Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([C:4]1[CH:5]=[C:6]([O:13][CH3:14])[C:7](O)=[C:8]([CH:11]=1)[CH:9]=[O:10])[CH:2]=[CH2:3].C1C=CC(N(S(C(F)(F)F)(=O)=O)S(C(F)(F)F)(=O)=O)=CC=1.CCN(CC)CC.CN([CH:46]=[O:47])C.[CH3:48][OH:49]>ClCCl.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.[Fe+2]>[CH2:1]([C:4]1[CH:5]=[C:6]([O:13][CH3:14])[C:7]([C:48]([O:47][CH3:46])=[O:49])=[C:8]([CH:9]=[O:10])[CH:11]=1)[CH:2]=[CH2:3]
Reactant: C=CCc1cc(C=O)c(O)c(OC)c1
Reactant: CN(C)C=O
Reactant: CO
Agent: [Fe+2]
Agent: O=S(=O)(N(c1ccccc1)S(=O)(=O)C(F)(F)F)C(F)(F)F
Agent: c1ccc(P(c2ccccc2)[c-]2cccc2)cc1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: C=CCc1cc(C=O)c(C(=O)OC)c(OC)c1
Temperature: 25 °C
Reaction time: 48 h

Procedure:
To a flask containing 5-allyl-2-hydroxy-3-methoxybenzaldehyde (5.0 g, 26.0 mmol) and N-phenyl-trifluoromethanesulfonimide was added DCM (75 mL). The flask was placed at 0° C. and treated with Et3N (4 mL) and stirred for 2 days at room temp. The mixture was diluted with dichloromethane and washed with 1N HCl, saturated sodium bicarbonate solution, and brine, then dried (Na2SO4) and concentrated. The residue in a flask was treated with dppf (0.18 g, 0.45 mmol), PdOAc2 (0.1 g, 0.44 mmol), and Et3N (8 mL, 56 mmol) followed by addition of DMF (45 mL) and MeOH (30 mL). The reaction mixture was then degassed and purged with CO 3 times and stirred under CO for 6 h at 70° C. When LC indicated consumption of starting material, the solution was concentrated to dryness. The organic residue was purified by MPLC (hexanes/EtOAc=1/0.2) to provide methyl 4-allyl-2-formyl-6-methoxybenzoate.
Reaction SMILES: [CH3:1][C:2]([CH3:14])([S:4]([NH:6][C:7]1(/[C:10](=[N:12]/[OH:13])/[NH2:11])[CH2:9][CH2:8]1)=[O:5])[CH3:3].[CH2:15](OC(OCC)OCC)C>CC(O)=O>[O:13]1[CH:15]=[N:11][C:10]([C:7]2([NH:6][S:4]([C:2]([CH3:14])([CH3:1])[CH3:3])=[O:5])[CH2:9][CH2:8]2)=[N:12]1
Reactant: CCOC(OCC)OCC
Reactant: CC(C)(C)S(=O)NC1(/C(N)=N/O)CC1
Solvent: CC(=O)O
Product: CC(C)(C)S(=O)NC1(c2ncon2)CC1
Temperature: 25 °C
Reaction time: 16 h
Yield: 32.6 %

Procedure:
(Z)-1-(1,1-dimethylethylsulfinamido)-N′-hydroxycyclopropanecarboximidamide (1.0 g, 4.6 mmol) in triethoxymethane (6.0 ml, 36 mmol) was treated with AcOH (6 ml) at rt. The reaction was allowed to stir at rt for 16 h. The reaction was concentrated to dryness azeotroping with toluene 3×. The resulting yellow oil which was purified on silica gel (Biotage, EtOAc/hexanes gradient (Rf ˜approximately 2 in 70% EtOAc/Hex) to give the expected product N-(1-(1,2,4-oxadiazol-3-yl)cyclopropyl)-2-methylpropane-2-sulfinamide (340 mg, 1.5 mmol, 33% yield) consistent by LCMS and NMR. LC-MS retention time: 1.06 min; m/z (MH+): 230. LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a Phenomenex-Luna 3u C18 2.0×30 mm column using a SPD-10AV UV-Vis detector at a detector wave length of 220 nM. The elution conditions employed a flow rate of 1 mL/min, a gradient of 100% solvent A/0% solvent B to 0% solvent A/100% solvent B, a gradient time of 2 min, a hold time of 1 min, and an analysis time of 3 min where solvent A was 10% acetonitrile/90% H2O/0.1% trifluoroacetic acid and solvent B was 10% H2O/90% acetonitrile/0.1% trifluoroacetic acid. MS data was determined using a Micromass Platform for LC in electrospray mode. 1H NMR (400 MHz, DMSO-d6) δ 9.44 (s, 1H), 6.36 (s, 1H), 1.57-1.51 (m, 1H), 1.45-1.32 (m, 3H), 1.15 (s, 9H).
Reaction SMILES: B1([C@H]2[C@H](C)[C@@H]3C(C)(C)[C@H](C3)C2)C2CCCC1CCC2.[Cl:20][CH2:21][C:22]([C:24]1[CH:25]=[N:26][C:27]([N:30]2[C:34]([CH3:35])=[CH:33][CH:32]=[C:31]2[CH3:36])=[CH:28][CH:29]=1)=[O:23]>>[Cl:20][CH2:21][C@@H:22]([C:24]1[CH:25]=[N:26][C:27]([N:30]2[C:34]([CH3:35])=[CH:33][CH:32]=[C:31]2[CH3:36])=[CH:28][CH:29]=1)[OH:23]
Reactant: Cc1ccc(C)n1-c1ccc(C(=O)CCl)cn1
Agent: C[C@@H]1[C@H]2C[C@H](C[C@H]1B1C3CCCC1CCC3)C2(C)C
Product: Cc1ccc(C)n1-c1ccc([C@@H](O)CCl)cn1
Temperature: 0 °C
Reaction time: 96 h
Yield: 37.3 %

Procedure:
(R)-Alpine borane (1.5 L, 0.5 M in tetrahydrofuran) was added slowly to a cooled (0° C.), neat, 2-chloro-1-[6-(2,5-dimethyl-pyrrol-1-yl)-pyridin-3-yl]-ethanone (Example 140; 93 g). The mixture was warmed to room temperature and reduced to one third its original volume by distilling tetrahydrofuran. After four days, the mixture was cooled to 0° C. and 3 M aqueous solution of K2CO3 (600 mL) was added. Then the reaction mixture was oxidized by drop wise addition of 30% H2O2 (250 mL). After stirring at room temperature for 3 h, the reaction mixture was diluted ethyl acetate, organic layer was separated. Aqueous portion was extracted (ethyl acetate), combined organic extracts were washed with water and dried. After concentration in vacuo, the resulting oil was purified by chromatography on silica gel (hexanes/ethyl acetate as eluent) to afford a yellow solid (35 g). 1H NMR (CDCl3, 300 MHz) δ 8.59 (m, 1 H), 7.88 (dd, 8.1 Hz, 2.2 Hz, 1 H), 7.26 (m, 1 H), 5.91 (m, 2 H), 4.96 (m, 1 H), 3.78 (m, 2 H), 3.35 (br s, 1 H), 2.11 (2, 6 H); MS (FAB) m/z 251 (MH+); Anal. calcd for C13H15N2OCl: C, 62.28; H, 6.03; N, 11.17. Found: C, 61.95; H, 6.03; N, 10.92; Rf =0.4 (60:40 hexanes/ethyl acetate).
Reaction SMILES: [C:1]1(=[O:7])[O:6][C:4](=[O:5])[CH2:3][CH2:2]1.[C:8]1([O:18][CH2:19][CH2:20][OH:21])[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[CH:11]=[CH:10][CH:9]=1.[CH:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1>S(=O)(=O)(O)O.O>[C:8]1([O:18][CH2:19][CH2:20][O:21][C:4](=[O:5])[CH2:3][CH2:2][C:1]([O:6][CH2:9][CH2:8][O:18][C:22]2[C:27]3[C:26](=[CH:10][CH:11]=[CH:12][CH:13]=3)[CH:25]=[CH:24][CH:23]=2)=[O:7])[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[CH:11]=[CH:10][CH:9]=1
Reactant: O=C1CCC(=O)O1
Reactant: c1ccccc1
Reactant: OCCOc1cccc2ccccc12
Agent: O=S(=O)(O)O
Solvent: O
Product: O=C(CCC(=O)OCCOc1cccc2ccccc12)OCCOc1cccc2ccccc12
Yield: 74.7 %

Procedure:
50 g (0.5 mole) of succinic anhydride, 188 g (1 mole) of β-naphthoxy-ethanol and 10 drops of concentrated sulfuric acid are added to 300 ml of dry benzene. The reaction mixture is stirred and refluxed for 8 hours under a Marcusson water separator. The mixture is allowed to cool, the separated product is filtered off by suction, washed with water, then three times with an aqueous sodium carbonate solution, and finally with water again. The product is dried at room temperature. 171 g (74.7%) of the title compound are obtained.
Reaction SMILES: [CH:1]1([CH2:4][N:5]([CH3:22])[CH2:6][CH2:7][N:8]2[CH:12]=[C:11]([C:13]3[CH:18]=[C:17]([C:19]([OH:21])=O)[CH:16]=[CH:15][N:14]=3)[N:10]=[CH:9]2)[CH2:3][CH2:2]1.[N:23]#[C:24][NH2:25].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[C:24]([NH:25][C:19]([C:17]1[CH:16]=[CH:15][N:14]=[C:13]([C:11]2[N:10]=[CH:9][N:8]([CH2:7][CH2:6][N:5]([CH2:4][CH:1]3[CH2:2][CH2:3]3)[CH3:22])[CH:12]=2)[CH:18]=1)=[O:21])#[N:23]
Reactant: N#CN
Reactant: CN(CCn1cnc(-c2cc(C(=O)O)ccn2)c1)CC1CC1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Product: CN(CCn1cnc(-c2cc(C(=O)NC#N)ccn2)c1)CC1CC1
Temperature: 25 °C
Reaction time: 1 h
Yield: 61.7 %

Procedure:
A mixture of 2-(1-{2-[(cyclopropylmethyl)(methyl)amino]ethyl}-1H-imidazol-4-yl)pyridine-4-carboxylic acid (10 mg, 0.03 mmol, Example 59), cyanamide (4 mg, 0.1 mmol), HATU (38 mg, 0.1 mmol), TEA (29 μL, 0.2 mmol) in DMF (2 mL) was stirred at r.t. for 1 hr. The reaction mixture was purified by ISCO flash column chromatography (MeOH/DCM=0-50%) to give the title compound as off-white solid (6 mg, 60%). 1HNMR (400 MHz, DMSO-d6): δ 0.43 (2H, m), 0.79 (2H, m), 1.15 (1H, m), 2.30 (5H, m), 2.76 (2H, m), 4.11 (2H, t, J=4.2 Hz), 7.29 (1H, m), 7.73 (1H, d, J=11.4 Hz), 8.27 (1H, s), 8.29 (1H, s), 8.49 (1H, s). [M+H] Calc'd for C17H20N6O, 325. Found, 325.
Reaction SMILES: [C:1]1([CH2:7][CH2:8][SH:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[H-].[Na+].Br[CH2:13][CH2:14][C:15]1[C:19]2[CH:20]=[CH:21][CH:22]=[C:23]([O:24][CH:25](C)[C:26]([O:28][CH3:29])=[O:27])[C:18]=2[O:17][CH:16]=1.[C:31](O)(=O)C>CN(C=O)C.O>[C:1]1([CH2:7][CH2:8][S:9][CH2:13][CH2:14][C:15]2[C:19]3[CH:20]=[CH:21][CH:22]=[C:23]([O:24][CH2:25][C:26]([O:28][CH3:29])=[O:27])[C:18]=3[O:17][C:16]=2[CH3:31])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: COC(=O)C(C)Oc1cccc2c(CCBr)coc12
Reactant: CC(=O)O
Reactant: SCCc1ccccc1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: COC(=O)COc1cccc2c(CCSCCc3ccccc3)c(C)oc12
Temperature: 25 °C
Reaction time: 0.67 h
Yield: 98 %

Procedure:
2-phenylethanethiol (0.42 ml) was dissolved in DMF (5 ml) and sodium hydride (60%, 132 mg) was added to the obtained solution, followed by stirring the resulting mixture at room temperature for 40 minutes. To this reaction solution, a solution of methyl 3-(2-bromoethyl)-2-methyl-benzofuran-7-yloxyacetate (900 mg) in DMF (8 ml) was added dropwise and the resulting solution was stirred for 30 minutes. Acetic acid (0.5 ml) was added to the reaction solution and the solution was poured into water layer (100 ml), followed by extraction of the resultant twice with ethyl acetate (30 ml). The organic layers were combined and washed with saturated brine, followed by drying over sodium sulfate. After removing the sodium sulfate by filtration, the solvent was removed under reduced pressure and the residue was purified by column chromatography (solvent: cyclohexane/ethyl acetate=3/1) using silica gel to obtain the desired compound (1.03 g, yield: 98%).
Reaction SMILES: Br.C([N:9]1[C:13]2=[C:14]([N+:29]([O-:31])=[O:30])[C:15]([NH:20][C:21]3[CH:26]=[CH:25][C:24]([I:27])=[CH:23][C:22]=3[F:28])=[C:16]([CH3:19])[C:17](=[O:18])[N:12]2[CH2:11][CH2:10]1)C1C=CC=CC=1.C(OC(=O)C)C.C([O-])(O)=O.[Na+]>C(O)(=O)C>[F:28][C:22]1[CH:23]=[C:24]([I:27])[CH:25]=[CH:26][C:21]=1[NH:20][C:15]1[C:14]([N+:29]([O-:31])=[O:30])=[C:13]2[NH:9][CH2:10][CH2:11][N:12]2[C:17](=[O:18])[C:16]=1[CH3:19]
Reactant: Cc1c(Nc2ccc(I)cc2F)c([N+](=O)[O-])c2n(c1=O)CCN2Cc1ccccc1
Agent: Br
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CC(=O)O
Solvent: CCOC(C)=O
Product: Cc1c(Nc2ccc(I)cc2F)c([N+](=O)[O-])c2n(c1=O)CCN2
Temperature: 25 °C
Reaction time: 2 h
Yield: 72.6 %

Procedure:
HBr in acetic acid (30 mL) was added to 1-benzyl-7-(2-fluoro-4-iodo-phenylamino)-6-methyl-8-nitro-2,3-dihydro-1H-imidazo[1,2-a]pyridin-5-one (I-3b: 2.5 g) and the resulting mixture was stirred at room temperature for 2 hours. The reaction was monitored by TLC (100% ethylacetate). The reaction mixture was basified with NaHCO3 solution and partitioned between ice water and ethyl acetate. The organic layer was concentrated to afford the crude product. Purification by column chromatography on silica gel (60% ethylacetate in hexane) afforded 1.5 g of the product (75% yield).
Reaction SMILES: [CH3:1][C:2]([C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)([CH2:14][CH2:15][N:16]1[C@H:21]2[CH2:22][CH2:23][C@@H:17]1[CH2:18][CH:19]([N:24]1[C:28]3[CH:29]=[CH:30][CH:31]=[CH:32][C:27]=3[N:26]=[C:25]1[CH3:33])[CH2:20]2)[CH2:3][NH:4][S:5]([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)(=[O:7])=[O:6].[H-].[Na+].I[CH3:43].O>C1COCC1>[CH3:43][N:4]([CH2:3][C:2]([CH3:1])([C:34]1[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=1)[CH2:14][CH2:15][N:16]1[C@H:21]2[CH2:22][CH2:23][C@@H:17]1[CH2:18][CH:19]([N:24]1[C:28]3[CH:29]=[CH:30][CH:31]=[CH:32][C:27]=3[N:26]=[C:25]1[CH3:33])[CH2:20]2)[S:5]([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)(=[O:7])=[O:6]
Reactant: Cc1nc2ccccc2n1C1C[C@H]2CC[C@@H](C1)N2CCC(C)(CNS(=O)(=O)c1ccccc1)c1ccccc1
Reactant: CI
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: O
Product: Cc1nc2ccccc2n1C1C[C@H]2CC[C@@H](C1)N2CCC(C)(CN(C)S(=O)(=O)c1ccccc1)c1ccccc1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 74.8 %

Procedure:
To a solution of the title compound from example 19 (65 mg, 0.12 mmol) in dry THF (2 mL) was added sodium hydride (6 mg, 0.14 mmol) as a 60% suspension in mineral oil and the solution stirred under a nitrogen atmosphere at room temperature for 30 min. Iodomethane (0.03 mL, 0.48 mmol) was added and the reaction stirred at room temperature for 1 h. An additional portion of iodomethane (0.02 mL, 0.32 mmol) was added and the solution stirred for 1 h more at room temperature. Water was added and the reaction partitioned between ethyl acetate and water. The organic layer was dried (MgSO4) and concentrated in vacuo. The residue was purified by silica gel chromatography eluting with 0-4% methanol/CH2Cl2 to afford the title compound (50 mg, 75%) as a white solid.
Reaction SMILES: I[C:2]1[CH:3]=[N:4][N:5]2[CH:10]=[C:9]([C:11]3[CH:12]=[N:13][N:14]([CH3:16])[CH:15]=3)[CH:8]=[C:7]([O:17][CH3:18])[C:6]=12.[CH3:19][Si:20]([C:23]#[CH:24])([CH3:22])[CH3:21].C(N(CC)CC)C.[Al]>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.[Cu]I.CN(C=O)C>[CH3:18][O:17][C:7]1[C:6]2[N:5]([N:4]=[CH:3][C:2]=2[C:24]#[C:23][Si:20]([CH3:22])([CH3:21])[CH3:19])[CH:10]=[C:9]([C:11]2[CH:12]=[N:13][N:14]([CH3:16])[CH:15]=2)[CH:8]=1
Reactant: COc1cc(-c2cnn(C)c2)cn2ncc(I)c12
Reactant: C#C[Si](C)(C)C
Agent: [Cu]I
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: [Al]
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: COc1cc(-c2cnn(C)c2)cn2ncc(C#C[Si](C)(C)C)c12
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
3-iodo-4-methoxy-6-(1-methyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridine (860. mg, 2.43 mmol), tetrakis(triphenylphosphine)palladium(0) (281 mg, 0.243 mmol), trimethylsilylacetylene (1.01 ml, 7.29 mmol) and copper (I) iodide (277 mg, 1.46 mmol) were combined in a round bottom flask. DMF (25 mL) and triethylamine (0.677 mL, 4.86 mmol) were added, then the flask was wrapped with aluminum foil and sparged with nitrogen for 5 minutes. The reaction was stirred at ambient temperature for 30 mins, then diluted with ethyl acetate and washed with saturated aqueous sodium bicarbonate. The organic layer was separated and the aqueous layer was back extracted two times with ethyl acetate. The combined organic layers were dried over sodium sulfate, filtered and concentrated. The liquid was purified by column chromatography on silica gel (methanol/ethyl acetate gradient) to give 4-methoxy-6-(1-methyl-1H-pyrazol-4-yl)-3-[(trimethylsilyl)ethynyl]pyrazolo[1,5-a]pyridine LRMS (ESI) calculated for C17H21N4OSi [M+H]+, 325.1; found 325.1.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][CH:13]=1)[NH:10][CH:9]=[C:8]([C:14]#[N:15])[C:7]2=O)([O-:3])=[O:2].P(Cl)(Cl)([Cl:19])=O>>[Cl:19][C:7]1[C:6]2[C:11](=[CH:12][CH:13]=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=2)[N:10]=[CH:9][C:8]=1[C:14]#[N:15]
Reactant: O=P(Cl)(Cl)Cl
Reactant: N#Cc1c[nH]c2ccc([N+](=O)[O-])cc2c1=O
Product: N#Cc1cnc2ccc([N+](=O)[O-])cc2c1Cl

Procedure:
A mixture of 31.3 g (0.147 mol) of 6-nitro-4-oxo-1,4-dihydro-quinoline-3-carbonitrile and 160 mL of phosphorous oxychloride was refluxed for 5.5 h. The phosphorous oxychloride was removed in vacuo and the residue was poured over ice and neutralized with sodium bicarbonate. The product was collected, washed with water and dried in vacuo (50° C.). There was obtained 33.5 g of tan solid; solid: mass spectrum (electrospray, m/e): M+H 234.
Reaction SMILES: C(OC([N:8]1[CH2:17][CH2:16][C:15]2[C:11](=[C:12](OS(C(F)(F)F)(=O)=O)[N:13]([CH:18]3[CH2:22][CH2:21][CH2:20][CH2:19]3)[N:14]=2)[CH2:10][CH2:9]1)=O)(C)(C)C.[S:31]1[CH:35]=[CH:34][C:33](B(O)O)=[CH:32]1>>[CH:18]1([N:13]2[C:12]([C:33]3[CH:34]=[CH:35][S:31][CH:32]=3)=[C:11]3[C:15]([CH2:16][CH2:17][NH:8][CH2:9][CH2:10]3)=[N:14]2)[CH2:19][CH2:20][CH2:21][CH2:22]1
Reactant: OB(O)c1ccsc1
Reactant: CC(C)(C)OC(=O)N1CCc2nn(C3CCCC3)c(OS(=O)(=O)C(F)(F)F)c2CC1
Product: c1cc(-c2c3c(nn2C2CCCC2)CCNCC3)cs1
Yield: 89.9 %

Procedure:
The title compound (114 mg) was prepared as in Example 177, Steps C and D, using 200 mg of 2-cyclopentyl-3-trifluoromethanesulfonyloxy-4,5,7,8-tetrahydro-2H-1,2,6-triaza-azulene-6-carboxylic acid tert-butyl ester (Example 180, Step A) and 169 mg of 3-thiopheneboronic acid. MS (ESI): exact mass calculated for C16H21N3S, 287.15. found, m/z 288.4 [M+H]+. 1H NMR (500 MHz, CDCl3): 7.68-7.63 (m, 1H), 7.56-7.51 (m, 1H), 7.17-7.12 (m, 1H), 4.58 (m, 1H), 3.43-3.37 (m, 2H), 3.34-3.28 (m, 2H), 3.19-3.14 (m, 2H), 2.86-2.80 (m, 2H), 2.04-1.85 (m, 6H), 1.67-1.57 (m, 2H).
Reaction SMILES: [C:1]([O:9][CH2:10][CH2:11][N:12]1[C:24]2[C:23]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[N+:17]([O-])=[CH:16][C:15]=2[N:14]=[CH:13]1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.P(Cl)(Cl)([Cl:28])=O>>[C:1]([O:9][CH2:10][CH2:11][N:12]1[C:24]2[C:23]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[N:17]=[C:16]([Cl:28])[C:15]=2[N:14]=[CH:13]1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=C(OCCn1cnc2c[n+]([O-])c3ccccc3c21)c1ccccc1
Reactant: O=P(Cl)(Cl)Cl
Product: O=C(OCCn1cnc2c(Cl)nc3ccccc3c21)c1ccccc1

Procedure:
A mixture of 50 g (0.15 mole) of 1-(2-benzoyloxyethyl)-1H-imidazo[4,5-c]quinolin-5-oxide (from Example 119) and 200 ml of phosphorus oxychloride was heated for two hours on a steam bath. The mixture was then partially evaporated in vacuo. The mixture was then poured over ice and the solution was neutralized with sodium hydroxide. The product was separated by filtration, dissolved in dichloromethane, and the solution was washed with aqueous sodium bicarbonate solution and then dried. Evaporation provided a solid which was recrystallized from a 50:50 methanol:dichloromethane solution to provide white 1-(2-benzoyloxyethyl)-4-chloro-1H-imidazo[4,5-c]quinoline, m.p. 186°-190° C. Analysis: Calculated for C19H14ClN3O2 : %C, 64.9; %H, 4.0; %N, 12.0; Found: %C, 64.8; %H, 3.8; %N, 12.1.
Reaction SMILES: Br[CH2:2][C:3]1[CH2:8][CH2:7][CH2:6][CH2:5][CH:4]=1.[NH2:9][CH2:10][CH2:11][OH:12]>ClC=C(Cl)Cl.[OH-].[Na+]>[OH:12][CH2:11][CH2:10][NH:9][CH2:2][C:3]1[CH2:8][CH2:7][CH2:6][CH2:5][CH:4]=1
Reactant: NCCO
Reactant: BrCC1=CCCCC1
Agent: [Na+]
Agent: [OH-]
Solvent: ClC=C(Cl)Cl
Product: OCCNCC1=CCCCC1
Reaction time: 72 h
Yield: 62 %

Procedure:
A solution of 1-bromomethyl-1-cyclohexene (3.25 g) and 2-aminoethanol (6 mL) in trichloroethylene (40 mL) was heated at the reflux temp. for 3 d, cooled to room temp., and diluted with a 1N NaOH solution (30 mL). The aqueous layer was extracted with CH2Cl2 (4×20 mL) and the combined organic layers were washed with H2O (30 mL) and a saturated NaCl solution (30 mL), dried (Na2SO4) and concentrated under reduced pressure. The residue was purified by vacuum distillation to give N-hydroxyethyl-N-cyclohex-1-enylmethylamine as a colorless oil (1.78 g, 62%): bp 92-94° C. (6 mmHg),
Reaction SMILES: [CH2:1]([NH:17][C:18]1[CH:19]=[C:20]([C:23]([OH:25])=O)[S:21][CH:22]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16].COCCOC.C(Cl)[Cl:33]>>[ClH:33].[CH2:1]([NH:17][C:18]1[CH:19]=[C:20]([C:23]([Cl:33])=[O:25])[S:21][CH:22]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16]
Reactant: ClCCl
Reactant: CCCCCCCCCCCCCCCCNc1csc(C(=O)O)c1
Solvent: COCCOC
Product: CCCCCCCCCCCCCCCCNc1csc(C(=O)Cl)c1
Product: Cl

Procedure:
A cold solution of 25 g. of 4-hexadecylamino-2-thiophenecarboxylic acid in 500 ml. of 1,2-dimethoxyethane-methylene chloride (4:1) is prepared and dry hydrochloric acid is bubbled through the solution until no more precipitate forms. The solution is treated with 25 ml. thionyl chloride and refluxed until all of the precipitate has dissolved. The solvents are evaporated to yield the product as an orange semi-crystalline mass.
Reaction SMILES: [CH:1]12[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH2:2]1)[CH2:8]2.[OH:11]N1[C:16](=[O:17])[C:15]2=[CH:18][CH:19]=[CH:20][CH:21]=[C:14]2C1=O.O=O>C(O)(=O)C>[C:1]12([OH:11])[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH2:2]1)[CH2:8]2.[CH:15]12[CH2:14][CH:21]3[CH2:20][CH:19]([CH2:8][CH:1]([CH2:2]3)[C:16]1=[O:17])[CH2:18]2
Reactant: O=C1c2ccccc2C(=O)N1O
Reactant: C1C2CC3CC1CC(C2)C3
Agent: O=O
Solvent: CC(=O)O
Product: O=C1C2CC3CC(C2)CC1C3
Product: OC12CC3CC(CC(C3)C1)C2
Yield: 4 %
Yield: 50 %

Procedure:
To 25 milliliters of acetic acid were added 10 millimoles of adamantane, 1 millimole of N-hydroxyphthalimide and 0.05 millimole of acetylacetonatocopper(II) Cu(AA)2. In an oxygen atmosphere, the resultant mixture was stirred at a temperature of 75° C. for 6 hours. Adamantane was transformed, with a transformation rate of 53%, into 1-adamantanol (yield 50%) and 2-adamantanone (yield 4%). The selectivity for the alcohol and ketone was 97%.
Reaction SMILES: C(O[C:4](=[N:6][C:7](=O)[C:8]1[CH:13]=[CH:12][CH:11]=[C:10]([Cl:14])[CH:9]=1)[CH3:5])C.[NH:16]([C:18]1[N:23]=[CH:22][C:21]([S:24]([NH2:27])(=[O:26])=[O:25])=[CH:20][CH:19]=1)[NH2:17].O>ClCCl.CO>[Cl:14][C:10]1[CH:9]=[C:8]([C:7]2[N:16]([C:18]3[N:23]=[CH:22][C:21]([S:24]([NH2:27])(=[O:26])=[O:25])=[CH:20][CH:19]=3)[N:17]=[C:4]([CH3:5])[N:6]=2)[CH:13]=[CH:12][CH:11]=1
Reactant: NNc1ccc(S(N)(=O)=O)cn1
Reactant: CCOC(C)=NC(=O)c1cccc(Cl)c1
Solvent: CO
Solvent: ClCCl
Solvent: O
Product: Cc1nc(-c2cccc(Cl)c2)n(-c2ccc(S(N)(=O)=O)cn2)n1
Reaction time: 8 h
Yield: 49 %

Procedure:
N-(1-ethoxy-ethylidene)-3-chloro-benzamide 472 mg (2.09 mmol) was dissolved in a mixed solvent of dichloromethane 20 ml and methanol 10 ml, and 6-hydrazinopyridine-3-sulfonic acid amide 433 mg (2.23 mmol) was added to the solution and stirred for 8 hours. After completing the reaction, water 20 ml was added to the reacting solution and extracted two times with dichloromethane, and then, the collected organic layer was washed with saturated brine. The organic layer was dried with anhydrous magnesium sulfate, filtered and concentrated under reduced pressure, and the resulting product was re-crystallized in acetone and hexane phase. As a result, 6-[5-(3-chloro-phenyl)-3-methyl-[1,2,4]triazole-1-yl]-pyridine-3-sulfonic acid amide (358 mg, yield: 49%) was obtained as a solid phase.
Reaction SMILES: [OH:1][CH:2]1[CH2:7][CH2:6][NH:5][CH2:4][CH2:3]1.Cl.Cl[C:10]1[CH:15]=[CH:14][N:13]=[CH:12][CH:11]=1.C(=O)([O-])O.[Na+]>C(O)CC(C)C>[OH:1][CH:2]1[CH2:7][CH2:6][N:5]([C:10]2[CH:15]=[CH:14][N:13]=[CH:12][CH:11]=2)[CH2:4][CH2:3]1
Reactant: Clc1ccncc1
Reactant: OC1CCNCC1
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CC(C)CCO
Product: OC1CCN(c2ccncc2)CC1
Yield: 34.1 %

Procedure:
A mixture of 4-hydroxypiperidine (30 g), 4-chloropyridine hydrochloride (45 g), sodium hydrogen carbonate (60 g) and isoamylalcohol (300 ml) was refluxed for 60 hours. The reaction solution was cooled, and insoluble materials were filtered off. The filtrate was concentrated, and the resulting crystals were washed with ether and dried to give 4-hydroxy-1-(4-pyridyl)piperidine (18 g).
Reaction SMILES: [H-].[Na+].[CH2:3]([OH:8])[CH2:4][CH2:5][CH2:6][OH:7].[Br:9][C:10]1[C:11]([Cl:29])=[CH:12][C:13](F)=[C:14]([CH:27]=1)[C:15]([NH:17][C:18]1[C:23]([CH3:24])=[CH:22][CH:21]=[CH:20][C:19]=1[O:25][CH3:26])=[O:16].[CH3:30]N(C=O)C>>[Br:9][C:10]1[C:11]([Cl:29])=[CH:12][C:13]([O:7][CH2:6][CH2:5][CH2:4][CH2:3][OH:8])=[C:14]([CH:27]=1)[C:15]([N:17]([C:18]1[C:23]([CH3:24])=[CH:22][CH:21]=[CH:20][C:19]=1[O:25][CH3:26])[CH3:30])=[O:16]
Reactant: OCCCCO
Reactant: CN(C)C=O
Reactant: COc1cccc(C)c1NC(=O)c1cc(Br)c(Cl)cc1F
Agent: [H-]
Agent: [Na+]
Product: COc1cccc(C)c1N(C)C(=O)c1cc(Br)c(Cl)cc1OCCCCO
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
NaH (373 mg, 9.3 mmol, 60% in mineral oil) was added to 1,4-butanediol (3.5 g, 38.9 mmol) in dry DMF (50 mL). The mixture was stirred at room temperature for 15 minutes. 5-Bromo-4-chloro-2-fluoro-N-(2-methoxy-6-methyl-phenyl)-benzamide (3.0 g, 7.8 mmol) in DMF (25 mL) was added slowly. The mixture was then heated at 50° C. for 2 hrs, cooled to room temperature and partitioned between DCM and water. The organic layer was separated, washed with 1H HCl, sat NaHCO3 and brine, then dried over Na2SO4. The filtrate was concentrated and the residue purified using column chromatography with a gradient of 50% ethyl acetate in hexanes to 100% ethyl acetate to yield 5-bromo-4-chloro-2-(4-hydroxy-butoxy)-N-(2-methoxy-6-methyl-phenyl)-N-methyl-benzamide (2.3 g). MS: 457.9 (M+H)+, tR=2.38 min (method 1).