Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([O:4][C@@H:5]1[C@H:9]([O:10][C:11](=[O:13])[CH3:12])[C@@H:8]([C:14]#[CH:15])[O:7][C@H:6]1[N:16]1[CH:24]=[N:23][C:22]2[C:17]1=[N:18][CH:19]=[N:20][C:21]=2Cl)(=[O:3])[CH3:2].[OH:26][N:27]1[C:31]2[CH:32]=[CH:33][CH:34]=[CH:35][C:30]=2[N:29]=[N:28]1.Cl>CN(C=O)C>[C:1]([O:4][C@@H:5]1[C@H:9]([O:10][C:11](=[O:13])[CH3:12])[C@@H:8]([C:14]#[CH:15])[O:7][C@H:6]1[N:16]1[CH:24]=[N:23][C:22]2[C:17]1=[N:18][CH:19]=[N:20][C:21]=2[O:26][N:27]1[C:31]2[CH:32]=[CH:33][CH:34]=[CH:35][C:30]=2[N:29]=[N:28]1)(=[O:3])[CH3:2]
Reactant: C#C[C@H]1O[C@@H](n2cnc3c(Cl)ncnc32)[C@H](OC(C)=O)[C@@H]1OC(C)=O
Reactant: On1nnc2ccccc21
Agent: Cl
Solvent: CN(C)C=O
Product: C#C[C@H]1O[C@@H](n2cnc3c(On4nnc5ccccc54)ncnc32)[C@H](OC(C)=O)[C@@H]1OC(C)=O
Yield: 112 %

Procedure:
(2R,3R,4R,5R)-4-(acetyloxy)-2-(6-chloro-9H-purin-9-yl)-5-ethynyltetrahydrofuran-3-yl acetate (104 mg) was treated with 1-hydroxybenzotriazole (136 mg) in dry DMF (3 ml) for 45 h at 22° C. The mixture was poured into ice cooled 1M hydrochloric acid (50 ml) and extracted with dichloromethane (3×25 ml); the organic layers were washed with water (20 ml) and saturated aqueous sodium bicarbonate (20 ml), dried (MgSO4) and evaporated in vacuo to give a colourless gum (148 mg).
Reaction SMILES: [Br-:1].[C:2]([C:5](=[CH2:53])[CH2:6][N+:7]1[CH:12]=[CH:11][C:10]([S:13][CH2:14][C:15]2[CH2:22][S:21][C@H:20]3[N:17]([C:18](=[O:36])[C@H:19]3[NH:23][C:24](=[O:35])[CH2:25][S:26][C:27]3[CH:32]=[C:31]([Cl:33])[CH:30]=[CH:29][C:28]=3[Cl:34])[C:16]=2[C:37]([O:39]C(C2C=CC=CC=2)C2C=CC=CC=2)=[O:38])=[CH:9][CH:8]=1)([OH:4])=[O:3].N#N.C1(OC)C=CC=CC=1.FC(F)(F)C(O)=O>C(Cl)Cl>[Br-:1].[C:2]([C:5](=[CH2:53])[CH2:6][N+:7]1[CH:8]=[CH:9][C:10]([S:13][CH2:14][C:15]2[CH2:22][S:21][C@H:20]3[N:17]([C:18](=[O:36])[C@H:19]3[NH:23][C:24](=[O:35])[CH2:25][S:26][C:27]3[CH:32]=[C:31]([Cl:33])[CH:30]=[CH:29][C:28]=3[Cl:34])[C:16]=2[C:37]([OH:39])=[O:38])=[CH:11][CH:12]=1)([OH:4])=[O:3]
Reactant: C=C(C[n+]1ccc(SCC2=C(C(=O)OC(c3ccccc3)c3ccccc3)N3C(=O)[C@@H](NC(=O)CSc4cc(Cl)ccc4Cl)[C@H]3SC2)cc1)C(=O)O
Agent: N#N
Agent: [Br-]
Solvent: O=C(O)C(F)(F)F
Solvent: COc1ccccc1
Solvent: ClCCl
Product: C=C(C[n+]1ccc(SCC2=C(C(=O)O)N3C(=O)[C@@H](NC(=O)CSc4cc(Cl)ccc4Cl)[C@H]3SC2)cc1)C(=O)O
Temperature: 25 °C
Reaction time: 1 h
Yield: 68.4 %

Procedure:
A slurry of 1-[2-carboxy-2-propen-1-yl]-4-[[(6R)-trans-2-(diphenylmethyl carboxy)-8-oxo-7-[(2,5-dichlorophenylthio)acetamido]-5-thia-1-azabicyclo[4.2.0]-oct-2-en-3-yl]methylthio]pyridinium bromide (580 mg, 0.665 mmol) in 22 mL of CH2Cl2 was cooled to 0° C. (ice bath) under an atomosphere of N2. Anisole (2.8 mL) was added followed by trifluoroacetic acid (8 mL). The cooling bath was removed, and the reaction was allowed to stir at rt for 1 h. The solution was concentrated in vacuo to remove the CH2Cl2 and most of the trifluoroacetic acid. The residue was treated with ether to precipitate a yellow solid. This solid was collected by filtration washing with ether. The solid was stirred with ethyl acetate for 30 min. stirred with acetone for 30 min., collected by filtration, and dried in vacuo to give 322 mg (66%) of 1-[2-carboxy-2-propen-1-yl]-4-[[(6R)-trans-2-carboxy-8-oxo-7-[(2,5-dichlorophenylthio)acetamido]-5-thia-1-azabicyclo[4.2.0]-oct-2-en-3-yl]methylthio]pyridinium bromide as a tan solid. 1H NMR (DMSO-d6) δ9.27 (d, J=8 Hz, 1H), 8.73 (d, J=6 Hz, 2H), 8.06 (d, J=6 Hz, 2H), 7.45-8.48 (m, 2H), 7.24 (dd, J=2,9 Hz, 2H), 6.41 (s, 1H), 6.08 (s, 1H), 5.63 (dd, J=5,8 Hz, 1H), 5.19 (s, 2H), 5.09 (d, J=5 Hz, 1H), 4.43 (s, 2H), 3.92 (s, 2H), 3.70 (d, J=18 Hz, 1H), 3.48 (d, J=18 Hz, 1H). IR (KBr) 1774, 1702, 1680, 1628, 1106 cm-1 ; MS (ESI) 626 (MH)+, Anal: Calcd for C25H21N3O6S3Cl2 ×HBr×0.5Me2CO; C, 42.44; H, 3.13; N, 5.94. Found: C, 43.25; H, 3.42, N, 5.71.
Reaction SMILES: [OH:1][C:2]1[CH:9]=[C:8]([O:10][CH2:11][CH2:12][C:13]2[N:14]=[C:15]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[O:16][C:17]=2[CH3:18])[CH:7]=[CH:6][C:3]=1[CH:4]=[O:5].N1C=CN=C1.[C:30]([Si:36]([CH3:39])([CH3:38])Cl)([CH:33]([CH3:35])[CH3:34])([CH3:32])[CH3:31]>CN(C)C=O.CCOC(C)=O>[CH3:38][Si:36]([CH3:39])([C:30]([CH3:32])([CH3:31])[CH:33]([CH3:35])[CH3:34])[O:1][C:2]1[CH:9]=[C:8]([O:10][CH2:11][CH2:12][C:13]2[N:14]=[C:15]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[O:16][C:17]=2[CH3:18])[CH:7]=[CH:6][C:3]=1[CH:4]=[O:5]
Reactant: Cc1oc(-c2ccccc2)nc1CCOc1ccc(C=O)c(O)c1
Reactant: CC(C)C(C)(C)[Si](C)(C)Cl
Agent: c1c[nH]cn1
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: Cc1oc(-c2ccccc2)nc1CCOc1ccc(C=O)c(O[Si](C)(C)C(C)(C)C(C)C)c1
Temperature: 0 °C
Reaction time: 0.83 h

Procedure:
To a solution of 2-hydroxy-4-[2-(5-methyl-2-phenyl-oxazol-4-yl)-ethoxy]-benzaldehyde (540 mg, 1.67 mmol) in 8 ml N,N-dimethylformamide cooled to 0° C., were added 398 mg (5.85 mol) imidazole and 1.1 ml (5.85 mmol) thexyl-dimethylchlorosilane. The reaction mixture was stirred 50 minutes at 0° C., diluted with AcOEt, washed with water/ice, HCl (1M)/ice and brine and the aqueous layer was extracted with AcOEt. The combined organic layers were dried over Na2SO4 and evaporated. Chromatography (SiO2; AcOEt/heptane) delivered 346 mg (45%) of the title compound as an oil.
Reaction SMILES: [CH2:1]([N:8]1[CH2:14][CH:13]2[C:15]([C:18]3[CH:23]=[CH:22][CH:21]=[C:20](Br)[CH:19]=3)([O:16][CH3:17])[CH:10]([CH2:11][CH2:12]2)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:25][N:26](C=O)C>[C-]#N.[Zn+2].[C-]#N.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH2:1]([N:8]1[CH2:14][CH:13]2[C:15]([C:18]3[CH:23]=[CH:22][CH:21]=[C:20]([C:25]#[N:26])[CH:19]=3)([O:16][CH3:17])[CH:10]([CH2:11][CH2:12]2)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: COC1(c2cccc(Br)c2)C2CCC1CN(Cc1ccccc1)C2
Reactant: CN(C)C=O
Agent: [Pd]
Agent: [C-]#N
Agent: [Zn+2]
Product: COC1(c2cccc(C#N)c2)C2CCC1CN(Cc1ccccc1)C2
Temperature: 85 °C

Procedure:
3-Benzyl-8-(3-bromo-phenyl)-8-methoxy-3-aza-bicyclo[3.2.1]octane (2.17 g, 5.62 mmol) and zinc cyanide (0.99 g, 8.43 mmol) were combined in DMF (30 ml), degassed (evac./N2 purge 3×) then charged with tetrakis(triphenylphosphine) palladium (0) (3.24 g, 2.81 mmol). The resulting reaction mixture was heated to 85° C. in an oil bath for 5 h. Upon cooling to room temperature, the reaction mixture was filtered through a Celite pad and rinsed with EtOAc. The filtrate was extracted with 1 N HCl (2×50 ml) then neutralized to pH 8 with 1 N NaOH and saturated aqueous NaHCO3, causing an emulsion to form. The product was extracted with EtOAc (3×100 ml), washed with saturated aqueous NaCl solution (2×100 ml), dried over Na2SO4, filtered, and concentrated. The resulting crude product was dissolved in ether (100 ml) then washed with 50% saturated aqueous NaCl solution (4×100 ml), dried over Na2SO4, filtered and concentrated to a yellow oil (1.40 g, 75%). (TLC 20% EtOAc/hexanes Rf 0.40); 1H NMR (400 MHz, CDCl3) δ 7.69 (m, 2H), 7.56 (d, J=7.9 Hz, 1H), 7.45 (t, J=7.9 Hz, 1H), 7.36–7.20 (m, 5H), 3.58 (br s, 2H), 2.82 (s, 3H), 2.75 (d, J=10.3 Hz, 2H), 2.54 (br d, J=10.3 Hz, 2H), 2.43 (br s, 2H), 1.83 (d, J=8.1 Hz, 2H), 1.33 (m, 2H); APCI MS m/z 333.2 (M+1)+.
Reaction SMILES: [CH:1]1([S:4]([C:7]2[CH:12]=[CH:11][C:10]([C@@H:13]([CH2:23][C@H:24]3[CH2:28][CH2:27][NH:26][CH2:25]3)[C:14]([NH:16][C:17]3[S:18][C:19]([F:22])=[CH:20][N:21]=3)=[O:15])=[CH:9][CH:8]=2)(=[O:6])=[O:5])[CH2:3][CH2:2]1.C(N(CC)CC)C.[C:36](Cl)(=[O:38])[CH3:37]>ClCCl>[C:36]([N:26]1[CH2:27][CH2:28][C@H:24]([CH2:23][C@H:13]([C:10]2[CH:9]=[CH:8][C:7]([S:4]([CH:1]3[CH2:3][CH2:2]3)(=[O:5])=[O:6])=[CH:12][CH:11]=2)[C:14]([NH:16][C:17]2[S:18][C:19]([F:22])=[CH:20][N:21]=2)=[O:15])[CH2:25]1)(=[O:38])[CH3:37]
Reactant: O=C(Nc1ncc(F)s1)[C@H](C[C@H]1CCNC1)c1ccc(S(=O)(=O)C2CC2)cc1
Reactant: CC(=O)Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CC(=O)N1CC[C@H](C[C@@H](C(=O)Nc2ncc(F)s2)c2ccc(S(=O)(=O)C3CC3)cc2)C1
Reaction time: 0.33 h
Yield: 76 %

Procedure:
The (R)-2-(4-(cyclopropylsulfonyl)phenyl)-N-(5-fluorothiazol-2-yl)-3-((S)-pyrrolidin-3-yl)propanamide (1.17 g, 2.77 mmol) obtained in Step 1 of Example 2 was dissolved in dichloromethane (27 mL), and thereafter, triethylamine (0.806 mL, 5.81 mmol) and acetyl chloride (0.207 mL, 2.91 mmol) were added to the above obtained solution under ice-cold condition. The obtained mixture was stirred for 20 minutes. Thereafter, the reaction solution was washed with a 1 M aqueous solution of hydrochloric acid and a saturated aqueous solution of sodium hydrogen carbonate. The resultant was dried over anhydrous sodium sulfate, and was then concentrated in vacuo. The obtained residue was purified by silica gel chromatography (chloroform/methanol=1%→15%) to obtain the captioned compound (980 mg, 76%) in the form of a white solid.
Reaction SMILES: [C:1]1([CH:9]=[CH:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[CH:6]=[CH:5][C:4]([CH:7]=[O:8])=[CH:3][CH:2]=1>C(OCC)(=O)C.[Pd]>[CH2:9]([C:1]1[CH:2]=[CH:3][C:4]([CH:7]=[O:8])=[CH:5][CH:6]=1)[CH2:10][C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1
Reactant: O=Cc1ccc(C=Cc2ccccc2)cc1
Agent: [Pd]
Solvent: CCOC(C)=O
Product: O=Cc1ccc(CCc2ccccc2)cc1
Reaction time: 2 h
Yield: 50.5 %

Procedure:
To a solution of 4-stilbenecarboxaldehyde (5.14 g, 24.68 mmol) in 125 mL of ethyl acetate was added 0.13 g of 5% Pd/C catalyst. The reaction was stirred under hydrogen (1 atm) for 2 hours. An additional 0.14 g of 5% Pd/C catalyst was added and the reaction mixture was stirred under hydrogen (1 atm) again for 1 hour. The catalyst was removed by filtration through a pad of Celite. The residue was washed with ethyl acetate (2×30 mL) and the filtrate was concentrated on a rotavap. The residue oil was chromatographed with 15% ethyl acetate in hexanes on silica gel to give 2.62 g (50%) of the desired product as a white solid. 1HNMR (300 MHz, CDCl3) δ9.99 (1H, s), 7.81 (2H, d, J=8.14 Hz), 7.35-7.15 (7H, m), 2.99 (4H, m).
Reaction SMILES: [CH3:1][C:2]([N:6]1[CH:10]=[C:9]([NH:11][C:12](=[O:29])[CH:13]([NH:17][C:18](=[O:28])[CH2:19][C:20]2[CH:25]=[C:24]([F:26])[CH:23]=[C:22]([F:27])[CH:21]=2)[CH2:14][CH2:15][CH3:16])[N:8]=[CH:7]1)([CH3:5])[CH:3]=O.[C:30]1([CH:36]([NH2:38])[CH3:37])[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1>>[CH3:1][C:2]([N:6]1[CH:10]=[C:9]([NH:11][C:12](=[O:29])[CH:13]([NH:17][C:18](=[O:28])[CH2:19][C:20]2[CH:21]=[C:22]([F:27])[CH:23]=[C:24]([F:26])[CH:25]=2)[CH2:14][CH2:15][CH3:16])[N:8]=[CH:7]1)([CH3:5])[CH2:3][NH:38][CH:36]([C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[CH3:37]
Reactant: CC(N)c1ccccc1
Reactant: CCCC(NC(=O)Cc1cc(F)cc(F)c1)C(=O)Nc1cn(C(C)(C)C=O)cn1
Product: CCCC(NC(=O)Cc1cc(F)cc(F)c1)C(=O)Nc1cn(C(C)(C)CNC(C)c2ccccc2)cn1

Procedure:
2-[2-(3,5-Difluoro-phenyl)-acetylamino]-pentanoic acid [1-(1,1-dimethyl-2-oxo-ethyl)-1H-imidazol-4-yl]-amide was reacted with 1-phenyl-ethylamine to afford the title compound: C13 NMR (100 MHz, CDCl3) 13.9, 18.9, 24.9, 25.9, 26.9, 36.0, 43.1, 53.1, 57.9, 58.5, 58.9, 102.6, 102.9, 103.1, 105.2, 112.3, 112.5, 112.6, 126.7, 127.1, 128.6, 131.7, 137.7, 138.7, 145.7, 161.9, 164.4, 164.5, 169.2; MS m/z 512.3 (M+1).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([CH2:11][CH2:12][CH2:13][C:14]2[CH:15]=[CH:16][C:17]([OH:42])=[C:18]([CH:41]=2)[NH:19][C:20](=[O:40])[C:21]2[CH:26]=[CH:25][CH:24]=[C:23]([O:27][CH2:28][C:29]3[S:30][C:31]4[CH:37]=[C:36]([O:38][CH3:39])[CH:35]=[CH:34][C:32]=4[N:33]=3)[CH:22]=2)(=[O:10])=[O:9])=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].Br[CH2:50][C:51]([O:53]CC)=[O:52].CN(C)C=O>O>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([CH2:11][CH2:12][CH2:13][C:14]2[CH:15]=[CH:16][C:17]([O:42][CH2:50][C:51]([OH:53])=[O:52])=[C:18]([NH:19][C:20](=[O:40])[C:21]3[CH:26]=[CH:25][CH:24]=[C:23]([O:27][CH2:28][C:29]4[S:30][C:31]5[CH:37]=[C:36]([O:38][CH3:39])[CH:35]=[CH:34][C:32]=5[N:33]=4)[CH:22]=3)[CH:41]=2)(=[O:9])=[O:10])=[CH:4][CH:3]=1
Reactant: CCOC(=O)CBr
Reactant: COc1ccc2nc(COc3cccc(C(=O)Nc4cc(CCCS(=O)(=O)c5ccc(Cl)cc5)ccc4O)c3)sc2c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: COc1ccc2nc(COc3cccc(C(=O)Nc4cc(CCCS(=O)(=O)c5ccc(Cl)cc5)ccc4OCC(=O)O)c3)sc2c1
Temperature: 25 °C
Reaction time: 12 h
Yield: 43.8 %

Procedure:
A mixture of 5'-[3-(4-chlorophenylsulfonyl)propyl]-2'-hydroxy-3-(6-methoxy-2-benzothiazolylmethoxy)benzanilide (301 mg, 0.48 mmol), potassium carbonate (135 mg, 0.98 mmol), ethyl bromoacetate (81 mg, 0.49 mmol) and dimethylformamide (5 ml) was stirred at room temperature for 12 hours. Water was added to the reaction solution and the product formed was extracted with ethyl acetate. The extract was washed with water and brine in that order, dried over anhydrous sodium sulfate, and then concentrated under reduced pressure. Tetrahydrofuran (2 ml), methanol (1 ml) and 1 N sodium hydroxide were added to the resulting residue and the mixture was stirred at room temperature for 12 hours. The reaction solution was concentrated, and water was added to the resulting residue, and the mixture was adjusted to pH 3 with 10% citric acid aqueous solution. Thereafter, the solid material formed was collected by filtration and washed with acetonitrile to give 4-[3-(4-chlorophenylsulfonyl)propyl]-2-[3-[(6-methoxy-2-benzothiazolyl)methoxy]benzoylamino]phenoxyacetic acid (145 mg, 0.21 mmol, 44%).
Reaction SMILES: [O:1]=[C:2]1[C:10]2[CH:9]=[CH:8][CH:7]=[C:6]([C:11]#[N:12])[C:5]=2[CH2:4][CH2:3]1.[BH4-].[Na+]>CCO>[OH:1][CH:2]1[C:10]2[CH:9]=[CH:8][CH:7]=[C:6]([C:11]#[N:12])[C:5]=2[CH2:4][CH2:3]1
Reactant: N#Cc1cccc2c1CCC2=O
Agent: [BH4-]
Agent: [Na+]
Solvent: CCO
Product: N#Cc1cccc2c1CCC2O
Temperature: 25 °C
Reaction time: 2 h
Yield: 82 %

Procedure:
To a stirring suspension of 1-oxo-2,3-dihydro-1H-indene-4-carbonitrile INT-45 (1.2 g, 7.64 mmol) and silica gel (catalytic) in EtOH at 0° C. was added NaBH4 (237.2 mg, 7.64 mmol). The reaction was allowed to warm to room temperature and stirred for 2 h. The solvent was removed under reduced pressure, and the product was purified by chromatography (EA/hexane) to afford 1.02 g (82%) of 1-hydroxy-2,3-dihydro-1H-indene-4-carbonitrile INT-46 as a white solid. LCMS-ESI (m/z) calculated for C10H9NO; 159.2; found 160.1 [M+H]+, tR=2.39 min.
Reaction SMILES: [OH-].[Na+].S([O:8][CH3:9])(OC)(=O)=O.[OH:10][C:11]1[CH:20]=[CH:19][C:18]2[C:13](=[CH:14][C:15](O)=[CH:16][CH:17]=2)[CH:12]=1>ClCCl.O>[OH:10][C:11]1[CH:20]=[CH:19][C:18]2[C:13](=[CH:14][C:15]([O:8][CH3:9])=[CH:16][CH:17]=2)[CH:12]=1
Reactant: COS(=O)(=O)OC
Reactant: Oc1ccc2ccc(O)cc2c1
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: ClCCl
Product: COc1ccc2ccc(O)cc2c1
Temperature: 25 °C
Reaction time: 2 h
Yield: 30.1 %

Procedure:
Sodium hydroxide (20 ml, 1M) and dimethyl sulfate (15.0 ml, 158 mmol) were added dropwise to a solution of 2,7-dihydroxynaphthalene (6.6 g, 40 mmol) in dichloromethane (100 ml) and water (60 ml). Additional sodium hydroxide (20 ml, 1M) and dimethyl sulfate (15.0 ml, 158 mmol) were added and the resulting mixture was stirred at room temperature for 2 hours. The two phases were separated and the aqueous layer was extracted with dichloromethane twice. The combined organic extracts were washed with 1 M HCl, dried over magnesium sulfate and concentrated under vacuum. The crude material was purified by column chromatography (5:1 heptane/ethyl acetate) to give 2-hydroxy-7-methoxynaphthalene (2.1 g, 30%, 100% AUC HPLC): 1H NMR (300 MHz, CDCl3) δ 7.66-7.70 (m, 2H), 6.94-7.08 (m, 4H), 4.90 (s, 1H), 3.92 (s, 3H).
Reaction SMILES: Cl[C:2]1[C:11](=[O:12])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4](=[O:13])[C:3]=1[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH3:25].[OH-:26].[Na+].Cl>C(O)C>[CH2:14]([C:3]1[C:4](=[O:13])[C:5]2[C:10]([C:11](=[O:12])[C:2]=1[OH:26])=[CH:9][CH:8]=[CH:7][CH:6]=2)[CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH3:25]
Reactant: [OH-]
Reactant: CCCCCCCCCCCCC1=C(Cl)C(=O)c2ccccc2C1=O
Agent: Cl
Agent: [Na+]
Solvent: CCO
Product: CCCCCCCCCCCCC1=C(O)C(=O)c2ccccc2C1=O

Procedure:
A mixture of 10 parts of 3-chloro-2-n-dodecyl-1,4-naphthoquinone. 5 parts of 50% aqueous sodium hydroxide and 320 parts of 95% aqueous ethanol were heated at reflux for 15 minutes. The color of the mixture turned from yellow to dark red. The mixture was cooled to 25° and acidified with 10% aqueous hydrochloric acid. The color of the mixture was golden yellow after acidification. The product was filtered off and washed twice with water (25 parts) and twice with cold methanol (25 parts) to yield 8 parts of 2-n-dodecyl-3-hydroxy-1,4-naphthoquinone, mp. 85° - 87° C.
Reaction SMILES: [CH3:1][N:2]([C:28]1[CH:33]=[CH:32][CH:31]=[C:30]([N+:34]([O-])=O)[CH:29]=1)[C:3]1[CH:11]=[C:10]2[C:6]([C:7]([CH:20]=[CH:21][C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)=[N:8][N:9]2COCC[Si](C)(C)C)=[CH:5][CH:4]=1.CN(C1C=C2C(C(C=CC3C=CC=CC=3)=NN2COCC[Si](C)(C)C)=CC=1)C1C=CC=C(N)C=1>C(OCC)(=O)C.CCCCCC>[CH3:1][N:2]([C:3]1[CH:11]=[C:10]2[C:6]([C:7]([CH:20]=[CH:21][C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)=[N:8][NH:9]2)=[CH:5][CH:4]=1)[C:28]1[CH:33]=[CH:32][CH:31]=[C:30]([NH2:34])[CH:29]=1
Reactant: CN(c1cccc([N+](=O)[O-])c1)c1ccc2c(C=Cc3ccccc3)nn(COCC[Si](C)(C)C)c2c1
Agent: CN(c1cccc(N)c1)c1ccc2c(C=Cc3ccccc3)nn(COCC[Si](C)(C)C)c2c1
Solvent: CCCCCC
Solvent: CCOC(C)=O
Product: CN(c1cccc(N)c1)c1ccc2c(C=Cc3ccccc3)n[nH]c2c1

Procedure:
Methyl-(3-nitro-phenyl)-{3-styryl-1-[2-(trimethyl-silanyl)-ethoxymethyl]-1H-indazol-6-yl}-amine was converted to N-methyl-N-{3-styryl-1-[2-(trimethyl-silanyl)-ethoxymethyl]-1H-indazol-6-yl}-benzene-1,3-diamine as described in Example 11, step (iv). Rf sm 0.55, Rf p 0.31 (ethyl acetate:hexane 3:7); FTIR (thin film) 3455, 3360, 2951, 2893, 1621, 1601, 1494, 1449, 1249, 1074 cm−1; 1H NMR (300 MHz, CDCl3) δ 7.81 (d, 1H, J=8.8 Hz) 7.58 (d, 2H, J=7.21 Hz), 7.26-7.50 (m 5H), 7.12 (t, 1H, J=7.93 Hz), 7.01 (d, 1H, J=1.73 Hz), 6.95 (dd, 1H, J=1.99, 8.85 Hz), 5.67 (s, 2H), 3.63 (t, 2H, J=8.12 Hz), 3.38 (s, 3H), 0.93 (t, 2H, J=8.13 Hz), −0.04 (s, 9H); 13C NMR (75 MHz, CDCl3) δ 150.3, 149.0, 147.7, 143.4, 143.0, 137.6, 131.3, 130.4, 128.9, 128.0, 126.7, 121.2, 120.6, 117.3, 117.0, 113.1, 110.1, 109.3, 97.5, 77.8, 66.6, 41.0, 18.0, −1.2; LCMS (ESI) [M+H]/z Calc'd 471, Found 471.
Reaction SMILES: [CH:1]1([CH2:7][C@H:8]([NH:13]C(=O)OC(C)(C)C)[CH2:9][N:10]([CH3:12])[CH3:11])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.O1CCOCC1.[ClH:27]>O>[ClH:27].[ClH:27].[CH:1]1([CH2:7][C@H:8]([NH2:13])[CH2:9][N:10]([CH3:12])[CH3:11])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: CN(C)C[C@H](CC1CCCCC1)NC(=O)OC(C)(C)C
Agent: Cl
Solvent: C1COCCO1
Solvent: O
Product: CN(C)C[C@@H](N)CC1CCCCC1
Reaction time: 2 h
Yield: 100 %

Procedure:
Solid (S)-tert-butyl 1-cyclohexyl-3-(dimethylamino)propan-2-ylcarbamate (263 mg, 0.97 mmol) was dissolved in 4 M HCl in dioxane (10 mL, 40 mmol) and H2O (1 mL). After 2 h, the solvent was removed (50° C., 150 mm) and the residual solvent was azeotroped with toluene (2×10 mL) to afford (S)-3-Cyclohexyl-N1,N1-dimethylpropane-1,2-diamine dihydrochloride (245.3 mg, 100%) as a white solid. MS ESI+ve m/z 185 (M(−BOC)+1)+.
Reaction SMILES: [NH2:1][C:2]1[CH:10]=[CH:9][C:8]([Cl:11])=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].C(O[C:15]1(O[Si](C)(C)C)[CH2:17][CH2:16]1)C.C(O)(=O)C.C([BH3-])#N.[Na+]>CO>[Cl:11][C:8]1[CH:9]=[CH:10][C:2]([NH:1][CH:15]2[CH2:17][CH2:16]2)=[C:3]([CH:7]=1)[C:4]([OH:6])=[O:5]
Reactant: CCOC1(O[Si](C)(C)C)CC1
Reactant: Nc1ccc(Cl)cc1C(=O)O
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: CO
Solvent: CC(=O)O
Product: O=C(O)c1cc(Cl)ccc1NC1CC1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 50.7 %

Procedure:
To a solution of 500 mg of 2-amino-5-chloro-benzoic acid (2.91 mmol) in methanol were added 3 Å molecular sieves, 2.34 ml of [(1-ethoxycyclopropyl)oxy]trimethylsilane (11.66 mmol) and 1.67 ml of acetic acid and the mixture was stirred for 30 min at RT. Then 916 mg of sodium cyanoborohydride (14.57 mmol) were added and the reaction mixture was heated to reflux for 16 h. The reaction mixture was allowed to cool to RT, filtered and the filtrate was concentrated in vacuo. The remaining solid was dissolved in ethyl acetate and the solution was washed with 1N HCl and brine, dried (MgSO4), filtered and concentrated to give 312 mg of the crude title compound that was used in the following step without further purification. 1HNMR (DMSO-d6, 300 MHz): δ 0.46 (m, 2H), 0.79 (m, 2H), 3.44 (m, 1H), 7.10 (d, J=8.9 Hz, 1H), 7.44 (d, J=8.9 Hz, 1H), 7.70 (s, 1H), 7.89 (br s, 1H), 13.09 (br s, 1H).
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:10]=[CH:11][C:12]([N+:17]([O-])=O)=[C:13]([CH:16]=1)[NH:14][CH3:15])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.S(=O)(=O)(O)O>[C].[Pt].CC(O)C>[CH2:1]([O:8][C:9]1[CH:16]=[C:13]([NH:14][CH3:15])[C:12]([NH2:17])=[CH:11][CH:10]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CNc1cc(OCc2ccccc2)ccc1[N+](=O)[O-]
Agent: [Pt]
Agent: O=S(=O)(O)O
Solvent: CC(C)O
Product: CNc1cc(OCc2ccccc2)ccc1N
Reaction time: 0.5 h
Yield: 94.7 %

Procedure:
5% platinum carbon (0.50 g, (DRY)) was added to a 2-propanol (170 mL) suspension of 5-benzyloxy-N-methyl-2-nitroaniline (10.00 g, 38.7 mmol), and catalytic hydrogenation reaction was performed at ordinary pressure. The reaction solution was filtered to remove a catalyst. The catalyst was washed with 2-propanol (20 mL), and the washing liquid was added to the precedent filtrate. Under ice cooling, 97% sulfuric acid (1.06 mL, 19.3 mmol) was added to the mixture, and then the mixture was stirred under the same temperature for 30 minutes. The resulting precipitated crystals were collected by filtration, then washed with 2-propanol (40 mL), and dried at 40° C., thereby obtaining 9.07 g of a light-purple, crystal target compound (yield: 94.7%).
Reaction SMILES: [NH2:1][C:2]1[C:7]([C:8]#[N:9])=[C:6]([C:10]2[CH:35]=[CH:34][C:13]([O:14][CH2:15][CH2:16][O:17][C:18](=[O:33])[CH2:19][CH2:20][C@H:21]([NH:25][C:26](=[O:32])[CH2:27][CH2:28][C:29]([OH:31])=[O:30])[C:22]([OH:24])=[O:23])=[CH:12][CH:11]=2)[C:5]([C:36]#[N:37])=[C:4]([S:38][CH2:39][C:40]2[N:41]=[C:42]([C:45]3[CH:50]=[CH:49][C:48]([Cl:51])=[CH:47][CH:46]=3)[S:43][CH:44]=2)[N:3]=1.[OH-].[Na+:53]>C(#N)C.O>[Na+:53].[Na+:53].[NH2:1][C:2]1[C:7]([C:8]#[N:9])=[C:6]([C:10]2[CH:11]=[CH:12][C:13]([O:14][CH2:15][CH2:16][O:17][C:18](=[O:33])[CH2:19][CH2:20][C@H:21]([NH:25][C:26](=[O:32])[CH2:27][CH2:28][C:29]([OH:31])=[O:30])[C:22]([O-:24])=[O:23])=[CH:34][CH:35]=2)[C:5]([C:36]#[N:37])=[C:4]([S:38][CH2:39][C:40]2[N:41]=[C:42]([C:45]3[CH:50]=[CH:49][C:48]([Cl:51])=[CH:47][CH:46]=3)[S:43][CH:44]=2)[N:3]=1.[NH2:1][C:2]1[C:7]([C:8]#[N:9])=[C:6]([C:10]2[CH:11]=[CH:12][C:13]([O:14][CH2:15][CH2:16][O:17][C:18](=[O:33])[CH2:19][CH2:20][C@H:21]([NH:25][C:26](=[O:32])[CH2:27][CH2:28][C:29]([OH:31])=[O:30])[C:22]([O-:24])=[O:23])=[CH:34][CH:35]=2)[C:5]([C:36]#[N:37])=[C:4]([S:38][CH2:39][C:40]2[N:41]=[C:42]([C:45]3[CH:50]=[CH:49][C:48]([Cl:51])=[CH:47][CH:46]=3)[S:43][CH:44]=2)[N:3]=1
Reactant: N#Cc1c(N)nc(SCc2csc(-c3ccc(Cl)cc3)n2)c(C#N)c1-c1ccc(OCCOC(=O)CC[C@H](NC(=O)CCC(=O)O)C(=O)O)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CC#N
Product: N#Cc1c(N)nc(SCc2csc(-c3ccc(Cl)cc3)n2)c(C#N)c1-c1ccc(OCCOC(=O)CC[C@H](NC(=O)CCC(=O)O)C(=O)[O-])cc1

Procedure:
0.5 g (0.667 mmol) of the compound from example 9 is dissolved in 12.5 ml of acetonitrile and 62.5 ml of water, and 13 ml of 0.1 N sodium hydroxide solution are added. After brief stirring, the mixture is lyophilized. After drying under high vacuum, 0.53 g (quant.) of the title compound remain.