Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [H-].[Na+].[CH3:3][O:4][C:5]1[CH:10]=[CH:9][C:8]([C:11]2[N:12]=[N:13][C:14](=[O:16])[CH:15]=2)=[CH:7][CH:6]=1.S(O[CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][O:34][C:35]([C:37]1[CH:38]([C:49]2[CH:54]=[CH:53][CH:52]=[C:51]([Cl:55])[C:50]=2[Cl:56])[C:39]([C:45]([O:47][CH3:48])=[O:46])=[C:40]([CH3:44])[NH:41][C:42]=1[CH3:43])=[O:36])(C1C=CC(C)=CC=1)(=O)=O>CN(C)C=O>[CH3:3][O:4][C:5]1[CH:6]=[CH:7][C:8]([C:11]2[NH:12][N:13]=[C:14]([O:16][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][O:34][C:35]([C:37]3[CH:38]([C:49]4[CH:54]=[CH:53][CH:52]=[C:51]([Cl:55])[C:50]=4[Cl:56])[C:39]([C:45]([O:47][CH3:48])=[O:46])=[C:40]([CH3:44])[NH:41][C:42]=3[CH3:43])=[O:36])[CH:15]=2)=[CH:9][CH:10]=1
Reactant: COc1ccc(C2=CC(=O)N=N2)cc1
Reactant: COC(=O)C1=C(C)NC(C)=C(C(=O)OCCCCCCOS(=O)(=O)c2ccc(C)cc2)C1c1cccc(Cl)c1Cl
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: COC(=O)C1=C(C)NC(C)=C(C(=O)OCCCCCCOc2cc(-c3ccc(OC)cc3)[nH]n2)C1c1cccc(Cl)c1Cl
Temperature: 80 °C
Yield: 59.5 %

Procedure:
To a suspension of 0.262 g of sodium hydride (55% dispersion in mineral oil) in 10 ml of N,N-dimethylformamide, 1.33 g (7 mmole) of 3-p-methoxyphenyl-5-pyrazolone was added portionwise with stirring under ice cooling. To the above mixture was added dropwise a solution of 3.05 g (5 mmole) of 1,4-dihydro-2,6-dimethyl-4-(2,3-dichlorophenyl)-3-methoxycarbonylpyridine-5-carboxylic acid 6-tosyloxyhexyl ester in 7 ml of N,N-dimethylformamide at 0° to 10° C. with stirring and then the mixture was heated at 80° C. for 3 hours. The resulting reaction mixture was poured into ice water, and the precipitate was extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous sodium sulfate, and then evaporated in vacuo to obtain an oily residue. The residue was purified by silica gel column chromatography using a mixed solution of chloroform-methanol (the ratio by volume of 100:1) as an eluent, and the fractions containing desired compound were collected and evaporated in vacuo to dryness to give white crystalline residue. The residue was recrystallized from a mixed solution of ethyl acetate-normal hexane to give 1.87 g (yield 59.0%) of the 1,4-dihydro-2,6-dimethyl-4-(2,3-dichlorophenyl)-3-methoxycarbonylpyridine-5-carboxylic acid 6-(5-p-methoxyphenyl-3-pyrazolyloxy)hexyl ester as colorless needles.
Reaction SMILES: [NH2:1][CH:2]1[CH2:7][CH2:6][N:5]([C:8]2[S:9][C:10]([C:14]([O:16][CH2:17][CH3:18])=[O:15])=[C:11]([CH3:13])[N:12]=2)[CH2:4][CH2:3]1.[Cl:19][C:20]1[N:21]=[C:22]([C:27](O)=[O:28])[NH:23][C:24]=1[CH2:25][CH3:26].CCN=C=NCCCN(C)C.Cl.ON1C2C=CC=CC=2N=N1.CN1CCOCC1>>[Cl:19][C:20]1[N:21]=[C:22]([C:27]([NH:1][CH:2]2[CH2:7][CH2:6][N:5]([C:8]3[S:9][C:10]([C:14]([O:16][CH2:17][CH3:18])=[O:15])=[C:11]([CH3:13])[N:12]=3)[CH2:4][CH2:3]2)=[O:28])[NH:23][C:24]=1[CH2:25][CH3:26]
Reactant: CCc1[nH]c(C(=O)O)nc1Cl
Reactant: CCOC(=O)c1sc(N2CCC(N)CC2)nc1C
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CN1CCOCC1
Product: CCOC(=O)c1sc(N2CCC(NC(=O)c3nc(Cl)c(CC)[nH]3)CC2)nc1C
Yield: 92.6 %

Procedure:
The same operation as in Example (217c) was performed using ethyl 2-(4-aminopiperidin-1-yl)-4-methyl-1,3-thiazole-5-carboxylate obtained in Example (239a) (139 mg, 0.52 mmol), 4-chloro-5-ethyl-1H-imidazole-2-carboxylic acid obtained in Example (1d) (90 mg, 0.52 mmol), WSC hydrochloride (296 mg, 1.55 mmol), 1-hydroxybenzotriazole (70 mg, 0.52 mmol) and N-methylmorpholine (0.11 mL, 1.03 mmol), to obtain 205 mg of the title compound as a white solid (94%).
Reaction SMILES: [Cl:1][C:2]1[N:18]=[CH:17][C:5]2[C:6]3[N:10]([CH2:11][CH2:12][O:13][C:4]=2[CH:3]=1)[CH:9]=[C:8]([C:14]([NH2:16])=[O:15])[N:7]=3.CO[CH:21](OC)[N:22]([CH3:24])[CH3:23]>C1(C)C=CC=CC=1>[CH3:21][N:22]([CH3:24])[CH:23]=[N:16][C:14]([C:8]1[N:7]=[C:6]2[N:10]([CH2:11][CH2:12][O:13][C:4]3[CH:3]=[C:2]([Cl:1])[N:18]=[CH:17][C:5]=32)[CH:9]=1)=[O:15]
Reactant: NC(=O)c1cn2c(n1)-c1cnc(Cl)cc1OCC2
Reactant: COC(OC)N(C)C
Solvent: Cc1ccccc1
Product: CN(C)C=NC(=O)c1cn2c(n1)-c1cnc(Cl)cc1OCC2
Temperature: 95 °C

Procedure:
To a solution of 8-Chloro-4,5-dihydro-6-oxa-1,3a,9-triaza-benzo[e]azulene-2-carboxylic acid amide (2.40 g, 0.00907 mol) in Toluene (40 mL) was added 1,1-Dimethoxy-N,N-dimethylmethanamine (4.82 mL, 0.0363 mol). The flask was sealed and heated to 95° C. for 8 h. The reaction was deemed complete by TLC. The solvent was removed in vacuo to give 8-Chloro-4,5-dihydro-6-oxa-1,3a,9-triaza-benzo[e]azulene-2-carboxylic acid 1-dimethylamino-methylideneamide which was used crude. MS(ESI+) 320.1
Reaction SMILES: [CH2:1]([O:5][C:6]1[N:14]=[C:13]2[C:9]([N:10]=[C:11]([O:23]C)[N:12]2[CH2:15][CH2:16][CH:17]2[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]2)=[C:8]([NH2:25])[N:7]=1)[CH2:2][CH2:3][CH3:4].I[CH2:27][CH:28]([CH3:30])[CH3:29]>>[NH2:25][C:8]1[N:7]=[C:6]([O:5][CH2:1][CH2:2][CH2:3][CH3:4])[N:14]=[C:13]2[C:9]=1[NH:10][C:11](=[O:23])[N:12]2[CH2:15][CH2:16][CH:17]1[CH2:18][CH2:19][N:20]([CH2:27][CH:28]([CH3:30])[CH3:29])[CH2:21][CH2:22]1
Reactant: CC(C)CI
Reactant: CCCCOc1nc(N)c2nc(OC)n(CCC3CCNCC3)c2n1
Product: CCCCOc1nc(N)c2[nH]c(=O)n(CCC3CCN(CC(C)C)CC3)c2n1

Procedure:
Prepared similarly to Example 80 from 2-(butyloxy)-8-(methyloxy)-9-[2-(4-piperidinyl)ethyl]-9H-purin-6-amine and 1-iodo-2-methylpropane.
Reaction SMILES: C(O[C:4](=[O:11])[CH2:5][N:6]1[N:10]=[CH:9][CH:8]=[N:7]1)C.O.[NH2:13][NH2:14]>C(O)C>[N:10]1[N:6]([CH2:5][C:4]([NH:13][NH2:14])=[O:11])[N:7]=[CH:8][CH:9]=1
Reactant: NN
Reactant: CCOC(=O)Cn1nccn1
Solvent: CCO
Solvent: O
Product: NNC(=O)Cn1nccn1
Temperature: 25 °C
Yield: 68 %

Procedure:
As described for example 112a, [1,2,3]triazol-2-yl-acetic acid ethyl ester in ethanol was reacted with hydrazine hydrate (2 equivalents) and the resulting mixture heated under reflux for 3 h. The mixture was cooled to rt and the precipitated product was filtered off and dried to afford the title compound as a white solid (yield: 68%). MS: m/e=141.1 [M]+.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:16]([CH2:17][C:18]([OH:20])=O)[C:11]3=[N:12][CH:13]=[CH:14][CH:15]=[C:10]3[N:9]=2)=[CH:4][CH:3]=1.C(N1C=CN=C1)(N1C=CN=C1)=O.[CH2:33]([N:35]([CH2:40][CH3:41])[CH2:36][CH2:37][CH2:38][NH2:39])[CH3:34]>O1CCCC1.C(O)(C)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[N:16]([CH2:17][C:18]([NH:39][CH2:38][CH2:37][CH2:36][N:35]([CH2:40][CH3:41])[CH2:33][CH3:34])=[O:20])[C:11]3=[N:12][CH:13]=[CH:14][CH:15]=[C:10]3[N:9]=2)=[CH:6][CH:7]=1
Reactant: CCN(CC)CCCN
Reactant: O=C(O)Cn1c(-c2ccc(Cl)cc2)nc2cccnc21
Agent: O=C(n1ccnc1)n1ccnc1
Solvent: C1CCOC1
Solvent: CC(C)O
Product: CCN(CC)CCCNC(=O)Cn1c(-c2ccc(Cl)cc2)nc2cccnc21
Temperature: 25 °C
Reaction time: 2 h
Yield: 62.2 %

Procedure:
A suspension of 2-(4-chlorophenyl)-3H-imidazo[4,5-b]pyridine-3-acetic acid (5.0 g, 0.0174 mole), 1,1'-carbonyldiimidazole (2.82 g, 0.0174 mole) and dry tetrahydrofuran (100 ml) was stirred at room temperature for 2 hours with nitrogen bubbling through it. A solution of 3-diethylaminopropylamine (6.8 g, 0.0522 mole) in tetrahydrofuran (10 ml) was added and the reaction mixture was stirred at room temperature overnight under nitrogen. The reaction mixture was evaporated under reduced pressure to give a white solid. The solid was triturated with water (50 ml), filtered and rinsed twice with water, twice with a 5% potassium hydroxide solution and twice with water to yield a white solid. The solid was dissolved in hot isopropyl alcohol and filtered. Addition of water and cooling to room temperature gave a white solid which was collected by filtration and rinsed with water to give 4.33 g (61%) of a solid. A 1.0-g sammple of the solid was dried at high vacuum, mp 172°-174° C.
Reaction SMILES: [OH:1][C:2]1[CH:7]=[C:6]([OH:8])[N:5]=[C:4]([SH:9])[N:3]=1.CN1C(=O)CCC1.[CH2:17](Br)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.Cl>[OH-].[Na+]>[C:18]1([CH2:17][S:9][C:4]2[N:5]=[C:6]([OH:8])[CH:7]=[C:2]([OH:1])[N:3]=2)[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1
Reactant: Oc1cc(O)nc(S)n1
Reactant: BrCc1ccccc1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CN1CCCC1=O
Product: Oc1cc(O)nc(SCc2ccccc2)n1
Temperature: 25 °C
Reaction time: 24 h

Procedure:
To a solution of 4,6-dihydroxy-2-mercaptopyrimidine (100 g) in 5M NaOH (360 ml) was added first NMP (200 ml), then benzyl bromide (90 ml) dropwise over 2 hours. The reaction was stirred at room temperature for 24 hours, then acidified to pH 2 with conc HCl (100 ml) added dropwise over 2 hours at −5° C. to give a pink precipitate. This was isolated by decanting off the solution followed by trituration with diethyl ether (1 liter) to give the subtitled product as a white powder after filtration and drying (210 g).
Reaction SMILES: [NH2:1][C:2]1[N:3]=[CH:4][N:5]([CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=2[F:17])[C:6]=1[C:7]([NH2:9])=[O:8].[F:18][C:19]1[CH:27]=[CH:26][CH:25]=[CH:24][C:20]=1[C:21](Cl)=[O:22]>>[F:18][C:19]1[CH:27]=[CH:26][CH:25]=[CH:24][C:20]=1[C:21]([NH:1][C:2]1[N:3]=[CH:4][N:5]([CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=2[F:17])[C:6]=1[C:7]([NH2:9])=[O:8])=[O:22]
Reactant: O=C(Cl)c1ccccc1F
Reactant: NC(=O)c1c(N)ncn1Cc1ccccc1F
Product: NC(=O)c1c(NC(=O)c2ccccc2F)ncn1Cc1ccccc1F
Yield: 97 %

Procedure:
An amidation reaction and post-treatment were carried out under the same conditions as in Example 22, using 1.50 g (6.40 mol) of 4-amino-1-(2-fluorobenzyl)-5-imidazole carboxamide which was prepared in the same manner as in Example 113 and 2-fluorobenzoyl chloride instead of benzoyl chloride to obtain 2.21 g of 4-(2-fluorobenzoylamino)-1-(2-fluorobenzyl)-5-imidazolecarboxamide (yield 97%).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][N:10]=1)[C:5]([NH2:7])=[O:6].C(O[CH:14](OCC)[N:15]([CH3:17])[CH3:16])C>>[Br:1][C:2]1[CH:3]=[C:4]([C:5](/[N:7]=[CH:14]/[N:15]([CH3:17])[CH3:16])=[O:6])[CH:8]=[CH:9][N:10]=1
Reactant: CCOC(OCC)N(C)C
Reactant: NC(=O)c1ccnc(Br)c1
Product: CN(C)/C=N/C(=O)c1ccnc(Br)c1
Temperature: 120 °C
Reaction time: 1.5 h
Yield: 98 %

Procedure:
2-bromo-isonicotinamide (406.2 mg, 2.021 mmol) and N,N-dimethylformamide diethyl acetal (0.48 ml, 2.80 mmol) were combined and heated to 120° C. A short path distillation apparatus was used to collect the ethanol that was liberated during the reaction. The reaction mixture was a light orange solution that slowly turned darker until it had become a dark amber solution. After 1.5 hours, the reaction mixture was cooled to room temperature. The reaction mixture solidified upon cooling and was placed under high vacuum overnight to give the title compound (507.4 mg) as an off-white solid.
Reaction SMILES: [O:1]=[C:2]1[CH2:7][O:6][C:5]2[CH:8]=[CH:9][C:10]3[CH2:11][CH2:12]/[C:13](=[CH:15]\[C:16]#[N:17])/[C:14]=3[C:4]=2[NH:3]1.Cl>[Ni].N.C(O)C>[NH2:17][CH2:16][CH2:15][CH:13]1[C:14]2[C:4]3[NH:3][C:2](=[O:1])[CH2:7][O:6][C:5]=3[CH:8]=[CH:9][C:10]=2[CH2:11][CH2:12]1
Reactant: N#C/C=C1\CCc2ccc3c(c21)NC(=O)CO3
Agent: [Ni]
Agent: Cl
Agent: N
Solvent: CCO
Product: NCCC1CCc2ccc3c(c21)NC(=O)CO3
Temperature: 40 °C
Reaction time: 6 h
Yield: 61.5 %

Procedure:
(E)-(1,2,3,7,8,9-Hexahydro-2-oxoindeno[5,4-b][1,4] oxazin-9-ylidene)acetonitrile (3.0 g, 13.3 mmol.) and Raney nickel (14.0 g) were suspended in a saturated ammonia/ethanol solution (300 mL). The suspension was stirred for 6 hours at 40° C. under hydrogen atmosphere (5 kgf/cm2). The reaction mixture was cooled, and, then, the Raney nickel catalyst was filtered off. From the filtrate, the solvent was distilled off under reduced pressure to leave an oily residue. The residue was poured into 2N HCl, which was washed with ethyl acetate. The pH of the aqueous layer was adjusted to 10 with a 4N aqueous solution of sodium hydroxide. The organic matter was extracted from the aqueous layer with a mixture solvent of chloroform/methanol (10:1). The extract solution was dried over anhydrous magnesium sulfate, then the solvent was distilled off under reduced pressure. The residue was recrystallized from ethyl acetate/isopropyl ether to afford the title compound (yield 1.9 g, 62%).
Reaction SMILES: [C:1]1([CH:7]([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[CH2:8][NH:9][C:10]2[N:18]=[C:17]([CH2:19][NH:20][C:21]([NH:23][CH2:24][CH2:25][N:26]3[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]3)=[O:22])[N:16]=[C:15]3[C:11]=2[N:12]=[CH:13][NH:14]3)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:38]([O:46][C@H:47]1[C@@H:51]([O:52][C:53](=[O:60])[C:54]2[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=2)[C@@H:50](OC(=O)C)[O:49][C@@H:48]1[C:65]([NH:67][CH2:68][CH3:69])=[O:66])(=[O:45])[C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1.C(O[C@H]1[C@@H](OC(=O)C2C=CC=CC=2)[C@H](OC(=O)C)O[C@@H]1C(NCC)=O)(=O)C1C=CC=CC=1.C[Si](OS(C(F)(F)F)(=O)=O)(C)C>ClC(Cl)(Cl)C.C(OCC)(=O)C>[C:38]([O:46][C@H:47]1[C@@H:51]([O:52][C:53](=[O:60])[C:54]2[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=2)[C@H:50]([N:14]2[CH:13]=[N:12][C:11]3[C:15]2=[N:16][C:17]([CH2:19][NH:20][C:21]([NH:23][CH2:24][CH2:25][N:26]2[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]2)=[O:22])=[N:18][C:10]=3[NH:9][CH2:8][CH:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[O:49][C@@H:48]1[C:65]([NH:67][CH2:68][CH3:69])=[O:66])(=[O:45])[C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1
Reactant: CCNC(=O)[C@H]1O[C@H](OC(C)=O)[C@H](OC(=O)c2ccccc2)[C@@H]1OC(=O)c1ccccc1
Reactant: O=C(NCCN1CCCCC1)NCc1nc(NCC(c2ccccc2)c2ccccc2)c2nc[nH]c2n1
Agent: CCNC(=O)[C@H]1O[C@@H](OC(C)=O)[C@H](OC(=O)c2ccccc2)[C@@H]1OC(=O)c1ccccc1
Agent: C[Si](C)(C)OS(=O)(=O)C(F)(F)F
Solvent: CCOC(C)=O
Solvent: CC(Cl)(Cl)Cl
Product: CCNC(=O)[C@H]1O[C@@H](n2cnc3c(NCC(c4ccccc4)c4ccccc4)nc(CNC(=O)NCCN4CCCCC4)nc32)[C@H](OC(=O)c2ccccc2)[C@@H]1OC(=O)c1ccccc1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
N,O-Bistrimethylsilylacetamide (0.34 ml, 1.4 mmol) was added to a stirred suspension of N-({6-[(2,2-diphenylethyl)amino]-9H-purin-2-yl}methyl)-N′-[2-(1-piperidinyl)ethyl]urea (100 mg, 0.2 mmol) (Preparation 5) in 1,1,1-trichloroethane (20 ml) at 50° C. The reaction mixture was stirred at this temperature for 30 minutes, allowed to cool to room temperature and then evaporated under reduced pressure. Toluene (5 ml) was added and the solvent was removed under reduced pressure. The residue was redissolved in toluene (20 ml). (2S,3S,4R,5R)-5-(Acetyloxy)-4-(benzoyloxy)-2-[(ethylamino)carbonyl]tetrahydro-3-furanyl benzoate and (2S,3S,4R,5S)-5-(acetyloxy)-4-(benzoyloxy)-2-[(ethylamino)carbonyl]tetrahydro-3-furanyl benzoate (Preparation 18) and then trimethylsilyltrifluoromethanesulphonate (0.1 ml, 0.35 mmol) were added and the reaction mixture was heated under reflux for 2 hours. The reaction was then allowed to cool to room temperature and diluted with ethyl acetate (100 ml). The solution was washed with saturated aqueous sodium hydrogen carbonate solution (2×50 ml) and saturated aqueous sodium chloride solution (50 ml) and then dried (anhydrous magnesium sulphate). The solvent was removed to give a residue that was purified by column chromatography on silica gel eluting with dichloromethane:methanol:0.88 concentrated aqueous ammonia (95:5:0.5 by volume). This gave an impure oil (100 mg) which was used without further purification in subsequent experiments.
Reaction SMILES: [CH2:1]([O:8][C@@H:9]1[C@H:16](OS(C2C=CC(C)=CC=2)(=O)=O)[C@@H:15]([CH2:28][OH:29])[O:14][C@H:11]([O:12][CH3:13])[CH2:10]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[BH4-].[Na+]>CS(C)=O.CCOCC>[CH2:1]([O:8][C@@H:9]1[CH2:16][C@@H:15]([CH2:28][OH:29])[O:14][C@H:11]([O:12][CH3:13])[CH2:10]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CO[C@@H]1C[C@H](OCc2ccccc2)[C@H](OS(=O)(=O)c2ccc(C)cc2)[C@@H](CO)O1
Agent: [BH4-]
Agent: [Na+]
Solvent: CCOCC
Solvent: CS(C)=O
Product: CO[C@@H]1C[C@H](OCc2ccccc2)C[C@@H](CO)O1
Temperature: 80 °C
Yield: 81.3 %

Procedure:
Methyl 3-O-benzyl-4-O-tosyl-2-deoxy-α-D-ribohexopyranoside (6.55 g, 15.50 mmoles) is dissolved in dry DMSO (50 ml). Sodium borohydride (2.35 g; 62.01 mmoles) is added and the reaction is stirred under nitrogen in a bath maintained at 80° C. for four days. The reaction is cooled to room temperature and diluted with ether and extracted with water. The aqueous extract is then extracted four times with ether. The combined ether extracts are dried (MgSO4), filtered, and the solvent evaporated in vacuo to give crude product. This crude product is purified by flash chromatography on a 60 mm×150 mm column eluting with 15% (by volume) acetone in methylene chloride. A small portion (0.9 g) containing an impurity is rechromatographed on a 30 mm×130 mm column with the same eluant to give a combined total of 3.18 g of methyl 3-O-benzyl-2,4-dideoxy-α-D-erythro-hexopyranoside as a gum, [α]D25 +58.56 (c, 0.7, CHCl3)
Reaction SMILES: [CH2:1]([O:3][C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([CH:10]=O)[C:5]=1[B:12]([OH:14])[OH:13])[CH3:2].[OH-].[Na+].[N+:17]([CH3:20])([O-:19])=[O:18].Cl>CCCCCCCCCCCCCCCC[N+](C)(C)C.[Br-].O.C1COCC1>[CH2:1]([O:3][C:4]1[C:5]2[B:12]([OH:13])[O:14][CH:10]([CH2:20][N+:17]([O-:19])=[O:18])[C:6]=2[CH:7]=[CH:8][CH:9]=1)[CH3:2]
Reactant: CCOc1cccc(C=O)c1B(O)O
Reactant: C[N+](=O)[O-]
Agent: CCCCCCCCCCCCCCCC[N+](C)(C)C
Agent: Cl
Agent: [Br-]
Solvent: C1CCOC1
Solvent: O
Product: CCOc1cccc2c1B(O)OC2C[N+](=O)[O-]
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 94.7 %

Procedure:
The mixture of 2-ethoxy-6-formylphenylboronic acid (80 g, 0.41 mol), NaOH (16.5 g, 0.41 mol) and CTAB (7.7 g, 20 mmol) in H2O (100 mL) and THF (500 mL) was stirred for 0.5 h at room temperature After dropwise addition of nitromethane (14 mL, 2.4 mol), the reaction mixture was stirred at room temperature for 3 h. Then the cyclization was afforded by adding the diluted HCl (2 N) to pH=2 and then extracted with EtOAc (3×300 mL). The combined organic layers were washed with brine (250 mL), dried over anhydrous Na2SO4 and concentrated to dryness in vacuo. The residue was purified by column chromatography on silica gel to give the target compound as white solid (92 g, yield 94%). 1H NMR (400 MHz, DMSO-d6 δ 9.06 (s, 1H), 7.46-7.43 (t, 1H), 7.07-7.05 (d, 1H), 6.89-6.87 (d, 1H), 5.71-5.69 (m, 1H), 5.31-5.27 (m, 1H), 4.57-4.51 (m, 1H), 4.12-4.07 (m, 2H), 1.34-1.30 (t, 3H).
Reaction SMILES: [Br:1]CC(C1C=CC(Cl)=C(S(=O)(=O)N(C)C)C=1)=O.C(NC(=S)NC1C=CC=CC=1)CCCCC.Br.[Cl:35][C:36]1[CH:41]=[CH:40][C:39]([C:42]2(O)[CH2:46][S:45][C:44](=[N:47][C:48]3[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=3)[N:43]2[CH2:54][CH2:55][CH2:56][CH2:57][CH2:58][CH3:59])=[CH:38][C:37]=1[S:61](=[O:66])(=[O:65])[N:62]([CH3:64])[CH3:63]>>[BrH:1].[Cl:35][C:36]1[CH:41]=[CH:40][C:39]([C:42]2[N:43]([CH2:54][CH2:55][CH2:56][CH2:57][CH2:58][CH3:59])[C:44](=[N:47][C:48]3[CH:49]=[CH:50][CH:51]=[CH:52][CH:53]=3)[S:45][CH:46]=2)=[CH:38][C:37]=1[S:61](=[O:66])(=[O:65])[N:62]([CH3:64])[CH3:63]
Reactant: CCCCCCN1C(=Nc2ccccc2)SCC1(O)c1ccc(Cl)c(S(=O)(=O)N(C)C)c1
Reactant: CN(C)S(=O)(=O)c1cc(C(=O)CBr)ccc1Cl
Agent: Br
Agent: CCCCCCNC(=S)Nc1ccccc1
Product: CCCCCCn1c(-c2ccc(Cl)c(S(=O)(=O)N(C)C)c2)csc1=Nc1ccccc1

Procedure:
Obtained (a) by a procedure analogous to that indicated in Example 1(a), from 2-bromo-4'-chloro-3'-dimethylsulfamoylacetophenone and 3-n-hexyl-1-phenylthiourea, or (b) by a procedure analogous to that indicated in Example 1(b), from 4-(4-chloro-3-dimethylsulfamoylphenyl)-3-n-hexyl-2-phenyliminothiazolidin-4-ol hydrobromide. Colorless crystals; melting point 234° C. (with decomposition).
Reaction SMILES: C([N:14]1[CH2:17][CH:16]([N:18]2[CH:22]=[CH:21][N:20]=[N:19]2)[CH2:15]1)(C1C=CC=CC=1)C1C=CC=CC=1.[ClH:23]>C(O)C.[Pd]>[ClH:23].[N:18]1([CH:16]2[CH2:17][NH:14][CH2:15]2)[CH:22]=[CH:21][N:20]=[N:19]1
Reactant: c1ccc(C(c2ccccc2)N2CC(n3ccnn3)C2)cc1
Agent: [Pd]
Agent: Cl
Solvent: CCO
Product: c1cn(C2CNC2)nn1
Reaction time: 18 h
Yield: 51 %

Procedure:
To a mixture of 0.88 g (3.03 mmol) of N-benzhydryl-3-(1,2,3-triazol-1-yl) azetidine in 25 ml of 98% ethanol was added 3 ml of 1N hydrochloric acid. To this solution was added 0.3 g of Pd/C (10%) and the mixture was then hydrogenated at 50 psi for 18 hr. After filtration of the Pd/C the solvent was removed under reduced pressure, and the residue was crystallized from methanol-ether to yield 0.25 g (51%) of the desired product m.p. 158°-160° C. 1H NMR (D2O) 6 8.16 (S, 1H), 7.92 (S, 1H), 5.95-5.75 (m, 1H), 4.97-4.65 (m, 4H).
Reaction SMILES: S(=O)(=O)(O)O.[CH3:6][O:7][C:8]1[C:13]([O:16][CH3:17])([O:14][CH3:15])[C:12]([O:18][CH3:19])=[CH:11][C:10](OC)([CH3:20])[CH:9]=1.C(=O)([O-])O.[Na+]>C(Cl)(Cl)Cl>[CH3:19][O:18][C:12]1[C:13]([O:14][CH3:15])([O:16][CH3:17])[C:8]([O:7][CH3:6])=[CH:9][C:10](=[CH2:20])[CH:11]=1
Reactant: COC1=CC(C)(OC)C=C(OC)C1(OC)OC
Agent: O=C([O-])O
Agent: O=S(=O)(O)O
Agent: [Na+]
Solvent: ClC(Cl)Cl
Product: C=C1C=C(OC)C(OC)(OC)C(OC)=C1
Temperature: 25 °C
Reaction time: 1 h
Yield: 92.9 %

Procedure:
A 6 mg quantity of concentrated sulfuric acid was added to a solution of 244 mg of 1,3,5,6,6-pentamethoxy-3-methyl-1,4-cyclohexadiene and 10 ml of chloroform. Then the mixture was stirred at room temperature for 1 hour. Thereafter the reaction mixture was neutralized by adding sodium hydrogen carbonate and filtered. The filtrate was concentrated at reduced pressure. The residue was extracted with dichloromethane, the solvent was removed at reduced pressure and the residue was concentrated, recovering 210 mg of an oily crude product. The crude product was purified by silica gel column chromatography using a 20:1 benzene-ethyl acetate mixture, giving 197 mg of 1,5,6,6-tetramethoxy-3-methylidene-1,4-cyclohexadiene in 93% of theoretical yield. The compound thus obtained was identified by NMR.
Reaction SMILES: Cl[Si](Cl)(Cl)Cl.[N-:6]=[N+:7]=[N-:8].[Na+].[CH3:10][O:11][C:12]([C:14]1[CH:15]=[C:16]([C:24]2[CH:29]=[CH:28][C:27]([CH3:30])=[CH:26][CH:25]=2)[CH:17]=[C:18]([NH:20][C:21](=O)[CH3:22])[CH:19]=1)=[O:13]>C(#N)C>[CH3:10][O:11][C:12]([C:14]1[CH:15]=[C:16]([C:24]2[CH:29]=[CH:28][C:27]([CH3:30])=[CH:26][CH:25]=2)[CH:17]=[C:18]([N:20]2[C:21]([CH3:22])=[N:8][N:7]=[N:6]2)[CH:19]=1)=[O:13]
Reactant: COC(=O)c1cc(NC(C)=O)cc(-c2ccc(C)cc2)c1
Reactant: [N-]=[N+]=[N-]
Agent: Cl[Si](Cl)(Cl)Cl
Agent: [Na+]
Solvent: CC#N
Product: COC(=O)c1cc(-c2ccc(C)cc2)cc(-n2nnnc2C)c1
Temperature: 25 °C
Reaction time: 16 h
Yield: 85 %

Procedure:
A mixture of tetrachlorosilane (10.07 mmol, 2 mL), NaN3 (30.21 mmol, 1.96 g) and 5-acetylamino-4′-methyl-biphenyl-3-carboxylic acid methyl ester (3.36 mmol, 950.9 mg) in 10 ml of dry acetonitrile was stirred at room temperature for 16 hours. The reaction mixture were poured into ice-cold aqueous Na2CO3 solution and extracted with ethyl acetate (100 mL). The organic layer was washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated in vacuo. The resulting crude 4′-methyl-5-(5-methyl-tetrazol-1-yl)-biphenyl-3-carboxylic acid methyl ester was used for next step directly (880 mg, 85% yield).
Reaction SMILES: [NH2:1][C:2]1[N:7]=[C:6]([C:8]2[NH:12][C:11]([C:13]3[CH:18]=[C:17]([Cl:19])[CH:16]=[CH:15][C:14]=3[CH3:20])=[C:10]([C:21]([OH:23])=[O:22])[CH:9]=2)[CH:5]=[CH:4][N:3]=1.[I:24]I>CN(C=O)C.FC(F)(F)C([O-])=O.[Ag+]>[NH2:1][C:2]1[N:7]=[C:6]([C:8]2[NH:12][C:11]([C:13]3[CH:18]=[C:17]([Cl:19])[CH:16]=[CH:15][C:14]=3[CH3:20])=[C:10]([C:21]([OH:23])=[O:22])[CH:9]=2)[C:5]([I:24])=[CH:4][N:3]=1
Reactant: II
Reactant: Cc1ccc(Cl)cc1-c1[nH]c(-c2ccnc(N)n2)cc1C(=O)O
Agent: [Ag+]
Agent: O=C([O-])C(F)(F)F
Solvent: CN(C)C=O
Product: Cc1ccc(Cl)cc1-c1[nH]c(-c2nc(N)ncc2I)cc1C(=O)O
Temperature: -40 °C
Reaction time: 7 h
Yield: 81.6 %

Procedure:
5-(2-Amino-pyrimidin-4-yl)-2-(5-chloro-2-methyl-phenyl)-1H-pyrrole-3-carboxylic acid (0.70 g, 2.13 mmol) and Iodine (1.134 g, 4.47 mmol) in dry DMF (5 mL), under a nitrogen atmosphere, were stirred at −40° C. (internal temperature) and treated drop wise with silver trifluoroacetate (0.987 g, 4.47 mmol) in DMF (5 mL). The mixture was stirred at −40° C. for 7 h and then filtered over a short plug of celite. The panel was washed with DMF (5 mL) and the filtrate was collected in a flask containing 10% Na2S2O3 (50 mL). Precipitation of a pale yellow solid occurred. Dilution with water (50 mL) and filtration of the solid afforded 0.79 g of crude product, which was reacted in the next step with no further purification.