Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cs].[CH3:2][CH:3]([CH3:15])[CH2:4][CH2:5][CH:6]1[N:10]([CH3:11])[S:9](=[O:13])(=[O:12])[NH:8][C:7]1=[O:14].CC(C)CCC1N(C)S(=O)(=O)NC1=O.[C:30]1([S:36][CH2:37]Cl)[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1>CO.CN(C=O)C>[C:30]1([S:36][CH2:37][N:8]2[C:7](=[O:14])[CH:6]([CH2:5][CH2:4][CH:3]([CH3:15])[CH3:2])[N:10]([CH3:11])[S:9]2(=[O:13])=[O:12])[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1
Reactant: CC(C)CCC1C(=O)NS(=O)(=O)N1C
Reactant: ClCSc1ccccc1
Agent: [Cs]
Solvent: CO
Solvent: CN(C)C=O
Product: CC(C)CCC1C(=O)N(CSc2ccccc2)S(=O)(=O)N1C
Temperature: 85 °C
Yield: 70.6 %

Procedure:
A mixture of 4-(3-methylbutyl)-5-methyl-1,2,5-thiadiazolidin-3-one 1,1-dioxide cesium salt (prepared by reacting 7.7 g (34.95 mmol) of 4-(3-methylbutyl)-5-methyl-1,2,5-thiadiazolidin-3-one 1,1-dioxide in methanol with 5.13 g of CS2CO3 followed by removal of the solvent and drying under high vacuum) and phenylthiomethyl chloride (6.65 g, 41.94 mmol) suspended in DMF was heated at 85° C. for 17 hours. The mixture was cooled, and poured into 300 ml of ice/water. The reaction mixture was extracted with ethyl acetate (3×) and the organic layer was washed with water and brine, and dried over sodium sulfate. The organic layer was concentrated in vacuo and the residue was purified by silica column chromatography (10% ethyl acetate in hexane) to afford 8.15 g (70.6%) of 2-phenylthiomethyl-4-(3-methylbutyl)-5-methyl-1,2,5-thiadiazolidin-3-one 1,1-dioxide (Formula VII: R1 =H; R2 =(CH2)2CH(CH3)2 ; R3 =CH3) as an oil.
Reaction SMILES: [CH:1]1(O)[CH2:5][CH2:4][CH:3]=[CH:2]1.[Cl:7][C:8]1[N:16]=[C:15]2[C:11]([NH:12][CH:13]=[N:14]2)=[C:10]([Cl:17])[N:9]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>C1COCC1>[Cl:7][C:8]1[N:16]=[C:15]2[C:11]([N:12]=[CH:13][N:14]2[CH:1]2[CH2:5][CH2:4][CH:3]=[CH:2]2)=[C:10]([Cl:17])[N:9]=1
Reactant: OC1C=CCC1
Reactant: Clc1nc(Cl)c2[nH]cnc2n1
Agent: CCOC(=O)N=NC(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: Clc1nc(Cl)c2ncn(C3C=CCC3)c2n1
Temperature: 25 °C
Reaction time: 60 h
Yield: 40.6 %

Procedure:
Add to a stirred solution of 2-cyclopenten-1-ol (2c, 2.60 g, 30.9 mmol), 2,6-dichloropurine (1, 7.00 g, 37.0 mmol) and triphenyl phosphine (9.70 g, 37.0 mmol) in dry THF (120 ml) at 0° C., diethyl azodicarboxylate (5.85 ml, 37.0 mmol) dropwise over a period of 15 min. under a nitrogen atmosphere. Stir the resulting solution for 60 hrs at room temperature. Concentrate the reaction mixture, charge the residue directly onto a silica gel column and elute with hexane:ethyl acetate (3:1) to give of 2,6-dichloro-9-cyclopent-2-enyl-9H-purine (3c) (3.20 g, 41%.)
Reaction SMILES: [O:1]1[CH:6]=[CH:5][CH2:4][CH2:3][CH2:2]1.[OH:7][C@H:8]([CH3:17])[C:9]([N:11]1[CH2:16][CH2:15][O:14][CH2:13][CH2:12]1)=[O:10].O.C1(C)C=CC(S(O)(=O)=O)=CC=1>ClCCl>[O:1]1[CH2:2][CH2:3][CH2:4][CH2:5][CH:6]1[O:7][C@H:8]([CH3:17])[C:9]([N:11]1[CH2:12][CH2:13][O:14][CH2:15][CH2:16]1)=[O:10]
Reactant: C1=COCCC1
Reactant: C[C@@H](O)C(=O)N1CCOCC1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: ClCCl
Solvent: O
Product: C[C@@H](OC1CCCCO1)C(=O)N1CCOCC1
Temperature: 0 °C
Yield: 95 %

Procedure:
3,4-Dihydro-2H-pyran (90.5 ml, 1.2 eq) was added dropwise to a mixture of 4-[(R)-2-hydroxypropionyl]morpholine (132 g) and p-toluenesulfonic acid monohydrate (500 mg, 0.003 eq) in dry dichloromethane (500 ml) over a period of 15 min with stirring at 0° C. After being stirred for 30 min at 0° C., the mixture was washed with aqueous sodium bicarbonate, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. Purification of the residue by silica gel chromatography, using n-hexane: ethyl acetate (8:1)˜ethyl acetate as an eluent, gave 4-[(2R)-2-(3,4,5,6-Tetrahydro-2H-pyran-2-yloxy)propionyl]morpholine (191.6 g, 95% yield) as a pale yellow oil.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([Mg]Br)=[CH:4][CH:3]=1.[F:10][C:11]1[CH:18]=[CH:17][C:14]([CH:15]=[O:16])=[C:13]([C:19]([F:22])([F:21])[F:20])[CH:12]=1.ClC1C=C(Cl)C=CC=1C(O)C1C=CC(Cl)=CC=1>>[F:21][C:19]([F:20])([F:22])[C:13]1[CH:12]=[C:11]([F:10])[CH:18]=[CH:17][C:14]=1[CH:15]([OH:16])[C:5]1[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=1
Reactant: Clc1ccc([Mg]Br)cc1
Reactant: O=Cc1ccc(F)cc1C(F)(F)F
Agent: OC(c1ccc(Cl)cc1)c1ccc(Cl)cc1Cl
Product: OC(c1ccc(Cl)cc1)c1ccc(F)cc1C(F)(F)F

Procedure:
This material was prepared from 4-chlorophenylmagnesium bromide (28.6 mmol) and 4-fluoro-2-(trifluoromethyl)benzaldehyde (26.0 mmol) using the procedure described for compound (2) (6.04 g, 76%).
Reaction SMILES: [OH:1][C:2]1[C:11]2[C:10](=[O:12])[O:9][C:8]([CH3:14])([CH3:13])[O:7][C:6]=2[CH:5]=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].[CH2:21](Br)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1>CN(C)C=O>[CH2:21]([O:1][C:2]1[C:11]2[C:10](=[O:12])[O:9][C:8]([CH3:14])([CH3:13])[O:7][C:6]=2[CH:5]=[CH:4][CH:3]=1)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1
Reactant: CC1(C)OC(=O)c2c(O)cccc2O1
Reactant: BrCc1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CC1(C)OC(=O)c2c(OCc3ccccc3)cccc2O1
Reaction time: 0.17 h
Yield: 99.9 %

Procedure:
A solution of 5-hydroxy-2,2-dimethyl-4H-benzo[d][1,3]dioxin-4-one (6.00 g, 30.9 mmol) (Hadfield, A. et al., Synthetic Communications, 24(7):1025-1028 (1994)) in N,N-dimethylformamide (35 mL) was treated with powdered anhydrous potassium carbonate (5.15 g, 37.26 mmol) added all at once. The resulting mixture was stirred in vacuo for 10 min. and then flushed with nitrogen. The reaction flask was placed in a water bath (22° C.) and treated with benzyl bromide (5.55 g, 32.16 mmol) added dropwise over 15 min. The resulting mixture was then stirred at 22° C. for 18 h. The solid formed was filtered and washed with N,N-dimethylformamide. The filtrate was evaporated in vacuo and the residual oil was diluted with ethyl acetate (300 mL), washed with cold 0.1 N hydrochloric acid, saturated sodium bicarbonate and brine. After drying over anhydrous magnesium sulfate, evaporation of the solvent gave a thick syrup. Chromatography on silica gel (4×13 cm, elution toluene-ethyl acetate 0-5%) gave 8.78 g (100% yield) of the title material as a white solid. LC (Method A): 1.982 min. 1H NMR (CDCl3, 600 MHz) δ ppm: 1.69 (s, 6H), 5.23 (s, 2H), 6.53 (d, J=8.2 Hz, 1H), 6.62 (d, J=8.4 Hz, 1H), 7.24-7.3 (m, 1H), 7.34-7.4 (m, 3H), 7.52 (broad d, J=7.4 Hz 2H).
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:14][CH:15]=O)[C:10]([O:12][CH3:13])=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl[C:18]([F:23])([F:22])C([O-])=O.[Na+].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>CN(C)C=O>[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:14][CH:15]=[C:18]([F:23])[F:22])[C:10]([O:12][CH3:13])=[O:11])=[O:7])([CH3:2])([CH3:3])[CH3:4]
Reactant: O=C([O-])C(F)(F)Cl
Reactant: COC(=O)[C@H](CC=O)NC(=O)OC(C)(C)C
Agent: [Na+]
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CN(C)C=O
Product: COC(=O)[C@H](CC=C(F)F)NC(=O)OC(C)(C)C
Temperature: 115 °C
Yield: 13.3 %

Procedure:
A solution of (S)-methyl 2-((tert-butoxycarbonyl)amino)-4-oxobutanoate (5.97 g, 25.8 mmol), sodium 2-chloro-2,2-difluoroacetate (11.8 g, 77.0 mmol), triphenylphosphine (20.3 g, 77.0 mmol), and N,N-dimethylformamide (50 mL) was charged to a 500 mL 3-necked flask and heated to 115° C. for 15 min. The resulting mixture was filtered through diatomaceous earth (Celite®) and concentrated under reduced pressure. The crude material was purified over SiO2 (5-40% ethyl acetate/hexanes gradient elution) to afford (S)-methyl 2-((tert-butoxycarbonyl)amino)-5,5-difluoropent-4-enoate (0.91 g, 3.43 mmol, 13% yield) as a colorless oil. 1H NMR (400 MHz, CDCl3) δ ppm 5.25-5.06 (br. s., 1H), 4.42 (br. s., 1H), 4.24-4.10 (m, 1H), 3.78 (s, 3H), 2.59 (dd, J=14.4, 6.7 Hz, 1H), 2.51-2.31 (m, 1H), 1.47 (s, 9H).
Reaction SMILES: C[O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[N:9]=[CH:8][C:7]([C:13]([OH:15])=[O:14])=[CH:6]2.B(Br)(Br)Br>ClCCl>[OH:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[N:9]=[CH:8][C:7]([C:13]([OH:15])=[O:14])=[CH:6]2
Reactant: COc1ccc2ncc(C(=O)O)cc2c1
Agent: BrB(Br)Br
Solvent: ClCCl
Product: O=C(O)c1cnc2ccc(O)cc2c1
Temperature: -78 °C
Reaction time: 0.5 h
Yield: 137.5 %

Procedure:
6-Methoxyquinoline-3-carboxylic acid (2.5 g, 12.3 mmol) was suspended in anhydrous dichloromethane (20 mL) under nitrogen; the suspension was cooled to −78° C. A solution of BBr3 in dichloromethane (100 mL of 1M solution, 100 mmol) was added dropwise. The mixture was stirred for 30 min at −78° C., warmed slowly to RT, and allowed to stir at room temperature overnight. The reaction was quenched by dropwise addition of ice-water. The resulting solids were collected by filtration, and washed with water to yield 3.2 g (97%) of 6-hydroxyquinoline-3-carboxylic acid as an HBr salt. LCMS: >98%; MS: 190.27 (M+1, free base).
Reaction SMILES: Cl.[CH3:2][C:3]1[CH:4]=[C:5](C=[CH:13][C:14]=1[CH3:15])[CH2:6][C:7]1[NH:8][CH2:9][CH2:10][N:11]=1.CC1CCCN(C)C1(C)C.[C:26]1([N:32]=[C:33]=[O:34])[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.[OH-].[K+]>C(Cl)(Cl)Cl>[C:26]1([NH:32][C:33]([N:8]2[CH2:9][CH2:10][N:11]=[C:7]2[C:6]2[CH:5]=[CH:4][C:3]([CH3:2])=[C:14]([CH3:13])[CH:15]=2)=[O:34])[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1
Reactant: Cc1ccc(CC2=NCCN2)cc1C
Reactant: O=C=Nc1ccccc1
Agent: CC1CCCN(C)C1(C)C
Agent: Cl
Agent: [K+]
Solvent: ClC(Cl)Cl
Product: Cc1ccc(C2=NCCN2C(=O)Nc2ccccc2)cc1C
Temperature: 25 °C
Reaction time: 4 h

Procedure:
2-(3,4-Dimethylbenzyl)-2-imidazoline hydrochloride (3.43 g; 0.01 mole) was suspended in dry chloroform (50 ml). The so obtained mixture was treated with tetramethylpiperidine (1.41 g; 0.01 mole) in dry chloroform (20 ml) and stirred at ambient temperature for approximately 4 hours with intermittent shaking, any large pieces of solid being broken up by means of a glass rod. Phenylisocyanate (1.20 g; 0.01 mole) in dry chloroform (10 ml) was then added dropwise to the cooled reaction mixture and the resulting mixture stirred overnight at ambient temperature. The solvent was evaporated under reduced pressure, the residue shaken up with water (60 to 100 ml) and filtered. The white solid so obtained was then transferred to a vacuum dessicator over fresh potassium hydroxide and left until the material had a constant melting point, to give 1-N-phenylcarbamoyl-2-(3,4-dimethylphenyl)-2-imidazoline, m.p. 139°-142° C. The 1H NMR spectrum was consistent with the assigned structure.
Reaction SMILES: [CH3:1][C:2]([C@H:4]([C@H:6]([C@H:8]([CH2:10][OH:11])[OH:9])[OH:7])[OH:5])=[O:3].CC([C@@H]([C@H]([C@H](CO)O)O)O)=O.C(S)[C@@H](O)[C@@H](O)CS>>[CH3:1][C@H:2]([C@H:4]([C@H:6]([C@H:8]([CH2:10][OH:11])[OH:9])[OH:7])[OH:5])[OH:3]
Reactant: CC(=O)[C@@H](O)[C@@H](O)[C@@H](O)CO
Agent: CC(=O)[C@H](O)[C@@H](O)[C@@H](O)CO
Agent: O[C@H](CS)[C@@H](O)CS
Product: C[C@@H](O)[C@@H](O)[C@@H](O)[C@@H](O)CO

Procedure:
1-Deoxy L-psicose prepared via a reaction of 1-deoxy L-fructose with DTE was reduced to obtain 1-deoxy L-allitol, which was then oxidized microbially (IK7), to produce 6-deoxy D-psicose. 1-Deoxy D-psicose thus obtained reacted with DTE. The reaction conditions are as follows.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([C:8](Cl)=[O:9])[CH:5]=[C:4]([Cl:11])[N:3]=1.[CH3:12][O:13][C:14]1[CH:20]=[CH:19][C:17]([NH2:18])=[C:16]([N+:21]([O-:23])=[O:22])[CH:15]=1>>[Cl:1][C:2]1[CH:7]=[C:6]([C:8]([NH:18][C:17]2[CH:19]=[CH:20][C:14]([O:13][CH3:12])=[CH:15][C:16]=2[N+:21]([O-:23])=[O:22])=[O:9])[CH:5]=[C:4]([Cl:11])[N:3]=1
Reactant: O=C(Cl)c1cc(Cl)nc(Cl)c1
Reactant: COc1ccc(N)c([N+](=O)[O-])c1
Product: COc1ccc(NC(=O)c2cc(Cl)nc(Cl)c2)c([N+](=O)[O-])c1

Procedure:
The title compound was prepared from 2,6-dichloropyridine-4-carbonyl chloride and 4-methoxy-2-nitroaniline and was obtained as a yellow solid as described in Example 1. 1H NMR (CDCl3): 11.12 (s, 1H), 8.78 (d, J=9.3, 1H), 7.77 (d, J=3.0, 1H), 7.75 (s, 2H), 7.35-7.31 (m, 1H), 3.91 (s, 3H).
Reaction SMILES: C([O-])=O.[NH4+].[CH3:5][O:6][C:7]1[CH:8]=[C:9]([CH:13]([OH:18])[CH2:14][N+:15]([O-])=O)[CH:10]=[CH:11][CH:12]=1>O1CCCC1.CO.[C].[Pd]>[NH2:15][CH2:14][CH:13]([C:9]1[CH:10]=[CH:11][CH:12]=[C:7]([O:6][CH3:5])[CH:8]=1)[OH:18]
Reactant: COc1cccc(C(O)C[N+](=O)[O-])c1
Agent: [Pd]
Agent: O=C[O-]
Agent: [NH4+]
Solvent: CO
Solvent: C1CCOC1
Product: COc1cccc(C(O)CN)c1
Temperature: 25 °C
Reaction time: 18 h
Yield: 72.6 %

Procedure:
Palladium-carbon (10%, 0.64 g) and ammonium formate (4.8 g) were added to a mixed solution of the compound of Example B142 (3.0 g, 15 mmol) in tetrahydrofuran (43 ml) and methanol (43 ml), and this mixture was stirred at room temperature for 18 hours. The catalyst was removed by filtration, the filtrate was diluted with ether, precipitates were removed by filtration, and the obtained filtrate was concentrated to give the title compound (1.82 g). This compound was used in the following reaction without further purification.
Reaction SMILES: [CH3:1][C:2]1[O:3][C:4]2[CH:13]=[C:12]([O:14][C:15]3[CH:20]=[CH:19][N:18]=[C:17]4[CH:21]=[CH:22][S:23][C:16]=34)[CH:11]=[CH:10][C:5]=2[C:6]=1[C:7](O)=[O:8].[F:24][C:25]1[CH:33]=[C:32]2[C:28]([C:29]([CH2:34][CH2:35][NH2:36])=[CH:30][NH:31]2)=[CH:27][CH:26]=1>>[F:24][C:25]1[CH:33]=[C:32]2[C:28]([C:29]([CH2:34][CH2:35][NH:36][C:7]([C:6]3[C:5]4[CH:10]=[CH:11][C:12]([O:14][C:15]5[CH:20]=[CH:19][N:18]=[C:17]6[CH:21]=[CH:22][S:23][C:16]=56)=[CH:13][C:4]=4[O:3][C:2]=3[CH3:1])=[O:8])=[CH:30][NH:31]2)=[CH:27][CH:26]=1
Reactant: Cc1oc2cc(Oc3ccnc4ccsc34)ccc2c1C(=O)O
Reactant: NCCc1c[nH]c2cc(F)ccc12
Product: Cc1oc2cc(Oc3ccnc4ccsc34)ccc2c1C(=O)NCCc1c[nH]c2cc(F)ccc12

Procedure:
This material was prepared from 2-methyl-6-[thieno[3,2-b]pyridin-7-yloxy]benzofuran-3-carboxylic acid 100 and 2-(6-fluoro-1H-indol-3-yl)ethylamine in a similar manner as that described for example 102. 1H NMR (CD3CN) δ 8.48 (1H, d, J=5.6 Hz), 7.91 (1H, d, J=5.6 Hz), 7.63–7.59 (2H, m), 7.54 (1H, d, J=5.6 Hz), 7.38 (1H, d, J=2.3 Hz), 7.17 (1H, d, J=2.3 Hz), 7.14 (1H, t, J=2.3 Hz), 7.11 (1H, d, J=2.3 Hz), 6.85 (1H, m), 6.65 (1H, bm), 6.61 (1H, d, J=5.6 Hz), 3.69 (2H, q, J=7.1 Hz), 3.06 (2H, t, J=7.1 Hz), 2.57 (3H, s).
Reaction SMILES: Br[C:2]1[CH:3]=[CH:4][C:5](O)=[C:6]([C:8]2[CH:17]=[CH:16][C:15]3[C:10](=[CH:11][CH:12]=[C:13]([C:18]4[N:22]([CH:23]5[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]5)[C:21]5[CH:29]=[CH:30][C:31]([C:33]([OH:35])=[O:34])=[CH:32][C:20]=5[N:19]=4)[CH:14]=3)[N:9]=2)[CH:7]=1.[CH:37]1[C:46]2CCCCC=2C=[CH:39][C:38]=1C(=O)C.[OH-].[K+]>C(O)C>[CH:23]1([N:22]2[C:21]3[CH:29]=[CH:30][C:31]([C:33]([OH:35])=[O:34])=[CH:32][C:20]=3[N:19]=[C:18]2[C:13]2[CH:14]=[C:15]3[C:10](=[CH:11][CH:12]=2)[N:9]=[C:8]([C:6]2[CH:5]=[CH:4][C:3]4[CH2:39][CH2:38][CH2:37][CH2:46][C:2]=4[CH:7]=2)[CH:17]=[CH:16]3)[CH2:24][CH2:25][CH2:26][CH2:27][CH2:28]1
Reactant: O=C(O)c1ccc2c(c1)nc(-c1ccc3nc(-c4cc(Br)ccc4O)ccc3c1)n2C1CCCCC1
Reactant: CC(=O)c1ccc2c(c1)CCCC2
Agent: [K+]
Agent: [OH-]
Solvent: CCO
Product: O=C(O)c1ccc2c(c1)nc(-c1ccc3nc(-c4ccc5c(c4)CCCC5)ccc3c1)n2C1CCCCC1
Yield: 60 %

Procedure:
Following the procedure and workup for Compound 354, Compound 354e (100 mg, 0.256 mmol) was reacted with 1-(5,6,7,8-tetrahydro-naphthalen-2-yl)-ethanone (0.256 mmol) in ethanol (2 mL) using 10% w/v KOH in Ethanol (506 μL, 0.64 mmol) to produce the title compound (65 mg, 60% yield).
Reaction SMILES: [F:1][C:2]1[CH:14]=[CH:13][C:5]2[C:6](=[O:12])[O:7][C:8](=O)[N:9]([CH3:10])[C:4]=2[CH:3]=1.C[O-].[Na+]>CO>[F:1][C:2]1[CH:14]=[CH:13][C:5]([C:6]([O:7][CH3:8])=[O:12])=[C:4]([NH:9][CH3:10])[CH:3]=1
Reactant: Cn1c(=O)oc(=O)c2ccc(F)cc21
Agent: C[O-]
Agent: [Na+]
Solvent: CO
Product: CNc1cc(F)ccc1C(=O)OC

Procedure:
A mixture of 7-fluoro-1-methyl-1H-3,1-benzoxazine-2,4-dione (20.0 g) and methanol (103 ml) was boiled under reflux. To the boiling mixture was added dropwise a solution of sodium methoxide (0.06 g) in methanol (50 ml.) during 19 minutes. The mixture was distilled in vacuo to remove solvent and give the product as a residue. There was thus obtained the novel compound methyl 4-fluoro-2-methylaminobenzoate as an oil which solidified on standing and was suitable for use in the next stage of synthesis. An analytical sample was prepared by distillation in vacuo followed by recrystallisation of the distillate from aqueous isopropanol. This sample had m.p. 39°-39.5°.
Reaction SMILES: C[C@@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](N=C(N)N)[C@@H](O)[C@@H]2N=C(N)N)[C@H]([O:25][C@@H:26]2[O:31][C@@H:30]([CH2:32][OH:33])[C@H:29]([OH:34])[C@@H:28]([OH:35])[C@@H:27]2NC)[C@@]1(O)C=O.[OH:41]S(O)(=O)=O.N[C@H](C(O)=O)CCCCN>>[O:33]=[CH:32][C@@H:30]([C@H:29]([C@@H:28]([C@@H:27]([CH2:26][OH:25])[OH:41])[OH:35])[OH:34])[OH:31]
Reactant: O=S(=O)(O)O
Reactant: CN[C@@H]1[C@H](O[C@H]2[C@H](O[C@H]3[C@H](O)[C@@H](O)[C@H](N=C(N)N)[C@@H](O)[C@@H]3N=C(N)N)O[C@@H](C)[C@]2(O)C=O)O[C@@H](CO)[C@H](O)[C@H]1O
Agent: NCCCC[C@H](N)C(=O)O
Product: O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO
Reaction time: 20 h

Procedure:
196ΔcadAΔldcCΔfadR/pCABD2 strain was cultured at 37° C. for 20 hours on the LB agar medium containing 20 mg/L of streptomycin sulfate. The cells on the agar medium were scraped, inoculated into 4 mL of an L-lysine production medium containing 20 mg/L of streptomycin sulfate contained in a large diameter test tube, and cultured at a culture temperature of 37° C. for 24 hours. For the main culture, the saccharified solution of Example 4 (1) prepared from starches produced by Chlorella kessleri (1.33 g/L in terms of glucose amount), and the hydrolysis reaction mixture of Example 4 (1) prepared from starches and fat or oil were used as carbon sources. As a control, the culture was performed in a medium containing glucose at the same concentration as a carbon source.
Reaction SMILES: [NH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3][CH2:2]1.[C:11]1([CH:17]=O)[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1>>[CH:17](=[C:9]1[C:10]2[N:1]=[C:2]([CH:3]=[CH:4][C:5]3[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=3)[CH:3]=[CH:4][C:5]=2[CH2:6][CH2:7][CH2:8]1)[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1
Reactant: O=Cc1ccccc1
Reactant: c1ccc2c(c1)CCCN2
Product: C(=Cc1ccc2c(n1)C(=Cc1ccccc1)CCC2)c1ccccc1
Temperature: 165 °C
Yield: 197.8 %

Procedure:
A 1 L round-bottomed flask equipped with a stirring bar, condenser and nitrogen gas inlet was charged with 2-methyl-5,6,7,8-tetrahydroquinoline (2, 80.5 g, 0.547 mol), PhCHO (222 mL, 2.19 mol), and Ac20 (206 mL, 2.19 mol). The mixture was heated under reflux at 160-170° C. under nitrogen atmosphere for 5 days. Then all volatile materials were removed by distillation under atmospheric pressure at ˜170° C. The residue was mixed with hot EtOH (200 mL) and stirred at 70° C. The stirred solution was cooled to room temperature and seeded with crystals of the product 3 to facilitate crystallization. The precipitate was collected by vacuum filtration, washed with EtOH (100 mL) and dried in vacuo to give the pale brown solid (175 g), which was impure. The crude material was chromatographed over silica gel (hexane only) to give bisbenzylidene 3 (142.4 g, 83%) as a pale yellow solid. Physical data see A. B. Khasanov's Ph. D. Thesis (2000).
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[C:7](=[O:14])[NH:8][N:9](C(=O)C)[CH:10]=1)=[O:5])[CH3:2].[CH2:15](Br)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.C(=O)([O-])[O-].[K+].[K+].Cl>CN(C)C=O>[CH2:1]([O:3][C:4]([C:6]1[C:7]([O:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[N:8][NH:9][CH:10]=1)=[O:5])[CH3:2]
Reactant: CCOC(=O)c1cn(C(C)=O)[nH]c1=O
Reactant: BrCc1ccccc1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CCOC(=O)c1c[nH]nc1OCc1ccccc1
Temperature: 40 °C
Reaction time: 20 h

Procedure:
A suspension of 1-acetyl-3-oxo-2,3-dihydro-1H-pyrazole-4-carboxilic acid ethyl ester (2.7 g, This compound was prepared in a similar manner to that described in Bioorganic & Medicinal Chemistry Letters (2002), 12 (16), 2105-2108), benzylbromide (2.5 g), potassium carbonate (2.1 g) in N,N-dimethylformamide (20 mL) was stirred at 40° C. for 20 hours. To this reaction mixture was added 1 mol/L hydrochloric acid, and this mixture was extracted with ethyl acetate. This organic layer was washed with brine, and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure. The residue was purified by column chromatography on aminopropyl silica gel (eluent: ethyl acetate/n-hexane) to give the title compound (1.6 g).
Reaction SMILES: C([O:3][CH:4](OCC)[CH2:5][O:6][CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)C.S(=O)(=O)(O)O>>[CH2:7]([O:6][CH2:5][CH:4]=[O:3])[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1
Reactant: CCOC(COCc1ccccc1)OCC
Agent: O=S(=O)(O)O
Product: O=CCOCc1ccccc1

Procedure:
In accordance with Scheme IV, benzyloxyacetaldehyde diethyl acetal is hydrolyzed with dilute sulfuric acid giving benzyloxyacetaldehyde, which is then reacted with allyl magnesium bromide to give 1-phenylmethoxy-4-penten-2-ol. This alcohol, is brominated with bromine in carbon tetrachloride or dichloromethane at -20° C. to 0° C. to give 4,5-dibromo-1-(phenylmethoxy)-2-pentanol. This dibromo alcohol, in aqueous methanol, is cyclized with calcium hydroxide in the presence of calcium bromide, to give a racemic mixture of trans and cis-4-bromo-2-[(phenylmethoxy)methyl]tetrahydrofuran, IX and X respectively, which is separated by flash column chromatography using silica gel. The trans bromide, IX, is reacted with potassium thioacetate, in a dipolar aprotic solvent, to give cis-[5-[(phenylmethoxy)methyl]-3-tetrahydrofuranyl]ethanethioate, XI. The thioacetate, XI, is reacted with iodotrimethylsilane to give cis-[5-(hydroxymethyl)-3-tetrahydrofuranyl]ethanethioate, XIII. In the same manner, the cis bromide, X, is converted to the trans-[5-(hydroxymethyl)-3-tetrahydrofuranyl]ethanethioate, XIV.
Reaction SMILES: O=O.[CH2:3]([N:10]1[CH2:14][C:13]([C:15]2[CH:20]=[CH:19][C:18]([Cl:21])=[C:17]([F:22])[CH:16]=2)=[C:12]([C:23]([OH:25])=[O:24])[CH2:11]1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.COC1C(C2C(OC)=CC=CC=2P(C2OC=CC=2)C2OC=CC=2)=C(P(C2OC=CC=2)C2OC=CC=2)C=CC=1.[H][H]>CO>[CH2:3]([N:10]1[CH2:14][C@@H:13]([C:15]2[CH:20]=[CH:19][C:18]([Cl:21])=[C:17]([F:22])[CH:16]=2)[C@@H:12]([C:23]([OH:25])=[O:24])[CH2:11]1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1
Reactant: [H][H]
Reactant: O=C(O)C1=C(c2ccc(Cl)c(F)c2)CN(Cc2ccccc2)C1
Agent: COc1cccc(P(c2ccco2)c2ccco2)c1-c1c(OC)cccc1P(c1ccco1)c1ccco1
Agent: O=O
Solvent: CO
Product: O=C(O)[C@H]1CN(Cc2ccccc2)C[C@H]1c1ccc(Cl)c(F)c1

Procedure:
An autoclave was charged under argon in a glove box (O2 content<2 ppm) with 1-Benzyl-4-(4-chloro-3-fluoro-phenyl)-2,5-dihydro-1H-pyrrole-3-carboxylic acid (1.00 g, 3.01 mmol), [Ru(OAc)2((S)-2-furyl-MeOBIPHEP)] (9.18 mg, 0.012 mmol) (2-furyl-MeOBIPHEP=(6,6′-dimethoxybiphenyl-2,2′-diyl)bis(di-2-furylphosphine) and methanol (30 mL). The asymmetric hydrogenation was run for 20 h at 30° C. under 40 bar of hydrogen. After the pressure was released, the grey suspension was evaporated to dryness to yield the crude title compound. MS m/e: 332.1 [M−H].
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][N:3]=1.C([Li])CCC.[CH2:14]([Sn:18](Cl)([CH2:23][CH2:24][CH2:25][CH3:26])[CH2:19][CH2:20][CH2:21][CH3:22])[CH2:15][CH2:16][CH3:17]>CCOCC>[CH3:8][C:5]1[CH:6]=[CH:7][C:2]([Sn:18]([CH2:19][CH2:20][CH2:21][CH3:22])([CH2:23][CH2:24][CH2:25][CH3:26])[CH2:14][CH2:15][CH2:16][CH3:17])=[N:3][CH:4]=1
Reactant: Cc1ccc(Br)nc1
Reactant: CCCC[Sn](Cl)(CCCC)CCCC
Agent: [Li]CCCC
Solvent: CCOCC
Product: CCCC[Sn](CCCC)(CCCC)c1ccc(C)cn1
Temperature: -78 °C
Reaction time: 1 h

Procedure:
A solution containing 2-bromo-5-methylpyridine (1.42 g, 8.23 mmol) in ether (15 mL) at −78° C. was treated with n-butyllithium (5.14 mL, 1.6 M in hexanes) dropwise, stirred at −78° C. for 1 hour, treated with tributyltin chloride (3.35 mL, 12.35 mmol), stirred at 0° C. for 4 hours, quenched with saturated ammonium chloride solution and partitioned between ether and water. The organic phase was washed with brine and dried over MgSO4, filtered and concentrated. The residue was purified by chromatography on neutral alumina eluting with 10% ethyl acetate in dichloromethane to give the title compound.