Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [F:1][C:2]([F:13])([F:12])[C:3]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[OH:11])=[O:4].Cl.[CH3:15][N:16]([CH2:18][CH2:19]Cl)[CH3:17].C1(C)C=CC=CC=1.O>CCOCC>[CH3:15][N:16]([CH2:18][CH2:19][O:11][C:6]1[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=1[C:3](=[O:4])[C:2]([F:12])([F:13])[F:1])[CH3:17]
Reactant: CN(C)CCCl
Reactant: O=C(c1ccccc1O)C(F)(F)F
Agent: Cl
Solvent: Cc1ccccc1
Solvent: O
Solvent: CCOCC
Product: CN(C)CCOc1ccccc1C(=O)C(F)(F)F
Temperature: 25 °C
Yield: 71.8 %

Procedure:
A mixture of 2-trifluoroacetylphenol (380 mg, 2.0 mmol), 2-[N,N-dimethylamino]ethyl chloride, hydrochloride (432 mg, 6.0 mmol) potassium carbonate (1.38 g, 10 mmol) and toluene (5 ml) was refluxed for 3.5 h. After cooling to r.t., the mixture was treated with water and ether. The organic layer was washed twice with brine, dried over sodium sulfate and concentrated in vacuo. The residue was chromatographed on silica gel (acetone/ether 1:1 to 1:0) to give the title compound (375 mg, 72%) as a white solid.
Reaction SMILES: [NH2:1][C:2]1[C:7](/[CH:8]=[CH:9]/[C:10]([OH:12])=O)=[CH:6][C:5]([Cl:13])=[CH:4][N:3]=1.[CH3:14][NH:15][CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.C(OC(C)C)(C)C>>[NH2:1][C:2]1[C:7](/[CH:8]=[CH:9]/[C:10]([N:15]([CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH3:14])=[O:12])=[CH:6][C:5]([Cl:13])=[CH:4][N:3]=1
Reactant: Nc1ncc(Cl)cc1/C=C/C(=O)O
Reactant: CNCc1ccccc1
Solvent: CC(C)OC(C)C
Product: CN(Cc1ccccc1)C(=O)/C=C/c1cc(Cl)cnc1N

Procedure:
The title compound was prepared from (E)-3-(2-amino-5-chloro-3-pyridinyl)-2-propenoic acid and N-methyl benzylamine as a yellow solid following crystallisation from diisopropyl ether:
Reaction SMILES: [C:1]([O:4][C@@H:5]1[C@@H:19]([O:20][C:21](=[O:23])[CH3:22])[C@H:18]([O:24][C:25](=[O:27])[CH3:26])[CH2:17][S:16][C@H:6]1[O:7][C:8]1[C:9]([F:15])=[N:10][CH:11]=[C:12](Br)[CH:13]=1)(=[O:3])[CH3:2].[N:28]1[CH:33]=[CH:32][C:31](B(O)O)=[CH:30][CH:29]=1>>[C:1]([O:4][C@@H:5]1[C@@H:19]([O:20][C:21](=[O:23])[CH3:22])[C@H:18]([O:24][C:25](=[O:27])[CH3:26])[CH2:17][S:16][C@H:6]1[O:7][C:8]1[C:9]([F:15])=[N:10][CH:11]=[C:12]([C:31]2[CH:32]=[CH:33][N:28]=[CH:29][CH:30]=2)[CH:13]=1)(=[O:3])[CH3:2]
Reactant: OB(O)c1ccncc1
Reactant: CC(=O)O[C@@H]1[C@@H](OC(C)=O)[C@H](OC(C)=O)CS[C@H]1Oc1cc(Br)cnc1F
Product: CC(=O)O[C@@H]1[C@@H](OC(C)=O)[C@H](OC(C)=O)CS[C@H]1Oc1cc(-c2ccncc2)cnc1F

Procedure:
By carrying out the operation analogously to example 1, starting from 5-bromo-2-fluoro-3-pyridinyl 2,3,4-tri-O-acetyl-5-thio-β-D-xylopyranoside, obtained according to preparation VIII, and 4-pyridineboronic acid, the desired product is obtained in the form of a beige foam (yield=53%).
Reaction SMILES: [C:1]([C:4]1[CH:9]=[CH:8][C:7]([S:10][CH2:11][C:12]([OH:14])=O)=[CH:6][CH:5]=1)(=[O:3])[CH3:2].S(Cl)(Cl)=O.[Cl-].[Cl-].[Cl-].[Al+3]>ClC(Cl)C.CN(C=O)C>[C:1]([C:4]1[CH:9]=[CH:8][C:7]2[S:10][CH2:11][C:12](=[O:14])[C:6]=2[CH:5]=1)(=[O:3])[CH3:2]
Reactant: CC(=O)c1ccc(SCC(=O)O)cc1
Agent: [Al+3]
Agent: [Cl-]
Solvent: CN(C)C=O
Solvent: CC(Cl)Cl
Solvent: O=S(Cl)Cl
Product: CC(=O)c1ccc2c(c1)C(=O)CS2
Temperature: 50 °C
Yield: 78 %

Procedure:
(4-Acetyl-phenylsulfanyl)-acetic acid (1.0 g, 4.8 mmol) is suspended in dichloroethane, under nitrogen at ambient temperature. To this is added thionyl chloride (0.694 ml, 9.6 mmol) followed immediately by 1 drop of DMF. After maintaining the reaction mixture at 50° C. for 30 min., the mixture became homogenous. After cooling to ambient temperature, nitrogen was bubbled into the mixture to remove any trace gasses (10 min.), then aluminum trichloride (1.9 g, 14.4 mmol) was added in 4 portions which caused the reaction temperature to raise to 40° C. After the reaction had cooled to ambient temperature (2 hr), the reaction mixture was poured into 200 mL of and ice/water mixture and extracted with dichloromethane (3×100 ml). The combined organic layers were washed with saturated bicarbonate solution, and brine, then dried over MgSO4, filtered and concentrated in vacuo to yield 5-acetyl-benzo[b]thiophen-3-one as a red brown solid (720 mg, 79%). This material was used without further purification. 1H NMR (250 MHz, CDCl3): δ 8.23 (d, 1H, J=2.1), 8.15 (dd, 1H, J=7.5,J=2.1), 7.48 (d, 1H, J=7.5), 3.83 (s, 2H), 2.56 (s, 3H). MS [EI+] 193 (M+H)+, [EI−] 191 (M−H)−.
Reaction SMILES: [CH2:1]([O:8][C:9]1[N:14]2[CH:15]=[CH:16][N:17]=[C:13]2[CH:12]=[C:11]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[I:24]N1C(=O)CCC1=O>C(#N)C.C(OCC)(=O)C>[CH2:1]([O:8][C:9]1[N:14]2[C:15]([I:24])=[CH:16][N:17]=[C:13]2[CH:12]=[C:11]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH:10]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: O=C1CCC(=O)N1I
Reactant: c1ccc(COc2cc(-c3ccccc3)cc3nccn23)cc1
Solvent: CCOC(C)=O
Solvent: CC#N
Product: Ic1cnc2cc(-c3ccccc3)cc(OCc3ccccc3)n12
Temperature: 25 °C
Reaction time: 12 h

Procedure:
To a solution of 5-(benzyloxy)-7-phenylimidazo[1,2-a]pyridine (Compound 11-1) (60 mg, 0.20 mmol) in acetonitrile (4 mL) was added N-iodosuccinimide (59 mg, 0.26 mmol) at room temperature. The reaction was stirred at room temperature for 12 h, diluted with ethyl acetate, and washed with 1N aqueous sodium hydroxide. The organic layer was separated, and the aqueous layer was back extracted one time with ethyl acetate. The combined organic layers were dried over sodium sulfate, filtered and concentrated. The residue was purified by column chromatography on silica gel (ethyl acetate/isohexane gradient) to give 5-(benzyloxy)-3-iodo-7-phenylimidazo[1,2-a]pyridine. 1H NMR (500 MHz, CDCl3) δ 7.55-7.59 (m, 4H), 7.54 (s, 1H), 7.36-7.47 (m, 7H), 6.34 (s, 1H), 5.34 (s, 2H). LRMS (ESI) calculated for C20H16IN2O [M+H]+, 427.0; found 426.9.
Reaction SMILES: C(=O)([O-])[O-].[K+].[K+].I[C:8]1[CH:13]=[CH:12][C:11]([OH:14])=[CH:10][CH:9]=1.[CH3:15][C@@:16]([S:39]([CH3:42])(=[O:41])=[O:40])([CH2:22][CH2:23][C:24]1[CH:29]=[CH:28][C:27](B2OC(C)(C)C(C)(C)O2)=[CH:26][CH:25]=1)[C:17]([O:19][CH2:20][CH3:21])=[O:18]>[Pd+2].O1CCOCC1.O>[OH:14][C:11]1[CH:12]=[CH:13][C:8]([C:27]2[CH:26]=[CH:25][C:24]([CH2:23][CH2:22][C@@:16]([CH3:15])([S:39]([CH3:42])(=[O:41])=[O:40])[C:17]([O:19][CH2:20][CH3:21])=[O:18])=[CH:29][CH:28]=2)=[CH:9][CH:10]=1
Reactant: CCOC(=O)[C@@](C)(CCc1ccc(B2OC(C)(C)C(C)(C)O2)cc1)S(C)(=O)=O
Reactant: Oc1ccc(I)cc1
Agent: [Pd+2]
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: C1COCCO1
Solvent: O
Product: CCOC(=O)[C@@](C)(CCc1ccc(-c2ccc(O)cc2)cc1)S(C)(=O)=O
Yield: 54 %

Procedure:
A mixture of palladium (II) EnCat (0.1 equiv), potassium carbonate (3.0 equiv), 4-iodophenol and ethyl(2R)-2-methyl-2-(methylsulfonyl)-4-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]butanoate, which may be prepared as in Preparation 8A, was heated to 80° C. in 10:1 1,4-dioxane-water to provide the title compound (54%) after purification by flash chromatography on silica gel. MS (LCMS) m/z 399.5 (M+Na). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.33 (t, J=7.13 Hz, 3H) 1.72 (s, 3H) 2.18-2.28 (m, 1H) 2.47-2.58 (m, 2H) 2.72-2.84 (m, 1H) 3.04 (s, 3H) 4.22-4.31 (m, 2H) 4.91 (s, 1H) 6.85-6.92 (m, 2H) 7.17-7.24 (m, 2H) 7.40-7.51 (m, 4H).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5](B(O)O)=[C:4]([CH3:11])[CH:3]=1.[O:12]=[S:13]1(=[O:30])[CH2:18][CH2:17][N:16]2[CH2:19][CH2:20][CH2:21][C@@H:22]([C:23]3[CH:28]=[CH:27][C:26]([OH:29])=[CH:25][CH:24]=3)[C:15]2=[N:14]1.N1C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CC#N.C(O[Cu]OC(=O)C)(=O)C>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([O:29][C:26]2[CH:25]=[CH:24][C:23]([C@H:22]3[C:15]4=[N:14][S:13](=[O:30])(=[O:12])[CH2:18][CH2:17][N:16]4[CH2:19][CH2:20][CH2:21]3)=[CH:28][CH:27]=2)=[C:4]([CH3:11])[CH:3]=1
Reactant: Cc1cc(Cl)ccc1B(O)O
Reactant: O=S1(=O)CCN2CCC[C@@H](c3ccc(O)cc3)C2=N1
Agent: CC(=O)O[Cu]OC(C)=O
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: c1ccncc1
Solvent: CC#N
Product: Cc1cc(Cl)ccc1Oc1ccc([C@@H]2CCCN3CCS(=O)(=O)N=C23)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 5.1 %

Procedure:
A mixture of (4-chloro-2-methylphenyl)boronic acid (912 mg), 4-[(9S)-2,2-dioxido-3,4,6,7,8,9-hexahydropyrido[2,1-c][1,2,4]thiadiazin-9-yl]phenol (500 mg), pyridine (3.60 mL), cesium carbonate (581 mg), diacetoxycopper (648 mg) and powdered 4A MS (5.00 g) in MeCN (18 mL) was stirred at room temperature overnight. The mixture was added with NH silica gel, concentrated in vacuo, and purified by column chromatography (NH silica gel, eluted with MeOH in EtOAc) to give the title compound (37.0 mg) as a white solid.
Reaction SMILES: [C:1]([C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:10]=[N:11][N:12]([C:15]3[CH:23]=[CH:22][C:18]([C:19](O)=[O:20])=[CH:17][N:16]=3)[C:13]=2[OH:14])=[C:5]([CH3:24])[CH:4]=1)#[N:2].C1N=CN(C(N2C=NC=C2)=O)C=1.[CH2:37]([N:39]1[CH2:44][CH2:43][NH:42][CH2:41][CH2:40]1)[CH3:38].Cl>C1COCC1.CN(C1C=CN=CC=1)C.CS(C)=O.O>[CH2:37]([N:39]1[CH2:44][CH2:43][N:42]([C:19]([C:18]2[CH:22]=[CH:23][C:15]([N:12]3[C:13]([OH:14])=[C:9]([C:6]4[CH:7]=[CH:8][C:3]([C:1]#[N:2])=[CH:4][C:5]=4[CH3:24])[CH:10]=[N:11]3)=[N:16][CH:17]=2)=[O:20])[CH2:41][CH2:40]1)[CH3:38]
Reactant: Cc1cc(C#N)ccc1-c1cnn(-c2ccc(C(=O)O)cn2)c1O
Reactant: CCN1CCNCC1
Agent: CN(C)c1ccncc1
Agent: Cl
Agent: O=C(n1ccnc1)n1ccnc1
Solvent: CS(C)=O
Solvent: O
Solvent: C1CCOC1
Product: CCN1CCN(C(=O)c2ccc(-n3ncc(-c4ccc(C#N)cc4C)c3O)nc2)CC1
Temperature: 25 °C
Reaction time: 0.75 h
Yield: 90 %

Procedure:
Combined 6-(4-(4-cyano-2-methylphenyl)-5-hydroxy-1H-pyrazol-1-yl)nicotinic acid (0.524 g, 1.636 mmol) in THF (3 mL) and added DMSO (1 mL) and DMAP (3.00 mg, 0.025 mmol) followed by a dropwise addition of a solution of CDI (0.292 g, 1.80 mmol) in DMSO (1 mL). The resulting clear solution was stirred at ambient temperature for 45 minutes and an additional portion of CDI (73.0 mg, 0.450 mmol) was added. The mixture was stirred for a total of 2 hours and 1-ethylpiperazine (0.270 mL, 2.127 mmol) was added. The resulting mixture was stirred for 4.5 hours and then diluted with water (6 mL, dropwise), acidified to pH=7 with 6N aqueous hydrochloric acid, and then further diluted with water (4 mL) to give a solid. The solid was filtered and dried in vacuum to give the title compound (0.613 g, 90%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.06 (t, J=7.07 Hz, 3 H) 2.43 (s, 3 H) 2.53-2.63 (m, 4 H) 3.57 (br. s., 6 H) 7.61 (d, J=8.08 Hz, 1 H) 7.67 (s, 1 H) 7.90 (d, J=8.08 Hz, 1 H) 8.02 (dd, J=8.59, 2.27 Hz, 1 H) 8.06 (s, 1 H) 8.42 (d, J=8.59 Hz, 1 H) 8.52 (d, J=1.77 Hz, 1 H); MS (M+H)+ 417.
Reaction SMILES: [CH:1]1([N:4]2[C:13]3[C:8](=[C:9]([F:17])[C:10]([F:16])=[C:11](F)[C:12]=3[F:14])[C:7](=[O:18])[C:6]([C:19]([OH:21])=[O:20])=[CH:5]2)[CH2:3][CH2:2]1.[NH2:22][C:23]1([CH3:28])[CH2:27][CH2:26][NH:25][CH2:24]1>C(#N)C>[NH2:22][C:23]1([CH3:28])[CH2:27][CH2:26][N:25]([C:11]2[C:12]([F:14])=[C:13]3[C:8]([C:7](=[O:18])[C:6]([C:19]([OH:21])=[O:20])=[CH:5][N:4]3[CH:1]3[CH2:3][CH2:2]3)=[C:9]([F:17])[C:10]=2[F:16])[CH2:24]1
Reactant: O=C(O)c1cn(C2CC2)c2c(F)c(F)c(F)c(F)c2c1=O
Reactant: CC1(N)CCNC1
Solvent: CC#N
Product: CC1(N)CCN(c2c(F)c(F)c3c(=O)c(C(=O)O)cn(C4CC4)c3c2F)C1
Temperature: 50 °C
Reaction time: 0.5 h
Yield: 80 %

Procedure:
A mixture of 1-cyclopropyl-5,6,7,8-tetrafluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic acid (0.8 g), 3-amino-3-methylpyrrolidine (0.8 g), and acetonitrile (35 ml) was stirred at 50° C. for 30 minutes. The precipitated crystals were collected by filtration, and washed with water. The crystals were dissolved in 10% aqueous ammonia, treated with activated carbon, and concentrated under reduced pressure. The precipitated crystals were collected by filtration, washed with water and dried to give 7-(3-amino-3-methyl-1-pyrrolidinyl)-1-cyclopropyl-5,6,8-trifluoro-1,4-dihydro-4-oxoquinoline 3-carboxylic acid (0.81 g), m.p. 280°-282° C.
Reaction SMILES: [N+:1]([C:4]1[CH:12]=[CH:11][CH:10]=[C:9]2[C:5]=1[CH2:6][CH2:7][CH2:8]2)([O-])=O.[CH3:13][C:14](OC(C)=O)=[O:15]>CO.N1C=CC=CC=1.[Pd]>[CH2:8]1[C:9]2[C:5](=[C:4]([NH:1][C:14](=[O:15])[CH3:13])[CH:12]=[CH:11][CH:10]=2)[CH2:6][CH2:7]1
Reactant: O=[N+]([O-])c1cccc2c1CCC2
Reactant: CC(=O)OC(C)=O
Agent: [Pd]
Solvent: CO
Solvent: c1ccncc1
Product: CC(=O)Nc1cccc2c1CCC2
Temperature: 25 °C
Reaction time: 8 h

Procedure:
A suspension of commercially available 4-nitroindane (10 g, 61.3 mmol) and 10% Pd/C (1 g) in MeOH (200 mL) was stirred vigorously under an atmosphere of hydrogen overnight at rt. The reaction was filtered through a pad of Celite® and concentrated, and residual solvent was removed by combining the reaction with toluene followed by evaporation. The crude reaction was taken up in pyridine (100 mL), and Ac2O (20 mL) was added and the reaction stirred for 16 h at rt. The reaction was evaporated and the crude product was purified by flash chromatography (5% MeOH in EtOAc/hexane(1:1) to give the title compound (9.12 g).
Reaction SMILES: I[C:2]1[C:10]2[CH:9]=[N:8][CH:7]=[N:6][C:5]=2[N:4]([Si:11]([CH:18]([CH3:20])[CH3:19])([CH:15]([CH3:17])[CH3:16])[CH:12]([CH3:14])[CH3:13])[CH:3]=1.C([Mg]Cl)(C)C.[C:26]([O:30][C:31](=[O:49])[N:32]([CH2:41][C:42]1[CH:47]=[CH:46][C:45]([Cl:48])=[CH:44][CH:43]=1)[C:33]1[CH:38]=[CH:37][C:36]([CH:39]=[O:40])=[CH:35][N:34]=1)([CH3:29])([CH3:28])[CH3:27].C(=O)(O)[O-].[Na+]>O1CCCC1>[C:26]([O:30][C:31](=[O:49])[N:32]([CH2:41][C:42]1[CH:43]=[CH:44][C:45]([Cl:48])=[CH:46][CH:47]=1)[C:33]1[CH:38]=[CH:37][C:36]([CH:39]([OH:40])[C:2]2[C:10]3[CH:9]=[N:8][CH:7]=[N:6][C:5]=3[N:4]([Si:11]([CH:18]([CH3:20])[CH3:19])([CH:15]([CH3:17])[CH3:16])[CH:12]([CH3:14])[CH3:13])[CH:3]=2)=[CH:35][N:34]=1)([CH3:29])([CH3:27])[CH3:28]
Reactant: CC(C)(C)OC(=O)N(Cc1ccc(Cl)cc1)c1ccc(C=O)cn1
Reactant: CC(C)[Si](C(C)C)(C(C)C)n1cc(I)c2cncnc21
Agent: CC(C)[Mg]Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: C1CCOC1
Product: CC(C)[Si](C(C)C)(C(C)C)n1cc(C(O)c2ccc(N(Cc3ccc(Cl)cc3)C(=O)OC(C)(C)C)nc2)c2cncnc21
Temperature: -20 °C
Yield: 51.7 %

Procedure:
5-Iodo-7-triisopropylsilanyl-7H-pyrrolo[2,3-d]pyrimidine (38, 0.160 g, 0.4 mmol) was dissolved in 0.7 mL of tetrahydrofuran under an atmosphere of nitrogen. The reaction was cooled to −20° C. and isopropylmagnesium chloride (0.24 mL, 2.0 M in tetrahydrofuran, 0.48 mmol) was added and the reaction was stirred and allowed to come to 0° C. The reaction was cooled to −20° C. and (4-chloro-benzyl)-(5-formyl-pyridin-2-yl)-carbamic acid tert-butyl ester (13, 0.110 g, 0.32 mmol) in 2.0 mL of tetrahydrofuran was added to the reaction mixture. The reaction was stirred, allowing to come to 0° C., then poured into aqueous saturated sodium bicarbonate and extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous sodium sulfate, filtered and the filtrate concentrated under vacuum. The resulting material was purified by silica gel column chromatography eluting with a gradient of 10-80% ethyl acetate in hexanes. Appropriate fractions were combined and concentrated under vacuum to provide the desired compound (43, 0.103 g, 52%). MS (ESI) [M+H+]+=622.94.
Reaction SMILES: C([Mg:3][Br:4])C.Br[C:6]1[C:11]([F:12])=[C:10]([F:13])[C:9]([F:14])=[C:8]([F:15])[C:7]=1[F:16]>O1CCCC1>[F:12][C:11]1[C:6]([Mg:3][Br:4])=[C:7]([F:16])[C:8]([F:15])=[C:9]([F:14])[C:10]=1[F:13]
Reactant: Fc1c(F)c(F)c(Br)c(F)c1F
Reactant: CC[Mg]Br
Solvent: C1CCOC1
Product: Fc1c(F)c(F)c([Mg]Br)c(F)c1F
Temperature: 35 °C

Procedure:
Air inside a reaction vessel of the same type as the one used in Example 1 was replaced with a nitrogen gas in a satisfactory manner, after which 50 ml of a tetrahydrofuran solution containing 0.018 mol of ethyl magnesium bromide was charged to the reaction vessel. Meanwhile, 0.018 mol of bromopentafluorobenzene was charged to the dropping funnel. Then, bromopentafluorobenzene in the dropping funnel was dropped to the reaction vessel over 10 minutes at room temperature with the stirring of the tetrahydrofuran solution in the reaction vessel, and the reaction solution was heated to 35° C. for 1 hour. Consequently, pentafluorophenyl magnesium bromide was obtained in the form of a light yellow tetrahydrofuran solution. The yield of pentafluorophenyl magnesium bromide measured in the same manner as Example 1 was 93.9 mol % based on bromopentafluorobenzene.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[CH:4][C:5](I)=[C:6]([CH:9]=1)[CH:7]=[O:8].[CH2:11]([O:13][C:14](=[O:33])[CH2:15][C:16]1[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[C:18](B2OC(C)(C)C(C)(C)O2)[CH:17]=1)[CH3:12]>>[CH2:11]([O:13][C:14](=[O:33])[CH2:15][C:16]1[CH:17]=[C:18]([C:5]2[CH:4]=[CH:3][C:2]([Br:1])=[CH:9][C:6]=2[CH:7]=[O:8])[C:19]([O:22][CH3:23])=[CH:20][CH:21]=1)[CH3:12]
Reactant: O=Cc1cc(Br)ccc1I
Reactant: CCOC(=O)Cc1ccc(OC)c(B2OC(C)(C)C(C)(C)O2)c1
Product: CCOC(=O)Cc1ccc(OC)c(-c2ccc(Br)cc2C=O)c1

Procedure:
Prepared according to the procedure described in Example 1, Step 4, using the following starting materials: 5-bromo-2-iodo-benzaldehyde and [4-methoxy-3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-acetic acid ethyl ester.
Reaction SMILES: [F:1][C:2]([F:20])([F:19])[C:3]([NH:5][CH2:6][C:7]([C:9]1[CH:14]=[CH:13][C:12]([CH:15]([CH3:17])[CH3:16])=[CH:11][C:10]=1[OH:18])=O)=[O:4].C([SiH]([CH2:26][CH3:27])CC)C.F[C:29](F)(F)[C:30]([OH:32])=[O:31]>>[CH:15]([C:12]1[CH:13]=[CH:14][C:9]([CH2:7][CH2:6][NH:5][C:3](=[O:4])[C:2]([F:20])([F:19])[F:1])=[C:10]([CH:11]=1)[O:18][CH2:29][C:30]([O:32][CH2:26][CH3:27])=[O:31])([CH3:17])[CH3:16]
Reactant: CC[SiH](CC)CC
Reactant: O=C(O)C(F)(F)F
Reactant: CC(C)c1ccc(C(=O)CNC(=O)C(F)(F)F)c(O)c1
Product: CCOC(=O)COc1cc(C(C)C)ccc1CCNC(=O)C(F)(F)F
Temperature: 25 °C
Reaction time: 13 h

Procedure:
To a solution of 500 mg of 2,2,2-trifluoro-N-[2-(2-hydroxy-4-isopropylphenyl)-2-oxoethyl]acetamide in 2.63 mL of trifluoroacetic acid was added 0.94 mL of triethylsilane. After being stirred at room temperature for 13 hours, the reaction mixture was concentrated and dried thoroughly. The obtained residue and 382 mg of potassium carbonate were suspended in 10 mL of N,N-dimethylformamide, and 0.288 mL of ethyl bromoacetate was added to the stirred mixture under ice-cooling. The mixture was stirred at room temperature for 15 hours, and to the reaction mixture was added water. After the mixture was extracted with ethyl acetate, the organic layer was washed successively with water and brine, and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure, and the obtained residue was purified by column chromatography on silica gel (eluent: ethyl acetate-hexane) to give 535 mg of ethyl [5-isopropyl-2-[2-(2,2,2-trifluoroacetylamino)ethyl]-phenoxy]acetate.
Reaction SMILES: S(Br)([Br:3])=O.[C:5]1([NH:11][C:12]2[N:17]=[C:16]([CH2:18]O)[CH:15]=[C:14]([CH:20]3[CH2:22][CH2:21]3)[N:13]=2)[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1.N1C=CC=CC=1.C(=O)([O-])O.[Na+]>C(OCC)C.O>[C:5]1([NH:11][C:12]2[N:17]=[C:16]([CH2:18][Br:3])[CH:15]=[C:14]([CH:20]3[CH2:22][CH2:21]3)[N:13]=2)[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1
Reactant: OCc1cc(C2CC2)nc(Nc2ccccc2)n1
Reactant: O=S(Br)Br
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCOCC
Solvent: c1ccncc1
Solvent: O
Product: BrCc1cc(C2CC2)nc(Nc2ccccc2)n1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
15.6 g (75 mmol) of thionyl bromide in 50 ml of diethyl ether are added dropwise within a period of half an hour, with stirring, to 12 g (50 mmol) of 2-phenylamino-4-hydroxymethyl-6-cyclopropylpyrimidine and 0.4 g (50 mmol) of pyridine in 350 ml of diethyl ether. After stirring for 2 hours at room temperature, a further 0.4 g (50 mmol) of pyridine are added and the mixture is heated under reflux for 5 hours. After cooling to room temperature, 200 ml of water are added and the pH is adjusted to 7 by the dropwise addition of 140 ml of saturated sodium hydrogen carbonate solution. The diethyl ether phase is separated off and then washed twice with 100 ml of water each time, dried over sodium sulfate and filtered, and the solvent is evaporated. The brown oil which remains is purified by column chromatography over silica gel (toluene/chloroform/diethyl ether/petroleum ether (b.p. 50°-70° C.): 5/3/1/1). After the eluant mixture has been evaporated off, the yellow oil is diluted with diethyl ether/petroleum ether (b.p. 50°-70° C.) and crystallised at reduced temperature. The yellow crystalline powder melts at 77.5°-79.5° C. Yield: 9.7 g (32 mmol; 64% of the theoretical yield).
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]([C:15]([O:17][CH3:18])=[O:16])[CH:5]=[C:6]([C:8]2[CH:13]=[CH:12][C:11]([CH3:14])=[CH:10][CH:9]=2)[CH:7]=1.C(=O)([O-])[O-].[K+].[K+].Br[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][N:27]=1.CS(C)=O>CCOC(C)=O>[CH3:14][C:11]1[CH:10]=[CH:9][C:8]([C:6]2[CH:7]=[C:2]([O:1][C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][N:27]=3)[CH:3]=[C:4]([C:15]([O:17][CH3:18])=[O:16])[CH:5]=2)=[CH:13][CH:12]=1
Reactant: Brc1ccccn1
Reactant: COC(=O)c1cc(O)cc(-c2ccc(C)cc2)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CS(C)=O
Solvent: CCOC(C)=O
Product: COC(=O)c1cc(Oc2ccccn2)cc(-c2ccc(C)cc2)c1
Temperature: 135 °C
Reaction time: 8 h

Procedure:
A mixture of methyl 5-hydroxy-4′-methylbiphenyl-3-carboxylate (100 mg, 0.41 mmol), potassium carbonate (100 mg, 0.72 mmol), 2-bromopyridine (0.40 mL, 4.2 mmol), and dimethyl sulfoxide (2 mL) was stirred at 135° C. overnight. After cooling, the mixture was diluted with EtOAc and washed with aq. NaHCO3 (sat.), dried over anhydrous MgSO4, filtered, and concentrated. The residue was purified by flash chromatography (0-20% EtOAc/hexane) to afford the title compound.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][N:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[CH2:15](Br)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1>CN(C=O)C.O>[CH2:15]([O:8][C:5]1[CH:6]=[CH:7][C:2]([Cl:1])=[N:3][CH:4]=1)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1
Reactant: BrCc1ccccc1
Reactant: Oc1ccc(Cl)nc1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Solvent: O
Product: Clc1ccc(OCc2ccccc2)cn1
Temperature: 23 °C
Reaction time: 6 h
Yield: 79 %

Procedure:
2-Chloro-5-hydroxypyridine (2.6 g, 20 mmol) and cesium carbonate (7.2 g, 22 mmol) in 8 mL of DMF were treated with benzyl bromide (2.6 mL). After stirring at 23° C. for 6 hours, the reaction mixture was diluted with water, adjusted to pH 7 with saturated aqueous NaH2PO4, and extracted with dichloromethane. The organic extract was dried over Na2SO4, filtered and the filtrate concentrated under reduced pressure. The residue was purified by flash chromatography (eluting with CH2Cl2) to provide the title compound as a white solid (3.44 g, 79%). mp <50° C.; Rf=0.4 (CH2Cl2); MS 220 (M+H)+; 1H NMR (300 MHz, DMSO-d6) δ 8.20 (d, 1H, J=2.7 Hz), 7.55 (dd, 1H, J=9, 2.7 Hz), 7.3–7.5 (m, 6H), 5.19 (s, 2H).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][C:10]=1[Cl:11])[N:7]([C:12](=[O:15])[NH:13][CH3:14])[C:6](=[O:16])[C:5]2=[O:17].[NH2:18][C:19]([NH2:21])=[S:20].C(N(CC)CC)C>O1CCCC1>[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][C:10]=1[Cl:11])[NH:7][C:12](=[O:15])[N:13]([CH3:14])[C:5]2([OH:17])[C:6]([NH:18][C:19]([NH2:21])=[S:20])=[O:16]
Reactant: NC(N)=S
Reactant: CNC(=O)N1C(=O)C(=O)c2cc(Cl)c(Cl)cc21
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: CN1C(=O)Nc2cc(Cl)c(Cl)cc2C1(O)C(=O)NC(N)=S
Temperature: 25 °C
Reaction time: 5 h
Yield: 33.4 %

Procedure:
5,6-Dichloro-1-methylcarbamoylisatin (9.6 g) is suspended in tetrahydrofuran (100 ml) and thereto are added thiourea (3.0 g) and triethylamine (5.6 ml), and the mixture is stirred at room temperature for 5 hours. The resulting precipitates are taken by filtration to give 6,7-dichloro-3-methyl-4-hydroxy-4-thioureidocarbonyl-2-oxo-1,2,3,4-tetrahydroquinazoline (4.1 g). M.p. 225-228° C.