Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [OH:1][CH2:2][C:3]1[CH:12]=[CH:11][C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[N:4]=1>C(O)C.O1CCCC1.[Pt]>[OH:1][CH2:2][CH:3]1[CH2:12][CH2:11][C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[NH:4]1
Reactant: OCc1ccc2ccccc2n1
Agent: [Pt]
Solvent: C1CCOC1
Solvent: CCO
Product: OCC1CCc2ccccc2N1

Procedure:
Sodium borohydride (21.7 g, 0.57 mol) was added in portions to a solution of quinoline-2-carboxaldehyde (30 g, 0.191 mol) in ethanol (300 mL) at 0° C. The reaction mixture was warmed to room temperature, stirred at room temperature for 2 hrs, and quenched by water. Volatiles were removed under reduced pressure and the residue dissolved in ethyl acetate, washed with water and saturated aqueous sodium chloride, dried over sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel chromatography. Fractions containing product were combined and concentrated under reduced pressure to provide the desired compound and 2-(hydroxymethyl)quinoline. A solution of the recovered 2-(hydroxymethyl)quinoline in ethanol (250 mL) and tetrahydrofuran (250 mL) was hydrogenated at 60 psi in the presence of 5% platinum on carbon at 40° C. for 48 hours. The reaction mixture was filtered and the filtrate concentrated under reduced pressure to provide the title compound.
Reaction SMILES: Cl[C:2]([O:4][CH2:5][CH2:6]Cl)=[O:3].[NH:8]1[CH:12]=[CH:11][N:10]=[CH:9]1.O.[Cl:14]CCl>>[Cl:14][CH:5]([O:4][C:2]([C:9]1[NH:8][CH:12]=[CH:11][N:10]=1)=[O:3])[CH3:6]
Reactant: c1c[nH]cn1
Reactant: O=C(Cl)OCCCl
Reactant: ClCCl
Solvent: O
Product: CC(Cl)OC(=O)c1ncc[nH]1
Temperature: 25 °C
Reaction time: 4 h

Procedure:
28.6 g (0.2 mole) of chloroethyl chloroformate are added dropwise to a solution of 27.2 g (0.4 mole) of imidazole in 200 ml of dichloromethane cooled in a water bath. The mixture is stirred at room temperature for 4 hours, and 50 ml of iced water are then added. The organic phase is washed with 2×50 ml of water and then dried over magnesium sulphate. After evaporation and distillation, 38.1 g (73%) of α-chloroethoxycarbonylimidazole [B.p. 80° C./66.6 Pa (0.5 mm Hg)] are obtained in the form of a colourless liquid which crystallises spontaneously at room temperature, m.p. 50° C. ##STR57##
Reaction SMILES: Cl.[CH:2]1([N:7]2[CH2:11][CH2:10][CH2:9][C@@H:8]2[CH2:12][NH:13][C:14]2[C:15](=[O:25])[N:16]([CH2:21][C:22]([OH:24])=O)[C:17]([CH3:20])=[CH:18][N:19]=2)[CH2:6][CH2:5][CH2:4][CH2:3]1.[NH:26]1[C:34]2[C:29](=[CH:30][C:31]([CH2:35][NH2:36])=[CH:32][CH:33]=2)[CH:28]=[CH:27]1>>[NH3:7].[CH:2]1([N:7]2[CH2:11][CH2:10][CH2:9][C@@H:8]2[CH2:12][NH:13][C:14]2[C:15](=[O:25])[N:16]([CH2:21][C:22]([NH:36][CH2:35][C:31]3[CH:30]=[C:29]4[C:34](=[CH:33][CH:32]=3)[NH:26][CH:27]=[CH:28]4)=[O:24])[C:17]([CH3:20])=[CH:18][N:19]=2)[CH2:3][CH2:4][CH2:5][CH2:6]1
Reactant: Cc1cnc(NC[C@H]2CCCN2C2CCCC2)c(=O)n1CC(=O)O
Reactant: NCc1ccc2[nH]ccc2c1
Agent: Cl
Product: Cc1cnc(NC[C@H]2CCCN2C2CCCC2)c(=O)n1CC(=O)NCc1ccc2[nH]ccc2c1
Product: N
Yield: 16 %

Procedure:
The title compound was prepared from 2-[3-({[(2R)-1-cyclopentylpyrrolidinyl]methyl}amino)-6-methyl-2-oxo-1(2H)-pyrazinyl]acetic acid hydrochloride (preparation 145) and 1H-indol-5-ylmethylamine (preparation 8), following the procedure described in preparation 45. The crude product was purified by chromatography using a Biotage™ (KP-Sil™ 60 Å silica gel) cartridge and dichloromethane:methanol:0.88 ammonia (95:5:0.5) as eluant. The product was further purified using preparative tic and dichloromethane:methanol:0.88 ammonia (90:10:1) as eluant to afford the title compound, (11 mg, 16%).
Reaction SMILES: [C:1]([C:3]1[CH:10]=[CH:9][C:6]([CH2:7]Br)=[CH:5][CH:4]=1)#[N:2].P(OCC)(OCC)[O:12]CC.[CH2:21]([N:28]1[CH2:33][CH2:32][CH2:31][CH2:30][C:29]1=O)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.[OH-].[K+]>O.C(O)C.C1(C)C=CC=CC=1>[CH2:21]([N:28]1[CH2:33][CH2:32][C:31](=[CH:7][C:6]2[CH:9]=[CH:10][C:3]([C:1]([NH2:2])=[O:12])=[CH:4][CH:5]=2)[CH2:30][CH2:29]1)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1
Reactant: N#Cc1ccc(CBr)cc1
Reactant: CCOP(OCC)OCC
Reactant: O=C1CCCCN1Cc1ccccc1
Agent: [K+]
Agent: [OH-]
Solvent: O
Solvent: CCO
Solvent: Cc1ccccc1
Product: NC(=O)c1ccc(C=C2CCN(Cc3ccccc3)CC2)cc1
Temperature: 60 °C
Yield: 43.1 %

Procedure:
4-Cyanobenzyl bromide (4.90 g, 25.0 mmol), triethyl phosphite (4.77 mL, 27.5 mmol) and toluene (4.9 mL) were charged, and the mixture was stirred with heating under reflux for 3 hrs., while distilling away the solvent at normal pressure. The mixture was allowed to return to room temperature, and concentrated under reduced pressure to give a colorless transparent oil which solidified by standing. N-benzylpiperidone (4.73 g, 25.0 mmol), ethanol (35 mL), water (451 mg, 25.0 mmol) and potassium hydroxide (pellet, 7.01 g, 125 mmol) were added successively, and the mixture was stirred at room temperature for 30 min. to give a yellow solution. The solution was stirred at 65–70° C. for 2 hrs. and cooled to 60° C. to allow precipitation of crystals to give a yellow suspension. Iced water (200 mL) was added, and the mixture was stirred at 0–5° C. After dissolution once, a yellow suspension was formed. The suspension was stirred at 0–5° C. for 30 min. and the crystals were collected by filtration and dried in vacuo at 40° C. to give the title compound (3.30 g, yield 43.0%) as white crystals.
Reaction SMILES: [CH3:1][Si:2]([CH3:42])([CH3:41])[CH2:3][CH2:4][O:5][CH2:6][N:7]([CH2:33][O:34][CH2:35][CH2:36][Si:37]([CH3:40])([CH3:39])[CH3:38])[C:8]1[N:13]2[N:14]=[CH:15][C:16](I)=[C:12]2[N:11]=[C:10]([CH:18]2[CH2:24][CH:23]3[N:25]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH:20]([CH2:21][CH2:22]3)[CH2:19]2)[CH:9]=1.[F:43][C:44]1[CH:49]=[CH:48][CH:47]=[C:46]([F:50])[C:45]=1[C:51]1[CH:56]=[CH:55][C:54](B2OC(C)(C)C(C)(C)O2)=[CH:53][N:52]=1.ClCCl.C(=O)([O-])[O-].[K+].[K+]>>[CH3:1][Si:2]([CH3:42])([CH3:41])[CH2:3][CH2:4][O:5][CH2:6][N:7]([CH2:33][O:34][CH2:35][CH2:36][Si:37]([CH3:40])([CH3:39])[CH3:38])[C:8]1[N:13]2[N:14]=[CH:15][C:16]([C:54]3[CH:53]=[N:52][C:51]([C:45]4[C:46]([F:50])=[CH:47][CH:48]=[CH:49][C:44]=4[F:43])=[CH:56][CH:55]=3)=[C:12]2[N:11]=[C:10]([CH:18]2[CH2:24][CH:23]3[N:25]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH:20]([CH2:21][CH2:22]3)[CH2:19]2)[CH:9]=1
Reactant: CC1(C)OB(c2ccc(-c3c(F)cccc3F)nc2)OC1(C)C
Reactant: CC(C)(C)OC(=O)N1C2CCC1CC(c1cc(N(COCC[Si](C)(C)C)COCC[Si](C)(C)C)n3ncc(I)c3n1)C2
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: ClCCl
Product: CC(C)(C)OC(=O)N1C2CCC1CC(c1cc(N(COCC[Si](C)(C)C)COCC[Si](C)(C)C)n3ncc(-c4ccc(-c5c(F)cccc5F)nc4)c3n1)C2
Temperature: 95 °C
Yield: 50.3 %

Procedure:
tert-Butyl 3-[7-(bis{[2-(trimethylsilyl)ethoxy]methyl}amino)-3-iodopyrazolo[1,5-a]pyrimidin-5-yl]-8-azabicyclo[3.2.1]octane-8-carboxylate (1.26 g, 1.73 mmol), 2-(2,6-difluorophenyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (0.88 g, 2.1 mmol), [1,1′-Bis(diphenylphosphino)ferrocene]dichloropalladium(II)complex with dichloromethane (1:1) (141 mg, 0.173 mmol), and potassium carbonate (0.716 g, 5.18 mmol) were placed in a 100-mL round bottom flask equipped with a reflux condenser and rubber septa. Then, the reaction vessel was evacuated and back filled with nitrogen 3 times before adding 1,4-dioxane (3.50 mL) and water (0.933 mL). Then, the reaction was sparged with nitrogen for 8 minutes, then maintained under nitrogen with a balloon and heated at 95° C. for 6 hr. The reaction mixture was then cooled to ambient temperature, diluted with dichloromethane (100 mL), filtered through a plug of Magnesol (ca. 60 mL). and the filtrate was concentrated. The crude product was purified by flash chromatography, (0 to 10% ethylacetate/dichloromethane) to afford the title compound (690 mg, 50%) as an ivory foam.
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([O:8]C(C(C)(C)C)=O)=[CH:4][C:3]=1[CH2:15][CH2:16][CH2:17][C:18]1[CH:26]=[CH:25][C:21]([C:22]([OH:24])=[O:23])=[CH:20][CH:19]=1.C(=O)([O-])[O-].[K+].[K+].[CH2:33](Br)[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1.C(OCC)(=O)C>CN(C=O)C.O>[CH2:33]([O:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][C:3]=1[CH2:15][CH2:16][CH2:17][C:18]1[CH:19]=[CH:20][C:21]([C:22]([OH:24])=[O:23])=[CH:25][CH:26]=1)[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1
Reactant: CC(C)(C)C(=O)Oc1ccc(O)c(CCCc2ccc(C(=O)O)cc2)c1
Reactant: BrCc1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: O=C(O)c1ccc(CCCc2cc(O)ccc2OCc2ccccc2)cc1
Reaction time: 18 h

Procedure:
To a mixture of 4-[3-(2-hydroxy-5-(t-butylcarbonyloxy)phenyl)propyl]benzoic acid (3 g) and potassium carbonate (3.5 g) in DMF (10 ml) was added benzyl bromide (2.97 ml). The mixture was stirred for 18 hours, poured into ethyl acetate (100 ml) and water (100 ml). The organic solution was washed with brine (100 ml), dried (magnesium sulphate) filtered and evaporated. The residue was purified by subjecting to chromatography on silica gel using ethyl acetate:hexane (1:9) as eluant. There was thus obtained benzyl 4-[3-(2-benzyloxy-5-(t-butylcarbonyloxy) phenyl)propyl]benzoate (2 g)
Reaction SMILES: Cl[C:2]([O:4][CH2:5][CH3:6])=[O:3].[CH2:7]([O:9][CH:10]([O:15][CH2:16][CH3:17])[CH2:11][CH2:12][CH2:13][NH2:14])[CH3:8].N1C=CC=CC=1.O>ClCCl>[CH2:16]([O:15][CH:10]([O:9][CH2:7][CH3:8])[CH2:11][CH2:12][CH2:13][NH:14][C:2](=[O:3])[O:4][CH2:5][CH3:6])[CH3:17]
Reactant: CCOC(=O)Cl
Reactant: CCOC(CCCN)OCC
Solvent: c1ccncc1
Solvent: ClCCl
Solvent: O
Product: CCOC(=O)NCCCC(OCC)OCC
Reaction time: 0.5 h

Procedure:
Ethyl chloroformate (0.3 ml, 3.1 mmol) was added dropwise to a solution of 4-aminobutanal diethyl acetal (0.5 ml, 2.9 mmol) and pyridine (0.28 ml, 3.5 mmol) in dichloromethane (10 ml) at 5° C. The mixture was stirred for 30 min. Water was added and the mixture was extracted with ether. The ether was dried (sodium sulphate) and evaporated to give the product as a yellow oil, MS (+EI) 232 ([M-H]+), 1H NMR (CDCl3) 4.69 (1H, s), 4.4 (1H, t), 4.00 (2H, q), 3.5-3.65 (2H, m), 3.35-3.5 (2H, m), 3.05-3.15 (2H, m), 1.5-1.6 (4H, m), 1.1-1.2 (9H, m).
Reaction SMILES: [C:1]1([N:7]2[C:12](=[O:13])[C:11]3[S:14][CH:15]=[C:16]([C:17]4[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=4)[C:10]=3[N:9]=[CH:8]2)[CH:6]=[CH:5]C=[CH:3][CH:2]=1.NC1C(C2C=CC=CC=2[F:35])=CSC=1C(OC)=O.C(OCC)(OCC)OCC.C1(N)CCCC1>C(O)(=O)C>[CH:1]1([N:7]2[C:12](=[O:13])[C:11]3[S:14][CH:15]=[C:16]([C:17]4[CH:18]=[CH:19][CH:20]=[CH:21][C:22]=4[F:35])[C:10]=3[N:9]=[CH:8]2)[CH2:2][CH2:3][CH2:5][CH2:6]1
Reactant: O=c1c2scc(-c3ccccc3)c2ncn1-c1ccccc1
Reactant: COC(=O)c1scc(-c2ccccc2F)c1N
Agent: NC1CCCC1
Solvent: CCOC(OCC)OCC
Solvent: CC(=O)O
Product: O=c1c2scc(-c3ccccc3F)c2ncn1C1CCCC1
Yield: 59.7 %

Procedure:
In the same manner as the synthesis of Compound 1, methyl 3-amino-4-(2-fluorophenyl)thiophene-2-carboxylate (100 mg, 0.40 mmol), triethyl orthoformate (1.0 ml), cyclopentylamine (0.09 ml, 0.92 mmol), and acetic acid (0.1 ml) were used to give 75 mg (0.24 mmol, 59.7% yield) of the title compound.
Reaction SMILES: [NH2:1][C@H:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]([C:12]([C:14]2[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=2)=[O:13])[C@@H:4]([CH3:22])[CH2:3]1.[CH:23](=O)[CH3:24].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(N(CC)C(C)C)(C)C.[Cl:49][C:50]1[CH:58]=[CH:57][C:53]([C:54](Cl)=[O:55])=[CH:52][CH:51]=1>ClCCl>[Cl:49][C:50]1[CH:58]=[CH:57][C:53]([C:54]([N:1]([CH2:23][CH3:24])[C@H:2]2[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[N:5]([C:12](=[O:13])[C:14]3[CH:15]=[CH:16][C:17]([O:20][CH3:21])=[CH:18][CH:19]=3)[C@@H:4]([CH3:22])[CH2:3]2)=[O:55])=[CH:52][CH:51]=1
Reactant: O=C(Cl)c1ccc(Cl)cc1
Reactant: COc1ccc(C(=O)N2c3ccccc3[C@H](N)C[C@@H]2C)cc1
Reactant: CC=O
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: CCN(C(=O)c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(OC)cc2)c2ccccc21
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 25.4 %

Procedure:
(2S,4R)-4-Chloro-N-ethyl-N-[1-(4-methoxy-benzoyl)-2-methyl-1,2,3,4-tetrahydro-quinolin-4-yl]-benzamide was synthesized as described in general procedure C, except following benzyl carbamate removal the amine was modified in the following manner. To a solution of (2S,4R)-(4-amino-2-methyl-3,4-dihydro-2H-quinolin-1-yl)-(4-methoxy-phenyl)-methanone (200 mg, 0.68 mmol) in 20 ml dichloromethane was added acetaldehyde (0.042 mL, 0.75 mmol). The reaction mixture was stirred 30 min at room temperature. Then sodium triacetoxyborohydride (0.156 g, 0.75 mmol) was added and the resulting reaction mixture was stirred at room temperature for 6 hours. N,N-diisopropylethylamine (0.3 mL, 2.3 mmol) and 4-chlorobenzoyl chloride (0.4 mL, 3.1 mmol) was added and stirred at room temperature overnight. Dichloromethane (40 ml) was added. The mixture was washed with 30 ml sodium hydroxide (1N). The organic layer was dried with magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by silica gel chromatography, eluting with ethyl acetate-dichloromethane (1:4) to give 80 mg (24%) title compound
Reaction SMILES: [CH3:1][N:2]1[CH2:7][CH2:6][N:5]([C:8]2[O:9][C:10]3[CH:16]=[CH:15][CH:14]=[CH:13][C:11]=3[N:12]=2)[CH2:4][CH2:3]1.[CH2:17]([Br:24])[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1>C1COCC1>[Br-:24].[CH2:17]([N+:2]1([CH3:1])[CH2:3][CH2:4][N:5]([C:8]2[O:9][C:10]3[CH:16]=[CH:15][CH:14]=[CH:13][C:11]=3[N:12]=2)[CH2:6][CH2:7]1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1
Reactant: CN1CCN(c2nc3ccccc3o2)CC1
Reactant: BrCc1ccccc1
Solvent: C1CCOC1
Product: C[N+]1(Cc2ccccc2)CCN(c2nc3ccccc3o2)CC1
Product: [Br-]
Reaction time: 1 h

Procedure:
A 300 mg portion of 2-(4-methyl-1-piperazinyl)-benzoxazole was dissolved in 5 ml of THF. Under cooling with ice, 354 mg of benzyl bromide was added to the thus prepared solution, and the reaction was carried out for 1 hour at the same temperature and then for 22 hours at room temperature. The thus formed precipitate was collected by filtration and washed with acetone. The filtrate was concentrated under a reduced pressure, and the resulting residue was dissolved in 50 ml of water, washed with ethyl acetate and then lyophilized to obtain 496 mg of the title compound.
Reaction SMILES: [CH3:1][O:2][N:3]([CH3:27])[C:4]([C:6]1[C:11]([NH:12][S:13]([C:16]2[CH:21]=[CH:20][C:19]([Cl:22])=[C:18]([C:23]([F:26])([F:25])[F:24])[CH:17]=2)(=[O:15])=[O:14])=[CH:10][CH:9]=[CH:8][N:7]=1)=[O:5].C(=O)([O-])[O-].[K+].[K+].[CH3:34][O:35][CH2:36]Cl.COCNC(C1C(N(COC)S(C2C=CC(Cl)=C(C(F)(F)F)C=2)(=O)=O)=CC(Cl)=CN=1)=O>C1COCC1>[CH3:1][O:2][N:3]([CH3:27])[C:4]([C:6]1[C:11]([N:12]([S:13]([C:16]2[CH:21]=[CH:20][C:19]([Cl:22])=[C:18]([C:23]([F:26])([F:24])[F:25])[CH:17]=2)(=[O:15])=[O:14])[CH2:34][O:35][CH3:36])=[CH:10][CH:9]=[CH:8][N:7]=1)=[O:5]
Reactant: CON(C)C(=O)c1ncccc1NS(=O)(=O)c1ccc(Cl)c(C(F)(F)F)c1
Reactant: COCCl
Agent: COCNC(=O)c1ncc(Cl)cc1N(COC)S(=O)(=O)c1ccc(Cl)c(C(F)(F)F)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: C1CCOC1
Product: COCN(c1cccnc1C(=O)N(C)OC)S(=O)(=O)c1ccc(Cl)c(C(F)(F)F)c1

Procedure:
Prepared from 1.05 g (2.48 mmol) of 3-(4-chloro-3-trifluoromethyl-benzenesulfonylamino)-pyridine-2-carboxylic acid methoxy-methyl-amide, 1.71 g of potassium carbonate and 566 μL of methoxymethyl chloride in 7 mL THF using procedure used in the preparation of Intermediate 12. Yield: 420 mg of a white solid. LC-MSD, m/z for C17H17ClF3N3O5S [M+Na]+=490.0, 491.9; HPLC retention time: 2.5 minutes.
Reaction SMILES: [CH3:1][C:2]1[CH:12]=[CH:11][CH:10]=[CH:9][C:3]=1[CH:4]=[CH:5][C:6]([OH:8])=[O:7].[C:13]1([CH2:19][CH2:20]O)[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1>C1(C)C=CC(S(O)(=O)=O)=CC=1.C1(C)C=CC=CC=1>[CH3:1][C:2]1[CH:12]=[CH:11][CH:10]=[CH:9][C:3]=1[CH:4]=[CH:5][C:6]([O:8][CH2:20][CH2:19][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)=[O:7]
Reactant: OCCc1ccccc1
Reactant: Cc1ccccc1C=CC(=O)O
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: Cc1ccccc1
Product: Cc1ccccc1C=CC(=O)OCCc1ccccc1
Reaction time: 15 h
Yield: 74 %

Procedure:
A solution of 324.0 g (2.00 moles) of o-methylcinnamic acid, 428.0 g (3.5 moles) of 2-phenylethanol, 10.0 g (0.058 moles) of p-toluenesulfonic acid and 1,200 ml of toluene was refluxed under a water separator. After 15 hours, the calculated amount of water had separated off. The reaction solution was washed first with water and then with saturated sodium bicarbonate solution. The combined washwater was extracted once with ether, and the ether phase was combined with the organic phase. The combined, organic phases were fractionated over a 10 cm Vigreux column. The solvents were separated off under atmospheric pressure and in a vacuum from a water pump. The Vigreux column was replaced by a column head and the product was distilled under 0.01 mm Hg (b.p. 154°-155° C./0.01 mm Hg). 394.0 g of phenylethyl o-methylcinnamate of melting point 52° to 53° C. were obtained.
Reaction SMILES: [F:1][C:2]([F:23])([S:19](F)(=[O:21])=[O:20])[C:3]([F:18])([F:17])[C:4]([F:16])([F:15])[C:5]([F:14])([F:13])[C:6]([F:12])([F:11])[C:7]([F:10])([F:9])[F:8].C[Si](C)(C)[O-:26].[K+:29]>C1(C)C=CC=CC=1>[F:1][C:2]([F:23])([S:19]([O-:26])(=[O:21])=[O:20])[C:3]([F:18])([F:17])[C:4]([F:16])([F:15])[C:5]([F:14])([F:13])[C:6]([F:12])([F:11])[C:7]([F:10])([F:9])[F:8].[K+:29]
Reactant: C[Si](C)(C)[O-]
Reactant: O=S(=O)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F
Agent: [K+]
Solvent: Cc1ccccc1
Product: O=S(=O)([O-])C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F
Yield: 65.4 %

Procedure:
The procedure of Example 1 was followed using perfluorohexanesulfonyl fluoride (7.90 g, 19.6 mmol), potassium trimethylsilanolate (2.20 g, 17.1 mmol), and dry toluene (50 mL), while heating at 40° for 3.5 h. Potassium perfluorohexanesulfonate (4.9 g, 65% yield) was isolated as a white solid: 19F NMR (methanol) data were closely similar to those reported in Example 23.
Reaction SMILES: [Cl:1][C:2]1[C:7](=[O:8])[NH:6][C:5]([CH2:9][C:10]([O-:12])=O)=[N:4][C:3]=1[N:13]1[CH2:18][CH2:17][O:16][CH2:15][CH2:14]1.[Na+].[CH3:20][C@H:21]1[CH2:29][C:28]2[C:23](=[CH:24][CH:25]=[CH:26][C:27]=2[F:30])[NH:22]1>>[Cl:1][C:2]1[C:7](=[O:8])[NH:6][C:5]([CH2:9][C:10]([N:22]2[C:23]3[C:28](=[C:27]([F:30])[CH:26]=[CH:25][CH:24]=3)[CH2:29][C@@H:21]2[CH3:20])=[O:12])=[N:4][C:3]=1[N:13]1[CH2:18][CH2:17][O:16][CH2:15][CH2:14]1
Reactant: C[C@H]1Cc2c(F)cccc2N1
Reactant: O=C([O-])Cc1nc(N2CCOCC2)c(Cl)c(=O)[nH]1
Agent: [Na+]
Product: C[C@H]1Cc2c(F)cccc2N1C(=O)Cc1nc(N2CCOCC2)c(Cl)c(=O)[nH]1
Yield: 33.4 %

Procedure:
The product is prepared by following the procedure described in example 1a (step 5a) using 220 mg of sodium (5-chloro-4-morpholin-4-yl-6-oxo-1,6-dihydropyrimidin-2-yl)acetate and 110 mg of (S)-2-methyl-4-fluoro-2,3-dihydro-1H-indole (which can be prepared according to Krasnov, V. P. et al. (Mendeleev Commun. 2002, 12(1), 27-28)). After silica column purification: eluent 99/01 then 98/02 then 97/03 dichloromethane/methanol, 99 mg of 5-chloro-2-[2-((S)-2-methyl-4-fluoro-2,3-dihydroindol-1-yl)-2-oxoethyl]-6-morpholin-4-yl-3H-pyrimidin-4-one are obtained in the form of a solid, the characteristics of which are the following:
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([OH:11])=[O:10])=[CH:4][CH:3]=1.[S:12]1[CH:16]=[CH:15][C:14](B(O)O)=[CH:13]1.C([O-])(O)=O.[Na+]>COCCOC.O.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>[S:12]1[CH:16]=[CH:15][C:14]([C:2]2[CH:7]=[CH:6][C:5]([CH2:8][C:9]([OH:11])=[O:10])=[CH:4][CH:3]=2)=[CH:13]1
Reactant: O=C(O)Cc1ccc(Br)cc1
Reactant: OB(O)c1ccsc1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O
Solvent: COCCOC
Product: O=C(O)Cc1ccc(-c2ccsc2)cc1
Yield: 51.3 %

Procedure:
A mixture of 4-bromophenylacetic acid (1.08 g, 5 mmol), 3-thiopheneboronic acid (0.7 g, 5.5 mmol), NaHCO3 (1.68 g, 20 mmol), and dichlorobis(triphenylphosphine)palladium (0.35 g, 0.5 mmol) in DME-water (21 mL-7 mL) was heated at reflux temperature for 2 hours under nitrogen. After cooling, the reaction mixture was partitioned between Et2O (80 mL) and saturated aqueous NaHCO3 (30 mL). The organic layer was washed with saturated aqueous NaHCO3 (30 mL) again. The combined aqueous layer was acidified with 2N HCl solution and the whole extracted with CH2Cl2 (50 mL×3). The combined organic layer was washed with brine, dried over MgSO4, and concentrated in vacuo. The residue was purified by flash chromatography (SiO2) eluting with ethyl acetate/hexane (1/1) to give the subtitle compound (0.56 g, 51% yield).
Reaction SMILES: [NH:1]1[CH:5]=[CH:4][N:3]=[CH:2]1.[Li][CH2:7][CH2:8][CH2:9]C.CN([CH:14]=[O:15])C>C1COCC1>[CH:8]([N:1]1[CH:5]=[CH:4][N:3]=[C:2]1[CH:14]=[O:15])([CH3:9])[CH3:7]
Reactant: [Li]CCCC
Reactant: CN(C)C=O
Reactant: c1c[nH]cn1
Solvent: C1CCOC1
Product: CC(C)n1ccnc1C=O
Temperature: 0 °C
Reaction time: 0.42 h
Yield: 65.5 %

Procedure:
A solution of the imidazole (890 mg, 8.08 mmol) in THF (10 mL) under nitrogen was cooled to −78° C. and n-BuLi (2.5M in hexanes, 4.5 mL, 11.3 mmol) was added. The bright yellow solution was stirred at 0° C. for 25 minutes, then DMF (1.5 mL, 19 mmol) was added. The reaction was stirred at room temperature for one hour, then was quenched by the addition of saturated aqueous NH4Cl (10 mL). The layers were separated and the aqueous solution was extracted with EtAOc (10 mL×2). The combined organic solution was dried (Na2SO4), filtered and concentrated under reduced pressure. Purification by flash column chromatography on silica (hexane/EtOAc, 1:1) gave the aldehyde as a pale yellow solid (731 mg, 5.29 mmol, 65%). 1H NMR (CDCl3) δ 1.46 (d, 6H, J=6.6 Hz), 5.46 (septet, 1H, J=6.8 Hz), 7.29 (s, 1H), 7.31 (s, 1H), 9.81 (s, 1H).
Reaction SMILES: [CH3:1][N:2]1[C:6]2[CH:7]=[CH:8][C:9]([CH2:11][CH2:12][NH:13][CH3:14])=[CH:10][C:5]=2[S:4](=[O:15])[CH2:3]1.O1CCOCC1.ClC[C:24]#[N:25].[C:26](=O)([O-])[O-].[K+].[K+].[I-].[K+]>>[CH3:1][N:2]1[C:6]2[CH:7]=[CH:8][C:9]([CH2:11][CH2:12][N:13]([CH3:26])[CH2:14][C:24]#[N:25])=[CH:10][C:5]=2[S:4](=[O:15])[CH2:3]1
Reactant: O=C([O-])[O-]
Reactant: N#CCCl
Reactant: CNCCc1ccc2c(c1)S(=O)CN2C
Agent: [I-]
Agent: [K+]
Solvent: C1COCCO1
Product: CN(CC#N)CCc1ccc2c(c1)S(=O)CN2C
Temperature: 60 °C
Reaction time: 48 h

Procedure:
In a round-bottomed flask, 6.8 mmol of 3-methyl-6-[2-(N-methylamino)ethyl]benzothiazolinone are dissolved in 50 mol of dioxane in the presence of 20 mmol of chloro-acetonitrile, 20 mmol of potassium carbonate and a catalytic amount of potassium iodide. The mixture is stirred at 60° C. for 48 hours. After cooling, the solvent is evaporated off and the reaction mixture is extracted with chloroform after adding water. After washing, drying and evaporation of the organic phase, the expected product is obtained after purification by chromatography on a silica column, followed by crystallization.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][C:10]=1[F:11])[NH:7][C:6](=[O:12])[C:5]2=[O:13].N1C2C(=CC=CC=2)C(=O)C1=O.[CH2:25]([O:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=1I)[CH3:26]>>[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][C:10]=1[F:11])[NH:7][C:6](=[O:12])[C:5]2([C:29]1[CH:30]=[CH:31][CH:32]=[CH:33][C:28]=1[O:27][CH2:25][CH3:26])[OH:13]
Reactant: CCOc1ccccc1I
Reactant: O=C1Nc2cc(F)c(Cl)cc2C1=O
Agent: O=C1Nc2ccccc2C1=O
Product: CCOc1ccccc1C1(O)C(=O)Nc2cc(F)c(Cl)cc21

Procedure:
The title compound was prepared in analogy to example a.1 using 5-chloro-6-fluoroisatin as isatin II and ethoxyiodobenzene (to form the Grignard reagent).
Reaction SMILES: [CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[C:11]1[S:15][CH:14]([C:16]([O:18][CH2:19][CH3:20])=[O:17])[NH:13][N:12]=1.[C:21]([S:24][CH2:25][CH2:26][C:27](Cl)=[O:28])(=[O:23])[CH3:22]>>[C:21]([S:24][CH2:25][CH2:26][C:27]([N:13]1[N:12]=[C:11]([C:2]2[CH:3]=[CH:4][C:5]3[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=3)[CH:1]=2)[S:15][CH:14]1[C:16]([O:18][CH2:19][CH3:20])=[O:17])=[O:28])(=[O:23])[CH3:22]
Reactant: CCOC(=O)C1NN=C(c2ccc3ccccc3c2)S1
Reactant: CC(=O)SCCC(=O)Cl
Product: CCOC(=O)C1SC(c2ccc3ccccc3c2)=NN1C(=O)CCSC(C)=O

Procedure:
Prepared from the crude product of step (b) and 3-acetylthiopropanoyl chloride by the process of Example 3, step (b). mp 107°-108°