Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Br:1][C:2]1[S:6][C:5]([C:7]([OH:9])=O)=[CH:4][CH:3]=1.S(Cl)(Cl)=O.[C:14]([NH2:18])([CH3:17])([CH3:16])[CH3:15]>C(Cl)Cl>[Br:1][C:2]1[S:6][C:5]([C:7]([NH:18][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:9])=[CH:4][CH:3]=1
Reactant: CC(C)(C)N
Reactant: O=C(O)c1ccc(Br)s1
Solvent: ClCCl
Solvent: O=S(Cl)Cl
Product: CC(C)(C)NC(=O)c1ccc(Br)s1
Yield: 83.4 %

Procedure:
A mixture of 5-bromothiophene-2-carboxylic acid (10.0 g, 48 mmol) and thionyl chloride (3.5 ml, 48 mmol) was boiled under reflux for 3 hrs. Excess of thionyl chloride was removed by distillation under reduced pressure. The residue was taken up in DCM (30 ml) and a solution of tert-butylamine (7.0 g, 96 mmol) in DCM (30 ml) was added with stirring, the temperature of the mixture being kept below 10° C. The resulting solution was stirred at 25° C. for 12 hrs, washed with water (3×20 ml) and dried over MgSO4. The combined washings were basified to pH11 with 5M KOH(aq) and extracted with DCM (3×100 ml) and dried over MgSO4. The combined organic solutions were evaporated under reduced pressure to give the crude product (12.5 g). Recrystallization from (C6H12/CHCl3) gave the pure amide (10.5 g) as a white solid. MS (ES+): 263 (M+H)+.
Reaction SMILES: [OH:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[CH:4][CH:3]=1.[CH3:10][O:11][C:12]1[CH:19]=[CH:18][C:15]([CH2:16]Cl)=[CH:14][CH:13]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[CH3:10][O:11][C:12]1[CH:19]=[CH:18][C:15]([CH2:16][O:1][C:2]2[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[CH:4][CH:3]=2)=[CH:14][CH:13]=1
Reactant: COc1ccc(CCl)cc1
Reactant: O=Cc1ccc(O)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: COc1ccc(COc2ccc(C=O)cc2)cc1
Temperature: 25 °C
Reaction time: 5 h
Yield: 98.2 %

Procedure:
A 500 mL round bottom flask was charged with 4-hydroxybenzaldehyde (40 g, 328 mmol) and DMF (250 mL). 4-methoxybenzyl chloride (57.8 mL, 426 mmol) was added, followed by potassium carbonate (90 g, 656 mmol). The reaction mixture was stirred at room temperature for 5 h then poured into ice water (2.5 L). The product was collected by filtration and rinsed with water. After drying thoroughly, 78 g (98%) of aldehyde 12.1 was obtained as a light yellow powder. 1H NMR (400 MHz)(DMSO-d6) δ 9.88 (s, 1H); 7.88 (d, 2H, J=8.7 Hz); 7.42 (d, 2H, J=8.8 Hz); 7.21 (d, 2H, J=8.8 Hz); 6.97 (d, 2H, J=8.6 Hz); 5.16 (s, 2H); 3.77 (s, 3H). MS ESI (pos.) m/e: 243.1 (M+H).
Reaction SMILES: [OH:1][C:2]1[C:15]2[C:14](=[O:16])[C:13]3[CH:12]=[C:11]4[CH:17]=[CH:18][CH:19]=[CH:20][C:10]4=[CH:9][C:8]=3[O:7][C:6]=2[CH:5]=[C:4]([OH:21])[CH:3]=1.C([O-])([O-])=O.[K+].[K+].CN(C=O)C.[CH2:33]([CH:35]1[O:37][CH2:36]1)Cl>O>[OH:1][C:2]1[C:15]2[C:14](=[O:16])[C:13]3[CH:12]=[C:11]4[CH:17]=[CH:18][CH:19]=[CH:20][C:10]4=[CH:9][C:8]=3[O:7][C:6]=2[CH:5]=[C:4]([O:21][CH2:33][CH:35]2[CH2:36][O:37]2)[CH:3]=1
Reactant: O=c1c2cc3ccccc3cc2oc2cc(O)cc(O)c12
Reactant: ClCC1CO1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: O=c1c2cc3ccccc3cc2oc2cc(OCC3CO3)cc(O)c12
Yield: 10.8 %

Procedure:
1,3-dihydroxy-12H-benzo[b]xanthen-12-one (0.1 g, 0.36 mmol) synthesized in Step 1 of Example 18, K2CO3 (0.2 g, 1.44 mmol), and DMF (5 mL) were added to a dry round-bottom flask, and epichlorohydrin (0.19 g, 2.16 mmol) was added thereto with stirring using a syringe. The reaction mixture was stirred under a nitrogen atmosphere (75° C., overnight). After the reaction was completed, water was added to the reaction mixture which was then extracted twice with ethyl acetate. The organic layer was combined, washed with brine and dried over anhydrous Na2SO4. This liquid was filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was separated and purified by silica gel column chromatography (developing solvent: ethyl acetate:n-hexane=1:3 (v/v)) to give the title compound (13 mg, 10.8%) as a yellow solid.
Reaction SMILES: [CH3:1][C:2]([C:5]1[CH:10]=[CH:9][C:8]([N:11]([S:15]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)(=[O:17])=[O:16])[C:12](=[O:14])[CH3:13])=[C:7]([O:24][CH3:25])[CH:6]=1)(O)[CH3:3].C(=O)([O-])O.[Na+]>C(Cl)Cl.FC(F)(F)C(O)=O.C([SiH](CC)CC)C>[CH3:25][O:24][C:7]1[CH:6]=[C:5]([CH:2]([CH3:1])[CH3:3])[CH:10]=[CH:9][C:8]=1[N:11]([S:15]([C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1)(=[O:16])=[O:17])[C:12](=[O:14])[CH3:13]
Reactant: COc1cc(C(C)(C)O)ccc1N(C(C)=O)S(=O)(=O)c1ccccc1
Agent: CC[SiH](CC)CC
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: COc1cc(C(C)C)ccc1N(C(C)=O)S(=O)(=O)c1ccccc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 97.5 %

Procedure:
To a solution of 1-methyl-1-[4-(N-acetyl-phenylsulfonylamino)-3-methoxyphenyl]ethanol (2.50 g; prepared in Reference Example 39.) in methylene chloride (10 ml), trifluoroacetic acid (10 ml) and triethylsilane (3.3 ml) were added at 0° C. The mixture was stirred for 1 hour at room temperature. The reaction mixture was added to saturated sodium hydrogencarbonate carefully The mixture was extracted with ethyl acetate. The organic layer was washed, dried over and concentrated. The residue was purified on silica gel column chromatography (hexane:AcOEt=3:1) to give the title compound (2.33 g) having the following physical data.
Reaction SMILES: [H-].[Na+].[Cl:3][C:4]1[N:9]=[CH:8][N:7]=[C:6]([C:10]([C:12]2[CH:21]=[C:20]([CH3:22])[C:15]3[NH:16][C:17](=[O:19])[O:18][C:14]=3[CH:13]=2)=[O:11])[CH:5]=1.I[CH3:24]>CN(C=O)C>[Cl:3][C:4]1[N:9]=[CH:8][N:7]=[C:6]([C:10]([C:12]2[CH:21]=[C:20]([CH3:22])[C:15]3[N:16]([CH3:24])[C:17](=[O:19])[O:18][C:14]=3[CH:13]=2)=[O:11])[CH:5]=1
Reactant: CI
Reactant: Cc1cc(C(=O)c2cc(Cl)ncn2)cc2oc(=O)[nH]c12
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: Cc1cc(C(=O)c2cc(Cl)ncn2)cc2oc(=O)n(C)c12
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
0.35 g (8.0 mmol) sodium hydride (55%, suspension in mineral oil) were added to 2.2 g (7.6 mmol) of 6-(6-chloropyrimidine-4-carbonyl)-4-methyl-3H-benzoxazol-2-one in 10 mL N,N′-dimethylformamide. The reaction mixture was stirred for 30 min at RT. Then 0.95 mL (15.0 mmol) iodomethane were added and the mixture was stirred for 1 h at RT. The reaction mixture was combined with ice water, the aqueous phase was extracted several times with EtOAc. The combined organic phases were dried on sodium sulphate, filtered and concentrated to dryness by rotary evaporation. The residue was triturated with diethyl ether, suction filtered and dried.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:23])[C@@H:4]([N:9]1[C:18](=[O:19])[C:17]2[C:12](=[CH:13][C:14]([O:20][CH3:21])=[CH:15][CH:16]=2)[NH:11][C:10]1=[O:22])[CH2:5][CH2:6][CH2:7][CH3:8].[I-].[CH3:25][N:26]1[C:34]2[C:29](=[C:30]([CH3:35])[CH:31]=[CH:32][CH:33]=2)[C:28]([CH2:36][N+](C)(C)C)=[CH:27]1.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C.CCOC(C)=O>[CH3:1][O:2][C:3](=[O:23])[C@@H:4]([N:9]1[C:18](=[O:19])[C:17]2[C:12](=[CH:13][C:14]([O:20][CH3:21])=[CH:15][CH:16]=2)[N:11]([CH2:36][C:28]2[C:29]3[C:34](=[CH:33][CH:32]=[CH:31][C:30]=3[CH3:35])[N:26]([CH3:25])[CH:27]=2)[C:10]1=[O:22])[CH2:5][CH2:6][CH2:7][CH3:8]
Reactant: CCCC[C@@H](C(=O)OC)n1c(=O)[nH]c2cc(OC)ccc2c1=O
Reactant: Cc1cccc2c1c(C[N+](C)(C)C)cn2C
Agent: O=C([O-])[O-]
Agent: [I-]
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: CCCC[C@@H](C(=O)OC)n1c(=O)c2ccc(OC)cc2n(Cc2cn(C)c3cccc(C)c23)c1=O
Temperature: 60 °C
Reaction time: 4 h
Yield: 97.9 %

Procedure:
To a mixture of (S)-2-(7-methoxy-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)-hexanoic acid methyl ester (100 mg, 0.31 mmol) and (1,4-dimethyl-1H-indol-3-ylmethyl)-trimethylammonium iodide (160 mg, 0.47 mmol) in DMF (2.5 mL) is added K2CO3 (100 mg, 0.72 mmol). The mixture is stirred at 60° C. for 4 hours. The reaction mixture is allowed to cool to room temperature, diluted with EtOAc (50 mL) and washed with H2O (50 mL×3). The organic layer is dried over sodium sulfate and concentrated. The resulting residue is triturated with EtOAc and hexanes to afford (S)-2-[1-(1,4-dimethyl-1H-indol-3-ylmethyl)-7-methoxy-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl]-hexanoic acid methyl ester (145 mg, 97%).
Reaction SMILES: [CH3:1][C:2]([OH:10])([C:4]#[C:5][C:6]([CH3:9])(O)[CH3:7])[CH3:3].[OH2:11]>OS(O)(=O)=O>[CH3:3][C:2]1([CH3:1])[C:4](=[O:11])[CH2:5][C:6]([CH3:7])([CH3:9])[O:10]1
Reactant: CC(C)(O)C#CC(C)(C)O
Reactant: O
Agent: O=S(=O)(O)O
Product: CC1(C)CC(=O)C(C)(C)O1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 89 %

Procedure:
Mercuric oxide (600 mg) was dissolved in 200 mL of water containing 2 mL of concentrated H2SO4. Solid 2,5-dimethyl-3-hexyne-2,5-diol (50.0g, 352 mmol) was added and the solution was heated until the homogeneous solution turned cloudy. Heating was stopped and the flask was stirred in a room temperature water bath for 30 min. The solution was distilled and 250 mL of distillate was collected (more H2O was added). The biphasic material was taken up into ether, separated, washed with brine, dried over MgSO4, filtered, evaporated and distilled (150° C.) to give 44.5 g (89%) of dihydro-2,2,5,5-tetramethyl-3(2H)-furanone as a water-white oil. Dihydro-2,2,5,5-tetramethyl-3(2H)furanone (32.1 g, 226 mmol) in 50 mL of ether was added dropwise to a suspension of sodium hydride (18.1 g of 60%, 453 mmol) in 400 mL of ether containing two drops of ethanol and 36.5 mL (453 mmol) of ethyl formate stirred at 0° C. After stirring overnight at room temperature, the reaction mixture was taken up into water, washed with additional ether, acidified with 6N HCl and extracted into ether. The combined ether layers were washed with water and brine, dried over MgSO4, decolorized with charcoal, filtered through celite and evaporated. The solid residue was recrystallized from a small volume of ether and a large quantity of hexanes. The solid was isolated by filtration and dried to give 30.4 g (79%) of 4-hydroxymethylene-dihydro-2,2,5,5-tetramethyl-3(2H)-furanone as an off-white solid. Ethylenediamine (1.15 mL, 17.4 mmol) was added to a solution of 4-hydroxymethylene-dihydro-2,2,5,5-tetramethyl-3(2H)furanone (5.9 g, 34.7 mmol) in 40 mL of THF. This solution was refluxed for one hour. The solvents were evaporated under high vacuum with moderate heating. The solid residue was slurried in 50 mL of cold ether and filtered to give 5.3 g (76%) of off-white solid. Recrystallization from 50 mL of THF followed by drying at 70° C. (1 Torr) for 6 hours gave 4.0 g of 1,2-bis[dihydro-2,2,5,5-tetramethyl3(2H)furanone-4-methyleneamino]ethane as a white solid: Anal. Calc'd for C20H32N2O4 : C, 65.93; H, 8.79; N, 7.69. Found: C, 65.68; H, 8.90; N, 7.65.
Reaction SMILES: [CH3:1][C:2]([C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)([CH3:28])[CH2:3][N:4]1[CH2:8][CH2:7][C@@H:6]([NH:9][C:10]2[N:11]=[CH:12][C:13](/[CH:16]=[CH:17]/[C:18]([NH:20][O:21]C3CCCCO3)=[O:19])=[N:14][CH:15]=2)[CH2:5]1.[ClH:35].CC(C)=O>CCO>[ClH:35].[ClH:35].[OH:21][NH:20][C:18](=[O:19])/[CH:17]=[CH:16]/[C:13]1[CH:12]=[N:11][C:10]([NH:9][C@@H:6]2[CH2:7][CH2:8][N:4]([CH2:3][C:2]([CH3:1])([C:29]3[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=3)[CH3:28])[CH2:5]2)=[CH:15][N:14]=1
Reactant: CC(C)(CN1CC[C@@H](Nc2cnc(/C=C/C(=O)NOC3CCCCO3)cn2)C1)c1ccccc1
Agent: Cl
Solvent: CC(C)=O
Solvent: CCO
Product: CC(C)(CN1CC[C@@H](Nc2cnc(/C=C/C(=O)NO)cn2)C1)c1ccccc1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To a solution of (2E)-3-[5-({(3R)-1-[2-methyl-2-phenylpropyl]-3-pyrrolidinyl}amino)-2-pyrazinyl]-N-(tetrahydro-2H-pyran-2-yloxy)acrylamide (130 mg) in EtOH (0.7 mL) was added 2N—HCl solution in EtOH (0.7 mL) and the reaction mixture was stirred for 2 hours at ambient temperature. Acetone was added to the mixture and filtered. The filtrate was evaporated and dried to give (2E)-N-hydroxy-3-[5-[{(3R)-1-(2-methyl-2-phenylpropyl)-3-pyrrolidinyl}amino]-2-pyrazinyl]acrylamide dihydrochloride (108 mg).
Reaction SMILES: [CH2:1]([N:4]1[CH2:13][CH2:12][C:11]2[C:6](=[CH:7][CH:8]=[C:9]([OH:14])[CH:10]=2)[CH2:5]1)[CH:2]=[CH2:3].[Na].CS(O[CH2:21][CH:22]1[CH2:26][O:25][C:24]([C:33]2[CH:38]=[CH:37][C:36]([Cl:39])=[CH:35][C:34]=2[Cl:40])([CH2:27][N:28]2[CH:32]=[CH:31][N:30]=[CH:29]2)[O:23]1)(=O)=O>C(O)C>[CH2:1]([N:4]1[CH2:13][CH2:12][C:11]2[C:6](=[CH:7][CH:8]=[C:9]([O:14][CH2:21][CH:22]3[CH2:26][O:25][C:24]([C:33]4[CH:38]=[CH:37][C:36]([Cl:39])=[CH:35][C:34]=4[Cl:40])([CH2:27][N:28]4[CH:32]=[CH:31][N:30]=[CH:29]4)[O:23]3)[CH:10]=2)[CH2:5]1)[CH:2]=[CH2:3]
Reactant: CS(=O)(=O)OCC1COC(Cn2ccnc2)(c2ccc(Cl)cc2Cl)O1
Reactant: C=CCN1CCc2cc(O)ccc2C1
Agent: [Na]
Solvent: CCO
Product: C=CCN1CCc2cc(OCC3COC(Cn4ccnc4)(c4ccc(Cl)cc4Cl)O3)ccc2C1
Reaction time: 0.25 h

Procedure:
1.89 g of 2-allyl-6-hydroxy-1,2,3,4-tetrahydroisoquinoline are added to a freshly prepared solution of alcoholate from 0.23 g of sodium in 30 ml of dry ethanol, the mixture is stirred for 15 minutes, 4.07 g of (2RS,4SR)-2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-ylmethyl methanesulfonate are added, and the mixture is then heated under reflux for 8 hours. After cooling, the ethanol is removed in a rotary evaporator, and the residue is taken up with a mixture of 50 ml of water and 50 ml of methylene chloride. The organic phase is shaken twice more with water, dried over magnesium sulfate and evaporated in a rotary evaporator. The residue is purified by column chromatography on silica gel using a mixture of ethyl acetate/methanol 4:1. 1.3 g of a colorless resin (26% of theory) which gradually crystallizes is obtained. Melting point 94°-95° C.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([O:8][CH2:9][O:10][CH3:11])=[CH:4][C:3]=1[O:12][CH2:13][O:14][CH3:15].CN(C)CCN(C)C.C([Li])CCC.[CH2:29]1[O:39][C:32]2([CH2:37][CH2:36][C:35](=[O:38])[CH2:34][CH2:33]2)[O:31][CH2:30]1.Cl>C1COCC1.C(OCC)(=O)C>[CH3:15][O:14][CH2:13][O:12][C:3]1[CH:4]=[C:5]([O:8][CH2:9][O:10][CH3:11])[CH:6]=[CH:7][C:2]=1[C:35]1([OH:38])[CH2:36][CH2:37][C:32]2([O:39][CH2:29][CH2:30][O:31]2)[CH2:33][CH2:34]1
Reactant: COCOc1ccc(Br)c(OCOC)c1
Reactant: O=C1CCC2(CC1)OCCO2
Agent: CN(C)CCN(C)C
Agent: Cl
Agent: [Li]CCCC
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: COCOc1ccc(C2(O)CCC3(CC2)OCCO3)c(OCOC)c1
Temperature: -78 °C
Reaction time: 1 h
Yield: 55.5 %

Procedure:
A round bottomed flask was loaded with 1-bromo-2,4-bis(methoxymethoxy)benzene (2.00 g) and THF (50 mL). N,N,N′,N′-Tetramethylethylene diamine (2.3 ml) was added and the solution was cooled to −78° C. n-Butyl lithium (9.5 ml, 1.6M in hexane) was added. The resulting solution was stirred for 1 hr at −78° C. and 1,4-cyclohexanedione monoethylene ketal (1.35 g) was added as a solution in THF (25 ml). The resulting solution was stirred at −78° C. for 1 hr and then allowed to warm to room temperature overnight. Hydrochloric acid (20 ml, 2M) was added and the reaction mixture stirred vigorously for 15 min. Ethyl acetate (100 ml) was added and the mixture poured into a separating funnel. The phases were separated and the aqueous phase was extracted with ethyl acetate (3×20 ml). The combined organic phases were washed with brine (20 ml), dried over anhydrous magnesium sulfate, filtered and concentrated affording an orange oil, which was purified by flash column chromatography (SiO2, ethyl acetate/petroleum ether, 45:55, v/v). The title product (1.42 g, 56%) was isolated as a colourless oil. m/z (ES+) 337 (M−H2O+H+); δH (CDCl3) 1.61-1.64(2H, m), 2.00-2.18(6H, m), 3.44(3H, s), 3.48(3H, s), 3.90-3.97(4H, m), 5.11(2H, s), 5.24(2H, s), 6.64(1H, dd), 6.82(1H, d), 7.20(1H, d).
Reaction SMILES: [Cl:1][CH2:2][C:3]([N:5]([CH3:15])[C:6]1[CH:14]=[CH:13][C:9]([C:10]([OH:12])=O)=[CH:8][CH:7]=1)=[O:4].[C:16]([O:20][C:21](=[O:30])[NH:22][CH:23]1[CH2:28][CH2:27][CH2:26][CH2:25][CH:24]1[NH2:29])([CH3:19])([CH3:18])[CH3:17].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C>[C:16]([O:20][C:21](=[O:30])[NH:22][CH:23]1[CH2:28][CH2:27][CH2:26][CH2:25][CH:24]1[NH:29][C:10](=[O:12])[C:9]1[CH:8]=[CH:7][C:6]([N:5]([C:3](=[O:4])[CH2:2][Cl:1])[CH3:15])=[CH:14][CH:13]=1)([CH3:19])([CH3:17])[CH3:18]
Reactant: CN(C(=O)CCl)c1ccc(C(=O)O)cc1
Reactant: CC(C)(C)OC(=O)NC1CCCCC1N
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: CN(C(=O)CCl)c1ccc(C(=O)NC2CCCCC2NC(=O)OC(C)(C)C)cc1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 94.4 %

Procedure:
Part A. 4-[(2-Chloro-acetyl)-methyl-amino]-benzoic acid (0.23 g, 1.0 mmol.) was stirred in DMF (2 mL) at RT under N2. (2-Amino-cyclohexyl)-carbamic acid tert-butyl ester (0.21 g, 1.0 mmol), HATU (0.57 g, 1.5 eq) and DIEA (0.5 mL, 2.9 eq) were added. The mixture was stirred at RT for 30 min. It was partitioned between EtOAc and water. The organic layer was washed with brine, dried over MgSO4, filtered, and concentrated to dryness to give (2-{4-[(2-chloro-acetyl)-methyl-amino]-benzoylamino}-cyclohexyl)-carbamic acid tert-butyl ester (0.40 g, yield: 95%).
Reaction SMILES: [H-].[Na+].[NH2:3][C@@H:4]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[C@H:7]([OH:14])[CH2:6][CH2:5]1.F[C:16]1[CH:17]=[CH:18][C:19]2[N:20]([C:22]([N:25]([CH:29]([CH3:31])[CH3:30])[CH:26]([CH3:28])[CH3:27])=[N:23][N:24]=2)[CH:21]=1>CN(C=O)C>[NH2:3][C@@H:4]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[C@H:7]([O:14][C:16]2[CH:17]=[CH:18][C:19]3[N:20]([C:22]([N:25]([CH:29]([CH3:31])[CH3:30])[CH:26]([CH3:27])[CH3:28])=[N:23][N:24]=3)[CH:21]=2)[CH2:6][CH2:5]1
Reactant: N[C@H]1CC[C@@H](O)c2ccccc21
Reactant: CC(C)N(c1nnc2ccc(F)cn12)C(C)C
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CC(C)N(c1nnc2ccc(O[C@@H]3CC[C@H](N)c4ccccc43)cn12)C(C)C
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 68.2 %

Procedure:
To a suspension of sodium hydride (60% in mineral oil, 136 mg, 3.39 mmol) in DMF (5 mL) was added Intermediate A (138 mg, 0.85 mmol) and the reaction mixture was stirred for 15 min at RT. A solution of Intermediate 103b (200 mg, 0.85 mmol) in DMF (3 mL) was added and the reaction mixture was heated at 60° C. for 1 h. The reaction mixture was quenched by careful addition of MeOH and then loaded onto an SCX cartridge. The cartridge was washed with MeOH and the product eluted with 2M NH3 in MeOH. The product containing fractions were concentrated in vacuo and the resultant residue was purified by FCC on silica, using a gradient of 0-10% [2M NH3 in MeOH] in DCM, to give the title compound (220 mg, 68%). LCMS (Method 4): Rt 2.07 min, m/z 380 [MH+].
Reaction SMILES: [OH:1][N:2]=[C:3]([NH2:14])[CH2:4][C:5]1[CH:10]=[CH:9][C:8]([N+:11]([O-:13])=[O:12])=[CH:7][CH:6]=1.CN(C)[C:17](=O)[CH3:18].C(Cl)(=O)C>O>[CH3:17][C:18]1[O:1][N:2]=[C:3]([CH2:4][C:5]2[CH:6]=[CH:7][C:8]([N+:11]([O-:13])=[O:12])=[CH:9][CH:10]=2)[N:14]=1
Reactant: NC(Cc1ccc([N+](=O)[O-])cc1)=NO
Reactant: CC(=O)N(C)C
Solvent: O
Solvent: CC(=O)Cl
Product: Cc1nc(Cc2ccc([N+](=O)[O-])cc2)no1
Temperature: 25 °C
Reaction time: 15 h
Yield: 37 %

Procedure:
To a mixture of N′-hydroxy-2-(4-nitrophenyl)ethanimidamide (2.38 g) and N,N-dimethylacetamide (30 mL) was added acetyl chloride (0.96 g) at room temperature and the mixture was stirred at room temperature for 15 hrs. Water was poured into the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate and concentrated. A mixture of obtained residue and xylene (100 mL) was heated under reflux for 24 hrs. The reaction mixture was concentrated and ethyl acetate was added to the obtained residue. The mixture was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated. The residue was subjected to silica gel column chromatography to give 5-methyl-3-(4-nitrobenzyl)-1,2,4-oxadiazole as orange crystals (1.00 g, yield 37%) from a fraction eluted with hexane-ethyl acetate (4:1-3:1, v/v). Recrystallization thereof from ethyl acetate-hexane gave orange prism crystals. melting point: 66-67° C.
Reaction SMILES: [NH2:1][CH2:2][C:3]([OH:5])=[O:4].[CH:6]1[C:18]2[CH:17]([CH2:19][O:20][C:21](Cl)=[O:22])[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[C:10]=2[CH:9]=[CH:8][CH:7]=1.O>O1CCOCC1>[NH:1]([C:21]([O:20][CH2:19][CH:17]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[C:10]2[C:18]1=[CH:6][CH:7]=[CH:8][CH:9]=2)=[O:22])[CH2:2][C:3]([OH:5])=[O:4]
Reactant: O=C(Cl)OCC1c2ccccc2-c2ccccc21
Reactant: NCC(=O)O
Solvent: C1COCCO1
Solvent: O
Product: O=C(O)CNC(=O)OCC1c2ccccc2-c2ccccc21

Procedure:
Glycine (Gly) (0.5 g, 6.66 mmole) was dissolved in 10% NaCO3 (14 ml) under stirring in a 50-ml flask. To the resulting solution, which had been put into an ice bath, 9-fluorenylmethoxycarbonyl chloride (Fmoc-Cl) (1.72 g, 6.66 mmol) in dioxane (12 ml) was gradually added. The reaction mixture was stirred at room temperature for 4 hours, and water (150 ml) was then added. The aqueous phase layer was separated from the reaction mixture and stripped with ether three times (75 ml×3). The stripped aqueous layer was acidified with 2N HCl aqueous solution to a pH value of 2, followed by extraction with ethyl acetate three times (75 ml×3). The organic phase layer was recovered and concentrated to obtain crude product of 1.70 g. The crude product was recrystallized in a mixed solvent of ethyl acetate hexane=1:2 (30 ml), and white solid denoted as Fmoc-Gly was obtained after filtration at a reduced pressure. Yield: 1.69 g (85%).
Reaction SMILES: C([Si]([O:8][C:9]1[CH:14]=[CH:13][C:12]([Cl:15])=[CH:11][C:10]=1[Cl:16])(C)C)(C)(C)C.C([Li])CCC.CN(C)[CH:24]=[O:25].Cl>O1CCCC1.O>[Cl:16][C:10]1[C:9]([OH:8])=[CH:14][CH:13]=[C:12]([Cl:15])[C:11]=1[CH:24]=[O:25]
Reactant: CC(C)(C)[Si](C)(C)Oc1ccc(Cl)cc1Cl
Reactant: CN(C)C=O
Agent: Cl
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: O
Product: O=Cc1c(Cl)ccc(O)c1Cl
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
To tert-butyl-(2,4-dichloro-phenoxy)-dimethyl-silane (113, 4.00 g, 0.0144 mol) in tetrahydrofuran (50.0 mL), under an atmosphere of nitrogen at −78° C., n-butyllithium (2.50 M in hexane, 6.06 mL) was added slowly. After 30 minutes, N,N-dimethylformamide (1.34 mL, 0.0173 mol) was added to the reaction. After 1 hour, the reaction was allowed to warm to room temperature. 1N HCl (40 mL) was added to the reaction. The reaction was poured into water and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated and purified by silica gel column chromatography eluting with 20% ethyl acetate in hexane to give a yellow solid (114, 2.0 g, 72.6%).
Reaction SMILES: [Cl:1][Si:2]([Cl:9])([Cl:8])[CH2:3][CH2:4][SiH:5]([Cl:7])[Cl:6].O1CCO[CH2:12][CH2:11]1>>[Cl:1][Si:2]([Cl:9])([Cl:8])[CH2:3][CH2:4][Si:5]([Cl:7])([Cl:6])[CH:11]=[CH2:12]
Reactant: Cl[SiH](Cl)CC[Si](Cl)(Cl)Cl
Reactant: C1COCCO1
Product: C=C[Si](Cl)(Cl)CC[Si](Cl)(Cl)Cl
Temperature: 0 °C

Procedure:
40.00 g (0.152 mol) 1,1,1,4,4-pentachloro-1,4-disilabutane was dissolved in 1000 ml 1,4-dioxane in a 2000 ml vessel. The solution was cooled down to 0° C. and acetylene was bubbled to solution until it was saturated. The solution thus obtained was slowly warmed up to room temperature. 1,4-dioxane was evaporated and obtained crude 1,1,1,4,4-pentachloro-1,4-disila-5-hexene was purified by distillation.