Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1](=O)(OC(Cl)(Cl)Cl)[O:2]C(Cl)(Cl)Cl.[NH2:13][C:14]1[CH:15]=[C:16]([CH:33]=[CH:34][C:35]=1[F:36])[O:17][C:18]1[N:23]=[C:22]2[S:24][C:25]([NH:27][C:28]([CH:30]3[CH2:32][CH2:31]3)=[O:29])=[N:26][C:21]2=[CH:20][CH:19]=1.C(N(CC)CC)C.[F:44][C:45]([F:56])([F:55])[O:46][C:47]1[CH:48]=[C:49]([CH2:53][NH2:54])[CH:50]=[CH:51][CH:52]=1>O1CCCC1.C(OCC)(=O)C>[F:36][C:35]1[CH:34]=[CH:33][C:16]([O:17][C:18]2[N:23]=[C:22]3[S:24][C:25]([NH:27][C:28]([CH:30]4[CH2:32][CH2:31]4)=[O:29])=[N:26][C:21]3=[CH:20][CH:19]=2)=[CH:15][C:14]=1[NH:13][C:1](=[O:2])[NH:54][CH2:53][C:49]1[CH:50]=[CH:51][CH:52]=[C:47]([O:46][C:45]([F:55])([F:56])[F:44])[CH:48]=1
Reactant: NCc1cccc(OC(F)(F)F)c1
Reactant: O=C(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl
Reactant: Nc1cc(Oc2ccc3nc(NC(=O)C4CC4)sc3n2)ccc1F
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: O=C(NCc1cccc(OC(F)(F)F)c1)Nc1cc(Oc2ccc3nc(NC(=O)C4CC4)sc3n2)ccc1F
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 148.4 %

Procedure:
To a solution of bis(trichloromethyl) carbonate (30 mg, 0.102 mmol) in tetrahydrofuran (2 mL) was added dropwise a suspension of N—[5-(3-amino-4-fluorophenoxy)[1,3]thiazolo[5,4-b]pyridin-2-yl]cyclopropanecarboxamide (100 mg, 0.290 mmol) produced in Example 16(vi) and triethylamine (80 μL, 0.580 mmol) in tetrahydrofuran (2 ml) at 0° C., and the mixture was stirred at 0° C. for 30 min. 1-[3-(Trifluoromethoxy)phenyl]methanamine (59 μL, 0.348 mmol) was added to the reaction mixture, and the mixture was stirred at room temperature for 2 hr. The reaction mixture was diluted with ethyl acetate (20 mL), and washed successively with aqueous sodium hydrogen carbonate solution (15 mL) and saturated brine (5 ml). The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The obtained residue was purified by basic silica gel column chromatography (ethyl acetate/hexane=50/50→80/20), and the obtained solution was concentrated under reduced pressure. The obtained residue was recrystallized from tetrahydrofuran (3 mL)/ethyl acetate (2 mL) to give the title compound (85 mg, 52%) as a white solid.
Reaction SMILES: [C:1]1([C:7]2([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[O:13][CH:8]2[C:9]([O:11][CH3:12])=[O:10])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:20]1([OH:26])[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1>>[OH:13][CH:8]([C:7]([O:26][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[C:1]1[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1)[C:9]([O:11][CH3:12])=[O:10]
Reactant: Oc1ccccc1
Reactant: COC(=O)C1OC1(c1ccccc1)c1ccccc1
Product: COC(=O)C(O)C(Oc1ccccc1)(c1ccccc1)c1ccccc1
Yield: 71.8 %

Procedure:
5 g (19.6 mmol) of methyl 3,3-diphenyl-2,3-epoxypropionate and 5.6 g (60 mmol) of phenol were heated together at 100° C. for 6 h. Removal of the excess phenol by distillation under high vacuum and purification of the residue by chromatography on silica gel with hexane/ethyl acetate mixtures resulted in 4.9 g (77%) of a pale yellow oil.
Reaction SMILES: [NH2:1][C:2]1[CH:9]=[CH:8][CH:7]=[CH:6][C:3]=1C=O.[C:10]([OH:13])(=O)[CH3:11].[C:14]1(=O)[CH2:18][CH2:17][CH2:16][CH2:15]1>O>[CH:14]1([NH:1][C:2]2[CH:3]=[CH:6][C:11]([CH:10]=[O:13])=[C:8]([CH3:7])[CH:9]=2)[CH2:18][CH2:17][CH2:16][CH2:15]1
Reactant: Nc1ccccc1C=O
Reactant: O=C1CCCC1
Reactant: CC(=O)O
Solvent: O
Product: Cc1cc(NC2CCCC2)ccc1C=O
Temperature: 25 °C
Reaction time: 1 h
Yield: 80 %

Procedure:
In a 1-l flask, place 92.11 g (0.4 m) of the blocked aminobenzaldehyde, 250 ml of acetic acid and 67.3 g (0.8 m) of cyclopentanone. Heat the mixture to 40 C. Add 23.57 g (0.4 m) of borane-dimethylamine complex slowly keeping the temperature at 60 C. Stir the mixture at 60-65 C. for 1 hour, and cool to room temperature. Add 375 ml of water and stir for 15 minutes. Collect solids, wash with water, and deliquor as much as possible. In a 1-l flask, place the wet intermediate, 200 ml of methanol, and 120 g of 50% NaOH solution. Heat the mixture under reflux for 1 hour. Add 220 ml of hot water and distill off methanol till approximately 240 ml of distillate is collected and pot temperature reaches close to 100 C. Heat the mixture under reflux for 1 hour, and then cool to room temperature. Add 300 ml of propyl acetate, stir for 5 minutes, and let layers settle. Separate bottom water layer. Wash the propyl acetate solution with 200 ml of brine. Dry over magnesium sulfate and distill propyl acetate under a reduced pressure to a red viscous oil. Add 300 ml of heptanes with vigorous stirring. Stir the resulting slurry at room temperature for 45 minutes. Collect product, wash with heptanes, and dry to give 65.1 g (80%) of 4-cyclopentylamino-2-methylbenzaldehyde as yellow solids.
Reaction SMILES: [I:1][C:2]1[CH:9]=[C:6]([CH:7]=[O:8])[C:5]([OH:10])=[CH:4][CH:3]=1.[C:11]([O-])([O-])=O.[K+].[K+].CI>CN(C=O)C>[CH3:11][O:10][C:5]1[CH:4]=[CH:3][C:2]([I:1])=[CH:9][C:6]=1[CH:7]=[O:8]
Reactant: O=C([O-])[O-]
Reactant: O=Cc1cc(I)ccc1O
Agent: [K+]
Solvent: CI
Solvent: CN(C)C=O
Product: COc1ccc(I)cc1C=O
Temperature: 25 °C
Reaction time: 8 h
Yield: 97.3 %

Procedure:
5-Iodo-salicylaldehyde (1.0 g, 4.0 mmol) was dissolved in DMF (10 mL) and to the stirred solution K2CO3 (0.828 g, 6.0 mmol) and CH3I (1.14 g, 8.0 mmol) were added. The mixture was stirred at room temperature overnight. The suspension was concentrated in vacuo, and the residue was partitioned between water (30 mL) and Et2O (30 mL). The aqueous phase was separated and extracted with ether (20 mL×2). The combined organic phases were dried over Na2SO4, filtered and concentrated to give 67 (1.02 g, 98%). 1H NMR (CDCl3, 300 MHz) δ 10.34(s, 1H), 7.82-7.78 (m, 1H), 7.26 (s, 1H), 6.78 (d, J=8.7 Hz, 1H), 3.91 (s, 3H). MS (m/e) (positive FAB) 262.1 (M+H)+, m.p. 140-142° C.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH2:20][C:21]([OH:23])=O)[CH:6]=[CH:7][C:8]=1[NH:9][C:10]([NH:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[CH3:19])=[O:11].F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C.[NH:57]1[C:65]2[C:60](=[CH:61][C:62]([CH:66]([CH3:73])[CH2:67][C:68]([O:70][CH2:71][CH3:72])=[O:69])=[CH:63][CH:64]=2)[CH2:59][CH2:58]1>CN(C)C=O>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH2:20][C:21]([N:57]2[C:65]3[C:60](=[CH:61][C:62]([CH:66]([CH3:73])[CH2:67][C:68]([O:70][CH2:71][CH3:72])=[O:69])=[CH:63][CH:64]=3)[CH2:59][CH2:58]2)=[O:23])[CH:6]=[CH:7][C:8]=1[NH:9][C:10]([NH:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[CH3:19])=[O:11]
Reactant: COc1cc(CC(=O)O)ccc1NC(=O)Nc1ccccc1C
Reactant: CCOC(=O)CC(C)c1ccc2c(c1)CCN2
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: CCOC(=O)CC(C)c1ccc2c(c1)CCN2C(=O)Cc1ccc(NC(=O)Nc2ccccc2C)c(OC)c1
Reaction time: 1 h
Yield: 57.3 %

Procedure:
A solution of [3-methoxy-4-(3-o-tolyl-ureido)-phenyl]-acetic acid (2.9 g) and O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (3.7 g) in dimethylformamide (about 40 ml) was treated with diisopropylethylamine (10 ml), followed after about 30 seconds by a solution of (R/S) ethyl 3-(2,3-dihydro-1H-indol-5-yl)butyrate [about 2.5 g, Reference Example 5(a)] in dimethylformamide (about 10 ml). The resulting clear, dark brown solution was kept at room temperature for about one hour then evaporated to low bulk. The residue was partitioned between water and ethyl acetate and the organic layer was washed with dilute hydrochloric acid, then with aqueous sodium bicarbonate solution, then with brine, then dried and then evaporated. The residual brown gum was subjected to flash chromatography on silica eluting with a mixture of ethyl acetate and petrol (3:2 to 3:1, v/v) to give the title compound (2.8 g) as a light yellow, amorphous foam. MS (ES+) 552 (M−Na+).
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([CH:10]=[O:11])=[CH:2]1.[CH3:12][S:13](Cl)(=[O:15])=[O:14].C(N(C(C)C)CC)(C)C.C(=O)([O-])O.[Na+]>C(Cl)Cl>[CH3:12][S:13]([N:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([CH:10]=[O:11])=[CH:2]1)(=[O:15])=[O:14]
Reactant: O=Cc1c[nH]c2ccccc12
Reactant: CS(=O)(=O)Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: CS(=O)(=O)n1cc(C=O)c2ccccc21
Temperature: 25 °C
Reaction time: 8 h
Yield: 90.9 %

Procedure:
A solution of 1H-indole-3-carboxaldehyde (2.90 g, 20.0 mmol) in methylene chloride (40 mL) was added with methanesulfonyl chloride (1.86 mL, 24.0 mmol) and diisopropylethylamine (3.10 g, 24.0 mmol), and the mixture was stirred overnight at room temperature. The reaction mixture was added with saturated aqueous sodium hydrogencarbonate to terminate the reaction, and then extracted three times with methylene chloride. The organic layer was dried over anhydrous magnesium sulfate, then the solvent was evaporated, and the resulting residue was purified by silica gel column chromatography (hexane/ethyl acetate) to obtain the objective 1-(methanesulfonyl)-1H-indole-3-carboxaldehyde (4.06 g, 91%).
Reaction SMILES: [CH3:1][C:2]1[O:3][CH:4]=[CH:5][C:6]=1/[CH:7]=[CH:8]/[C:9]([OH:11])=O.S(Cl)([Cl:14])=O>>[CH3:1][C:2]1[O:3][CH:4]=[CH:5][C:6]=1/[CH:7]=[CH:8]/[C:9]([Cl:14])=[O:11]
Reactant: O=S(Cl)Cl
Reactant: Cc1occc1/C=C/C(=O)O
Product: Cc1occc1/C=C/C(=O)Cl

Procedure:
(E)-3-(2-Methyl-3-furyl)acrylic acid (0.30 g, 2 mmol) was dissolved into thionyl chloride (5 ml) and the mixture was heated to reflux for 80 min. Volatiles were removed by evaporation to give crude (E)-3-(2-methyl-3-furyl)acryloyl chloride. The titled compound was prepared from 2-amino4-methoxy-N-(2-pyridyl)aniline (0.43 g, 2 mmol) and (E)-3-(2-methyl-3-furyl)acryloyl chloride obtained as above according to the preparation of (E)-1-(2-pyridyl)-2-styryl-1H-benzimidazole (Example 1, method A). Recrystallization from a mixture of isopropyl ether (3 ml) and ethyl acetate (3 ml) to give 0.10 g (16%) of the titled compound. MW: 331.38; mp: 139.0-140.0° C.; 1H-NMR (CDCl3) δ: 8.75 (1H, dd, J=5.8, 2.2 Hz), 7.97 (1H, ddd, J=7.7, 7.7, 2.2 Hz), 7.79 (1H, d, J=15.8 Hz), 7.77-7.40 (2H, m), 7.33 (1H, d, J=8.8 Hz), 7.30 (1H, d, J=1.8 Hz), 7.24 (1H, d, J=2.0 Hz), 6.88 (1H, dd, J=9.2, 2.0 Hz), 6.72 (1H, d, J=15.8 Hz), 6.44 (1H, d, J=1.8 Hz), 3.89 (3H, s). 2.43 (3H, s).
Reaction SMILES: [F:1][C:2]1[C:7]([B-:8]([C:31]2[C:36]([F:37])=[C:35]([F:38])[C:34]([F:39])=[C:33]([F:40])[C:32]=2[F:41])([C:20]2[C:25]([F:26])=[C:24]([F:27])[C:23]([F:28])=[C:22]([F:29])[C:21]=2[F:30])[C:9]2[C:14]([F:15])=[C:13]([F:16])[C:12]([F:17])=[C:11]([F:18])[C:10]=2[F:19])=[C:6]([F:42])[C:5]([F:43])=[C:4]([F:44])[C:3]=1[F:45].[Li+].Cl.[CH2:48]([N:50]([CH2:53][CH3:54])[CH2:51][CH3:52])[CH3:49]>O>[F:37][C:36]1[C:31]([B-:8]([C:9]2[C:14]([F:15])=[C:13]([F:16])[C:12]([F:17])=[C:11]([F:18])[C:10]=2[F:19])([C:7]2[C:6]([F:42])=[C:5]([F:43])[C:4]([F:44])=[C:3]([F:45])[C:2]=2[F:1])[C:20]2[C:21]([F:30])=[C:22]([F:29])[C:23]([F:28])=[C:24]([F:27])[C:25]=2[F:26])=[C:32]([F:41])[C:33]([F:40])=[C:34]([F:39])[C:35]=1[F:38].[CH2:48]([NH+:50]([CH2:53][CH3:54])[CH2:51][CH3:52])[CH3:49]
Reactant: CCN(CC)CC
Agent: Cl
Agent: Fc1c(F)c(F)c([B-](c2c(F)c(F)c(F)c(F)c2F)(c2c(F)c(F)c(F)c(F)c2F)c2c(F)c(F)c(F)c(F)c2F)c(F)c1F
Agent: [Li+]
Solvent: O
Product: CC[NH+](CC)CC

Procedure:
Further, lithium tetrakis(pentafluorophenyl)borate (16 mmol) was reacted with triethylamine hydrochloride (16 mmol) in water to obtain 12.8 mmol of triethylammonium tetrakis(pentafluorophenyl)borate as a white solid product.
Reaction SMILES: [CH2:1]([N:3]1[CH:7]=[CH:6][NH:5][C:4]1=[O:8])[CH3:2].ClC([O:12][C:13](=[O:27])[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH3:26])C.[H-].[Na+]>C(Cl)(Cl)Cl.C1C=CC=CC=1>[CH2:1]([N:3]1[CH:7]=[CH:6][NH:5][C:4]1=[O:8])[CH3:2].[CH2:1]([CH:15]([CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH3:26])[CH2:14][C:13]([O-:12])=[O:27])[CH3:2]
Reactant: CCCCCCCCCCCCCC(=O)OC(C)Cl
Agent: CCn1cc[nH]c1=O
Agent: [H-]
Agent: [Na+]
Solvent: c1ccccc1
Solvent: ClC(Cl)Cl
Product: CCCCCCCCCCCC(CC)CC(=O)[O-]
Temperature: 25 °C
Reaction time: 8 h
Yield: 10 %

Procedure:
1-Ethyl-4-imidazolin-2-one (1 gm, 0.009 mol) and 1-chloroethyltetradecanoate (2.6 gm, 0.009 mol) were dissolved in 13 ml of dry chloroform and a suspension of sodium hydride in dry benzene (3 ml) was added portionwise. The reaction mixture was stirred at room temperature overnight and was followed by the workup presented in the preceeding examples. After purification by liquid chromatography using silica gel as the supporting material and chloroform as the eluant (EM Silica gel 500 G, 60-200 mesh was used), 1-ethyl-4-imidazolin-2-one-3-α-ethyltetradecanoate was obtained in a yield of 10% (350 mg). 1H n.m.r.(CC14): δ0.90(3H, t, J=5 Hz, CH3 [CH2 ]11CH2 --); 1.28(22H, s, broad, CH3 [CH2 ]11CH2 --); 1.30(3H, t, J=7 Hz, CH3CH2N--); 1.61(3H, d, J=6 Hz, --CHCH3 --); 2.25(2H, t, J=6 Hz, CH3 [CH2 ]10CH2 --); 3.60(2H, q, J=6 Hz, CH3CH2N--); 6.10(1H, d, J=3 Hz, HC=CH); 6.23(1H, d, J=3 Hz, HC=CH); 6.43(1H, q, J=6 Hz, CH3CH--). νmax (film): 3200, 3180(HC=CH), 1745, 1705, 1690(C=O); 1250 cm-1 (C-O-C). m/e+1 367, C21H38N2O3 requires 366.
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]([C:8]2[C:17]3[C:12](=[C:13]([C:18]([F:21])([F:20])[F:19])[CH:14]=[CH:15][CH:16]=3)[N:11]=[CH:10][C:9]=2[C:22]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)=[O:23])[CH:5]=[CH:6][CH:7]=1.Br[CH2:31][C:32]1[C:37]([Cl:38])=[CH:36][CH:35]=[CH:34][C:33]=1[Cl:39]>>[Cl:38][C:37]1[CH:36]=[CH:35][CH:34]=[C:33]([Cl:39])[C:32]=1[CH2:31][O:1][C:2]1[CH:3]=[C:4]([C:8]2[C:17]3[C:12](=[C:13]([C:18]([F:21])([F:19])[F:20])[CH:14]=[CH:15][CH:16]=3)[N:11]=[CH:10][C:9]=2[C:22]([C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=2)=[O:23])[CH:5]=[CH:6][CH:7]=1
Reactant: Clc1cccc(Cl)c1CBr
Reactant: O=C(c1ccccc1)c1cnc2c(C(F)(F)F)cccc2c1-c1cccc(O)c1
Product: O=C(c1ccccc1)c1cnc2c(C(F)(F)F)cccc2c1-c1cccc(OCc2c(Cl)cccc2Cl)c1

Procedure:
The title compound was prepared from [4-(3-hydroxyphenyl)-8-(trifluoromethyl)quinolin-3-yl](phenyl)methanone and 2-Bromomethyl-1,3-dichlorobenzene following the procedure of Example 478: MS (ESI) m/z 552.
Reaction SMILES: [OH:1][C:2]1[CH:17]=[CH:16][C:5]([C:6]([O:8][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[O:7])=[CH:4][CH:3]=1.C(N([CH2:23][CH3:24])CC)C.[C:25](Cl)(=[O:35])[C:26]1[CH:34]=[CH:33][C:29]([C:30](Cl)=[O:31])=[CH:28][CH:27]=1>C1(C)C=CC=CC=1>[CH2:9]([O:8][C:6]([C:5]1[CH:16]=[CH:17][C:2]([O:1][C:25](=[O:35])[C:26]2[CH:34]=[CH:33][C:29]([C:30]([O:1][C:2]3[CH:3]=[CH:4][C:5]([C:6]([O:8][CH2:9][C:24]4[CH:23]=[CH:15][CH:10]=[CH:11][CH:12]=4)=[O:7])=[CH:16][CH:17]=3)=[O:31])=[CH:28][CH:27]=2)=[CH:3][CH:4]=1)=[O:7])[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1
Reactant: O=C(OCc1ccccc1)c1ccc(O)cc1
Reactant: CCN(CC)CC
Reactant: O=C(Cl)c1ccc(C(=O)Cl)cc1
Solvent: Cc1ccccc1
Product: O=C(OCc1ccccc1)c1ccc(OC(=O)c2ccc(C(=O)Oc3ccc(C(=O)OCc4ccccc4)cc3)cc2)cc1

Procedure:
Into a 500 ml four-neck flask equipped with a condenser tube and a thermometer are charged 56 g of benzyl p-hydroxybenzoate, 25 g of triethylamine and 60 ml of toluene. A suspension of 25 g of terephthalic dichloride in 100 ml of toluene is added dropwise with stirring while retaining the mixture at 0°-5° C. over 3 hours. After addition, the mixture is further allowed to react at 0°-5° C. for 1 hour. Thereafter the resulting reaction product is collected by filtration to obtain white crystals. The crystals are washed with 1500 ml of water twice and then with 1000 ml of methanol twice and subsequently, recrystallized from chloroform to give di(p-benzyloxycarbonylphenyl)terephthalate melting at 186°-187° C. as white crystals.
Reaction SMILES: [C:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1)(=[O:3])[CH3:2]>CC(O)C>[C:4]1([C@H:1]([OH:3])[CH3:2])[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1
Reactant: CC(=O)c1ccccc1
Solvent: CC(C)O
Product: C[C@@H](O)c1ccccc1
Temperature: 25 °C
Reaction time: 2.5 h
Yield: 99.6 %

Procedure:
Acetophenone (200 ml, 1.5 mol) was charged to the catalyst solution, followed by 2-propanol (0.5 l). The pressure was reduced (28.5 mmHg) and then a sodium 2-propoxide solution (120 ml of 0.1M solution in 2-propanol) was charged. The mixture was stirred at ambient temperature under nitrogen for 2.5 h, at hourly intervals the flask was back filled with nitrogen and sufficient 2-propanol charged to compensate for the volume removed by distillation. This gave (R)-1-phenylethanol Yield 99.6%, ee 82.9%. The turnover number, integrated over 1 h, was 454 h−1.
Reaction SMILES: Cl[C:2]1[C:11]2[N:10]=[C:9]([CH3:12])[CH:8]=[CH:7][C:6]=2[C:5](B(O)O)=[CH:4][N:3]=1.Br[C:17]1[S:21][N:20]=[C:19]([CH3:22])[N:18]=1.[NH2:23][C:24]1[N:25]=[C:26]([CH3:29])[S:27][CH:28]=1>>[CH3:12][C:9]1[CH:8]=[CH:7][C:6]2[C:11](=[C:2]([NH:23][C:24]3[N:25]=[C:26]([CH3:29])[S:27][CH:28]=3)[N:3]=[CH:4][C:5]=2[C:17]2[S:21][N:20]=[C:19]([CH3:22])[N:18]=2)[N:10]=1
Reactant: Cc1nc(N)cs1
Reactant: Cc1nsc(Br)n1
Reactant: Cc1ccc2c(B(O)O)cnc(Cl)c2n1
Product: Cc1ccc2c(-c3nc(C)ns3)cnc(Nc3csc(C)n3)c2n1

Procedure:
The title compound, MS: m/e=355.2 (M+H+), was prepared in accordance with the general method of example 15 step 1 and step 3 from 8-chloro-2-methyl-[1,7]naphthyridine-5-boronic acid (Example L), 5-bromo-3-methyl-[1,2,4]thiadiazole (Example M) and 4-amino-2-methylthiazole (Example F).
Reaction SMILES: [CH2:1]([O:4][C:5]([C:7]1[CH:8]=[C:9]([CH2:13][O:14][CH2:15][C@@H:16]([NH:19][C:20](=[O:38])[C@H:21]([CH2:30][C:31]2[CH:36]=[CH:35][CH:34]=[C:33]([CH3:37])[CH:32]=2)[NH:22]C(OC(C)(C)C)=O)[C:17]#[N:18])[CH:10]=[CH:11][CH:12]=1)=[O:6])[CH:2]=[CH2:3]>C(O)=O>[CH2:1]([O:4][C:5]([C:7]1[CH:8]=[C:9]([CH2:13][O:14][CH2:15][C@@H:16]([NH:19][C:20](=[O:38])[C@H:21]([CH2:30][C:31]2[CH:36]=[CH:35][CH:34]=[C:33]([CH3:37])[CH:32]=2)[NH2:22])[C:17]#[N:18])[CH:10]=[CH:11][CH:12]=1)=[O:6])[CH:2]=[CH2:3]
Reactant: C=CCOC(=O)c1cccc(COC[C@H](C#N)NC(=O)[C@H](Cc2cccc(C)c2)NC(=O)OC(C)(C)C)c1
Solvent: O=CO
Product: C=CCOC(=O)c1cccc(COC[C@H](C#N)NC(=O)[C@@H](N)Cc2cccc(C)c2)c1

Procedure:
A solution of N-[2-[(3-(allyloxycarbonyl)-phenyl)methoxy]-1(S)-cyanoethyl]-3-methyl-Nα-(t-butoxycarbonyl)-L-phenylalaninamide (3.18 g, 6.10 mmol) in 96% formic acid (40 mL) is stirred at room temperature for 5.5 hours. Formic acid is evaporated (high vacuum, 25° C.), and the residue is taken up in water (50 mL) and basified with saturated NaHCO3 (100 mL). The resulting mixture is extracted with EtOAc (3×50 mL), and then washed with water (2×100 mL) and brine (1×100 mL), dried over MgSO4, and evaporated to yield N-[2-[(3-(allyloxycarbonyl)-phenyl)methoxy]-1(S)-cyanoethyl]-3-methyl-L-phenylalaninamide as a clear thick oil.
Reaction SMILES: [OH-].[Na+].O.[F:4][C:5]1[CH:6]=[CH:7][C:8]([CH3:13])=[C:9]([CH:12]=1)[CH:10]=O.[CH3:14][C:15]([CH3:17])=[O:16]>>[F:4][C:5]1[CH:6]=[CH:7][C:8]([CH3:13])=[C:9]([CH:10]=[CH:14][C:15](=[O:16])[CH3:17])[CH:12]=1
Reactant: CC(C)=O
Reactant: Cc1ccc(F)cc1C=O
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: CC(=O)C=Cc1cc(F)ccc1C
Reaction time: 1 h

Procedure:
To a mixture of acetone (80 ml), sodium hydroxide (3.7 g) and water (100 ml) was added dropwise at room temperature a solution of 5-fluoro-2-methylbenzaldehyde (11.5 g) in acetone (30 ml), and the mixture was stirred at the same temperature for 1 hour. Under reduced pressure, acetone was evaporated, and the residue was extracted with ethyl acetate. The organic layer was washed with water and saturated brine, and concentrated under reduced pressure to give 4-(5-fluoro-2-methylphenyl)-3-buten-2-one (13.4 g).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]2[C:10](=[O:25])[NH:11][N:12]=[CH:13][C:14]=2[C:15]2[CH:20]=[CH:19][C:18]([S:21]([CH3:24])(=[O:23])=[O:22])=[CH:17][CH:16]=2)=[CH:4][CH:3]=1.Br[C:27]1[CH:32]=[CH:31][C:30]([F:33])=[C:29]([F:34])[CH:28]=1.N>O>[F:33][C:30]1[CH:31]=[C:32]([N:11]2[C:10](=[O:25])[C:9]([CH2:8][C:5]3[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=3)=[C:14]([C:15]3[CH:20]=[CH:19][C:18]([S:21]([CH3:24])(=[O:23])=[O:22])=[CH:17][CH:16]=3)[CH:13]=[N:12]2)[CH:27]=[CH:28][C:29]=1[F:34]
Reactant: CS(=O)(=O)c1ccc(-c2cn[nH]c(=O)c2Cc2ccc(F)cc2)cc1
Reactant: Fc1ccc(Br)cc1F
Agent: N
Solvent: O
Product: CS(=O)(=O)c1ccc(-c2cnn(-c3ccc(F)c(F)c3)c(=O)c2Cc2ccc(F)cc2)cc1

Procedure:
The title compound was prepared according to the method of Example 62 substituting 4-(4-fluorophenylmethyl)-5-[4-(methylsulfonyl)phenyl]-3(2H)-pyridazinone in place of 4-(4-fluorophenyl)-5-[4-(methylsulfonyl)phenyl]-3(2H)-pyridazinone and substituting 1-bromo-3,4-difluorobenzene in place of 4-iodo-1-fluorobenzene (yield: 0.085 g, 54%). mp 157–159° C. 1H NMR (300 MHz, DMSO d6) δ 3.30 (s, 3H), 3.88 (bs, 2H), 7.04 (m, 4H), 7.49–7.66 (m, 2H), 7.70 (m, 2H), 7.81 (m, 1H), 8.12 (s, 1H). MS (DCI/NH3) m/z 471 (M+H)+, 488 (M+NH4)+. Anal. calc. for C24H17F3N2O3S.0.25 H2O: C, 60.69; H, 3.71; N, 5.84. Found: C, 6.39; H, 3.76; N, 5.81.
Reaction SMILES: CS(O[CH2:6][C@H:7]1[CH2:12][CH2:11][C@H:10]([CH2:13][O:14][Si:15]([C:18]([CH3:21])([CH3:20])[CH3:19])([CH3:17])[CH3:16])[CH2:9][CH2:8]1)(=O)=O.[I-].[Na+].[C-:24]#[N:25].[Na+]>CN(C)C=O>[Si:15]([O:14][CH2:13][C@H:10]1[CH2:11][CH2:12][C@H:7]([CH2:6][C:24]#[N:25])[CH2:8][CH2:9]1)([C:18]([CH3:21])([CH3:20])[CH3:19])([CH3:17])[CH3:16]
Reactant: CC(C)(C)[Si](C)(C)OC[C@H]1CC[C@H](COS(C)(=O)=O)CC1
Reactant: [C-]#N
Agent: [I-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CC(C)(C)[Si](C)(C)OC[C@H]1CC[C@H](CC#N)CC1
Temperature: 110 °C
Reaction time: 0.75 h

Procedure:
In 100 ml of dry dimethylformamide were suspended 11.0 g of trans-4-methanesulfonyloxymethyl-1-t-butyldimethylsilyloxymethylcyclohexane, 5.87 g of sodium iodide and 1.92 g of sodium cyanide, and the mixture was stirred at 50° C. for 1 hour and 45 minutes and further at 110° C. for 45 minutes. The reaction mixture was poured into 100 ml of ice-water and the mixture was extracted with 300 ml of ether. The extracts were washed with an aqueous citric acid solution, an aqueous sodium chloride solution, an aqueous sodium bicarbonate solution and an aqueous sodium chloride solution and dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography employing cyclohexane-ethyl acetate (20:1-5:1) as an eluting solvent to obtain 7.41 g of the desired compound as a colorless oil.
Reaction SMILES: [Br:1]Br.N1C=CC=CC=1.[C:9]([C:11]1[CH:12]=[C:13]2[C:18](=[CH:19][CH:20]=1)[N:17]=[CH:16][CH:15]=[CH:14]2)#[N:10]>C(Cl)(Cl)(Cl)Cl>[Br:1][C:15]1[CH:16]=[N:17][C:18]2[C:13]([CH:14]=1)=[CH:12][C:11]([C:9]#[N:10])=[CH:20][CH:19]=2
Reactant: BrBr
Reactant: N#Cc1ccc2ncccc2c1
Solvent: ClC(Cl)(Cl)Cl
Solvent: c1ccncc1
Product: N#Cc1ccc2ncc(Br)cc2c1
Reaction time: 2 h

Procedure:
In an amount of 37.8 mg of 6-cyanoquinoline (Justus Liebigs Ann. Chem., 1966, 699, 98-106) was dissolved in 1 ml of carbon tetrachloride, added with 13 μl of bromine, and then stirred under reflux. After 2 hours, the reaction mixture was added with 20 μl of pyridine, and further stirred for 23 hours under reflux. The reaction mixture was concentrated under reduced pressure, and the resulting residue was purified by silica gel column chromatography (hexane/ethyl acetate (4:1)) to obtain 34.8 mg of the title compound.
Reaction SMILES: C([O-])([O-])=O.[K+].[K+].[CH2:7]([SH:9])[CH3:8].[CH2:10]([O:12][C:13]([C:15]1[C:16](Cl)=[N:17][C:18]2[C:23]([C:24]=1[CH3:25])=[CH:22][CH:21]=[C:20]([C:26]([CH3:29])([CH3:28])[CH3:27])[CH:19]=2)=[O:14])[CH3:11].CCCCCC>CN(C=O)C.O>[CH2:10]([O:12][C:13]([C:15]1[C:16]([S:9][CH2:7][CH3:8])=[N:17][C:18]2[C:23]([C:24]=1[CH3:25])=[CH:22][CH:21]=[C:20]([C:26]([CH3:29])([CH3:28])[CH3:27])[CH:19]=2)=[O:14])[CH3:11]
Reactant: CCS
Reactant: CCOC(=O)c1c(Cl)nc2cc(C(C)(C)C)ccc2c1C
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Solvent: CCCCCC
Product: CCOC(=O)c1c(SCC)nc2cc(C(C)(C)C)ccc2c1C
Temperature: 60 °C
Reaction time: 16 h
Yield: 65.2 %

Procedure:
190 mg (1.38 mmol) K2CO3 and 100 μl (1.38 mmol) ethanethiol were added to a solution of 140 mg (0.46 mmol) 7-tert-butyl-2-chloro-4-methyl-quinoline-3-carboxylic acid ethyl ester in DMF (3 ml) and the mixture was stirred for 16 h at 60° C. Then it was diluted with water and extracted with EE. The organic phase was washed with brine, dried over Na2SO4, filtered and concentrated to small volume under vacuum. Column chromatography (hexane/EE 19:1) of the residue yielded 100 mg (0.30 mmol, 65%) 7-tert-butyl-2-ethylsulfanyl-4-methyl-quinoline-3-carboxylic acid ethyl ester.