Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: N12CCCN=C1CCCC[CH2:2]2.[NH2:12][C:13]1[N:14]=[CH:15][C:16]([C:28]2[NH:32][N:31]=[C:30]([CH:33]3[CH2:38][CH2:37][N:36]([C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])[CH2:35][CH2:34]3)[N:29]=2)=[N:17][C:18]=1[C:19]1[O:20][C:21]([C:24]([CH3:27])([CH3:26])[CH3:25])=[N:22][N:23]=1.C.IC>O>[NH2:12][C:13]1[N:14]=[CH:15][C:16]([C:28]2[N:32]([CH3:2])[N:31]=[C:30]([CH:33]3[CH2:38][CH2:37][N:36]([C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])[CH2:35][CH2:34]3)[N:29]=2)=[N:17][C:18]=1[C:19]1[O:20][C:21]([C:24]([CH3:26])([CH3:27])[CH3:25])=[N:22][N:23]=1
Reactant: C1CCC2=NCCCN2CC1
Reactant: CC(C)(C)OC(=O)N1CCC(c2n[nH]c(-c3cnc(N)c(-c4nnc(C(C)(C)C)o4)n3)n2)CC1
Solvent: O
Solvent: CI
Product: Cn1nc(C2CCN(C(=O)OC(C)(C)C)CC2)nc1-c1cnc(N)c(-c2nnc(C(C)(C)C)o2)n1
Temperature: -5 °C
Reaction time: 16 h
Yield: 50.1 %

Procedure:
1,8-Diazabicyclo[5.4.0]undec-7-ene (19.87 mL, 132.90 mmol) was added to a suspension of tert-butyl 4-(5-(5-amino-6-(5-tert-butyl-1,3,4-oxadiazol-2-yl)pyrazin-2-yl)-1H-1,2,4-triazol-3-yl)piperidine-1-carboxylate (48 g, 102.23 mmol) in 2-methylTHF (300 mL). A dark solution was obtained after 5 minutes which was treated with charcoal and filtered through a celite pad, washing the charcoal and charcoal with additional 2-methylTHF (100 mL). The filtrate was stirred with an air stirrer at −5° C. in a 3 L jacketed fixed vessel under an atmosphere of nitrogen. 2-methylTHF (100 mL) was added to help stir the yellow suspension. Iodomethane (7.96 mL, 127.78 mmol) was added dropwise over 15 minutes. The mixture was stirred for 2 hours and the reaction mixture was warmed to room temperature. After 16 hours, additional iodomethane (6 mL) and DBU (20 mL) was added and stirring was continued for 16 hours. The mixture was poured into water and stirred for 5 minutes. The insoluble material was isolated as a beige solid and dried in vacuo to afford tert-butyl 4-(5-(5-amino-6-(5-tert-butyl-1,3,4-oxadiazol-2-yl)pyrazin-2-yl)-1-methyl-1H-1,2,4-triazol-3-yl)piperidine-1-carboxylate (24.77 g, 50.1%). The mother liquors were concentrated under reduced pressure and the residue was purified by flash column chromatography on silica using MTBE as the eluant. A second crop of the desired product (13.04 g, 26%), was thus obtained as a yellow solid: 1H NMR Spectrum: (DMSO-d6) 1.47 (9H, s), 1.51 (9H, s), 1.57-1.76 (2H, m), 1.94-2.1 (2H, m), 2.87-3.09 (3H, m), 3.9-4.08 (2H, m), 4.26 (3H, s), 7.97 (2H, br, s), 8.92 (1H, s); Mass Spectrum [M+H]+=484
Reaction SMILES: [NH:1]1[CH:5]=[C:4]([C:6]2[C:7]3[CH:14]=[CH:13][N:12]([CH2:15][O:16][CH2:17][CH2:18][Si:19]([CH3:22])([CH3:21])[CH3:20])[C:8]=3[N:9]=[CH:10][N:11]=2)[CH:3]=[N:2]1.[CH2:23]([S:25]([N:28]1[CH2:31][C:30](=[CH:32][C:33]#[N:34])[CH2:29]1)(=[O:27])=[O:26])[CH3:24].C1CCN2C(=NCCC2)CC1>C(#N)C>[CH2:23]([S:25]([N:28]1[CH2:29][C:30]([CH2:32][C:33]#[N:34])([N:1]2[CH:5]=[C:4]([C:6]3[C:7]4[CH:14]=[CH:13][N:12]([CH2:15][O:16][CH2:17][CH2:18][Si:19]([CH3:22])([CH3:21])[CH3:20])[C:8]=4[N:9]=[CH:10][N:11]=3)[CH:3]=[N:2]2)[CH2:31]1)(=[O:26])=[O:27])[CH3:24]
Reactant: C[Si](C)(C)CCOCn1ccc2c(-c3cn[nH]c3)ncnc21
Reactant: CCS(=O)(=O)N1CC(=CC#N)C1
Solvent: CC#N
Solvent: C1CCC2=NCCCN2CC1
Product: CCS(=O)(=O)N1CC(CC#N)(n2cc(-c3ncnc4c3ccn4COCC[Si](C)(C)C)cn2)C1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 97.3 %

Procedure:
To a suspension of 4-(1H-pyrazol-4-yl)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidine (5, 440 g, 1.395 mol) and 2-(1-(ethylsulfonyl)azetidin-3-ylidene)acetonitrile (11, 312.4 g, 1.68 mol, 1.2 equiv) in acetonitrile (4.4 L) was added DBU (249.8 mL, 1.67 mol, 1.2 equiv) drop wise to keep the reaction temperature between 15-25° C. After adding DBU, the reaction mixture became homogeneous, but a precipitate appeared in 30 min. The reaction mixture was stirred for 3 h at room temperature. When HPLC showed that the reaction was deemed complete, the reaction mixture was quenched with water (11 L). The resulting mixture was stirred at room temperature for additional 30 min and then filtered. The solid cake was washed with water (4 L), MTBE (2 L) and dried in vacuum oven at 35° C. for 24 h to afford crude 2-(1-(ethylsulfonyl)-3-(4-(7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)azetidin-3-yl)acetonitrile (12, 681 g, 699.8 g theoretical, 97.3% yield) as white solids, which was found to be sufficiently pure for the subsequent reaction without further purification. For 12: 1HNMR (CDCl3, 300 MHz), 6 8.86 (s, 1H), 8.45 (s, 1H), 8.35 (s, 1H), 7.43 (d, 1H), 6.80 (d, 1H), 5.68 (s, 2H), 4.65 (d, 2H), 4.27 (d, 2H), 3.55 (s, 2H), 3.4 (t, 2H), 3.07 (m, 2H), 1.42 (m, 3H), 0.92 (m, 2H), -0.05 (s, 9H) ppm; C22H31N7O3SSi (MW, 501.68), LCMS (EI) m/e 502 (M++H).
Reaction SMILES: FC(F)(F)C(O)=O.C1(OC)C=CC=CC=1.[CH3:16][N:17]([CH2:39][C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1)[C:18](=[O:38])[C@@H:19]([NH:30]C(OC(C)(C)C)=O)[CH2:20][C:21]1[C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[NH:23][CH:22]=1>>[CH3:16][N:17]([CH2:39][C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1)[C:18](=[O:38])[C@@H:19]([NH2:30])[CH2:20][C:21]1[C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[NH:23][CH:22]=1
Reactant: CN(Cc1ccccc1)C(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)OC(C)(C)C
Solvent: O=C(O)C(F)(F)F
Solvent: COc1ccccc1
Product: CN(Cc1ccccc1)C(=O)[C@@H](N)Cc1c[nH]c2ccccc12
Temperature: 0 °C
Reaction time: 0.25 h
Yield: 114 %

Procedure:
Cold trifluoroacetic acid (TFA, 4 mL) and 0.36 mL of anisole (3.28 mmol) were added to 1.215 g (2.98 mmol) of N-methyl-N-benzyl-2-(S)-t-butyloxycarbonylamino-3-(3-indolyl)propionamide and the resulting solution was stirred at 0° C. for 15 min. The ice bath was removed and the solution was allowed to warm to room temperature. After 30 min the reaction mixture was concentrated and the residue was partitioned between saturated NaHCO3 and CH2Cl2. The organic layer was washed with brine, dried and concentrated leaving 1.044 g of the title compound which was used in the next step without purification.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([S:9]([N:12]2[CH2:17][CH2:16][C:15]3=[N:18][NH:19][C:20]([NH:21][C:22](=[O:27])[C:23]([F:26])([F:25])[F:24])=[C:14]3[CH2:13]2)(=[O:11])=[O:10])[CH:5]=[C:6]([F:8])[CH:7]=1.C(N(CC)CC)C.[C:35](Cl)([C:48]1[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=1)([C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1)[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1>ClCCl>[F:8][C:6]1[CH:5]=[C:4]([S:9]([N:12]2[CH2:17][CH2:16][C:15]3[N:18]([C:35]([C:36]4[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=4)([C:48]4[CH:49]=[CH:50][CH:51]=[CH:52][CH:53]=4)[C:42]4[CH:43]=[CH:44][CH:45]=[CH:46][CH:47]=4)[N:19]=[C:20]([NH:21][C:22](=[O:27])[C:23]([F:24])([F:25])[F:26])[C:14]=3[CH2:13]2)(=[O:11])=[O:10])[CH:3]=[C:2]([F:1])[CH:7]=1
Reactant: O=C(Nc1[nH]nc2c1CN(S(=O)(=O)c1cc(F)cc(F)c1)CC2)C(F)(F)F
Reactant: ClC(c1ccccc1)(c1ccccc1)c1ccccc1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: O=C(Nc1nn(C(c2ccccc2)(c2ccccc2)c2ccccc2)c2c1CN(S(=O)(=O)c1cc(F)cc(F)c1)CC2)C(F)(F)F
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a mixture of N-[5-(3,5-difluoro-benzenesulfonyl)-4,5,6,7-tetrahydro-2H-pyrazolo[4,3-c]pyridin-3-yl]-2,2,2-trifluoro-acetamide (43.76 g, 106.65 mmol) and triethylamine (44.6 mL, 319.95 mmol) in dichloromethane (1 L), at room temperature, trityl chloride (31.22 g, 111.98 mmol) was added. The reaction was stirred at room temperature for 1 hour. The organic phase was washed with NaHCO3 saturated solution, water and brine, dried over sodium sulfate filtered and evaporated to dryness affording the crude title compound as white solid.
Reaction SMILES: [OH:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[CH:4][CH:3]=1.Br[CH2:11][CH2:12][CH:13]1[O:18][CH2:17][CH2:16][CH2:15][O:14]1.[I-].[K+].C(=O)([O-])[O-].[K+].[K+]>C(OCC)(=O)C.C(#N)C>[O:14]1[CH2:15][CH2:16][CH2:17][O:18][CH:13]1[CH2:12][CH2:11][O:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[CH:4][CH:3]=1
Reactant: O=Cc1ccc(O)cc1
Reactant: BrCCC1OCCCO1
Agent: O=C([O-])[O-]
Agent: [I-]
Agent: [K+]
Solvent: CC#N
Solvent: CCOC(C)=O
Product: O=Cc1ccc(OCCC2OCCCO2)cc1
Yield: 100.2 %

Procedure:
In a 500 ml flask, 120 ml of acetonitrile, 13.8 g of 4-hydroxybenzaldehyde, 21.1 g of 2-(2-bromoethyl)-1,3-dioxane, 1.8 g of potassium iodide, and 35.8 g of potassium carbonate were placed and then, reacted at 80° C. for 5 hrs. Thereafter, 200 ml of ethyl acetate was added to the reaction mixture and washed once with a saturated aqueous potassium carbonate solution, distilled water, and saturated saline. The washed organic phase was dried over anhydrous magnesium sulfate and removed solvent, to give 25.6 g of 4-(2-[1,3]-dioxane-2-yl-ethoxy)benzaldehyde.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([S:8][C:9]#N)=[CH:4][C:3]=1[N+:11]([O-:13])=[O:12].CN(C)C=O.[BH4-].[Na+].[Br:21][CH2:22][CH2:23]CBr>O>[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([S:8][CH2:9][CH2:23][CH2:22][Br:21])=[CH:4][C:3]=1[N+:11]([O-:13])=[O:12]
Reactant: BrCCCBr
Reactant: N#CSc1ccc(N)c([N+](=O)[O-])c1
Agent: [BH4-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: Nc1ccc(SCCCBr)cc1[N+](=O)[O-]
Reaction time: 1 h

Procedure:
5.85 G. of 1-amino-2-nitro-4-thiocyanatobenzene in 20 ml. dimethylformamide is treated under nitrogen with 1.14 g. sodium borohydride at not greater than 30°. The mixture is stirred for one hour at 15°-20°, then treated with 12 g. of 1,3-dibromopropane at 20°-25°. After a further 3 hours, water is added and the crude product extracted with chloroform. The dried chloroform solution is passed through a column of silica gel to remove polar material. Pure 1-amino-2-nitro-4-(3-bromopropylthio)benzene is obtained from the eluate.
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6](F)[CH:5]=[C:4]([CH3:9])[N:3]=1.[Cl:10][C:11]1[CH:16]=[C:15]([S:17][CH3:18])[C:14]([Cl:19])=[CH:13][C:12]=1[OH:20].C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[F:1][C:2]1[CH:7]=[C:6]([O:20][C:12]2[CH:13]=[C:14]([Cl:19])[C:15]([S:17][CH3:18])=[CH:16][C:11]=2[Cl:10])[CH:5]=[C:4]([CH3:9])[N:3]=1
Reactant: Cc1cc(F)cc(F)n1
Reactant: CSc1cc(Cl)c(O)cc1Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CSc1cc(Cl)c(Oc2cc(C)nc(F)c2)cc1Cl
Temperature: 0 °C

Procedure:
Amounts of 12.9 gm (0.1 mol) of 2,4-difluoro-6-methylpyridine, 20.7 gm (0.1 mol) of 2,5-dichloro-4-methylmercaptophenol, and 13.8 gm (0.1 mol) of potassium carbonate in 100 ml of dimethylformamide were stirred for 10 hours at 100° C. The resulting solution was then poured onto 500 ml of ice water, and the precipitate formed was recovered by suction filtration and washed with water. It was then taken up in methylene chloride, and this solution was dried over sodium sulphate and evaporated down. The oil obtained was purified over a silica gel column (ethylene chloride as the eluant) and 16.3 gm (57% of theory) of the desired ether were obtained.
Reaction SMILES: [N:1]1[N:2]=[C:3]([S:6]([CH2:8][C:9]2[CH:17]=[CH:16][C:12]([C:13]([OH:15])=O)=[CH:11][CH:10]=2)=[O:7])[NH:4][CH:5]=1.N1N=C(S(CC2C=CC(C(O)=O)=CC=2)(=O)=O)NC=1.[Cl:36][C:37]1[CH:43]=[CH:42][C:40]([NH2:41])=[CH:39][C:38]=1[C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][N:45]=1>>[N:1]1[N:2]=[C:3]([S:6]([CH2:8][C:9]2[CH:10]=[CH:11][C:12]([C:13]([NH:41][C:40]3[CH:42]=[CH:43][C:37]([Cl:36])=[C:38]([C:44]4[CH:49]=[CH:48][CH:47]=[CH:46][N:45]=4)[CH:39]=3)=[O:15])=[CH:16][CH:17]=2)=[O:7])[NH:4][CH:5]=1
Reactant: Nc1ccc(Cl)c(-c2ccccn2)c1
Reactant: O=C(O)c1ccc(CS(=O)c2nnc[nH]2)cc1
Agent: O=C(O)c1ccc(CS(=O)(=O)c2nnc[nH]2)cc1
Product: O=C(Nc1ccc(Cl)c(-c2ccccn2)c1)c1ccc(CS(=O)c2nnc[nH]2)cc1

Procedure:
500 mg of methyl 4-(bromomethyl)benzoate was reacted with 4H-1,2,4-triazole-3-thiol via Procedure Q. 542 mg of methyl 4-((4H-1,2,4-triazol-3-ylthio)methyl)benzoate was subsequently reacted via Procedure R to give an approximate 1:9 mixture of methyl 4-((4H-1,2,4-triazol-3-ylsulfinyl)methyl)benzoate and methyl 4-((4H-1,2,4-triazol-3-ylsulfonyl)methyl)benzoate. The mixture of 467 mg was hydrolyzed via Procedure M to give 4-((4H-1,2,4-triazol-3-ylsulfinyl)methyl)benzoic acid and 4-((4H-1,2,4-triazol-3-ylsulfonyl)methyl)benzoic acid. 107 mg of the mixture of 4-((4H-1,2,4-triazol-3-ylsulfinyl)methyl)benzoic acid and 4-((4H-1,2,4-triazol-3-ylsulfonyl)methyl)benzoic acid was coupled to 75 mg of 4-chloro-3-(pyridin-2-yl)aniline via Procedure G. The mixture was seperated on reverse phase HPLC to give 4-((4H-1,2,4-triazol-3-ylsulfinyl)methyl)-N-(4-chloro-3-(pyridin-2-yl)phenyl)benzamide. MS (Q1) 438.1 (M)+.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[C:11]1[N:16]=[CH:15][C:14]([O:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH3:25])=[CH:13][N:12]=1)[C:5](O)=[O:6].S(Cl)([Cl:28])=O>>[F:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[C:11]1[N:16]=[CH:15][C:14]([O:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH3:25])=[CH:13][N:12]=1)[C:5]([Cl:28])=[O:6]
Reactant: O=S(Cl)Cl
Reactant: CCCCCCCCOc1cnc(-c2ccc(C(=O)O)cc2F)nc1
Product: CCCCCCCCOc1cnc(-c2ccc(C(=O)Cl)cc2F)nc1

Procedure:
3-Fluoro-4-(5-n-octyloxypyrimidine-2-yl)benzoic acid (1.60 g) was heated together with excess thionyl chloride for 8 hours under reflux and thereafter, unaltered thionyl chloride was distilled off to obtain 3-fluoro-4-(5-n-octyloxypyrimidine-2-yl)benzoic acid chloride.
Reaction SMILES: [NH2:1][C:2]1[CH:10]=[C:9]([N:11]2[CH2:16][CH2:15][O:14][CH2:13][CH2:12]2)[CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].CN([Si](C)(C)C)C(=O)C(F)(F)F.[CH3:29][S:30](Cl)(=[O:32])=[O:31].C(N(CC)CC)C>C(Cl)Cl>[CH3:29][S:30]([NH:1][C:2]1[CH:10]=[C:9]([N:11]2[CH2:12][CH2:13][O:14][CH2:15][CH2:16]2)[CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=[O:5])(=[O:32])=[O:31]
Reactant: CS(=O)(=O)Cl
Reactant: Nc1cc(N2CCOCC2)ccc1C(=O)O
Agent: CN(C(=O)C(F)(F)F)[Si](C)(C)C
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CS(=O)(=O)Nc1cc(N2CCOCC2)ccc1C(=O)O
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To a suspension of 2-amino-4-morpholin-4-ylbenzoic acid (230 mg; 1.04 mmol) in CH2Cl2 (3 mL) was added N-methyl-N-(trimethylsilyl)trifluoroacetamide (0.4 mL; 2.1 mmol) via syringe at room temperature under a nitrogen atmosphere. The resulting mixture was heated to reflux for 10 minutes, then allowed to cool to room temperature. Methanesulfonyl chloride (1.2 eq.) and triethylamine (1.2 eq.) were added, and the resulting mixture allowed to stir for 2 hours. The reaction was diluted with CH2Cl2 (30 mL) and washed with water (2×10 mL) and brine, then dried (MgSO4), filtered, and concentrated in vacuo to provide the sulfonamide as a white solid (280 mg; 90%).
Reaction SMILES: [I:1][C:2]1[CH:10]=[C:9]2[C:5]([CH2:6][CH2:7][CH2:8]2)=[CH:4][C:3]=1[C:11]#N.CC(C[AlH]CC(C)C)C.C1(C)C=CC=CC=1.Cl.CC[O:32]CC>ClCCl>[I:1][C:2]1[CH:10]=[C:9]2[C:5]([CH2:6][CH2:7][CH2:8]2)=[CH:4][C:3]=1[CH:11]=[O:32]
Reactant: N#Cc1cc2c(cc1I)CCC2
Reactant: CCOCC
Agent: CC(C)C[AlH]CC(C)C
Agent: Cl
Solvent: Cc1ccccc1
Solvent: ClCCl
Product: O=Cc1cc2c(cc1I)CCC2
Temperature: -78 °C
Reaction time: 0.25 h
Yield: 73 %

Procedure:
To a solution of 6-iodoindane-5-carbonitrile (36.5 mg, 0.136 mmol) in dichloromethane (1.0 mL) under N2 at −78° C. was added a solution of 1N DIBALH in toluene (272 μL, 0.272 mmol) dropwise. The reaction was stirred at −78° C. for 15 min. Keeping the temperature at −78° C., another two portions of DIBALH (100 μL each) were added until the starting material disappeared by TLC. The reaction mixture was poured into 2N HCl (45 mL) and diluted with Et2O. The mixture was stirred for 0.5 h. The Et2O layer was separated. The aqueous layer was extracted with Et2O (2×). The organic extracts were combined, dried (Na2SO4) and concentrated in vacuo. The residue was purified by flash chromatography (Si, hexanes/EtOAc) to afford 6-iodoindane-5-carbaldehyde (27 mg, 73%). 1H NMR (500 MHz, CDCl3) δ 10.08 (s, 1H), 7.83 (s, 1H), 7.79 (s, 1H), 2.98 (t, J=7.5 Hz, 2H), 2.94 (t, J=7.5 Hz, 2H,), 2.19-2.13 (m, 2H).
Reaction SMILES: C1[O:3]C1.O[C:5]1[CH:10]=[CH:9][C:8]([C:11]([C:14]2[CH:19]=[CH:18][C:17]([OH:20])=CC=2)(C)C)=[CH:7][CH:6]=1.C1OC1C.C(O)(=O)C1C=CC(C(O)=O)=CC=1.C([Sn](=O)CCCC)CCC>>[CH:14]([CH:19]=[CH:18][C:17]([OH:20])=[O:3])=[CH:11][C:8]1[CH:7]=[CH:6][CH:5]=[CH:10][CH:9]=1
Reactant: CC(C)(c1ccc(O)cc1)c1ccc(O)cc1
Reactant: C1CO1
Agent: CC1CO1
Agent: CCCC[Sn](=O)CCCC
Agent: O=C(O)c1ccc(C(=O)O)cc1
Product: O=C(O)C=CC=Cc1ccccc1

Procedure:
In a reaction vessel equipped with a condenser, a stirrer and a nitrogen inlet tube, 682 parts of ethylene oxide 2 mol adduct of bisphenol A, 81 parts of propylene oxide 2 mol adduct of bisphenol A, 283 parts of terephthalic acid, 22 parts of trimellitic anhydride, and 2 parts of dibutyltin oxide were added. The mixture was subjected to a reaction for 8 hours at 230° C. under normal pressure, and subsequently reacted for 5 hours under a reduced pressure of from 10 mmHg to 15 mmHg. Thus [Intermediate Polyester 1] was obtained. The [Intermediate Polyester 1] was found to have a number average molecular weight of 2,100, a mass average molecular weight of 9,500, a glass transition temperature (Tg) of 55° C., an acid value of 0.5 mgKOH/g and a hydroxyl value of 51 mgKOH/g.
Reaction SMILES: Cl.[NH2:2][OH:3].C([O-])(=O)C.[Na+].[CH3:9][CH2:10][C:11]([C:13]1[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][CH:14]=1)=O>O.C(O)C>[CH3:20][O:19][C:16]1[CH:17]=[CH:18][C:13]([C:11](=[N:2][OH:3])[CH2:10][CH3:9])=[CH:14][CH:15]=1
Reactant: CCC(=O)c1ccc(OC)cc1
Reactant: NO
Agent: CC(=O)[O-]
Agent: Cl
Agent: [Na+]
Solvent: CCO
Solvent: O
Product: CCC(=NO)c1ccc(OC)cc1
Reaction time: 8 h
Yield: 97.8 %

Procedure:
A solution of hydroxylamine hydrochloride (3.33 grams, 48 mmol) and sodium acetate (4.92 grams, 60 mmol) in 20 milliliters of water was added to a stirred solution of 4-methoxypropiophenone (5.26 grams, 30.0 mmol) in a mixture of water (30 milliliters) and ethanol (30 milliliters), a further 20 milliliters of ethanol was added to get a homogenous solution, which was stirred overnight. The resulting slurry was filtered, the filtrate was partially concentrated, to remove the ethanol and a white solid precipitated. The slurry was filtered and the solid was washed with water, and dried in vacuo (25° C., <1 mm) to afford 5.26 grams (98%) of product as a white solid: 1H NMR (CDCl3) δ7.64-7.42 (m , 2H), 7.04-6.81(m, 2H), 3.82(s, 3H), 2.81(q , J=7.6 Hz), 2H), 1.17(t , J=7.6 Hz, 3H).
Reaction SMILES: [CH2:1]([O:4][CH2:5][CH2:6][N:7]1[C:19]2[C:18]3[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=3[N:12]=[C:11]([NH2:20])[C:10]=2[N:9]=[CH:8]1)[C:2]#[CH:3].[CH3:21][C:22]1[CH:27]=[CH:26][CH:25]=[C:24]([CH3:28])[C:23]=1I>>[CH3:21][C:22]1[CH:27]=[CH:26][CH:25]=[C:24]([CH3:28])[C:23]=1[C:3]#[C:2][CH2:1][O:4][CH2:5][CH2:6][N:7]1[C:19]2[C:18]3[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=3[N:12]=[C:11]([NH2:20])[C:10]=2[N:9]=[CH:8]1
Reactant: C#CCOCCn1cnc2c(N)nc3ccccc3c21
Reactant: Cc1cccc(C)c1I
Product: Cc1cccc(C)c1C#CCOCCn1cnc2c(N)nc3ccccc3c21
Yield: 8 %

Procedure:
Using the general method of Example 7, 1-[2-(2-propynyloxy)ethyl]-1H-imidazo[4,5-c]quinolin-4-amine (0.50 g, 1.88 mmol) was reacted with 2,6-dimethyl iodobenzene (0.61 g, 2.63 mmol). The crude product was purified by column chromatography eluting with 95/5 dichloromethane/methanol to provide 0.056 g of 1-(2-{[3-(2,6-dimethylphenyl)-2-propynyl]oxy}ethyl)-1H-imidazo[4,5-c]quinolin-4-amine as a solid, m.p. 200-201° C.
Reaction SMILES: Cl.[NH2:2][C@H:3]([C:14]([O:16][CH3:17])=[O:15])[CH2:4][C:5]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[NH:7][CH:6]=1.C(N(CC)CC)C.[F:25][C:26]1[CH:36]=[CH:35][C:29]([CH:30]=[CH:31][C:32](O)=[O:33])=[CH:28][CH:27]=1.CCN=C=NCCCN(C)C.Cl>C(Cl)Cl>[F:25][C:26]1[CH:27]=[CH:28][C:29]([CH:30]=[CH:31][C:32]([NH:2][C@H:3]([C:14]([O:16][CH3:17])=[O:15])[CH2:4][C:5]2[C:13]3[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=3)[NH:7][CH:6]=2)=[O:33])=[CH:35][CH:36]=1
Reactant: O=C(O)C=Cc1ccc(F)cc1
Reactant: COC(=O)[C@@H](N)Cc1c[nH]c2ccccc12
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: COC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)C=Cc1ccc(F)cc1
Yield: 74.7 %

Procedure:
The same procedures as in Example 2 were carried out from methyl L-tryptophanate hydrochloride (4.0 g), triethylamine (4.8 mL), 4-fluorocinnamic acid (2.9 g), WSC.HCl (3.3 g), and methylene chloride (150 mL), to give the captioned compound (4.3 g, 74%) as an oily product.
Reaction SMILES: C(O[CH:4]=[C:5]([C:8]#[N:9])[C:6]#[N:7])C.C(N(CC)CC)C.Cl.[CH:18]1([NH:24][NH2:25])[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]1>C(O)C>[NH2:9][C:8]1[N:24]([CH:18]2[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]2)[N:25]=[CH:4][C:5]=1[C:6]#[N:7]
Reactant: CCOC=C(C#N)C#N
Reactant: NNC1CCCCC1
Agent: Cl
Solvent: CCO
Solvent: CCN(CC)CC
Product: N#Cc1cnn(C2CCCCC2)c1N

Procedure:
First ethoxymethylenemalononitrile (2.43 g, 19.9 mmol) and then 8 ml of triethylamine are added to a solution of cyclohexylhydrazine hydrochloride (3 g, 19.9 mmol) in 36 ml of ethanol at room temperature. The mixture is refluxed for 20 min and then cooled. The solvent is stripped off in a rotary evaporator, and the residue is taken up in DCM, washed with aqueous sodium bicarbonate solution, dried over sodium sulfate, filtered and concentrated in vacuo. The crude product is chromatographed on silica gel (mobile phase: dichloromethane/methanol 0-10%).
Reaction SMILES: [C:1]([C:3]1[C:8](=[O:9])[NH:7][C:6]2[O:10][CH2:11][C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=3[C:5]=2[CH:4]=1)#[N:2].N1C=CC=CC=1.[SH2:24]>C(N(CC)CC)C>[CH:4]1[C:5]2[C:13]3[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=3[CH2:11][O:10][C:6]=2[NH:7][C:8](=[O:9])[C:3]=1[C:1](=[S:24])[NH2:2]
Reactant: S
Reactant: N#Cc1cc2c([nH]c1=O)OCc1ccccc1-2
Solvent: c1ccncc1
Solvent: CCN(CC)CC
Product: NC(=S)c1cc2c([nH]c1=O)OCc1ccccc1-2

Procedure:
Add 4.20 gm of 2-cyano-4,6-dihydro-3H[2]benzopyrano[3,4-b]-pyridin-3-one to 50 gm of pyridine. Add 3.0 ml of triethylamine to the system. Cool the system to 0°-5° and treat the system with hydrogen sulfide gas until the reaction is complete as indicated by thin layer chromatography. Isolate the title compound.
Reaction SMILES: [Br-].[C:2]([CH2:4][CH2:5][CH2:6][P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)#[N:3].[CH2:26]([N:33]1[CH2:38][CH2:37][CH2:36][C:35](=O)[CH2:34]1)[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1>>[CH2:26]([N:33]1[CH2:38][CH2:37][CH2:36][C:35](=[CH:6][CH2:5][CH2:4][C:2]#[N:3])[CH2:34]1)[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1
Reactant: N#CCCC[P+](c1ccccc1)(c1ccccc1)c1ccccc1
Reactant: O=C1CCCN(Cc2ccccc2)C1
Agent: [Br-]
Product: N#CCCC=C1CCCN(Cc2ccccc2)C1
Temperature: 0 °C
Reaction time: 8 h

Procedure:
77.3 g (188.3 mmol) 3-cyanopropyl triphenylphosphonium bromide are suspended in 300 ml tolueneand added to 22.0 g (191.9 mmol) potassium-tert-butylate. The mixture is cooled to ca. 0° C. under moisture exclusion and a solution of 34.6 g (182.8 mmol) 1-benzyl-3-piperidone in 50 ml tolueneare added dropwise under cooling. The batch is left to stand overnight at ca. 0° C., subsequently diluted with 200 ml tolueneand washed twice, each with 100 ml water. The organic phase is extracted with 150 ml half-concentrated hydrochloric acid. Subsequently, the aqueous phase is made basic with 200 ml 10% sodium hydroxide solution and extracted twice, each with 250 ml toluol. The solvent is removed under vacuum and the residue is chromatographically purified over silica gel with CHCl3/CH3OH (97/3). After drawing off the solvent, a light brown oil remains which is further processed without additional purification. Yield: 47.4 g (90%).