2,3,4-tetrahydropyrido[2,3-b]pyrazin-7-yl]benzoic acid (13 mg) was reacted with 1-methyl piperazine as in General Procedure 8 to give the title compound as an off-white foam (45% yield). M.p. (foam), LCMS: m/z=512.07 (M+H+), 1H-NMR (DMSO-d6, 400 MHz) δ 2.30-2.43 (m, 2H), 2.83 (s, 3H), 3.06-3.18 (m, 2H), 3.21-3.33 (m, 2H), 3.40-3.48 (m, 2H), 4.08 (s, 2H), 5.39 (s, 2H), 7.28 (bs, 1H), 7.22-7.32 (m, 1H), 7.46 (s, 1H), 7.50 (d, J=8.3 Hz, 2H), 7.62 (d, J=8.3 Hz, 2H), 8.05 (s, 1H).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[C:16]([C:17]3[CH:22]=[CH:21][N:20]=[C:19]([NH:23][CH:24]4[CH2:28][CH2:27][CH2:26][CH2:25]4)[N:18]=3)=[C:15]3[N:10]([CH:11]=[N:12][CH:13]=[CH:14]3)[N:9]=2)[CH:5]=[CH:6][CH:7]=1.C([N-]C(C)C)(C)C.[Li+].[CH3:37][S:38]SC>O1CCCC1>[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[C:16]([C:17]3[CH:22]=[CH:21][N:20]=[C:19]([NH:23][CH:24]4[CH2:28][CH2:27][CH2:26][CH2:25]4)[N:18]=3)=[C:15]3[N:10]([C:11]([S:38][CH3:37])=[N:12][CH:13]=[CH:14]3)[N:9]=2)[CH:5]=[CH:6][CH:7]=1
Reactant: CSSC
Reactant: Clc1cccc(-c2nn3cnccc3c2-c2ccnc(NC3CCCC3)n2)c1
Agent: CC(C)[N-]C(C)C
Agent: [Li+]
Solvent: C1CCOC1
Product: CSc1nccc2c(-c3ccnc(NC4CCCC4)n3)c(-c3cccc(Cl)c3)nn12
Temperature: -78 °C
Reaction time: 0.17 h
Yield: 57.3 %

Procedure:
To a cold (−78° C.) solution of 4-[2-(3-chlorophenyl)pyrazolo[1,5-c]pyrimidin-3-yl]-N-cyclopentyl-2-pyrimidinamine (267 mg, 0.683 mmol) in tetrahydrofuran (8 mL) was added lithium diisopropylamide (12.8 mL, 0.16 M in tetrahydrofuran, 2.05 mmol, made from 5 mL n—BuLi (1.6 M in hexanes) and 1.19 mL diisopropylamine in 43.5 mL tetrahydrofuran at 0° C.) dropwise. The reaction mixture was stirred at −78° C. for 10 minutes followed by the addition of methyl disulfide (246 μL, 2.73 mmol). The resultant mixture was stirred at −78° C. for 10 minutes then quenched with water. Upon warming to room temperature, the mixture was extracted with ethyl acetate. The organic layer was washed with water and brine, then dried over magnesium sulfate. Filtration and concentration followed by flash chromatography (4:1 to 3:1 hexanes:ethyl acetate) provided 4-[2-(3-chlorophenyl)-7-(methylthio)pyrazolo[1,5-c]pyrimidin-3-yl]-N-cyclopentylpyrimidin-2-amine (171 mg, 57%) as a white solid. Rf 0:10 (4:1 hexanes:ethyl acetate); 1H NMR (CDCl3) δ 8.12 (d, 1H), 7.99–7.91 (m, 2H), 7.73 (s,1H), 7.51 (d, 1H), 7.48–7.34 (m, 2H), 6.35 (d,1H), 5.19 (d, 1H), 4.30 (m, 1H), 2.76 (s, 3H), 2.05 (m, 2H), 1.82–1.50 (m, 6H); MS m/z 437 (M+1).
Reaction SMILES: [CH:1]1[CH:6]=[C:5]2[C:7]([C:9]3[CH:16]=[CH:15][C:14]([OH:17])=[C:13]([OH:18])[C:10]=3[C:11](=[O:12])[C:4]2=[CH:3][CH:2]=1)=[O:8].[C:19](OC(=O)C)(=[O:21])[CH3:20].Cl>N1C=CC=CC=1>[CH3:20][C:19]([O:17][C:14]1[CH:15]=[CH:16][C:9]2[C:7](=[O:8])[C:5]3[CH:6]=[CH:1][CH:2]=[CH:3][C:4]=3[C:11](=[O:12])[C:10]=2[C:13]=1[OH:18])=[O:21]
Reactant: CC(=O)OC(C)=O
Reactant: O=C1c2ccccc2C(=O)c2c1ccc(O)c2O
Agent: Cl
Solvent: c1ccncc1
Product: CC(=O)Oc1ccc2c(c1O)C(=O)c1ccccc1C2=O
Reaction time: 16 h

Procedure:
This substrate was prepared using a method familiar to those skilled in the art. Two grams of Alizarin were dissolved in 5 ml of Pyridine and treated with a mixture of 2.5 ml of Acetic anhydride and 5 ml of Pyridine. After 16 hours at room temperature, the yellow solution was poured into 100 ml of hydrochloric acid containing ice. The precipitated Acetate was recovered by filtration with aspiration and then washed in water. Recrystallization from Acetone yielded 1.4 g of Alizarin-2-acetate in the form of yellow crystals.
Reaction SMILES: CC(O)CCCCCC.[CH:10]([OH:23])([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1>>[C:10]([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)(=[O:23])[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1
Reactant: OC(c1ccccc1)c1ccccc1
Solvent: CCCCCCC(C)O
Product: O=C(c1ccccc1)c1ccccc1
Yield: 99.4 %

Procedure:
Example 3 was repeated, replacing catalyst (IV) to 0.69 g (0.25 mmol), of catalyst (V), replacing 2-octanol with 9.20 g (50 mmol) of benzhydrol, and reducing the reaction time to 1 hour. 9.04 g (49.7 mmol) of benzophenone were thus obtained (GCL purity>99%), which corresponds to a 99% yield.
Reaction SMILES: [CH3:1][S:2]([C:5]1[CH:10]=[CH:9][C:8]([CH2:11][C:12]([OH:14])=O)=[CH:7][CH:6]=1)(=[O:4])=[O:3].S(Cl)([Cl:17])=O>>[CH3:1][S:2]([C:5]1[CH:10]=[CH:9][C:8]([CH2:11][C:12]([Cl:17])=[O:14])=[CH:7][CH:6]=1)(=[O:4])=[O:3]
Reactant: O=S(Cl)Cl
Reactant: CS(=O)(=O)c1ccc(CC(=O)O)cc1
Product: CS(=O)(=O)c1ccc(CC(=O)Cl)cc1
Temperature: 90 °C
Yield: 101.1 %

Procedure:
First, a mixture of 110 g (0.51 mole) of 4-methylsulfonylphenylacetic acid and 110 ml (1.51 moles) of thionyl chloride was heated at 90° C. for 2 hours. After completion of the reaction, an excess of thionyl chloride was distilled off under reduced pressure, giving about 120 g of 4-methylsulfonylphenylacetyl chloride as a light brown solid. The solid thus obtained was subjected to the subsequent reaction without isolation and purification.
Reaction SMILES: C(N(CC)CC)C.[I-].[Cl:9][C:10]1[C:25]([Cl:26])=[CH:24][C:13]2[N+:14]([CH2:22][CH3:23])=[C:15]([CH:19]=NO)[N:16]([CH2:17][CH3:18])[C:12]=2[CH:11]=1.[Cl:27]([O-:31])(=[O:30])(=[O:29])=[O:28].Cl[C:33](C)=[CH:34][C:35]1[S:36][C:37]2[CH:45]=[CH:44][CH:43]=[CH:42][C:38]=2[N+:39]=1[CH2:40][CH3:41]>C(#N)C.CCOCC>[Cl:27]([O-:31])(=[O:30])(=[O:29])=[O:28].[Cl:26][C:25]1[C:10]([Cl:9])=[CH:11][C:12]2[N+:16]([CH2:17][CH3:18])=[C:15]([C:19]#[C:33][CH:34]=[C:35]3[N:39]([CH2:40][CH3:41])[C:38]4[CH:42]=[CH:43][CH:44]=[CH:45][C:37]=4[S:36]3)[N:14]([CH2:22][CH3:23])[C:13]=2[CH:24]=1
Reactant: CC[n+]1c(C=C(C)Cl)sc2ccccc21
Reactant: CCn1c(C=NO)[n+](CC)c2cc(Cl)c(Cl)cc21
Agent: [I-]
Agent: [O-][Cl+3]([O-])([O-])[O-]
Solvent: CCOCC
Solvent: CCN(CC)CC
Solvent: CC#N
Product: CCN1C(=CC#Cc2n(CC)c3cc(Cl)c(Cl)cc3[n+]2CC)Sc2ccccc21
Reaction time: 0.08 h

Procedure:
Triethylamine (2.8 ml; 0.02 mol) is added to a stirred suspension of 5,6-Dichloro-1,3-diethyl-2-hydroxyiminomethyl benzimidazolium iodide (1.83g, 0.005 mol), 2-(2-chloropropenyl)-3-ethyl benzothiazolium perchlorate andacetic anhydride (0.64 g, 0.006 mol) in acetonitrile (25 ml). The mixture is stirred for 5 minutes, then diluted to 200 ml with ether. The ether is decanted and the residue treated with methanol (25 ml) and chilled. After recrystallization from methanol, the yield of purified dye is 0.37 g (14%)mp indistinct.
Reaction SMILES: Cl.[CH:2]([NH:5][OH:6])([CH3:4])[CH3:3].C(OCC)C.[OH-].[Na+].[CH3:14][O:15][C:16]1[CH:17]=[C:18]([N:26]=[C:27]=[O:28])[CH:19]=[C:20]([O:24][CH3:25])[C:21]=1[O:22][CH3:23]>O>[OH:6][N:5]([CH:2]([CH3:4])[CH3:3])[C:27]([NH:26][C:18]1[CH:17]=[C:16]([O:15][CH3:14])[C:21]([O:22][CH3:23])=[C:20]([O:24][CH3:25])[CH:19]=1)=[O:28]
Reactant: CC(C)NO
Reactant: COc1cc(N=C=O)cc(OC)c1OC
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CCOCC
Product: COc1cc(NC(=O)N(O)C(C)C)cc(OC)c1OC
Reaction time: 0.17 h
Yield: 73.9 %

Procedure:
A solution of N-isopropylhydroxylamine hydrochloride (1.2 g, 11 mmol) in water (5 mL) was combined with diethyl ether (35 mL) then cooled in an ice bath. A solution of sodium hydroxide (0.5 g, 12.5 mmol) in water (7 mL) was added over a 10 minute period. The reaction mixture was stirred for 10 minutes then 3,4,5-trimethoxyphenyl isocyanate (2.1 g, 10 mmol) was added as a solid. The reaction mixture was stirred at ambient temperature for 18 hours then filtered to remove a white precipitate. The filtrate was concentrated under vacuum to provide 2.1 g of the desired product as a white solid. An analytical sample was prepared by recrystallization from hexanes:ethyl acetate, m.p. 140.0°-141.0 ° C. Analysis: Calculated for C13H20N2O5 : %C, 54.92; %H, 7.09; %N, 9.85; Found: %C, 55.12; %H, 7.06; %N, 9.77.
Reaction SMILES: C(OC([N:8]1[CH2:13][CH2:12][CH:11]([C:14]#[C:15][C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([CH:22]([C:31]3[NH:35][C:34]4[CH:36]=[CH:37][CH:38]=[CH:39][C:33]=4[N:32]=3)[O:23][CH:24]3[CH2:29][CH2:28][N:27]([CH3:30])[CH2:26][CH2:25]3)[CH:17]=2)[CH2:10][CH2:9]1)=O)(C)(C)C.C1(O)C=CC=CC=1.Cl[Si](C)(C)C>ClCCCl>[CH3:30][N:27]1[CH2:26][CH2:25][CH:24]([O:23][CH:22]([C:18]2[CH:19]=[CH:20][CH:21]=[C:16]([C:15]#[C:14][CH:11]3[CH2:10][CH2:9][NH:8][CH2:13][CH2:12]3)[CH:17]=2)[C:31]2[NH:32][C:33]3[CH:39]=[CH:38][CH:37]=[CH:36][C:34]=3[N:35]=2)[CH2:29][CH2:28]1
Reactant: CN1CCC(OC(c2cccc(C#CC3CCN(C(=O)OC(C)(C)C)CC3)c2)c2nc3ccccc3[nH]2)CC1
Agent: C[Si](C)(C)Cl
Solvent: Oc1ccccc1
Solvent: ClCCCl
Product: CN1CCC(OC(c2cccc(C#CC3CCNCC3)c2)c2nc3ccccc3[nH]2)CC1
Temperature: 100 °C

Procedure:
To a solution of 4-{3-[(1H-benzimidazol-2-yl)(1-methylpiperidin-4-yloxy)-methyl]phenylethynyl}piperidine-1-carboxylic acid tert-butyl ester (160 mg) in 1,2-dichloroethane (10 mL) are added phenol (940 mg) and chlorotrimethylsilane (1.26 mL). The reaction mixture is heated to 100° C. for 30 minutes. Volatiles are removed under reduced pressure. The residue is purified by chromatography (gradient dichloromethane/methanol/ammonia from 100/0/0 to 85/15/1.5) to afford 2-[(1-methylpiperidin-4-yloxy)(3-piperidin-4-ylethynyl-phenyl)methyl]-1H-benzimidazole.
Reaction SMILES: Br[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][C:9]1[O:10][C:11]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)=[C:12]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[N:13]=1.[C:26]([O:33][CH3:34])(=[O:32])[CH2:27][C:28]([O:30][CH3:31])=[O:29].CC(C)([O-])C.[K+].O1CCCC1>Cl.C(OCC)C>[C:14]1([C:12]2[N:13]=[C:9]([CH2:8][CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2][CH:27]([C:26]([O:33][CH3:34])=[O:32])[C:28]([O:30][CH3:31])=[O:29])[O:10][C:11]=2[C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1
Reactant: BrCCCCCCCc1nc(-c2ccccc2)c(-c2ccccc2)o1
Reactant: COC(=O)CC(=O)OC
Agent: CC(C)(C)[O-]
Agent: Cl
Agent: [K+]
Solvent: C1CCOC1
Solvent: CCOCC
Product: COC(=O)C(CCCCCCCc1nc(-c2ccccc2)c(-c2ccccc2)o1)C(=O)OC
Reaction time: 17.5 h
Yield: 84.3 %

Procedure:
A mixture of 2-(7-bromoheptyl)-4,5-diphenyloxazole (10.00 g, 25 mmol), dimethyl malonate (9.95 g, 8.60 mL, 75 mmol), potassium tert-butoxide (8.44 g, 75 mmol), Eighteen Crown 6 ether (catalytic amount) and tetrahydrofuran (200 mL) was heated to reflux under an atmosphere of nitrogen. After 17.5 hours, the mixture was cooled, diluted with 2N hydrochloric acid solution and extracted with CH2Cl2. The combined extracts were dried over sodium sulfate and concentrated in vacuo to leave an oil. Chromatography on a column of silica gel using a mixture of hexanes and diethyl ether (9:1) as eluent afforded dimethyl 2-[7-(4,5-diphenyl-2-oxazolyl)heptyl]propanedioate (9.47 g, 83%) as an oil. An analytical sample (hydrated) was prepared by rechromatographing a 3.28 g sample on silica gel using a mixture of hexane and diethyl ether (4:1) as the mobile phase.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([C:9]2[CH2:18][CH2:17][C:12]3([O:16][CH2:15][CH2:14][O:13]3)[CH2:11][CH:10]=2)[CH:5]=[CH:6][C:7]=1[F:8].C(N(CC)CC)C.[H][H]>[Pd].C1(C)C=CC=CC=1.CC(C)=O>[F:1][C:2]1[CH:3]=[C:4]([CH:9]2[CH2:10][CH2:11][C:12]3([O:13][CH2:14][CH2:15][O:16]3)[CH2:17][CH2:18]2)[CH:5]=[CH:6][C:7]=1[F:8]
Reactant: Fc1ccc(C2=CCC3(CC2)OCCO3)cc1F
Reactant: [H][H]
Agent: [Pd]
Solvent: CC(C)=O
Solvent: Cc1ccccc1
Solvent: CCN(CC)CC
Product: Fc1ccc(C2CCC3(CC2)OCCO3)cc1F

Procedure:
A solution of 6.44 g of 8-(3,4-difluorophenyl)-1,4-dioxa-7-spiro[4.5]decene, 1 ml of triethylamine and 125 ml of toluene/acetone (vol. 4:1) was hydrogenated with 1 g of palladium/carbon (10%) at room temperature and normal pressure until the hydrogen uptake came to a standstill. The catalyst was filtered off from the reaction mixture and the filtrate was concentrated. There were obtained 6.30 g of colourless, solid 8-(3,4-difluorophenyl)-1,4-dioxaspiro[4.5]decane.
Reaction SMILES: I[C:2]1[C:12]2[O:11][CH2:10][CH2:9][C:8]([C:13]([O:15][CH3:16])=[O:14])=[CH:7][C:6]=2[CH:5]=[CH:4][CH:3]=1.ClCCl.[C]=O.C([SiH](CC)CC)C.CN(C)[CH:31]=[O:32]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].O.C(OCC)(=O)C.C(N(CC)CC)C>[CH:31]([C:2]1[C:12]2[O:11][CH2:10][CH2:9][C:8]([C:13]([O:15][CH3:16])=[O:14])=[CH:7][C:6]=2[CH:5]=[CH:4][CH:3]=1)=[O:32]
Reactant: COC(=O)C1=Cc2cccc(I)c2OCC1
Reactant: CN(C)C=O
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: CC[SiH](CC)CC
Solvent: ClCCl
Solvent: O
Solvent: CCN(CC)CC
Product: COC(=O)C1=Cc2cccc(C=O)c2OCC1
Temperature: 25 °C
Reaction time: 72 h

Procedure:
To a mixture of methyl 2,3-dihydro-9-iodo-1-benzoxepin-4-carboxylate (15 g) and [1,1′-bis(diphenylphosphino)-ferrocene]dichloropalladium(II), complex with dichloromethane (1:1) (1.9 g) in N,N-dimethylformamide (225 ml) was introduced carbon monoxide for 15 minutes. To the mixture was added the triethylamine (15.8 ml) and triethylsilane (14.5 ml) and to the mixture was introduced carbon monoxide for 1hour. Additionally, the reaction mixture was stirred for 3 days at ambient temperature under carbon monoxide atmosphere. To the reaction mixture was added a mixture of ethyl acetate and water, and catalyst ws filtered off. The separated organic layer was washed with a water, dried over magnesium sulfate and evaporated in vacuo. The residue was triturated with a mixture of diisopropyl ether and hexane (1:1) to give methyl 2,3-dihydro-9-formyl-1-benzoxepin-4-carboxylate (7.7 g).
Reaction SMILES: [C:1]([NH:20][C:21]1[S:22][CH:23]=[C:24]([C:26](=[N:30][O:31][C:32]([C:45]2[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=2)([C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)[C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[C:27]([O-])=[O:28])[N:25]=1)([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Na+].CS(Cl)(=O)=O.N1C=CC=CC=1.[NH2:63][C@@H:64]1[C:95](=[O:96])[N:66]2[C:67]([C:79]([O:81][CH:82]([C:89]3[CH:94]=[CH:93][CH:92]=[CH:91][CH:90]=3)[C:83]3[CH:88]=[CH:87][CH:86]=[CH:85][CH:84]=3)=[O:80])=[C:68]([S:71][CH2:72][C:73]3[C:74](=[O:78])[O:75][CH2:76][CH:77]=3)[CH2:69][S:70][C@H:65]12>CN(C)C=O>[O:78]=[C:74]1[C:73]([CH2:72][S:71][C:68]2[CH2:69][S:70][C@@H:65]3[C@H:64]([NH:63][C:27](=[O:28])/[C:26](/[C:24]4[N:25]=[C:21]([NH:20][C:1]([C:14]5[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=5)([C:8]5[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=5)[C:2]5[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=5)[S:22][CH:23]=4)=[N:30]\[O:31][C:32]([C:45]4[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=4)([C:39]4[CH:40]=[CH:41][CH:42]=[CH:43][CH:44]=4)[C:33]4[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=4)[C:95](=[O:96])[N:66]3[C:67]=2[C:79]([O:81][CH:82]([C:83]2[CH:88]=[CH:87][CH:86]=[CH:85][CH:84]=2)[C:89]2[CH:94]=[CH:93][CH:92]=[CH:91][CH:90]=2)=[O:80])=[CH:77][CH2:76][O:75]1
Reactant: N[C@@H]1C(=O)N2C(C(=O)OC(c3ccccc3)c3ccccc3)=C(SCC3=CCOC3=O)CS[C@H]12
Reactant: O=C([O-])C(=NOC(c1ccccc1)(c1ccccc1)c1ccccc1)c1csc(NC(c2ccccc2)(c2ccccc2)c2ccccc2)n1
Agent: CS(=O)(=O)Cl
Agent: [Na+]
Solvent: c1ccncc1
Solvent: CN(C)C=O
Product: O=C1OCC=C1CSC1=C(C(=O)OC(c2ccccc2)c2ccccc2)N2C(=O)[C@@H](NC(=O)/C(=N\OC(c3ccccc3)(c3ccccc3)c3ccccc3)c3csc(NC(c4ccccc4)(c4ccccc4)c4ccccc4)n3)[C@H]2SC1
Temperature: -50 °C
Reaction time: 0.5 h

Procedure:
A stirred solution of sodium 2-(2-tritylaminothiazol-4-yl)-2-trityloxyiminoacetate (420 mg) in dimethylformamide (5 ml) was cooled to -50° C. whilst under an inert atmosphere. Methanesulphonyl chloride (0.047 ml) was added and the reaction stirred at -50° C. for 30 min. Pyridine (0.049 ml) was added followed by a solution of diphenylmethyl 7β-amino-3-(2,5-dihydro-2-oxofuran-3-ylmethylthio)ceph-3-em-4-carboxylate (300 mg) in dimethylformamide (3 ml) and the reaction was allowed to warm to 0° C. After stirring at 0° C. for 90 min the mixture was partitioned between ethyl acetate and water. The organic phase was separated and washed twice with water followed by saturated sodium bicarbonate and finally brine. After drying over magnesium sulphate and evaporation of solvent the residue was purified by chromatography on silica gel (Keiselgel, 2:3 ethyl acetate:hexane rising to 7:3 ethyl acetate:hexane). The title compound was isolated as a foam (422 mg). υmax (CH2Cl2) 3380, 1785, 1760 and 1725cm-1 ; δ H (CDCl3) 3.25 (1H, d, J 17.3Hz), 3.49-3.56 (3H, m), 4.68 (2H, s), 5.08 (1H, d, J 4.9Hz), 6.00 (1H, dd, J 8.8Hz, 4.9Hz), 6.44 (1H, s), 6.74 (1H, bs), 6.98 (1H, s), 7.12 (1H, s), 7.16-7.49 (41H, m). [mass spectrum: +ve ion (3NOBA, Na+) MNa+ 1170].
Reaction SMILES: [CH:1]1([C:4]([C:6]2[CH:11]=[CH:10][C:9]([F:12])=[CH:8][C:7]=2[OH:13])=[O:5])[CH2:3][CH2:2]1.[IH:14]>>[F:12][C:9]1[CH:10]=[CH:11][C:6]([C:4](=[O:5])[CH2:1][CH2:2][CH2:3][I:14])=[C:7]([OH:13])[CH:8]=1
Reactant: O=C(c1ccc(F)cc1O)C1CC1
Reactant: I
Product: O=C(CCCI)c1ccc(F)cc1O
Temperature: 0 °C
Reaction time: 1.5 h
Yield: 70 %

Procedure:
30.6 Parts of cyclopropyl (4-fluoro-2-hydroxyphenyl)methanone were added portionwise to 450 parts of hydroiodic acid solution 50%. The whole was heated to reflux and stirring was continued for 1.50 hours at reflux temperature. The reaction mixture was cooled to 0° C. The precipitated product was filtered off and dissolved in 300 parts of trichloromethane. The solution was dried, filtered and evaporated. The residue was dissolved in 210 parts of petroleum ether while heating. The solution was treated twice with activated charcoal and the latter was filtered off each time. The filtrate was evaporated and the residue was suspended in 35 parts of petroleumether. After cooling to 0° C., the product was filtered off and dried, yielding 36.4 parts (70%) of 1-(4-fluoro-2-hydroxyphenyl)-4-iodo-1-butanone; mp. 41.4° C. (intermediate 89).
Reaction SMILES: [N+:1]([CH:4]([C:8](=O)[CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[CH2:5][CH2:6][CH3:7])([O-])=O.Cl.[N:22]#[C:23][NH2:24]>[Pd]>[C:14]1([CH2:13][CH2:12][CH2:11][CH2:10][CH2:9][C:8]2[N:22]=[C:23]([NH2:24])[NH:1][C:4]=2[CH2:5][CH2:6][CH3:7])[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1
Reactant: CCCC(C(=O)CCCCCc1ccccc1)[N+](=O)[O-]
Reactant: N#CN
Agent: [Pd]
Agent: Cl
Product: CCCc1[nH]c(N)nc1CCCCCc1ccccc1

Procedure:
4-Nitro-10-phenyldecan-5-one (0.084 g, 0.30 mmol) reacted with concentrated HCl (1.50 mmol) and palladium, 5 wt. % on activated carbon (0.129 g, 0.060 mmol) under H2, then reacted with cyanamide (0.064 g, 1.50 mmol) according to the general procedure. Purification by column chromatography gave 0.025 g (30%) over two steps as a yellow oil: 1H NMR (300 MHz, CD3OD) δ 7.20 (m, 2H), 7.15 (m, 3H), 2.60 (t, J=7.2 Hz, 2H), 2.40 (m, 4H), 1.56 (m, 6H), 1.30 (m, 2H), 0.92 (t, J=7.2 Hz, 3H) ppm; 13C NMR (100 MHz, CD3OD) δ 146.4, 142.5, 128.3, 128.1, 125.6, 122.1, 121.9, 35.5, 31.1, 28.8, 28.2, 25.0, 23.0, 22.3, 12.6 ppm; IR νmax (cm−1) 3165, 2931, 1680, 1453, 1031, 747, 699; HRMS (FAB) calcd for C17H25N3 (MH+) 272.2121, found 272.2127.
Reaction SMILES: [CH3:1][C:2]1[C:7]([CH3:8])=[CH:6][C:5]([C:9]2[CH2:10][CH2:11][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:13][CH:14]=2)=[C:4]([C:22](=[O:25])[CH2:23][CH3:24])[CH:3]=1>C(O)C.[Pd]>[CH3:1][C:2]1[C:7]([CH3:8])=[CH:6][C:5]([CH:9]2[CH2:10][CH2:11][N:12]([C:15]([O:17][C:18]([CH3:19])([CH3:20])[CH3:21])=[O:16])[CH2:13][CH2:14]2)=[C:4]([C:22](=[O:25])[CH2:23][CH3:24])[CH:3]=1
Reactant: CCC(=O)c1cc(C)c(C)cc1C1=CCN(C(=O)OC(C)(C)C)CC1
Agent: [Pd]
Solvent: CCO
Product: CCC(=O)c1cc(C)c(C)cc1C1CCN(C(=O)OC(C)(C)C)CC1
Reaction time: 2 h

Procedure:
A mixture of piperidine 84 (2.94 g, 8.5 mmol) and 10% Pd on carbon (144 mg, 0.65 mmol) in ethanol (10 mL) was hydrogenated at atmospheric pressure for approximately 2 h. The resulting mixture was filtered through a short plug of Celite®, eluting copiously with ethanol. The filtrate was concentrated in vacuo and the crude residue purified by flash chromatography on silica gel (gradient elution; 0%-25% EtOAc/hexanes as eluent) to afford 85 as a colorless oil.
Reaction SMILES: [CH3:1][C@H:2]1[O:7][C@@H:6]([O:8][C@H:9]2[C:18]3[C:13](=[C:14]([OH:28])[C:15]([C:20]([NH:22][C@@H:23]([C:25]([OH:27])=[O:26])[CH3:24])=[O:21])=[C:16]([CH3:19])[CH:17]=3)[C:12]3[C:29]([OH:46])=[C:30]4[C:41](=[O:42])[C:40]5[C:35](=[C:36]([OH:45])[CH:37]=[C:38]([O:43][CH3:44])[CH:39]=5)[C:33](=[O:34])[C:31]4=[CH:32][C:11]=3[C@@H:10]2[OH:47])[C@H:5]([OH:48])[C@@H:4]([O:49][C@@H:50]2[O:55][CH2:54][C@@H:53]([OH:56])[C@H:52]([OH:57])[C@H:51]2[OH:58])[C@H:3]1[NH2:59].Cl.Cl>O>[CH3:1][C@H:2]1[O:7][C@@H:6]([O:8][C@H:9]2[C:18]3[C:13](=[C:14]([OH:28])[C:15]([C:20]([NH:22][CH:23]([C:25]([OH:27])=[O:26])[CH3:24])=[O:21])=[C:16]([CH3:19])[CH:17]=3)[C:12]3[C:29]([OH:46])=[C:30]4[C:41](=[O:42])[C:40]5[C:35](=[C:36]([OH:45])[CH:37]=[C:38]([O:43][CH3:44])[CH:39]=5)[C:33](=[O:34])[C:31]4=[CH:32][C:11]=3[C@@H:10]2[OH:47])[C@H:5]([OH:48])[C@@H:4]([O:49][C@@H:50]2[O:55][CH2:54][C@@H:53]([OH:56])[C@H:52]([OH:57])[C@H:51]2[OH:58])[C@H:3]1[NH2:59]
Reactant: COc1cc(O)c2c(c1)C(=O)c1c(cc3c(c1O)-c1c(cc(C)c(C(=O)N[C@H](C)C(=O)O)c1O)[C@H](O[C@@H]1O[C@H](C)[C@H](N)[C@H](O[C@@H]4OC[C@@H](O)[C@H](O)[C@H]4O)[C@H]1O)[C@H]3O)C2=O
Agent: Cl
Solvent: O
Product: COc1cc(O)c2c(c1)C(=O)c1c(cc3c(c1O)-c1c(cc(C)c(C(=O)NC(C)C(=O)O)c1O)[C@H](O[C@@H]1O[C@H](C)[C@H](N)[C@H](O[C@@H]4OC[C@@H](O)[C@H](O)[C@H]4O)[C@H]1O)[C@H]3O)C2=O

Procedure:
Benanomicin B hydrochloride (130 mg) was dissolved in 10 ml of water, followed by addition of 10 ml of concentrated hydrochloric acid. The resultant mixture was sealed in a glass tube. After effecting the hydrolysis reaction at 110° C. for 12 hours, the resultant precipitate was collected by filtration. The precipitate was extracted three times with 10 ml of dioxane, so that 47.5 mg of benanomicinone (aglycone of benanomicin B) was obtained. The residue which remained after the extraction was purified by a preparative silica gel thin layer chromatography (on silica gel "Art. 5744", trade name, product of Merck & Co., Inc.; as developed with a mixed solvent of butanol-acetic acid-pyridine=6:1:4), whereby Fraction 1 containing dexylosylbenanomicin B and Fraction 2 containing benanomicinone were obtained separately. Fraction 1 was adsorbed on 20 ml of an adsorbent "DIAION HP-20". After washing the adsorbent with water (60 ml), the adsorbent was eluted four times with 40 ml of methanol. The eluate was concentrated to dryness, the residue obtained was dissolved in 3 ml of water, and the resultant solution was adjusted to pH 2 with 0.1N hydrochloric acid. When concentrating the solution to dryness, 17.8 mg of a purified dexylosylbenanomicin B hydrochloride was obtained. Similarly, Fraction 2 was purified chromatogrophically using the adsorbent "DIAION HP-20", when 9.5 mg of benanomicinone was recovered.