Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([C:12]([NH:14][CH2:15][CH2:16][C:17]3[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][CH:18]=3)=O)[CH2:11][CH2:10][CH2:9]2)=[CH:4][CH:3]=1.P(Cl)(Cl)(Cl)=O>C1(C)C=CC=CC=1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([C:12]3[C:22]4[C:17](=[CH:18][CH:19]=[C:20]([O:23][CH3:24])[CH:21]=4)[CH2:16][CH2:15][N:14]=3)[CH2:11][CH2:10][CH2:9]2)=[CH:4][CH:3]=1
Reactant: COc1ccc(CCNC(=O)C2(c3ccc(Cl)cc3)CCC2)cc1
Solvent: Cc1ccccc1
Solvent: O=P(Cl)(Cl)Cl
Product: COc1ccc2c(c1)C(C1(c3ccc(Cl)cc3)CCC1)=NCC2
Temperature: 25 °C

Procedure:
1-(4-Chlorophenyl)-N-[2-(4-methoxyphenyl)ethyl]cyclobutanecarboxamide (10.58 g, 30.8 mmol) was treated with toluene (100 mL). Phosphoryl trichloride (4.72 g, 30.8 mmol) was added and the reaction mixture was heated under reflux for 8 h. After cooling to room temperature the reaction mixture was concentrated in vacuo and then slowly poured in ice water. Ethyl acetate was added and the organic layer was washed with water (2×), dried (MgSO4) and concentrated in vacuo to give an orange oil. Yield: 10.25 g.
Reaction SMILES: FC1C=[C:4](C=C(F)C=1)[CH2:5][N:6]1C=CN=C1S.[CH3:16][O:17][C:18]1[CH:23]=[CH:22][C:21]([N:24]2[CH:28]=[CH:27][N:26]=[C:25]2[SH:29])=[CH:20][CH:19]=1>>[NH2:6][CH2:5][CH2:4][S:29][C:25]1[N:24]([C:21]2[CH:22]=[CH:23][C:18]([O:17][CH3:16])=[CH:19][CH:20]=2)[CH:28]=[CH:27][N:26]=1
Reactant: Fc1cc(F)cc(Cn2ccnc2S)c1
Reactant: COc1ccc(-n2ccnc2S)cc1
Product: COc1ccc(-n2ccnc2SCCN)cc1

Procedure:
The Example 1 procedure wherein 1-(3,5-difluorobenzyl)-2-mercaptoimidazole is replaced by 1-(4-methoxyphenyl)-2-mercaptoimidazole yields 2-(2-aminoethylthio)-1-(4-methoxyphenyl)imidazole.
Reaction SMILES: [CH2:1]=[C:2]1[CH2:21][CH:5]2[C:6](=[O:20])[N:7]([C:9]3[CH:14]=[CH:13][C:12]([O:15][C:16]([F:19])([F:18])[F:17])=[CH:11][CH:10]=3)[CH2:8][CH:4]2[CH2:3]1.C1C=C(Cl)C=C(C(OO)=[O:30])C=1.C([O-])(O)=O.[Na+]>ClCCl>[F:18][C:16]([F:17])([F:19])[O:15][C:12]1[CH:11]=[CH:10][C:9]([N:7]2[CH2:8][CH:4]3[CH2:3][C:2]4([CH2:21][CH:5]3[C:6]2=[O:20])[CH2:1][O:30]4)=[CH:14][CH:13]=1
Reactant: C=C1CC2CN(c3ccc(OC(F)(F)F)cc3)C(=O)C2C1
Reactant: O=C(OO)c1cccc(Cl)c1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Product: O=C1C2CC3(CO3)CC2CN1c1ccc(OC(F)(F)F)cc1
Temperature: 25 °C
Reaction time: 6 h

Procedure:
To a solution of 5-Methylene-2-(4-trifluoromethoxy-phenyl)-hexahydro-cyclopenta[c]pyrrol-1-one (0.78 g, 2.6 mmol) in dichloromethane (20 mL) was added mCPBA (0.9 g, 5.2 mmol) at 0° C., and the mixture was stirred for 6 h at room temperature. Saturated solution of NaHCO3 (30 mL) was added and stirred for another 0.5 h. The mixture was extracted with dichloromethane (2×30 mL), washed with brine (60 mL) and dried over Na2SO4. The solvent was removed and the residue was purified by prep-TLC with petroleum ether/ethyl acetate (1:1) to yield rac-(3aR,5S,6aS)-2-[4-(trifluoromethoxy)phenyl]hexahydro-1H-spiro[cyclopenta[c]pyrrole-5,2′-oxiran]-1-one
Reaction SMILES: [NH2:1][C:2]1[C:7]([C:8]([NH2:10])=[O:9])=[C:6]([N:11]2[CH2:16][CH2:15][CH:14]([C:17]3[N:18]([CH3:33])[CH:19]=[C:20]([C:22]4[CH:27]=[CH:26][C:25]([F:28])=[C:24]([C:29]([F:32])([F:31])[F:30])[CH:23]=4)[N:21]=3)[CH2:13][CH2:12]2)[N:5]=[CH:4][N:3]=1.NC1C(C#N)=C(N2CCC(C3N(C[CH2:66][NH:67][CH2:68][CH:69]4[CH2:71][CH2:70]4)C=C(C4C=CC(F)=C(C(F)(F)F)C=4)N=3)CC2)N=CN=1>>[NH2:1][C:2]1[C:7]([C:8]([NH2:10])=[O:9])=[C:6]([N:11]2[CH2:16][CH2:15][CH:14]([C:17]3[N:18]([CH2:33][CH2:66][NH:67][CH2:68][CH:69]4[CH2:71][CH2:70]4)[CH:19]=[C:20]([C:22]4[CH:27]=[CH:26][C:25]([F:28])=[C:24]([C:29]([F:32])([F:31])[F:30])[CH:23]=4)[N:21]=3)[CH2:13][CH2:12]2)[N:5]=[CH:4][N:3]=1
Reactant: N#Cc1c(N)ncnc1N1CCC(c2nc(-c3ccc(F)c(C(F)(F)F)c3)cn2CCNCC2CC2)CC1
Reactant: Cn1cc(-c2ccc(F)c(C(F)(F)F)c2)nc1C1CCN(c2ncnc(N)c2C(N)=O)CC1
Product: NC(=O)c1c(N)ncnc1N1CCC(c2nc(-c3ccc(F)c(C(F)(F)F)c3)cn2CCNCC2CC2)CC1

Procedure:
The title compound was prepared in an analogous manner as 4-Amino-6-{4-[4-(4-fluoro-3-trifluoromethyl-phenyl)-1-methyl-1H-imidazol-2-yl]-piperidin-1-yl}-pyrimidine-5-carboxamide using 4-Amino-6-{4-[1-[2-(cyclopropylmethyl-amino)-ethyl]-4-(4-fluoro-3-trifluoromethyl-phenyl)-1H-imidazol-2-yl]-piperidin-1-yl}-pyrimidine-5-carbonitrile instead of 4-amino-6-(4-{4-[4-fluoro-3-(trifluoromethyl)phenyl]-1-methyl-1H-imidazol-2-yl}piperidin-1-yl)pyrimidine-5-carbonitrile. LC-MS: (M+1=547, obsd.=547).
Reaction SMILES: C([O-])([O-])=O.[Na+].[Na+].Br[C:8]1[CH:9]=[C:10]2[C:15](=[CH:16][CH:17]=1)[N:14]=[CH:13][C:12]([C:18]([CH:20]1[CH2:22][CH2:21]1)=[O:19])=[C:11]2[NH:23][C@H:24]1[CH2:29][CH2:28][C@H:27]([CH2:30][N:31]([CH3:33])[CH3:32])[CH2:26][CH2:25]1.[Cl:34][C:35]1[CH:40]=[C:39](B2OC(C)(C)C(C)(C)O2)[CH:38]=[C:37]([Cl:50])[C:36]=1[OH:51]>>[CH:20]1([C:18]([C:12]2[CH:13]=[N:14][C:15]3[C:10]([C:11]=2[NH:23][C@H:24]2[CH2:25][CH2:26][C@H:27]([CH2:30][N:31]([CH3:33])[CH3:32])[CH2:28][CH2:29]2)=[CH:9][C:8]([C:39]2[CH:40]=[C:35]([Cl:34])[C:36]([OH:51])=[C:37]([Cl:50])[CH:38]=2)=[CH:17][CH:16]=3)=[O:19])[CH2:21][CH2:22]1
Reactant: CC1(C)OB(c2cc(Cl)c(O)c(Cl)c2)OC1(C)C
Reactant: CN(C)C[C@H]1CC[C@H](Nc2c(C(=O)C3CC3)cnc3ccc(Br)cc23)CC1
Agent: O=C([O-])[O-]
Agent: [Na+]
Product: CN(C)C[C@H]1CC[C@H](Nc2c(C(=O)C3CC3)cnc3ccc(-c4cc(Cl)c(O)c(Cl)c4)cc23)CC1

Procedure:
Following general procedure F except 2M Na2CO3 was used instead of 1M Cs2CO3, (6-bromo-4-(trans-4-((dimethylamino)methyl)cyclohexylamino)quinolin-3-yl)(cyclopropyl)methanone (4.29 g, 9.96 mmol) was reacted with 2,6-dichloro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol (4.32 g, 14.95 mmol) to afford the desired product (3.0 g, 59%) as a yellow solid: 1H NMR (300 MHz, DMSO-d6) δ 9.77 (br s, 1H), 9.05 (s, 1H), 8.36 (d, J=2.1 Hz, 1H), 8.03 (dd, J=8.7, 1.8 Hz, 1H), 7.85 (d, J=8.7 Hz, 1H), 7.73 (s, 2H), 3.96-3.86 (m, 1H), 2.97-2.82 (m, 1H), 2.19 (s, 6H), 2.17-2.06 (m, 4H), 1.86 (d, J=12.7 Hz, 2H), 1.60-1.36 (m, 3H), 1.15-0.91 (m, 6H); APCI MS m/z 512 [C28H31Cl2N3O2+H]+; HPLC>99% (AUC), tR=5.15 min.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[C:6]([CH3:8])[N:5]2[N:9]=[CH:10][CH:11]=[C:4]2[N:3]=1.[N+:12]([O-])([OH:14])=[O:13]>OS(O)(=O)=O>[CH3:1][C:2]1[CH:7]=[C:6]([CH3:8])[N:5]2[N:9]=[CH:10][C:11]([N+:12]([O-:14])=[O:13])=[C:4]2[N:3]=1
Reactant: O=[N+]([O-])O
Reactant: Cc1cc(C)n2nccc2n1
Agent: O=S(=O)(O)O
Product: Cc1cc(C)n2ncc([N+](=O)[O-])c2n1
Temperature: 25 °C
Reaction time: 0.75 h

Procedure:
5,7-Dimethyl pyrazolo[1,5-a]pyrimidine [1.0g (6.8 mmoles)] was dissolved in H2SO4 (10 ml) keeping the temperature below 5°. Fuming HNO3 [4 ml; sp. gr. 1.5] was added dropwise to the cold H2SO4 solution, with good stirring. The temperature during this addition was maintained below 10°. After the addition was complete, the solution was stirred at room temperature for 45 minutes and then added to 100 g of ice. The precipitated product was separated by filtration, washed well with H2O, and dried. Recrystallization from CH3OH afforded 0.75 g (57%) of analytically pure product; mp 156°-7°.
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:16]3[C:11](=[N:12][CH:13]=[CH:14][CH:15]=3)[N:10]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[N:9]=2)=[CH:4][CH:3]=1.Br[CH2:24][C:25]([O:27][CH2:28][CH3:29])=[O:26].C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[C:17]1([N:10]2[C:11]3=[N:12][CH:13]=[CH:14][CH:15]=[C:16]3[C:8]([C:5]3[CH:4]=[CH:3][C:2]([O:1][CH2:24][C:25]([O:27][CH2:28][CH3:29])=[O:26])=[CH:7][CH:6]=3)=[N:9]2)[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1
Reactant: CCOC(=O)CBr
Reactant: Oc1ccc(-c2nn(-c3ccccc3)c3ncccc23)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CCOC(=O)COc1ccc(-c2nn(-c3ccccc3)c3ncccc23)cc1
Temperature: 70 °C
Yield: 54.8 %

Procedure:
In 400 ml of dimethylformamide were suspended 39.3 g of 3-(4-hydroxyphenyl)-1-phenyl-1H-pyrazolo[3,4-b]pyridine, 34.4 g of ethyl bromoacetate and 28.4 g of potassium carbonate. The mixture was stirred under heating at 70° C. for 2 hours. The reaction mixture was concentrated under reduced pressure and the residue was extracted with benzene-water. The organic layer was concentrated. Hexane was added to the residue for crystallization. The obtained crude crystals were recrystallized from isopropyl ether to give 28 g of ethyl 4-(1-phenyl-1H-pyrazolo[3,4-b]pyridin-3-yl)phenoxyacetate, m.p. 118°-120° C.
Reaction SMILES: [F-:1].C([N+](CCCC)(CCCC)CCCC)CCC.CC1C=CC(S(O[CH2:30][CH2:31][CH:32]2[CH2:36][C:35](=[O:37])[N:34]([CH2:38][C:39]3[N:46]4[C:42]([S:43][C:44]([CH2:47][O:48][CH3:49])=[N:45]4)=[N:41][C:40]=3[Cl:50])[CH2:33]2)(=O)=O)=CC=1.O>C1COCC1>[Cl:50][C:40]1[N:41]=[C:42]2[N:46]([C:39]=1[CH2:38][N:34]1[CH2:33][CH:32]([CH2:31][CH2:30][F:1])[CH2:36][C:35]1=[O:37])[N:45]=[C:44]([CH2:47][O:48][CH3:49])[S:43]2
Reactant: COCc1nn2c(CN3CC(CCOS(=O)(=O)c4ccc(C)cc4)CC3=O)c(Cl)nc2s1
Reactant: [F-]
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Solvent: O
Solvent: C1CCOC1
Product: COCc1nn2c(CN3CC(CCF)CC3=O)c(Cl)nc2s1
Yield: 22 %

Procedure:
A 1M solution of tetrabutylammonium fluoride in THF solution (4 ml) is added to 2-(1-{[6-chloro-2-(methoxymethyl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl]methyl}-5-oxopyrrolidin-3-yl)ethyl 4-methylbenzenesulfonate a39 (308 mg, 0.617 mmol, 1 eq). The resulting solution is irradiated in a microwave apparatus (Biotage) at 100° C. for 1 h. Water (10 ml) is added to the reaction mixture, and the crude compound is extracted by ethyl acetate (4×10 ml). The cumulated organic layer are washed successively by a saturated NH4Cl aqueous solution (2×10 ml), water (2×10 ml), dried over MgSO4, filtered and condensed under reduced pressure. The residue is purified by flash chromatography over silicagel (eluent: CH2Cl2/MeOH 99:1) to afford 47 mg of pure 1-{[6-chloro-2-(methoxymethyl)-imidazo[2,1-b][1,3,4]thiadiazol-5-yl]methyl}-4-(2-fluoroethyl)pyrrolidin-2-one 28.
Reaction SMILES: Cl.[CH3:2][O:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[C:10]1[C:18]2[C:13](=[N:14][CH:15]=[C:16]([C:19]3[CH:20]=[C:21]([CH:24]=[CH:25][CH:26]=3)[C:22]#[N:23])[CH:17]=2)[N:12](COCC[Si](C)(C)C)[N:11]=1.C[CH2:36][O:37]CC>CO>[CH3:2][O:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[C:10]1[C:18]2[C:13](=[N:14][CH:15]=[C:16]([C:19]3[CH:20]=[C:21]([CH:24]=[CH:25][CH:26]=3)[C:22](=[NH:23])[O:37][CH3:36])[CH:17]=2)[NH:12][N:11]=1
Reactant: CCOCC
Reactant: COc1ccccc1-c1nn(COCC[Si](C)(C)C)c2ncc(-c3cccc(C#N)c3)cc12
Agent: Cl
Solvent: CO
Product: COC(=N)c1cccc(-c2cnc3[nH]nc(-c4ccccc4OC)c3c2)c1
Temperature: 25 °C
Reaction time: 23 h

Procedure:
HCl gas was bubbled through a suspension of 3-[3-(2-Methoxy-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]-benzonitrile (40 mg, 0.088 mmol) in 2.5 ml of anhydrous MeOH for 3 minutes at 0° C. After stirring for 23 hours at room temperature, ether (10 mL) was added and precipitation occurred. The solid was collected after filtration and dried to afford methyl 3-(3-(2-methoxyphenyl)-1H-pyrazolo[3,4-b]pyridin-5-yl)benzimidate as a yellow solid.
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([NH:10][C:11]3[C:20]4[C:15](=[CH:16][C:17]([O:21]C)=[CH:18][CH:19]=4)[N:14]=[CH:13][C:12]=3[C:23]#[N:24])[CH:8]=2)[CH:3]=[N:2]1.Cl.N1C=CC=CC=1.[NH4+].[OH-]>>[OH:21][C:17]1[CH:16]=[C:15]2[C:20]([C:11]([NH:10][C:7]3[CH:8]=[C:9]4[C:4]([CH:3]=[N:2][NH:1]4)=[CH:5][CH:6]=3)=[C:12]([C:23]#[N:24])[CH:13]=[N:14]2)=[CH:19][CH:18]=1
Reactant: COc1ccc2c(Nc3ccc4cn[nH]c4c3)c(C#N)cnc2c1
Agent: Cl
Agent: [NH4+]
Agent: [OH-]
Solvent: c1ccncc1
Product: N#Cc1cnc2cc(O)ccc2c1Nc1ccc2cn[nH]c2c1
Temperature: 205 °C
Yield: 99.8 %

Procedure:
A reaction mixture of 1.74 g (5.52 mmol) of 4-(1H-Indazol-6-ylamino)-7-methoxy-quinoline-3-carbonitrile and 15.3 g of pyridine hydrochloride was heated at 200-210° C. for 1.5 hr. After cooling, the mixture was taken into 3% NH4OH aqueous solution. The precipitate was collected by filtration and washed with water. Drying in vacuo afforded 1.66 g (63.8%) of the product as deep brown solid, m.p.>250° C., mass (electrospray, m/e): M+H 301.9. HRCIMS: calcd 302.1042 for C17H11N5O (M+) obsd 302.1079.
Reaction SMILES: [CH:1]1([NH:4][C:5]2[CH:10]=[C:9]([Cl:11])[N:8]=[C:7](Cl)[N:6]=2)[CH2:3][CH2:2]1.[CH2:13]([NH2:15])[CH3:14]>C(O)C>[CH2:13]([NH:15][C:7]1[N:6]=[C:5]([NH:4][CH:1]2[CH2:3][CH2:2]2)[CH:10]=[C:9]([Cl:11])[N:8]=1)[CH3:14]
Reactant: Clc1cc(NC2CC2)nc(Cl)n1
Reactant: CCN
Solvent: CCO
Product: CCNc1nc(Cl)cc(NC2CC2)n1
Yield: 74.9 %

Procedure:
A mixture of 130.5 g (0.64 mol) of 4-cyclopropylamino-2,6-dichloropyrimidine, 576 g (6.4 mols) of ethylamine and 500 ml of ethanol is heated to the reflux temperature for 3 hours. The isomer 6-ethylamino-4-cyclopropylamino-2-chloropyrimidine which crystallises out on cooling is removed by filtration. The filtrate is concentrated to dryness on a rotary evaporator and the residue is recrystallised from methanol. 102 g of colourless crystals of melting point 86°-88° are thus obtained.
Reaction SMILES: C(OC(=O)[NH:7][CH2:8][CH2:9][CH2:10][N:11]([CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([C:23]2[CH:28]=[CH:27][N:26]=[C:25](Cl)[N:24]=2)[CH:18]=1)[S:12]([CH3:15])(=[O:14])=[O:13])(C)(C)C.[N:31]1[CH:36]=[CH:35][C:34]([CH2:37][CH2:38][NH2:39])=[CH:33][CH:32]=1>>[NH2:7][CH2:8][CH2:9][CH2:10][N:11]([CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([C:23]2[CH:28]=[CH:27][N:26]=[C:25]([NH:39][CH2:38][CH2:37][C:34]3[CH:35]=[CH:36][N:31]=[CH:32][CH:33]=3)[N:24]=2)[CH:18]=1)[S:12]([CH3:15])(=[O:13])=[O:14]
Reactant: NCCc1ccncc1
Reactant: CC(C)(C)OC(=O)NCCCN(Cc1cccc(-c2ccnc(Cl)n2)c1)S(C)(=O)=O
Product: CS(=O)(=O)N(CCCN)Cc1cccc(-c2ccnc(NCCc3ccncc3)n2)c1

Procedure:
Intermediate 4 was coupled with 2-pyridin-4-yl-ethylamine following procedure F and the resulting product deprotected following procedure G. LC-MS showed the product had the expected M+H+ of 441. 1H NMR (Varian 300 MHz, CDCl3—CD3OD, shifts relative to the solvent peak at 7.24 ppm) δ 8.6 (m, 2H) 8.3 (m, 1H) 8.1 (m, 3H) 7.9 (m, 1H) 7.6 (m, 1H) 7.5 (m, 1H) 7.3 (m, 1H) 4.4 (m, 2H) 4.0 (m, 2H) 3.3 (m, 2H) 2.9 (m, 4H) 1.8 (m, 2H).
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH:22]=[CH:23][N:24]=1)[C:5]([N:7]1[CH2:12][CH2:11][CH:10]([CH2:13][NH:14]C(=O)OC(C)(C)C)[CH2:9][CH2:8]1)=[O:6].C(O)(C(F)(F)F)=O>ClCCl>[NH2:14][CH2:13][CH:10]1[CH2:11][CH2:12][N:7]([C:5]([C:4]2[CH:22]=[CH:23][N:24]=[C:2]([F:1])[CH:3]=2)=[O:6])[CH2:8][CH2:9]1
Reactant: CC(C)(C)OC(=O)NCC1CCN(C(=O)c2ccnc(F)c2)CC1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: NCC1CCN(C(=O)c2ccnc(F)c2)CC1
Reaction time: 10 h

Procedure:
To a solution of tert-butyl (1-(2-fluoroisonicotinoyl)piperidin-4-yl)methylcarbamate 93-3 (1.81 g, 5.0 mmol) in dichloromethane (10 mL) was added TFA (5 mL) dropwise at room temperature. The mixture was stirred for 10 hours, and then the solvents were removed by rotary evaporation. The residue was dissolved in ethyl acetate (100 mL), washed with saturated aqueous NaHCO3 solution, H2O and brine, dried over Na2SO4 and concentrated to dryness by rotary evaporation to give (4-(aminomethyl)piperidin-1-yl)(2-fluoropyridin-4-yl)methanone 93-4 as a yellow oil. MS m/z 238.1 (M+1)
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[CH2:7][NH:8][CH2:9][CH2:10][CH2:11][S:12][C:13]1[CH:18]=[CH:17][N:16]=[CH:15][CH:14]=1.C(N(CC)CC)C.[C:26](Cl)(=[O:28])[CH3:27]>C(Cl)Cl>[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[CH2:7][N:8]([CH2:9][CH2:10][CH2:11][S:12][C:13]1[CH:18]=[CH:17][N:16]=[CH:15][CH:14]=1)[C:26](=[O:28])[CH3:27]
Reactant: c1ccc(CNCCCSc2ccncc2)nc1
Reactant: CC(=O)Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CC(=O)N(CCCSc1ccncc1)Cc1ccccn1
Yield: 85.6 %

Procedure:
To a solution of 1.62 g (6.24 mmol) of 4-[3-(N-2pyridylmethylamino)propylthio]pyridine and 1.10 ml (7.80 mmol) of triethylamine in 10 ml of methylene chloride, 0.51 ml (7.80 mmol) of acetyl chloride was added under ice-cooling with stirring. The mixture was stirred at room temperature for 30 minutes. The reaction mixture was washed with a saturated aqueous solution of sodium bicarbonate and water and dried, and the solvent was distilled off. The residue was purified by column chromatography (eluent: ethyl acetate/methanol=10:1) to obtain 1.61 g of the desired compound (yield: 85.6%, yellow oil).
Reaction SMILES: Cl[O-].[Na+].[CH2:4]=[C:5]1[CH2:10][CH2:9][CH2:8][N:7]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:6]1.[CH:18](=[N:25][OH:26])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1>C(Cl)Cl>[C:19]1([C:18]2[CH2:4][C:5]3([CH2:10][CH2:9][CH2:8][N:7]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:6]3)[O:26][N:25]=2)[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1
Reactant: C=C1CCCN(C(=O)OC(C)(C)C)C1
Reactant: ON=Cc1ccccc1
Agent: [Na+]
Agent: [O-]Cl
Solvent: ClCCl
Product: CC(C)(C)OC(=O)N1CCCC2(CC(c3ccccc3)=NO2)C1
Reaction time: 2 h
Yield: 73.2 %

Procedure:
A 10% aqueous sodium hypochlorite solution (2.88 mL, 4.66 mmol) was added dropwise to a solution of tert-butyl 3-methylenepiperidine-1-carboxylate (230 mg, 1.166 mmol) and benzaldehyde oxime (282 mg, 2.332 mmol) in CH2Cl2 (5 mL) at 0° C. After 2 h at 0° C., the mixture was diluted CH2Cl2 (50 mL) and washed with water (10 mL). The aqueous phase was extracted with CH2Cl2 (3×20 mL). The combined organic extracts were washed with brine (10 mL), dried (MgSO4) and concentrated. Silica gel chromatography, eluting with 0 to 15% ethyl acetate in hexanes, gave the expected product as a colorless oil (270 mg, 73% yield). LCMS: (M+Na)+=339.12. 1H NMR (400 MHz, chloroform-d) δ ppm 7.55-7.79 (2H, m), 7.31-7.47 (3H, m), 3.57-3.93 (2H, m), 2.90-3.29 (4H, m), 1.78-2.04 (2H, m), 1.51-1.65 (2H, m), 1.46 (9H, s).
Reaction SMILES: C(C1C=C(NC(=O)CCCC2C=CC([B:25]([OH:27])[OH:26])=CC=2)C=CC=1S(CC)(=O)=O)#N.[CH2:29]([O:36][C:37]([N:39]([CH2:41][C:42]1[CH:43]=[C:44]([NH:48][C:49]([O:51][CH2:52][CH2:53][C:54]2[CH:59]=[CH:58][C:57](Br)=[CH:56][C:55]=2[CH3:61])=[O:50])[CH:45]=[CH:46][CH:47]=1)[CH3:40])=[O:38])[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1>>[CH2:29]([O:36][C:37]([N:39]([CH2:41][C:42]1[CH:43]=[C:44]([NH:48][C:49]([O:51][CH2:52][CH2:53][C:54]2[CH:59]=[CH:58][C:57]([B:25]([OH:27])[OH:26])=[CH:56][C:55]=2[CH3:61])=[O:50])[CH:45]=[CH:46][CH:47]=1)[CH3:40])=[O:38])[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1
Reactant: CCS(=O)(=O)c1ccc(NC(=O)CCCc2ccc(B(O)O)cc2)cc1C#N
Reactant: Cc1cc(Br)ccc1CCOC(=O)Nc1cccc(CN(C)C(=O)OCc2ccccc2)c1
Product: Cc1cc(B(O)O)ccc1CCOC(=O)Nc1cccc(CN(C)C(=O)OCc2ccccc2)c1
Yield: 28 %

Procedure:
Using a procedure analogous to that used to prepare 6D, 60C (2.9 g, 5.6 mmol) was reacted with 5,5′,5′-tetramethyl-[2,2′]bi[[1,3,2]dioxaborinanyl] to give 60D (720 mg, 28%) as a solid. MS (ESI) m/z 475.3 (M−H)−.
Reaction SMILES: [CH3:1][C:2]1[N:3]2[CH:9]=[C:8]([CH2:10]Cl)[N:7]=[C:4]2[S:5][CH:6]=1.[NH:12]1[CH2:17][CH2:16][O:15][CH2:14][CH2:13]1>O>[CH3:1][C:2]1[N:3]2[CH:9]=[C:8]([CH2:10][N:12]3[CH2:17][CH2:16][O:15][CH2:14][CH2:13]3)[N:7]=[C:4]2[S:5][CH:6]=1
Reactant: C1COCCN1
Reactant: Cc1csc2nc(CCl)cn12
Solvent: O
Product: Cc1csc2nc(CN3CCOCC3)cn12
Reaction time: 1 h

Procedure:
3.4 g of 3-methyl-6-chloromethyl-imidazo-(2,1-b)thiazole are slowly added into 50 ml of cooled and stirred morpholine. The stirring is continued for 1 hour at room temperature and another hour at 40°-50°. The suspension obtained is filtered and the filtrate is evaporated. The residue obtained is dissolved in water and the aqueous solution obtained is extracted with chloroform. The chloroform solution is washed at pH 5-6 with water and after drying it is evaporated. Ethyl acetate is added to the residue to yield 4.5 g of 3-methyl-6-morpholinomethyl-imidazo-(2,1-b)thiazole; m.p. 203°-204° (methyl-ethyl-ketone).
Reaction SMILES: Cl[C:2]1[S:3][C:4]2[CH:10]=[CH:9][CH:8]=[CH:7][C:5]=2[N:6]=1.[NH:11]1[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]1.C(N(CC)CC)C>C(O)C>[N:11]1([C:2]2[S:3][C:4]3[CH:10]=[CH:9][CH:8]=[CH:7][C:5]=3[N:6]=2)[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]1
Reactant: C1CNCCN1
Reactant: Clc1nc2ccccc2s1
Solvent: CCN(CC)CC
Solvent: CCO
Product: c1ccc2sc(N3CCNCC3)nc2c1

Procedure:
A solution of 1.7 g (0.01 mol) of 2-chlorobenzothiazole, 4.76 g (0.05 mol) of piperazine and 7 ml (0.05 mol) of triethylamine in 50 ml of ethanol is stirred for 48 hours at ambient temperature. The reaction mixture is concentrated by evaporation, mixed with water and extracted twice with dichloromethane. The combined organic phases are dried over sodium sulphate, the drying agent is filtered off and the filtrate is concentrated by evaporation. The residue is washed with diethylether.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]=[C:10]3[N:14]([C:15]=2[CH2:16][C:17]([OH:19])=O)[C:13]2[CH:20]=[C:21]([CH3:24])[CH:22]=[CH:23][C:12]=2[N:11]3[CH3:25])=[CH:4][CH:3]=1.[CH3:26][NH2:27]>O1CCCC1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[N:9]=[C:10]3[N:14]([C:15]=2[CH2:16][C:17]([NH:27][CH3:26])=[O:19])[C:13]2[CH:20]=[C:21]([CH3:24])[CH:22]=[CH:23][C:12]=2[N:11]3[CH3:25])=[CH:6][CH:7]=1
Reactant: CN
Reactant: Cc1ccc2c(c1)n1c(CC(=O)O)c(-c3ccc(Cl)cc3)nc1n2C
Solvent: C1CCOC1
Product: CNC(=O)Cc1c(-c2ccc(Cl)cc2)nc2n(C)c3ccc(C)cc3n12
Reaction time: 6 h

Procedure:
Under a nitrogen stream, a suspension of 1.0 g (0.0028 mol) of 2-(4-chlorophenyl)-6,9-dimethyl-9H-imidazo[1,2-a]benzimidazole-3-acetic acid is prepared in 50 ml of dry tetrahydrofuran. 1.0 g (0.0063 mol) of N,N'-carbonyldiimidazole in solution in 50 ml of dry tetrahydrofuran is added and the mixture is stirred for 6 h. The solution is then treated with an excess of dry gaseous methylamine and again stirred for 4 h. The solvent is evaporated under reduced pressure. The residue is taken up in water, drained, washed with water and dried. 0.65 g of product is obtained which is purified by silica gel column chromatography, eluting with a chloroform/acetone 93/7 mixture. 0.26 g of compound is finally isolated. Melting point: 258°-260° C.
Reaction SMILES: I[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=1.[CH2:8]([C:12]1[N:16]([CH3:17])[C:15]2[CH:18]=[CH:19][CH:20]=[CH:21][C:14]=2[N:13]=1)[CH2:9][C:10]#[CH:11]>>[CH3:17][N:16]1[C:15]2[CH:18]=[CH:19][CH:20]=[CH:21][C:14]=2[N:13]=[C:12]1[CH2:8][CH2:9][C:10]#[C:11][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=1
Reactant: C#CCCc1nc2ccccc2n1C
Reactant: Ic1ccccn1
Product: Cn1c(CCC#Cc2ccccn2)nc2ccccc21
Yield: 30.6 %

Procedure:
The title compound was prepared in accordance with the general method of Example 1, from 2-iodo-pyridine (100 mg, 0.49 mmol) and 2-but-3-ynyl-1-methyl-1H-benzoimidazole (90 mg, 0.49 mmol). Reaction time: 18 hours. The crude residue was purified by flash chromatography (DCM/MeOH 98:2) to yield 39 mg (0.15 mmol, 31%) of 1-methyl-2-(4-(pyridin-2-yl)but-3-ynyl)-1H-benzo[d]imidazole as a brown solid.
Reaction SMILES: [C:1](OCC12CC3CC(CC(O)(C3)C1)C2)(=[O:4])[CH:2]=[CH2:3].[CH3:18][C:19]12[CH2:28][C:23]3([OH:29])[CH2:24][CH:25]([CH2:27][C:21]([CH3:30])([CH2:22]3)[CH2:20]1)[CH2:26]2>>[CH3:18][C:19]12[CH2:28][C:23]3([O:29][C:1](=[O:4])[CH:2]=[CH2:3])[CH2:24][CH:25]([CH2:27][C:21]([CH3:30])([CH2:22]3)[CH2:20]1)[CH2:26]2
Reactant: C=CC(=O)OCC12CC3CC(CC(O)(C3)C1)C2
Reactant: CC12CC3CC(C)(C1)CC(O)(C3)C2
Product: C=CC(=O)OC12CC3CC(C)(CC(C)(C3)C1)C2
Yield: 96 %

Procedure:
The reaction was conducted in the same manner as said (2) except that 1,3-dimethyl-5-hydroxyadamantane was used instead of the 1,3-dimethyl-5,7-dihydroxyadamantane, and, as a result, a 1,3-dimethyl-5-acryloyloxyadamantane (yield: 96%, colorless liquid) was produced.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([C:9]2([O:16][CH3:17])[CH2:13][CH2:12][N:11]([CH2:14][CH3:15])[CH2:10]2)[CH:5]=[CH:6][C:7]=1[F:8].ClC1C=C(C=CC=1)C(OO)=[O:23]>ClCCl>[F:1][C:2]1[CH:3]=[C:4]([C:9]2([O:16][CH3:17])[CH2:13][CH2:12][N+:11]([O-:23])([CH2:14][CH3:15])[CH2:10]2)[CH:5]=[CH:6][C:7]=1[F:8]
Reactant: CCN1CCC(OC)(c2ccc(F)c(F)c2)C1
Reactant: O=C(OO)c1cccc(Cl)c1
Solvent: ClCCl
Product: CC[N+]1([O-])CCC(OC)(c2ccc(F)c(F)c2)C1

Procedure:
Preparation according to Example 32: Enantiomer 1 of 3-(3,4-difluorophenyl)-1-ethyl-3-methoxypyrrolidine (0.009 g, 0.037 mmol), dichloromethane (2 ml), 3-chloroperoxybenzoic acid (77%) (0.017 g, 0.075 mmol). The crude product was analyzed by LCMS (Qtrap, Applied Biosystems, Q1 MS), analysis showed <95% conversion: MS (m+1)/z; 258 (M+1, bp), 257 (7), 226 (3), 214 (5), 211 (3).