Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][C:2]1[C:11]2[N:12]=[C:13]([CH2:34][CH2:35][CH3:36])[N:14]([CH2:15][CH2:16][CH2:17][CH2:18][N:19]([O:26]C(OC(C)(C)C)=O)C(=O)C(C)(C)C)[C:10]=2[C:9]2[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=2[N:3]=1.[ClH:37].O1CCOCC1>ClCCl>[ClH:37].[OH:26][NH:19][CH2:18][CH2:17][CH2:16][CH2:15][N:14]1[C:10]2[C:9]3[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=3[N:3]=[C:2]([NH2:1])[C:11]=2[N:12]=[C:13]1[CH2:34][CH2:35][CH3:36]
Reactant: CCCc1nc2c(N)nc3ccccc3c2n1CCCCN(OC(=O)OC(C)(C)C)C(=O)C(C)(C)C
Agent: Cl
Solvent: ClCCl
Solvent: C1COCCO1
Product: CCCc1nc2c(N)nc3ccccc3c2n1CCCCNO
Temperature: 25 °C
Reaction time: 8 h

Procedure:
A mixture of N-[4-(4-amino-2-propyl-1H-imidazo[4,5-c]quinolin-1-yl)butyl]-N-[(tert-butoxycarbonyl)oxy]-2,2-dimethylpropanamide (3.35 g, 6.52 mmol), dichloromethane (50 mL), and 4 M HCl in dioxane (13.0 mL, 52.2 mmol) was stirred at room temperature overnight. The reaction mixture was concentrated under reduced pressure. The residue was concentrated twice from dichloromethane (2×25 mL) to provide 1-[4-(hydroxyamino)butyl]-2-propyl-1H-imidazo[4,5-c]quinolin-4-amine hydrochloride.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([N:9]2[C:13]([C:14]3[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=3)=[N:12][C:11]([OH:22])=[N:10]2)=[CH:5][CH:4]=1.C(=O)([O-])[O-].[K+].[K+].CN(C)C=O.C(OCC)(=O)C.Br[CH2:41][F:42]>O>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([N:9]2[C:13]([C:14]3[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=3)=[N:12][C:11]([O:22][CH2:41][F:42])=[N:10]2)=[CH:7][CH:8]=1
Reactant: COc1ccc(-c2nc(O)nn2-c2ccc(OC)cc2)cc1
Reactant: FCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Solvent: O
Product: COc1ccc(-c2nc(OCF)nn2-c2ccc(OC)cc2)cc1
Temperature: 100 °C
Reaction time: 3.5 h

Procedure:
A mixture of 1,5-bis(4-methoxyphenyl)-1H-1,2,4-triazol-3-ol (0.3 g, 1.01 mmol) and potassium carbonate (418 mg, 3.03 mmol) in bromofluoromethane (1 mL)-dimethylformamide (3 mL) was heated at 100° C. with stirring for 3.5 hours. After cooling, ethyl acetate and water were poured into the mixture. The organic layer was separated, washed with water and brine, and dried over magnesium sulfate. The solvent was removed under reduced pressure. The residue was purified by silica gel column chromatography (hexane-ethyl acetate). The desired product was triturated with hexane, isolated by filtration, and dried in vacuo to give 1,5-bis(4-methoxyphenyl)-3-(fluoromethoxy)-1H-1,2,4-triazole.
Reaction SMILES: [CH3:1][C:2]1([CH3:9])[CH2:7][C:6](=[O:8])[O:5][C:3]1=[O:4].[CH2:10]([N:12]1[CH2:17][CH2:16][N:15]([C:18]([C@@H:20]2[CH2:23][C@H:22]([NH:24][C:25]([C@:27]34[CH2:53][CH2:52][C@@H:51]([C:54]([CH3:56])=[CH2:55])[C@@H:28]3[C@@H:29]3[C@@:42]([CH3:45])([CH2:43][CH2:44]4)[C@@:41]4([CH3:46])[C@@H:32]([C@:33]5([CH3:50])[C@@H:38]([CH2:39][CH2:40]4)[C:37]([CH3:48])([CH3:47])[C@@H:36]([OH:49])[CH2:35][CH2:34]5)[CH2:31][CH2:30]3)=[O:26])[C:21]2([CH3:58])[CH3:57])=[O:19])[CH2:14][CH2:13]1)[CH3:11]>CN(C1C=CN=CC=1)C.N1C=CC=CC=1.CCOC(C)=O>[CH2:10]([N:12]1[CH2:17][CH2:16][N:15]([C:18]([C@@H:20]2[CH2:23][C@H:22]([NH:24][C:25]([C@:27]34[CH2:53][CH2:52][C@@H:51]([C:54]([CH3:56])=[CH2:55])[C@@H:28]3[C@@H:29]3[C@@:42]([CH3:45])([CH2:43][CH2:44]4)[C@@:41]4([CH3:46])[C@@H:32]([C@:33]5([CH3:50])[C@@H:38]([CH2:39][CH2:40]4)[C:37]([CH3:47])([CH3:48])[C@@H:36]([O:49][C:6](=[O:8])[CH2:7][C:2]([CH3:9])([CH3:1])[C:3]([OH:5])=[O:4])[CH2:35][CH2:34]5)[CH2:31][CH2:30]3)=[O:26])[C:21]2([CH3:57])[CH3:58])=[O:19])[CH2:14][CH2:13]1)[CH3:11]
Reactant: CC1(C)CC(=O)OC1=O
Reactant: C=C(C)[C@@H]1CC[C@]2(C(=O)N[C@H]3C[C@@H](C(=O)N4CCN(CC)CC4)C3(C)C)CC[C@]3(C)[C@H](CC[C@@H]4[C@@]5(C)CC[C@H](O)C(C)(C)[C@@H]5CC[C@]43C)[C@@H]12
Agent: CN(C)c1ccncc1
Solvent: CCOC(C)=O
Solvent: c1ccncc1
Product: C=C(C)[C@@H]1CC[C@]2(C(=O)N[C@H]3C[C@@H](C(=O)N4CCN(CC)CC4)C3(C)C)CC[C@]3(C)[C@H](CC[C@@H]4[C@@]5(C)CC[C@H](OC(=O)CC(C)(C)C(=O)O)C(C)(C)[C@@H]5CC[C@]43C)[C@@H]12
Yield: 60.6 %

Procedure:
2,2-Dimethylsuccinic anhydride (238 mg) was added to a stirred solution of (1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-N-((1S,3R)-3-(4-ethylpiperazine-1-carbonyl)-2,2-dimethylcyclobutyl)-9-hydroxy-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)icosahydro-1H-cyclopenta[a]chrysene-3a-carboxamide (Example 67, 125 mg) and DMAP (45 mg) in dry pyridine (10 mL) at room temperature. After addition, the reaction mixture was refluxed for 14 hours. After completion of the reaction (monitored by TLC), it was diluted with EtOAc, the organic layer was washed with aqueous 1N HCl, then washed with water and brine, and dried with Na2SO4. The solvent was evaporated and purified by silica gel column (100-200, elution 35% EtOAc in hexane) to afford 90 mg of title compound (60.8% yield) as an off white solid with 81.67% HPLC purity. 1H-NMR (300 MHz, CDCl3): δ 5.92 (d, J=7.8 Hz, 1H), 4.73 (s, 1H), 4.58 (s, 1H), 4.52-4.44 (m, 1H), 4.19-4.09 (m, 1H), 3.90 (m, 2H), 3.7 (m, 2H), 3.15-3.04 (m, 1H), 2.87-2.82 (m, 6H), 2.60 (m, 3H), 2.5-2.3 (m, 3H), 2.00-1.91 (m, 3H), 1.75-1.10 (m, 36H), 0.947, 0.914, 0.900 (s, 18H); Mass: [M+1]+ 806 (100%); IR (KBr, cm−1): 3394, 2957, 2873, 1724, 1623, 1455, 1374, 1367, 1244, 1188, 1146, 980, 883, 765; M.R: 63.8° C.-122.5° C.
Reaction SMILES: C(N(CC)CC)C.S(Cl)(C1C=CC(C)=CC=1)(=O)=O.[C:19]([NH:38][C:39]1[S:40][CH:41]=[C:42]([C:44](=[N:48][O:49][CH3:50])[C:45]([OH:47])=O)[N:43]=1)([C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)([C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.[CH3:51][C:52]([O:54][CH2:55][C:56]1[CH2:65][S:64][C@@H:59]2[C@H:60]([NH2:63])[C:61](=[O:62])[N:58]2[C:57]=1[C:66]([OH:68])=[O:67])=[O:53]>CC(N(C)C)=O.C(Cl)Cl>[C:52]([O:54][CH2:55][C:56]1[CH2:65][S:64][C@@H:59]2[CH:60]([NH:63][C:45](=[O:47])[C:44]([C:42]3[N:43]=[C:39]([NH:38][C:19]([C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=4)([C:32]4[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=4)[C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=4)[S:40][CH:41]=3)=[N:48][O:49][CH3:50])[C:61](=[O:62])[N:58]2[C:57]=1[C:66]([OH:68])=[O:67])(=[O:53])[CH3:51]
Reactant: CC(=O)OCC1=C(C(=O)O)N2C(=O)[C@@H](N)[C@H]2SC1
Reactant: CON=C(C(=O)O)c1csc(NC(c2ccccc2)(c2ccccc2)c2ccccc2)n1
Agent: Cc1ccc(S(=O)(=O)Cl)cc1
Solvent: CC(=O)N(C)C
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CON=C(C(=O)NC1C(=O)N2C(C(=O)O)=C(COC(C)=O)CS[C@H]12)c1csc(NC(c2ccccc2)(c2ccccc2)c2ccccc2)n1

Procedure:
Another preferred embodiment of the process of the invention comprises reacting at low temperatures in dimethylacetamide in the presence of triethylamine, tosyl chloride and the syn isomer of 2-(2-tritylamino-4-thiazolyl)-2-methoxyiminoacetic acid and reacting the resulting product with a solution of 7-amino-cephalosporanic acid in methylene chloride in the presence of triethylamine to obtain the syn isomer of 3-acetoxymethyl-7-[2-(2-tritylamino-4-thiazolyl)-2-methoxyimino-acetamido]-ceph-3-eme-4-carboxylic acid.
Reaction SMILES: C(Cl)(=O)C(Cl)=O.CS(C)=O.[CH2:11]([O:18][C:19]1[CH:24]=[CH:23][C:22]([S:25][CH3:26])=[CH:21][C:20]=1[C:27]([CH3:32])([CH3:31])[CH2:28][CH2:29][OH:30])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.O>ClCCl>[CH2:11]([O:18][C:19]1[CH:24]=[CH:23][C:22]([S:25][CH3:26])=[CH:21][C:20]=1[C:27]([CH3:32])([CH3:31])[CH2:28][CH:29]=[O:30])[C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1
Reactant: CSc1ccc(OCc2ccccc2)c(C(C)(C)CCO)c1
Agent: O=C(Cl)C(=O)Cl
Solvent: CS(C)=O
Solvent: O
Solvent: ClCCl
Product: CSc1ccc(OCc2ccccc2)c(C(C)(C)CC=O)c1
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 78.6 %

Procedure:
To a solution of 1.57 mL of oxalyl chloride in 15 mL of dichloromethane at −60° C. was added a solution of 2.55 mL of DMSO in 5 mL of dichloromethane. After 10 minutes, a solution of 3-(2-benzyloxy-5-methylsulfanylphenyl)-3-methylbutan-1-ol (2.84 g, 8.9 mmol) in 5 mL of dichloromethane was added (solids quickly precipitated), followed 15 minutes later by 7.5 mL triethylamine and the reaction mixture became very thick with solids. The reaction mixture was then warmed to room temperature and monitored by TLC. After 1 hour, TLC of an aliquot showed reaction was complete, so water was added to the reaction mixture and the resulting layers were separated. The aqueous layer was washed with dichloromethane and the organics were combined, washed four times with water, washed with brine, dried over magnesium sulfate, and concentrated in vacuo to afford a yellow oil. The residue was purified on SiO2 (0% to 10% ethyl acetate-hexanes) to give 2.2 g (78.7% yield) of 3-(2-benzyloxy-5-methylsulfanylphenyl)-3-methylbutyraldehyde as a colorless oil that slowly crystallized upon standing.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:10]=[C:11]([CH:15]=[CH:16][CH:17]=1)[C:12]([OH:14])=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.S(Cl)(Cl)=O.[NH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=1[S:29]([NH2:32])(=[O:31])=[O:30].C(=O)(O)[O-].[Na+]>O1CCOCC1.C1C=CC=CC=1>[C:23](#[N:22])[CH3:24].[CH2:1]([O:8][C:9]1[CH:10]=[C:11]([CH:15]=[CH:16][CH:17]=1)[C:12]([NH:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=1[S:29](=[O:31])(=[O:30])[NH2:32])=[O:14])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: Nc1ccccc1S(N)(=O)=O
Reactant: O=C(O)c1cccc(OCc2ccccc2)c1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: C1COCCO1
Solvent: c1ccccc1
Solvent: O=S(Cl)Cl
Product: CC#N
Product: NS(=O)(=O)c1ccccc1NC(=O)c1cccc(OCc2ccccc2)c1
Temperature: 25 °C
Reaction time: 1 h
Yield: 1.1 %

Procedure:
A benzene (40 ml) solution containing 2 g (8.8 mol) of 3-benzyloxybenzoic acid and 8 ml of thionyl chloride was heated under reflux for 2 hours and then the solvent was evaporated. A dioxane (10 ml) solution of the resulting residue was added dropwise to a water-dioxane 1:1 (20 ml) solution containing 1.5 g (8.8 mol) of 2-aminobenzenesulfonamide and 1.62 g (19 mol) of sodium bicarbonate, and the mixture was stirred at room temperature for 1 hour. After completion of the reaction, dioxane was evaporated, the resulting residue was acidified by adding 1 N HCl under ice-cooling and extracted with ethyl acetate. The extract was washed with water and saturated brine and dried over anhydrous sodium sulfate, and then the solvent was evaporated under a reduced pressure. By recrystallizing the resulting residue from acetonitrile 2.0 g (yield: 60%) of the title compound was obtained.
Reaction SMILES: S(Cl)(Cl)=O.[C:5]1([C:11]2([C:14]([OH:16])=O)[CH2:13][CH2:12]2)[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1.[NH3:17]>C1(C)C=CC=CC=1.CN(C=O)C.Cl>[C:5]1([C:11]2([C:14]([NH2:17])=[O:16])[CH2:13][CH2:12]2)[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1
Reactant: O=C(O)C1(c2ccccc2)CC1
Reactant: N
Agent: Cl
Solvent: Cc1ccccc1
Solvent: O=S(Cl)Cl
Solvent: CN(C)C=O
Product: NC(=O)C1(c2ccccc2)CC1
Temperature: 23 °C
Reaction time: 8 h
Yield: 95 %

Procedure:
Thionyl chloride (0.225 mL, 3.08 mmol) was slowly added to a solution of 1-phenylcyclopropanecarboxylic acid (0.50 g, 3.08 mmol) in toluene (10 mL) and DMF (0.3 mL). The reaction was then heated at reflux for 2 hours, then cooled down to 23° C. and treated (slow addition) with a solution of ammonia (2M in methanol, 10 mL). The reaction was then stirred at 23° C. overnight. The reaction was then diluted with hydrochloric acid (1N) and extracted with ethyl acetate (3×). The combined organic layers were dried over anhydrous magnesium sulfate, filtered and concentrated to give the crude title material (0.474 g, 95%) as a solid which was used as such in the next reaction. 1H NMR (400 MHz, CDCl3) δ: 1.11 (2H, q, J=3.79 Hz), 1.60-1.66 (2H, m), 5.34 (1H, br s), 5.91 (1H, br s), 7.31-7.41 (3H, m), 7.43-7.47 (2H, m). HPLC ret. time (Condition B): 1.225 min.
Reaction SMILES: [OH:1][C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][CH:3]=1.[CH2:10](Br)[CH:11]=[CH2:12].C(=O)([O-])[O-].[Cs+].[Cs+].O>CN(C=O)C>[CH2:12]([O:1][C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][CH:3]=1)[CH:11]=[CH2:10]
Reactant: C=CCBr
Reactant: N#Cc1ccc(O)cc1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Solvent: O
Product: C=CCOc1ccc(C#N)cc1

Procedure:
4-Hydroxybenzonitrile (30.0 g, 251.8 mmol), allyl bromide (39.6 g, 327.4 mmol), and cesium carbonate (98.5 g, 302.2 mmol) were dissolved in DMF (900 mL), and 1 mL water was added. After stirring for 12 h at ambient temperature, most of the DMF was removed in vacuo. Water was added and the reaction mixture was extracted with ethyl acetate. The combined organic layers were washed with H2O and brine. The organic layer was dried over Na2SO4, filtered, and the solvent was removed in vacuo. The title compound was obtained as a white crystalline material (40 g, 100%). 1H NMR (400 MHz, CDCl3) δ 4.60 (d, 2H), 5.34 (d, 1H), 5.43 (d, 1H), 6.03 (m, 1H), 6.96 (d, 2H), 7.58 (d, 2H).
Reaction SMILES: Cl.Cl.[NH2:3][CH2:4][CH2:5][CH2:6][S:7][C:8]1[CH:13]=[CH:12][N:11]=[CH:10][CH:9]=1.C(N(CC)CC)C.[C:21]1([C:27]2[CH:35]=[CH:34][C:30]([C:31]([Cl:33])=[O:32])=[CH:29][CH:28]=2)[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1>C(Cl)Cl>[ClH:33].[C:21]1([C:27]2[CH:28]=[CH:29][C:30]([C:31]([NH:3][CH2:4][CH2:5][CH2:6][S:7][C:8]3[CH:13]=[CH:12][N:11]=[CH:10][CH:9]=3)=[O:32])=[CH:34][CH:35]=2)[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1
Reactant: O=C(Cl)c1ccc(-c2ccccc2)cc1
Reactant: NCCCSc1ccncc1
Agent: Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: O=C(NCCCSc1ccncc1)c1ccc(-c2ccccc2)cc1
Yield: 61.3 %

Procedure:
To a solution of 1.00 g (4.15 mmol) of 4-(3-aminopropylthio)pyridine dihydrochloride and 2.89 ml (19.9 mmol) of triethylamine in 40 ml of methylene chloride was added 1.08 ml (4.98 mmol) of 4-phenylbenzoyl chloride under ice-cooling with stirring and the mixture was stirred at room temperature for 30 minutes. The reaction solution was washed with an aqueous saturated sodium bicarbonate solution and water and dried. The solvent was distilled off. The residue was purified by column chromatography (eluent: methanol/ethyl acetate=1:10) to obtain the powder which was washed with ether and dried to obtain 980 mg of the desired compound (free base) (67.8%, pale yellow powder), mp: 169.0°-170.0° C.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:22]=[C:21]3[C:17]([CH:18]=[N:19][NH:20]3)=[CH:16][CH:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[OH-].[K+].[I:25]I>CN(C)C=O.C(OCC)(=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][N:11]([C:14]2[CH:22]=[C:21]3[C:17]([C:18]([I:25])=[N:19][NH:20]3)=[CH:16][CH:15]=2)[CH2:12][CH2:13]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: II
Reactant: CC(C)(C)OC(=O)N1CCN(c2ccc3cn[nH]c3c2)CC1
Agent: [K+]
Agent: [OH-]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: CC(C)(C)OC(=O)N1CCN(c2ccc3c(I)n[nH]c3c2)CC1
Reaction time: 16 h
Yield: 38 %

Procedure:
A stirred solution of 6-[4-(t-butoxycarbonyl)piperazin-1-yl]-1H-indazole (7.20 g, 23.8 mmol) in N,N-dimethylformamide at 0° C. is treated with powdered potassium hydroxide (5.40 g, 95.4 mmol) followed by the dropwise addition of a solution of iodine (10.9 g, 42.9 mmol) in N,N-dimethylformamide, stirred at ambient temperatures for 16 h, diluted with ethyl acetate and quenched with 10% aqueous sodium metabisulfite solution. The phases are separated. The aqueous phase is extracted with ethyl acetate. The extracts are combined with the organic phase, washed with brine, dried over sodium sulfate and concentrated in vacuo. The resulting crude material is purified by flash chromatography (silica gel, 30:70 ethyl acetate/hexanes) to afford the title compound as a yellow solid, 3.4 g (38% yield) identified by NMR and mass spectral analyses.
Reaction SMILES: [C:1]([O:4][C:5]1[CH:10]=[CH:9][C:8]([CH2:11][OH:12])=[CH:7][CH:6]=1)(=[O:3])[CH3:2].[CH2:13]([CH2:15][NH2:16])[OH:14].C(N(CC)CC)C.[C:24](OCC)(=[O:26])C>C(Cl)Cl>[OH:14][CH2:13][CH2:15][NH:16][C:24](=[O:26])[O:12][CH2:11][C:8]1[CH:9]=[CH:10][C:5]([O:4][C:1](=[O:3])[CH3:2])=[CH:6][CH:7]=1
Reactant: NCCO
Reactant: CC(=O)Oc1ccc(CO)cc1
Reactant: CCOC(C)=O
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CC(=O)Oc1ccc(COC(=O)NCCO)cc1
Reaction time: 4 h
Yield: 76 %

Procedure:
Crude 61 (from 321 mg of 60, max 1.9 mmol) was taken up in 8 mL of CH2Cl2 and the solution was added to a mixture of ethanolamine (140 μL, 2.3 mmol) and triethylamine (540 μL, 3.9 mmol) in 7 mL of CH2Cl2 cooled in an ice bath. The mixture was stirred in the same bath, which was left unmaintained. After 4 h, it was diluted with 100 mL of ethyl acetate and washed with 50 mL of each of 1% HCl in 2/3 saturated brine, 2/3 saturated brine and saturated aqueous NaHCO3 (twice). The organics were dried over Na2SO4 and concentrated in vacuo to furnish 62 (364 mg, 1.44 mmol, 76% over two steps) as a gum. 1H NMR (400 MHz, CDCl3) δ 2.30 (s, 3H), 3.35 (broad q, J=5.2 Hz, 2H), 3.72 (broad q, J=5.2 Hz, 2H), 5.09 (s, 2H), 5.15 (broad s, 1H), 7.07 (d, J=8.5 Hz, 2H), 7.37 (d, J=8.4 Hz, 2H).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C@@H:12]([C:13]3[CH:18]=[CH:17][CH:16]=[C:15]([O:19][CH3:20])[CH:14]=3)[C@H:11]([CH2:21]O)[O:10][C:9]2=[O:23])=[CH:4][CH:3]=1.[C:24]1([C:30]2[NH:34][N:33]=[N:32][N:31]=2)[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C>C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[C@@H:12]([C:13]3[CH:18]=[CH:17][CH:16]=[C:15]([O:19][CH3:20])[CH:14]=3)[C@H:11]([CH2:21][N:32]3[N:33]=[N:34][C:30]([C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=4)=[N:31]3)[O:10][C:9]2=[O:23])=[CH:6][CH:7]=1
Reactant: COc1cccc([C@H]2[C@H](CO)OC(=O)N2c2ccc(Cl)cc2)c1
Reactant: c1ccc(-c2nnn[nH]2)cc1
Agent: CC(C)OC(=O)/N=N/C(=O)OC(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Product: COc1cccc([C@H]2[C@H](Cn3nnc(-c4ccccc4)n3)OC(=O)N2c2ccc(Cl)cc2)c1
Temperature: 0 °C
Reaction time: 8 h

Procedure:
(4S,5R)-3-(4-Chlorophenyl)-5-(hydroxymethyl)-4-(3-methoxyphenyl)oxazolidin-2-one (40 mg, 0.12 mmol) and phenyltetrazole (17 mg, 0.12 mmol) are dissolved in DCM (1 mL), cooled to 0° C. and are then subsequently treated with triphenylphosphine (29 mg, 0.11 mmol) and diisopropylazodicarboxylate (0.024 mL, 0.12 mmol). The mixture is allowed to stir to room temperature overnight and is then purified by flash chromatography (4 g Redisep cartridge, 10-30% Ethyl acetate-hexanes) to give the title compound. 1H NMR (acetone-d6, 400 MHz) δ 8.05-8.03 (m, 2H), 7.54-7.50 (m, 3H), 7.47-7.43 (m, 2H), 7.32 (t, J=7.9 Hz, 1H), 7.30-7.24 (m, 2H), 7.09 (t, J=2.08 Hz, 1H), 7.05-7.03 (app d, J=7.8 Hz, 1H), 6.90 (ddd, J=8.3, 2.6, 0.9 Hz, 1H), 5.72 (d, J=5.1 Hz, 1H), 5.50 (dd, J=14.7, 8.7 Hz, 1H), 5.43 (dd, J=14.7, 10.6 Hz, 1H), 5.12-5.08 (m, 1H), 3.76 (s, 3H); HPLC-MS calculated C24H20ClN5O3 (M+H+) 462.1, found 462.1.
Reaction SMILES: [CH3:1][CH:2]([S:5][C:6]1[CH:11]=[CH:10][C:9]([SH:12])=[CH:8][CH:7]=1)[CH2:3][CH3:4].C(=O)([O-])[O-].[K+].[K+].Br[CH2:20][CH2:21][N:22]1[C:26](=[O:27])[C:25]2=[CH:28][CH:29]=[CH:30][CH:31]=[C:24]2[C:23]1=[O:32].O>CSC.CN(C=O)C>[CH3:1][CH:2]([S:5][C:6]1[CH:7]=[CH:8][C:9]([S:12][CH2:20][CH2:21][N:22]2[C:26](=[O:27])[C:25]3=[CH:28][CH:29]=[CH:30][CH:31]=[C:24]3[C:23]2=[O:32])=[CH:10][CH:11]=1)[CH2:3][CH3:4]
Reactant: O=C1c2ccccc2C(=O)N1CCBr
Reactant: CCC(C)Sc1ccc(S)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: CSC
Solvent: O
Product: CCC(C)Sc1ccc(SCCN2C(=O)c3ccccc3C2=O)cc1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To 4-(1-methylpropylthio)benzenethiol (8.79 g, 44.3 mmol) in 25 ml of DMS is added, under N2, potassium carbonate (7.05 g, 51.0 mmol) followed by dropwise addition of N-(bromoethyl)-phthalimide (12.94 g, 51.0 mmol) in 30 ml of DMF. The mixture is stirred at RT overnight. Water is then added and the aqueous phase is extracted with ether. The combined organic layers are washed with 5% sodium hydroxide, with water and with brine, dried and the solvent removed to give N-{2-[4-(1-methylpropylthio)-phenylthio]ethyl}phthalimide. Following the procedures of Example 13, the above phthalimide (2.12 g, 5.7 mmol is reacted with hydrazine hydrate (0.28 ml, 5.7 mmol) to give 2-[4-(1-methylpropylthio)phenylthio ethylamine.
Reaction SMILES: C[O-].[Na+].[ClH:4].[NH2:5][OH:6].Cl[C:8]1[CH:17]=[CH:16][CH:15]=[C:14]2[C:9]=1[CH:10]=[CH:11][CH:12]=[C:13]2[CH2:18][C:19]#[N:20]>CO>[OH:6][N:5]=[C:19]([NH2:20])[CH2:18][C:13]1[C:14]2[C:9](=[C:8]([Cl:4])[CH:17]=[CH:16][CH:15]=2)[CH:10]=[CH:11][CH:12]=1
Reactant: Cl
Reactant: N#CCc1cccc2c(Cl)cccc12
Reactant: NO
Agent: C[O-]
Agent: [Na+]
Solvent: CO
Product: NC(Cc1cccc2c(Cl)cccc12)=NO
Reaction time: 8 h
Yield: 68.3 %

Procedure:
A mixture of NaOMe (25 wt % in MeOH, 1.02 mL, 4.46 mmol), MeOH (4 mL), and hydroxylamine hydrochloride (310 mg, 4.46 mmol) was heated at reflux for 20 minutes. 5-Chloro-2-naphthalenylacetonitrile (600 mg, 2.98 mmol) and additional MeOH (4 mL) were added and heating was continued overnight. Additional hydroxylamine hydrochloride (150 mg, 2.16 mmol) and NaOMe (25 wt % in MeOH, 490 μL, 2.14 mmol) were added and heating was resumed for 4 hours. The mixture was cooled, concentrated, and suspended in H2O. The solid was collected by filtration and triturated with ether to give a pale yellow solid (478 mg, 69%), m.p. 121°-125° C.
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([C:8]2[CH:9]=[C:10]([CH:26]=[CH:27][C:28]=2[O:29][CH3:30])[CH2:11][N:12]2[CH2:17][CH2:16][N:15](C(OC(C)(C)C)=O)[CH2:14][C@@H:13]2[CH3:25])[CH:5]=[CH:4][N:3]=1.[NH2:31][CH2:32][CH2:33][C:34]1[CH:39]=[CH:38][C:37]([OH:40])=[CH:36][CH:35]=1>>[CH3:30][O:29][C:28]1[CH:27]=[CH:26][C:10]([CH2:11][N:12]2[CH2:17][CH2:16][NH:15][CH2:14][C@@H:13]2[CH3:25])=[CH:9][C:8]=1[C:6]1[CH:5]=[CH:4][N:3]=[C:2]([NH:31][CH2:32][CH2:33][C:34]2[CH:39]=[CH:38][C:37]([OH:40])=[CH:36][CH:35]=2)[N:7]=1
Reactant: NCCc1ccc(O)cc1
Reactant: COc1ccc(CN2CCN(C(=O)OC(C)(C)C)C[C@@H]2C)cc1-c1ccnc(Cl)n1
Product: COc1ccc(CN2CCNC[C@@H]2C)cc1-c1ccnc(NCCc2ccc(O)cc2)n1

Procedure:
Intermediate 146 from above was coupled with tyramine following procedure F. The product was deprotected by procedure G2. LC-MS showed the product had the expected M+H+ of 434. 1H NMR (Varian 300 MHz, DMSO-d6, shifts relative to the solvent peak at 2.49 ppm) δ 8.4 (d, 1H) 7.8 (s, 1H) 7.3 (d, 1H) 7.1 (m, 3H), 6.6 (m, 3H), 3.9 (s, 3H) 3.6 (m, 4H) 3.5 (d, 2H) 3.43-3.37 (m, 2H) 3.2 (m, 2H) 2.8 (t, 2H), 1.5 (d, 3H).