Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]1([N:7]2[CH2:12][CH2:11][NH:10][CH2:9][CH2:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(N(CC)CC)C.Br[CH2:21][C:22]([C:24]1[CH:25]=[C:26]2[CH2:32][C:31](=[O:33])[N:30]([CH3:34])[C:27]2=[N:28][CH:29]=1)=[O:23]>O1CCOCC1>[C:1]1([N:7]2[CH2:12][CH2:11][N:10]([CH2:21][C:22]([C:24]3[CH:25]=[C:26]4[CH2:32][C:31](=[O:33])[N:30]([CH3:34])[C:27]4=[N:28][CH:29]=3)=[O:23])[CH2:9][CH2:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: c1ccc(N2CCNCC2)cc1
Reactant: CN1C(=O)Cc2cc(C(=O)CBr)cnc21
Solvent: CCN(CC)CC
Solvent: C1COCCO1
Product: CN1C(=O)Cc2cc(C(=O)CN3CCN(c4ccccc4)CC3)cnc21
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 78 %

Procedure:
Add 63 mg (3.9×10-4 mol) of N-phenylpiperazine and then, very slowly, 0.08 ml (5.57×10-4 mol) of triethylamine to a previously prepared solution of 100 mg (3.72×10-4 mol) of 1,3-dihydro-5-bromoacetyl-1-methyl-2H-pyrrolo[2,3-b]pyridin-2-one (Preparation 19) in 3 ml of dioxane. After 30 minutes' stirring at room temperature, the resulting precipitate is removed by filtration and the flitrate is concentrated under reduced pressure to obtain the title product in a yield of 78%. ##STR75##
Reaction SMILES: O[C:2]1([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=2[O:23][CH3:24])[CH2:8][CH:7]2[N:9](C(OC(C)(C)C)=O)[CH:4]([CH2:5][CH2:6]2)[CH2:3]1>ClCCl.C(#N)C>[CH3:24][O:23][C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][C:17]=1[C:2]1[CH2:3][CH:4]2[NH:9][CH:7]([CH2:6][CH2:5]2)[CH:8]=1
Reactant: COc1ccccc1C1(O)CC2CCC(C1)N2C(=O)OC(C)(C)C
Solvent: ClCCl
Solvent: CC#N
Product: COc1ccccc1C1=CC2CCC(C1)N2
Temperature: 0 °C
Reaction time: 1 h

Procedure:
Crude 10a from above (4.124 g) was dissolved in dichloromethane (10 mL) and cooled in an ice-H2O bath. The solution was slowly treated with ice-cold trifluoroacetic acid (10 mL) and stirred at 0° C. for 1 h. The reaction was then concentrated under reduced pressure and the oil obtained re-dissolved in acetonitrile and re-concentrated under reduced pressure. The crude TFA salt was cooled in an ice-H2O bath and treated slowly with ice-cold 1.0 N NaOH (75 mL). The product was extracted into dichloromethane (2×75 mL) and the pooled extracts washed successively with H2O, saturated NaHCO3 and saturated brine, dried over Na2SO4 and filtered. The filtrate was concentrated in vacuo to afford 1.223 g crude 3-(2-methoxyphenyl)-8-azabicyclo[3.2.1]oct-2-ene 10b as a pale amber oil, which was taken to the next step without further purification. LC/MS (RP-C18, 10-99% CH3CN/0.05% TFA gradient over 5 min) m/z 216.2 [M+H]+, retention time 1.75 min.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[C:5]([S:9][CH2:10][C:11]([F:14])([F:13])[F:12])=[CH:4][C:3]=1[OH:15].ClC1C=CC=C(C(OO)=[O:24])C=1.S([O-])([O-])(=O)=S.[Na+].[Na+]>C(Cl)(Cl)Cl>[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[C:5]([S:9]([CH2:10][C:11]([F:12])([F:14])[F:13])=[O:24])=[CH:4][C:3]=1[OH:15]
Reactant: Oc1cc(SCC(F)(F)F)c(Cl)cc1Cl
Reactant: O=C(OO)c1cccc(Cl)c1
Agent: O=S([O-])([O-])=S
Agent: [Na+]
Solvent: ClC(Cl)Cl
Product: O=S(CC(F)(F)F)c1cc(O)c(Cl)cc1Cl
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 87.9 %

Procedure:
In 80 ml of chloroform was dissolved 10.0 g (36.08 mmol) of 2,4-dichloro-5-(2,2,2-trifluoroethylthio)phenol. Thereto was added 9.80 g (39.75 mmol) of 3-chloroperbenzoic acid (purity: about 70%) under ice cooling, and the mixture was stirred for 30 minutes at room temperature. Then, saturated aqueous solution of sodium thiosulfate was added to the reaction mixture to decompose excess peroxide. Thereafter, the solvent was distilled off under reduced pressure, and extraction was conducted by adding ethyl acetate and water. The organic phase obtained was washed by aqueous potassium carbonate solution and saturated aqueous sodium chloride solution in this order, and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, to obtain 9.30 g (yield: 88%) of an intended product.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[S:8]([NH:11][C:12]1[C:17]([C:18]([O:20][CH3:21])=[O:19])=[C:16]([O:22][CH3:23])[C:15]([CH2:24][CH3:25])=[CH:14][CH:13]=1)(=[O:10])=[O:9].[Cl:26][C:27]1[CH:32]=[CH:31][C:30](/[CH:33]=[CH:34]/B(O)O)=[CH:29][CH:28]=1>>[Cl:26][C:27]1[CH:32]=[CH:31][C:30](/[CH:33]=[CH:34]/[C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=2[S:8]([NH:11][C:12]2[C:17]([C:18]([O:20][CH3:21])=[O:19])=[C:16]([O:22][CH3:23])[C:15]([CH2:24][CH3:25])=[CH:14][CH:13]=2)(=[O:10])=[O:9])=[CH:29][CH:28]=1
Reactant: OB(O)/C=C/c1ccc(Cl)cc1
Reactant: CCc1ccc(NS(=O)(=O)c2ccccc2Br)c(C(=O)OC)c1OC
Product: CCc1ccc(NS(=O)(=O)c2ccccc2/C=C/c2ccc(Cl)cc2)c(C(=O)OC)c1OC

Procedure:
The title compound-was prepared from Example 574D (0.215 g, 0.5 mmol) and trans-2-(4-chlorophenyl)vinyl boronic acid according to the procedure of Example 230B, yielding 0.252 g, 100%. 1H NMR (DMSO-d6) δ 1.02 (t, 3H), 2.42 (q, 2H), 3.52 (s, 3H), 3.54 (s, 3H), 6.90 (d, 1H), 7.16 (d, 1H), 7.22 (d, 1H), 7.40-7.70 (m, 7H), 7.80 (d, 1H), 7.90 (d, 1H), 10.00 (s, 1H); MS (ESI(−)) m/e 484 (M−H)−.
Reaction SMILES: O[CH2:2][C:3]1[CH:30]=[CH:29][C:6]2[N:7]([CH2:24][CH2:25][CH:26]([CH3:28])[CH3:27])[C:8]([CH2:10][N:11]3[C:15]4[CH:16]=[CH:17][CH:18]=[CH:19][C:14]=4[N:13]([CH:20]([CH3:22])[CH3:21])[C:12]3=[O:23])=[N:9][C:5]=2[CH:4]=1.CCN(S(F)(F)[F:37])CC>C(Cl)Cl>[F:37][CH2:2][C:3]1[CH:30]=[CH:29][C:6]2[N:7]([CH2:24][CH2:25][CH:26]([CH3:28])[CH3:27])[C:8]([CH2:10][N:11]3[C:15]4[CH:16]=[CH:17][CH:18]=[CH:19][C:14]=4[N:13]([CH:20]([CH3:22])[CH3:21])[C:12]3=[O:23])=[N:9][C:5]=2[CH:4]=1
Reactant: CC(C)CCn1c(Cn2c(=O)n(C(C)C)c3ccccc32)nc2cc(CO)ccc21
Reactant: CCN(CC)S(F)(F)F
Solvent: ClCCl
Product: CC(C)CCn1c(Cn2c(=O)n(C(C)C)c3ccccc32)nc2cc(CF)ccc21
Yield: 78.3 %

Procedure:
To a solution of 1-[5-hydroxymethyl-1-(3-methyl-butyl)-1H-benzoimidazol-2-ylmethyl]-3-isopropyl-1,3-dihydro-benzoimidazol-2-one (41 mg, 0.10 mmol) in DCM (1 mL) was added DAST (32 mg, 0.20 mmol) at 0° C. The final solution was stirred at ambient temperature for 12 h then washed with sat. NaHCO3 and brine. The organic layer was dried over MgSO4 and evaporated. The residue was purified by slash chromatography (hexanes:EtOAc 2:1 to 1:1) to give 32 mg (78%) of 1-[5-fluoromethyl-1-(3-methyl-butyl)-1H-benzoimidazol-2-ylmethyl]-3-isopropyl-1,3-dihydro-benzoimidazol-2-one as a white solid.
Reaction SMILES: [CH3:1][NH:2][C:3](=[O:20])[C:4]1[CH:9]=[CH:8][CH:7]=[N:6][C:5]=1[CH2:10][C:11](=O)[C:12]1[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][CH:13]=1.[OH-].[Na+].C>C(Cl)(Cl)Cl>[Cl:18][C:15]1[CH:16]=[CH:17][C:12]([C:11]2[N:2]([CH3:1])[C:3](=[O:20])[C:4]3[CH:9]=[CH:8][CH:7]=[N:6][C:5]=3[CH:10]=2)=[CH:13][CH:14]=1
Reactant: CNC(=O)c1cccnc1CC(=O)c1ccc(Cl)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: ClC(Cl)Cl
Product: Cn1c(-c2ccc(Cl)cc2)cc2ncccc2c1=O
Temperature: 25 °C
Reaction time: 3 h

Procedure:
5 ml. of trifluromethanesulfonic acid were added to 4.6 g. (16.0 mmol.) of 2-(4'-chlorobenzoylmethyl)nicotinic acid N-methylamide (Compound XX) in 30 ml. chloroform stirred at 0° C. The resulting reaction mixture was then stirred at room temperature for 3 hours, chilled to 0° C. and made basic with 10% sodium hydroxide solution. Celite and charcoal were added and the entire reaction mixture was filtered through Celite. The phases were separated and the aqueous phase was extracted with methylene chloride. The organic phase and the methylene chloride extract were combined, dried over anhydrous magnesium sulfate and concentrated at reduced pressure to give the crude product as a light brown solid. The crude product was recrystallized from methylene chloride/diethyl ether and then from ethanol to give the product (2.5 g.), m.p. 139°-140° C.
Reaction SMILES: [C:1]([N:5]=[C:6]=[S:7])([CH3:4])([CH3:3])[CH3:2].Cl.[NH2:9][C@H:10]([CH2:16][CH2:17][CH2:18][NH:19][C:20]([O:22][CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)=[O:21])[C:11]([O:13][CH2:14][CH3:15])=[O:12]>C(O)C>[CH2:23]([O:22][C:20]([NH:19][CH2:18][CH2:17][CH2:16][C@@H:10]([NH:9][C:6]([NH:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[S:7])[C:11]([O:13][CH2:14][CH3:15])=[O:12])=[O:21])[C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1
Reactant: CC(C)(C)N=C=S
Reactant: CCOC(=O)[C@H](N)CCCNC(=O)OCc1ccccc1
Agent: Cl
Solvent: CCO
Product: CCOC(=O)[C@@H](CCCNC(=O)OCc1ccccc1)NC(=S)NC(C)(C)C
Temperature: 20 °C
Reaction time: 48 h

Procedure:
7.5 cm3 of tert-butyl isothiocyanate are added to a solution of 13 g of ethyl (2R)-2-amino-5-[(benzyloxy)carbonyl]amino-pentanoate hydrochloride in 200 cm3 of ethanol, and the mixture is then stirred at a temperature in the region of 20° C. After 48 hours, the reaction medium is concentrated under reduced pressure (1 kPa) at a temperature in the region of 40° C. to give 16 g of ethyl (2R)-5-{[(benzyloxy)carbonyl]amino}-2-(3-tert-butyl-thioureido)pentanoate in the form of a colourless oil [mass spectrum: EI m/z=409 M+ m/z=232 (C13H14NO3)+ m/z=142 (232-PhCH)+ m/z=91 (C7H7)+].
Reaction SMILES: C(Cl)(=O)C(Cl)=O.CS(C)=O.[OH:11][CH2:12][C:13]1[CH:18]=[N:17][CH:16]=[C:15]2[S:19][C:20]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])=[CH:21][C:14]=12.C(N(CC)CC)C>ClCCl>[CH:12]([C:13]1[CH:18]=[N:17][CH:16]=[C:15]2[S:19][C:20]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])=[CH:21][C:14]=12)=[O:11]
Reactant: CC(C)(C)OC(=O)c1cc2c(CO)cncc2s1
Agent: O=C(Cl)C(=O)Cl
Solvent: ClCCl
Solvent: CS(C)=O
Solvent: CCN(CC)CC
Product: CC(C)(C)OC(=O)c1cc2c(C=O)cncc2s1
Temperature: -78 °C
Reaction time: 0.33 h
Yield: 89.6 %

Procedure:
To a stirred solution of oxalyl chloride (0.10 mL, 1.17 mmol) in anhydrous dichloromethane (10 mL) at −78° C. was added DMSO (0.19 mL, 2.65 mmol). After 20 minutes, a solution of dimethylethyl 4-(hydroxymethyl)thieno[2,3-c]pyridine-2-carboxylate (0.28 g, 1.06 mmol) in anhydrous dichloromethane (4 mL) was added dropwise. The reaction was stirred 1 hours at −78° C. then treated with triethylamine (0.74 mL, 5.30 mmol). After 5 minutes, reaction was allowed to warm to room temperature over 30 minutes. The reaction was quenched with water (5 mL) and partitioned between dichoromethane (50 mL) and 50% sat. aq NaHCO3 (50 mL). The organic phase was washed with 50% sat. aq NaHCO3 (1×50 mL), dried (Na2SO4), filtered, and concentrated and dried in a desiccator to yield the title as a solid (0.25 g, 90%).
Reaction SMILES: Br[C:2]1[CH:3]=[N:4][C:5](=[O:9])[N:6]([CH3:8])[CH:7]=1.[CH3:10][C:11]1[CH:17]=[C:16](B2OC(C)(C)C(C)(C)O2)[CH:15]=[C:14]([CH3:27])[C:12]=1[NH2:13]>>[NH2:13][C:12]1[C:14]([CH3:27])=[CH:15][C:16]([C:2]2[CH:3]=[N:4][C:5](=[O:9])[N:6]([CH3:8])[CH:7]=2)=[CH:17][C:11]=1[CH3:10]
Reactant: Cc1cc(B2OC(C)(C)C(C)(C)O2)cc(C)c1N
Reactant: Cn1cc(Br)cnc1=O
Product: Cc1cc(-c2cnc(=O)n(C)c2)cc(C)c1N
Temperature: 70 °C
Reaction time: 12 h

Procedure:
The title compound is prepared from 5-bromo-1-methylpyrimidin-2(1H)-one and 2,6-dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline following a procedure analogous to that described in Step 2 of Intermediate 62. The mixture is stirred for 12 hours at 70° C. LC (method 9): tR=0.63 min; Mass spectrum (ESI+): m/z=230 [M+H]+.
Reaction SMILES: C[Si]([N-][Si](C)(C)C)(C)C.[K+].[CH2:11]([O:13][C:14]([C:16]1[CH:17]=[C:18]([CH:22]2[CH2:27][CH2:26][N:25]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[C:24](=[O:35])[CH2:23]2)[CH:19]=[CH:20][CH:21]=1)=[O:15])[CH3:12].[CH3:36]I>C1COCC1>[CH2:11]([O:13][C:14]([C:16]1[CH:17]=[C:18]([CH:22]2[CH2:27][CH2:26][N:25]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[C:24](=[O:35])[CH:23]2[CH3:36])[CH:19]=[CH:20][CH:21]=1)=[O:15])[CH3:12]
Reactant: CI
Reactant: CCOC(=O)c1cccc(C2CCN(C(=O)OC(C)(C)C)C(=O)C2)c1
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [K+]
Solvent: C1CCOC1
Product: CCOC(=O)c1cccc(C2CCN(C(=O)OC(C)(C)C)C(=O)C2C)c1
Temperature: -78 °C
Reaction time: 0.5 h
Yield: 26 %

Procedure:
Potassium bis(trimethylsilyl)amide (14 g, 71 mmol) was mixed with 300 mL of THF in a 1000 mL flame-dried round bottomed flask and the resulting mixture was cooled to −78° C. tert-butyl 4-[3-(ethoxycarbonyl)phenyl]-2-oxopiperidine-1-carboxylate (22.5 g, 64.8 mmol) dissolved in 150 mL of THF was added slowly to the mixture, via an addition funnel, and the resulting reaction mixture was stirred at −78° C. for 30 min. Methyl iodide (12.1 mL, 195 mmol) was then added dropwise and the reaction mixture was allowed to stir at −78° C. for 4 h before being allowed to warm to room temperature overnight. The reaction was quenched with saturated ammonium chloride and extracted 3 times with ether. The combined ethereal layers were washed with brine and dried over MgSO4, filtered, and concentrated under reduced pressure. The product was purified by flash chromatography (10-20% EA/hexanes) to give 6.1 g of the trans racemate of tert-butyl 4-[3-(ethoxycarbonyl)phenyl]-3-methyl-2-oxopiperidine-1-carboxylate (26%).
Reaction SMILES: [Br:1][C:2]1[C:3]2[N:4]([C:12]([C:15]([OH:17])=O)=[CH:13][N:14]=2)[CH:5]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:7]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl.[CH:43]12[NH:50][CH:47]([CH2:48][CH2:49]1)[CH2:46][O:45][CH2:44]2.C(=O)(O)[O-].[Na+]>CN(C=O)C.C(N(CC)CC)C>[CH:47]12[N:50]([C:15]([C:12]3[N:4]4[CH:5]=[C:6]([C:8]([F:9])([F:10])[F:11])[CH:7]=[C:2]([Br:1])[C:3]4=[N:14][CH:13]=3)=[O:17])[CH:43]([CH2:49][CH2:48]1)[CH2:44][O:45][CH2:46]2
Reactant: C1CC2COCC1N2
Reactant: O=C(O)c1cnc2c(Br)cc(C(F)(F)F)cn12
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: Cl
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: O=C(c1cnc2c(Br)cc(C(F)(F)F)cn12)N1C2CCC1COC2
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 80.3 %

Procedure:
To a solution of 8-bromo-6-(trifluoromethyl)imidazo[1,2-a]pyridine-3-carboxylic acid (300 mg) in DMF (6 mL) were added HATU (443 mg) and triethylamine (0.311 mL), and the mixture was stirred at room temperature for 10 min. To the reaction mixture was added 3-oxa-8-azabicyclo[3.2.1]octane hydrochloride (160 mg), and the mixture was stirred at room temperature for 30 min. To the reaction mixture was added saturated aqueous sodium bicarbonate solution, and the mixture was extracted with ethyl acetate. The extract was washed with water and saturated brine, and dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (NH, ethyl acetate/hexane) to give the title compound (315 mg).
Reaction SMILES: [F:1][CH:2]([F:18])[S:3]([C:6]1[CH:11]=[CH:10][C:9]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[CH:8][CH:7]=1)(=[O:5])=[O:4].[Cl:19][CH2:20][C:21](Cl)=[O:22].[Cl-].[Al+3].[Cl-].[Cl-]>ClCCl>[Cl:19][CH2:20][C:21]([C:15]1[CH:16]=[CH:17][C:12]([C:9]2[CH:8]=[CH:7][C:6]([S:3]([CH:2]([F:1])[F:18])(=[O:5])=[O:4])=[CH:11][CH:10]=2)=[CH:13][CH:14]=1)=[O:22]
Reactant: O=S(=O)(c1ccc(-c2ccccc2)cc1)C(F)F
Reactant: O=C(Cl)CCl
Agent: [Al+3]
Agent: [Cl-]
Solvent: ClCCl
Product: O=C(CCl)c1ccc(-c2ccc(S(=O)(=O)C(F)F)cc2)cc1
Temperature: 27.5 °C
Reaction time: 13 h
Yield: 82 %

Procedure:
To a 500-mL sidearm flask equipped with a vented addition funnel, overhead stirrer, thermometer, and nitrogen bubbler connected to a caustic scrubber was charged 26.8 g (0.098 mol, assay=98%) 4-[(difluoromethyl)sulfonyl]-1,1'-biphenyl, of 13.4 g (0.20 mol) of chloroacetyl chloride, and 150 mL of dichloromethane. Granular anhydrous aluminum chloride (28.0 g, 0.210 mol) was added in portions over 20 minutes, and the mixture was allowed to stir at 25-30° C. for 8-18 h. The violet solution was poured onto 300 g of ice with efficient stirring, 300 mL of dichloromethane was added to the resulting yellow slurry, and the mixture was filtered to remove undissolved 4'-(chloroacetyl)[1,1'-biphenyl]-4-sulfinic acid. After phase separation, the dichloromethane solution was washed with aqueous HCl, aqueous NaHCO3, dried with MgSO4, filtered, and concentrated to dryness. The residue was slurried in 200 mL of isopropanol, filtered, and washed with 50 mL of isopropanol to afford 27.7 g (ca. 79%) of crude 2-chloro-1-[4'-[(difluoromethyl)sulfonyl][1,1'-biphenyl]-4-yl]ethanone as a pale yellow solid assaying at 96% by gc-area. A 98%-pure sample was obtained by chromatography on silica-gel and crystallization from EtOAc/hexane, m.p. 157-159° C. IR(KBr) 1696, 1604, 1594, 1397, 1344, 1308, 1210, 1168, 1118, 1081, 999, 816, 750, 631 cm-1. UV (CH2Cl2): λmax =287 nm (ε=33.1×103) 1H-NMR (CDCl3): δ4.75 (s, 2H), 6.25 (t, 1H, J=60 Hz), 7.77 (d, 2H), 7.89 (d, 2H), 8.10 (2 d, 4H). 13C-NMR (DMSO-d6): δ47.6, 114.7 (t, JCF =283 Hz), 191.3 ppm. 19F-NMR (CDCl3): δ-121.6 ppm (d, JHF =53 Hz). Mass spectrum m/z=344 (M+), 295 (M+ --CH2Cl, base peak), 245, 229, 180, 165, 152 amu.
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.CN(C)C=O.[H-].[Na+].Br[CH:31]([CH2:37][CH3:38])[C:32]([O:34][CH2:35][CH3:36])=[O:33]>O.C(OCC)(=O)C>[CH3:20][Si:19]([CH3:22])([CH3:21])[CH2:18][CH2:17][O:16][CH2:15][N:12]1[C:8]2[N:9]=[CH:10][N:11]=[C:6]([C:4]3[CH:5]=[N:1][N:2]([CH:31]([CH2:37][CH3:38])[C:32]([O:34][CH2:35][CH3:36])=[O:33])[CH:3]=3)[C:7]=2[CH:14]=[CH:13]1
Reactant: C[Si](C)(C)CCOCn1ccc2c(-c3cn[nH]c3)ncnc21
Reactant: CCOC(=O)C(Br)CC
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Solvent: O
Product: CCOC(=O)C(CC)n1cc(-c2ncnc3c2ccn3COCC[Si](C)(C)C)cn1
Reaction time: 0.25 h
Yield: 111.6 %

Procedure:
To a 0° C. solution of 4-(1H-pyrazol-4-yl)-7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidine (2.0 g, 0.0063 mol) in N,N-dimethylformamide (40 mL, 0.5 mol) was added sodium hydride (0.30 g, 0.0076 mol). After 15 minutes, ethyl 2-bromobutyrate (1.4 mL, 0.0095 mol) was added. After 4.5 hours, ethyl acetate and water were added. The organic phase was washed with water twice and saturated NaCl. The organic phase was then and the solvent was removed by rotary evaporation to give 3.02 g of a thick orange oil (110% yield). 1H NMR (400 MHz, CDCl3): δ 8.92 (1H, s); 8.49 (1H, s); 8.35 (1H, s); 7.45 (1H, d); 6.85 (1H, d); 6.75 (2H, s); 5.0 (1H, t); 4.35 (2H, m); 3.6 (2H, t); 2.35 (2H, m); 1.35 (6H, m); (1.0 (3H, m); 0 (9H, s). LCMS (M+1): 430.
Reaction SMILES: Cl[CH2:2][C:3]([N:5]([O:7][CH3:8])[CH3:6])=[O:4].S[C:10]1[CH:11]=[C:12](O)C=[CH:14][CH:15]=1.C([O-])([O-])=O.[K+].[K+].OO.C(O[K])(C)(C)C.ICCCC=C>CN(C=O)C.CCCC[N+](CCCC)(CCCC)CCCC.[I-]>[CH3:8][O:7][N:5]([CH3:6])[C:3](=[O:4])[CH:2]=[CH:12][CH2:11][CH2:10][CH:15]=[CH2:14]
Reactant: Oc1cccc(S)c1
Reactant: CON(C)C(=O)CCl
Agent: C=CCCCI
Agent: CC(C)(C)O[K]
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Solvent: CN(C)C=O
Product: C=CCCC=CC(=O)N(C)OC
Temperature: 23 °C
Reaction time: 8 h
Yield: 3.9 %

Procedure:
To a solution of 2-chloro-N-methoxy-N-methylacetamide (6.0 g, 48.8 mmol) in dry DMF (20 mL) at 23° C. was added 3-mercaptophenol (4.44 mL, 48.8 mmol) and K2CO3 (6.7 g, 48.8 mmol). The resulting suspension was stirred at 23° C. overnight. After this period of time, Merrifield resin (24 g, <2 mmol·g−1, <48.8 mmol) was added to the mixture followed by K2CO3 (11.4 g, 83.0 mmol) as well as TBAI (catalytic amount), and the suspension was heated up to 50° C. After 12 hours at this temperature, the resin was filtered and washed several times: HClaq. (50 mL), MeOH (50 mL), CH2Cl2 (50 mL) and Et2O (50 mL). The resin was dried under reduced pressure to constant mass of 29.2 g. The final mass gain (5.2 g, 27.3 mmol) indicated an estimate loading of 0.81 mmol·g−1. Resin 2-49 (10 g, 0.81 mmol·g−1) was suspended in a 1:1 mixture of HFIP/CH7Cl2 (50 mL). To this suspension, H2O2 (3 mL, 16.0 mmol) was added at 23° C. and the resulting mixture was shaken for 12 h. Resin 2-113 was then filtered, washed using MeOH (50 mL), CH2Cl2 (50 mL) and Et2O (50 mL) and dried under reduced pressure to constant mass before subsequent use. Resin 2-113 (4.0 g, <0.81 mmol·g−1) was suspended in DMSO (40 mL) followed by the addition of tBuOK (336 mg, 3.0 mmol). After shaking the reaction for 1 h at room temperature, 5-iodo-1-pentene (588 mg, 3.0 mmol) was added to the suspension and the mixture was shaken for 3 h. The resin was filtered, washed and dried as before. Then, it was suspended in toluene and heated at 80° C. After 8 h at this temperature, the resin was filtered and washed several times with more toluene. The combined toluene solutions were evaporated giving pure compound 2-114 as a colourless oil (321 mg, 77%) of 95% purity judged by NMR. 1H NMR (400 MHz, CDCl3, 25° C.): δ=6.94 (dt, J=15.7, 6.7 Hz, 1H), 6.39 (d, J=15.2 Hz, 1H), 5.84-5.74 (m, 1H), 5.02 (dd, J=17.4, 1.7 Hz, 1H), 4.97 (d, J=10.1 Hz, 1H), 3.67 (s, 3H), 3.21 (s, 3H), 2.34-2.29 (m, 2H), 2.23-2.18 (m, 2H); 13C NMR (100 MHz, CDCl3, 25° C.): δ=166.8, 146.7, 137.3, 119.1, 115.3, 61.6, 32.3, 31.7, (one carbon is not detected); I.R. (film): νmax=2934, 1681, 1638, 1378, 1179 cm−1.
Reaction SMILES: [C:1]1([Sb:7](=O)([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH3:21][O:22][C:23](=[O:34])[C:24]1[CH:33]=[CH:32][C:27]([C:28]([O:30][CH3:31])=[O:29])=[CH:26][CH:25]=1>>[CH3:31][O:30][C:28](=[O:29])[C:27]1[CH:32]=[CH:33][C:24]([C:23]([O:22][CH3:21])=[O:34])=[CH:25][CH:26]=1.[C:14]1([Sb:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1
Reactant: O=[Sb](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: COC(=O)c1ccc(C(=O)OC)cc1
Product: c1ccc([Sb](c2ccccc2)c2ccccc2)cc1

Procedure:
Triphenyl antimony oxide and dimethylterephthalate were reacted to yield triphenyl antimony dimethylterephthalate. ##STR9##
Reaction SMILES: [CH:1]1([C:7]([C:9]2[N:13]([CH3:14])[C:12]([S:15]([NH2:18])(=[O:17])=[O:16])=[CH:11][CH:10]=2)=O)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.NN.O.[OH-].[K+]>C(O)COCCO.O>[CH:1]1([CH2:7][C:9]2[N:13]([CH3:14])[C:12]([S:15]([NH2:18])(=[O:17])=[O:16])=[CH:11][CH:10]=2)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1
Reactant: Cn1c(C(=O)C2CCCCC2)ccc1S(N)(=O)=O
Agent: NN
Agent: [K+]
Agent: [OH-]
Solvent: O
Solvent: OCCOCCO
Product: Cn1c(CC2CCCCC2)ccc1S(N)(=O)=O
Yield: 44 %

Procedure:
To a solution of compound 25d (1.1 g, 4.1 mmol) in diethylene glycol (50 mL) was added NH2NH2.H2O (0.28 g, 4.5 mmol). The mixture was refluxed for 2 h and then the water and excess NH2NH2.H2O was removed under vacuum. Then KOH (0.46 g, 8.2 mmol) was added and the mixture was refluxed for 4 h, cooled, diluted with water and extracted with EA. The combined organic layers were washed with brine, dried over Na2SO4, evaporated and purified by prep-TLC to give compound 25e (462 mg, 46%).
Reaction SMILES: [Cl:1][C:2]1[C:7]([F:8])=[CH:6][C:5]([C:9]2[N:10]=[C:11]([N:18]3[CH2:23][CH2:22][NH:21][CH2:20][CH2:19]3)[C:12]3[S:17][CH:16]=[CH:15][C:13]=3[N:14]=2)=[C:4]([F:24])[CH:3]=1.[CH2:25]1[O:27][C@@H:26]1[CH2:28][OH:29].C1COCC1.[ClH:35].O1CCOCC1>CCO>[ClH:1].[ClH:35].[Cl:1][C:2]1[C:7]([F:8])=[CH:6][C:5]([C:9]2[N:10]=[C:11]([N:18]3[CH2:19][CH2:20][N:21]([CH2:25][C@H:26]([OH:27])[CH2:28][OH:29])[CH2:22][CH2:23]3)[C:12]3[S:17][CH:16]=[CH:15][C:13]=3[N:14]=2)=[C:4]([F:24])[CH:3]=1
Reactant: Fc1cc(-c2nc(N3CCNCC3)c3sccc3n2)c(F)cc1Cl
Reactant: OC[C@@H]1CO1
Agent: Cl
Solvent: CCO
Solvent: C1CCOC1
Solvent: C1COCCO1
Product: OC[C@@H](O)CN1CCN(c2nc(-c3cc(F)c(Cl)cc3F)nc3ccsc23)CC1
Reaction time: 21 h

Procedure:
A mixture of 870 mg of 2-(4-chloro-2,5-difluorophenyl)-4-piperazine-1-ylthieno[3,2-d]pyrimidine, 1.08 ml of (R)-glycidol and 15 ml of THF was stirred for 21 hours heated to reflux. The reaction mixture was concentrated under reduced pressure and the obtained residue was purified by silica gel column chromatography (chloroform-MeOH) to give a foam-like substance. After the obtained foam-like substance was dissolved in 10 ml of EtOH and was added to 2 ml of 4M HCl-dioxane solution, it was concentrated under reduced pressure to give a solid. This solid was recrystallized from ethanol to give 898 mg of (S)-3-{4-[2-(4-chloro-2,5-difluorophenyl)thieno[3,2-d]pyrimidine-4-yl]piperazine-1-yl}propane-1,2-diol dihydrochloride.