Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:16]=[CH:15][C:6]([CH2:7]N=C([O-])C(Cl)(Cl)Cl)=[CH:5][CH:4]=1.B(F)(F)F.C[CH2:22][O:23][CH2:24][CH3:25].[C:26]([O-:29])(O)=O.[Na+]>C(Cl)Cl>[CH3:22][O:23][C:24]1[CH:25]=[CH:5][C:4]([CH2:26][O:29][CH2:7][C:6]2[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:16][CH:15]=2)=[CH:3][CH:16]=1
Reactant: CCOCC
Reactant: COc1ccc(CN=C([O-])C(Cl)(Cl)Cl)cc1
Reactant: O=C([O-])O
Agent: FB(F)F
Agent: [Na+]
Solvent: ClCCl
Product: COc1ccc(COCc2ccc(OC)cc2)cc1
Reaction time: 0.17 h
Yield: 96 %

Procedure:
To a stirred 0° C. solution of the alcohol (755 mg, 1.22 mmol) and p-methoxybenzyltrichloroacetimidate (3.446 g, 12.2 mmol) in CH2Cl2 (120 mL) at 0° C. was added a 0.1 M solution of BF3.OEt2 in CH2Cl2 (50 μL). The resulting orange solution was stirred for 10 min, at which time TLC showed no remaining starting material. Saturated aqueous NaHCO3 (40 mL) was added, and after vigorous mixing the separated organic phase was dried over Na2SO4, filtered, and concentrated. The residue was chromatographed on silica gel (hexanes/ethyl acetate; 5:1) to give the p-methoxybenzyl ether (866 mg, 1.17 mmol, 96% yield) as a clear oil.
Reaction SMILES: C([N:8]1[C:16]2[C:11](=[CH:12][C:13](B3OC(C)(C)C(C)(C)O3)=[CH:14][CH:15]=2)[CH:10]=[N:9]1)(OC(C)(C)C)=O.Br[C:27]1[C:28]([Cl:33])=[N:29][CH:30]=[CH:31][CH:32]=1.C([O-])([O-])=O.[Na+].[Na+].O1CCOCC1>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CCOC(C)=O.O>[Cl:33][C:28]1[C:27]([C:13]2[CH:12]=[C:11]3[C:16](=[CH:15][CH:14]=2)[NH:8][N:9]=[CH:10]3)=[CH:32][CH:31]=[CH:30][N:29]=1
Reactant: CC(C)(C)OC(=O)n1ncc2cc(B3OC(C)(C)C(C)(C)O3)ccc21
Reactant: Clc1ncccc1Br
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O
Solvent: C1COCCO1
Solvent: CCOC(C)=O
Product: Clc1ncccc1-c1ccc2[nH]ncc2c1
Temperature: 100 °C
Reaction time: 12 h
Yield: 50 %

Procedure:
A single necked round bottom flask equipped with a magnetic stir bar was charged with 1-Boc-indazole-5-boronic acid pinacol ester (3.0 g, 8.7 mmol), 3-bromo-2-chloropyridine (2.0 g, 10.4 mmol), Pd(PPh3)4 (1 g, 0.86 mmol) and 2M aq. Na2CO3 (10 mL, 20 mmol) and 1,4-dioxane under nitrogen atmosphere. The reaction flask was fitted with a reflux condenser containing three-way stopcock equipped with argon filled balloon. The reaction contents were stirred and air was removed from the closed reaction system by vacuum and back filled with argon. Following three cycles of degassing, the reaction mixture was heated at 100° C. (oil-bath) under argon. Initial clear heterogeneous reaction mixture turned to clear biphasic off-yellow solution. After 12 h with no additional change in the proportion of the product, as analyzed by LC/MS, the reaction mixture was cooled to room temperature. Upon concentration of the reaction mixture, EtOAc/water (200 mL/100 mL) was transferred to the concentrate and stirred for 30 min. The organic layer was separated and the aqueous layer extracted with EtOAc (2×75 mL). MgSO4 and Celite® were added to combined organic layers, stirred for 20 min and the contents suction filtered. The filter cake was washed with EtOAc (100 mL) and the combined filtrates concentrated by rotary evaporator under vacuum. The crude concentrate was dissolved in 1% MeOH/CH2Cl2 and absorbed on silica gel (20g) by evaporating the solvent followed by drying. Subsequent purification by flash silica gel column purification of the dry powder (Combiflash® companion System® with RediSep® silica gel column 120 g, 30-70% EtOAc/hexanes eluting solvent) provided 5-(2-chloropyridin-3-yl)-1H-indazole (1.0 g, 50%) as a white crystalline solid after concentration of the desired product fractions. 1H NMR (DMSO-d6): δ 13.2 (s, 1H), 8.41 (dd, 1H, J=1.8 and 4.7 Hz), 8.13 (s, 1H), 7.90 (dd, 1H, J=1.7 and 4.7 Hz), 7.84 (s, 1H), 7.62 (d, 1H, J=8.8 Hz), 7.51 (dd, 1H, J=4.7 and 7.3 Hz), 7.42 (dd, 1H, J=1.4 and 8.5 Hz). LCMS: 95%, MS (m/e) 230 (MH+).
Reaction SMILES: [CH3:1][C:2]1[S:3][CH:4]=[CH:5][C:6]=1[CH3:7].[Br:8][C:9]1[CH:16]=[CH:15][C:12]([CH2:13]Br)=[CH:11][CH:10]=1>C1COCC1>[Br:8][C:9]1[CH:16]=[CH:15][C:12]([CH2:13][C:4]2[S:3][C:2]([CH3:1])=[C:6]([CH3:7])[CH:5]=2)=[CH:11][CH:10]=1
Reactant: Cc1ccsc1C
Reactant: BrCc1ccc(Br)cc1
Solvent: C1CCOC1
Product: Cc1cc(Cc2ccc(Br)cc2)sc1C
Yield: 60.5 %

Procedure:
The title compound was prepared according to the procedure in Example 5, step 1 using 2,3-dimethylthiophene (5.10 g, 45.5 mmol), 2.5M BuLi/hexanes (18.2 mL, 45.5 mmol) and 4-bromobenzyl bromide (11.4 g, 45.5 mmol) in THF. Purification on Biotage KP-Sil eluting with 100% pet ether gave 7.74 g (60%) of the title compound. 1H NMR: consistent.
Reaction SMILES: [C:1]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[S:11]([NH:14][CH2:15][C:16]#[N:17])(=[O:13])=[O:12])([O:3]C)=O.C(N(CC)CC)C.[CH3:25][O:26][CH2:27][CH2:28][O:29][CH2:30]Cl>ClCCl>[C:16]([C:15]1[N:14]([CH2:25][O:26][CH2:27][CH2:28][O:29][CH3:30])[S:11](=[O:13])(=[O:12])[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=2[C:1]=1[OH:3])#[N:17]
Reactant: COC(=O)c1ccccc1S(=O)(=O)NCC#N
Reactant: COCCOCCl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: COCCOCN1C(C#N)=C(O)c2ccccc2S1(=O)=O
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a solution of o-carbomethoxy-N-cyanomethylbenzenesulfonamide (6.25 g) in dichloromethane (50 ml) was added triethylamine (2.5 g) and then beta-methoxyethoxymethyl chloride (3.12 g) at 5°-10° C. After being stirred for 1 hour at room temperature, the mixture was washed with water, dried over sodium sulfate and concentrated. To the resulting oil was added toluene (33 ml) and then 28% sodium methoxide in methanol (4.6 ml) and stirring was continued for an additional 16 hours at room temperature. The mixture was extracted with water (50 ml) and the aqueous layer was acidified to pH 2 with 6N HCl and extracted with dichloromethane. The resulting organic layer was washed with water, dried over sodium sulfate and concentrated to a viscous oil, which was submitted to silica gel column chromatography (SiO2, 100 g) and eluted with a mixed solvent (CH2Cl2 :CH3OH 4:1) to give the title product as a viscous oil.
Reaction SMILES: [C:1]([C:3]1[CH:8]=[CH:7][C:6]([CH2:9][CH2:10][CH:11]([CH:13]2[CH2:15][CH2:14]2)O)=[CH:5][CH:4]=1)#[N:2].[Br-:16].[Li+].N1C(C)=CC(C)=CC=1C.O>CCOCC>[Br:16][CH2:15][CH2:14][CH:13]=[CH:11][CH2:10][CH2:9][C:6]1[CH:7]=[CH:8][C:3]([C:1]#[N:2])=[CH:4][CH:5]=1
Reactant: N#Cc1ccc(CCC(O)C2CC2)cc1
Reactant: [Br-]
Agent: [Li+]
Solvent: O
Solvent: CCOCC
Solvent: Cc1cc(C)nc(C)c1
Product: N#Cc1ccc(CCC=CCCBr)cc1
Temperature: -60 °C
Reaction time: 2 h
Yield: 97.2 %

Procedure:
to a solution of 9.8 g of 4-cyanophenylethyl cyclopropyl carbinol in 140 ml of ether was added 4.24 g of lithium bromide and 3 ml of 2,4,6-collidine. The mixture was cooled to -60° C. and 9.8 g of phosphrous tribromide was added over a five minute period. The reaction mixture was allowed to warm to 0° C., kept at that temperature for two hours and then allowed to warm to 18° C. Collidine (18 ml) was added, and after 15 minutes of stirring, the mixture was poured into 200 ml of water and 100 ml of ether. The ether extracts were washed with dilute aqueous sulfuric acid and water, dried over anhydrous magnesium sulfate and concentrated to a volume of 150 ml. Zinc bromide (11.6 g) was then added with cooling, and the mixture was stirred at room temperature for 29 hours. The ether solution was washed with water, dried and concentrated to give 12.5 g of 4-(6-bromohex-3-enyl)benzonitrile as a yellow oil.
Reaction SMILES: [C:1]1(=[N:7]O)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[C:9]1(=[O:16])N[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]1.C1(=NO)CCCCCCCCCCC1>>[C:9]1(=[O:16])[NH:7][CH2:1][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2][CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]1
Reactant: ON=C1CCCCC1
Reactant: O=C1CCCCCN1
Agent: ON=C1CCCCCCCCCCC1
Product: O=C1CCCCCCCCCCCN1

Procedure:
An oxime can be converted into an amide compound by Beckmann rearrangement reaction, particularly an oxime derived from a cyclic ketone can be converted into a lactam. For example, cyclohexanone oxime gives ε-caprolactam which is a starting material for Nylon 6 and cyclododecanone oxime gives laurolactam which is a starting material for Nylon 12.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([N:9]2[CH2:14][CH2:13][N:12]([C:15]3[CH:20]=[CH:19][C:18]([NH:21][C:22]([NH:24][NH2:25])=[S:23])=[CH:17][CH:16]=3)[CH2:11][CH2:10]2)=[CH:5][CH:4]=1.[C:26](O)(=O)C.C(=N)N.O(C(C)C)C(C)C>C(O)CCC>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([N:9]2[CH2:10][CH2:11][N:12]([C:15]3[CH:20]=[CH:19][C:18]([N:21]4[CH:26]=[N:25][N:24]=[C:22]4[SH:23])=[CH:17][CH:16]=3)[CH2:13][CH2:14]2)=[CH:5][CH:4]=1
Reactant: COc1ccc(N2CCN(c3ccc(NC(=S)NN)cc3)CC2)cc1
Reactant: CC(=O)O
Agent: N=CN
Solvent: CCCCO
Solvent: CC(C)OC(C)C
Product: COc1ccc(N2CCN(c3ccc(-n4cnnc4S)cc3)CC2)cc1

Procedure:
A mixture of 23 parts of N-{4-[4-(4-methoxyphenyl)-1-piperazinyl]phenyl}hydrazinecarbothioamide, 23 parts of methanimidamide acetate and 80 parts of 1-butanol is stirred and refluxed for 1 hour. The reaction mixture is cooled and poured onto water. 2,2'-oxybispropane is added. The precipitated product is filtered off, washed with water and with methanol and crystallized from 1-butanol, yielding 17.7 parts of 4-{4-[4-(4-methoxyphenyl)-1-piperazinyl]phenyl}-4H-1,2,4-triazole-3-thiol; mp. 231.9° C.
Reaction SMILES: [CH3:1][NH:2][C:3]1[S:4][C:5]2[CH:11]=[CH:10][C:9]([NH:12][CH2:13][C:14]3[CH:22]=[CH:21][C:17]([C:18]([OH:20])=O)=[CH:16][CH:15]=3)=[CH:8][C:6]=2[N:7]=1.[C:23]1([NH2:30])[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=1[NH2:29].F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.C(N(CC)CC)C>C(#N)C>[NH2:29][C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][C:23]=1[NH:30][C:18](=[O:20])[C:17]1[CH:16]=[CH:15][C:14]([CH2:13][NH:12][C:9]2[CH:10]=[CH:11][C:5]3[S:4][C:3]([NH:2][CH3:1])=[N:7][C:6]=3[CH:8]=2)=[CH:22][CH:21]=1
Reactant: Nc1ccccc1N
Reactant: CNc1nc2cc(NCc3ccc(C(=O)O)cc3)ccc2s1
Agent: CN(C)[P+](On1nnc2ccccc21)(N(C)C)N(C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(CC)CC
Solvent: CC#N
Product: CNc1nc2cc(NCc3ccc(C(=O)Nc4ccccc4N)cc3)ccc2s1
Reaction time: 8 h
Yield: 35 %

Procedure:
A mixture of acid 456c (729 mg; 2.54 mmol), 1,2-phenylenediamine (376 mg; 3.47 mmol; 1.36 eq) and BOP (1.43 g; 3.23 mmol; 1.27 eq) was dissolved in acetonitrile (15 mL), treated with triethylamine (3 mL) and stirred overnight. The reaction mixture was quenched with methanol, concentrated and purified by chromatographic column on silica gel (40% EtOAc in DCM) and the obtained material crystallized from DCM to give 358 mg (0.88 mmol; 35% yield) of pure compound 456. 1H-NMR (300 MHz; DMSO-d6) δ (ppm): 9.57 (s, 1H), 7.92 (d, J=7.9 Hz, 2H), 7.66 (d, J=4.8 Hz, 1H), 7.48 (d, J=8.3 Hz, 2H), 7.26 (d, J=8.3 Hz, 1H), 7.15 (d, J=7.9 Hz, 1H), 6.95 (t, J=7.5 Hz, 1H), 6.76 4.87 (bs, 2H), 6.58 (t, J=7.5 Hz, 1H), 6.54 (d, J=1.8 Hz, 1H), 6.13 (dd, J=1.8, 8.3 Hz, 1H), 6.27 (t, J=5.7 Hz, 1H), 4.87 (bs, 2H), 4.36 (d, J=5.7 Hz, 2H), 2.85 (d, J=4.8 Hz, 3H). LRMS: calc: 403.5008. found: 404.2 (M+NH) and 202.6 (M+2H)/2.
Reaction SMILES: [Cl:1]C[CH:3]1[C:12]2[C:7](=[CH:8][C:9]([O:15][CH3:16])=[C:10]([O:13][CH3:14])[CH:11]=2)[CH2:6][CH2:5][O:4]1.[NH:17]1[CH2:22][CH2:21][O:20][CH2:19][CH2:18]1>>[ClH:1].[CH3:16][O:15][C:9]1[CH:8]=[C:7]2[C:12](=[CH:11][C:10]=1[O:13][CH3:14])[CH:3]([N:17]1[CH2:22][CH2:21][O:20][CH2:19][CH2:18]1)[O:4][CH2:5][CH2:6]2
Reactant: COc1cc2c(cc1OC)C(CCl)OCC2
Reactant: C1COCCN1
Product: COc1cc2c(cc1OC)C(N1CCOCC1)OCC2
Product: Cl

Procedure:
A mixture of 5 g. of 1-chloromethyl-6,7-dimethoxyisochroman and 10 g of morpholine was heated at 150° C for 6 hours and, after cooling, the reaction mixture was concentrated under reduced pressure. The residue was diluted with 50 ml of water and extracted with chloroform. The extract was rinsed with water, dried and concentrated under reduced pressure. To the residue was added alcoholic hydrochloric acid and the resultant hydrochloride was crystallized by the addition of ethyl ether. The above procedure provided 5.1 g of 6,7-dimethoxy-1-morpholinoisochroman hydrochloride as colorless needles melting at 237°-239° C.
Reaction SMILES: [NH2:1][C:2]1[CH:18]=[CH:17][C:5]([O:6][C:7]2[CH:8]=[C:9]([CH:14]=[CH:15][CH:16]=2)[C:10]([O:12][CH3:13])=[O:11])=[CH:4][C:3]=1[OH:19].[N:20]#[C:21]Br>O1CCCC1.C(OCC)(=O)C>[NH2:20][C:21]1[O:19][C:3]2[CH:4]=[C:5]([O:6][C:7]3[CH:8]=[C:9]([CH:14]=[CH:15][CH:16]=3)[C:10]([O:12][CH3:13])=[O:11])[CH:17]=[CH:18][C:2]=2[N:1]=1
Reactant: N#CBr
Reactant: COC(=O)c1cccc(Oc2ccc(N)c(O)c2)c1
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: COC(=O)c1cccc(Oc2ccc3nc(N)oc3c2)c1
Temperature: 25 °C
Reaction time: 16 h
Yield: 94.7 %

Procedure:
To a solution of methyl 3-(4-amino-3-hydroxyphenoxy)benzoate (13.1 g, 50.5 mmol) in tetrahydrofuran (200 mL) was added cyanogen bromide (9.76 g, 92.1 mmol), and the mixture was stirred at room temperature for 16 hr. To the reaction mixture was added cyanogen bromide (1.78 g, 16.8 g), and the mixture was further stirred at room temperature for 3 days. The reaction mixture was diluted with ethyl acetate (300 mL), washed with saturated aqueous sodium hydrogencarbonate solution (150 mL×2) and saturated brine (150 mL), successively, and dried over anhydrous magnesium sulfate. The insoluble material was filtered off, and the filtrate was concentrated under reduced pressure to give the title compound (13.6 g, yield (total of 4 steps) 95%) as brown crystals.
Reaction SMILES: [C:1]([Cl:4])(=O)C.CO.[OH:7][C@H:8]1[CH2:12][NH:11][C@H:10]([C:13]([OH:15])=[O:14])[CH2:9]1>COC(C)(C)C>[ClH:4].[CH3:1][O:14][C:13](=[O:15])[C@@H:10]1[CH2:9][C@@H:8]([OH:7])[CH2:12][NH:11]1
Reactant: O=C(O)[C@@H]1C[C@@H](O)CN1
Reactant: CC(=O)Cl
Solvent: COC(C)(C)C
Solvent: CO
Product: COC(=O)[C@@H]1C[C@@H](O)CN1
Product: Cl
Temperature: 0 °C
Yield: 94.1 %

Procedure:
Acetyl chloride (249 mL, 3.47 mol) was added dropwise to methanol (2090 mL) with stirring and cooling to maintain the temperature below 30° C. After complete addition, stirring was continued for a further 60 min. before addition of trans-4-hydroxy-L-proline (325 g, 2.48 mol) as a solid. The reaction mixture was heated to reflux for 24 h, cooled to 0° C., and tert-butyl methyl ether (TBME, 5220 ML) was added slowly over 30 min. The precipitated solid was collected on a filter and washed with ice-cold TMBE (2×1 L). The product was dried at 40° C. overnight in a vacuum to yield 424 g of the desired ester.
Reaction SMILES: [N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[N:4]=[CH:3][C:2]=1[NH:11][C:12]1[O:13][C@:14]2([CH2:22][N:23]=1)[CH:19]1[CH2:20][CH2:21][N:16]([CH2:17][CH2:18]1)[CH2:15]2.ClC1C=C(C=CC=1)C(OO)=[O:29]>C1COCC1>[N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[N:4]=[CH:3][C:2]=1[NH:11][C:12]1[O:13][C@:14]2([CH2:22][N:23]=1)[CH:19]1[CH2:18][CH2:17][N+:16]([O-:29])([CH2:21][CH2:20]1)[CH2:15]2
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: c1ccc2nc(NC3=NC[C@@]4(CN5CCC4CC5)O3)cnc2c1
Solvent: C1CCOC1
Product: [O-][N+]12CCC(CC1)[C@]1(CN=C(Nc3cnc4ccccc4n3)O1)C2
Yield: 96.1 %

Procedure:
A solution of (R)—N-(quinoxalin-2-yl)-4H-1′-azaspiro[oxazole-5,3′-bicyclo[2.2.2]octan]-2-amine (190 mg, 0.614 mmol) and 3-chlorobenzoperoxoic acid (165 mg, 0.737 mmol) in 4 mL THF was stirred at room temperature for 2 h. The reaction was concentrated and the crude product was purified by flash chromatography on a 40 g silica gel cartridge with 1 to 30% [9:1 MeOH/NH4OH] in EtOAc. Pure fractions were pooled, concentrated, redissolved in CHCl3, and filtered through a 0.45 u filter to yield (S)-2-(quinoxalin-2-ylamino)-4H-1′-azaspiro[oxazole-5,3′-bicyclo[2.2.2]octane]1′-oxide (192 mg, 96% yield). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 9.89 (1H, br. s.), 8.58 (1H, s), 7.93 (1H, dd, J=8.31, 1.26 Hz), 7.70 (1H, dd, J=8.31, 1.01 Hz), 7.60 (1H, ddd, J=8.25, 6.99, 1.38 Hz), 7.50 (1H, ddd, J=8.25, 6.99, 1.38 Hz), 4.01 (1H, d, J=10.07 Hz), 3.84 (1H, d, J=9.82 Hz), 3.78-3.83 (1H, m), 3.64 (1H, dd, J=14.35, 2.27 Hz), 3.26-3.58 (4H, m), 2.50-2.65 (1H, m), 2.27 (1H, br. s.), 2.06-2.19 (1H, m, J=14.26, 10.42, 4.15, 4.15 Hz), 1.88-2.03 (2H, m). LCMS: RT=0.72 min, MH+=326.1 [ Waters Acquity SDS: 2 to 98% B, 1 min gradient; hold 98% B, 0.5 min; flow rate 0.8 mL/min; Solvent A: 100% H2O/0.05% TFA; Solvent B: 100% ACN/0.05% TFA]. LCMS: RT=1.15 min, MH-=324.2, MH+=326.2 [ Phenomenex LUNA C18 3 m (2.0×30 mm); 0 to 100% B, 2 min gradient; flow rate 1 mL/min; Solvent A: 5% MeOH: 95% water: 10 mM NH4OAc; Solvent B: 95% MeOH: 5% water: 10 mM NH4OAc; 220 nM].
Reaction SMILES: [NH:1]1[CH2:5][CH2:4][CH2:3][CH:2]1[CH2:6][OH:7].Br[CH2:9][C:10]#[N:11].CCN(CC)CC>C1COCC1>[OH:7][CH2:6][CH:2]1[CH2:3][CH2:4][CH2:5][N:1]1[CH2:9][C:10]#[N:11]
Reactant: N#CCBr
Reactant: OCC1CCCN1
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: N#CCN1CCCC1CO
Yield: 63.9 %

Procedure:
The method follows that of S3 using 2-pyrrolidinemethanol (24.27 g, 0.241 mol), BrCH2CN (31.81 g, 0.265 mol), Et3N (37 mL, 0.265 mol) and dry THF (150 mL). The product was obtained as a straw-coloured oil (21.60 g, 64%) after purification by flash chromatography using ether/CH3OH (19:1). δH (250 MHz; CDCl3); 1.5-2.0 (m, 5H, CH2CH2CH2, CH2CH2CH, OH), 2.7 (m, 1H), 2.85 (m, 1H), 3.05 (m, 1H), 3.45 (2×d, 1H, J=4 Hz and J=11 Hz, 1×CHCH2OH), 3.65 (2×d, 1H, J=4 Hz and 11 Hz, 1×CHCH2OH) and 3.75 (d, 2H, NCH2CN); δC(62.9 MHz; CDCl3); 23.37, 27.45, 40.96, 53.95, 62.43, 63.06 and 115.48(CN); IR υmax/cm−1; 3375 (NH2), 3300 (NH2), 3200 (OH), 2970-2800 (CH2, CH3), 1600, 1475, 1375, 1230 and 1060; FAB MS, m/z(M+H)+ 141.
Reaction SMILES: Cl[C:2]1[CH:7]=[C:6]([O:8][CH3:9])[N:5]=[C:4]([S:10][CH3:11])[N:3]=1.[C:12]1([S:18]([N:21]2[C:25]3=[N:26][CH:27]=[CH:28][CH:29]=[C:24]3[C:23](B3OC(C)(C)C(C)(C)O3)=[CH:22]2)(=[O:20])=[O:19])[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.C([O-])([O-])=O.[K+].[K+]>COCCOC>[CH3:9][O:8][C:6]1[N:5]=[C:4]([S:10][CH3:11])[N:3]=[C:2]([C:23]2[C:24]3[C:25](=[N:26][CH:27]=[CH:28][CH:29]=3)[N:21]([S:18]([C:12]3[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=3)(=[O:20])=[O:19])[CH:22]=2)[CH:7]=1
Reactant: COc1cc(Cl)nc(SC)n1
Reactant: CC1(C)OB(c2cn(S(=O)(=O)c3ccccc3)c3ncccc23)OC1(C)C
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: COCCOC
Product: COc1cc(-c2cn(S(=O)(=O)c3ccccc3)c3ncccc23)nc(SC)n1

Procedure:
A mixture of 4-chloro-6-methoxy-2-(methylthio)pyrimidine (10.2 g, 53.7 mmol), 1-(phenylsulfonyl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine (18.8 g, 48.8 mmol), 2M aqueous K2CO3 (48.8 mL, 98.0 mmol), 1,2-dimethoxyethane/dimethylfomamide (9/1, 200 mL) and
Reaction SMILES: [N+:1]([C:4]1[CH:14]=[C:8]2[C:9]([NH:11][C:12](=[O:13])[C:7]2=[CH:6][CH:5]=1)=[O:10])([O-:3])=[O:2].[C:15](=[O:18])([O-])[O-].[K+].[K+].Cl[CH2:22][C:23](=O)[CH3:24]>>[N+:1]([C:4]1[CH:14]=[C:8]2[C:9]([N:11]([CH2:22][C:23](=[C:15]=[O:18])[CH3:24])[C:12](=[O:13])[C:7]2=[CH:6][CH:5]=1)=[O:10])([O-:3])=[O:2]
Reactant: O=C([O-])[O-]
Reactant: O=C1NC(=O)c2cc([N+](=O)[O-])ccc21
Reactant: CC(=O)CCl
Agent: [K+]
Product: CC(=C=O)CN1C(=O)c2ccc([N+](=O)[O-])cc2C1=O
Temperature: 100 °C

Procedure:
After 4.0 g of 5-nitro-phthalimide were mixed with 5.74 g of potassium carbonate thoroughly, the resulting mixture was poured into a 25 mL flask followed by adding 6.6 mL of chloroacetone, and heated to 90-110° C. (a reflux condensing tube was needed to be equipped on the flask, the system was protected with argon). After the reaction was conducted for 3-4 hr, excess of chloroacetone was removed under a reduced pressure, into the residue was added a great deal of water, then filtrated with Buchner's filter. The resulting solid was washed twice with 10 ml of 10% NaOH, and 5-6 times with water respectively, dried in vacuum to obtain 5-nitro-N-(2-carbonyl-propyl)-phthalimide;
Reaction SMILES: N(C(OCC)=O)=NC(OCC)=O.[OH:13][C@@H:14]1[CH2:19][CH2:18][O:17][C:15]1=[O:16].[F:20][C:21]([F:30])([F:29])[C:22]1[CH:27]=[CH:26][C:25](O)=[CH:24][CH:23]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C1COCC1>[F:20][C:21]([F:30])([F:29])[C:22]1[CH:27]=[CH:26][C:25]([O:13][C@H:14]2[CH2:19][CH2:18][O:17][C:15]2=[O:16])=[CH:24][CH:23]=1
Reactant: O=C1OCC[C@H]1O
Reactant: Oc1ccc(C(F)(F)F)cc1
Agent: CCOC(=O)N=NC(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: O=C1OCC[C@@H]1Oc1ccc(C(F)(F)F)cc1
Temperature: 0 °C
Reaction time: 8 h

Procedure:
Diethyl azodicarboxylate (2.31 ml, 14.7 mmol) is slowly added to a solution of (R)-(+)-α-hydroxy-γ-butyrolactone (1 g, 9.8 mmol), 4-trifluoromethylphenol (1.58 g, 9.8 mmol) and triphenylphosphine (3.86 g, 14.7 mmol) in anhydrous THF (80 ml) cooled to 0° C. After stirring for 5 minutes at 0° C. and overnight at room temperature, the solvent is evaporated off and the triphenylphosphine oxide is then precipitated from ether and filtered off. The filtrate is then washed with water, dried over magnesium sulphate and evaporated. After purification by flash chromatography (3/1 heptane/EtOAc), the expected compound is obtained in the form of a white powder (1.14 g, 47%).
Reaction SMILES: [O:1]1[C@@:5]2([CH:10]3[CH2:11][CH2:12][N:7]([CH2:8][CH2:9]3)[CH2:6]2)[CH2:4][NH:3][C:2]1=[O:13].Br[C:15]1[CH:19]=[CH:18][O:17][CH:16]=1>>[O:17]1[CH:18]=[CH:19][C:15]([N:3]2[CH2:4][C@:5]3([CH:10]4[CH2:11][CH2:12][N:7]([CH2:8][CH2:9]4)[CH2:6]3)[O:1][C:2]2=[O:13])=[CH:16]1
Reactant: Brc1ccoc1
Reactant: O=C1NC[C@@]2(CN3CCC2CC3)O1
Product: O=C1O[C@]2(CN3CCC2CC3)CN1c1ccoc1

Procedure:
The title compound was prepared by a method analogous to that described in Preparation 3 from (S)-spiro[1-azabicyclo[2.2.2]octan-3,5′-oxazolidin]-2′-one and 3-bromofuran. The title compound (445 mg) was obtained as a pale-yellow solid, m/z 249 (MH+).
Reaction SMILES: [CH3:1][S:2][C:3]1[C:4]2[CH:11]=[C:10]([CH:12]=[N:13][CH3:14])[S:9][C:5]=2[N:6]=[CH:7][N:8]=1.COC1C=C(C=CC=1OC)CN=CC1SC2N=CN=CC=2C=1.CC1C=CC(S([CH:47]([C:50]2[CH:55]=[CH:54][C:53]([I:56])=[CH:52][CH:51]=2)[N+:48]#[C-:49])(=O)=O)=CC=1>>[I:56][C:53]1[CH:52]=[CH:51][C:50]([C:47]2[N:48]=[CH:49][N:13]([CH3:14])[C:12]=2[C:10]2[S:9][C:5]3[N:6]=[CH:7][N:8]=[C:3]([S:2][CH3:1])[C:4]=3[CH:11]=2)=[CH:55][CH:54]=1
Reactant: [C-]#[N+]C(c1ccc(I)cc1)S(=O)(=O)c1ccc(C)cc1
Reactant: CN=Cc1cc2c(SC)ncnc2s1
Agent: COc1ccc(CN=Cc2cc3cncnc3s2)cc1OC
Product: CSc1ncnc2sc(-c3c(-c4ccc(I)cc4)ncn3C)cc12

Procedure:
The title compound was prepared by a similar process to that described for Example 6 but using N-[4-(methylthio)thieno[2,3-d]pyrimidin-6-ylmethylidene]methanamine (Intermediate 16) in place of N-(3,4-Dimethoxybenzyl)-N-[thieno[2,3-d]pyrimidin-6-ylmethylidene]amine (intermediate 14) and using (4-Iodophenyl)(isocyano)methyl 4-methylphenyl sulfone (Intermediate 61) in place of PhTosMIC. Solid (0.8 g, 37%);
Reaction SMILES: O.[N+]([O-])([O-])=O.[Ag+:6].[C:7]([OH:30])(=[O:29])[CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH3:28]>C1(C)C=CC=CC=1>[C:7]([O-:30])(=[O:29])[CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH3:28].[Ag+:6]
Reactant: CCCCCCCCCCCCCCCCCCCCCC(=O)O
Agent: [Ag+]
Agent: O=[N+]([O-])[O-]
Solvent: O
Solvent: Cc1ccccc1
Product: CCCCCCCCCCCCCCCCCCCCCC(=O)[O-]
Reaction time: 0.5 h

Procedure:
The solution in which 54.4 g of behenic acid were dissolved in 1200 ml of toluene, was added with 2400 ml of water and the aqueous solution thus obtained was homogenized by means of a high-speed homogenizer. Ammoniacal silver nitrate solution of 400 ml containing 27.2 g of silver nitrate were dropped into said solution, taking 30 minutes with keeping the temperature of the reacting solution at 60° C. under agitation and the further agitation was applied thereto for another 30 minutes, and then the crystals thus produced were filtrated, washed, cleaned with methanol and dried up under reduced pressure in succession, and thus 65.0 g of silver behenate were obtained.