Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([NH:3][C:4]1[CH:9]=[C:8]([O:10][CH3:11])[CH:7]=[CH:6][C:5]=1[CH:12]1[CH2:21][CH2:20][C:19]2[CH:18]=[C:17]([O:22]C(=O)C(C)(C)C)[CH:16]=[CH:15][C:14]=2[CH2:13]1)[CH3:2].[N:29]1([CH2:36][CH2:37][C:38]2[S:42][C:41]([C:43]([O-])=O)=[CH:40][CH:39]=2)[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31][CH2:30]1.[Li+]>>[N:29]1([CH2:36][CH2:37][C:38]2[S:42][C:41]([CH2:43][N:3]([CH2:1][CH3:2])[C:4]3[CH:9]=[C:8]([O:10][CH3:11])[CH:7]=[CH:6][C:5]=3[CH:12]3[CH2:21][CH2:20][C:19]4[CH:18]=[C:17]([OH:22])[CH:16]=[CH:15][C:14]=4[CH2:13]3)=[CH:40][CH:39]=2)[CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35]1
Reactant: O=C([O-])c1ccc(CCN2CCCCCC2)s1
Reactant: CCNc1cc(OC)ccc1C1CCc2cc(OC(=O)C(C)(C)C)ccc2C1
Agent: [Li+]
Product: CCN(Cc1ccc(CCN2CCCCCC2)s1)c1cc(OC)ccc1C1CCc2cc(O)ccc2C1
Yield: 86.4 %

Procedure:
Synthesized from pivalic acid 6-(2-ethylamino-4-methoxyphenyl)-5,6,7,8-tetrahydronaphthalen-2-yl ester (40 mg) and lithium 5-(2-azepan-1-ylethyl)thiophene-2-carboxylate (110 mg) according to an analogous synthetic method to Example 152, the title compound (47 mg) was obtained.
Reaction SMILES: [Cl:1][C:2]1[N:3]([C:16]2[C:21]([CH3:22])=[CH:20][C:19]([CH3:23])=[CH:18][C:17]=2[CH3:24])[C:4]2[N:5]([CH:15]=1)[C:6]([CH2:13]O)=[C:7]([C:9]([F:12])([F:11])[F:10])[N:8]=2.S(Cl)([Cl:27])=O>ClCCl>[Cl:1][C:2]1[N:3]([C:16]2[C:21]([CH3:22])=[CH:20][C:19]([CH3:23])=[CH:18][C:17]=2[CH3:24])[C:4]2[N:5]([C:6]([CH2:13][Cl:27])=[C:7]([C:9]([F:12])([F:11])[F:10])[N:8]=2)[CH:15]=1
Reactant: O=S(Cl)Cl
Reactant: Cc1cc(C)c(-n2c(Cl)cn3c(CO)c(C(F)(F)F)nc23)c(C)c1
Solvent: ClCCl
Product: Cc1cc(C)c(-n2c(Cl)cn3c(CCl)c(C(F)(F)F)nc23)c(C)c1
Yield: 100 %

Procedure:
A solution of [6-chloro-2-trifluoromethyl-7-(2,4,6-trimethyl-phenyl)-7H-imidazo[1,2-a]imidazol-3-yl]-methanol (614.8 mg, 1.718 mmol) and thionyl chloride (1.25 mL) in dichloromethane was stirred at 0° C. for 15 min. Thionyl chloride and the solvent were removed in vacuo and the residue was dried under high vacuum to yield the desired product as a yellow solid (646.3 mg, 100%). LC/MS: tR=1.46 min., MS: [MH−Cl+OMe]=373.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[C:9](=O)[CH:8]([CH2:14][C:15]([O:17][CH3:18])=[O:16])[CH2:7][CH2:6]2.P(Cl)(Cl)(Cl)(Cl)[Cl:20]>C1C=CC=CC=1>[Cl:20][C:9]1[C:10]2[C:5](=[CH:4][C:3]([O:2][CH3:1])=[CH:12][CH:11]=2)[CH:6]=[CH:7][C:8]=1[CH2:14][C:15]([O:17][CH3:18])=[O:16]
Reactant: ClP(Cl)(Cl)(Cl)Cl
Reactant: COC(=O)CC1CCc2cc(OC)ccc2C1=O
Solvent: c1ccccc1
Product: COC(=O)Cc1ccc2cc(OC)ccc2c1Cl
Reaction time: 5 h

Procedure:
To a mixture of 25 g. of 6-methoxy-2-(methoxycarbonylmethyl)-1-tetralone and 150 ml. of benzene, 21 g. of phosphorus pentachloride are slowly added. After the addition, the chlorination mixture is allowed to stand for an additional 5 hours; then it is added to 500 g. of ice and extracted with xylene. The extracts, containing methyl 1-chloro-6-methoxy-3,4-dihydro-2-naphthylacetate, are combined, washed with water to neutrality and dried over sodium sulfate; the 23 g. of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone are added and the resulting mixture is refluxed for 5 hours. The dehydrogenation mixture is cooled, filtered, and evaporated. The residue is taken up in acetone and chromatographed on alumina and evaporated to yield methyl 1-chloro-6-methoxy-2-naphthylacetate.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8][CH2:9][C:10](=[O:17])[C:11]([CH3:16])([CH3:15])[CH2:12][CH2:13][Cl:14])=[CH:4][CH:3]=1.[Br:18]Br>C(Cl)(Cl)Cl>[Br:18][CH:9]([S:8][C:5]1[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=1)[C:10](=[O:17])[C:11]([CH3:15])([CH3:16])[CH2:12][CH2:13][Cl:14]
Reactant: CC(C)(CCCl)C(=O)CSc1ccc(Cl)cc1
Reactant: BrBr
Solvent: ClC(Cl)Cl
Product: CC(C)(CCCl)C(=O)C(Br)Sc1ccc(Cl)cc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 99.3 %

Procedure:
137 g (0.47 mole) of 1-(4-chlorophenylthio)-5-chloro-3,3-dimethyl-2-pentanone are dissolved in 1,000 ml of chloroform. 75.3 g (0.47 mole) of bromine are added dropwise at room temperature such that the solution is always decolorized. The reaction mixture is then subsequently stirred at room temperature for 1 hour and is concentrated by distilling off the solvent. 172.7 g (99.3% of theory) of 1-bromo-1-(4-chlorophenylthio)-5-chloro-3,3-dimethyl-2-pentanone of refractive index nD20 1.5796 are obtained. ##STR94##
Reaction SMILES: [C:1]([O:4][C:5](=O)[CH3:6])(=[O:3])[CH3:2].[O:8]1[C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=2[N:10]=[C:9]1[S:17][CH2:18][CH2:19][N:20]1[CH2:25][CH2:24][N:23]([CH2:26][C:27]([NH:29][C:30]2[C:35]([CH:36]([CH3:38])[CH3:37])=CC=[C:32](O)[C:31]=2[CH:40]([CH3:42])[CH3:41])=[O:28])[CH2:22][CH2:21]1.C(=O)(O)[O-].[Na+]>N1C=CC=CC=1>[O:8]1[C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=2[N:10]=[C:9]1[S:17][CH2:18][CH2:19][N:20]1[CH2:21][CH2:22][N:23]([CH2:26][C:27]([NH:29][C:30]2[C:31]([CH:40]([CH3:41])[CH3:42])=[CH:32][CH:6]=[C:5]([O:4][C:1](=[O:3])[CH3:2])[C:35]=2[CH:36]([CH3:38])[CH3:37])=[O:28])[CH2:24][CH2:25]1
Reactant: CC(=O)OC(C)=O
Reactant: CC(C)c1ccc(O)c(C(C)C)c1NC(=O)CN1CCN(CCSc2nc3ccccc3o2)CC1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: c1ccncc1
Product: CC(=O)Oc1ccc(C(C)C)c(NC(=O)CN2CCN(CCSc3nc4ccccc4o3)CC2)c1C(C)C
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 73 %

Procedure:
Acetic anhydride (2 ml) was added to a solution of 2-[4-[2-(benzoxazol-2-ylthio)ethyl]piperazin-1-yl]-N-(2,6-d iisopropyl-3-hydroxyphenyl)acetamide (176 mg, 0.354 mmol) in pyridine (1 ml) and the mixture was stirred at room temperature for 90 minutes. The reaction solution was neutralized with an aqueous solution of sodium bicarbonate and extracted with ethyl acetate. The organic layer was washed with water and a saturated sodium chloride solution successively and dried over sodium sulfate and the solvent was evaporated therefrom. The residue was purified by a silica gel column chromatography (20 g of silica gel; developing solvent, chloroform:methanol=30:1→20:1) and the resulting crude crystals were recrystallized from acetone-hexane to provide 140 mg (yield 73%) of the desired compound as colorless needles.
Reaction SMILES: [Cl:1][C:2]1[N:7]=[C:6]([N:8]2[CH:12]=[C:11]([C:13](OCC)=[O:14])[C:10]([CH3:18])=[N:9]2)[CH:5]=[CH:4][N:3]=1.CC1C(CN2CC(O)C2)=CN(C2C=CN=C(NC3C=C4C(=CC=3)N(C)C=C4)N=2)N=1.[H-].C([Al+]CC(C)C)C(C)C>O1CCCC1.C1(C)C=CC=CC=1>[Cl:1][C:2]1[N:7]=[C:6]([N:8]2[CH:12]=[C:11]([CH2:13][OH:14])[C:10]([CH3:18])=[N:9]2)[CH:5]=[CH:4][N:3]=1
Reactant: CCOC(=O)c1cn(-c2ccnc(Cl)n2)nc1C
Agent: CC(C)C[Al+]CC(C)C
Agent: Cc1nn(-c2ccnc(Nc3ccc4c(ccn4C)c3)n2)cc1CN1CC(O)C1
Agent: [H-]
Solvent: C1CCOC1
Solvent: Cc1ccccc1
Product: Cc1nn(-c2ccnc(Cl)n2)cc1CO
Temperature: 25 °C
Reaction time: 2 h
Yield: 66 %

Procedure:
To a solution of ethyl 1-(2-chloropyrimidin-4-yl)-3-methyl-1H-pyrazole-4-carboxylate intermediate 1 (6.5 g, 24.0 mmol) in 50 mL of anhydrous tetrahydrofuran (THF), was slowly added 109 mL (4.5 equiv.) of 1M solution of di-isobutylaluminum hydride (DIBAL-H) in toluene with ice bath cooling. After being stirred for 2 hours at room temperature, the reaction was quenched by slow addition of 1N—NaOH solution. It was diluted with ethyl acetate and washed with brine. The collected organic layer was dried over anhydrous sodium sulfate and then partially concentrated in vacuo. To this, was heptane added to form pale yellow precipitates. The resulting solids were collected by filtration and rinsed with heptanes and then dried under high vacuum to give 3.6 g (66%) of intermediate alcohol 6. MS (ESI) m/z 225 [M+H]+.
Reaction SMILES: [CH2:1]([S-:3])[CH3:2].[Na+].[Cl:5][C:6]1[CH:11]=[C:10](I)[CH:9]=[CH:8][C:7]=1[NH:13][C:14](=[O:22])[C@:15]([OH:21])([CH3:20])[C:16]([F:19])([F:18])[F:17]>N1C2C(=CC=CC=2)C=CC=1.N1C=CC=CC=1.C(OCC)(=O)C.[Cu]Cl>[Cl:5][C:6]1[CH:11]=[C:10]([S:3][CH2:1][CH3:2])[CH:9]=[CH:8][C:7]=1[NH:13][C:14](=[O:22])[C@:15]([OH:21])([CH3:20])[C:16]([F:19])([F:18])[F:17]
Reactant: CC[S-]
Reactant: C[C@@](O)(C(=O)Nc1ccc(I)cc1Cl)C(F)(F)F
Agent: Cl[Cu]
Agent: [Na+]
Solvent: c1ccncc1
Solvent: CCOC(C)=O
Solvent: c1ccc2ncccc2c1
Product: CCSc1ccc(NC(=O)[C@@](C)(O)C(F)(F)F)c(Cl)c1
Temperature: 200 °C
Yield: 84 %

Procedure:
Copper (I) chloride (0.5 g) and sodium ethanethiolate (0.54 g) were added sequentially to a deoxygenated solution of (R)-N-(2-chloro-4-iodophenyl)-2-hydroxy-2-methyl-3,3,3-trifluoropropanamide (Example 197) (2.0 g) in quinoline (6 ml) and pyridine (1.5 ml). The mixture was heated to 200° C. under argon for 18 hours, cooled dissolved in ethyl acetate (200 ml), washed with dilute aqueous hydrochloric acid (2×100 ml) and brine (2×50 ml) and then dried. Volatile material was removed by evaporation and the residue was purified by chromatography on silica gel eluting with 10-40% ethyl acetate/iso-hexane to give the title compound as a gum (1.4 g). NMR (CDCl3): 1.29 (t, 3H), 1.57 (s, 3H), 2.91 (q, 2H), 3.69 (s, 1H), 7.24 (d, 1H), 7.35 (s, 1H), 8.24 (d, 1H), 8.77 (s, 1H); MS (ESP−): 326.
Reaction SMILES: [NH2:1][C:2]1([CH3:15])[CH2:7][CH2:6][N:5](C(OC(C)(C)C)=O)[CH2:4][CH2:3]1.CO.O.[C:19]1([CH3:29])[CH:24]=[CH:23][C:22]([S:25]([OH:28])(=[O:27])=[O:26])=[CH:21][CH:20]=1>CC(O)C>[CH3:29][C:19]1[CH:20]=[CH:21][C:22]([S:25]([OH:28])(=[O:27])=[O:26])=[CH:23][CH:24]=1.[CH3:29][C:19]1[CH:20]=[CH:21][C:22]([S:25]([OH:28])(=[O:27])=[O:26])=[CH:23][CH:24]=1.[CH3:15][C:2]1([NH2:1])[CH2:7][CH2:6][NH:5][CH2:4][CH2:3]1
Reactant: CC1(N)CCN(C(=O)OC(C)(C)C)CC1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: O
Solvent: CO
Solvent: CC(C)O
Product: CC1(N)CCNCC1
Temperature: 60 °C

Procedure:
A solution of tert-butyl 4-amino-4-methylpiperidine-1-carboxylate (1.96 g, 9.15 mmol) in MeOH (15.2 mmol) was added dropwise over 30 minutes to a solution of p-toluenesulfonic acid monohydrate (4.00 g, 21.0 mmol) in 2-propanol (7.9 mL) at 60° C. The reaction mixture was then heated to 60° C. for 16 h. After cooling to 0° C. the precipitate was filtered off and washed with 2-propanol and dried to give the title compound (3.91 g, 93%) as a white solid.
Reaction SMILES: [NH2:1][C:2]1[C:3]([C:9]([O:11][CH3:12])=[O:10])=[N:4][C:5](Br)=[CH:6][N:7]=1.[O:13]1[CH:17]=[CH:16][C:15](B(O)O)=[CH:14]1.C([O-])(=O)C.[K+].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>O1CCOCC1>[NH2:1][C:2]1[C:3]([C:9]([O:11][CH3:12])=[O:10])=[N:4][C:5]([C:15]2[CH:16]=[CH:17][O:13][CH:14]=2)=[CH:6][N:7]=1
Reactant: COC(=O)c1nc(Br)cnc1N
Reactant: OB(O)c1ccoc1
Agent: CC(=O)[O-]
Agent: [K+]
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1COCCO1
Product: COC(=O)c1nc(-c2ccoc2)cnc1N

Procedure:
(Step 8-iv) Methyl 3-amino-6-bromopyrazine-2-carboxylate (700 mg, 3 mmol) was dissolved in dioxane (4 mL) with 3-furan boronic acid (0.36 g, 3.2 mmol), potassium acetate (980 mg 10 mmol) and tetrakispalladium triphenylphosphine (200 mg, 0.17 mmol) in a microwave vessel. Nitrogen was bubbled through for 5 minutes, followed by sealing the vessel and microirradiating the mixture for 20 minutes at 170° C. The reaction mixture was diluted with ethyl acetate/saturated sodium bicarbonate, dried over sodium sulfate, and concentrated to give a solid, which was purified by silica gel column chromatography (0 to 70% EtOAc/hexanes) to give methyl 3-amino-6-(furan-3-yl)pyrazine-2-carboxylate as a solid. This methyl ester was dissolved in THF/MeOH and an aqueous solution of LiOH hydrate (150 mg, 3.6 mmol) was added. The reaction mixture was stirred for 1 hour at room temperature, concentrated to half the volume, and diluted with ethyl acetate/10% aqueous citric acid solution. The organic layer was washed with brine, dried, and concentrated in vacuo to yield 3-amino-6-(furan-3-yl)pyrazine-2-carboxylic acid as a solid (0.46 g, 2.3 mmol, 77% overall yield).
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:12][N:11]=[C:10]([CH3:13])[C:9]=2[CH2:14][C:15]([F:25])([F:24])[CH2:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[CH:4][CH:3]=1.[CH2:26]([O:28][C:29](=[O:49])[CH2:30][C:31]1([C:34]2[CH:39]=[CH:38][C:37](B3OC(C)(C)C(C)(C)O3)=[CH:36][CH:35]=2)[CH2:33][CH2:32]1)[CH3:27]>>[CH2:26]([O:28][C:29](=[O:49])[CH2:30][C:31]1([C:34]2[CH:39]=[CH:38][C:37]([C:2]3[CH:7]=[CH:6][C:5]([C:8]4[O:12][N:11]=[C:10]([CH3:13])[C:9]=4[CH2:14][C:15]([F:25])([F:24])[CH2:16][CH2:17][C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)=[CH:4][CH:3]=3)=[CH:36][CH:35]=2)[CH2:33][CH2:32]1)[CH3:27]
Reactant: CCOC(=O)CC1(c2ccc(B3OC(C)(C)C(C)(C)O3)cc2)CC1
Reactant: Cc1noc(-c2ccc(Br)cc2)c1CC(F)(F)CCc1ccccc1
Product: CCOC(=O)CC1(c2ccc(-c3ccc(-c4onc(C)c4CC(F)(F)CCc4ccccc4)cc3)cc2)CC1

Procedure:
Prepared according to the procedure described in Example 110, Step 3, using 5-(4-bromo-phenyl)-4-(2,2-difluoro-4-phenyl-butyl)-3-methyl-isoxazole and {1-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-cyclopropyl}-acetic acid ethyl ester.
Reaction SMILES: [CH3:1][C:2]1([CH3:27])[O:7][C:6]2[CH:8]=[CH:9][C:10]([C@H:12]3[O:16][C:15](=[O:17])[N:14]([CH2:18][CH2:19][C:20]4[CH:25]=[CH:24][C:23]([OH:26])=[CH:22][CH:21]=4)[CH2:13]3)=[CH:11][C:5]=2[CH2:4][O:3]1.C(=O)([O-])[O-].[Cs+].[Cs+].[C:34]([O:37][C:38]1[CH:43]=[CH:42][CH:41]=[C:40]([CH2:44][CH2:45][CH2:46][CH2:47]Br)[CH:39]=1)(=[O:36])[CH3:35]>CN(C=O)C>[C:34]([O:37][C:38]1[CH:43]=[CH:42][CH:41]=[C:40]([CH2:44][CH2:45][CH2:46][CH2:47][O:26][C:23]2[CH:22]=[CH:21][C:20]([CH2:19][CH2:18][N:14]3[CH2:13][C@@H:12]([C:10]4[CH:9]=[CH:8][C:6]5[O:7][C:2]([CH3:27])([CH3:1])[O:3][CH2:4][C:5]=5[CH:11]=4)[O:16][C:15]3=[O:17])=[CH:25][CH:24]=2)[CH:39]=1)(=[O:36])[CH3:35]
Reactant: CC1(C)OCc2cc([C@@H]3CN(CCc4ccc(O)cc4)C(=O)O3)ccc2O1
Reactant: CC(=O)Oc1cccc(CCCCBr)c1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Product: CC(=O)Oc1cccc(CCCCOc2ccc(CCN3C[C@@H](c4ccc5c(c4)COC(C)(C)O5)OC3=O)cc2)c1
Temperature: 50 °C
Reaction time: 24 h

Procedure:
A solution of (5R)-5-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)-3-[2-(4-hydroxyphenyl)ethyl]-1,3-oxazolidin-2-one (Example 28 v) (37 mg) in dry DMF (0.4 mL) was treated with caesium carbonate (65 mg) and 3-(4bromobutyl)phenyl acetate (0.2 mmol) as a solution in DMF (0.5 mL). Further DMF was added (1 mL) and the reaction mixture stirred at 50° C. for 24 h. The reaction mixture was cooled to room temperature and concentrated in vacuo in a genevac. The residue was suspended in chloroform and filtered to remove inorganic salts. The filtrate was added to the top of a pre-conditioned NH2 propyl cartridge (1 g). The cartridge was washed with chloroform and methanol and the title compound eluted with 2M NH3-MeOH. LCMS RT=3.86 min
Reaction SMILES: [CH3:1][C:2]1([CH3:28])[C:14]2[CH:13]=[C:12]([C:15]3[C:20]4[S:21][C:22]5[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=5[C:19]=4[CH:18]=[CH:17][CH:16]=3)[CH:11]=[CH:10][C:9]=2[C:8]2[C:3]1=[CH:4][CH:5]=[CH:6][CH:7]=2.C([Li])(CC)C.C(O[B:38]1[O:42][C:41]([CH3:44])([CH3:43])[C:40]([CH3:46])([CH3:45])[O:39]1)(C)C>C1COCC1.C1CCCCC1>[CH3:1][C:2]1([CH3:28])[C:14]2[CH:13]=[C:12]([C:15]3[C:20]4[S:21][C:22]5[C:27]([B:38]6[O:42][C:41]([CH3:44])([CH3:43])[C:40]([CH3:46])([CH3:45])[O:39]6)=[CH:26][CH:25]=[CH:24][C:23]=5[C:19]=4[CH:18]=[CH:17][CH:16]=3)[CH:11]=[CH:10][C:9]=2[C:8]2[C:3]1=[CH:4][CH:5]=[CH:6][CH:7]=2
Reactant: CC(C)OB1OC(C)(C)C(C)(C)O1
Reactant: CC1(C)c2ccccc2-c2ccc(-c3cccc4c3sc3ccccc34)cc21
Agent: [Li]C(C)CC
Solvent: C1CCCCC1
Solvent: C1CCOC1
Product: CC1(C)c2ccccc2-c2ccc(-c3cccc4c3sc3c(B5OC(C)(C)C(C)(C)O5)cccc34)cc21
Temperature: -78 °C
Reaction time: 2 h
Yield: 65.4 %

Procedure:
Into a solution of 4-(9,9-dimethyl-9H-fluoren-2-yl)dibenzo[b,d]thiophene (10.637 g, 28.3 mmol) in THF (200 ml), a solution of sec-butyllithium 1.4 M (27.2 ml, 38.1 mmol) in cyclohexane at −78° C. was added slowly. The resulting mixture was stirred at −78° C. for 2 hours before quenching with 2-isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (8.65 ml, 42.4 mmol) added at one portion. The mixture was gradually warmed to room temperature, stirred overnight, and then quenched with methanol. The solvent was evaporated. The residue was purified by column chromatography on silica gel with a heptane/DCM (4/1 to 1/1) eluent and then precipitation in MeOH to yield 2-(6-(9,9-dimethyl-9H-fluoren-2-yl)dibenzo[b,d]thiophen-4-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (9.3 g, 65.5% yield) as a white solid.
Reaction SMILES: [C:1]1(=[O:11])[NH:5][C:4](=[O:6])[C:3]2=[CH:7][CH:8]=[CH:9][CH:10]=[C:2]12.[K].CS(O[CH2:18][CH:19]([O:21][S:22]([CH3:25])(=[O:24])=[O:23])[CH3:20])(=O)=O>CN(C)C=O>[CH3:25][S:22]([O:21][CH:19]([CH3:20])[CH2:18][N:5]1[C:1](=[O:11])[C:2]2=[CH:10][CH:9]=[CH:8][CH:7]=[C:3]2[C:4]1=[O:6])(=[O:24])=[O:23]
Reactant: CC(COS(C)(=O)=O)OS(C)(=O)=O
Reactant: O=C1NC(=O)c2ccccc21
Agent: [K]
Solvent: CN(C)C=O
Product: CC(CN1C(=O)c2ccccc2C1=O)OS(C)(=O)=O
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 41.5 %

Procedure:
5.55 g (30 mmoles) of potassium phthalimide are added in small portions, within 1 hour, to a solution of 7.0 g (30 mmoles) of 1,2-bis(methanesulfonyloxy)-propane in 70 ml of dry dimethyl formamide, heated to 100°-105° C. The mixture is stirred at the same temperature for additional 0.5 hours, thereafter it is cooled and poured onto 350 ml of ice water. The separated crystalline substance is filtered off, washed with water and dried. This crude product, weighing 4.36 g (m.p.: 111°-121° C.) is recrystallized from 25 ml of isopropanol to obtain 3.53 g (41.5%) of N-(β-methanesulfonyloxy-propyl)-phthalimide; m.p.: 129°-132° C.
Reaction SMILES: C[O-].[Na+].[CH3:4][O:5][C:6]1[CH:13]=[CH:12][C:9]([CH2:10][SH:11])=[CH:8][CH:7]=1.Br[C:15]([CH3:20])([CH3:19])[C:16]([OH:18])=[O:17].II>O1CCCC1.[OH-].[Na+].CO>[CH3:4][O:5][C:6]1[CH:13]=[CH:12][C:9]([CH2:10][S:11][C:15]([CH3:20])([CH3:19])[C:16]([OH:18])=[O:17])=[CH:8][CH:7]=1
Reactant: CC(C)(Br)C(=O)O
Reactant: COc1ccc(CS)cc1
Agent: C[O-]
Agent: II
Agent: [Na+]
Solvent: CO
Solvent: C1CCOC1
Product: COc1ccc(CSC(C)(C)C(=O)O)cc1
Temperature: 25 °C
Yield: 58.5 %

Procedure:
Sodium methoxide (81 g, 1.5 mol) was added to 50 ml methanol and 375 ml freshly distilled tetrahydrofuran. The slurry was stirred in an ice bath and 4-methoxybenzylmercaptan (80 g, 0.52 mol) was added slowly. The cloudy orange solution was stirred at room temperature for 1.25 hours, 2-bromo-2-methylproprionic acid (83.5 g, 0.5 mol) was dissolved in 200 ml tetrahydrofuran and added to the mixture. The thick slurry was stirred at reflux for 70 h, then cooled to room temperature. Iodine crystals were added until a red colour persisted. The mixture was dissolved in 2000 ml 0.5M sodium hydroxide solution, and washed with 2×1000 ml ether. The aqueous layer was acidified and extracted with 2×1000 ml ether. The ether layer was washed with 2×1000 ml saturated sodium chloride solution, dried over sodium sulphate, and filtered. The solvent was removed by rotary evaporation to yield an orange solid. This was recrystallised from ethyl acetate to give 70.3 g of the desired product (59% yield) as white crystals. 1H NMR (60 MHz, CDCl3): 1.57 (s, 6H), 3.73 (s, 3H), 3.83 (s, 2H), 6.5-7.5 (m, 4H), 10.90 (brs, 1H) ppm. TLC (50% ether/hexane) Rf 0.30.
Reaction SMILES: FC(F)(F)C(O)=O.[S:8]1[C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=2[N:10]=[C:9]1[S:17]([N:20]1[CH2:25][CH2:24][NH:23][CH2:22][C:21]1=[O:26])(=[O:19])=[O:18].[N:27]1([CH2:36][C:37](O)=[O:38])[CH:35]=[C:33]([CH3:34])[C:31](=[O:32])[NH:30][C:28]1=[O:29].C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C>CN(C=O)C>[S:8]1[C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=2[N:10]=[C:9]1[S:17]([N:20]1[CH2:25][CH2:24][N:23]([C:37](=[O:38])[CH2:36][N:27]2[CH:35]=[C:33]([CH3:34])[C:31](=[O:32])[NH:30][C:28]2=[O:29])[CH2:22][C:21]1=[O:26])(=[O:19])=[O:18]
Reactant: O=C1CNCCN1S(=O)(=O)c1nc2ccccc2s1
Reactant: Cc1cn(CC(=O)O)c(=O)[nH]c1=O
Agent: F[P-](F)(F)(F)(F)F
Agent: c1ccc2c(c1)nnn2O[P+](N1CCCC1)(N1CCCC1)N1CCCC1
Solvent: CN(C)C=O
Solvent: O=C(O)C(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Product: Cc1cn(CC(=O)N2CCN(S(=O)(=O)c3nc4ccccc4s3)C(=O)C2)c(=O)[nH]c1=O
Reaction time: 4 h

Procedure:
To the mixture of 1-(benzothiazole-2-sulfonyl)-piperazin-2-one trifluoroacetic acid salt (0.83 g, 2.5 mmol), (thymin-1-yl)-acetic acid (0.46 g, 2.5 mmol), and PyBOP (1.43 g, 2.75 mmol) in DMF (12 mL) was added diisopropylethylamine (0.61 ml, 3.75 mmol) at ambient temperature. The resulting reaction mixture was stirred for 4 h at the same temperature and the solvent was removed in vacuo. The residue was dissolved in dichloromethane (20 mL) and the solution was washed with water, saturated sodium bicarbonate solution, 1N HCl solution, and saline. The resulting solution was dried over magnesium sulfate and filtered. The filtrate was evaporated in vacuo. The resulting residue was recrystallized in dichloromethane-ethyl ether to afford the title compound. 1H NMR (500 MHz; DMSO-d6) δ 11.30 (d, 1H), 8.34 (d, 1H), 8.26 (m, 1H), 7.71 (m, 2H), 7.34 (s, 0.6H), 7.27 (s, 0.4H), 4.67 (s, 1.2H), 4.57 (s, 0.8H), 4.42 (s, 0.8H), 4.27 (s, 1.2H), 4.21 (t, 1.2H), 4.07 (t, 0.8H), 3.95 (t, 1.2H), 3.85 (t, 0.8H), 1.74 (s, 3H).
Reaction SMILES: [F:1][C:2]([F:24])([F:23])[O:3][C:4]1[CH:5]=[C:6]([C:10]2[C:14]3[CH:15]=[C:16]([C:19]([NH:21][NH2:22])=[O:20])[CH:17]=[CH:18][C:13]=3[O:12][CH:11]=2)[CH:7]=[CH:8][CH:9]=1.[Cl:25][CH2:26][C:27](OC)(OC)OC>>[Cl:25][CH2:26][C:27]1[O:20][C:19]([C:16]2[CH:17]=[CH:18][C:13]3[O:12][CH:11]=[C:10]([C:6]4[CH:7]=[CH:8][CH:9]=[C:4]([O:3][C:2]([F:23])([F:1])[F:24])[CH:5]=4)[C:14]=3[CH:15]=2)=[N:21][N:22]=1
Reactant: NNC(=O)c1ccc2occ(-c3cccc(OC(F)(F)F)c3)c2c1
Reactant: COC(CCl)(OC)OC
Product: FC(F)(F)Oc1cccc(-c2coc3ccc(-c4nnc(CCl)o4)cc23)c1
Temperature: 80 °C
Reaction time: 3 h
Yield: 67.9 %

Procedure:
A mixture of 3-[3-(trifluoromethoxy)phenyl]-1-benzofuran-5-carbohydrazide (3.00 g, 8.92 mmol) and 2-chloro-1,1,1-trimethoxyethane (4.70 mL, 24.4 mmol) was stirred at 80° C. for 3 hr. The reaction mixture was purified by silica gel column chromatography (hexane/ethyl acetate=1/1) and recrystallized from hexane/ethyl acetate to give the title compound (2.39 g, yield 68%) as colorless crystals.
Reaction SMILES: [CH2:1]([SH:19])[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][CH2:16][CH2:17][CH3:18].[CH3:20]/[CH:21]=[CH:22]/[C:23]#[N:24]>C(Cl)Cl.C[O-].[Na+]>[CH2:1]([S:19][CH:21]([CH3:20])[CH2:22][C:23]#[N:24])[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][CH2:16][CH2:17][CH3:18]
Reactant: C/C=C/C#N
Reactant: CCCCCCCCCCCCCCCCCCS
Agent: C[O-]
Agent: [Na+]
Solvent: ClCCl
Product: CCCCCCCCCCCCCCCCCCSC(C)CC#N
Yield: 79.9 %

Procedure:
Preparation of ##STR42## Sodiummethoxide (100 mg) was suspended in stearyl mercaptan (57.2 g, 0.2 mol). Crotonitril (16.8 g, 0.25 mol) was added dropwise under N2 -atmosphere at 50° C. After 12 hours the reaction solution was taken up in methylene chloride. The solution was washed with 2 n sulfuric acid and with water, dried and the solvent removed under vacuum. The resulting crystalline mass was recrystallized from ethanol to give 56.5 g, 80% yield of 3-(stearylmercapto)-butyronitrile, melting at 38° C.
Reaction SMILES: S(=O)(=O)(O)O.[O:6]1[CH2:10][CH2:9][CH2:8][CH2:7]1>O>[CH3:7][CH2:8][CH2:9][CH2:10][O:6][C@H:9]([CH2:10][OH:6])[CH2:8][CH3:7]
Reactant: C1CCOC1
Agent: O=S(=O)(O)O
Solvent: O
Product: CCCCO[C@@H](CC)CO
Temperature: 0 °C

Procedure:
In the same reaction apparatus as in Example 1, 150 g of 25% fuming sulfuric acid was dropwise added over a period of one hour to 500 g of tetrahydrofuran maintained at 0° C., and the mixture was subjected to reaction at 0° C. for 2 hours. The reaction mixture remained liquid even after completion of the reaction, and the conversion was 68%. This reaction mixture was then treated in the same way as in Example 1, except that 630 g of ion exchanged water was added, to obtain colorless PTMG. The results of the analyses of the obtained PTMG and the catalytic efficiency α were as shown in Table 1, which indicates far lower catalyst utilization efficiency than in the process of this invention. In the hope of obtaining PTMG having a molecular weight of around 650 according to this method, experiments were carried out by changing the amount of fuming sulfuric acid used, the SO3 concentration, the fuming sulfuric acid dropping rate and the polymerization time after dropping, but any of the resulting PTMG's had a molecular weight above 850, and it was impossible to obtain PTMG with a molecular weight of around 650.