Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]1([CH:7]2[CH2:10][C:9](=[N:11]O)[CH2:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[H-].[Al+3].[Li+].[H-].[H-].[H-].O.[OH-].[Na+]>C1COCC1>[C:1]1([CH:7]2[CH2:8][CH:9]([NH2:11])[CH2:10]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: ON=C1CC(c2ccccc2)C1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: O
Solvent: C1CCOC1
Product: NC1CC(c2ccccc2)C1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 66 %

Procedure:
To a solution of 3-phenylcyclobutanone oxime (0.167 g, 1.04 mmol) in THF (5 ml) was added 1M lithium aluminum hydride in THF (2.18 ml, 2.18 mmol) dropwise over 3 minutes. The reaction was heated to reflux for 4 hours, then cooled to ambient temperature. Water (0.083 ml), 1M sodium hydroxide (0.083 ml), and additional water (0.248 ml) were added, and the reaction was stirred an additional 30 minutes. The reaction was filtered, and the solids were washed with THF. The filtrates were combined and concentrated to yield 101 mg of the title compound (66.2% yield).
Reaction SMILES: BrC1SC(N[C:8](=[O:10])C)=NN=1.[NH2:11][CH2:12][CH2:13][N:14]1[CH2:19][CH2:18][CH:17]([NH:20][C:21]2[N:25]([CH2:26][C:27]3[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=3)[C:24]3[CH:34]=[CH:35][CH:36]=[CH:37][C:23]=3[N:22]=2)[CH2:16][CH2:15]1.C(=O)([O-])[O-].[Na+].[Na+]>CN(C)C=O>[F:33][C:30]1[CH:31]=[CH:32][C:27]([CH2:26][N:25]2[C:24]3[CH:34]=[CH:35][CH:36]=[CH:37][C:23]=3[N:22]=[C:21]2[NH:20][CH:17]2[CH2:18][CH2:19][N:14]([CH2:13][CH2:12][NH:11][CH:8]=[O:10])[CH2:15][CH2:16]2)=[CH:28][CH:29]=1
Reactant: NCCN1CCC(Nc2nc3ccccc3n2Cc2ccc(F)cc2)CC1
Reactant: CC(=O)Nc1nnc(Br)s1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: O=CNCCN1CCC(Nc2nc3ccccc3n2Cc2ccc(F)cc2)CC1
Reaction time: 8 h

Procedure:
A mixture of 4.4 parts of N-(5-bromo-1,3,4-thiadiazol-2-yl)acetamide, 7.3 parts of N-[1-(2-aminoethyl)-4-piperidinyl]-1-[(4-fluorophenyl)methyl]-1H-benzimidazol-2-amine, 3.18 parts of sodium carbonate and 135 parts of N,N-dimethylformamide was stirred overnight at 80°-90° C. The reaction mixture was evaporated. The residue was purified by column chromatography over silica gel using a mixture of trichloromethane and methanol (90:10 by volume) as eluent. The pure fractions were collected and the eluent was evaporated. The residue was crystallized from a mixture of acetonitrile and 2,2'-oxybispropane, yielding 1.7 parts of N-[2-[4-[[1[(4fluorophenyl)methyl]-1H-benzimidazol-2-yl]amino]-1-piperidinyl] ethyl]formamide; mp. 153.2° C. (intermediate 156).
Reaction SMILES: [Cl:1][C:2]1[C:7]([Cl:8])=[C:6]([O:9][CH3:10])[CH:5]=[CH:4][C:3]=1[SH:11].[H-].[Na+].Br[CH:15]([CH2:19][CH3:20])[C:16]([OH:18])=[O:17].Cl>CN(C)C=O.O>[Cl:1][C:2]1[C:7]([Cl:8])=[C:6]([O:9][CH3:10])[CH:5]=[CH:4][C:3]=1[S:11][CH:15]([CH2:19][CH3:20])[C:16]([OH:18])=[O:17]
Reactant: COc1ccc(S)c(Cl)c1Cl
Reactant: CCC(Br)C(=O)O
Agent: Cl
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: CCC(Sc1ccc(OC)c(Cl)c1Cl)C(=O)O
Temperature: 25 °C
Reaction time: 1 h
Yield: 90.1 %

Procedure:
To a solution of 4.4 g of 2,3-dichloro-4-methoxythiophenol in 30 ml of anhydrous dimethylformamide is added 1.2 g of sodium hydride in small portions. The mixture is stirred at room temperature until gas evolution subsides (20-30 minutes) and 3.34 g of α-bromobutyric acid in 10 ml of dimethylformamide is added. After stirring at room temperature for 1 hour, the mixture is diluted with water and acidified with conc. hydrochloric acid. The white crystalline solid is filtered, air dried and recrystallized from acetone-hexane to give 5.32 g of α-(2,3-dichloro-4-methoxyphenylthio)butyric acid as granular crystals, mp 143°-145°.
Reaction SMILES: [NH2:1][CH2:2][CH2:3][CH2:4][C:5]1[CH:21]=[CH:20][CH:19]=[CH:18][C:6]=1[O:7][C:8]([CH3:17])([CH3:16])[C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10].C(N(C(C)C)CC)(C)C.Cl[C:32]1[O:33][C:34]2[CH:40]=[CH:39][CH:38]=[CH:37][C:35]=2[N:36]=1.C(OCC)(=O)C>O1CCCC1>[O:33]1[C:34]2[CH:40]=[CH:39][CH:38]=[CH:37][C:35]=2[N:36]=[C:32]1[NH:1][CH2:2][CH2:3][CH2:4][C:5]1[CH:21]=[CH:20][CH:19]=[CH:18][C:6]=1[O:7][C:8]([CH3:16])([CH3:17])[C:9]([O:11][C:12]([CH3:15])([CH3:13])[CH3:14])=[O:10]
Reactant: Clc1nc2ccccc2o1
Reactant: CC(C)(C)OC(=O)C(C)(C)Oc1ccccc1CCCN
Solvent: CCN(C(C)C)C(C)C
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: CC(C)(C)OC(=O)C(C)(C)Oc1ccccc1CCCNc1nc2ccccc2o1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
tert-Butyl 2-[2-(3-aminopropyl)phenoxy]-2-methylpropionate (1.44 g, 4.9 mmol) was dissolved in tetrahydrofuran (5 mL). Subsequently, diisopropylethylamine (762 mg, 5.9 mmol) and then 2-chlorobenzoxazole (904 mg, 5.9 mmol) were added thereto, and the mixture was stirred overnight at room temperature. Ethyl acetate was added thereto. The resultant mixture was sequentially washed with water and saturated brine, followed by drying over sodium sulfate, filtration, concentration under reduced pressure, and purification by silica gel column chromatography (n-hexane/ethyl acetate=6/1), whereby the target compound was obtained (2.03 g, q.).
Reaction SMILES: [CH3:1][C:2]1([CH2:8][O:9][C:10]2[CH:18]=[CH:17][C:13]([C:14](O)=[O:15])=[CH:12][CH:11]=2)[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3]1.S(Cl)(Cl)=O.C[N:24](C=O)C>>[CH3:1][C:2]1([CH2:8][O:9][C:10]2[CH:18]=[CH:17][C:13]([C:14]([NH2:24])=[O:15])=[CH:12][CH:11]=2)[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3]1
Reactant: CC1(COc2ccc(C(=O)O)cc2)CCCCC1
Reactant: CN(C)C=O
Solvent: O=S(Cl)Cl
Product: CC1(COc2ccc(C(N)=O)cc2)CCCCC1
Reaction time: 1.5 h
Yield: 94 %

Procedure:
Add a drop of anhydrous DMF to a mixture of 4-(1-methyl-cyclohexylmethoxy)-benzoic acid (prepared by following the procedure described in Chem. Pharm. Bull. 1982, 30, 3601-3616) (1 g, 4.03 mmol) and thionyl chloride (3.5 mL) at room temperature. Stir the mixture for 1.5 h and then remove the excess of thionyl chloride in vacuo. Take-up the crude acid chloride in anhydrous THF (10 mL) and add the resulting solution to cold concentrated NH4OH (50 mL). Stir for 2.5 h at room temperature and concentrate in vacuo. Collect the solid formed via filtration and dry in vacuo to obtain the desired intermediate (0.94 g, 94%). MS (ES+) m/z: 248 (M+H)+.
Reaction SMILES: [CH2:1]([N:8]1[CH2:13][CH2:12][C:11]([O:16][C:17](=[O:19])N)([C:14]#[CH:15])[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Br.C(O)(=[O:23])C>>[CH2:1]([N:8]1[CH2:13][CH2:12][C:11]2([O:16][C:17](=[O:19])[O:23][C:14]2=[CH2:15])[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: C#CC1(OC(N)=O)CCN(Cc2ccccc2)CC1
Reactant: CC(=O)O
Agent: Br
Product: C=C1OC(=O)OC12CCN(Cc1ccccc1)CC2
Yield: 59.3 %

Procedure:
5.16 g of 1-benzyl-4-carbamoyloxy-4-ethynylpiperidine are stirred in 30 ml of 30% by weight solution of hydrogen bromide in acetic acid at room temperature for 6 hours. After evaporating the solvent under reduced pressure and adding 50 ml of water to the residue the base is liberated by sodium hydrogen carbonate. The solid product obtained is filtered, washed to bromide-free with water, dried and recrystallized from n-hexane to give the title compound in 59.3% yield the physical characteristics of which are in agreement with those given in Example 1.
Reaction SMILES: Br[C:2]1[C:7](=[O:8])[N:6]([CH2:9][C:10]2[CH:15]=[CH:14][C:13]([C:16]3[C:17]([C:22]#[N:23])=[CH:18][CH:19]=[CH:20][CH:21]=3)=[CH:12][CH:11]=2)[C:5]([CH2:24][CH2:25][CH3:26])=[N:4][C:3]=1[CH2:27][CH3:28].[CH:29]([O:32][C:33]1[N:38]=[CH:37][C:36](B(O)O)=[CH:35][CH:34]=1)([CH3:31])[CH3:30].C(=O)([O-])[O-].[Cs+].[Cs+].O1CCOCC1>C(OCC)(=O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].ClCCl>[CH2:27]([C:3]1[N:4]=[C:5]([CH2:24][CH2:25][CH3:26])[N:6]([CH2:9][C:10]2[CH:15]=[CH:14][C:13]([C:16]3[C:17]([C:22]#[N:23])=[CH:18][CH:19]=[CH:20][CH:21]=3)=[CH:12][CH:11]=2)[C:7](=[O:8])[C:2]=1[C:36]1[CH:37]=[N:38][C:33]([O:32][CH:29]([CH3:31])[CH3:30])=[CH:34][CH:35]=1)[CH3:28]
Reactant: CCCc1nc(CC)c(Br)c(=O)n1Cc1ccc(-c2ccccc2C#N)cc1
Reactant: CC(C)Oc1ccc(B(O)O)cn1
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: O=C([O-])[O-]
Solvent: ClCCl
Solvent: CCOC(C)=O
Solvent: C1COCCO1
Product: CCCc1nc(CC)c(-c2ccc(OC(C)C)nc2)c(=O)n1Cc1ccc(-c2ccccc2C#N)cc1
Temperature: 100 °C
Reaction time: 12 h
Yield: 84.1 %

Procedure:
A mixture of 4′-[(5-bromo-4-ethyl-6-oxo-2-propylpyrimidin-1(6H)-yl)methyl]biphenyl-2-carbonitrile (0.6 g), (6-isopropoxypyridin-3-yl)boronic acid (0.43 g), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) dichloromethane adduct (0.05 g), 2 M aqueous cesium carbonate solution (5 mL) and 1,4-dioxane (5 mL) was stirred at 100° C. for 12 hr. The reaction mixture was diluted with ethyl acetate, washed with water and then with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the residue was purified by silica gel column chromatography to give the title compound as a colorless amorphous solid (0.57 g, 84%).
Reaction SMILES: [C:1]([OH:12])(=O)/[CH:2]=[CH:3]/[CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH3:10].[CH:13]([N:16]([CH:20]([CH3:22])[CH3:21])[CH2:17][CH2:18][NH2:19])([CH3:15])[CH3:14]>>[CH:13]([N:16]([CH:20]([CH3:22])[CH3:21])[CH2:17][CH2:18][NH:19][C:1](=[O:12])/[CH:2]=[CH:3]/[CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH3:10])([CH3:15])[CH3:14]
Reactant: CCCCCCC/C=C/C(=O)O
Reactant: CC(C)N(CCN)C(C)C
Product: CCCCCCC/C=C/C(=O)NCCN(C(C)C)C(C)C

Procedure:
The same operation as in Example 1-1 or 1-2 was carried out using trans-2-decenoic acid and N,N-diisopropylethane-1,2-diamine as starting materials to give the aimed compound.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:12])[C:4]1[CH:9]=[CH:8][C:7]([F:10])=[CH:6][C:5]=1[CH3:11].C1C(=O)N([Br:20])C(=O)C1>C(Cl)(Cl)(Cl)Cl.C(OOC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1>[CH3:1][O:2][C:3](=[O:12])[C:4]1[CH:9]=[CH:8][C:7]([F:10])=[CH:6][C:5]=1[CH2:11][Br:20]
Reactant: O=C1CCC(=O)N1Br
Reactant: COC(=O)c1ccc(F)cc1C
Agent: O=C(OOC(=O)c1ccccc1)c1ccccc1
Solvent: ClC(Cl)(Cl)Cl
Product: COC(=O)c1ccc(F)cc1CBr
Yield: 91.1 %

Procedure:
A mixture of 4-fluoro-2-methyl-benzoic acid methyl ester (12.7 g, 75.5 mmol), NBS (13.4 g, 75.5 mmol), and di-benzoyl peroxide (BPO) (0.85 g, 3.5 mmol) in CCl4 (200 mL) was heated to reflux for 3 hours until all starting material was consumed. After vacuum filtration, the filtrate concentrated in vacuo to give a crude product (17 g, yield 91%), which was used in the next step reaction without further purification.
Reaction SMILES: [CH2:1]([N:4]([CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][C:11]1[CH:12]=[C:13]2[C:17](=[CH:18][CH:19]=1)[NH:16][CH2:15][CH2:14]2)[CH3:5])[CH:2]=[CH2:3].[Cl:20][C:21]1[CH:26]=[CH:25][C:24](I)=[CH:23][CH:22]=1>>[CH2:1]([N:4]([CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][C:11]1[CH:12]=[C:13]2[C:17](=[CH:18][CH:19]=1)[N:16]([C:24]1[CH:25]=[CH:26][C:21]([Cl:20])=[CH:22][CH:23]=1)[CH:15]=[CH:14]2)[CH3:5])[CH:2]=[CH2:3]
Reactant: C=CCN(C)CCCCCc1ccc2c(c1)CCN2
Reactant: Clc1ccc(I)cc1
Product: C=CCN(C)CCCCCc1ccc2c(ccn2-c2ccc(Cl)cc2)c1

Procedure:
In analogy to example 12.7, Allyl-[5-(2,3-dihydro-1H-indol-5-yl)-pentyl]-methyl-amine and 1-chloro-4-iodobenzene were converted to yield Allyl-{5-[1-(4-chloro-phenyl)-1H-indol-5-yl]-pentyl}-methyl-amine as light brown semisolid, MS: 367(MH+, 1Cl).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[C:7]([N+:9]([O-:11])=[O:10])[CH:6]=[CH:5][C:4]=1[O-:12].[K+].OP([O-])(O)=O.[Na+].C(#N)C.[O:23]1[C:25]2([CH2:30][CH2:29][S:28][CH2:27][CH2:26]2)[CH2:24]1>O>[CH3:1][O:2][C:3]1[CH:8]=[C:7]([N+:9]([O-:11])=[O:10])[CH:6]=[CH:5][C:4]=1[O:12][CH2:24][C:25]1([OH:23])[CH2:30][CH2:29][S:28][CH2:27][CH2:26]1
Reactant: C1CC2(CCS1)CO2
Reactant: COc1cc([N+](=O)[O-])ccc1[O-]
Agent: O=P([O-])(O)O
Agent: [K+]
Agent: [Na+]
Solvent: CC#N
Solvent: O
Product: COc1cc([N+](=O)[O-])ccc1OCC1(O)CCSCC1
Temperature: 150 °C
Yield: 41.9 %

Procedure:
A mixture of potassium 2-methoxy-4-nitrophenolate (3.02 g, 14.59 mmol), sodium phosphate monobasic, monohydrate (2.014 g, 14.59 mmol), acetonitrile (12 mL), water (3 mL) and 1-oxa-6-thiaspiro[2.5]octane (1.90 g, 14.59 mmol), prepared as described in patent WO 2005/063729 A1, was heated at 150° C. for 3.5 h in a microwave reactor. After cooling to RT, acetonitrile was mostly removed under vacuum, the remaining material was partitioned between EtOAc (100 mL) and H2O (15 mL). The aqueous layer was extracted with EtOAc (2×15 mL) and the combined organic layers were dried (Na2SO4) and evaporated. The residue was purified by flash chromatography (silica gel, hexanes:EtOAc, 100:0 to 60:40) to afford 1.83 g (42%) of the title compound as a yellow solid: 1H NMR (500 MHz, DMSO-d6) δ 7.87 (dd, J=9.07, 2.47 Hz, 1H), 7.73 (d, J=2.75 Hz, 1H), 7.18 (d, J=9.35 Hz, 1H), 4.75 (s, 1H), 3.89 (s, 3H), 3.85 (s, 2H), 2.87-2.97 (m, 2H), 2.49 (s, 1H), 2.38 (d, J=13.20 Hz, 2H), 1.82-1.89 (m, 2H), 1.72-1.82 (m, 2H). HPLC retention time: 2.985 min; LCMS (ES): m/z 282 [M+H]+.
Reaction SMILES: [CH3:1][O:2][C:3]1[C:19]([CH2:20][OH:21])=[CH:18][C:6]2[N:7]([CH2:15][O:16][CH3:17])[C:8]3[N:14]=[CH:13][CH:12]=[N:11][C:9]=3[O:10][C:5]=2[CH:4]=1>ClCCCl.[O-2].[O-2].[Mn+4]>[CH3:1][O:2][C:3]1[C:19]([CH:20]=[O:21])=[CH:18][C:6]2[N:7]([CH2:15][O:16][CH3:17])[C:8]3[N:14]=[CH:13][CH:12]=[N:11][C:9]=3[O:10][C:5]=2[CH:4]=1
Reactant: COCN1c2cc(CO)c(OC)cc2Oc2nccnc21
Agent: [Mn+4]
Agent: [O-2]
Solvent: ClCCCl
Product: COCN1c2cc(C=O)c(OC)cc2Oc2nccnc21
Yield: 64.6 %

Procedure:
To a solution of 1.17 g of 7-methoxy-10-(methoxymethyl)-10H-pyrazino[2,3-b][1,4]-benzoxazine-8-methanol in 50 ml of 1,2-dichloroethane was added 3.2 g of manganese dioxide and the resulting mixture was heated under reflux for 2 hours. The reaction mixture was filtered through celite. After distilling off the solvent under reduced pressure, 0.75 g of the title compound was obtained as a brown solid.
Reaction SMILES: [CH:1]1([CH2:4][O:5][C:6]2[CH:14]=[CH:13][C:9]3[O:10][CH2:11][O:12][C:8]=3[C:7]=2[C:15]2[CH:20]=[CH:19][N:18]=[C:17]3[C:21]([C:33]([OH:35])=O)=[C:22]([CH3:32])[N:23]([CH2:24][O:25][CH2:26][CH2:27][Si:28]([CH3:31])([CH3:30])[CH3:29])[C:16]=23)[CH2:3][CH2:2]1.C(N(CC)CC)C.C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl.Cl.[NH2:58][CH:59]1[CH2:64][CH2:63][N:62]([C:65]([O:67][C:68]([CH3:71])([CH3:70])[CH3:69])=[O:66])[CH2:61][CH2:60]1>ClCCl>[CH:1]1([CH2:4][O:5][C:6]2[CH:14]=[CH:13][C:9]3[O:10][CH2:11][O:12][C:8]=3[C:7]=2[C:15]2[CH:20]=[CH:19][N:18]=[C:17]3[C:21]([C:33]([NH:58][CH:59]4[CH2:60][CH2:61][N:62]([C:65]([O:67][C:68]([CH3:71])([CH3:70])[CH3:69])=[O:66])[CH2:63][CH2:64]4)=[O:35])=[C:22]([CH3:32])[N:23]([CH2:24][O:25][CH2:26][CH2:27][Si:28]([CH3:31])([CH3:30])[CH3:29])[C:16]=23)[CH2:3][CH2:2]1
Reactant: CC(C)(C)OC(=O)N1CCC(N)CC1
Reactant: Cc1c(C(=O)O)c2nccc(-c3c(OCC4CC4)ccc4c3OCO4)c2n1COCC[Si](C)(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CCN(CC)CC
Solvent: ClCCl
Solvent: ClCCCl
Product: Cc1c(C(=O)NC2CCN(C(=O)OC(C)(C)C)CC2)c2nccc(-c3c(OCC4CC4)ccc4c3OCO4)c2n1COCC[Si](C)(C)C
Temperature: 25 °C
Reaction time: 1 h

Procedure:
7-[5-(Cyclopropylmethoxy)-1,3-benzodioxol-4-yl]-2-methyl-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[3,2-b]pyridine-3-carboxylic acid from example D.c1 (3.98 g; 8.0 mmol), triethylamine (2.43 g; 24.0 mmol) and HOBt (1.08 g; 8.0 mmol) is stirred in dry dichloromethane (40 mL) for 30 min, before addition of EDC (1.84 g; 9.6 mmol). The reaction mixture is stirred for one hour at ambient temperature. After addition of tert-butyl 4-amino-piperidine-1-carboxylate hydrochloride (2.27 g; 9.6 mmol) the reaction mixture is stirred at ambient temperature until the starting material is consumed according to LC-MS and chromatographed on silica gel (ethylacetate/cyclohexane—1:1) to yield the title compound as colorless foam.
Reaction SMILES: [Cl:1][C:2]1[CH:20]=[CH:19][C:5]2[N:6]=[C:7]([N:9]3[CH2:14][CH2:13][CH:12]([NH:15][CH:16]([CH3:18])[CH3:17])[CH2:11][CH2:10]3)[S:8][C:4]=2[CH:3]=1.[CH3:21][O:22][C:23](=[O:33])[CH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[C:27]([CH2:31]Br)[CH:26]=1.C(=O)([O-])[O-].[K+].[K+].CN(C)C=O>O>[CH3:21][O:22][C:23](=[O:33])[CH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[C:27]([CH2:31][N:15]([CH:12]2[CH2:11][CH2:10][N:9]([C:7]3[S:8][C:4]4[CH:3]=[C:2]([Cl:1])[CH:20]=[CH:19][C:5]=4[N:6]=3)[CH2:14][CH2:13]2)[CH:16]([CH3:18])[CH3:17])[CH:26]=1
Reactant: COC(=O)Cc1cccc(CBr)c1
Reactant: CC(C)NC1CCN(c2nc3ccc(Cl)cc3s2)CC1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: COC(=O)Cc1cccc(CN(C(C)C)C2CCN(c3nc4ccc(Cl)cc4s3)CC2)c1
Temperature: 80 °C
Reaction time: 8 h
Yield: 37.2 %

Procedure:
A mixture of [1-(6-chlorobenzothiazole-2-yl)piperidine-4-yl]isopropylamine (159 mg), (3-bromomethylphenyl)acetic acid methyl ester (138 mg), potassium carbonate (107 mg) and dimethylformamide (2 mL) was stirred at 80° C. for 8 hours. To the reaction solution was added water and extracted with ethyl acetate. The organic layer was washed with water and brine, and dried over magnesium sulphate. The solvent was evaporated under reduced pressure and the residue was purified by column chromatograph on silica gel to give the title compound (90 mg). Yield: 37%.
Reaction SMILES: [CH3:1][CH:2]1[CH:7]=[C:6]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([C:14]([F:17])([F:16])[F:15])[CH:9]=2)O[C:4](=[O:18])[CH2:3]1.C(N(CC)CC)C.[NH:26]([C:28]([O:30][CH2:31][CH3:32])=[O:29])[NH2:27]>ClCCl>[CH2:31]([O:30][C:28]([NH:26][N:27]1[C:6]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([C:14]([F:15])([F:16])[F:17])[CH:9]=2)=[CH:7][CH:2]([CH3:1])[CH2:3][C:4]1=[O:18])=[O:29])[CH3:32]
Reactant: CC1C=C(c2cccc(C(F)(F)F)c2)OC(=O)C1
Reactant: CCOC(=O)NN
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CCOC(=O)NN1C(=O)CC(C)C=C1c1cccc(C(F)(F)F)c1

Procedure:
A solution of 4 g (16 mmol) of 3,4-dihydro-4-methyl-6-(3'-trifluoromethylphenyl)-2-(1H)-pyrone in 100 ml dichloromethane is treated with 5.6 ml of triethylamine and 7.31 g (70 mmol) of ethyl hydrazinoformate, and the mixture is refluxed for 8 hours. After cooling, the reaction solution is washed alternately with distilled H2O, dilute HCl and distilled H2O, dried over Na2SO4 and concentrated on a rotary evaporator. The oil which remains is taken up in 150 ml of toluene, the solution is treated with a spatula-tip full of PTSA and the mixture is refluxed on a water separator until the reaction is complete. For working-up, the reaction solution is washed first with dilute K2CO3 solution and then with distilled H2O and subsequently dried over Na2SO4. The oil obtained after the solvent has been evaporated in vacuo is purified by column chromatography on silica gel (eluent: toluene:acetone=95:5).
Reaction SMILES: [N:1]([CH2:4][CH2:5][C:6]#[C:7][C:8]1[CH:9]=[C:10]([CH:29]=[CH:30][CH:31]=1)[O:11][Si:12]([C:25]([CH3:28])([CH3:27])[CH3:26])([C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)=[N+]=[N-]>[Pd].CO>[Si:12]([O:11][C:10]1[CH:9]=[C:8]([CH2:7][CH2:6][CH2:5][CH2:4][NH2:1])[CH:31]=[CH:30][CH:29]=1)([C:25]([CH3:26])([CH3:27])[CH3:28])([C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1
Reactant: CC(C)(C)[Si](Oc1cccc(C#CCCN=[N+]=[N-])c1)(c1ccccc1)c1ccccc1
Agent: [Pd]
Solvent: CO
Product: CC(C)(C)[Si](Oc1cccc(CCCCN)c1)(c1ccccc1)c1ccccc1

Procedure:
A solution of azide from Step C (57.0 mg, 0.134 mmol) and 10% palladium on carbon (57.0 mg) in methanol (5 mL) was placed under a hydrogen atmosphere (1 atm) for 16 hours. The reaction mixture was filtered through a Celite pad and concentrated in vacuo to provide the title compound.
Reaction SMILES: C([C:4]1[CH:12]=[N:11][CH:10]=[CH:9][C:5]=1[C:6]([OH:8])=[O:7])(=O)N.C([O-])(=O)C.C([O-])(=O)C.C([O-])(=O)C.C([O-])(=O)C.[Pb+4].C[N:31](C)[CH:32]=[O:33]>>[C:5]12[C:4](=[CH:12][N:11]=[CH:10][CH:9]=1)[NH:31][C:32](=[O:33])[O:8][C:6]2=[O:7]
Reactant: CN(C)C=O
Reactant: NC(=O)c1cnccc1C(=O)O
Agent: CC(=O)[O-]
Agent: [Pb+4]
Product: O=c1[nH]c2cnccc2c(=O)o1
Reaction time: 0.17 h

Procedure:
A 50 ml. flask was charged with 0.94 g. 3-carbamylisonicotinic acid suspended in 8 ml. dimethylformamide. A 2.5 g. portion of lead tetra-acetate was added to the suspension, and the reaction mixture was stirred at 20° for 10 minutes. The reaction mixture was then warmed to 45° and stirred for 10 minutes. The cooled mixture was poured onto 30 grams crushed ice and the pale yellow solids were collected by filtration and dried in vacuo. Extensive decomposition of the product occurred upon attempted recrystallization from organic solvents. The final yield of 4-azaisatoic anhydride amounted to 0.65 g., melting point 218°, with decomposition, and represented 70 percent of theory. The structure was identified by elemental analysis, infrared spectroscopy and mass spectrometry.
Reaction SMILES: [C:1]([CH2:9][CH2:10][CH2:11][C:12]([OH:14])=[O:13])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:15]O>S(=O)(=O)(O)O>[C:1]([CH2:9][CH2:10][CH2:11][C:12]([O:14][CH3:15])=[O:13])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=C(O)CCCC(=O)c1ccccc1
Reactant: CO
Agent: O=S(=O)(O)O
Product: COC(=O)CCCC(=O)c1ccccc1

Procedure:
Precursors suitable for preparation of fullerene derivatives were prepared. First, methyl 4-benzoylbutyrate was prepared as follows. A solution of 4-benzoylbutyric acid (11.9 g, 0.0619 mol) in MeOH (250 ml) with a catalytic amount of sulfuric acid (96%, 6 drops) was refluxed for 5 hours. Solvent was removed and 50 ml water was added. The reaction product was extracted with dichloromethane to provide an organic layer. The organic layer was separated, dried over MgSO4 and passed through a plug of silica, which was rinsed with 2% acetone in dichloromethane. Solvent was removed to afford the methyl ester as light-yellowish oil (12.57 g, 99%).
Reaction SMILES: [C:1]1(=[O:9])[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[CH2:10]([Mg]Br)[CH3:11].C(=O)(O)[O-].[Na+]>O1CCCC1>[CH2:10]([C:1]1([OH:9])[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1)[CH3:11]
Reactant: CC[Mg]Br
Reactant: O=C1CCCCCCC1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: C1CCOC1
Product: CCC1(O)CCCCCCC1
Reaction time: 8 h
Yield: 31.6 %

Procedure:
To a 1000-mL 3-necked round bottom flask equipped with a 500-mL pressure equalizing addition funnel, a nitrogen inlet with thermocouple and an overhead stirrer was added 100 g (0.79 mol) of cyclooctanone dissolved in 250 mL of dry tetrahydrofuran. The addition funnel was charged with 290 mL (0.869 mol, 10% excess) of ethyl magnesium bromide (2.0M solution in ether) which was then added to the cooled ketone over 2 hours. Stirring was continued at room temperature overnight followed by 8 hours at reflux. Excess Grignard reagent was discharged by the cautious addition of 100 mL of saturated sodium bicarbonate solution. The resulting suspension was filtered through a bed of Celite, the filtrate diluted with 500 mL of ether and the combined organics washed several times with saturated sodium bicarbonate, once with brine and then dried for 1 hr over anhydrous magnesium sulfate. Filtration and removal of the solvent at reduced pressure resulted in a light-colored oil which was distilled twice from Na2CO3 through a base-washed 15 cm Vigreux (bp 65° C.@ 1 mmHg) to yield 39 g (32%) of the title alcohol as a clear, colorless oil.