Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]1([C:17]([C:19]2[CH:28]=[CH:27][C:22]([C:23]([O:25]C)=[O:24])=[CH:21][CH:20]=2)=[O:18])[C:14]2[C:15]3=[C:16]4[C:11](=[CH:12][CH:13]=2)[CH:10]=[CH:9][CH:8]=[C:7]4[CH:6]=[CH:5][C:4]3=[CH:3][CH:2]=1.[OH-:29].[K+].Cl>C1C=CC=CC=1.CO>[C:1]1([C:17]([C:19]2[CH:20]=[CH:21][C:22]([C:23]([O:25][O:29][C:1]([CH3:17])([CH3:14])[CH3:2])=[O:24])=[CH:27][CH:28]=2)=[O:18])[C:14]2[C:15]3=[C:16]4[C:11](=[CH:12][CH:13]=2)[CH:10]=[CH:9][CH:8]=[C:7]4[CH:6]=[CH:5][C:4]3=[CH:3][CH:2]=1
Reactant: [OH-]
Reactant: COC(=O)c1ccc(C(=O)c2ccc3ccc4cccc5ccc2c3c45)cc1
Agent: Cl
Agent: [K+]
Solvent: CO
Solvent: c1ccccc1
Product: CC(C)(C)OOC(=O)c1ccc(C(=O)c2ccc3ccc4cccc5ccc2c3c45)cc1
Yield: 142.9 %

Procedure:
4-[(1-Pyrenyl)carbonyl]benzoic acid, methyl ester (2.55 g; 7 mmol) was dissolved in 25 ml of benzene. A solution of 354 mg (6.4 mmol) of KOH in 5 ml MeOH was added, and the mixture boiled. Precipitation of the potassium salt occurred. The mixture was extracted with water to give a yellow water layer which was acidified with dilute HCl to give a light yellow precipitate. Filtration gave 1.73 g (5 mmol) of the 4-[(pyrenyl)carbonyl]benzoic acid.
Reaction SMILES: Cl.[CH2:2]([O:4][C:5]([C@H:7]1[CH2:10][C@@H:9]([NH2:11])[CH2:8]1)=[O:6])[CH3:3].C(N(CC)CC)C.[CH3:19][C:20]1[CH:25]=[CH:24][C:23]([C:26]2[O:30][N:29]=[C:28]([C:31]3[CH:38]=[CH:37][C:34]([CH:35]=O)=[CH:33][CH:32]=3)[N:27]=2)=[CH:22][CH:21]=1.C([BH3-])#N.[Na+]>CC(O)=O.C1COCC1>[CH2:2]([O:4][C:5]([C@H:7]1[CH2:10][C@@H:9]([NH:11][CH2:35][C:34]2[CH:33]=[CH:32][C:31]([C:28]3[N:27]=[C:26]([C:23]4[CH:24]=[CH:25][C:20]([CH3:19])=[CH:21][CH:22]=4)[O:30][N:29]=3)=[CH:38][CH:37]=2)[CH2:8]1)=[O:6])[CH3:3]
Reactant: CCOC(=O)[C@H]1C[C@@H](N)C1
Reactant: Cc1ccc(-c2nc(-c3ccc(C=O)cc3)no2)cc1
Agent: Cl
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: CC(=O)O
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: CCOC(=O)[C@H]1C[C@@H](NCc2ccc(-c3noc(-c4ccc(C)cc4)n3)cc2)C1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 39495.4 %

Procedure:
A mixture of cis-3-amino-cyclobutanecarboxylic acid ethyl ester hydrochloride (50.7 mg, 0.282 mmol), triethylamine (0.058 mL, 0.423 mmol) and THF (2.5 mL) was stirred at room temperature for 30 minutes. 4-[5-(4-Methylphenyl)-1,2,4-oxadiazol-3-yl]benzaldehyde (74.5 mg, 0.282 mmol) and AcOH (0.50 mL) were added to the reaction mixture and stirred for 30 minutes. Sodium cyanoborohydride (35.4 g, 0.563 mmol) was added to the reaction mixture, stirred for 18 hours, quenched with sat. NaHCO3 and extracted with ethyl acetate. The organic phase was concentrated in vacuo. Purification by flash chromatography (silica, 2:8 EtOAc:hexanes) provided the title compound (43.6 g, 39.8% yield) as a solid.
Reaction SMILES: C(OC([N:8]1[C:19]2[C:11](=[C:12]3[C:16](=[CH:17][CH:18]=2)[NH:15][CH:14]([C:20]([N:22]2[C:33]4[C:25](=[C:26]5[C:30](=[CH:31][CH:32]=4)[NH:29][CH:28]([C:34]([O:36][CH2:37][CH2:38][C:39]4[CH:44]=[CH:43][C:42]([N+:45]([O-:47])=[O:46])=[CH:41][CH:40]=4)=[O:35])[CH2:27]5)[CH:24]=[CH:23]2)=[O:21])[CH2:13]3)[CH:10]=[CH:9]1)=O)(C)(C)C.C(=O)(O)[O-].[Na+]>FC(F)(F)C(O)=O>[CH:10]1[C:11]2=[C:12]3[C:16](=[CH:17][CH:18]=[C:19]2[NH:8][CH:9]=1)[NH:15][CH:14]([C:20]([N:22]1[C:33]2[C:25](=[C:26]4[C:30](=[CH:31][CH:32]=2)[NH:29][CH:28]([C:34]([O:36][CH2:37][CH2:38][C:39]2[CH:40]=[CH:41][C:42]([N+:45]([O-:47])=[O:46])=[CH:43][CH:44]=2)=[O:35])[CH2:27]4)[CH:24]=[CH:23]1)=[O:21])[CH2:13]3
Reactant: CC(C)(C)OC(=O)n1ccc2c3c(ccc21)NC(C(=O)n1ccc2c4c(ccc21)NC(C(=O)OCCc1ccc([N+](=O)[O-])cc1)C4)C3
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O=C(O)C(F)(F)F
Product: O=C(OCCc1ccc([N+](=O)[O-])cc1)C1Cc2c(ccc3c2ccn3C(=O)C2Cc3c(ccc4[nH]ccc34)N2)N1

Procedure:
5 grams of 16 are placed in a flask. 100 mL of trifluoroacetic acid is added, and the mixture is stirred. After an hour, the acid is evaporated on a rotary evaporator and 100 mL saturated sodium bicarbonate solution and 100 mL of water are added. The mixture is agitated or sonicated for ˜½ hours, then filtered and washed with water and then methanol, and dried in vacuo. The material may be recrystallized. It is dissolved in a minimum amount of warm DMF, and then approximately a threefold portion of methanol is added and the solution is sonicated a few minutes. A cream to brown material crystallizes out. This is washed with methanol, and dried in vacua The yield approaches theoretical values. 1H NMR (DMSO-d6) δ 11.96 (s, NH, 1H), 11.71 (s, NH, 1H), 8.30 (br s, aromatic proton, 1H), 8.27 (br s, aromatic proton, 1H), 8.19 (d, aromatic protons, J=8.5 Hz, 2H), 7.66 (d, aromatic protons, J=8.3 Hz, 2H), 7.34 (m, aromatic protons, 2H), 7.08 (s, aromatic proton, 1H), 7.03 (s, aromatic proton, 1H), 4.60 (m, aliphatic protons, 4H), 3.68 (t, J=8 Hz, aliphatic protons, 2H), 3.40 (t, J=8 Hz, aliphatic protons, 2H), 3.24 (m, aliphatic protons, 4H). Combustion Analysis: Found: C, 63.55%; H, 4.42%; N, 11.95%. Calculated, for ½ mole sodium bicarbonate contaminant: C, 63.43%; H, 4.45%; N, 12.13%.
Reaction SMILES: [CH3:1][O:2][C:3]1[C:8]2[CH:9]([NH:12][C:13]3[O:14][CH2:15][C:16]4[CH:22]=[C:21]([NH2:23])[CH:20]=[CH:19][C:17]=4[N:18]=3)[CH2:10][O:11][C:7]=2[CH:6]=[CH:5][CH:4]=1.[Cl:24][CH2:25][C:26](Cl)=[O:27]>>[Cl:24][CH2:25][C:26]([NH:23][C:21]1[CH:20]=[CH:19][C:17]2[N:18]=[C:13]([NH:12][CH:9]3[C:8]4[C:3]([O:2][CH3:1])=[CH:4][CH:5]=[CH:6][C:7]=4[O:11][CH2:10]3)[O:14][CH2:15][C:16]=2[CH:22]=1)=[O:27]
Reactant: O=C(Cl)CCl
Reactant: COc1cccc2c1C(NC1=Nc3ccc(N)cc3CO1)CO2
Product: COc1cccc2c1C(NC1=Nc3ccc(NC(=O)CCl)cc3CO1)CO2
Yield: 95.1 %

Procedure:
Prepared from rac-N2-(4-methoxy-2,3-dihydro-benzofuran-3-yl)-4H-benzo[d][1,3]oxazine-2,6-diamine (Example 6) (320 mg, 1.03 mmol) and chloroacetyl chloride (85.8 ul, 1.08 mmol) according to the procedure described for Example 3 step A. Obtained the title compound as an off-white solid (380 mg, 95%), MS (ISP) m/e=388.2 [(M+H)+] and 390 [(M+2+H)+].
Reaction SMILES: C([O:3][C:4]([C:6]1[CH:10]=[C:9]([CH2:11][CH2:12][CH2:13][CH3:14])[NH:8][N:7]=1)=[O:5])C.[OH-].[Na+].Cl>O1CCOCC1>[CH2:11]([C:9]1[NH:8][N:7]=[C:6]([C:4]([OH:5])=[O:3])[CH:10]=1)[CH2:12][CH2:13][CH3:14]
Reactant: CCCCc1cc(C(=O)OCC)n[nH]1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: C1COCCO1
Product: CCCCc1cc(C(=O)O)n[nH]1
Temperature: 55 °C
Reaction time: 2 h
Yield: 110.1 %

Procedure:
5-Butyl-1H-pyrazol-3-carboxylic acid ethyl ester (24 g, 122 mmol) and 1M NaOH solution (305 ml, 306 mmol) were dissolved in 1,4-dioxan (300 ml), the reaction was heated to 55° C. under nitrogen and stirred for 2 hours. The reaction mixture was cooled, adjusted to pH 2 using concentrated hydrochloric acid and the solvent was removed under reduced pressure. The residual solid was dissolved in ethyl acetate (300 ml) and washed with water (300 ml). The aqueous phase was removed, extracted with ethyl acetate (300 ml) and the combined organic extracts were dried over MgSO4. The solvent was removed under reduced pressure and the residue was azeotroped with dichloromethane (2×50 ml) to give 5-butyl-1H-pyrazol-3-carboxylic acid (22.6 g) as a white solid. 1H NMR (400 MHz, DMSO-D6): δ=12.50-13.00 (2H, brs), 6.41 (1H, s), 2.47-2.57 (2H, t), 1.46-1.56 (2H, quin), 1.19-1.29 (2H, sext), 1.15-1.19 (3H, t) ppm. LRMS (electrospray): m/z [M−H]+ 167. Anal. Found C, 57.01; H, 7.23; N, 16.50. C8H12N2O2 requires C, 57.13; H, 7.19; N, 16.66%.
Reaction SMILES: Br[C:2]1[CH:11]=[C:10]2[C:5]([C:6]([C:13]3[CH:18]=[CH:17][C:16]([C:19]([F:22])([F:21])[F:20])=[CH:15][C:14]=3[O:23][CH3:24])=[N:7][NH:8][C:9]2=[O:12])=[CH:4][CH:3]=1.C(N(CC)C(C)C)(C)C.[SH:34][CH2:35][C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1>O1CCOCC1.[Pd].[Pd].C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>[CH2:35]([S:34][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([C:13]3[CH:18]=[CH:17][C:16]([C:19]([F:22])([F:21])[F:20])=[CH:15][C:14]=3[O:23][CH3:24])=[N:7][NH:8][C:9]2=[O:12])=[CH:4][CH:3]=1)[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1
Reactant: COc1cc(C(F)(F)F)ccc1-c1n[nH]c(=O)c2cc(Br)ccc12
Reactant: SCc1ccccc1
Agent: [Pd]
Agent: CC1(C)c2cccc(P(c3ccccc3)c3ccccc3)c2Oc2c(P(c3ccccc3)c3ccccc3)cccc21
Agent: O=C(C=Cc1ccccc1)C=Cc1ccccc1
Solvent: C1COCCO1
Solvent: CCN(C(C)C)C(C)C
Product: COc1cc(C(F)(F)F)ccc1-c1n[nH]c(=O)c2cc(SCc3ccccc3)ccc12
Temperature: 80 °C
Yield: 60.1 %

Procedure:
To a pressure tube containing a solution of 7-bromo-4-(2-methoxy-4-(trifluoromethyl)phenyl)phthalazin-1(2H)-one (1.14 g, 2.86 mmol) and N,N-diisopropylethylamine (0.99 mL, 5.71 mmol) in 1,4-dioxane (20 mL) was added XantPhos (0.083 g, 0.143 mmol) and tris(dibenzylideneacetone) dipalladium (0) (0.065 g, 0.071 mmol) followed by (mercaptomethyl)benzene (0.352 mL, 3.00 mmol). The reaction tube was purged with nitrogen. The tube was sealed and heated at 80° C. for 30 min. After cooling to RT, the reaction was filtered over a pad of diatomaceous earth, rinsing well with EtOAc. The filtrate was concentrated. The crude material was absorbed onto a plug of silica gel and purified by chromatography through a silica gel column (120 g), eluting with a gradient of 0% to 50% EtOAc in heptane, to provide 7-(benzylthio)-4-(2-methoxy-4-(trifluoromethyl)phenyl)phthalazin-1(2H)-one (0.76 g, 60% yield) as a yellow solid. 1H NMR (500 MHz, CDCl3) δ ppm 3.77 (s, 3H), 4.44 (s, 2H), 7.15 (d, J=8.55 Hz, 1H), 7.21-7.28 (m, 1H), 7.32 (t, J=7.43 Hz, 2H), 7.40-7.50 (m, 4H), 7.57 (d, J=7.69 Hz, 1H), 7.72 (dd, J=8.60, 2.08 Hz, 1H), 8.11 (d, J=1.92 Hz, 1H), 12.85 (s, 1H). m/z (ESI) 443.0 (M+H)+.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:33])[C:5](=[CH:9][C:10]1[C:15]([CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH3:30])=[CH:14][CH:13]=[CH:12][C:11]=1[O:31][CH3:32])[C:6](=O)[CH3:7])[CH3:2].Cl.[CH3:35][O:36][C:37]1[CH:42]=[CH:41][C:40]([CH2:43][S:44][C:45](=[NH:47])[NH2:46])=[CH:39][CH:38]=1.C([O-])(=O)C.[Na+]>CN(C)C=O.CCOCC>[CH2:1]([O:3][C:4]([C:5]1[CH:9]([C:10]2[C:15]([CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH3:30])=[CH:14][CH:13]=[CH:12][C:11]=2[O:31][CH3:32])[N:46]=[C:45]([S:44][CH2:43][C:40]2[CH:41]=[CH:42][C:37]([O:36][CH3:35])=[CH:38][CH:39]=2)[NH:47][C:6]=1[CH3:7])=[O:33])[CH3:2]
Reactant: COc1ccc(CSC(=N)N)cc1
Reactant: CCCCCCCCCCCCCCCc1cccc(OC)c1C=C(C(C)=O)C(=O)OCC
Agent: CC(=O)[O-]
Agent: Cl
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: CCOCC
Product: CCCCCCCCCCCCCCCc1cccc(OC)c1C1N=C(SCc2ccc(OC)cc2)NC(C)=C1C(=O)OCC
Temperature: 70 °C

Procedure:
The reaction mixture containing 2-[[2-methoxy-6-pentadecyl phenyl]methylene]-3-oxobutanoic acid ethyl ester (3 g, 6.6 mmol), 2-((4-methoxyphenyl)methyl)-2-thiopseudourea hydrochloride (1.2 g, 6.6 mmol), and sodium acetate (0.6 g, 7 mmol) in dimethylformamide (30 mL) was heated at 70° C. for 4 h. The reaction was cooled to room temperature, diluted with ether, and filtered. The filtrate was washed with water, sodium bicarbonate, and brine and dried over anhydrous sodium sulfate. The solvent was evaporated, and the compound was obtained as brown viscous liquid.
Reaction SMILES: [Cl:1][C:2]1[CH:8]=[CH:7][CH:6]=[C:5]([Cl:9])[C:3]=1[NH2:4].Cl[S:11]([C:14]1[N:22]=[C:21]2[N:16]([C:17]([O:24][CH3:25])=[N:18][CH:19]=[C:20]2[Br:23])[N:15]=1)(=[O:13])=[O:12].N1C=CC=CC=1.CS(C)=O>CCCCCC.C(#N)C>[Cl:1][C:2]1[CH:8]=[CH:7][CH:6]=[C:5]([Cl:9])[C:3]=1[NH:4][S:11]([C:14]1[N:22]=[C:21]2[N:16]([C:17]([O:24][CH3:25])=[N:18][CH:19]=[C:20]2[Br:23])[N:15]=1)(=[O:12])=[O:13]
Reactant: Nc1c(Cl)cccc1Cl
Reactant: COc1ncc(Br)c2nc(S(=O)(=O)Cl)nn12
Solvent: CCCCCC
Solvent: CS(C)=O
Solvent: c1ccncc1
Product: COc1ncc(Br)c2nc(S(=O)(=O)Nc3c(Cl)cccc3Cl)nn12
Temperature: 0 °C
Yield: 26.3 %

Procedure:
2,6-Dichloroaniline (1.0 g, 6.2 mmol), 2-chlorosulfonyl-8-bromo-5-methoxy-1,2,4-triazolo[1,5-c]-pyrimidine (1.0 g, 3.1 mmol), and 20 mL of dry acetonitrile were placed in a 100 mL flask equipped with a gas inlet adapter and a magnetic stirring bar. The solution was cooled to 0° C. Pyridine (0.50 mL, 6.2 mmol) and dimethyl sulfoxide (0.06 mL, 0.8 mmol) were added with stirring under nitrogen and the mixture was allowed to react for 1 hr at 0° C. The volatiles were then removed by evaporation under reduced pressure and the residue was dissolved in 150 mL of methylene chloride. The solution obtained was extracted 2 times with 100 mL of 1N HCl and once with 100 mL of water, dried over MgSO4, filtered, and concentrated by evaporation under reduced pressure to obtain a yellow solid. This solid was stirred with 200 mL of hexane and filtered to give 0.37 g (26 percent yield) of the title compound as a yellow solid melting at 196°-198° C. (d).
Reaction SMILES: [C:1]([C:4]1[CH:5]2[NH:12][CH:8]([CH2:9][C:10]=1[CH3:11])[CH2:7][CH2:6]2)(=[O:3])[CH3:2].C=O.[C:15]([BH3-])#N.[Na+].[OH-].[NH4+]>C(#N)C.C(O)(=O)C>[C:1]([C:4]1[CH:5]2[N:12]([CH3:15])[CH:8]([CH2:9][C:10]=1[CH3:11])[CH2:7][CH2:6]2)(=[O:3])[CH3:2]
Reactant: CC(=O)C1=C(C)CC2CCC1N2
Reactant: [BH3-]C#N
Agent: C=O
Agent: [NH4+]
Agent: [Na+]
Solvent: CC#N
Solvent: CC(=O)O
Product: CC(=O)C1=C(C)CC2CCC1N2C
Reaction time: 0.25 h

Procedure:
To a stirred mixture of 2-acetyl-3-methyl-8-azabicyclo [3.2.1]oct-2-ene (1,2083 g, 0.0073 mol) and aqueous formaldehyde (2.7 ml, 0.036 mol, 37 percent) in 15 ml acetonitrile was added sodium cyanoborohydride (0.7352 g, 0.0117 mol). After stirring for 15 minutes, the reaction was made acidic by addition of 15 ml glacial acetic acid over a 45 minute period. The solution was made basic by the addition of an aqueous solution of ammonium hydroxide. The basic solution was extracted 3 times with ethyl acetate, the organic layer was then dried using sodium sulfate and concentrated under reduced pressure. Purification on silica gel column chromatography using 9 parts diethyl ether and 1 part triethylamine followed by bulb-to-bulb distillation (80° C. 0.4 mmHg)) to give 2-acetyl-3,8-dimethyl-8-azabicyclo[3.2.1]oct-2-ene as a brownish liquid.
Reaction SMILES: C([C:4]1[CH:5]=[CH:6][C:7]2[O:11][C@:10]([CH2:16][CH3:17])([C:12]([O:14][CH3:15])=[O:13])[CH2:9][C:8]=2[CH:18]=1)(=O)C.ClC1C=CC=C(C(OO)=[O:27])C=1.C([O-])(O)=O.[Na+]>ClCCl>[CH3:15][O:14][C:12]([C:10]1([CH2:16][CH3:17])[CH2:9][C:8]2[CH:18]=[C:4]([OH:27])[CH:5]=[CH:6][C:7]=2[O:11]1)=[O:13]
Reactant: CC[C@@]1(C(=O)OC)Cc2cc(C(C)=O)ccc2O1
Reactant: O=C(OO)c1cccc(Cl)c1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Product: CCC1(C(=O)OC)Cc2cc(O)ccc2O1

Procedure:
Methyl (2S)-5-acetyl-2-ethyl-2,3-dihydro-benzofuran-2-carboxylate (3.8 g, ca. 15 mmol), m-chloroperbenzoic acid (70%, 7.7 g, 30 mmol) and NaHCO3 (3.8 g, 45 mmol) in dichloromethane (150 mL) was stirred under reflux for 2 hrs. The reaction mixture was washed successively with saturated aqueous sodium sulfite (100 mL) and aqueous NaHCO3 (2×100 mL). After removal of solvent, the residue was dissolved in methanol (100 mL) and treated with aqueous KOH (5 N, 3 mL) at 0° C. for 5 min. The reaction was neutralized with excess solid sodium bicarbonate, filtered and concentrated. The residue was purified by chromatography on silica gel eluting with 8:2 hexane:ethyl acetate to give the title compound.
Reaction SMILES: [Cl-].[F:2][C:3]1[CH:25]=[CH:24][C:6]([C:7]([CH2:9][CH2:10][CH2:11][N+:12]2[CH:17]=[CH:16][C:15]([C:18]3[S:19][CH:20]=[C:21]([CH3:23])[N:22]=3)=[CH:14][CH:13]=2)=[O:8])=[CH:5][CH:4]=1.CO.[BH4-].[Na+]>O>[F:2][C:3]1[CH:25]=[CH:24][C:6]([CH:7]([OH:8])[CH2:9][CH2:10][CH2:11][N:12]2[CH2:13][CH:14]=[C:15]([C:18]3[S:19][CH:20]=[C:21]([CH3:23])[N:22]=3)[CH2:16][CH2:17]2)=[CH:5][CH:4]=1
Reactant: Cc1csc(-c2cc[n+](CCCC(=O)c3ccc(F)cc3)cc2)n1
Agent: [BH4-]
Agent: [Cl-]
Agent: [Na+]
Solvent: CO
Solvent: O
Product: Cc1csc(C2=CCN(CCCC(O)c3ccc(F)cc3)CC2)n1

Procedure:
To a 0.4 g. portion of 1-(3-p-fluorobenzoylpropyl)-4-(4-methyl-2-thiazolyl)pyridinium chloride, prepared as described in Example 4, in 20 ml. of methanol is added portionwise with stirring 0.4 g. of sodium borohydride. The mixture is stirred for 2 hours and then poured into water causing the formation of a white solid which is separated and recrystallized from acetone and water, m.p. 89°-90.5°C.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[OH:9].[Na+].[I-:11].[OH-].[Na+].[O-]Cl.[Na+].[O-]S([O-])(=S)=O.[Na+].[Na+].Cl>CO>[I:11][C:4]1[CH:5]=[C:6]([Cl:8])[CH:7]=[C:2]([CH3:1])[C:3]=1[OH:9]
Reactant: [I-]
Reactant: Cc1cc(Cl)ccc1O
Agent: Cl
Agent: O=S([O-])([O-])=S
Agent: [Na+]
Solvent: CO
Product: Cc1cc(Cl)cc(I)c1O
Temperature: 0 °C

Procedure:
To a stirred solution of 5.00 g (35.00 mmol) of 2-methyl-4-chlorophenol (available from Aldrich Chemical Company) in 100 mL of methanol at 0° C., add 6.83 g (45.57 mmol) of NaI and 1.40 g (35.00 mmol) of NaOH. To the resulting mixture add 65 mL of 5% aqueous NaOCl solution (commercial bleach) over one hour period. The resulting slurry is stirred for one more hour at 0° C. After the addition of 20 mL of 10% Na2S2O3 solution, the reaction mixture is acidified by dilute hydrochloric acid. The mixture is extracted with methylene chloride. The organic layer is washed with brine and dried over anhydrous magnesium sulfate. Removal of the solvent followed by purification by recrystallization from hexanes gives 3.80 g (40.5%) of (P11) as white solid.
Reaction SMILES: [C:1]([C:5]1[CH:10]=[CH:9][C:8]([S:11]([NH:14][C:15]2[N:20]=[C:19]([C:21]3[N:26]=[CH:25][CH:24]=[CH:23][N:22]=3)[N:18]=[C:17]([O:27][CH2:28][CH2:29][OH:30])[C:16]=2[O:31][C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=2[O:38][CH3:39])(=[O:13])=[O:12])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].CS(C)=[O:42]>>[OH:30][CH2:29][CH2:28][O:27][C:17]1[C:16]([O:31][C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=2[O:38][CH3:39])=[C:15]([NH:14][S:11]([C:8]2[CH:7]=[CH:6][C:5]([C:1]([CH3:4])([CH3:2])[CH2:3][OH:42])=[CH:10][CH:9]=2)(=[O:12])=[O:13])[N:20]=[C:19]([C:21]2[N:22]=[CH:23][CH:24]=[CH:25][N:26]=2)[N:18]=1
Reactant: COc1ccccc1Oc1c(NS(=O)(=O)c2ccc(C(C)(C)C)cc2)nc(-c2ncccn2)nc1OCCO
Reactant: CS(C)=O
Product: COc1ccccc1Oc1c(NS(=O)(=O)c2ccc(C(C)(C)CO)cc2)nc(-c2ncccn2)nc1OCCO
Reaction time: 48 h

Procedure:
Streptomyces rimosus subsp. rimosus ATCC10970 maintained on a quarter strength ATCC172 agar slope was inoculated as a loopful of spores into a 300 ml Erlenmeyer flask containing 50 ml of AS-7H inoculum medium. This was allowed to incubate for 2 days at 28° C., 200 rpm on an Infors Multitron™ Shaker with 1″ throw. 2 mls of this inoculum medium was then transferred to one 300 ml Erlenmeyer flask containing 50 ml of AP-5H production medium and incubated under the same conditions for a further 24 hours. At this point 1 mg of 4-tert butyl-N-[4-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)-2-(2-pyrimidinyl)pyrimidin-6-yl]benzenesulphonamide (CA 2071193) dissolved in 0.5 ml of dimethylsulfoxide was added to each of the flasks and the fermentation allowed to continue under the same conditions for a further 24 hours. The flask was then extracted with 200 mls of ethyl acetate and the combined ethyl acetate solubles concentrated to dryness to give a gum solid.
Reaction SMILES: [CH3:1][NH:2][CH2:3][CH2:4][OH:5].Cl[C:7]1[CH:12]=[CH:11][C:10]([C:13]([F:16])([F:15])[F:14])=[CH:9][C:8]=1[N+:17]([O-:19])=[O:18].[Cl-].[NH4+]>CN(C)C=O>[CH3:1][N:2]([C:7]1[CH:12]=[CH:11][C:10]([C:13]([F:16])([F:14])[F:15])=[CH:9][C:8]=1[N+:17]([O-:19])=[O:18])[CH2:3][CH2:4][OH:5]
Reactant: O=[N+]([O-])c1cc(C(F)(F)F)ccc1Cl
Reactant: CNCCO
Agent: [Cl-]
Agent: [NH4+]
Solvent: CN(C)C=O
Product: CN(CCO)c1ccc(C(F)(F)F)cc1[N+](=O)[O-]
Temperature: 25 °C
Reaction time: 1 h

Procedure:
2-(Methylamino)ethanol (17.3 g, 231 mmol) was added dropwise to a solution of 4-chloro-3-nitrobenzotrifluoride (26.0 g, 115 mmol) in N,N-dimethylformamide (100 ml) at 0° C. After the reaction temperature was raised to room temperature, the reaction mixture was stirred at room temperature for 1 hour, poured into a saturated aqueous ammonium chloride solution, and then extracted twice with ethyl acetate. The organic layer was washed with a 5% aqueous sodium chloride solution and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure and the resulting residue was purified by a silica gel column chromatography (eluent: chloroform/methanol = 97/3) to obtain an oil of 4-[N-methyl-N-(2-hydroxy-ethyl) amino]-3-nitrobenzotrifluoride.
Reaction SMILES: COC[O:4][C:5]1[C:6]([CH3:14])=[C:7](B(O)O)[CH:8]=[CH:9][CH:10]=1.Br[C:16]1[CH:25]=[CH:24][C:19]([C:20]([O:22][CH3:23])=[O:21])=[CH:18][C:17]=1[CH3:26].C(=O)([O-])[O-].[K+].[K+].S(=O)(=O)(O)O>COCCOC.CO.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C(OCC)C.O>[OH:4][C:5]1[C:6]([CH3:14])=[C:7]([C:16]2[CH:25]=[CH:24][C:19]([C:20]([O:22][CH3:23])=[O:21])=[CH:18][C:17]=2[CH3:26])[CH:8]=[CH:9][CH:10]=1
Reactant: COCOc1cccc(B(O)O)c1C
Reactant: COC(=O)c1ccc(Br)c(C)c1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: O=S(=O)(O)O
Solvent: O
Solvent: COCCOC
Solvent: CCOCC
Product: COC(=O)c1ccc(-c2cccc(O)c2C)c(C)c1
Temperature: 80 °C
Reaction time: 24 h

Procedure:
1.03 g (5.2 mmol) of 3-methoxymethoxy-2-methylbenzene-1-boronic acid, 1 g (4.4 mmol) of methyl 4-bromo-3-methylbenzoate and 4.4 mL of 2.0M potassium carbonate solution are dissolved in 20 mL of ethylene glycol dimethyl ether. The mixture is degassed using a stream of nitrogen for 10 minutes, and 250 mg (0.22 mmol) of tetrakis(triphenylphosphine)palladium are then added and the medium is stirred for 24 hours at 80° C. After cooling and the usual treatment, the residue obtained is dissolved in 30 mL of methanol and 0.5 mL of sulphuric acid is added. The medium is stirred at room temperature for 6 hours and then poured into an ethyl ether/water mixture. After extraction with ether, the residue is purified by chromatography on silica gel (eluent: 9 heptane/1 ethyl acetate). The desired product is obtained in the form of a thick, colourless oil (m=890 mg; Y=79%).
Reaction SMILES: [CH2:1]([O:8][C@H:9]1[C@H:16]([O:17][CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[C@@H:15]([CH2:25][O:26][CH2:27][C:28]2[CH:33]=[CH:32][C:31]([Cl:34])=[CH:30][CH:29]=2)[O:14][C@@H:11]([O:12][CH3:13])[C@@H:10]1[OH:35])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:36](OC(=O)C)(=[O:38])[CH3:37]>C(Cl)Cl.CN(C1C=CN=CC=1)C>[C:36]([O:35][C@@H:10]1[C@@H:9]([O:8][CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[C@H:16]([O:17][CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[C@@H:15]([CH2:25][O:26][CH2:27][C:28]2[CH:29]=[CH:30][C:31]([Cl:34])=[CH:32][CH:33]=2)[O:14][C@H:11]1[O:12][CH3:13])(=[O:38])[CH3:37]
Reactant: CO[C@@H]1O[C@H](COCc2ccc(Cl)cc2)[C@@H](OCc2ccccc2)[C@H](OCc2ccccc2)[C@H]1O
Reactant: CC(=O)OC(C)=O
Agent: CN(C)c1ccncc1
Solvent: ClCCl
Product: CO[C@@H]1O[C@H](COCc2ccc(Cl)cc2)[C@@H](OCc2ccccc2)[C@H](OCc2ccccc2)[C@H]1OC(C)=O
Temperature: 25 °C
Reaction time: 1 h
Yield: 88.7 %

Procedure:
Methyl 3,4-di-O-benzyl-6-O-(4-chlorobenzyl)-β-D-glucopyranoside (0.233 g, 0.467 mmol) was dissolved in 5 mL CH2Cl2. Acetic anhydride (53 μL, 0.560 mmol) and DMAP (0.114 g, 0.934 mmol) were added and the reaction mixture was stirred at room temperature for 1 h. The solution was filtered through silica, eluted with EtOAc and concentrated. Purification by flash column chromatography on silica gel (30% EtOAc/Hexanes) gave 224 mg (89%) of 20 as a colorless oil. [α]24D: −0.5° (c 0.79, CH2Cl2); IR (thin film) 2867, 1747, 1233, 1087, 1060 cm−1; 1H-NMR (CDCl3) δ 7.35-7.27 (m, 12H), 7.20-7.18 (m, 2H), 5.00 (dd, J=7.9, 8.8 Hz, 1H), 4.81 (d, J=10.7 Hz, 1H), 4.80 (d, J=11.6 Hz, 1H), 4.68 (d, J=11.3 Hz, 1H), 4.59 (d, J=12.5 Hz, 1H), 4.56 (d, J=10.7 Hz, 1H), 4.52 (d, J=12.2 Hz, 1H), 4.30 (d, J=7.9 Hz, 1H), 3.74-3.67 (m, 4H), 3.51-3.37 (m, 4H), 1.99 (s, 3H); 13C-NMR (CDCl3) δ 169.8, 138.2, 138.0, 136.8, 129.2, 128.7, 128.6, 128.2, 128.1, 128.0, 102.0, 83.2, 78.1, 75.3, 75.2, 73.2, 72.9, 68.9, 56.9, 21.2; FAB MS m/z (M+Na)+: calcd 563.1813, obsd 563.1817.