Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][C:2]1[S:3][C:4]([CH2:7][CH3:8])=[N:5][N:6]=1.[I:9][C:10]1[CH:17]=[CH:16][C:13]([CH2:14][Br:15])=[CH:12][CH:11]=1>CO>[BrH:15].[CH2:7]([C:4]1[S:3][C:2](=[NH:1])[N:6]([CH2:14][C:13]2[CH:16]=[CH:17][C:10]([I:9])=[CH:11][CH:12]=2)[N:5]=1)[CH3:8]
Reactant: BrCc1ccc(I)cc1
Reactant: CCc1nnc(N)s1
Solvent: CO
Product: Br
Product: CCc1nn(Cc2ccc(I)cc2)c(=N)s1
Yield: 52.6 %

Procedure:
A solution of 2-amino-5-ethyl-1,3,4-thiadiazole (645 mg) and 4-iodobenzyl bromide (1.49 g) in methanol (5 ml) was heated under reflux for 2 hours. After the reaction mixture was cooled, the crystals so precipitated were collected by filtration and then dried, whereby 1.12 g of the title compound was obtained.
Reaction SMILES: B(F)(F)F.CCOCC.B(Cl)([C@H]1[C@H](C)[C@@H]2C(C)(C)[C@@H](C2)C1)[C@H]1[C@H](C)[C@@H]2C(C)(C)[C@@H](C2)C1.[CH:32]([O:35][C:36]1[C:41]([CH3:42])=[CH:40][CH:39]=[CH:38][C:37]=1[CH2:43][C:44]([C:46]1[CH:51]=[CH:50][N:49]=[CH:48][CH:47]=1)=[O:45])([CH3:34])[CH3:33].Cl>C1COCC1.CO>[CH:32]([O:35][C:36]1[C:41]([CH3:42])=[CH:40][CH:39]=[CH:38][C:37]=1[CH2:43][C@@H:44]([C:46]1[CH:47]=[CH:48][N:49]=[CH:50][CH:51]=1)[OH:45])([CH3:34])[CH3:33]
Reactant: Cc1cccc(CC(=O)c2ccncc2)c1OC(C)C
Agent: C[C@@H]1[C@H]2C[C@@H](C[C@H]1B(Cl)[C@@H]1C[C@@H]3C[C@H]([C@H]1C)C3(C)C)C2(C)C
Agent: Cl
Agent: FB(F)F
Solvent: CO
Solvent: C1CCOC1
Solvent: CCOCC
Product: Cc1cccc(C[C@H](O)c2ccncc2)c1OC(C)C
Reaction time: 15 h

Procedure:
Under nitrogen, at −30° C. slowly add BF3.□Et2O (1.7 g, 12 mmol) to a solution of (−)-B-chlorodiisopinocampheylborane (6.1 g, 19 mmol) in THF (40 mL). Cool the solution to −40° and add 2-(2-isopropoxy-3-methylphenyl)-1-(4-pyridinyl)ethanone (3.2 g, 12 mmol). Allow the solution to slowly come to room temperature and stir for 15 hr. Add MeOH and 3M aqueous HCl to the reaction mixture and stir for an additional 45 min. Evaporate the solvent and dissolve the residue in 3M aqueous HCl and wash with heptane. Neutralize the aqueous fraction with 50% aqueous NaOH to pH 12 and extract with EtOAc. Wash the organic phase was with brine and dry over MgSO4. Evaporate the solvent to afford a yellow oil. Purify the oil by chromatography over SiO2 using EtOAc:heptane (1:1). Evaporate the product-containing fraction to give (S)-2-(2-isopropoxy-3-methylphenyl)-1-(4-pyridinyl)ethanol as an oil, 1.16 g (36%); 1H-NMR (CDCl3) δ 8.5-6.8 (m, 7H), 4.9 (m, 1H), 4.3 (m, 1H), 3.1-2.9 (m, 2H), 2.3 (s, 3H), 1.3 (d, 6H).
Reaction SMILES: [CH:1]1[C:6]([C:7]([NH2:9])=[O:8])=[CH:5][N:4]=[C:3]([NH2:10])[CH:2]=1.CN(C=O)C.CCN([CH2:21][CH3:22])CC.[Si:23](Cl)([CH2:28][CH3:29])([CH2:26][CH3:27])[CH2:24][CH3:25]>C(=O)=O>[CH2:24]([Si:23]([C:2]1[C:3]([NH2:10])=[N:4][C:5]([Si:23]([CH2:21][CH3:22])([CH2:26][CH3:27])[CH2:24][CH3:25])=[C:6]([CH:1]=1)[C:7]([NH2:9])=[O:8])([CH2:28][CH3:29])[CH2:26][CH3:27])[CH3:25]
Reactant: CCN(CC)CC
Reactant: CC[Si](Cl)(CC)CC
Reactant: NC(=O)c1ccc(N)nc1
Agent: O=C=O
Solvent: CN(C)C=O
Product: CC[Si](CC)(CC)c1cc(C(N)=O)c([Si](CC)(CC)CC)nc1N
Reaction time: 0.17 h

Procedure:
2.06 grams (15 m moles) of 6-AN and 35 ml dry DMF were added to a 250 ml flask and heated under Argon until the 6-AN dissolved. After cooling, but while the mixture was still warm, 25 ml (180 m moles) of Et3N was added to form a cloudy solution which was cooled in dry ice. After 10 minutes, 15 ml of Et3SiCl was added and the mixture kept in the dry ice for an additional 30 minutes. The mixture was left overnight at room temperature.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][CH:3]=1.[CH2:9]([OH:13])[CH2:10][C:11]#[CH:12]>C(N(CC)CC)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[F:8][C:5]1[CH:6]=[CH:7][C:2]([C:12]#[C:11][CH2:10][CH2:9][OH:13])=[CH:3][CH:4]=1
Reactant: Fc1ccc(Br)cc1
Reactant: C#CCCO
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Cu]I
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CCN(CC)CC
Product: OCCC#Cc1ccc(F)cc1
Reaction time: 5 h
Yield: 85.3 %

Procedure:
1 g of bis-(triphenylphosphine)-palladium(II) chloride, 3.8 g of copper(I) iodide and 8.7 g of triphenylphosphine were added in succession to a solution of 100 g of 4-bromofluorobenzene in 350 ml of triethylamine. This mixture was refluxed, after which 43.4 g of 3-butynol were added dropwise at this temperature (about 100° C.) in the course of 20 minutes. The mixture was stirred for a further 5 hours at this temperature. After the mixture had cooled, the triethylamine was distilled off. The residue was taken up in methyl tert-butyl ether and water. The aqueous phase was extracted twice with methyl tert-butyl ether, and the combined organic extracts were washed in succession with 1 N hydrochloric acid and with 10% strength sodium bicarbonate solution, dried over sodium sulfate and evaporated down in a rotary evaporator. Distillation under greatly reduced pressure gave 80 g (86%) of the desired compound.
Reaction SMILES: [OH:1][C@H:2]1[CH2:7][CH2:6][C@H:5]([C:8]([N:10]([O:12][CH3:13])[CH3:11])=[O:9])[CH2:4][CH2:3]1.N1C=CN=C1.[C:19]([Si:23]([CH3:26])([CH3:25])Cl)([CH3:22])([CH3:21])[CH3:20]>CN(C)C=O>[Si:23]([O:1][C@H:2]1[CH2:7][CH2:6][C@H:5]([C:8]([N:10]([O:12][CH3:13])[CH3:11])=[O:9])[CH2:4][CH2:3]1)([C:19]([CH3:22])([CH3:21])[CH3:20])([CH3:26])[CH3:25]
Reactant: CON(C)C(=O)[C@H]1CC[C@H](O)CC1
Reactant: CC(C)(C)[Si](C)(C)Cl
Agent: c1c[nH]cn1
Solvent: CN(C)C=O
Product: CON(C)C(=O)[C@H]1CC[C@H](O[Si](C)(C)C(C)(C)C)CC1
Temperature: 25 °C
Reaction time: 1.5 h

Procedure:
To a solution in N,N-dimethylformamide (91 mL) of the compound (8.52 g) obtained in step (1) above, imidazole (4.03 g) and tert-butyldimethylchlorosilane (6.86 g) were added and the mixture was stirred at room temperature for 1.5 hours. The reaction mixture was concentrated under reduced pressure and water was added to the resulting residue. After extraction with ethyl acetate, the combined organic layers were washed with water and saturated brine. The washed organic layers were dried over anhydrous magnesium sulfate and after removing the desiccant by filtration, the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=100:0-75:25) to give the titled compound as a colorless oil (10.5 g).
Reaction SMILES: [CH2:1]([OH:4])[CH2:2][OH:3].C1(C)C=CC(S(O)(=O)=O)=CC=1.[Br:16][C:17]1[CH:22]=[CH:21][C:20]([F:23])=[CH:19][C:18]=1[C:24](=O)[CH3:25].C([O-])(O)=O.[Na+]>C1C=CC=CC=1.O>[Br:16][C:17]1[CH:22]=[CH:21][C:20]([F:23])=[CH:19][C:18]=1[C:24]1([CH3:25])[O:4][CH2:1][CH2:2][O:3]1
Reactant: CC(=O)c1cc(F)ccc1Br
Reactant: OCCO
Agent: Cc1ccc(S(=O)(=O)O)cc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: c1ccccc1
Solvent: O
Product: CC1(c2cc(F)ccc2Br)OCCO1
Yield: 60.2 %

Procedure:
Ethylene glycol (25.6 mL, 458 mmol) and p-toluenesulfonic acid (4.36 g, 22.9 g) were added to a solution of 1-(2-bromo-5-fluorophenyl)ethanone (10.5 g, 45.8 mmol) stirring in benzene (250 mL). The reaction mixture was equipped with a Dean Stark trap containing 4.0 angstrom molecular sieves and refluxed for 16 h. The reaction was transferred to a separatory funnel containing a 1:1 mixture of H2O and sat. NaHCO3 (aq) and extracted with EtOAc (3×100 mL). The combined organics were washed with H2O, brine, dried over Na2SO4 and concentrated. The resulting oil was purified by column chromatography to give 2-(2-bromo-5-fluorophenyl)-2-methyl-1,3-dioxolane (7.20 g) in 58% yield. 1H NMR (CDCl3, 300 MHz) δ2.60 (s, 3 H) 4.02-4.20 (m, 4H), 6.85-6.90 (m, 1H), 7.29-7.33 (m, 1H), 7.48-7.56 (m, 1H).
Reaction SMILES: [ClH:1].[ClH:2].[NH:3]1[C:11]2[C:6](=[CH:7][C:8]([C:12]3[C:20]4[C:19]([NH2:21])=[N:18][CH:17]=[N:16][C:15]=4[N:14]([CH3:22])[CH:13]=3)=[CH:9][CH:10]=2)[CH2:5][CH2:4]1.N1[C:31]2[C:26](=[CH:27][C:28](C3C4C(N)=NC=NC=4N(C)C=3)=[CH:29][CH:30]=2)[CH2:25][CH2:24]1.CN(C([O:50]N1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>O>[Cl:1][C:28]1[CH:27]=[C:26]([CH2:25][C:24]([N:3]2[C:11]3[C:6](=[CH:7][C:8]([C:12]4[C:20]5[C:19]([NH2:21])=[N:18][CH:17]=[N:16][C:15]=5[N:14]([CH3:22])[CH:13]=4)=[CH:9][CH:10]=3)[CH2:5][CH2:4]2)=[O:50])[CH:31]=[C:30]([Cl:2])[CH:29]=1
Reactant: Cl
Reactant: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Reactant: Cn1cc(-c2ccc3c(c2)CCN3)c2c(N)ncnc21
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: O
Product: Cn1cc(-c2ccc3c(c2)CCN3C(=O)Cc2cc(Cl)cc(Cl)c2)c2c(N)ncnc21
Yield: 85.3 %

Procedure:
A solution of 5-(2,3-dihydro-1H-indol-5-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine 2HCl (250 mg, 0.739 mmol), 5-(2,3-dihydro-1H-indol-5-yl)-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine (250 mg, 0.739 mmol), HATU (281 mg, 0.739 mmol), DIEA (0.516 mL, 2.96 mmol) was stirred at room temperature overnight. LCMS indicated good conversion, so the reaction mixture was poured into water (10 mL), whereupon a precipitate formed. The precipitate was filtered and washed with water (10 ml) and dried at the pump for an hour. The residual pale green solid was adsorbed onto silica and purified by flash chromatography (100% EtOAc to 10% MeOH in EtOAc, 12-g column) to afford 5-{1-[(3,5-dichlorophenyl)acetyl]-2,3-dihydro-1H-indol-5-yl}-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine (285 mg, 85% yield) as a white solid. LC-MS (ES) m/z=452, 454 [M+H]+. 1H NMR (400 MHz, DMSO-d6) δ 3.25 (t, J=8.3 Hz, 2H), 3.74 (s, 3H), 3.95 (s, 2H), 4.24 (t, J=8.5 Hz, 2H), 6.25-5.87 (br. s, 2H), 7.28-7.20 (m, 2H), 7.33 (s, 1H), 7.39 (d, J=1.8 Hz, 2H), 7.52 (d, J=1.8 Hz, 1H), 8.11 (d, J=8.1 Hz, 1H), 8.15 (s, 1H).
Reaction SMILES: [H-].[Na+].[CH2:3]([O:5][C:6]([C:8]1([CH2:13][OH:14])[CH2:12][CH2:11][CH2:10][CH2:9]1)=[O:7])[CH3:4].I[CH3:16]>C1COCC1>[CH2:3]([O:5][C:6]([C:8]1([CH2:13][O:14][CH3:16])[CH2:12][CH2:11][CH2:10][CH2:9]1)=[O:7])[CH3:4]
Reactant: CCOC(=O)C1(CO)CCCC1
Reactant: CI
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: CCOC(=O)C1(COC)CCCC1
Temperature: 25 °C
Reaction time: 14 h
Yield: 73.9 %

Procedure:
60% Sodium hydride in mineral oil (6.2 g, 130.8 mmol) is added to a solution of 1-hydroxymethyl-cyclopentanecarboxylic acid ethyl ester (15.0 g, 87.2 mmol) in 100.0 mL of THF at 0° C., followed by the addition of iodomethane (13.6 g, 95.9 mmol) and the reaction mixture is stirred at room temperature for 14 hours. After this time, the reaction mixture is quenched with ice water and then extracted with ethyl acetate twice. The organics are combined and washed with water twice then brine, dried over Na2SO4, filtered and concentrated under reduced pressure to afford the crude product that is purified by silica gel chromatography to afford 12.0 g of the title compound. Yield: 74%; m/z 209 [M+Na].
Reaction SMILES: FC1C=CC(S(CCC)(=O)=O)=CC=1C#C[Si](C)(C)C.[C:20]([O:24][C:25](=[O:37])[CH2:26][O:27][C:28]1[CH:33]=[CH:32][C:31]([Cl:34])=[CH:30][C:29]=1[C:35]#[CH:36])([CH3:23])([CH3:22])[CH3:21].Br[C:39]1[CH:44]=[C:43]([S:45]([CH2:48][CH2:49][O:50][CH3:51])(=[O:47])=[O:46])[CH:42]=[CH:41][C:40]=1[F:52]>>[C:20]([O:24][C:25](=[O:37])[CH2:26][O:27][C:28]1[CH:33]=[CH:32][C:31]([Cl:34])=[CH:30][C:29]=1[C:35]#[C:36][C:41]1[CH:42]=[C:43]([S:45]([CH2:48][CH2:49][O:50][CH3:51])(=[O:47])=[O:46])[CH:44]=[CH:39][C:40]=1[F:52])([CH3:23])([CH3:22])[CH3:21]
Reactant: COCCS(=O)(=O)c1ccc(F)c(Br)c1
Reactant: C#Cc1cc(Cl)ccc1OCC(=O)OC(C)(C)C
Agent: CCCS(=O)(=O)c1ccc(F)c(C#C[Si](C)(C)C)c1
Product: COCCS(=O)(=O)c1ccc(F)c(C#Cc2cc(Cl)ccc2OCC(=O)OC(C)(C)C)c1
Yield: 80 %

Procedure:
Following the general method as outlined in Intermediate 107, starting from (4-chloro-2-ethynyl-phenoxy)-acetic acid tert-butyl ester (Intermediate 3) and 2-Bromo-1-fluoro-4-(2-methoxy-ethanesulfonyl)-benzene (Intermediate 132), the title compound was obtained as a colorless oil in 80% yield after purification by flash column chromatography (silica), eluting with cyclohexane containing increasing amounts of EtOAc.
Reaction SMILES: [C@H:1]12[CH2:6][C@H:5]1[CH2:4][C@@H:3]([CH2:7][NH:8][C:9]([C:11]1[N:18]3[C:14]([S:15][CH:16]=[CH:17]3)=[N:13][C:12]=1[CH3:19])=[O:10])[NH:2]2.[NH2:20][C:21]1[S:22][C:23]([C:29]2[CH:34]=[CH:33][CH:32]=[C:31]([F:35])[CH:30]=2)=[C:24]([C:26](O)=[O:27])[N:25]=1>>[NH2:20][C:21]1[S:22][C:23]([C:29]2[CH:34]=[CH:33][CH:32]=[C:31]([F:35])[CH:30]=2)=[C:24]([C:26]([N:2]2[C@H:3]([CH2:7][NH:8][C:9]([C:11]3[N:18]4[C:14]([S:15][CH:16]=[CH:17]4)=[N:13][C:12]=3[CH3:19])=[O:10])[CH2:4][C@H:5]3[C@@H:1]2[CH2:6]3)=[O:27])[N:25]=1
Reactant: Cc1nc2sccn2c1C(=O)NC[C@@H]1C[C@@H]2C[C@@H]2N1
Reactant: Nc1nc(C(=O)O)c(-c2cccc(F)c2)s1
Product: Cc1nc2sccn2c1C(=O)NC[C@@H]1C[C@@H]2C[C@@H]2N1C(=O)c1nc(N)sc1-c1cccc(F)c1

Procedure:
prepared by reaction of 6-methyl-imidazo[2,1-b]thiazole-5-carboxylic acid [(1S,3S,5S)-2-aza-bicyclo[3.1.0]hex-3-ylmethyl]-amide with 2-amino-5-(3-fluoro-phenyl)-thiazole-4-carboxylic acid. LC-MS (basic): tR=1.21 min; [M+H]+=497.1.
Reaction SMILES: [CH2:1]([O:3][P:4]([CH:8]([C:10]1[CH:15]=[CH:14][CH:13]=[C:12](Br)[CH:11]=1)[F:9])[O:5][CH2:6][CH3:7])[CH3:2].CC1CCCC(C)N1.[F:25][CH:26]([F:36])[O:27][C:28]1[CH:33]=[CH:32][C:31]([C:34]#[CH:35])=[CH:30][CH:29]=1>[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O>[CH2:1]([O:3][P:4]([CH:8]([C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([C:35]#[C:34][C:31]2[CH:30]=[CH:29][C:28]([O:27][CH:26]([F:25])[F:36])=[CH:33][CH:32]=2)[CH:11]=1)[F:9])[O:5][CH2:6][CH3:7])[CH3:2]
Reactant: CCOP(OCC)C(F)c1cccc(Br)c1
Reactant: C#Cc1ccc(OC(F)F)cc1
Agent: [Pd]
Agent: CC1CCCC(C)N1
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: O
Product: CCOP(OCC)C(F)c1cccc(C#Cc2ccc(OC(F)F)cc2)c1
Temperature: 80 °C
Reaction time: 5 h
Yield: 53.4 %

Procedure:
A mixture of diethyl[(3-bromophenyl)(fluoro)methyl]phosphonite (5.5 g, 17.0 mmol), 2,6-dimethylpiperidine (10 mL), and 1-(difluoromethoxy)-4-ethynylbenzene (3.38 g, 20.4 mmol) was degassed with argon for 5 minutes. Then, tetrakis(triphenylphosphine) palladium (0) (983 mg, 0.85 mmol) was added and the mixture was stirred at 80° C. for 5 hours. The mixture was poured into water and extracted with EtOAc. The organic extracts were dried over MgSO4. Evaporation and purification by ICSO (hexane/EtOAc 1/1) gave diethyl[(3-{[4-(difluoromethoxy)phenyl]ethynyl}phenyl)(fluoro)methyl]phosphonite (3.6 g) as a clear oil; MS m/e (M+H)+ 413.
Reaction SMILES: N1C=CC=CC=1.[CH3:7][N:8]1[CH2:13][CH2:12][CH:11]([S:14][C:15]2[CH:16]=[C:17]([NH2:21])[CH:18]=[CH:19][CH:20]=2)[CH2:10][CH2:9]1.[Cl:22][C:23]1[CH:31]=[C:30]([F:32])[CH:29]=[CH:28][C:24]=1[C:25](Cl)=[O:26]>ClCCl>[ClH:22].[Cl:22][C:23]1[CH:31]=[C:30]([F:32])[CH:29]=[CH:28][C:24]=1[C:25]([NH:21][C:17]1[CH:18]=[CH:19][CH:20]=[C:15]([S:14][CH:11]2[CH2:10][CH2:9][N:8]([CH3:7])[CH2:13][CH2:12]2)[CH:16]=1)=[O:26]
Reactant: O=C(Cl)c1ccc(F)cc1Cl
Reactant: CN1CCC(Sc2cccc(N)c2)CC1
Solvent: ClCCl
Solvent: c1ccncc1
Product: CN1CCC(Sc2cccc(NC(=O)c3ccc(F)cc3Cl)c2)CC1
Product: Cl
Temperature: 25 °C
Reaction time: 2 h

Procedure:
Combine pyridine (0.110 mL, 1.36 mmol), 3-(1-methyl-piperidin-4-ylsulfanyl)-phenylamine (preparation 76,151 mg, 0.679 mmol) in dichloromethane (6.5 mL) at 0° C. Stir and add 2-chloro-4-fluorobenzoyl chloride (0.105 mL, 0.815 mmol). Allow to warm to ambient temperature and stir. After 2 hr., dilute with dichloromethane (10 mL) and wash with sodium hydroxide (1N, 3×10 mL). Combine the organic layers, dry over sodium sulfate and concentrate under reduced pressure. Purification by flash chromatography, eluting with dichloromethane/ammonia (2.0 N in methanol) [20/1] to give the title compound as free base (184 mg, 72%). Dissolve the residue in diethyl ether and treat with ethereal hydrogen chloride (1.0 M). Triturate the resulting gum with ether to give the title compound as the hydrogen chloride salt. 1H NMR (free base, CDCl3): 8.37 (bs, 1H), 7.65 (s, 1H), 7.58 (t, J=6.8 Hz, 1H), 7.42 (d, J=7.7 Hz, 1H), 7.21 (t, J=7.8 Hz, 1H), 7.14-7.06 (m, 2H), 6.99-6.93 (m, 1H), 3.05 (bs, 1H), 2.71 (bd, J=11.5 Hz, 2H), 2.19 (s, 3H), 2.03-1.90 (m, 4H), 1.67-1.56 (m, 2H). 13C NMR (free base, CDCl3): 164.9, 162.2 (d, JC-F=167.7 Hz), 137.9, 135.8, 132.0, 131.7 (d, JC-F=8.6 Hz), 131.4, 129.3, 128.0, 123.0, 118.6, 117.5 (d, JC-F=25.0 Hz), 114.5 (d, JC-F=21.3 Hz), 54.9, 46.0, 43.6, 32.4.
Reaction SMILES: [CH:1]1[C:6]([C:7]([OH:9])=[O:8])=[CH:5][CH:4]=[C:3]([I:10])[CH:2]=1.S(=O)(=O)(O)O.C(=O)([O-])[O-].[Na+].[Na+].[CH2:22](O)[CH3:23]>>[CH2:22]([O:8][C:7](=[O:9])[C:6]1[CH:5]=[CH:4][C:3]([I:10])=[CH:2][CH:1]=1)[CH3:23]
Reactant: O=C(O)c1ccc(I)cc1
Reactant: CCO
Agent: O=C([O-])[O-]
Agent: O=S(=O)(O)O
Agent: [Na+]
Product: CCOC(=O)c1ccc(I)cc1
Temperature: 0 °C

Procedure:
A solution of 100 grams (0.403 mole) of p-iodobenzoic acid in 600 ml. of abs. ethanol containing 30 ml. of concentrated sulfuric acid is refluxed for 5 days. The cooled solution is poured over 350 grams of ice and is neutralized with saturated sodium carbonate solution. The oil that separates is extracted with six 150 ml. portions of ether. These ether extracts are combined, washed with water, dried over magnesium sulfate, and filtered. Evaporation of the ether gives 131.3 grams of ethyl-4-iodobenzoate as a chromatographically pure, clear, light oil.
Reaction SMILES: C([O:3][C:4]([CH:6]1[CH2:11][CH2:10][N:9]([C:12]2[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][N:13]=2)[CH2:8][CH2:7]1)=[O:5])C.O[Li].O>C1COCC1.CO.O>[CH3:19][O:18][C:15]1[CH:16]=[CH:17][C:12]([N:9]2[CH2:8][CH2:7][CH:6]([C:4]([OH:5])=[O:3])[CH2:11][CH2:10]2)=[N:13][CH:14]=1
Reactant: CCOC(=O)C1CCN(c2ccc(OC)cn2)CC1
Agent: [Li]O
Solvent: C1CCOC1
Solvent: CO
Solvent: O
Product: COc1ccc(N2CCC(C(=O)O)CC2)nc1
Reaction time: 3 h
Yield: 39.7 %

Procedure:
To a solution of 5′-Methoxy-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-4-carboxylic acid ethyl ester (0.17 g, 0.64 mmol) in 5 mL of THF/MeOH/H2O (1/1/1) was added LiOH.H2O (54 mg, 1.28 mmol). After 3 hours, the reaction was concentrated under vacuo, taken up in EtOAc, washed with aq. NH4Cl. The organic phase was dried over Na2SO4, and concentrated under vacuo to yield 60 mg (39%) of the title product as a light brown solid. ES-MS m/e: 235.1 (M−H+).
Reaction SMILES: [C:1]([O:6][CH2:7]C(O)C)(=[O:5])[C:2]([CH3:4])=[CH2:3].C1OC1.OC1C=CC(C(C2C=CC(O)=CC=2)(C)C)=CC=1>>[CH3:4][C:2]([C:1]([O-:6])=[O:5])=[CH2:3].[CH3:4][C:2]([C:1]([O:6][CH3:7])=[O:5])=[CH2:3]
Reactant: C=C(C)C(=O)OCC(C)O
Agent: CC(C)(c1ccc(O)cc1)c1ccc(O)cc1
Solvent: C1CO1
Product: C=C(C)C(=O)OC
Product: C=C(C)C(=O)[O-]

Procedure:
To a mixture of 50 parts of 2-hydroxypropyl methacrylate and 50 parts of dimethacrylate of a 2.6 mol-ethylene oxide adduct (an average addition amount) of Bisphenol A (NK ester BPE 2.6 produced by Shin-nakamura Kagaku Kogyo K.K., Japan, hereinafter referred to as BPE 2.6) was added 7.5 parts of an acrylic polymer having a polymerization degree of about 1,000 and a molecular weight of about 100,000 (DIANAL BR 75 produced by Mitsubishi Rayon K.K., Japan). The mixture was dissolved by heating at 80° C. for 2 hours. Thereto were then added 1.5 parts of SQ salt obtained in Reference example. The resulting mixture was dissolved by heating for 10 minutes, cooled to room temperature, then incorporated with 0.5 part of cumene hydroperoxide and 1.5 parts of water, and dissolved with stirring. To the resulting systems were added 0.1 part each of various polymerizable phosphates. Properties of the resulting composition were determined and shown in Table 1. Incidentally, the measurements of properties were conducted by the following methods.
Reaction SMILES: [OH:1][CH2:2][CH2:3][N:4]1[C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=2[N:6]=[C:5]1[CH2:13][N:14]1[C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][C:17]=2[N:16]=[N:15]1.C(N(C(C)C)CC)(C)C.[CH3:32][S:33](Cl)(=[O:35])=[O:34]>C(Cl)Cl>[CH3:32][S:33]([O:1][CH2:2][CH2:3][N:4]1[C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=2[N:6]=[C:5]1[CH2:13][N:14]1[C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][C:17]=2[N:16]=[N:15]1)(=[O:35])=[O:34]
Reactant: OCCn1c(Cn2nnc3ccccc32)nc2ccccc21
Reactant: CS(=O)(=O)Cl
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: CS(=O)(=O)OCCn1c(Cn2nnc3ccccc32)nc2ccccc21
Temperature: 0 °C
Reaction time: 1 h
Yield: 58.3 %

Procedure:
1-[1-(2-Hydroxylethyl)-1-H-benzimidazol-2-ylmethyl)-1H-benzotriazole (300 mg, 1.02 mmol) was suspended in anhydrous methylene chloride and cooled to 0° C. with an ice bath. Diisopropylethylamine (0.36 ml, 2.05 mmol) and methanesulfonyl chloride (0.16 mL, 2.05 mmol) were slowly added. The reaction was stirred at 0° C. for 1 hour during which the solution became clear. The solvent was stripped under vacuum, and the residue was purified by flash chromatography (EtOAc) to give 221 mg (58%) of the title compound as a white solid.
Reaction SMILES: N1C=CC=CC=1.[Cl:7][C:8]1[CH:9]=[CH:10][C:11]([OH:16])=[C:12]([CH:15]=1)[CH:13]=O.Cl.[NH2:18][OH:19].O>C(O)C>[Cl:7][C:8]1[CH:9]=[CH:10][C:11]([OH:16])=[C:12]([CH:15]=1)[CH:13]=[N:18][OH:19]
Reactant: NO
Reactant: O=Cc1cc(Cl)ccc1O
Agent: Cl
Solvent: c1ccncc1
Solvent: CCO
Solvent: O
Product: ON=Cc1cc(Cl)ccc1O
Reaction time: 18 h
Yield: 77.6 %

Procedure:
Pyridine (20 ml) was added to a stirred suspension of 5-chloro-2-hydroxybenzaldehyde (5.0 g) and hydroxylamine hydrochloride (2.77 g) in ethanol (20 ml) and stirring was continued for 18 hours. The mixture was then added to water (150 ml) and extracted with ether (3×50 ml). The combined extracts were washed with water (2×50 ml), dried (MgSO4) and concentrated to give a yellow oil which slowly crystallised on standing. The solid was collected by filtration and washed with hexane to give 5-chloro-2-hydroxybenzaldoxime (4.25 g) as white crystals, m.p. 125°-126° C.; NMR: 6.91(1H,d,J=5 Hz), 7.15(1H,d,J=2.5Hz), 7.22(1H,dd,J=8,2.5Hz); 7.55(1H,b), 8.16(1H,s), 9.26(1H,b).
Reaction SMILES: [H-].[Na+].[F:3][C:4]([F:27])([F:26])[S:5]([O:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][C:17]=1[OH:18])[CH2:14][CH:13]([N:19]([CH2:23][CH2:24][CH3:25])[CH2:20][CH2:21][CH3:22])[CH2:12]2)(=[O:7])=[O:6].[CH2:28](Br)[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1>CCCCCC.CN(C=O)C>[F:27][C:4]([F:26])([F:3])[S:5]([O:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][C:17]=1[O:18][CH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)[CH2:14][CH:13]([N:19]([CH2:23][CH2:24][CH3:25])[CH2:20][CH2:21][CH3:22])[CH2:12]2)(=[O:6])=[O:7]
Reactant: CCCN(CCC)C1Cc2cc(O)c(OS(=O)(=O)C(F)(F)F)cc2C1
Reactant: BrCc1ccccc1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: CCCCCC
Product: CCCN(CCC)C1Cc2cc(OCc3ccccc3)c(OS(=O)(=O)C(F)(F)F)cc2C1
Reaction time: 0.5 h

Procedure:
Sodium hydride (0.96 g, 24 mmol) was washed with hexane under nitrogen and suspended in DMF (10 mL). 2-(Dipropylamino)-2,3-dihydro-6-hydroxy-1H-inden-5-yl trifluoromethanesulfonate (69, 7.6 g, 20 mmol) in DMF (30 mL) was added dropwise at 0-5° C. over 30 min and the mixture stirred 30 min. Benzyl bromide (5.13 g, 30 mmol) in DMF (5 mL) was added and the resulting mixture was stirred 1 h. The reaction was quenched with saturated NaHCO3 and extracted with EtOAc. The organic layer was washed with water, brine, dried (MgSO4), filtered and concentrated to give the crude product. Chromatographic purification yielded pure product 70 as an oil that was converted into the HCl salt and crystallized from EtOAc/MeOH/hexane to give a white solid (mp 162-163° C.).