Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([C:10]1[CH:15]=[CH:14][C:13]([OH:16])=[CH:12][CH:11]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH3:9].[OH-].[K+].I[CH3:20]>C(Cl)Cl.O.[Br-].C([N+](CCCC)(CCCC)CCCC)CCC>[CH2:1]([C:10]1[CH:11]=[CH:12][C:13]([O:16][CH3:20])=[CH:14][CH:15]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH3:9]
Reactant: CI
Reactant: CCCCCCCCCc1ccc(O)cc1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [Br-]
Agent: [K+]
Solvent: O
Solvent: ClCCl
Product: CCCCCCCCCc1ccc(OC)cc1
Temperature: 40 °C
Reaction time: 1 h
Yield: 84 %

Procedure:
A solution of p-nonylphenol, 35 g, in 125 mL methylene chloride was mixed with a solution of 44.5 g KOH in 125 mL water. To this mixture was added 45 g iodomethane and 5.0 g tetra-n-butylammonium bromide. The whole mixture was vigorously stirred at 40° C. for one hour. After cooling to room temperature, the phases were separated and the aqueous phase extracted with 50 mL methylene chloride. The combined methylene chloride layers were concentrated to an oil which was taken up in 200 mL of petroleum ether and filtered to remove the residual phase transfer catalyst. Finally, the petroleum ether was removed under vacuum to give 31.1 g (84%) of p-nonylanisole.
Reaction SMILES: [CH3:1][O:2][C:3]1[N:8]=[CH:7][C:6]([CH2:9][S:10]([CH2:13][C:14](O)=O)(=[O:12])=[O:11])=[CH:5][C:4]=1[N+:17]([O-:19])=[O:18].N1CCCCC1.[CH3:26][O:27][C:28]1[CH:35]=[CH:34][CH:33]=[C:32]([O:36][CH3:37])[C:29]=1C=O>N1C=CC=CC=1>[CH3:26][O:27][C:28]1[CH:35]=[CH:34][CH:33]=[C:32]([O:36][CH3:37])[C:29]=1/[CH:14]=[CH:13]/[S:10]([CH2:9][C:6]1[CH:5]=[C:4]([N+:17]([O-:19])=[O:18])[C:3]([O:2][CH3:1])=[N:8][CH:7]=1)(=[O:12])=[O:11]
Reactant: COc1ncc(CS(=O)(=O)CC(=O)O)cc1[N+](=O)[O-]
Reactant: COc1cccc(OC)c1C=O
Solvent: C1CCNCC1
Solvent: c1ccncc1
Product: COc1cccc(OC)c1/C=C/S(=O)(=O)Cc1cnc(OC)c([N+](=O)[O-])c1

Procedure:
A solution of 2-((6-methoxy-5-nitropyridin-3-yl)methylsulfonyl)acetic acid (0.29 g, 1 mmol) in dry pyridine (20 mL) was treated with piperidine (2 mL), followed by 2,6-dimethoxybenzaldehyde (0.17 g, 1 mmol). The mixture was refluxed for 6 h, and evaporated to dryness. The residue was purified by column chromatography using a mixture of EtOAc/PE (1:2, v/v) to yield the titled compound. HR-MS (ESI+) m/z 394.8362; C17H18N2O7S requires 394.0835.
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9](=O)[CH2:10][CH2:11][C:12]([OH:14])=[O:13].[C:16]1(C)C=CC=CC=1.[I-].CP(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.CC(C)([O-])C.[Na+]>O>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9](=[CH2:16])[CH2:10][CH2:11][C:12]([OH:14])=[O:13]
Reactant: O=C(O)CCC(=O)c1ccc(F)cc1F
Reactant: Cc1ccccc1
Agent: CC(C)(C)[O-]
Agent: C[PH](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [I-]
Solvent: O
Product: C=C(CCC(=O)O)c1ccc(F)cc1F
Temperature: 52.5 °C
Reaction time: 7 h

Procedure:
To a mixture of 4-(2,4-difluorophenyl)-4-oxobutanoic acid (100 g) and toluene (1000 ml), added methyl triphenylphosphine iodide (377.5 g) and sodium tertiary butoxide (183 g) at 25-30° C. Heated the reaction mixture to 50-55° C. and stirred for 6-8 hours at the same temperature. After completion of the reaction, cooled the reaction mixture to 25-30° C. Water was added to the reaction mixture and both organic and aqueous layers were separated. pH of aqueous layer was adjusted to 11 using 50% hydrochloric acid. Extracted the aqueous layer with toluene and washed the aqueous layer with dichloromethane. pH of the aqueous layer was further adjusted to 2.5 using 50% HCl and the reaction mixture was stirred for 45 minutes. Filtered the obtained solid, washed with water and then dried to get the title compound. Cyclohexane (500 ml) was added to the obtained solid and heated to 45-50° C. Carbon (10 g) was added to the reaction mixture and stirred for 15 minutes. Filtered the reaction mixture and washed with hot cyclohexane. Distilled off half of the solvent under reduced pressure. Cooled the reaction mixture to 10-15° C. and stirred for 60 minutes at the same temperature. Filtered the solid and washed with chilled cyclohexane and dried to get the title compound. Yield: 65.75 g
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([Cl:8])[N:5]=[C:4]([CH3:9])[N:3]=1.[NH2:10][C@@H:11]1[C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[CH2:13][CH2:12]1.CCN(C(C)C)C(C)C.O>CN(C=O)C.C1(C)C=CC=CC=1>[Cl:8][C:6]1[N:5]=[C:4]([CH3:9])[N:3]=[C:2]([NH:10][C@@H:11]2[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[CH2:13][CH2:12]2)[N:7]=1
Reactant: Cc1nc(Cl)nc(Cl)n1
Reactant: N[C@H]1CCc2ccccc21
Solvent: Cc1ccccc1
Solvent: CN(C)C=O
Solvent: O
Product: Cc1nc(Cl)nc(N[C@H]2CCc3ccccc32)n1
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 52.9 %

Procedure:
To a solution of 2,4-dichloro-6-methyl-1,3,5-triazine (0.90 g, 0.0055 mol) in DMF (3.50 mL) and toluene (1.5 mL) at 0° C. was added (S)-(+)-1-aminoindan (0.64 mL, 0.0050 mol) followed by DIPEA (0.991 mL, 0.00569 mol). The mixture was stirred at 0° C. for 30 min. The reaction was poured into water and extracted with CH2Cl2. The organic layer was dried over MgSO4, filtered and concentrated. The residue was purified by flash chromatography (0 to 15% EtOAc/hexanes) to afford 0.69 g (53%) of the title compound.
Reaction SMILES: Br[CH2:2][C:3]1[C:8]([C:9]([F:12])([F:11])[F:10])=[CH:7][CH:6]=[CH:5][C:4]=1[Cl:13].C(=O)([O-])[O-].[K+].[K+].[C:20]([O:24][C:25](=[O:49])[CH2:26][C@@:27]1([C:33]([NH:35][CH:36]2[CH2:41][CH2:40][N:39]([C:42]([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=[O:43])[CH2:38][CH2:37]2)=[O:34])[C@H:31]([CH3:32])[CH2:30][NH:29][CH2:28]1)([CH3:23])([CH3:22])[CH3:21].C(OCC)(=O)C>CN(C)C=O>[C:20]([O:24][C:25](=[O:49])[CH2:26][C@@:27]1([C:33]([NH:35][CH:36]2[CH2:41][CH2:40][N:39]([C:42]([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=[O:43])[CH2:38][CH2:37]2)=[O:34])[C@H:31]([CH3:32])[CH2:30][N:29]([CH2:2][C:3]2[C:8]([C:9]([F:12])([F:11])[F:10])=[CH:7][CH:6]=[CH:5][C:4]=2[Cl:13])[CH2:28]1)([CH3:23])([CH3:21])[CH3:22]
Reactant: FC(F)(F)c1cccc(Cl)c1CBr
Reactant: C[C@@H]1CNC[C@]1(CC(=O)OC(C)(C)C)C(=O)NC1CCN(C(=O)OC(C)(C)C)CC1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: C[C@@H]1CN(Cc2c(Cl)cccc2C(F)(F)F)C[C@]1(CC(=O)OC(C)(C)C)C(=O)NC1CCN(C(=O)OC(C)(C)C)CC1
Temperature: 40 °C
Reaction time: 48 h
Yield: 63.8 %

Procedure:
2-(Bromomethyl)-1-chloro-3-(trifluoromethyl)benzene (443 mg, 1.62 mmol) and potassium carbonate (244 mg) were added to a solution of tert-butyl 4-[(3R*,4S*)-3-[2-(tert-butoxy)-2-oxoethyl]-4-methylpyrrolidin-3-amido]piperidine-1-carboxylate obtained in Example 3b (345 mg, 0.811 mmol) in N,N-dimethylformamide (dehydrated) (10 mL), which was stirred at 45° C. for six hours and at 40° C. for two days. Ethyl acetate was added to the reaction liquid, which was washed with a 1N aqueous sodium hydroxide solution and brine. This was dried over anhydrous magnesium sulfate and concentrated. The residue was purified by silica gel column chromatography (elution solvent: heptane/ethyl acetate) to give the title compound (320 mg, yield: 63.8%).
Reaction SMILES: [CH2:1]([NH2:9])[CH2:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[Br:10][C:11]1[CH:16]=[CH:15][C:14]([C:17](Cl)=[O:18])=[C:13]([O:20][CH3:21])[CH:12]=1.C(N(CC)CC)C>ClCCl>[CH2:1]([NH:9][C:17](=[O:18])[C:14]1[CH:15]=[CH:16][C:11]([Br:10])=[CH:12][C:13]=1[O:20][CH3:21])[CH2:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1
Reactant: NCCc1ccccc1
Reactant: COc1cc(Br)ccc1C(=O)Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: COc1cc(Br)ccc1C(=O)NCCc1ccccc1
Reaction time: 2 h
Yield: 90.1 %

Procedure:
Phenethylamine (0.79 mL, 6.31 mmol) was added slowly to a mixture of 4-Bromo-2-methoxy-1-benzenecarbonyl chloride (1.5 g, 6.01 mmol) and triethylamine (1.3 mL, 9.02 mmol) in dichloromethane (60 mL). After 2 hours, solvent was removed under reduced pressure. Ethyl acetate was added and the mixture was filtered. The filtrate was concentrated under reduced pressure and the residue was purified by flash column chromatography using dichloromethane/ethyl acetate (97:3) as mobile to give N1-phenethyl-4-bromo-2-methoxybenzamide (1.81 g, 90%). 1H NMR (DMSO-d6) δ 2.83 (m, 2H), 3.50 (m, 2H), 3.84 (s, 3H), 7.31 (m, 7H), 7.65 (d, J=8.28 Hz, 1H), 8.15 (m, 1H).
Reaction SMILES: [Cl:1][C:2]1[CH:12]=[CH:11][C:5](C(OCC)=O)=[C:4]([O:13][CH:14]([C:16]([O:18]C)=O)[CH3:15])[CH:3]=1.[H-].[Na+]>O1CCCC1>[Cl:1][C:2]1[CH:12]=[CH:11][C:5]2[C:16](=[O:18])[CH:14]([CH3:15])[O:13][C:4]=2[CH:3]=1
Reactant: CCOC(=O)c1ccc(Cl)cc1OC(C)C(=O)OC
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: CC1Oc2cc(Cl)ccc2C1=O
Temperature: 25 °C
Yield: 38.7 %

Procedure:
A solution of ethyl 4-chloro-2-(1-(methoxycarbonyl)ethoxy)benzoate (7.3 g) and 60% oil dispersion (1.5 g) of sodium hydride in tetrahydrofuran (70 ml) was heated at reflux for 30 minutes, and slowly cooled to room temperature. The reaction mixture was poured into ice-aqueous ammonium chloride and extracted with ether. The extract was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The resulting residue was subjected to chromatography on silica gel to give 6-chloro-2-methyl-3(2H)-benzofuranone (yield, 1.8 g).
Reaction SMILES: [Cl:1][C:2]1[C:7]([N+:8]([O-:10])=[O:9])=[C:6](Cl)[CH:5]=[CH:4][N:3]=1.[C:12]([O:16][C:17]([N:19]1[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]1)=[O:18])([CH3:15])([CH3:14])[CH3:13]>>[C:12]([O:16][C:17]([N:19]1[CH2:24][CH2:23][N:22]([C:6]2[CH:5]=[CH:4][N:3]=[C:2]([Cl:1])[C:7]=2[N+:8]([O-:10])=[O:9])[CH2:21][CH2:20]1)=[O:18])([CH3:15])([CH3:13])[CH3:14]
Reactant: O=[N+]([O-])c1c(Cl)ccnc1Cl
Reactant: CC(C)(C)OC(=O)N1CCNCC1
Product: CC(C)(C)OC(=O)N1CCN(c2ccnc(Cl)c2[N+](=O)[O-])CC1
Yield: 94.7 %

Procedure:
The specific operation referred to the step (1) described in Example 1 for details. 2,4-dichloro-3-nitropyridine (772 mg, 4.0 mmol), and piperazine-1-carboxylic acid tert-butyl ester (744 mg, 4.0 mmol) were charged to afford 1.299 g crude product with a yield of 94.7%, which was directly used in the subsequent reaction.
Reaction SMILES: [N:1]1([CH2:7][C:8]2[CH:13]=[CH:12][C:11]([C:14]3[CH:27]=[N:26][C:17]4[NH:18][C:19]5[CH:24]=[N:23][C:22]([NH2:25])=[CH:21][C:20]=5[C:16]=4[CH:15]=3)=[CH:10][CH:9]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[C:28](Cl)(=[O:32])[CH:29]([CH3:31])[CH3:30].CCN(C(C)C)C(C)C.C(=O)(O)[O-].[Na+]>C(Cl)Cl.CO.O>[N:1]1([CH2:7][C:8]2[CH:13]=[CH:12][C:11]([C:14]3[CH:27]=[N:26][C:17]4[NH:18][C:19]5[CH:24]=[N:23][C:22]([NH:25][C:28](=[O:32])[CH:29]([CH3:31])[CH3:30])=[CH:21][C:20]=5[C:16]=4[CH:15]=3)=[CH:10][CH:9]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: Nc1cc2c(cn1)[nH]c1ncc(-c3ccc(CN4CCCCC4)cc3)cc12
Reactant: CC(C)C(=O)Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CO
Solvent: O
Solvent: ClCCl
Product: CC(C)C(=O)Nc1cc2c(cn1)[nH]c1ncc(-c3ccc(CN4CCCCC4)cc3)cc12
Yield: 12.4 %

Procedure:
A suspension of 3-(4-piperidin-1-ylmethyl-phenyl)-9H-dipyrido[2,3-b;4′,3′-d]pyrrol-6-amine (80.9 mg, 0.226 mmol) in DCM (1.8 mL) was treated with isobutyryl chloride (26.3 μL, 0.249 mmol) and DIPEA (118 μL, 0.679 mmol). The reaction mixture was treated with saturated sodium bicarbonate and diluted with 20% MeOH in DCM and water. The layers were separated, the aqueous phase extracted into 20% MeOH in DCM, and the combined organic phase was dried over sodium sulfate and concentrated in vacuo. The resultant residue was dissolved in DCM/methanol, absorbed onto celite, and purified by preparative HPLC (0-30% MeCN/water modified with 0.1% formic acid) to afford an off-white solid (12 mg, 12%). 1H NMR (DMSO-D6, 400 MHz): 12.03 (s, 1H), 10.32 (s, 1H), 8.95 (d, J=2.2 Hz, 1H), 8.90-8.85 (m, 2H), 8.62 (s, 1H), 7.79 (d, J=8.1 Hz, 2H), 7.42 (d, J=8.1 Hz, 2H), 3.48 (s, 2H), 2.79 (dt, J=6.7, 13.5 Hz, 1H), 2.36 (m, 4H), 1.58-1.46 (m, 4H), 1.41 (m, 2H), 1.14 (d, J=6.8 Hz, 6H). LCMS (Method D): RT=7.73 min, M+H+=428.
Reaction SMILES: [C:1]([O:9]CC)(=O)[C:2]1[CH:7]=[CH:6][CH:5]=[N:4][CH:3]=1.[CH:12]1([C:15]([CH3:17])=[O:16])[CH2:14][CH2:13]1.C[O-].[Na+]>C1C=CC=CC=1>[CH:12]1([C:15](=[O:16])[CH2:17][C:1]([C:2]2[CH:3]=[N:4][CH:5]=[CH:6][CH:7]=2)=[O:9])[CH2:14][CH2:13]1
Reactant: CCOC(=O)c1cccnc1
Reactant: CC(=O)C1CC1
Agent: C[O-]
Agent: [Na+]
Solvent: c1ccccc1
Product: O=C(CC(=O)C1CC1)c1cccnc1

Procedure:
A mixture of 39 g. of ethyl nicotinate, 33 g. of cyclopropylmethyl ketone and 18 g. of sodium methoxide in 400 ml. of benzene is heated under reflux for 6 hours. The mixture is diluted with 400 ml. of water and the benzene phase is separated. The aqueous phase is made weakly acidic with dilute hydrochloric acid and extracted with chloroform. The chloroform solution is dried over magnesium sulfate and concentrated under reduced pressure to give a solid. This solid is recrystallized from hexane to give colorless crystals, melting point 69°-70°C.
Reaction SMILES: CS(C)=O.C(Cl)(=O)C(Cl)=O.[OH:11][CH2:12][C:13]1[CH:14]=[C:15]([N:19]([CH2:25][C:26]2[CH:27]=[N:28][CH:29]=[CH:30][CH:31]=2)[S:20]([CH2:23][CH3:24])(=[O:22])=[O:21])[CH:16]=[CH:17][CH:18]=1.N#N.C([O-])(O)=O.[Na+]>C(Cl)Cl.C(OCC)C>[CH:12]([C:13]1[CH:14]=[C:15]([N:19]([CH2:25][C:26]2[CH:27]=[N:28][CH:29]=[CH:30][CH:31]=2)[S:20]([CH2:23][CH3:24])(=[O:22])=[O:21])[CH:16]=[CH:17][CH:18]=1)=[O:11]
Reactant: CCS(=O)(=O)N(Cc1cccnc1)c1cccc(CO)c1
Agent: N#N
Agent: O=C(Cl)C(=O)Cl
Agent: O=C([O-])O
Solvent: CCOCC
Solvent: CS(C)=O
Solvent: ClCCl
Product: CCS(=O)(=O)N(Cc1cccnc1)c1cccc(C=O)c1
Temperature: 0 °C
Reaction time: 0.25 h
Yield: 5.7 %

Procedure:
Into a −78° C. solution of DMSO (20.8 mL, 0.269 mole, 3.1 eq) in DCM (460 mL) was added oxalyl chloride (16 mL, 0.109 mole, 1.25 eq) dropwise and stirred for 15 minutes. N-(3-(Hydroxymethyl)phenyl)-N-(ethanesulfonyl)pyrid-3-ylmethylamine (26.4 g, 0.86 mole, 1 eq) was added dropwise via addition funnel as a solution in DCM (146 mL). The reaction mixture was stirred for 30 min. then TEA (102 mL, 1 mole, 11.7 eq) was added via addition funnel. The reaction mixture was allowed to warmed to 0° C. with an ice bath and stirred for 1 hour with a N2 sweep through a bleach/caustic scrubber. The reaction mixture was poured into saturated NaHCO3 and diluted with diethyl ether (2000 mL). The layers were separated and the aqueous layer backextracted with diethyl ether (1000 mL). The combined organics were washed with brine (1000 mL), dried with MgSO4, filtered and concentrated. The residue was purified by flash chromatography, eluting with 1:1 DCM/EtOAc to give the title compound as a white solid (15.0 g, 57.2).
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][C:7]([C:10](=[O:12])[CH3:11])=[CH:6][CH:5]=1)([O-:3])=[O:2].CO[CH:15](OC)[N:16]([CH3:18])[CH3:17]>>[CH3:15][N:16]([CH3:18])/[CH:17]=[CH:11]/[C:10]([C:7]1[CH:6]=[CH:5][C:4]([N+:1]([O-:3])=[O:2])=[CH:9][CH:8]=1)=[O:12]
Reactant: CC(=O)c1ccc([N+](=O)[O-])cc1
Reactant: COC(OC)N(C)C
Product: CN(C)/C=C/C(=O)c1ccc([N+](=O)[O-])cc1

Procedure:
A solution of 1-(4-nitrophenyl)ethanone (2.2 g, 13 mmol) and N,N-dimethylformamide dimethyl acetal (25 ml) was heated to 120° C. in a sealed tube overnight. The volatiles were removed. The residue was dissolved in DCM and washed twice with H2O. The DCM layer was dried with MgSO4. The crude product was purified by flash chromatography (silica gel, 100% EtOAc) to isolate (E)-3-(dimethylamino)-1-(4-nitrophenyl)prop-2-en-1-one (2.2 g,) as a yellow solid. 1H NMR (400 MHz, CDCl3) δ 2.99 (s, 3H), 3.23 (s, 3H), 5.70 (d, J=12.4 Hz, 1H), 7.94 (d, J=12.4 Hz, 1H), 8.03 (m, 2H), 8.26 (m, 2H). MS (ESI): 221 (M+H+)
Reaction SMILES: [CH3:1][N:2]1[C:19](=[O:20])[CH2:18][CH2:17][C@@:16]2([CH3:21])[CH:3]1[CH2:4][C@H:5]([CH3:23])[C@@H:6]1[C@@H:15]2[CH2:14][CH2:13][C@@:11]2([CH3:12])[C@H:7]1[CH2:8][CH2:9][C@@H:10]2[OH:22].C1CCN2C(=NCCC2)CC1.[C:35]([N:39]=[C:40]=[O:41])([CH3:38])([CH3:37])[CH3:36]>C(Cl)Cl.C(OCC)(=O)C>[C:35]([NH:39][C:40]([O:22][C@H:10]1[CH2:9][CH2:8][C@H:7]2[C@H:6]3[C@H:15]([CH2:14][CH2:13][C@:11]12[CH3:12])[C@:16]1([CH3:21])[C@H:3]([N:2]([CH3:1])[C:19](=[O:20])[CH2:18][CH2:17]1)[CH2:4][CH:5]3[CH3:23])=[O:41])([CH3:38])([CH3:37])[CH3:36]
Reactant: CC(C)(C)N=C=O
Reactant: C[C@H]1CC2N(C)C(=O)CC[C@]2(C)[C@H]2CC[C@]3(C)[C@@H](O)CC[C@H]3[C@H]12
Solvent: ClCCl
Solvent: C1CCC2=NCCCN2CC1
Solvent: CCOC(C)=O
Product: CC1C[C@H]2N(C)C(=O)CC[C@]2(C)[C@H]2CC[C@]3(C)[C@@H](OC(=O)NC(C)(C)C)CC[C@H]3[C@H]12
Temperature: 25 °C
Reaction time: 48 h

Procedure:
To a solution of 70, 51 mg in 4 ml methylene chloride was added DBU (200 microliters) followed by 63.65 mg. t-butylisocyanate. After stirring the mixture for 48 hours at room temperature, the reaction mixture was diluted with ethyl acetate, the organic layer washed with water, brine, dried and concentrated to a residue which was purified by preparative chromatography over silica gel using 3:1 CHCl3 /acetone to yield pure title compound 72.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([CH:22]=[CH:23][CH:24]=1)[C:5]([NH:7][CH2:8][CH:9]([OH:21])[CH2:10][N:11]1[CH2:20][CH2:19][C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[CH2:12]1)=[O:6].[O:25]1[CH2:30][CH2:29][CH:28]([C:31](=O)[CH3:32])[CH2:27][CH2:26]1.CC(O)=O.[BH3-]C#N.[Na+]>CO>[CH2:12]1[C:13]2[C:18](=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH2:19][CH2:20][N:11]1[CH2:10][CH:9]([OH:21])[CH2:8][NH:7][C:5](=[O:6])[C:4]1[CH:22]=[CH:23][CH:24]=[C:2]([NH:1][CH:31]([CH:28]2[CH2:29][CH2:30][O:25][CH2:26][CH2:27]2)[CH3:32])[CH:3]=1
Reactant: Nc1cccc(C(=O)NCC(O)CN2CCc3ccccc3C2)c1
Reactant: CC(=O)C1CCOCC1
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: CO
Solvent: CC(=O)O
Product: CC(Nc1cccc(C(=O)NCC(O)CN2CCc3ccccc3C2)c1)C1CCOCC1
Temperature: 22 °C
Reaction time: 1 h
Yield: 8 %

Procedure:
A solution of 3-amino-N-(3-(3,4-dihydroisoquinolin-2(1H)-yl)-2-hydroxypropyl)benzamide (130 mg, 0.4 mmol), 1-(tetrahydro-2H-pyran-4-yl)ethanone (52 mg, 0.4 mmol) and AcOH (0.1 mL) in MeOH (10 mL). The mixture was stirred at 22° C. for 1 h, then NaBH3CN (76 mg, 1.2 mmol) was added. The mixture was stirred at 22° C. for 4 h. The reaction mixture was concentrated and quenched with water. The mixture solution was extracted with DCM, the combined organic layers were concentrated and the residue was purified by prep-TLC to give the desired compound (14.0 mg, Yield 8%). 1H NMR (CD3OD, 400 MHz): δ 6.90-7.07 (m, 6H), 6.81 (d, J=7.5 Hz, 1H), 6.64 (d, J=8.03 Hz, 1H), 3.98-4.04 (m, 1H), 3.87 (d, J=11.3 Hz, 2H), 3.70 (s, 2H), 3.28-3.45 (m, 5H), 2.82 (brs, 4H), 2.56-2.65 (m, 2H), 1.70 (d, J=13.8 Hz, 1H), 1.57 (brs, 1H), 1.17-1.37 (m, 3H), 1.04 (d, J=6.3 Hz, 3H). LCMS (m/z): 438.3 (M+1).
Reaction SMILES: [CH:1]1([O:6][C:7]2[CH:8]=[C:9]([C:15]3(/[CH:25]=[CH:26]/[C:27]4[CH:32]=[CH:31][CH:30]=[C:29]([C:33]#[N:34])[CH:28]=4)[CH2:20][CH2:19][C:18]4(OCC[O:21]4)[CH2:17][CH2:16]3)[CH:10]=[CH:11][C:12]=2[O:13][CH3:14])[CH2:5][CH2:4][CH2:3][CH2:2]1.Cl>O1CCCC1>[CH:1]1([O:6][C:7]2[CH:8]=[C:9]([C:15]3(/[CH:25]=[CH:26]/[C:27]4[CH:32]=[CH:31][CH:30]=[C:29]([C:33]#[N:34])[CH:28]=4)[CH2:16][CH2:17][C:18](=[O:21])[CH2:19][CH2:20]3)[CH:10]=[CH:11][C:12]=2[O:13][CH3:14])[CH2:2][CH2:3][CH2:4][CH2:5]1
Reactant: COc1ccc(C2(/C=C/c3cccc(C#N)c3)CCC3(CC2)OCCO3)cc1OC1CCCC1
Agent: Cl
Solvent: C1CCOC1
Product: COc1ccc(C2(/C=C/c3cccc(C#N)c3)CCC(=O)CC2)cc1OC1CCCC1
Temperature: 75 °C
Yield: 74.7 %

Procedure:
A solution of crude 4-(3-cyclopentyloxy-4-methoxyphenyl)-4-(2[E]-(3-cyanophenyl)ethenyl)-1,1-(ethylenedioxy)cyclohexane (0.58 g, 1.06 mmol) in tetrahydrofuran (20 mL) was treated with 3N aqueous hydrochloric acid (2.3 mL) under argon and heated at 75°-80° C. for 1 h. Additional hydrochloric acid (13 mL) was then added and the mixture heated at 75° C. for another 15 min. The reaction mixture was concentrated in vacuo, was extracted into methylene chloride, and the organic extract was washed with water, dilute sodium bicarbonate solution, brine, and was dried (sodium sulfate). Purification by chromatography (silica, 1 to 2% ethyl acetate in methylene chloride) and crystallization from ethyl ether gave the tided compound as a white solid (0.329 g, 74%). mp 116°-117° C. Anal. (C27H29NO3.1/6H2O) calcd: C 77.48, H 7.06, N 3.35, found: C 77.63, H 6.94, N 3.33. 1H-NMR (400 MHz, CDCl3) δ 7.60 (s, 1H), 7.55-7.45 (m, 2H), 7.39 (t, J=7.7 Hz, 1H), 6.97 (dd, J=2.4 Hz, J=8.5 Hz, 1H), 6.89 (d, J=8.4 Hz, 1H), 6.37 (d, J=16.1 Hz, 1H), 6.22 (d, J=16.2 Hz, 1H), 4.77 (p, J=4.5 Hz, 1H), 3.86 (s, 3H), 2.6-1.5 (m, 18H with H2O).
Reaction SMILES: C(O)[C@H]1O[C@H](O[C@@H]([C@H](O)[C@@H](O)CO)[C@H](O)CO)[C@H](O)[C@@H](O)[C@@H]1O.[CH2:24]1[C@H:32]([OH:33])[C@H:31]2[N:26]([CH2:27][C@H:28]([OH:36])[C@@H:29]([OH:35])[C@@H:30]2[OH:34])[CH2:25]1.C=CC(N)=O>>[CH2:24]1[C@H:32]([OH:33])[C@H:31]2[N:26]([C@H:27]([CH2:28][OH:36])[C@@H:29]([OH:35])[C@@H:30]2[OH:34])[CH2:25]1
Reactant: O[C@H]1[C@H](O)[C@@H](O)CN2CC[C@H](O)[C@H]12
Agent: C=CC(N)=O
Agent: OC[C@@H](O)[C@@H](O[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O)[C@H](O)[C@@H](O)CO
Product: OC[C@@H]1[C@@H](O)[C@H](O)[C@H]2[C@@H](O)CCN21

Procedure:
Materials. [2-3H] Mannose (15 Ci/mmole) and [6- 3H]galactose (15 Ci/mmole) were purchased from American Radiolabeled Chemicals, Inc. [4,5-3H]Leucine (50 Ci/mmole) was obtained from ICN, pronase was from Calbiochem, and endo-beta-N-acetylglucosaminidase H (Endo H1) was from Miles Scientific. Concanavalin A-Sepharose 4B, maltitol, amyloglucosidase (from Aspergillus niger), beta-glucosidase (from almonds), alpha-galactosidase (from Aspergillus niger), beta-galactosidase (from bovine liver), alpha-mannosidase (from jack bean), and all p-nitrophenyl-glycoside substrates were purchased from Sigma Chemical Company. Beta-Mannosidase was purified from Aspergillus niger as previously described (51). Glucosidase I and glucosidase II were partially purified from mung bean seedlings (50). [3H]Glucose-labeled Glc3Man9GlcNAc-oligosaccharide was isolated from influenza virus-infected MDCK cells labeled with [6-3H]galactose in the presence of castanospermine (52). Tissue culture materials were obtained from Flow Laboratories. Bio-Gel P-4 and Bio-Gel P-2 were purchased from Bio-Rad Laboratories, and Sephadex LH-20 was purchased from Pharmacia Fine Chemicals. Australine was isolated from Castanospermum australe mother liquors by ion exchange chromatography and TLC (53). Castanospermine was isolated from Castanospermum australe mother liquors by crystallization as reported elsewhere (2, 54). All additional chemicals were analytical grade.
Reaction SMILES: [O:1]1[C:5]2[CH:6]=[CH:7][C:8]([C:10]([OH:12])=O)=[CH:9][C:4]=2[O:3][CH2:2]1.[CH2:13]([C:15]1[CH:20]=[CH:19][C:18]([CH2:21][CH2:22][NH2:23])=[CH:17][CH:16]=1)[CH3:14]>>[CH2:13]([C:15]1[CH:20]=[CH:19][C:18]([CH2:21][CH2:22][NH:23][C:10]([C:8]2[CH:7]=[CH:6][C:5]3[O:1][CH2:2][O:3][C:4]=3[CH:9]=2)=[O:12])=[CH:17][CH:16]=1)[CH3:14]
Reactant: CCc1ccc(CCN)cc1
Reactant: O=C(O)c1ccc2c(c1)OCO2
Product: CCc1ccc(CCNC(=O)c2ccc3c(c2)OCO3)cc1

Procedure:
Prepared in a similar manner to example 4 using benzo[1,3]dioxole-5-carboxylic acid and 2-(4-ethyl-phenyl)-ethylamine. MS (M+H, 298.2).