Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[CH:4][C:5]2[O:10][CH2:9][C@H:8]([CH2:11][O:12][S:13]([C:16]3[CH:21]=[CH:20][C:19]([CH3:22])=[CH:18][CH:17]=3)(=[O:15])=[O:14])[O:7][C:6]=2[C:23]=1[CH:24]=[N:25]O.[CH:27](OCC)(OCC)OCC>>[O:7]1[C:6]2=[C:23]3[C:2](=[CH:3][CH:4]=[C:5]2[O:10][CH2:9][CH:8]1[CH2:11][O:12][S:13]([C:16]1[CH:17]=[CH:18][C:19]([CH3:22])=[CH:20][CH:21]=1)(=[O:14])=[O:15])[N:1]=[CH:27][N:25]=[CH:24]3
Reactant: CCOC(OCC)OCC
Reactant: Cc1ccc(S(=O)(=O)OC[C@H]2COc3ccc(N)c(C=NO)c3O2)cc1
Product: Cc1ccc(S(=O)(=O)OCC2COc3ccc4ncncc4c3O2)cc1

Procedure:
Toluene-4-sulfonic acid (2R)-7-amino-8-(hydroximino-methyl)-2,3-dihydrobenzo[1,4]dioxin-2-ylmethyl ester (3.0 g, 7.9 mmole) was suspended in triethyl orthoformate under nitrogen, brought to a rapid boil and refluxed for 18 hours. The reaction mixture was cooled and the solvent evaporated. The residue was dissolved in methylene chloride (100 mL) and the solution obtained was washed with saturated sodium chloride (100 mL), dried over magnesium sulfate and evaporated to a brown gum (2.7 g) which contained several impurities. Chromatography on silica gel using 1% methanol in chloroform and then 3% methanol in chloroform as eluants gave 0.9 g (30%) of the (R)-enantiomer of the title compound as an oil. 1H(DMSO-d6) singlet, 9.01 δ(1 H); singlet, 9.19 δ(1 H); doublet, 7.75 δ(2 H); doublet, 7.60 δ(1 H); doublet, 7.50 δ(1 H) doublet, 7.30 δ(2 H); multiplet, 4.75 δ(1 H); double doublet, 4.51 δ(1 H); double doublet, 4.46 δ(1 H) double doublet: 4.32 δ(1 H); double doublet, 4.22 δ(1 H); singlet, 2.32 δ(3 H).
Reaction SMILES: [CH2:1](O)[CH:2]=[CH:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.N1C(C)=CC(C)=CC=1C.[Cl-].[Li+].CS([Cl:26])(=O)=O>CN(C=O)C.CCOCC>[CH2:1]([Cl:26])/[CH:2]=[CH:3]\[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1
Reactant: CS(=O)(=O)Cl
Reactant: OCC=Cc1ccccc1
Agent: [Cl-]
Agent: [Li+]
Solvent: CCOCC
Solvent: CN(C)C=O
Solvent: Cc1cc(C)nc(C)c1
Product: ClC/C=C\c1ccccc1
Reaction time: 12 h

Procedure:
A solution of the cinnamyl alcohol (1-1) (17.8 g, 133 mmol; Fukuda, et al., Tetrahedron 55, 1999, pp 649-664) in DMF (75 mL) was treated with collidine (35.1 mL, 32.2 g, 266 mmol), lithium chloride (11.2 g, 266 mmol), and methanesulfonyl chloride (20.7 mL, 30.6 g, 173 mmol) at room temperature. After stirring for 12 h, the reaction was diluted with Et2O (300 mL) and washed with water, satd aq NH4Cl, and brine. The organic solution was dried over MgSO4, filtered, and concentrated. The residue was purified by flash chromatography (SiO2, 5% EtOAc/hexanes) to give allyl chloride (1-2) as a colorless oil. 1NMR (500 MHz, CDCl3) δ 7.40 (m, 2H), 7.32 (m, 3H), 6.68 (d, J=11 hz, 1H), 5.94 (m, 1H), 4.30 (m, 2H) ppm.
Reaction SMILES: F[C:2]1[CH:3]=[C:4]([CH:28]=[C:29](F)[CH:30]=1)[CH2:5][C@@H:6]([C@@H:10]([C@H:12]1[CH2:16][C@@H:15](OCC=C)[CH2:14]N1C(OC(C)(C)C)=O)O)C(O)=O.[F:32][C:33]1[CH:34]=[C:35]([CH:49]=[C:50]([F:52])[CH:51]=1)[CH2:36][C@H:37]1[C@@H:41]([CH:42]2[CH2:47][O:46][CH2:45][CH2:44][NH:43]2)[O:40][C:39](=[O:48])[NH:38]1.FC1C=C(C=C(F)C=1)C[C@H](C(N1[C@@H](CC2C=CC=CC=2)COC1=O)=O)[C@@H]([C@H]1C[C@@H](OCC=C)CN1C(OC(C)(C)C)=O)O.C(O)(C(F)(F)F)=O>C(Cl)Cl>[F:32][C:33]1[CH:34]=[C:35]([CH:49]=[C:50]([F:52])[CH:51]=1)[CH2:36][C@H:37]1[C@@H:41]([C@H:42]2[CH2:47][C@H:45]([OH:46])[CH2:44][N:43]2[CH:5]([C:4]2[CH:3]=[CH:2][CH:30]=[CH:29][CH:28]=2)[C:6]2[CH:10]=[CH:12][CH:16]=[CH:15][CH:14]=2)[O:40][C:39](=[O:48])[NH:38]1
Reactant: C=CCO[C@@H]1C[C@H]([C@@H](O)[C@H](Cc2cc(F)cc(F)c2)C(=O)O)N(C(=O)OC(C)(C)C)C1
Reactant: O=C1N[C@@H](Cc2cc(F)cc(F)c2)[C@@H](C2COCCN2)O1
Agent: C=CCO[C@@H]1C[C@H]([C@@H](O)[C@H](Cc2cc(F)cc(F)c2)C(=O)N2C(=O)OC[C@@H]2Cc2ccccc2)N(C(=O)OC(C)(C)C)C1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: O=C1N[C@@H](Cc2cc(F)cc(F)c2)[C@@H]([C@H]2C[C@H](O)CN2C(c2ccccc2)c2ccccc2)O1
Temperature: 25 °C
Reaction time: 1.5 h

Procedure:
Step L (6): (4S,5S)-4-(3,5-Difluorobenzyl)-5-(morpholin-3-yl)oxazolidin-2-one. A solution of tert-butyl 3-((4S,5S)-4-(3,5-difluorobenzyl)-2-oxooxazolidin-5-yl)morpholine-4-carboxylate (step L (5), 230 mg) in CH2Cl2 (4 mL) was treated with TFA (3 mL). This reaction mixture was stirred at rt for 1.5 h. The mixture was then concentrated in vacuo. Diethyl ether (50 mL) was added and the mixture was washed with 1N HCl solution (40 mL) twice. Aqueous layer was neutralized with 50% aqueous NaOH to pH=12. The mixture was extracted with ethyl acetate (80 mL) twice. The combined organic layers were dried (Na2SO4), and concentrated in vacuo to give 180 mg of the title compound: MS (ESI) (M+H)+ 299.17.
Reaction SMILES: [CH:1]1[CH2:5][CH:4]=[CH:3][CH:2]=1.C1C2C3C=CC(C2C=C1)C3.[C:16]1(=[O:22])[O:21][C:19](=[O:20])[CH:18]=[CH:17]1.B(F)(F)F.CCOCC>>[CH:1]12[CH2:5][CH:4]([CH2:3][CH2:2]1)[C:17]1[C:16]([O:21][C:19](=[O:20])[C:18]2=1)=[O:22]
Reactant: O=C1C=CC(=O)O1
Reactant: C1=CCC=C1
Agent: FB(F)F
Solvent: C1=CC2C3C=CC(C3)C2C1
Solvent: CCOCC
Product: O=C1OC(=O)C2=C1C1CCC2C1
Temperature: 100 °C

Procedure:
Mixed polybasic anhydride containing a plurality of 1,2 anhydrides is obtained by distilling, at 200° C., 66.10 gms. (1 mole) of cyclopentadiene directly from dicyclopentadiene into a reactor containing 98.06 gms. (1 mole) of maleic anhydride, heated to a temperature of 55° C. When the transfer is complete, the reaction mixture is heated to 100° C. for 2 hours. The reaction mixture is then stripped of any excess cyclopentadiene at 120° C. at 1 atmosphere. The resulting Diels-Adler adduct of cyclopentadiene and maleic anhydride is the anhydride of cis-5-norbornene-2,3-dicarboxylic acid. The reaction mixture is cooled to 50° C., and 4.90 gms. (0.03 moles) of boron trifluoride etherate is added slowly with stirring. The reaction mixture exotherms to 65° C. after which it is heated to 125° C., to decompose the BF3OEt and then cooled. The reaction is quenched by mixing with 3 liters of 10% sodium bicarbonate. The mixture is then neutralized with dilute 5% hydrochloric acid. The mixed polybasic anhydride of norbornene-2,3-dicarboxylic acid anhydride is obtained as a fine tan power, Mp. 200° C., and used for foam preparation without further purification.
Reaction SMILES: [CH2:1]([O:8][C@H:9]1[C@H:14]([O:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[C@@H:13]([O:23][CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[C@H:12]([C:31]2[CH:36]=[CH:35][C:34]([Cl:37])=[C:33]([CH2:38][C:39]3[CH:44]=[CH:43][C:42]([O:45][CH2:46][CH3:47])=[CH:41][CH:40]=3)[CH:32]=2)[O:11][C:10]1([CH2:50][OH:51])[CH2:48][OH:49])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:52]1([CH3:62])[CH:57]=[CH:56][C:55]([S:58](Cl)(=[O:60])=[O:59])=[CH:54][CH:53]=1>N1C=CC=CC=1.C(OCC)(=O)C>[CH2:1]([O:8][C@H:9]1[C@H:14]([O:15][CH2:16][C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=2)[C@@H:13]([O:23][CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[C@H:12]([C:31]2[CH:36]=[CH:35][C:34]([Cl:37])=[C:33]([CH2:38][C:39]3[CH:44]=[CH:43][C:42]([O:45][CH2:46][CH3:47])=[CH:41][CH:40]=3)[CH:32]=2)[O:11][C:10]1([CH2:48][O:49][S:58]([C:55]1[CH:56]=[CH:57][C:52]([CH3:62])=[CH:53][CH:54]=1)(=[O:60])=[O:59])[CH2:50][OH:51])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CCOc1ccc(Cc2cc([C@@H]3OC(CO)(CO)[C@@H](OCc4ccccc4)[C@H](OCc4ccccc4)[C@H]3OCc3ccccc3)ccc2Cl)cc1
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Solvent: c1ccncc1
Solvent: CCOC(C)=O
Product: CCOc1ccc(Cc2cc([C@@H]3OC(CO)(COS(=O)(=O)c4ccc(C)cc4)[C@@H](OCc4ccccc4)[C@H](OCc4ccccc4)[C@H]3OCc3ccccc3)ccc2Cl)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 319.9 %

Procedure:
To a stirred solution of {(3S,4R,5S,6S)-3,4,5-tris-benzyloxy-6-[4-chloro-3-(4-ethoxy-benzyl)-phenyl]-2-hydroxymethyl-tetrahydro-pyran-2-yl}-methanol (Example 9, 500 mg, 0.70 mmol) in pyridine (15 mL) was added p-toluene sulfonyl chloride (670 mg, 0.21 mmol). After stirring for overnight at room temperature, reaction mixture was heated to 80° C. for another 18 h. The volatiles were evaporated, resulting residue was taken in ethyl acetate and washed with 1N HCl, brine, concentrated to furnish toluene-4-sulfonic acid (3S,4R,5S,6S)-3,4,5-tris-benzyloxy-6-[4-chloro-3-(4-ethoxy-benzyl)-phenyl]-2-hydroxymethyl-tetrahydro-pyran-2-ylmethyl ester (580 mg). The crude product was used as such for next step without purification which also contains small amount of bis-tosylate.
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1([S:11]([C:14]2[CH:19]=[CH:18][C:17]([O:20][CH2:21][C:22]#[C:23][CH3:24])=[CH:16][CH:15]=2)(=[O:13])=[O:12])[CH2:10][CH2:9][NH:8][CH2:7][CH2:6]1)=[O:4].C(N(CC)CC)C.[F:32][C:33]([F:39])([F:38])[S:34](Cl)(=[O:36])=[O:35].CN(C1C=CC=CN=1)C>C(Cl)(Cl)Cl>[CH2:21]([O:20][C:17]1[CH:16]=[CH:15][C:14]([S:11]([C:5]2([C:3]([O:2][CH3:1])=[O:4])[CH2:10][CH2:9][N:8]([S:34]([C:33]([F:39])([F:38])[F:32])(=[O:36])=[O:35])[CH2:7][CH2:6]2)(=[O:13])=[O:12])=[CH:19][CH:18]=1)[C:22]#[C:23][CH3:24]
Reactant: CC#CCOc1ccc(S(=O)(=O)C2(C(=O)OC)CCNCC2)cc1
Reactant: O=S(=O)(Cl)C(F)(F)F
Agent: CN(C)c1ccccn1
Solvent: CCN(CC)CC
Solvent: ClC(Cl)Cl
Product: CC#CCOc1ccc(S(=O)(=O)C2(C(=O)OC)CCN(S(=O)(=O)C(F)(F)F)CC2)cc1
Temperature: 25 °C
Reaction time: 15 h
Yield: 56.3 %

Procedure:
To a solution of 4-(4-but-2-ynyloxy-benzenesulfonyl)-piperidine-4-carboxylic acid methyl ester (350 mg, 0.90 mmol) in chloroform (10 ml) was added triethylamine (182 mg, 1.81 mmol), trifluoromethanesulfonyl chloride (0.125 ml, 1.17 mmol) followed by a catalytic amount of dimethylaminopyridine. The resulting mixture was stirred for 15 hours at room temperature, quenched with water and extracted with methylene chloride. The organic layer was dried over anhydrous sodium sulfate and concentrated to give 245 mg (56%) of the product as a solid. HR-MS: m/z Calculated for C18H20F3NO7S2 484.0706; Found 484.0700.
Reaction SMILES: C(N(CC)C(C)C)(C)C.[F:10][C:11]([F:22])([F:21])[CH2:12]OS(C(F)(F)F)(=O)=O.[C:23]1([S:29]([N:32]2[C:36]3[CH:37]=[N:38][C:39]([C:48]#[N:49])=[C:40]([CH2:41][CH:42]4[CH2:47][CH2:46][NH:45][CH2:44][CH2:43]4)[C:35]=3[C:34]3[CH:50]=[CH:51][CH:52]=[N:53][C:33]2=3)(=[O:31])=[O:30])[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1>C1COCC1>[C:23]1([S:29]([N:32]2[C:36]3[CH:37]=[N:38][C:39]([C:48]#[N:49])=[C:40]([CH2:41][CH:42]4[CH2:47][CH2:46][N:45]([CH2:12][C:11]([F:10])([F:21])[F:22])[CH2:44][CH2:43]4)[C:35]=3[C:34]3[CH:50]=[CH:51][CH:52]=[N:53][C:33]2=3)(=[O:31])=[O:30])[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=1
Reactant: N#Cc1ncc2c(c1CC1CCNCC1)c1cccnc1n2S(=O)(=O)c1ccccc1
Reactant: O=S(=O)(OCC(F)(F)F)C(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: C1CCOC1
Product: N#Cc1ncc2c(c1CC1CCN(CC(F)(F)F)CC1)c1cccnc1n2S(=O)(=O)c1ccccc1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 85 %

Procedure:
N,N-Diisopropylethylamine (100 mg, 0.77 mmol) and trifluoromethane sulfonic acid 2,2,2-trifluoroethyl ester (100 mg, 0.43 mmol) in THF (1 mL) were added to a solution of 9-benzenesulfonyl-5-piperidin-4-ylmethyl-9H-dipyrido[2,3-b;4′,3′-d]pyrrole-6-carbonitrile in THF (4 mL) and resultant mixture stirred at ambient temperature for 30 min. The mixture was then filtered through a 2 g Sill SPE cartridge, eluting with THF. The THF washings were concentrated in vacuo and the resultant residue was purified by flash chromatography (silica, 2 g column, Si H SPE, 0-20% ethyl acetate in DCM) to afford title compound as a white solid (0.16 g, 85%). 1H NMR (CDCl3, 400 MHz): 9.81 (d, J=2.9 Hz, 1H), 8.81-8.75 (m, 1H), 8.34 (d, J=8.1 Hz, 1H), 8.28 (d, J=7.9 Hz, 2H), 7.66-7.59 (m, 1H), 7.55-7.45 (m, 3H), 3.35-3.27 (m, 2H), 3.02-2.88 (m, 5H), 2.32-2.21 (m, 2H), 1.86-1.60 (m, 4H).
Reaction SMILES: [C:1]([N:5]1[C:9]([C:10]2[CH:15]=[CH:14][C:13]([CH3:16])=[CH:12][CH:11]=2)=[CH:8][C:7]([CH2:17][CH2:18][CH:19]=O)=[N:6]1)([CH3:4])([CH3:3])[CH3:2].[C:21]1([N:27]2[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]2)[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.CCN(C(C)C)C(C)C.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>>[C:1]([N:5]1[C:9]([C:10]2[CH:15]=[CH:14][C:13]([CH3:16])=[CH:12][CH:11]=2)=[CH:8][C:7]([CH2:17][CH2:18][CH2:19][N:30]2[CH2:31][CH2:32][N:27]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[CH2:28][CH2:29]2)=[N:6]1)([CH3:4])([CH3:3])[CH3:2]
Reactant: Cc1ccc(-c2cc(CCC=O)nn2C(C)(C)C)cc1
Reactant: c1ccc(N2CCNCC2)cc1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: CCN(C(C)C)C(C)C
Product: Cc1ccc(-c2cc(CCCN3CCN(c4ccccc4)CC3)nn2C(C)(C)C)cc1

Procedure:
91 mg (90%) of target compound was obtained by using a method same as in Example 1 by using 3-(1-tert-butyl-5-p-tolyl-1H-pyrazol-3-yl)propanal (60 mg, 0.222 mmol), 1-phenylpiperazine (0.033 mL, 0.222 mmol), DIPEA (0.06 mL, 0.333 mmol) and NaBH(OAc)3 (141 mg, 0.666 mmol).
Reaction SMILES: [CH:1]1[C:10]2[CH2:9][CH2:8][CH2:7][CH2:6][C:5]=2[CH:4]=[CH:3][N:2]=1.C(=O)([O-])[O-].[K+].[K+].[CH3:17][S:18]([O:21][CH2:22][CH2:23][S:24][S:25][CH2:26][CH2:27]OS(C)(=O)=O)(=[O:20])=[O:19]>C(#N)C>[CH3:17][S:18]([O-:21])(=[O:20])=[O:19].[CH3:17][S:18]([O-:21])(=[O:20])=[O:19].[S:25]([CH2:26][CH2:27][N+:2]1[CH:3]=[CH:4][C:5]2[CH2:6][CH2:7][CH2:8][CH2:9][C:10]=2[CH:1]=1)[S:24][CH2:23][CH2:22][N+:2]1[CH:3]=[CH:4][C:5]2[CH2:6][CH2:7][CH2:8][CH2:9][C:10]=2[CH:1]=1
Reactant: c1cc2c(cn1)CCCC2
Reactant: CS(=O)(=O)OCCSSCCOS(C)(=O)=O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: CS(=O)(=O)[O-]
Product: c1c[n+](CCSSCC[n+]2ccc3c(c2)CCCC3)cc2c1CCCC2
Temperature: 80 °C

Procedure:
3.2 g of 5,6,7,8-tetrahydroisoquinoline and 0.7 g of potassium carbonate were mixed in 3 ml of acetonitrile and brought to 80° C. A solution of 3.4 g of disulfanediyldiethane-2,1-diyl dimethane sulfonate in 3 ml of acetonitrile was added in 10 min. Stirring was maintained for 8 h at 80° C. and then the reaction medium was brought back to ambient temperature, filtered, and concentrated under vacuum. 6 ml of dichloromethane were added and the solution was poured dropwise into 500 ml of ethyl ether. The oil that had been separated by settling out was reprocessed twice by diluting in 6 ml of methanol and adding to 500 ml of ethyl ether, and a final time by diluting in 6 ml of dichloromethane and adding to 500 ml of ethyl ether. After drying under vacuum, 5.2 g of brown solid were recovered. The analyses were in compliance with the expected structure.
Reaction SMILES: [OH:1][C:2]1[C:10]([CH:11]=[O:12])=[CH:9][CH:8]=[C:7]2[C:3]=1[CH2:4][CH2:5][CH2:6]2.[C:13](=O)([O-])[O-].[K+].[K+].CI.O>CN(C)C=O>[CH3:13][O:1][C:2]1[C:10]([CH:11]=[O:12])=[CH:9][CH:8]=[C:7]2[C:3]=1[CH2:4][CH2:5][CH2:6]2
Reactant: O=C([O-])[O-]
Reactant: O=Cc1ccc2c(c1O)CCC2
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Solvent: CI
Product: COc1c(C=O)ccc2c1CCC2
Temperature: 26.5 °C
Reaction time: 4 h
Yield: 53.2 %

Procedure:
To a stirred suspension of 4-Hydroxy-indan-5-carbaldehyde (52.0 gm, 0.320 mole) and Potassium carbonate (57.2 gm, 0.414 mole) in Dimethylformamide (200 ml) solution of Methyl iodide (22 ml, 0.351 mole) in 60 ml Dimethylformamide was added at 0-5° C. The reaction mixture was stirred at 25-28° C. for 4 hours and then poured into water (200 ml), further it was extracted with Ethyl acetate (2×500 ml). The organic layer was dried over Sodium sulphate, distilled under vacuum to give crude product which was purified through column chromatography using Ethyl acetate:Hexane (3:97) as mobile phase. The collected fractions were distilled under vacuum to give 30 gm of desired product as a viscous oil.
Reaction SMILES: [N-:1]=[N+:2]=[N-:3].[Na+].CS(O[CH2:10][CH2:11][CH2:12][C:13]1([O:19][Si:20]([C:23]([CH3:26])([CH3:25])[CH3:24])([CH3:22])[CH3:21])[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]1)(=O)=O>CN(C)C=O.C(OCC)C>[N:1]([CH2:10][CH2:11][CH2:12][C:13]1([O:19][Si:20]([C:23]([CH3:24])([CH3:26])[CH3:25])([CH3:21])[CH3:22])[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18]1)=[N+:2]=[N-:3]
Reactant: [N-]=[N+]=[N-]
Reactant: CC(C)(C)[Si](C)(C)OC1(CCCOS(C)(=O)=O)CCCCC1
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: CCOCC
Product: CC(C)(C)[Si](C)(C)OC1(CCCN=[N+]=[N-])CCCCC1
Reaction time: 60 h
Yield: 95.2 %

Procedure:
Sodium azide (1.78 g, 27.4 mmol) was added to a solution of 3-(1-{[tert-butyl(dimethyl)silyl]oxy}cyclohexyl)propyl methanesulfonate (prepared as described in Part D, 24.9 mmol) in dimethylformamide (100 mL). The reaction mixture was stirred for 2.5 d and additional sodium azide (160 mg) was added. The mixture was stirred an additional 1 d, then was diluted with diethyl ether (250 mL) and washed with water (3×75 mL). The combined aqueous layers were back-extracted with diethyl ether (50 mL). The combined organic layers were washed with brine (100 mL), dried over MgSO4, filtered, and concentrated to afford {[1-(3-azidopropyl)cyclohexyl]oxy}(tert-butyl)dimethylsilane (7.05 g, 95% over two steps) as a pale yellow oil. A mixture of the {[1-(3-azidopropyl)cyclohexyl]oxy}(tert-butyl)dimethylsilane (7.05 g, 23.7 mmol) and 5% palladium on carbon (0.71 g) in ethanol (100 mL) was hydrogenated at 30 psi (2.1×105 Pa) for 4 h on a Parr apparatus. The reaction mixture was filtered through CELITE filter agent, which was rinsed afterwards with dichloromethane, and the filtrate was concentrated to give 3-(1-{[tert-butyl(dimethyl)silyl]oxy}cyclohexyl)propan-1-amine as a pale yellow oil (6.57 g, 102%) that contained a trace amount of solvent.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([N:9]2[C:13]([C:14]([O:16][CH3:17])=[O:15])=[CH:12][C:11]([C:18]([OH:20])=[O:19])=[N:10]2)=[CH:5][CH:4]=1.[CH:21](N(C(C)C)CC)(C)[CH3:22].C(O)C>S(Cl)(Cl)=O>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([N:9]2[C:13]([C:14]([O:16][CH3:17])=[O:15])=[CH:12][C:11]([C:18]([O:20][CH2:21][CH3:22])=[O:19])=[N:10]2)=[CH:5][CH:4]=1
Reactant: COC(=O)c1cc(C(=O)O)nn1-c1ccc(OC)cc1
Reactant: CCN(C(C)C)C(C)C
Solvent: O=S(Cl)Cl
Solvent: CCO
Product: CCOC(=O)c1cc(C(=O)OC)n(-c2ccc(OC)cc2)n1
Temperature: 25 °C
Reaction time: 24 h
Yield: 44.9 %

Procedure:
A solution of 1-[(4-methoxy)phenyl]-5-(methoxycarbonyl)pyrazole-3-carboxylic acid (7.50 g, 27.1 mmol) in 50 mL of thionyl chloride was stirred at 80° C. for 1 h. The volatiles were then removed and the residue was azeotroped with 20 mL of toluene and dried in vacuo. The residue was dissolved in 100 mL of tetrahydrofuran and then there was added diisopropylethylamine (11.8 mL, 67.9 mmol) and absolute ethanol (3.2 mL, 54.3 mmol). The reaction mixture was allowed to stir at ambient temperature for 24 h. The volatiles were removed and the residue was dissolved in ethyl acetate. This solution was filtered through a pad of silica gel and was concentrated in vacuo to afford 3.7 g (45%) of the title compound which was used without purification. LRMS (DCI): 305.1 (M+H)+.
Reaction SMILES: [Cl:1]N1C(=O)CCC1=O.[CH3:9][O:10][C:11]1[CH:12]=[C:13]([CH:17]=[CH:18][CH:19]=1)[CH:14]=[N:15][OH:16].O>CN(C=O)C>[Cl:1][C:13]1([CH:14]=[N:15][OH:16])[CH:17]=[CH:18][CH:19]=[C:11]([O:10][CH3:9])[CH2:12]1
Reactant: O=C1CCC(=O)N1Cl
Reactant: COc1cccc(C=NO)c1
Solvent: CN(C)C=O
Solvent: O
Product: COC1=CC=CC(Cl)(C=NO)C1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
N-chlorosuccinimide (32.2 g, 241 mmol) was added to a solution of 3-methoxybenzaldehyde oxime (30.4 g, 201 mmol) in DMF (200 ml) at RT, causing the temperature to rise briefly to 50° C. The reaction mixture was cooled in an ice bath, stirred overnight at RT, mixed with water (250 ml) while being cooled with ice and the precipitate formed was removed by suction-filtration. The filtrate was extracted with ether (3×400 ml) and the combined organic phases were washed with water (300 ml) and sat. aq. NaCl solution (300 ml), dried and the solvent was removed under vacuum. The desired product 1-chloro-1-hydroxyiminomethyl-3-methoxybenzene was obtained as a yellowish solid (32.86 g).
Reaction SMILES: [CH3:1][C@H:2]([N:9]1[CH2:12][CH2:11][CH:10]1[C:13]([O:15][CH3:16])=[O:14])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[C:17]([OH:26])(=[O:25])[C@@H:18]([C@H:20]([C:22]([OH:24])=[O:23])[OH:21])[OH:19]>C(OC)(C)(C)C.CO>[C:17]([OH:26])(=[O:25])[CH:18]([CH:20]([C:22]([OH:24])=[O:23])[OH:21])[OH:19].[CH3:1][C@H:2]([N:9]1[CH2:12][CH2:11][C@H:10]1[C:13]([O:15][CH3:16])=[O:14])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1
Reactant: O=C(O)[C@H](O)[C@@H](O)C(=O)O
Reactant: COC(=O)C1CCN1[C@@H](C)c1ccccc1
Solvent: COC(C)(C)C
Solvent: CO
Product: COC(=O)[C@@H]1CCN1[C@@H](C)c1ccccc1
Product: O=C(O)C(O)C(O)C(=O)O
Temperature: 29 °C
Yield: 48 %

Procedure:
A solution of methyl N-[(S)-methylbenzyl]azetidine-2-carboxylate (29.91 g, the ratio: 2S isomer/2R isomer=52/48) in methyl tert-butyl ether was added dropwise to a solution of L-tartaric acid (16.55 g) in methanol (20.26 g) under reflux. Further, 21.43 g of methanol was added and the obtained homogeneous solution was cooled to 29° C. A small amount of the crystals obtained in Example 6 was fed as seed crystals to initiate crystallization. Then, after cooled to 5° C., crystals were collected by filtration, washed with methyl tert-butyl ether and dried in vacuo to give tartaric acid salt of methyl N-[(S)-methylbenzyl]azetidine-2-(S)-carboxylate (25.36 g, yield: 48%, 91% d.e.).
Reaction SMILES: [NH2:1][C:2]1[N:7]([CH2:8][C:9]2[CH:13]=[CH:12][NH:11][N:10]=2)[C:6](=[S:14])[NH:5][C:4](=[O:15])[CH:3]=1.[N:16]([O-])=O.[Na+].S(S([O-])=O)([O-])=O.[Na+].[Na+]>>[NH2:16][C:3]1[C:4](=[O:15])[NH:5][C:6](=[S:14])[N:7]([CH2:8][C:9]2[CH:13]=[CH:12][NH:11][N:10]=2)[C:2]=1[NH2:1]
Reactant: O=N[O-]
Reactant: Nc1cc(=O)[nH]c(=S)n1Cc1cc[nH]n1
Agent: O=S([O-])S(=O)[O-]
Agent: [Na+]
Product: Nc1c(N)n(Cc2cc[nH]n2)c(=S)[nH]c1=O
Yield: 68.1 %

Procedure:
The title compound was prepared in accordance with the general method described in Example 12(c) by using 6-amino-1-(1H-pyrazol-3-ylmethyl)-2-thioxo-2,3-dihydropyrimidin-4(1H)-one (0.87 g, 3.88 mmol, obtained from Example 13(b)), sodium nitrite (0.30 g, 4.27 mmol) and sodium dithionite (1.35 g, 7.77 mmol) which gave the title compound (0.63 g, 67% yield).
Reaction SMILES: [O:1]([CH:8]([OH:10])[CH3:9])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH:11][PH:12]([OH:14])=[O:13].O>C1(C)C(C)=CC=CC=1>[P:12]([O:10][CH:8]([O:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)[CH3:9])([OH:14])([OH:13])=[O:11]
Reactant: O=[PH](O)O
Reactant: CC(O)Oc1ccccc1
Solvent: O
Solvent: Cc1ccccc1C
Product: CC(Oc1ccccc1)OP(=O)(O)O

Procedure:
1 mol of phenoxyethanol is esterified azeotropically in the presence of 1.1 mol of H3PO3 in xylene on a water separator. The reaction product which precipitates on cooling is filtered off, washed with petroleum ether and dried to give a white powder. The amount of the phosphoric diester (2-phenoxyethanol hydrogensulphate, 0-50%) which may be formed in this reaction in addition to phenoxyethanol phosphate (phenoxyethanol dihydrogenphosphate) does not interfere in the polycondensation which subsequently takes place; it is also incorporated into the polycondensate.
Reaction SMILES: [N:1]1(O)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.Cl[N:9]1[C:13](=[O:14])[CH2:12][CH2:11][C:10]1=O>>[N:9]12[CH2:10][CH2:11][CH2:12][N:1]=[C:6]1[CH2:5][CH2:4][CH2:3][CH2:2][CH2:13]2.[NH:1]1[CH2:6][CH2:5][CH:4]([OH:14])[CH:3]=[CH:2]1
Reactant: ON1CCCCC1
Reactant: O=C1CCC(=O)N1Cl
Product: C1CCC2=NCCCN2CC1
Product: OC1C=CNCC1

Procedure:
reacting the piperidinol first with N-chlorosuccinimide and then with 1,8-diazabicyclo[5.4.0]undec-7-ene to give the corresponding 1,4,5,6-tetrahydro-4-pyridinol; and,
Reaction SMILES: [N+:1]([C:4]1[CH:10]=[C:9]([N+:11]([O-:13])=[O:12])[CH:8]=[CH:7][C:5]=1[NH2:6])([O-:3])=[O:2].[Cl:14]Cl.Cl>>[Cl:14][C:7]1[CH:8]=[C:9]([N+:11]([O-:13])=[O:12])[CH:10]=[C:4]([N+:1]([O-:3])=[O:2])[C:5]=1[NH2:6]
Reactant: Nc1ccc([N+](=O)[O-])cc1[N+](=O)[O-]
Reactant: ClCl
Agent: Cl
Product: Nc1c(Cl)cc([N+](=O)[O-])cc1[N+](=O)[O-]
Yield: 95 %

Procedure:
Once the total amount of 2,4-dinitroaniline and the corresponding amount of chlorine gas--an equimolar amount and c. 10 % excess of this latter--have been added to the hydrochloric acid, the batch is allowed to react for half an hour to 1 hour and then excess chlorine is expelled with nitrogen. The product is isolated by filtration, washed until neutral and dried. The 2-chloro-4,6-dinitroaniline is obtained by this process in a yield of 95 % with a content of less than 0.5 % by weight of unreacted starting material (dinitroaniline).