Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl[C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[N:5]=[C:4]([C:12]2[CH:13]=[N:14][CH:15]=[CH:16][CH:17]=2)[N:3]=1.[CH3:18][O:19][C:20]1[CH:21]=[CH:22][C:23]([CH3:27])=[C:24]([CH:26]=1)[NH2:25]>>[CH3:18][O:19][C:20]1[CH:21]=[CH:22][C:23]([CH3:27])=[C:24]([CH:26]=1)[NH:25][C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[N:5]=[C:4]([C:12]2[CH:13]=[N:14][CH:15]=[CH:16][CH:17]=2)[N:3]=1
Reactant: FC(F)(F)c1cc(Cl)nc(-c2cccnc2)n1
Reactant: COc1ccc(C)c(N)c1
Product: COc1ccc(C)c(Nc2cc(C(F)(F)F)nc(-c3cccnc3)n2)c1

Procedure:
The title compound was prepared from a mixture of 4-chloro-2-(3-pyridinyl)-6-(trifluoromethyl)pyrimidine (50 mg, 0.193 mmol) and 5-methoxy-2-methylaniline (26 mg, 0.193 mmol) similar to Example 13 and isolated as a tan solid (8 mg, 12%). 1H NMR (CDCl3): 9.72 (d, J=0.6 Hz, 1H), 8.74–8.68 (m, 2H), 7.70 (s, 1H), 7.44–7.40 (m, 1H), 7.27 (s, 1H), 7.25 (s, 1H), 6.99 (s, 1H), 6.85 (dd, J=2.7, 8.7 Hz, 1H), 6.64 (s, 1H), 3.83 (s, 3H), 2.24 (s, 3H).
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[C:6]([CH3:8])[NH:5][C:4](=[O:9])[C:3]=1[CH2:10][NH:11][C:12]([C:14]1[CH:19]=[C:18]([C:20]2[CH2:21][C:22]([CH3:29])([CH3:28])[NH:23][C:24]([CH3:27])([CH3:26])[CH:25]=2)[N:17]=[C:16]2[N:30]([CH:33]3[CH2:38][CH2:37][N:36](C(OC(C)(C)C)=O)[CH2:35][CH2:34]3)[N:31]=[CH:32][C:15]=12)=[O:13]>C(Cl)Cl.C(O)(C(F)(F)F)=O>[CH3:1][C:2]1[CH:7]=[C:6]([CH3:8])[NH:5][C:4](=[O:9])[C:3]=1[CH2:10][NH:11][C:12]([C:14]1[C:15]2[CH:32]=[N:31][N:30]([CH:33]3[CH2:38][CH2:37][NH:36][CH2:35][CH2:34]3)[C:16]=2[N:17]=[C:18]([C:20]2[CH2:21][C:22]([CH3:28])([CH3:29])[NH:23][C:24]([CH3:26])([CH3:27])[CH:25]=2)[CH:19]=1)=[O:13]
Reactant: Cc1cc(C)c(CNC(=O)c2cc(C3=CC(C)(C)NC(C)(C)C3)nc3c2cnn3C2CCN(C(=O)OC(C)(C)C)CC2)c(=O)[nH]1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: Cc1cc(C)c(CNC(=O)c2cc(C3=CC(C)(C)NC(C)(C)C3)nc3c2cnn3C2CCNCC2)c(=O)[nH]1
Temperature: 25 °C
Reaction time: 1 h
Yield: 96.6 %

Procedure:
To a stirred solution of tert-butyl 4-(4-(((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)carbamoyl)-6-(2,2,6,6-tetramethyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrazolo[3,4-b]pyridin-1-yl)piperidine-1-carboxylate (0.5 g, 0.8 mmol) in DCM (10 mL), TFA (0.3 mL) was added at 0° C. and reaction stirred at room temperature for 1 h. After completion of reaction, solvent was removed under reduced pressure and residue neutralized with saturated NaHCO3 solution Extraction was carried out using DCM; the combined organic layers were washed with water, brine and dried over anhydrous Na2SO4; filtered and concentrated under reduced pressure. Finally the residue was washed with diethyl ether to provide the desired compound (0.4 g, 95.7%).
Reaction SMILES: [CH3:1][O:2][C:3]1[C:12]2[NH:11][C:10]3=[CH:13][C:14]([C:16]([OH:18])=O)=[N:15][N:9]3[C:8](=[O:19])[C:7]=2[CH:6]=[C:5]([O:20][CH3:21])[CH:4]=1.C(N1C=CN=C1)(N1C=CN=C1)=O.O.[NH2:35][C:36]1[NH:40][N:39]=[N:38][N:37]=1>CN(C=O)C>[CH3:1][O:2][C:3]1[C:12]2[NH:11][C:10]3=[CH:13][C:14]([C:16]([NH:35][C:36]4[NH:40][N:39]=[N:38][N:37]=4)=[O:18])=[N:15][N:9]3[C:8](=[O:19])[C:7]=2[CH:6]=[C:5]([O:20][CH3:21])[CH:4]=1
Reactant: Nc1nnn[nH]1
Reactant: COc1cc(OC)c2[nH]c3cc(C(=O)O)nn3c(=O)c2c1
Agent: O=C(n1ccnc1)n1ccnc1
Solvent: O
Solvent: CN(C)C=O
Product: COc1cc(OC)c2[nH]c3cc(C(=O)Nc4nnn[nH]4)nn3c(=O)c2c1
Yield: 43.8 %

Procedure:
From 4,9-dihydro-5,7-dimethoxy-9-oxo-pyrazolo-[5,1-b]quinazoline-2-carboxylic acid (1.54 g; 5 mmole), DMF (300 ml), 1,1'-carbonyldiimidazole (1.8 g; 11 mmole) and 5-amino-1H-tetrazole, monohydrate (0.52 g; 5 mmole), following the procedure of Example 3, there is obtained 4,9-dihydro-5,7-dimethoxy-9-oxo-N-1H-tetrazol-5-yl-pyrazolo-[5,1-b]quinazoline-2-carboxamide (0.78 g); mp 338°-342° (d).
Reaction SMILES: [CH:1]1([CH2:4][CH2:5][C:6]([N:8]2[C@@H:12]([CH2:13][C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[CH2:11][O:10][C:9]2=[O:20])=[O:7])[CH2:3][CH2:2]1.C([N-]C(C)C)(C)C.[Li+].[C:29](Cl)(=[O:31])[CH3:30]>C1COCC1>[CH:1]1([CH2:4][C@H:5]([C:29](=[O:31])[CH3:30])[C:6]([N:8]2[C@@H:12]([CH2:13][C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[CH2:11][O:10][C:9]2=[O:20])=[O:7])[CH2:2][CH2:3]1
Reactant: CC(=O)Cl
Reactant: O=C(CCC1CC1)N1C(=O)OC[C@@H]1Cc1ccccc1
Agent: CC(C)[N-]C(C)C
Agent: [Li+]
Solvent: C1CCOC1
Product: CC(=O)[C@@H](CC1CC1)C(=O)N1C(=O)OC[C@@H]1Cc1ccccc1
Temperature: 25 °C
Reaction time: 0.75 h

Procedure:
Under a nitrogen atmosphere, a solution of the (4S)-3-(3-cyclopropyl-1-oxopropyl)-4-(phenylmethyl)-2-oxazolidinone (6.01 g, 22.0 mmol, described in example 3) in anhydrous THF (10 mL) was added to a cold (-78°) stirred solution of lithium diisopropylamide (963 mg, 9.0 mmol) in anhydrous THF (10 mL). The mixture was stirred at -78° for 45 min and then transferred by cannula into a cold (-78°) solution of acetyl chloride (0.86 mL, 12 mmol) in anhydrous THF (5 mL). The resultant mixture was stirred for 15 min at -78° C., then quenched with a saturated aqueous solution of NH4Cl, allowed to warm to room temperature (20°-22°) and diluted with Et2O. The layers were separated and the aqueous phase was extracted with Et2O.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]2[C:12](=[CH:13][CH:14]=1)[NH:11][C:10]1[C:9]([O:15][CH2:16][CH2:17][N:18]([CH3:20])[CH3:19])=[C:8]3[NH:21][C:22]4[CH:23]=[CH:24][C:25]([F:28])=[CH:26][C:27]=4[C:7]3=[CH:6][C:5]2=1.[Br:29]Br.C(Cl)Cl>CN(C=O)C>[Br:29][C:6]1[C:7]2[C:27]3[C:22](=[CH:23][CH:24]=[C:25]([F:28])[CH:26]=3)[NH:21][C:8]=2[C:9]([O:15][CH2:16][CH2:17][N:18]([CH3:19])[CH3:20])=[C:10]2[NH:11][C:12]3[CH:13]=[CH:14][C:2]([F:1])=[CH:3][C:4]=3[C:5]=12
Reactant: CN(C)CCOc1c2[nH]c3ccc(F)cc3c2cc2c1[nH]c1ccc(F)cc12
Reactant: BrBr
Solvent: ClCCl
Solvent: CN(C)C=O
Product: CN(C)CCOc1c2[nH]c3ccc(F)cc3c2c(Br)c2c1[nH]c1ccc(F)cc12
Temperature: 25 °C
Reaction time: 2 h
Yield: 73 %

Procedure:
To a solution of 2-(2,10-difluoro-5,7-dihydroindolo[2,3-b]carbazol-6-yloxy)-N,N-dimethylethanamine (213.9 mg, 0.5638 mmol) in DMF (20 mL) at 0° C. was added Br2 in CH2Cl2 (50 mg/mL, 1.982 mL, 0.6201 mmol). The reaction was warmed to room temperature and stirred for two hours. DMF was removed via vacuum pump. The residue was dissolved in ethyl acetate (100 mL) and washed with saturated aq. NaCO3. The organic layers was concentrated and subjected to flash chromatography to provide the title compound (188.4 mg, 73%). 1H-NMR (400 MHz, DMSO-d6) δ ppm 11.89 (br s, 2H), 8.39 (dd, J=10.0, 2.4 Hz, 2H), 7.55 (dd, J=8.8, 4.4 Hz, 2H), 7.31 (td, J=8.8, 2.4 Hz, 2H), 4.34 (t, J=5.2 Hz, 2H), 2.74 (t, J=5.6 Hz, 2H), 2.36 (s, 6H); MS (ESI) m/z 456.1 (M−H)−; MS (ESI) m/z 458.0 (M+H)+
Reaction SMILES: [CH2:1]([N:9]1[C:17](=[O:18])[C:16]2[C:11](=[C:12]3[CH:21]=[N:20][NH:19][C:13]3=[N:14][CH:15]=2)[C:10]1=[O:22])[CH2:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.C1C(=O)N([Br:30])C(=O)C1.O>C(Cl)Cl>[Br:30][C:21]1[C:12]2[C:13](=[N:14][CH:15]=[C:16]3[C:17](=[O:18])[N:9]([CH2:1][CH2:2][C:3]4[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=4)[C:10](=[O:22])[C:11]3=2)[NH:19][N:20]=1
Reactant: O=C1c2cnc3[nH]ncc3c2C(=O)N1CCc1ccccc1
Reactant: O=C1CCC(=O)N1Br
Solvent: O
Solvent: ClCCl
Product: O=C1c2cnc3[nH]nc(Br)c3c2C(=O)N1CCc1ccccc1
Temperature: 25 °C
Reaction time: 3 h
Yield: 79.2 %

Procedure:
To a solution of 7-phenethylpyrazolo[3,4-b]pyrrolo[3,4-d]pyridine-6,8(3H,7H)-dione (1 g, 3.4 mmol) in CH2Cl2 (15 mL), freshly recrystallised NBS (0.66 g, 3.76 mmol) was added and the reaction was stirred at room temperature for 3 h. The reaction was monitored by TLC, and on completion of the reaction; water (50 mL) was added and the reaction mixture was extracted with EtOAc (3×100 mL). The combined EtOAc layer was dried over sodium sulphate and evaporated under vacuo to give a residue which was purified by column chromatography (silica gel, gradient 0-10% EtOAc in a solution of 60:40 hexane and chloroform) to afford 1-bromo-7-phenethylpyrazolo[3,4-b]pyrrolo[3,4-d]pyridine-6,8(3H,7H)-dione (1 g, 79%) as a solid. 1HNMR (400 MHz, DMSO-d6) δ: 14.80 (s, 1H), 8.01 (s, 1H), 7.15-7.35 (m, 5H), 3.85 (t, 2H), 2.95 (t, 2H); LCMS: [M+H] 371.
Reaction SMILES: [CH3:1][N:2]1[CH:6]=[CH:5][CH:4]=[C:3]1[CH:7]=[O:8].[N+:9]([O-])([OH:11])=[O:10].[OH-].[Na+]>C(O)(=O)C>[CH3:1][N:2]1[CH:6]=[C:5]([N+:9]([O-:11])=[O:10])[CH:4]=[C:3]1[CH:7]=[O:8]
Reactant: O=[N+]([O-])O
Reactant: Cn1cccc1C=O
Agent: [Na+]
Agent: [OH-]
Solvent: CC(=O)O
Product: Cn1cc([N+](=O)[O-])cc1C=O
Temperature: 0 °C
Reaction time: 18 h
Yield: 49.6 %

Procedure:
N-methylpyrrol-2-carboxaldehyde (5 g) was dissolved in anhydrous acetic acid (50 ml), and to an ice-cold of the solution was slowly added dropwise nitric acid (1.84 ml) with stirring. The mixture was stirred at this temperature for 1 hour, and then at room temperature for 18 hours. After confirming the completion of the reaction, to the mixture was added an ice-water (200 ml), followed by slowly adding solid sodium hydroxide (20 g) thereto and stirring for 1 hour. The obtained mixture was extracted with ether (150 ml×3). The obtained organic layer was washed with aqueous sodium bicarbonate solution and saturated aqueous sodium chloride solution, dried over sodium sulfate, and then filtered. The filtrate was concentrated under reduced pressure and purified by column-chromatography (ethyl acetate/hexane=1/4) to yield the compound 22-1 (3.5 g, 49.6%).
Reaction SMILES: [OH:1][CH2:2][CH2:3][O:4][C:5]1[C:9]([C:10]2[CH:15]=[CH:14][C:13]([CH3:16])=[CH:12][CH:11]=2)=[C:8]([NH:17][S:18]([C:21]2[CH:26]=[CH:25][C:24]([CH:27]([CH3:29])[CH3:28])=[CH:23][N:22]=2)(=[O:20])=[O:19])[N:7]([CH3:30])[N:6]=1.[H-].[Na+].[Br:33][C:34]1[CH:35]=[N:36][C:37](Cl)=[N:38][CH:39]=1>C1COCC1.CC(N(C)C)=O>[Br:33][C:34]1[CH:35]=[N:36][C:37]([O:1][CH2:2][CH2:3][O:4][C:5]2[C:9]([C:10]3[CH:15]=[CH:14][C:13]([CH3:16])=[CH:12][CH:11]=3)=[C:8]([NH:17][S:18]([C:21]3[CH:26]=[CH:25][C:24]([CH:27]([CH3:28])[CH3:29])=[CH:23][N:22]=3)(=[O:19])=[O:20])[N:7]([CH3:30])[N:6]=2)=[N:38][CH:39]=1
Reactant: Clc1ncc(Br)cn1
Reactant: Cc1ccc(-c2c(OCCO)nn(C)c2NS(=O)(=O)c2ccc(C(C)C)cn2)cc1
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CC(=O)N(C)C
Product: Cc1ccc(-c2c(OCCOc3ncc(Br)cn3)nn(C)c2NS(=O)(=O)c2ccc(C(C)C)cn2)cc1
Reaction time: 0.08 h
Yield: 45.8 %

Procedure:
To a solution of N-[3-(2-hydroxyethoxy)-1-methyl-4-(4-methylphenyl)-1H-pyrazol-5-yl]-5-isopropyl-2-pyridinesulfonamide (Example 40) (1.00 g) in anhydrous THF (10 ml) at 0° C. and under an atmosphere of nitrogen was added sodium hydride (60% dispersion in oil, 195 mg) and the mixture was stirred for 5 minutes. To the mixture was added 5-bromo-2-chloropyrimidine (Liquid Crystals, 1993, 14(3), 741) (1.12 g) in dimethylacetamide (3 ml). After stirring for 1 hr, the reaction mixture was partitioned between ethyl acetate (100 ml) and saturated ammonium chloride solution (100 ml). The organic fraction was washed with brine (100 ml), followed by drying over magnesium sulfate, filtering and concentration under reduced pressure. Purification of the residue by preparative HPLC on a Phenomenex Magellen column using a 0.1M ammonium acetate:acetonitrile gradient (95:5 to 50:50 over 5 minutes) afforded the title compound as a white solid (625 mg).
Reaction SMILES: [F:1][C:2]([F:35])([F:34])[O:3][C:4]1[CH:33]=[CH:32][C:7]([CH2:8][NH:9][C:10]([C@H:12]2[CH2:17][NH:16][CH2:15][CH2:14][N:13]2[S:18]([C:21]2[CH:26]=[CH:25][C:24]([O:27][C:28]([F:31])([F:30])[F:29])=[CH:23][CH:22]=2)(=[O:20])=[O:19])=[O:11])=[CH:6][CH:5]=1.Br[C:37]1[S:47][C:40]2=[N:41][C:42](=[O:46])[CH:43]=[C:44]([CH3:45])[N:39]2[N:38]=1.C(N(CC)C(C)C)(C)C>C(O)C>[F:35][C:2]([F:1])([F:34])[O:3][C:4]1[CH:5]=[CH:6][C:7]([CH2:8][NH:9][C:10]([C@H:12]2[CH2:17][N:16]([C:37]3[S:47][C:40]4=[N:41][C:42](=[O:46])[CH:43]=[C:44]([CH3:45])[N:39]4[N:38]=3)[CH2:15][CH2:14][N:13]2[S:18]([C:21]2[CH:26]=[CH:25][C:24]([O:27][C:28]([F:29])([F:30])[F:31])=[CH:23][CH:22]=2)(=[O:19])=[O:20])=[O:11])=[CH:32][CH:33]=1
Reactant: O=C(NCc1ccc(OC(F)(F)F)cc1)[C@H]1CNCCN1S(=O)(=O)c1ccc(OC(F)(F)F)cc1
Reactant: Cc1cc(=O)nc2sc(Br)nn12
Solvent: CCN(C(C)C)C(C)C
Solvent: CCO
Product: Cc1cc(=O)nc2sc(N3CCN(S(=O)(=O)c4ccc(OC(F)(F)F)cc4)[C@@H](C(=O)NCc4ccc(OC(F)(F)F)cc4)C3)nn12
Temperature: 100 °C
Reaction time: 3 h
Yield: 64.1 %

Procedure:
To a mixed solution of the compound (0.038 g) obtained in Example 783, the compound (0.023 g) obtained in Step 3 and ethanol (1.0 ml) was added N,N-diisopropylethylamine (0.019 ml) at room temperature. After stirring at 100° C. for 3 hr, the reaction mixture was concentrated under reduced pressure, and the residue was purified by thin layer silica gel chromatography (methanol:chloroform=1:9) to give the title compound (0.032 g).
Reaction SMILES: C1COCC1.[C:6]1([CH:12]([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[C:13]2[N:14]=[N:15][N:16]([CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH3:29])[N:17]=2)[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.[Li]CCCC.[CH:41]([C:44]1[CH:49]=[CH:48][CH:47]=[C:46]([CH:50]([CH3:52])[CH3:51])[C:45]=1[N:53]=[C:54]=[O:55])([CH3:43])[CH3:42]>O>[CH3:43][CH:41]([C:44]1[CH:49]=[CH:48][CH:47]=[C:46]([CH:50]([CH3:51])[CH3:52])[C:45]=1[NH:53][C:54](=[O:55])[C:12]([C:6]1[CH:7]=[CH:8][CH:9]=[CH:10][CH:11]=1)([C:30]1[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=1)[C:13]1[N:14]=[N:15][N:16]([CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH3:29])[N:17]=1)[CH3:42]
Reactant: CCCCCCCCCCCCn1nnc(C(c2ccccc2)c2ccccc2)n1
Reactant: CC(C)c1cccc(C(C)C)c1N=C=O
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: O
Product: CCCCCCCCCCCCn1nnc(C(C(=O)Nc2c(C(C)C)cccc2C(C)C)(c2ccccc2)c2ccccc2)n1
Temperature: 25 °C
Yield: 79.5 %

Procedure:
To a THF solution (30 mL) of 5-(diphenylmethyl)-2-dodecyl-2H-tetrazole (1.0 g, 0.0025 mol) at -30° C. under a nitrogen atmosphere with stirring was added n-BuLi (1.62 mL, 1.6M in hexanes, 0.0026 mol). The resulting deep-red solution was stirred for 30 minutes before a THF solution (10 mL) of 2,6-diisopropylphenylisocyanate (0.53 mL, 0.0024 mol) was added dropwise over 10 minutes. The resulting yellow solution was allowed to warm to room temperature over 24 hours. Water (10 mL) was then added and the solution partitioned between ethyl acetate and water. The organic extract was washed with water, brine, dried over MgSO4, filtered, and concentrated in vacuo to yield a yellow oil which was flash chromatographed (5% EtOAc-Hex as eluant, SiO2) to yield 1.16 g of the title product as a clear oil.
Reaction SMILES: CS(O[C@H:6]([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[C@H:7]1[O:12][CH2:11][CH2:10][N:9]([C@@H:13]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH3:14])[CH2:8]1)(=O)=O.C(=O)([O-])[O-].[K+].[K+].[F:33][C:34]([F:43])([F:42])[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=1[SH:41]>>[C:15]1([C@H:13]([N:9]2[CH2:10][CH2:11][O:12][C@H:7]([C@H:6]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[S:41][C:36]3[CH:37]=[CH:38][CH:39]=[CH:40][C:35]=3[C:34]([F:33])([F:42])[F:43])[CH2:8]2)[CH3:14])[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1
Reactant: C[C@H](c1ccccc1)N1CCO[C@H]([C@H](OS(C)(=O)=O)c2ccccc2)C1
Reactant: FC(F)(F)c1ccccc1S
Agent: O=C([O-])[O-]
Agent: [K+]
Product: C[C@H](c1ccccc1)N1CCO[C@H]([C@@H](Sc2ccccc2C(F)(F)F)c2ccccc2)C1
Temperature: 25 °C
Reaction time: 72 h
Yield: 70.5 %

Procedure:
A mixture of 51 (0.035 g, 0.093 mmol), potassium carbonate (0.026 g, 0.19 mmol) and 2-trifluoromethylbenzenethiol (0.084 g, 0.47 mmol) in dry, degassed dimethylformamide (0.5 ml) was stirred under nitrogen at room temperature for 3 days. The reaction mixture was diluted with water and extracted with diethyl ether. The extracts was washed with water and brine, dried over magnesium sulphate, filtered and evaporated to give a colourless oil (0.03 g, 71%). Purification by flash column chromatography (eluent: ethyl acetate/heptane 20/80 [v/v]) gave 52 as a colourless oil (0.03 g, 71%); MW 457.56; C26H26F3NOS 1H NMR (CDCl3) 7.53 (1H, d), 7.10-7.28 (13H, m), 4.39 (1H, d), 3.85-4.04 (2H, m), 3.8 (1H, td), 3.35 (1H, q), 2.70 (1H, d), 2.40 (1H, d), 2.30 (1H, td), 2.10-2.20 (1H, m), 1.29 (3H, d). m/z [M+H]+ 458.
Reaction SMILES: [C:1]1([N:7]=[C:8]=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Cl:10][C:11]1[CH:23]=[CH:22][C:14]([CH2:15][NH:16][CH:17]2[CH2:21][CH2:20][CH2:19][CH2:18]2)=[CH:13][CH:12]=1>CCCCCC>[Cl:10][C:11]1[CH:12]=[CH:13][C:14]([CH2:15][N:16]([CH:17]2[CH2:21][CH2:20][CH2:19][CH2:18]2)[C:8]([NH:7][C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)=[O:9])=[CH:22][CH:23]=1
Reactant: Clc1ccc(CNC2CCCC2)cc1
Reactant: O=C=Nc1ccccc1
Solvent: CCCCCC
Product: O=C(Nc1ccccc1)N(Cc1ccc(Cl)cc1)C1CCCC1
Yield: 94.3 %

Procedure:
A solution of 12 grams (0.1 mole) of phenylisocyanate in 50 ml of hexane was added dropwise to 21 grams (0.1 mole) of N-4-chlorobenzyl-N-cyclopentylamine in 400 ml of hexane under cooling and stirring conditions. After the addition, the temperature of the reaction mixture was gradually raised, and the solution was then stirred at 50° C. for about 7 hours. The mixture was cooled and filtered. The residue was recrystallized from a mixed solvent of hexane-ethyl alcohol. 31 grams of N-4-chlorobenzyl-N-cyclopentyl-N'-phenylurea were obtained. Yield: 95%. Melting point: 129°-134° C.
Reaction SMILES: [O:1]=[CH:2][C@@H:3]([C@H]([C@@H]([C@@H](CO)O)O)O)O.[CH3:13][C@@:14]12[C@@H:23](CC[C@@](O)(C=C)C)[C@@:22]([OH:32])([CH3:31])[CH2:21][CH2:20][C@H:19]1[C:18]([CH3:34])([CH3:33])[CH2:17][CH2:16][CH2:15]2>>[OH:32][C:22]1([CH3:31])[CH2:21][CH2:20][CH:19]2[C:18]([CH3:33])([CH2:17][CH2:16][CH2:15][C:14]2([CH3:13])[CH3:23])[CH:34]1[CH2:3][CH2:2][OH:1]
Reactant: C=C[C@](C)(O)CC[C@@H]1[C@@]2(C)CCCC(C)(C)[C@@H]2CC[C@@]1(C)O
Reactant: O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO
Product: CC1(C)CCCC2(C)C1CCC(C)(O)C2CCO
Reaction time: 84 h

Procedure:
Four flasks, each containing an aqueous solution (100 mL) of 0.1% NH4NO3, 0.1% H2KPO4, 0.05% MgSO4.7H2O, trace minerals, and Vitamin B complex were sterilized at 120° C. for 20 minutes. A 50% aqueous solution of dextrose (5 mL) and Tween-80 (0.1 mL), containing Sclareol (4) (10 mg) was added to each flask. Each flask was inoculated with 5% by volume of three days grown cells CBS 214.83 (ATCC 20624). The cultures were then incubated at 25±1° C. on a rotary shaker (200 rpm) for 3 to 4 days. After the initial incubation period a mixture of Sclareol dissolved in Tween-80 (8.0 g) was added in portions during the next 5 days, afterwhich the incubation was continued for a further 4 days. At the end of the incubation period the contents of the four flasks were combined, extracted with ethyl acetate (3×200 mL) and dried (Na2SO4). Evaporation of the solvent provided a crude extract (4.0 g), which was crystallized from hexane/chloroform to provide decahydro-2-hydroxy-2,5,5,8a-tetramethylnaphthaleneethanol (3) (2.4 g), mp 130.5°-131.5° C., (lit. 132°-133° C.) GLC purity 100%, H-NMR (CDCl3) δ0.79 (6H, 2s), 0.87 (3H, 2), (3H, 2), 0.9-20 (16H, m), 3.41-3.49 (1H, m), 3.72-3.79 (1H, m). IR (CHCl3) νmax, 3580, 3360, 2950, 1460, 1380 cm. MS m/e 236, 221, 117, 137, 109. [α]22D =-16.8° (CHCl3). [Literature 132°-133° C., [α]D22.5 =-17.3° (CHCl3).] [See M. Stoll and M. Hinder Helv. Chim. Acta (1953) 36 1955-2008.]
Reaction SMILES: [CH3:1][O:2][C:3](=[O:17])[C:4]1[CH:9]=[CH:8][C:7]([CH2:10][CH:11]=[CH:12][N:13](C)C)=[CH:6][C:5]=1[Cl:16].[NH2:18]N>C(O)(=O)C>[CH3:1][O:2][C:3](=[O:17])[C:4]1[CH:9]=[CH:8][C:7]([C:10]2[CH:11]=[CH:12][NH:13][N:18]=2)=[CH:6][C:5]=1[Cl:16]
Reactant: NN
Reactant: COC(=O)c1ccc(CC=CN(C)C)cc1Cl
Solvent: CC(=O)O
Product: COC(=O)c1ccc(-c2cc[nH]n2)cc1Cl
Yield: 94.1 %

Procedure:
A solution of 2-chloro-4-(3-dimethylamino-2-propen-1-yl)-benzoic acid methyl ester of Step B (6.13 g, 22.9 mmol) and anhydrous hydrazine (1.44 mL, 45.8 mmol) in 15 mL of glacial acetic acid was heated at 90° C. for 30 minutes. The reaction mixture was concentrated in vacuo and the residue partitioned between ethyl acetate and water. The organic layer was washed with water and brine and dried over sodium sulfate. The solvent was evaporated and the residual solid triturated with diethyl ether-hexane to give the title compound (5.1 g) as an orange solid.
Reaction SMILES: [CH3:1][C:2]1[O:3][C:4](/[CH:7]=[CH:8]/[C:9]2[CH:14]=[CH:13][C:12]([N+:15]([O-])=O)=[CH:11][CH:10]=2)=[N:5][N:6]=1.O1CCCC1>[C].[Pd].CO>[CH3:1][C:2]1[O:3][C:4]([CH2:7][CH2:8][C:9]2[CH:14]=[CH:13][C:12]([NH2:15])=[CH:11][CH:10]=2)=[N:5][N:6]=1
Reactant: Cc1nnc(/C=C/c2ccc([N+](=O)[O-])cc2)o1
Agent: [Pd]
Solvent: CO
Solvent: C1CCOC1
Product: Cc1nnc(CCc2ccc(N)cc2)o1
Temperature: 25 °C
Reaction time: 6 h
Yield: 102.8 %

Procedure:
To a mixture of 2-methyl-5-[(E)-2-(4-nitrophenyl)ethenyl]-1,3,4-oxadiazole (2.00 g), tetrahydrofuran (75 mL) and methanol (75 mL) was added palladium-carbon (Pd: 10%, 50% in water, 200 mg), and the mixture was stirred under a hydrogen atmosphere at room temperature for 6 hr. The reaction mixture was filtered, and the filtrate was concentrated under reduced pressure to give the title compound (1.807 g).
Reaction SMILES: Cl[C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[C:4](Cl)[C:3]=1[N+:10]([O-:12])=[O:11].[CH2:13]([CH2:15][NH2:16])[OH:14]>>[Cl:8][C:6]1[CH:5]=[C:4]([NH:16][CH2:15][CH2:13][OH:14])[C:3]([N+:10]([O-:12])=[O:11])=[C:2]([NH:16][CH2:15][CH2:13][OH:14])[CH:7]=1
Reactant: O=[N+]([O-])c1c(Cl)cc(Cl)cc1Cl
Reactant: NCCO
Product: O=[N+]([O-])c1c(NCCO)cc(Cl)cc1NCCO
Temperature: 0 °C
Reaction time: 0.5 h

Procedure:
0.132 mole (30 g) of 2,4,6-trichloronitrobenzene is heated to 95° C. in 120 ml of ethanolamine. After 30 minutes, the reaction medium is poured into 240 g of an ice-water mixture. The product expected precipitates. It is drained, washed with water and then dried under vacuum in the presence of phosphorous pentoxide. After recrystallizing from absolute ethanol, it melts at 154° C.
Reaction SMILES: [CH3:1][C:2]1[C:15]2[C:14](=O)[C:13]3[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=3)[C:7](=O)[C:6]=2[C:5]([CH3:18])=[CH:4][CH:3]=1.[BH4-].[Na+]>C(O)(C)C>[CH3:18][C:5]1[C:6]2[C:15](=[CH:14][C:13]3[C:8]([CH:7]=2)=[CH:9][CH:10]=[CH:11][CH:12]=3)[C:2]([CH3:1])=[CH:3][CH:4]=1
Reactant: Cc1ccc(C)c2c1C(=O)c1ccccc1C2=O
Agent: [BH4-]
Agent: [Na+]
Solvent: CC(C)O
Product: Cc1ccc(C)c2cc3ccccc3cc12
Temperature: 25 °C
Yield: 90.9 %

Procedure:
To a solution of 1,4-dimethylanthraquinone (1 g, 4.24 mmol) suspended in 40 mL of isopropanol was added sodium borohydride (1.6 g, 42.4 mmol) in portions over 1 h at room temperature with stirring. The reaction mixture was left to stir at this temperature for an additional 30 min before heating to reflux overnight. The solution was then cooled to room temperature and quenched by pouring into 5% HCl solution. The mixture was left to stir for 1 hr and the solution was filtered to give a yellow solid. The solid was further recrystallized from ethanol to give the product 11 as a bright yellow solid (0.795 g, 92%): m.p. 70-72° C. (lit. m.p. 74° C.); 1H NMR (300 MHz, CDCl3): 8.56 (2H, s), 8.06 (2H, dd, J=6.5 and 3.3 Hz), 7.50 (2H, dd, J=6.5 and 3.3 Hz), 7.22 (2H, s), 2.82 (6H, s); HR-MS (EI) calcd. for C16H14 (M+): 206.11, found: 206.11.