Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH:1]1([CH2:4][NH:5][C:6]([NH2:8])=[S:7])[CH2:3][CH2:2]1.C[O-].[Na+].[C:12]([CH2:14][C:15](OCC)=[O:16])#[N:13]>C(O)C>[NH2:13][C:12]1[N:5]([CH2:4][CH:1]2[CH2:3][CH2:2]2)[C:6](=[S:7])[NH:8][C:15](=[O:16])[CH:14]=1
Reactant: CCOC(=O)CC#N
Reactant: NC(=S)NCC1CC1
Agent: C[O-]
Agent: [Na+]
Solvent: CCO
Product: Nc1cc(=O)[nH]c(=S)n1CC1CC1
Reaction time: 0.08 h
Yield: 56.2 %

Procedure:
To 1-cyclopropylmethyl-2-thiourea (0.60 g, 4.6 mmol) in ethanol (10 mL) was added sodium methoxide (0.26 g, 4.8 mmol) and, after 5 minutes, ethyl cyanoacetate (0.50 mL, 4.6 mmol). The resulting mixture was heated to reflux for 2 h and 40 minutes followed by evaporation of the solvent under reduced pressure and treatment of the resulting yellow solid with 2M aqueous acetic acid (10 mL) giving a white solid. The solid was collected by filtration and washed with 2M aqueous acetic acid (10 mL), stirred with ethanol (10 mL) followed by evaporation and drying under reduced pressure, giving the title compound (0.51 g, 56%).
Reaction SMILES: [CH3:1][C:2]1[O:6][C:5]([C:7]([O:9]C)=[O:8])=[CH:4][C:3]=1[C:11]1[N:15]([CH3:16])[N:14]=[CH:13][CH:12]=1.[OH-].[Na+]>O1CCCC1>[CH3:1][C:2]1[O:6][C:5]([C:7]([OH:9])=[O:8])=[CH:4][C:3]=1[C:11]1[N:15]([CH3:16])[N:14]=[CH:13][CH:12]=1
Reactant: COC(=O)c1cc(-c2ccnn2C)c(C)o1
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Product: Cc1oc(C(=O)O)cc1-c1ccnn1C
Yield: 62.6 %

Procedure:
A solution of methyl 5-methyl-4-(1-methyl-1H-pyrazol-5-yl)-2-furancarboxylate (200 mg, 0.91 mmol) in 6N sodium hydroxide (2.3 ml, 13.62 mmol) and tetrahydrofuran (4.5 ml) was stirred at 70° C. in a sealed tube for 1 h. The resulting solution was cooled and then partitioned between H2O-DCM. The aqueous phase was adjusted to pH ˜4 and then washed several times with DCM. The combined organic fractions were dried over Na2SO4 and concentrated affording 5-methyl-4-(1-methyl-1H-pyrazol-5-yl)-2-furancarboxylic acid (130 mg, 0.57 mmol, 63% yield) as a yellow oil: LCMS (ES) m/e 207 (M+H)+.
Reaction SMILES: [F:1][C:2]([F:26])([F:25])[C:3]1[CH:4]=[C:5]([NH:13][C:14](=[N:22][C:23]#[N:24])OC2C=CC=CC=2)[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[CH3:27][CH:28]([CH3:32])[CH2:29][CH2:30][NH2:31].C(N(CC)CC)C>C(#N)C>[C:23]([NH:22][C:14]([NH:13][C:5]1[CH:6]=[C:7]([C:9]([F:11])([F:10])[F:12])[CH:8]=[C:3]([C:2]([F:1])([F:26])[F:25])[CH:4]=1)=[N:31][CH2:30][CH2:29][CH:28]([CH3:32])[CH3:27])#[N:24]
Reactant: CC(C)CCN
Reactant: N#CN=C(Nc1cc(C(F)(F)F)cc(C(F)(F)F)c1)Oc1ccccc1
Solvent: CC#N
Solvent: CCN(CC)CC
Product: CC(C)CCN=C(NC#N)Nc1cc(C(F)(F)F)cc(C(F)(F)F)c1
Yield: 27.3 %

Procedure:
A solution of N-(3,5-bis(trifluoromethyl)phenyl)-N'-cyano-O-phenylisourea (1 mmol, 373 mg), 3-methylbutylamine (1.15 mmol,100 mg) and triethylamine (1.5 mmol, 150 mg) in acetonitrile (2 ml) was stirred for 24 h at 60° C. After concentration the residue was purified by column chromatography (heptane:ethyl acetate 1:1) to give the title compound (100 mg, 27%).
Reaction SMILES: [CH:1]1([C:6]#[N:7])[CH2:5][CH2:4][CH2:3][CH2:2]1.Cl.[CH3:9][CH2:10][OH:11]>>[CH:1]1([C:6](=[NH:7])[O:11][CH2:10][CH3:9])[CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: N#CC1CCCC1
Reactant: CCO
Agent: Cl
Product: CCOC(=N)C1CCCC1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
A solution of cyclopentanecarbonitrile (10.0 g, 105.1 mmol) in EtOH (7 mL) was treated with HCl (4.0 M in dioxane, 105 mL, 3.02 mol) and the mixture stirred at rt overnight. After this time, nitrogen gas was passed through the mixture and the mixture was concentrated. The residue was treated with ether and reconcentrated. The residue was again suspended in ether and filtered to afford the title compound (16.0 g, crude) as a white solid. MW=141.21. 1H NMR (CDCl3, 500 MHz) δ 4.79-4.46 (m, 2H), 3.43-3.23 (m, 1H), 2.76 (s, 1H), 2.20-2.00 (m, 2H), 1.86-1.63 (m, 6H), 1.55-1.40 (m, 3H); APCI MS m/z 142 [M+H]+.
Reaction SMILES: C(O[C:4]([C:6]1([CH2:12][CH2:13]OC)[CH2:11][CH2:10][NH:9][CH2:8][CH2:7]1)=[O:5])C.[CH3:16][CH:17]([CH3:23])[CH2:18][S:19](Cl)(=[O:21])=[O:20].[CH:24]1([O:29][C:30]2[CH:36]=[CH:35][C:33]([NH2:34])=[CH:32][CH:31]=2)[CH2:28][CH2:27][CH2:26][CH2:25]1>>[CH:24]1([O:29][C:30]2[CH:31]=[CH:32][C:33]([N:34]3[CH2:13][CH2:12][C:6]4([CH2:7][CH2:8][N:9]([S:19]([CH2:18][CH:17]([CH3:23])[CH3:16])(=[O:21])=[O:20])[CH2:10][CH2:11]4)[C:4]3=[O:5])=[CH:35][CH:36]=2)[CH2:28][CH2:27][CH2:26][CH2:25]1
Reactant: CCOC(=O)C1(CCOC)CCNCC1
Reactant: CC(C)CS(=O)(=O)Cl
Reactant: Nc1ccc(OC2CCCC2)cc1
Product: CC(C)CS(=O)(=O)N1CCC2(CCN(c3ccc(OC4CCCC4)cc3)C2=O)CC1

Procedure:
Pink solid. MS (ESI): 435.23 (MH+). This example was prepared in analogy to example 1 step C) to D) from 4-(2-methoxy-ethyl)-piperidine-4-carboxylic acid ethyl ester (example 1 step B)), 2-methyl-propane-1-sulfonyl chloride and 4-(cylopentyloxy)-aniline.
Reaction SMILES: N[C@@H](CCC(N[C@H:11]([C:14]([NH:16][CH2:17][C:18]([OH:20])=[O:19])=O)[CH2:12]S)=O)C(O)=O.CC1(C)S[C@@H]2[C@H](NC([C@H](N)C3C=CC=CC=3)=O)C(=[O:29])N2[C@H]1C(O)=O.N1CCC[C@H]1C(O)=O>>[NH:16]1[CH2:14][C@H:11]([OH:29])[CH2:12][C@H:17]1[C:18]([OH:20])=[O:19]
Reactant: N[C@@H](CCC(=O)N[C@@H](CS)C(=O)NCC(=O)O)C(=O)O
Reactant: CC1(C)S[C@@H]2[C@H](NC(=O)[C@H](N)c3ccccc3)C(=O)N2[C@H]1C(=O)O
Agent: O=C(O)[C@@H]1CCCN1
Product: O=C(O)[C@@H]1C[C@@H](O)CN1
Reaction time: 8 h

Procedure:
A plasmid (pD4-α2, FIG. 68) encoding the gene for the carboxy terminal 219 amino acids of human Type I (α2) collagen with optimized E. coli codon usage as constructed in accordance with Example 14A fused to the 3′-end of the gene for glutathione S-transferase and under control of the tac promoter and containing the gene for ampicillin resistance was used to transform by electroporation proline auxotrophic E. coli strain JM109 (F-). Transformation cultures were plated on LB agar containing 100 μg/ml ampicillin. After overnight incubation at 37° C., a single colony from a fresh transformation plate was used to inoculate 100 ml of LB media containing 100 μg/ml ampicillin. This culture was grown to an OD600 nm of 0.5 and 100 μl aliquots transferred to 1.5 ml tubes. The tubes were stored at −80° C. For expression, a tube was thawed on ice and used to inoculate 25 ml of LB media containing 400 μg/ml ampicillin. After overnight growth at 37° C., a four ml aliquot was withdrawn, centrifuged, the cell pellet washed once with 1 ml of 2×YT media containing 400 μg/ml ampicillin, and the washed cells used to inoculate 1 L of 2×YT medium containing 400 μg/ml ampicillin. This culture was grown at 37° C. to an OD600 nm of 0.8. The culture was centrifuged and the cell pellet washed once with 100 ml of M9 medium (1×M9 salts, 0.5% glucose, 1 mM MgCl2, 0.01% thiamine, 200 μg/ml glycine, 200 μg/ml alanine, 100 μg/ml of the other amino acids except proline, and 400 μg/ml ampicillin). The cells were resuspended in 910 ml of M9 medium (1×M9 salts, 0.5% glucose, 1 mM MgCl2, 0.01% thiamine, 200 μg/ml glycine, 200 μg/ml alanine, 100 μg/ml of the other amino acids except proline, and 400 μg/ml ampicillin) and allowed to grow at 37° C. for 30 minutes. NaCl (80 ml of 5 M), hydroxyproline (7.5 ml of 2M), and IPTG (500 μl of 1 M) were added and growth continued for 3 hours. Cells were harvested by centrifugation and stored at −20° C.
Reaction SMILES: [C:1]([C:3]1[C:4]([C:19]([F:22])([F:21])[F:20])=[C:5]2[C:9](=[CH:10][CH:11]=1)[N:8]([CH2:12][C:13](O)=[O:14])[C:7]([CH:16]1[CH2:18][CH2:17]1)=[CH:6]2)#[N:2].[F:23][C:24]([F:36])([F:35])[C:25]1[CH:26]=[C:27]([CH:32]=[CH:33][CH:34]=1)[C:28]([NH:30][NH2:31])=O>>[CH:16]1([C:7]2[N:8]([CH2:12][C:13]3[O:14][C:28]([C:27]4[CH:32]=[CH:33][CH:34]=[C:25]([C:24]([F:23])([F:35])[F:36])[CH:26]=4)=[N:30][N:31]=3)[C:9]3[C:5]([CH:6]=2)=[C:4]([C:19]([F:21])([F:22])[F:20])[C:3]([C:1]#[N:2])=[CH:11][CH:10]=3)[CH2:17][CH2:18]1
Reactant: NNC(=O)c1cccc(C(F)(F)F)c1
Reactant: N#Cc1ccc2c(cc(C3CC3)n2CC(=O)O)c1C(F)(F)F
Product: N#Cc1ccc2c(cc(C3CC3)n2Cc2nnc(-c3cccc(C(F)(F)F)c3)o2)c1C(F)(F)F

Procedure:
Synthesized as described in Example 35C using [5-cyano-2-cyclopropyl-4-(trifluoromethyl)-1H-indol-1-yl]acetic acid (Example 362B) and 3-(trifluoromethyl)benzohydrazide: 1H NMR (400 MHz, CDCl3) δ 8.20 (s, 1H), 8.11 (d, J=7.8 Hz, 1H), 7.80 (d, J=7.8 Hz, 1H), 7.71 (d, J=8.5 Hz, 1H), 7.64 (t, J=7.8 Hz 1H), 7.38 (d, J=8.5 Hz 1H), 6.51 (s, 1H), 5.79 (s, 2H), 2.08 (m, 1H), 1.22 (m, 2H), 0.93 (m, 2H); MS (ES) m/z 477 (M+1).
Reaction SMILES: [C:1]1([CH:7]2[CH2:12][CH2:11][N:10]([C:13]3[CH:18]=[CH:17][C:16]([S:19]([NH:22][CH2:23][C:24]([NH2:26])=[O:25])(=[O:21])=[O:20])=[CH:15][CH:14]=3)[CH2:9][CH2:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CO.[O:29]1CCCC1>C(Cl)(Cl)Cl.CO.[Pd]>[OH:29][NH:26][C:24](=[O:25])[CH2:23][NH:22][S:19]([C:16]1[CH:17]=[CH:18][C:13]([N:10]2[CH2:11][CH2:12][CH:7]([C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)[CH2:8][CH2:9]2)=[CH:14][CH:15]=1)(=[O:20])=[O:21]
Reactant: NC(=O)CNS(=O)(=O)c1ccc(N2CCC(c3ccccc3)CC2)cc1
Reactant: C1CCOC1
Agent: [Pd]
Solvent: ClC(Cl)Cl
Solvent: CO
Product: O=C(CNS(=O)(=O)c1ccc(N2CCC(c3ccccc3)CC2)cc1)NO
Reaction time: 10 h

Procedure:
A room temperature mixture of N-[phenyl-methyl)-oxy]-2-[4-(4-phenyl-piperidin-1-yl)-benzenesulfonyl-amino]-acetamide (0.1115 g, 0.0002325 mol) in methanol-tetrahydrofuran (1:1, 25 mL) was hydrogenated at 50 p.s.i. over 5% palladium on barium sulfate (0.018 g) for approximately 10 hours. Additional catalyst (0.020 g) was added, and the mixture hydrogenated again for approximately 10 hours. The mixture was filtered through celite, and the filtrate was rotary evaporated to give a glaze. The glaze was dissolved in chloroform-methanol, silica gel (1.6 g, 230-400 mesh) was added, and the mixture was rotary evaporated to dryness. The powder was poured onto a column of silica gel (10 g, 230-400 mesh) and eluted with hexanes-ethyl acetate-acetic acid (10:20:1, 16×10 mL and 10:20:2, 16×10 mL). Fractions containing product were rotary evaporated, and the residue triturated with chloroform. The chloroform suspension was filtered, and the filtercake was dried in vacuo; yield 0.0054 g (6.0%), mp=164-166° C.
Reaction SMILES: Br.[Br-].[NH2:3][CH2:4][CH2:5][N+:6]12[CH2:13][CH2:12][CH:9]([CH2:10][CH2:11]1)[C@@H:8]([O:14][C:15](=[O:30])[C:16]([OH:29])([C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[CH2:7]2.C(N(CC)CC)C.[C:38]([Br:46])(=[O:45])[C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1>C(Cl)Cl>[Br-:46].[C:38]([NH:3][CH2:4][CH2:5][N+:6]12[CH2:13][CH2:12][CH:9]([CH2:10][CH2:11]1)[C@@H:8]([O:14][C:15](=[O:30])[C:16]([OH:29])([C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)[CH2:7]2)(=[O:45])[C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1
Reactant: O=C(Br)c1ccccc1
Reactant: NCC[N+]12CCC(CC1)[C@@H](OC(=O)C(O)(c1ccccc1)c1ccccc1)C2
Agent: Br
Agent: [Br-]
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: O=C(NCC[N+]12CCC(CC1)[C@@H](OC(=O)C(O)(c1ccccc1)c1ccccc1)C2)c1ccccc1
Temperature: 0 °C
Reaction time: 1.5 h

Procedure:
To a stirred suspension of (R)-1-(2-Amino-ethyl)-3-(2-hydroxy-2,2-diphenyl-acetoxy)-1-azonia-bicyclo[2.2.2]octane bromide hydrobromide [50(H)] (0.28 g, 0.517 mmol) in DCM at 0° C. is added triethylamine (0.216 ml, 1.552 mmol) followed by benzoyl bromide (0.122 ml, 1.03 mmol). The reaction mixture is stirred at 0° C. for 1.5 hours and the solvent was removed in vacuo. Purification of the crude residue by chromatography on C18 silica, eluting with water:acetonitrile affords the title compound.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([C:8]2[N:13]=[C:12]([C:14]3[CH:19]=[CH:18][C:17]([C:20]([F:23])([F:22])[F:21])=[CH:16][CH:15]=3)[CH:11]=[C:10]([CH3:24])[N:9]=2)[CH:5]=[CH:6][CH:7]=1.[NH2:25][C:26]1[CH:31]=[CH:30][C:29](B2OC(C)(C)C(C)(C)O2)=[CH:28][N:27]=1>>[CH3:24][C:10]1[CH:11]=[C:12]([C:14]2[CH:19]=[CH:18][C:17]([C:20]([F:23])([F:22])[F:21])=[CH:16][CH:15]=2)[N:13]=[C:8]([C:4]2[CH:3]=[C:2]([C:29]3[CH:30]=[CH:31][C:26]([NH2:25])=[N:27][CH:28]=3)[CH:7]=[CH:6][CH:5]=2)[N:9]=1
Reactant: Cc1cc(-c2ccc(C(F)(F)F)cc2)nc(-c2cccc(Br)c2)n1
Reactant: CC1(C)OB(c2ccc(N)nc2)OC1(C)C
Product: Cc1cc(-c2ccc(C(F)(F)F)cc2)nc(-c2cccc(-c3ccc(N)nc3)c2)n1

Procedure:
The title compound was prepared from 2-(3-bromo-phenyl)-4-(4-trifluoromethylphenyl)-6-methyl-pyrimidine (example E.47) (0.197 g, 0.5 mmol) and commercially available 2-amino-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (0.14 g, 0.65 mmol) according to the general procedure VI. Obtained as an off-white solid (0.097 g, 48%). MS (ISP) 407.3 [(M+H)+]; mp 224° C.
Reaction SMILES: C(=O)([O-])[O-].[Na+].[Na+].[CH3:7][C@@H:8]1[CH2:13][CH2:12][C@H:11]([NH:14][C:15](=[O:30])[CH:16]=[CH:17][C:18]2[CH:23]=[CH:22][C:21]([O:24]C(=O)C)=[C:20]([O:28][CH3:29])[CH:19]=2)[CH2:10][CH2:9]1.Cl>CO>[CH3:7][C@@H:8]1[CH2:9][CH2:10][C@H:11]([NH:14][C:15](=[O:30])[CH:16]=[CH:17][C:18]2[CH:23]=[CH:22][C:21]([OH:24])=[C:20]([O:28][CH3:29])[CH:19]=2)[CH2:12][CH2:13]1
Reactant: COc1cc(C=CC(=O)N[C@H]2CC[C@@H](C)CC2)ccc1OC(C)=O
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CO
Product: COc1cc(C=CC(=O)N[C@H]2CC[C@@H](C)CC2)ccc1O
Temperature: 25 °C
Reaction time: 2 h

Procedure:
5 g of sodium carbonate was added to a solution of 2.8 g of N-(cis-4-methylcyclohexyl)-4-acetoxy-3-methoxycinnamamide (Example 104) in 100 ml of methanol. The solution was stirred for 2 hours at room temperature. After reaction, 2N hydrochloric acid was added to the reaction solution, acidifying the solution. The solution was extracted three times with 90 ml of ethyl acetate. The organic layer obtained was washed twice with an aqueous sodium chloride solution and dried over magnesium sulfate. Thereafter, the solvent was removed in vacuo. The product obtained was recrystallized from ethyl acetate/hexane, yielding 2.2 g of N-(cis-4-methylcyclohexyl)-4-hydroxy-3-methoxycinnamamide (a compound of the present invention) as white crystal, which had the following physiochemical properties:
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:22]=[CH:21][C:6]([C:7]([NH:9][CH2:10][CH2:11][C:12]2[CH:17]=[CH:16][C:15]([N+:18]([O-:20])=[O:19])=[CH:14][CH:13]=2)=[O:8])=[C:5]([N+:23]([O-:25])=[O:24])[C:4]=1[O:26][CH2:27][CH2:28][CH2:29][CH2:30][CH3:31].C1COCC1.[H-].[Na+].Br[CH2:40][C:41]([O:43][CH2:44][CH3:45])=[O:42]>O>[CH2:44]([O:43][C:41](=[O:42])[CH2:40][N:9]([C:7](=[O:8])[C:6]1[CH:21]=[CH:22][C:3]([O:2][CH3:1])=[C:4]([O:26][CH2:27][CH2:28][CH2:29][CH2:30][CH3:31])[C:5]=1[N+:23]([O-:25])=[O:24])[CH2:10][CH2:11][C:12]1[CH:13]=[CH:14][C:15]([N+:18]([O-:20])=[O:19])=[CH:16][CH:17]=1)[CH3:45]
Reactant: CCOC(=O)CBr
Reactant: CCCCCOc1c(OC)ccc(C(=O)NCCc2ccc([N+](=O)[O-])cc2)c1[N+](=O)[O-]
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: O
Product: CCCCCOc1c(OC)ccc(C(=O)N(CCc2ccc([N+](=O)[O-])cc2)CC(=O)OCC)c1[N+](=O)[O-]
Reaction time: 0.08 h
Yield: 68 %

Procedure:
4-Methoxy-2-nitro-N-[2-(4nitrophenyl)ethyl]-3-pentyloxybenzamide obtained in Example 2-47, THF (1 ml) and sodium hydride (13.3 mg, 0.556 mmol) were mixed, and the mixture was stirred for 5 minutes. Ethyl bromoacetate (0.0617 ml, 0.556 mmol) was added, and the mixture was stirred at 90° C. for 5.5 hours. Then, sodium hydride (6.7 mg, 0.278 mmol) and ethyl bromoacetate (6.7 mg, 0.278 mmol) were further added, and the mixture was stirred at 90° C. for 6.5 hours. To the mixture was added water (3 ml) to stop the reaction, and the organic layer was extracted 3 times with ethyl acetate (5 ml). The organic layers were combined and dried over anhydrous magnesium sulfate. The drying agent was fitered off, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by column chromatography on silica gel (hexane/ethyl acetate=4/1-2/3) to give ethyl{ (4-methoxy-2-nitro-3-pentyloxybenzoyl)-[2-(4nitrophenyl)ethyl]amino}acetate (0.137 g, 68%) as a pale-yellow oil.
Reaction SMILES: [C:1]([O:6][CH2:7][CH3:8])(=[O:5])[C@H:2]([CH3:4])[OH:3].C1(C)C=CC(S(O)(=O)=O)=CC=1.[O:20]1[CH:25]=[CH:24][CH2:23][CH2:22][CH2:21]1.C(=O)([O-])O.[Na+]>ClCCl>[O:20]1[CH2:25][CH2:24][CH2:23][CH2:22][CH:21]1[O:3][C@@H:2]([CH3:4])[C:1]([O:6][CH2:7][CH3:8])=[O:5]
Reactant: CCOC(=O)[C@H](C)O
Reactant: C1=COCCC1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Product: CCOC(=O)[C@H](C)OC1CCCCO1
Reaction time: 0.5 h
Yield: 100.6 %

Procedure:
In dichloromethane (200 ml) was dissolved (S)-(-)-ethyl lactate (35.4 g), to which was added, under ice-cooling, p-toluenesulfonic acid.hydrate (570 mg). To the mixture was added dropwise 3,4-dihyro-2H-pyran (30.2 g), taking 30 minutes, followed by stirring for one hour under ice-cooling. To the reaction mixture was added a 5% aqueous solution of sodium hydrogen carbonate (50 ml), which was vigorously stirred, then the organic layer was separated. The organic layer was further washed with a 5% aqueous solution of sodium hydrogen carbonate and dried over anhydrous magnesium sulfate, then the solvent was distilled off under reduced pressure to afford ethyl(2S)-2-(3,4,5,6-tetrahydro-2H-pyran-2-yloxy)propionate (61 g) as a pale yellow oily product.
Reaction SMILES: [Si:1]([O:18][CH2:19][CH2:20][CH2:21][CH2:22][C:23](=[S:25])[NH2:24])([C:14]([CH3:17])([CH3:16])[CH3:15])([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.O.O.O.O.O.[OH-].C(=O)(O)[O-].[Mg+2].[O:37]1[C:41]2[CH:42]=[CH:43][C:44]([C@@H:46]([CH2:53][C:54](=O)[CH2:55]Cl)[CH2:47][C:48]([O:50][CH2:51][CH3:52])=[O:49])=[CH:45][C:40]=2[O:39][CH2:38]1>O1CCOCC1>[O:37]1[C:41]2[CH:42]=[CH:43][C:44]([C@@H:46]([CH2:53][C:54]3[N:24]=[C:23]([CH2:22][CH2:21][CH2:20][CH2:19][O:18][Si:1]([C:14]([CH3:17])([CH3:15])[CH3:16])([C:8]4[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=4)[C:2]4[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=4)[S:25][CH:55]=3)[CH2:47][C:48]([O:50][CH2:51][CH3:52])=[O:49])=[CH:45][C:40]=2[O:39][CH2:38]1
Reactant: CCOC(=O)C[C@H](CC(=O)CCl)c1ccc2c(c1)OCO2
Reactant: CC(C)(C)[Si](OCCCCC(N)=S)(c1ccccc1)c1ccccc1
Agent: O=C([O-])O
Agent: [Mg+2]
Agent: [OH-]
Solvent: O
Solvent: C1COCCO1
Product: CCOC(=O)C[C@H](Cc1csc(CCCCO[Si](c2ccccc2)(c2ccccc2)C(C)(C)C)n1)c1ccc2c(c1)OCO2
Temperature: 60 °C

Procedure:
Dissolve 5-{[tert-butyl(diphenyl)silyl]oxy}pentanethioamide (4.97 g, 13.37 mmol) in 1,4-dioxane (50 mL). Add magnesium carbonate hydroxide pentahydrate (3.25 g, 0.5 mmol) and (3S)-ethyl 3-(1,3-benzodioxol-5-yl)-6-chloro-5-oxohexanoate (see Scheme 2, Example M) (4.18 g, 13.37 mmol). Heat to 60° C. for 5 hrs. Upon cooling, the reaction was filtered through a pad of celite and concentrated in vacuo, and purified via silica gel chromatography (eluent: 9:1 Hexane:Ethyl Acetate) to give the product as a yellow oil. Yield: 6.55 g (78%) 1H NMR (DMSO-d6) δ7.64–7.58 (m, 4H), 7.48–7.39 (m, 6H), 6.95–6.93 (m, 1H), 6.85–6.82 (m, 1H), 6.73–6.69 (m, 1H), 5.92 (s, 2H), 3.93–3.85 (q, 2H), 3.70–3.64 (t, 2H), 3.46–3.38 (m, 1H), 3.00–2.85 (m, 4H), 2.68–2.53 (m, 2H), 1.83–1.74 (m, 2H), 1.62–1.53 (m, 2H), 1.08–0.99 (t, 3H), 0.99 (s, 9H).
Reaction SMILES: [Si:1]([O:8][CH2:9][C:10]1[CH:11]=[C:12]([CH2:25][CH2:26][C:27]2[S:31][C:30]([C:32](=O)[CH2:33][CH3:34])=[CH:29][CH:28]=2)[CH:13]=[CH:14][C:15]=1[CH2:16][O:17][Si:18]([C:21]([CH3:24])([CH3:23])[CH3:22])([CH3:20])[CH3:19])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[Br-].[C:37]([CH2:40]CC[P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)([OH:39])=[O:38].[CH3:62][C:63](C)([O-])C.[K+]>>[Si:1]([O:8][CH2:9][C:10]1[CH:11]=[C:12]([CH2:25][CH2:26][C:27]2[S:31][C:30](/[C:32](/[CH2:62][CH3:63])=[CH:33]/[CH2:34][CH2:40][C:37]([OH:39])=[O:38])=[CH:29][CH:28]=2)[CH:13]=[CH:14][C:15]=1[CH2:16][O:17][Si:18]([C:21]([CH3:22])([CH3:23])[CH3:24])([CH3:20])[CH3:19])([C:4]([CH3:5])([CH3:7])[CH3:6])([CH3:2])[CH3:3]
Reactant: CCC(=O)c1ccc(CCc2ccc(CO[Si](C)(C)C(C)(C)C)c(CO[Si](C)(C)C(C)(C)C)c2)s1
Reactant: O=C(O)CCC[P+](c1ccccc1)(c1ccccc1)c1ccccc1
Reactant: CC(C)(C)[O-]
Agent: [Br-]
Agent: [K+]
Product: CC/C(=C\CCC(=O)O)c1ccc(CCc2ccc(CO[Si](C)(C)C(C)(C)C)c(CO[Si](C)(C)C(C)(C)C)c2)s1

Procedure:
In a manner similar to that of Example 6(i), by reaction of 5.08 g (9.5 mmol) of 1-{5-[2-(3,4-bis(tert-butyldimethylsilanyloxymethyl)phenyl)ethyl]-2-thienyl}-1-propanone with 6.1 g (14 mmol) of (3-carboxypropyl)triphenylphosphonium bromide and 3.1 g (28 mmol) of potassium tert-butoxide, the desired product is obtained in the form of a yellow oil (m=2.7 g; Y=48%).
Reaction SMILES: FC(F)(F)C([O-])=O.[NH2:8][C@H:9]([C@@H:17]([OH:24])[C@@H:18]([OH:23])[CH2:19][CH2:20][S:21][CH3:22])[CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.[Br:25][C:26]1[CH:27]=[C:28]([C:35]([N:37]([CH2:41][CH2:42][CH3:43])[CH2:38][CH2:39][CH3:40])=[O:36])[CH:29]=[C:30]([CH:34]=1)[C:31](O)=[O:32].CCN(C(C)C)C(C)C>>[Br:25][C:26]1[CH:34]=[C:30]([CH:29]=[C:28]([C:35]([N:37]([CH2:41][CH2:42][CH3:43])[CH2:38][CH2:39][CH3:40])=[O:36])[CH:27]=1)[C:31]([NH:8][C@H:9]([C@H:17]([C@@H:18]([CH2:19][CH2:20][S:21][CH3:22])[OH:23])[OH:24])[CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)=[O:32]
Reactant: CSCC[C@H](O)[C@H](O)[C@@H](N)Cc1ccccc1
Reactant: CCCN(CCC)C(=O)c1cc(Br)cc(C(=O)O)c1
Agent: O=C([O-])C(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Product: CCCN(CCC)C(=O)c1cc(Br)cc(C(=O)N[C@@H](Cc2ccccc2)[C@@H](O)[C@H](O)CCSC)c1

Procedure:
The trifluoroacetate salt of (2S,3R,4S)-2-Amino-6-methylsulfanyl-1-phenyl-hexane-3,4-diol (0.1 mmol) was reacted with 5-bromo-N,N-dipropyl-isophthalamic acid as described in method A (addition of an extra equivalent of DIEA to neutralize the amine salt) to give 2-({3-bromo-5-[(dipropylamino)carbonyl]benzoyl}amino)-1,2,5-trideoxy-6-S-methyl-1-phenyl-6-thio-D-xylo-hexitol. MS (ESI+) for C27H37BrN2O4S m/z 567 (M+H)+.
Reaction SMILES: [CH3:1][C:2]([CH3:31])([CH3:30])[CH2:3][N:4]1[C:12]2[C:7](=[N:8][C:9]([C:13]3[CH2:14][CH:15]4[CH2:19][N:18](C(OC(C)(C)C)=O)[CH2:17][CH:16]4[CH:27]=3)=[CH:10][CH:11]=2)[N:6]([CH3:28])[C:5]1=[O:29].FC(F)(F)C(O)=O>ClCCl>[CH3:1][C:2]([CH3:31])([CH3:30])[CH2:3][N:4]1[C:12]2[C:7](=[N:8][C:9]([C:13]3[CH2:14][CH:15]4[CH2:19][NH:18][CH2:17][CH:16]4[CH:27]=3)=[CH:10][CH:11]=2)[N:6]([CH3:28])[C:5]1=[O:29]
Reactant: Cn1c(=O)n(CC(C)(C)C)c2ccc(C3=CC4CN(C(=O)OC(C)(C)C)CC4C3)nc21
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: Cn1c(=O)n(CC(C)(C)C)c2ccc(C3=CC4CNCC4C3)nc21
Reaction time: 18 h

Procedure:
tert-Butyl 5-[1-(2,2-dimethylpropyl)-3-methyl-2-oxo-2,3-dihydro-1H-imidazo-[4,5-b]pyridin-5-yl]-3,3a,4,6a-tetrahydrocyclopenta[c]pyrrole-2(1H)-carboxylate (8-3, 1 g, 2.3 mmol) was added to a mixture of dichloromethane (18.7 mL) and trifluoroacetic acid (4.6 mL) at room temperature. After stirring for 18 h, the solvent was removed in vacuo. The resulting residue was then diluted with ethyl acetate (100 mL) and washed sequentially with saturated sodium bicarbonate (2×50 mL), water (1×50 mL) and brine (1×50 mL). The organics were dried over magnesium sulfate, filtered, and concentrated in vacuo to give 1-(2,2-Dimethylpropyl)-5-(1,2,3,3a,4,6a-hexahydrocyclopenta[c]pyrrol-5-yl)-3-methyl-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one (8-4) as a white solid. This material was carried on without further purification.
Reaction SMILES: [OH:1][C:2]1[C:7]([C:8]([CH3:11])([CH3:10])[CH3:9])=[CH:6][C:5]([CH3:12])=[CH:4][C:3]=1[N:13]1[N+:17]([O-])=[C:16]2[CH:19]=[CH:20][C:21]([Cl:23])=[CH:22][C:15]2=[N:14]1.S(=O)(=O)(O)O>O>[OH:1][C:2]1[C:7]([C:8]([CH3:10])([CH3:9])[CH3:11])=[CH:6][C:5]([CH3:12])=[CH:4][C:3]=1[N:13]1[N:17]=[C:16]2[CH:19]=[CH:20][C:21]([Cl:23])=[CH:22][C:15]2=[N:14]1
Reactant: Cc1cc(-n2nc3cc(Cl)ccc3[n+]2[O-])c(O)c(C(C)(C)C)c1
Agent: O=S(=O)(O)O
Solvent: O
Product: Cc1cc(-n2nc3ccc(Cl)cc3n2)c(O)c(C(C)(C)C)c1
Reaction time: 2 h
Yield: 89.5 %

Procedure:
In order to conduct the reaction of Process (c), the system was heated, and was stirred at 64° to 67° C. for two hours. As this result, the N-oxide disappeared, thus Process (c) being completed. Thereafter, water 50 ml was added to the reaction liquor, and the resultant reaction liquor was neutralized with 62% sulfuric acid 11 g to precipitate a crystal. The precipitated crystal was separated by filtration, and the separated crystal was fully washed with hot water of 60° to 70° C. and further with a small amount of methanol. The washed crystal was then dried, thus obtaining 9.4 g of 2-(2'-hydroxy-3'-t-butyl-5'-methylphenyl)-5-chlorobenzotriazole having a melting point of 138° to 140° C. at the yield of 89.5%.