Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[O:11][C:10]3[CH:12]=[CH:13][CH:14]=[CH:15][C:9]=3[N:8]=[C:7]([N:16]3[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]3)[C:6]=2[CH:22]=1.Br[CH2:24][C:25]([O:27][CH2:28][CH3:29])=[O:26].C(=O)([O-])[O-].[K+].[K+].O>CN(C)C=O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[O:11][C:10]3[CH:12]=[CH:13][CH:14]=[CH:15][C:9]=3[N:8]=[C:7]([N:16]3[CH2:21][CH2:20][N:19]([CH2:24][C:25]([O:27][CH2:28][CH3:29])=[O:26])[CH2:18][CH2:17]3)[C:6]=2[CH:22]=1
Reactant: CCOC(=O)CBr
Reactant: Clc1ccc2c(c1)C(N1CCNCC1)=Nc1ccccc1O2
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: CCOC(=O)CN1CCN(C2=Nc3ccccc3Oc3ccc(Cl)cc32)CC1
Reaction time: 3 h
Yield: 72 %

Procedure:
A mixture of 3.4 g of 2-chloro-11-(1-piperazinyl)dibenz[b,f][1,4]oxazepine, 2.00 g of ethyl bromoacetate and 1.38 g of potassium carbonate in 16 ml of N,N-dimethylformamide was stirred at 60°-70° C. for 3 hrs. After cooling, water was added to the reaction mixture and extracted with ether. The etheral layer was washed with water, dried and concentrated. The residue was chromatographed on silica gel using a mixture of n-hexane and ethyl acetate (2:1 and 1:1) as eluents to give 3.12 g of yellow crystals, which were recrystallized from n-hexane to give yellow prisms, mp 123°-123.5° C.
Reaction SMILES: [O:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6]1[N:10]([CH3:11])[N:9]=[CH:8][C:7]=1[C:12]#[N:13].S(=O)(=O)(O)[OH:15].[OH-].[Na+]>>[O:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6]1[N:10]([CH3:11])[N:9]=[CH:8][C:7]=1[C:12]([NH2:13])=[O:15]
Reactant: O=S(=O)(O)O
Reactant: Cn1ncc(C#N)c1-c1ccco1
Agent: [Na+]
Agent: [OH-]
Product: Cn1ncc(C(N)=O)c1-c1ccco1
Yield: 91 %

Procedure:
Stir 1.1 g of 5-(2-furyl)-1-methylpyrazole-4-carbonitrile together with 7 ml of concentrated sulfuric acid for 24 hours at room temperature. Pour the resulting mixture onto ice and adjust its pH-value to 4 with caustic soda. Then extract it with methylene chloride and reduce the organic phase to dryness to obtain 5-(2-furyl)-1-methylpyrazole-4-carboxamide [m.p. 115.5° to 116° C (from ethanol)] with a yield of 91%.
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[C:20]3[C:15](=[CH:16][CH:17]=[C:18]4[CH:24]=[C:23]([O:25][CH3:26])[CH:22]=[CH:21][C:19]4=3)[C:14]3[C:9]2=[CH:10][CH:11]=[CH:12][CH:13]=3)=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].Cl.Cl[CH2:35][CH2:36][N:37]1[CH2:42][CH2:41][CH2:40][CH2:39][CH2:38]1>CN(C)C=O>[CH3:26][O:25][C:23]1[CH:22]=[CH:21][C:19]2=[C:20]3[C:15](=[CH:16][CH:17]=[C:18]2[CH:24]=1)[C:14]1[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=1)[CH:8]3[C:5]1[CH:4]=[CH:3][C:2]([O:1][CH2:35][CH2:36][N:37]2[CH2:42][CH2:41][CH2:40][CH2:39][CH2:38]2)=[CH:7][CH:6]=1
Reactant: ClCCN1CCCCC1
Reactant: COc1ccc2c3c(ccc2c1)-c1ccccc1C3c1ccc(O)cc1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: COc1ccc2c3c(ccc2c1)-c1ccccc1C3c1ccc(OCCN2CCCCC2)cc1

Procedure:
Eight g of the compound of Example 2 was combined with 16.3 g of potassium carbonate and 4.6 g of 1-(2-chloroethyl)piperidine hydrochloride in 75 ml of dimethylformamide under anhydrous conditions, and the process was carried out and the product isolated as described in Example 6 above. The 9.5 g of product from the chromatography was recrystallized from isopropanol to obtain 8.74 g of the desired product, m.p. 130°-133° C.
Reaction SMILES: [Cl:1][C:2]1[C:12]2[CH2:11][CH2:10][NH:9][CH2:8][CH:7]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[C:6]=2[C:5]([Cl:19])=[C:4]([O:20][CH3:21])[C:3]=1[O:22][CH3:23].[OH-].[Na+].[CH3:26]COCC>C(O)=O.C=O>[Cl:1][C:2]1[C:12]2[CH2:11][CH2:10][N:9]([CH3:26])[CH2:8][CH:7]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[C:6]=2[C:5]([Cl:19])=[C:4]([O:20][CH3:21])[C:3]=1[O:22][CH3:23]
Reactant: COc1c(Cl)c2c(c(Cl)c1OC)C(c1ccccc1)CNCC2
Reactant: CCOCC
Agent: C=O
Agent: [Na+]
Agent: [OH-]
Solvent: O=CO
Product: COc1c(Cl)c2c(c(Cl)c1OC)C(c1ccccc1)CN(C)CC2

Procedure:
A mixture of 4 g of 6,9-dichloro-7,8-dimethoxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine in 15 ml of formic acid and 10 ml of formaldehyde is refluxed for 18 hours. The mixture is evaporated in vacuo. The residue is treated with 20 ml of 6 N hydrochloric acid. The solution is again evaporated to give a residue which is treated with 20 ml of 10% sodium hydroxide solution then taken into ether. The ethereal extracts are dried and evaporated to give 6,9-dichloro-7,8-dimethoxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine.
Reaction SMILES: Cl[C:2]1[CH:3]=[CH:4][C:5]([N+:9]([O-:11])=[O:10])=[C:6]([NH2:8])[CH:7]=1.[OH:12][CH:13]1[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]1.C([O-])([O-])=O.[K+].[K+].O>CN(C=O)C>[NH2:8][C:6]1[CH:7]=[C:2]([N:16]2[CH2:17][CH2:18][CH:13]([OH:12])[CH2:14][CH2:15]2)[CH:3]=[CH:4][C:5]=1[N+:9]([O-:11])=[O:10]
Reactant: OC1CCNCC1
Reactant: Nc1cc(Cl)ccc1[N+](=O)[O-]
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: Nc1cc(N2CCC(O)CC2)ccc1[N+](=O)[O-]
Temperature: 120 °C
Reaction time: 18 h

Procedure:
A mixture of 5-chloro-2-nitrophenylamine (1.3 g, 7.0 mmol), 4-hydroxypiperidine (2.2 g, 20 mmol), and K2CO3 (1.0 g, 7 mmol) in DMF (20 mL) was stirred at 120° C. for 18 h. The reaction mixture was cooled to room temperature, poured into water (50 mL) and extracted with EtOAc (3×50 mL). The combined organic extracts were dried over sodium sulfate, concentrated in vacuo, and the oily residue was triturated with 70/30 EtOAc/CHCl3 (8 mL) to yield a yellow solid. The solid product was collected by filtration, washed with 70:30 EtOAc/CHCl3 (8 mL), and dried in vacuo (0.63 g, 38%).
Reaction SMILES: [NH2:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:22]#[N:23])=[C:7]([C:13]3[CH:18]=[CH:17][C:16]([O:19][CH2:20][CH3:21])=[CH:15][CH:14]=3)[N:8]2[CH2:11][CH3:12])=[CH:4][CH:3]=1.[CH2:24]([N:26]=[C:27]=[O:28])[CH3:25]>ClCCl>[C:22]([C:6]1[C:5]2[C:9](=[CH:10][C:2]([NH:1][C:27]([NH:26][CH2:24][CH3:25])=[O:28])=[CH:3][CH:4]=2)[N:8]([CH2:11][CH3:12])[C:7]=1[C:13]1[CH:18]=[CH:17][C:16]([O:19][CH2:20][CH3:21])=[CH:15][CH:14]=1)#[N:23]
Reactant: CCOc1ccc(-c2c(C#N)c3ccc(N)cc3n2CC)cc1
Reactant: CCN=C=O
Solvent: ClCCl
Product: CCNC(=O)Nc1ccc2c(C#N)c(-c3ccc(OCC)cc3)n(CC)c2c1
Yield: 95.6 %

Procedure:
6-Amino-2-(4-ethoxyphenyl)-1-ethyl-1H-indole-3-carbonitrile (31 mg, 0.1 mmol) is treated with ethyl isocyanate (14 mg, 0.2 mmol) in dichloromethane (1.0 mL) at 40° C. overnight. The precipitate is collected via filtration, washed with dichloromethane and dried in air to furnish 1-[3-cyano-2-(4-ethoxy-phenyl)-1-ethyl-1H-indol-6-yl]-3-ethyl-urea (36 mg, 95%).
Reaction SMILES: C([O:8][C:9]1[CH:14]=[C:13]([O:15][CH3:16])[CH:12]=[CH:11][C:10]=1[CH:17]1[CH2:21][N:20]([C:22]2[CH:23]=[C:24]([CH:28]=[CH:29][CH:30]=2)[C:25]([NH2:27])=[O:26])[C:19](=[O:31])[CH2:18]1)C1C=CC=CC=1>CCO.CCOC(C)=O.[Pd]>[OH:8][C:9]1[CH:14]=[C:13]([O:15][CH3:16])[CH:12]=[CH:11][C:10]=1[CH:17]1[CH2:21][N:20]([C:22]2[CH:23]=[C:24]([CH:28]=[CH:29][CH:30]=2)[C:25]([NH2:27])=[O:26])[C:19](=[O:31])[CH2:18]1
Reactant: COc1ccc(C2CC(=O)N(c3cccc(C(N)=O)c3)C2)c(OCc2ccccc2)c1
Agent: [Pd]
Solvent: CCO
Solvent: CCOC(C)=O
Product: COc1ccc(C2CC(=O)N(c3cccc(C(N)=O)c3)C2)c(O)c1
Reaction time: 20 h
Yield: 85.1 %

Procedure:
3-[4-(2-Benzyloxy-4-methoxyphenyl)-2-oxo-pyrrolidin-1-yl]benzamide (1.8 g, crude) was dissolved in 50 mL of EtOH and 20 mL of EtOAc. 10% Pd/C (200 mg) was added and the mixture was stirred under H2 for 20 h. After filtration and concentration, the residue was purified on silica gel to give 1.2 g of the desired product.
Reaction SMILES: Cl[CH:2]([C:7]1[CH:12]=[C:11]([Cl:13])[CH:10]=[C:9]([CH3:14])[C:8]=1[O:15][CH3:16])[C:3]([O:5]C)=[O:4].S1CC(=[O:22])NC1=O>>[OH:22][CH:2]([C:7]1[CH:12]=[C:11]([Cl:13])[CH:10]=[C:9]([CH3:14])[C:8]=1[O:15][CH3:16])[C:3]([OH:5])=[O:4]
Reactant: COC(=O)C(Cl)c1cc(Cl)cc(C)c1OC
Reactant: O=C1CSC(=O)N1
Product: COc1c(C)cc(Cl)cc1C(O)C(=O)O

Procedure:
It was converted to methyl alpha-chloro-alpha-(5-chloro-2-methoxy-3-methylphenyl)acetate by the chlorination/esterification procedure of Preparation A. The product was used directly to prepare the thiazolidine-2,4-dione of Example 4.
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C@H:9]([C:15](=[O:21])[N:16]1[CH2:20][CH2:19][CH2:18][CH2:17]1)[CH2:10][C:11]([O:13][CH3:14])=[O:12])=[O:7])([CH3:4])([CH3:3])[CH3:2].C[Si](C)(C)[N-][Si](C)(C)C.[K+].[CH2:32](Br)[CH:33]=[CH2:34]>C1COCC1>[C:1]([O:5][C:6]([NH:8][C@@H:9]([C@H:10]([CH2:34][CH:33]=[CH2:32])[C:11]([O:13][CH3:14])=[O:12])[C:15](=[O:21])[N:16]1[CH2:17][CH2:18][CH2:19][CH2:20]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: COC(=O)C[C@H](NC(=O)OC(C)(C)C)C(=O)N1CCCC1
Reactant: C=CCBr
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [K+]
Solvent: C1CCOC1
Product: C=CC[C@H](C(=O)OC)[C@H](NC(=O)OC(C)(C)C)C(=O)N1CCCC1
Temperature: -78 °C
Reaction time: 0.5 h

Procedure:
To a stirred solution of the product from Step A (2.05 g, 6.83 mmol) in THF (30 mL) was added potassium hexamethyldisilazide (30.0 mL, 0.5M in toluene, 15.0 mmol) at −78° C. The resulting mixture was stirred at −78° C. for 30 min. Allyl bromide (3.0 mL, 34.7 mmol) was then added. After stirring at −78° C. for 2 h, the reaction was quenched with saturated aqueous ammonium chloride solution. The organic phase was separated and the aqueous phase was extracted with two portions of ethyl acetate. The combined organic layers were washed with brine and concentrated in vacuo. Purification by flash chromatography (30:70 hexanes/ethyl acetate) afforded the desired product (major diastereoisomer from the reaction).
Reaction SMILES: F[C:2]1[CH:7]=[C:6]([C:8]2[C:9]([O:16][CH3:17])=[N:10][C:11]([CH3:15])=[CH:12][C:13]=2[CH3:14])[CH:5]=[CH:4][C:3]=1[C:18]1[N:22]([CH:23]2[CH2:28][CH2:27][O:26][CH2:25][CH2:24]2)[N:21]=[CH:20][C:19]=1[C:29]([NH2:31])=[O:30].O>CN1C(=O)CCC1>[CH3:17][O:16][C:9]1[C:8]([C:6]2[CH:7]=[CH:2][C:3]3[C:18]4[N:22]([CH:23]5[CH2:28][CH2:27][O:26][CH2:25][CH2:24]5)[N:21]=[CH:20][C:19]=4[C:29](=[O:30])[NH:31][C:4]=3[CH:5]=2)=[C:13]([CH3:14])[CH:12]=[C:11]([CH3:15])[N:10]=1
Reactant: COc1nc(C)cc(C)c1-c1ccc(-c2c(C(N)=O)cnn2C2CCOCC2)c(F)c1
Solvent: O
Solvent: CN1CCCC1=O
Product: COc1nc(C)cc(C)c1-c1ccc2c(c1)[nH]c(=O)c1cnn(C3CCOCC3)c12
Temperature: 90 °C
Reaction time: 0.5 h
Yield: 60.2 %

Procedure:
KTB (655 mg) was added to a solution of 5-[2-fluoro-4-(2-methoxy-4,6-dimethylpyridin-3-yl)phenyl]-(tetrahydro-2H-pyran-4-yl)-1H-pyrazole-4-carboxamide (1.52 g) in NMP (15 mL), and the mixture was stirred at 90° C. for 30 minutes. KTB (40 mg) was added to the reaction mixture, and the mixture was stirred at 90° C. for 30 minutes. Further, KTB (40 mg) was added to the reaction mixture, and the mixture was stirred at 90° C. for 30 minutes. The reaction mixture was cooled to room temperature. Water (3 mL) was added to the reaction mixture. The solid was precipitated. After stirring for one hour directly, the precipitated solid was collected by filtration. The residue was washed with water (1 mL). The resulting solid was suspended in 1-propanol/water (9/1) (2 mL) and dissolved by heating under reflux. The solution was cooled to room temperature over one hour. The precipitated solid was collected by filtration. The resulting solid was dried under reduced pressure at 50° C. to give the title compound (872 mg). The instrumental data were identical to those of the title compound synthesized in Example 4.
Reaction SMILES: Br[CH2:2][C:3]1([C:6]2[CH:11]=[CH:10][C:9]([I:12])=[CH:8][CH:7]=2)[CH2:5][CH2:4]1.[N-:13]=[N+:14]=[N-:15].[Na+].CCOC(C)=O>CN(C=O)C>[N:13]([CH2:2][C:3]1([C:6]2[CH:11]=[CH:10][C:9]([I:12])=[CH:8][CH:7]=2)[CH2:5][CH2:4]1)=[N+:14]=[N-:15]
Reactant: BrCC1(c2ccc(I)cc2)CC1
Reactant: [N-]=[N+]=[N-]
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: [N-]=[N+]=NCC1(c2ccc(I)cc2)CC1
Yield: 80.1 %

Procedure:
Part A. 1-(1-Bromomethylcyclopropyl)-4-iodobenzene (2.0 g, 5.97 mmol) and NaN3 (1.0 g, 15.38 mmol, 2.6 eq) were stirred in DMF (10 mL) overnight. Analytical LC-MS showed completion of the reaction. EtOAc was added to the solution. The mixture was washed with H2O and brine, dried over MgSO4, and concentrated to give 1-(1-azidomethyl-cyclopropyl)-4-iodobenzene (1.43 g, yield: 80%). The azide (1.40 g, 4.68 mmol) and PPh3 (1.84 g, 7.02 mmol, 1.5 eq) were stirred in THF (10 mL) at RT for 40 min. H2O (2 mL) was added, and the solution was stirred at 50° C. for 6 h. LC-MS showed completion of the reaction. The mixture was extracted with Et2O (2×). The aqueous layer was basified with 50% NaOH, extracted with CH2Cl2 (2×), washed with H2O, brine, dried over MgSO4, and concentrated to give 1-(4-iodophenyl)cyclopropyl methylamine (0.98 g, yield: 75%).
Reaction SMILES: COC1C=CC(C([O:22][CH2:23][CH:24]([OH:29])[CH2:25][N:26]([CH3:28])[CH3:27])(C2C=CC=CC=2)C2C=CC(OC)=CC=2)=CC=1.C(N(CC)C(C)C)(C)C.[C:41]([Si:45]([CH3:48])([CH3:47])Cl)([CH3:44])([CH3:43])[CH3:42]>CN(C)C=O>[Si:45]([O:22][CH2:23][CH:24]([OH:29])[CH2:25][N:26]([CH3:27])[CH3:28])([C:41]([CH3:44])([CH3:43])[CH3:42])([CH3:48])[CH3:47]
Reactant: COc1ccc(C(OCC(O)CN(C)C)(c2ccccc2)c2ccc(OC)cc2)cc1
Reactant: CC(C)(C)[Si](C)(C)Cl
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: CN(C)CC(O)CO[Si](C)(C)C(C)(C)C
Reaction time: 3 h

Procedure:
3-Dimethylamino-1,2-propanediol (5), (50.1 g, 420.4 mmol) was weighed into a 2 L round bottomed flask with a stir bar. The flask was sealed, flushed with argon, charged with N,N-dimethylformamide (750 mL) and N,N-diisopropylethylamine (111 mL, 630.7 mmol) and cooled to 0° C. t-Butyldimethylchlorosilane (67.0 g, 1.05 equiv.) was weighed into a 500 mL round bottomed flask, sealed and then dissolved in N,N-dimethylformamide (250 mL). The t-butyldimethylchlorosilane solution was transferred to a pressure equalizing dropping funnel and added to the stirring reaction mixture slowly over 20 minutes. The reaction was allowed to come to room temperature while stirring over 3 hours. The reaction was concentrated in vacuo. Saturated bicarbonate (1500 mL) was added to the residue and the mixture transferred to a 4 L separatory funnel. The aqueous phase was extracted with ethyl acetate (3×500 mL). The organic phases were combined, dried over MgSO4, filtered, concentrated and dried under high vacuum to afford 97.81 g (99.7%) of clear, colorless oil that was used without further purification.
Reaction SMILES: FC(F)(F)C1C=C(C=C(C(F)(F)F)C=1)[CH2:6][N:7](C)[C:8](=[O:28])[C:9]1[C:14]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2[CH3:21])=[CH:13][C:12]([N:22]2[CH2:27][CH2:26][O:25][CH2:24][CH2:23]2)=[N:11][CH:10]=1.Cl[CH2:40][C:41]1[C:50]2[C:45](=[CH:46][CH:47]=[CH:48][CH:49]=2)[CH:44]=[CH:43][C:42]=1[CH3:51]>>[CH3:6][N:7]([CH2:40][C:41]1[C:50]2[C:45](=[CH:46][CH:47]=[CH:48][CH:49]=2)[CH:44]=[CH:43][C:42]=1[CH3:51])[C:8](=[O:28])[C:9]1[C:14]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2[CH3:21])=[CH:13][C:12]([N:22]2[CH2:23][CH2:24][O:25][CH2:26][CH2:27]2)=[N:11][CH:10]=1
Reactant: Cc1ccc2ccccc2c1CCl
Reactant: Cc1ccccc1-c1cc(N2CCOCC2)ncc1C(=O)N(C)Cc1cc(C(F)(F)F)cc(C(F)(F)F)c1
Product: Cc1ccccc1-c1cc(N2CCOCC2)ncc1C(=O)N(C)Cc1c(C)ccc2ccccc12

Procedure:
The parent compound was obtained as a white solid in comparable yield according to the procedure described above for the preparation of N-(3,5-bis-trifluoromethyl-benzyl)-N-methyl-6-morpholin-4-yl-4-o-tolyl-nicotinamide (Example 16, step d) using 1-chloromethyl-2-methylnaphthalene instead of 3,5-bis-trifluoromethyl-benzyl bromide.
Reaction SMILES: [C:1]1([C:7]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)([CH2:17][CH:18]=[CH2:19])[CH2:8][CH:9]2[CH2:14][CH:13]3[CH2:15][CH2:16][N:10]2[CH2:11][CH2:12]3)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[H][H]>C(O)C.[Pd]>[C:20]1([C:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)([CH2:17][CH2:18][CH3:19])[CH2:8][CH:9]2[CH2:14][CH:13]3[CH2:15][CH2:16][N:10]2[CH2:11][CH2:12]3)[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1
Reactant: C=CCC(CC1CC2CCN1CC2)(c1ccccc1)c1ccccc1
Reactant: [H][H]
Agent: [Pd]
Solvent: CCO
Product: CCCC(CC1CC2CCN1CC2)(c1ccccc1)c1ccccc1

Procedure:
0.50 Parts of 2-(2,2-diphenyl-4-pentenyl)-1-azabicyclo[2.2.2]octane is dissolved in 50 parts by volume of ethanol. This solution is then added to a Parr hydrogenation bottle which contains 0.05 parts of 5% palladium-on-carbon. The mixture is hydrogenated at room temperature and atmosphere pressure using a 50 ml buret to measure hydrogen uptake. After the hydrogenation is completed the catalyst is removed by filtration. The solution is then stripped in vacuo to afford a gum. Crystallization of this gum from methanol/water affords a white solid which is dried in vacuo at 60° C. for 4 hours to give 2-(2,2-diphenylpentyl)-1-azabicyclo[2.2.2]octane. This compound melts at about 115°-117.5° C. and is represented by the following structural formula ##STR8##
Reaction SMILES: [Br:1][C:2]1[CH:10]=[CH:9][C:5]([C:6](Cl)=[O:7])=[CH:4][CH:3]=1.[CH3:11][O:12][C:13](=[O:19])[CH:14]=[C:15]([NH:17][CH3:18])[CH3:16].N1C=CC=CC=1.Cl.N1C=CC=CC=1>C1COCC1>[CH3:11][O:12][C:13](=[O:19])[CH:14]([C:6](=[O:7])[C:5]1[CH:9]=[CH:10][C:2]([Br:1])=[CH:3][CH:4]=1)/[C:15](=[N:17]/[CH3:18])/[CH3:16]
Reactant: O=C(Cl)c1ccc(Br)cc1
Reactant: CNC(C)=CC(=O)OC
Agent: Cl
Solvent: c1ccncc1
Solvent: C1CCOC1
Product: C/N=C(\C)C(C(=O)OC)C(=O)c1ccc(Br)cc1
Temperature: 0 °C
Reaction time: 8 h

Procedure:
4-Bromobenzoyl chloride (17.14 g, 78.1 mmol) and 3-methylamino-but-2-enoic acid methyl ester (10.0 g, 78.1 mmol) were combined in THF (600 mL) and cooled to 0° C. Pyridine (6.8 mL, 85.9 mmol) was added by syringe, and the reaction was stirred overnight at room temperature. Solid pyridine hydrochloride was observed on the flask walls, so the solution was decanted and then concentrated to 10% of its original volume. The residue was diluted with EtOAc (400 mL) and washed twice with H2O. The organic layer was dried, filtered, and concentrated to give the title compound.
Reaction SMILES: [CH2:1]1[N:6](C(C2C=CC=CC=2)C2C=CC=CC=2)[C@H:5]([CH2:20][OH:21])[C@@H:4]([OH:22])[C@H:3]([OH:23])[C@H:2]1[OH:24]>CO.O.[Pd].[C]>[CH2:1]1[NH:6][C@H:5]([CH2:20][OH:21])[C@@H:4]([OH:22])[C@H:3]([OH:23])[C@H:2]1[OH:24]
Reactant: OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)CN1C(c1ccccc1)c1ccccc1
Agent: [Pd]
Solvent: CO
Solvent: O
Product: OC[C@H]1NC[C@H](O)[C@@H](O)[C@@H]1O
Reaction time: 2 h
Yield: 99 %

Procedure:
A mixture of N-benzhydryl-1-deoxynojirimycin as prepared in Example 2 (Formula VI, 1.00 g, 3.06 mmol) and 20% PD(OH)2 /carbon (0.20 g) in 40 mL of methanol was hydrogenated (60 psig) in a Parr apparatus for 24 h. The mixture was filtered through Celite, and the filtrate was concentrated to a light grey foam. The foam was washed with hexane and then dissolved in water (10 mL) and stirred over Dowex® 50W-X8 ion exchange beads for 2 h. The beads were washed with 1N aqueous NH4OH solution until TLC analysis indicated the product had been completely removed from the resin. The combined ammonia washings were lyophilized to give 0.49 g (99%) of 1-deoxynojirimycin as a white foam, mp 198°-201° C. (literature mp 198°-202° C.: Kinast, G.; Schedel, M. Angew. Chem. Int. Ed. Eng. 1981, 20, 805). The 400-MHz 1H NMR spectrum of the material was identical to that of an authentic sample of 1-deoxynojirimycin (Sigma).
Reaction SMILES: [C:1]([O:4][C:5](=[O:7])[CH3:6])(=O)[CH3:2].OCC[N:11]1[CH:15]=[CH:14][CH:13]=[CH:12]1.N1C=CC=CC=1>O>[C:5]([O:4][CH2:1][CH2:2][N:11]1[CH:15]=[CH:14][CH:13]=[CH:12]1)(=[O:7])[CH3:6]
Reactant: OCCn1cccc1
Reactant: CC(=O)OC(C)=O
Solvent: c1ccncc1
Solvent: O
Product: CC(=O)OCCn1cccc1
Temperature: 25 °C
Yield: 55 %

Procedure:
The resulting product is reacted with acetic anhydride in accordance with the method of F. F. Blicke and E. S. Blake, J. Am. Chem. Soc., 53, 1015(1931). A mixture of 1-(2-hydroxyethyl)pyrrole (147 g, 1.32 mole), pyridine (415 ml) and acetic anhydride (139 ml) is heated on a steam bath for 0.5 hours. The reaction mixture is cooled to room temperature, poured into water (one l) and the product is extracted into ethyl acetate (3×1 l ). The extract is washed successively with dilute hydrochloric acid, saturated sodium chloride solution, dilute sodium bicarbonate solution, and again with saturated sodium chloride solution. The extract is dried over sodium sulfate, evaporated in vacuo and the residue (150 g) is subjected to column chromatography on Florisil® activated magnesium silicate. The desired product is eluted with hexane-dichloromethane (1:1) to give 128 g (55%) 1-(2-acetoxyethyl)pyrrole, an oil.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([C@@H:15]([O:18][Si:19]([CH2:24][CH3:25])([CH2:22][CH3:23])[CH2:20][CH3:21])[CH2:16]I)=[CH:11][C:10]=1[NH:26][S:27]([CH3:30])(=[O:29])=[O:28])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:31]([NH2:38])[C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1>>[CH2:31]([NH:38][CH2:16][C@@H:15]([C:12]1[CH:13]=[CH:14][C:9]([O:8][CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)=[C:10]([NH:26][S:27]([CH3:30])(=[O:29])=[O:28])[CH:11]=1)[O:18][Si:19]([CH2:24][CH3:25])([CH2:22][CH3:23])[CH2:20][CH3:21])[C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1
Reactant: NCc1ccccc1
Reactant: CC[Si](CC)(CC)O[C@@H](CI)c1ccc(OCc2ccccc2)c(NS(C)(=O)=O)c1
Product: CC[Si](CC)(CC)O[C@@H](CNCc1ccccc1)c1ccc(OCc2ccccc2)c(NS(C)(=O)=O)c1
Temperature: 65 °C
Reaction time: 22 h
Yield: 81.4 %

Procedure:
N-[2-benzyloxy-5-((1R)-2-iodo-1-triethylsilanyloxy-ethyl)-phenyl]-methanesulfonamide (0.56 g, 1 mmol) was dissolved in benzylamine (0.54 g, 5 mmol) and stirred at 65° C. for 22 h. The mixture was then cooled to room temperature, and stirred with hexanes. The hexanes solution was filtered through a pad of silica gel, and the residue was stirred with ether (10 ml). The ether solution was diluted with 10 ml of hexanes, and passed through the silica gel pad. The filter pad was eluted with ether-hexanes (1:1 to 3:1), and the filtrate was evaporated. The residue was washed with isooctane to give 0.44 g of a colorless gum; MS (ES) m/z 541.1 (MH+); HRMS (EI) Calcd. for C29H40N2O4SSi (M+): 540.2478, Found: 540.2472.
Reaction SMILES: [C:1]([O:9][CH3:10])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20]CO.C(OC(C)C)(C)C>>[C:1]([O:9][CH2:10][CH2:20][CH2:19][CH2:18][CH2:17][CH2:16][CH2:15][CH2:14][CH2:13][CH2:12][NH2:11])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: NCCCCCCCCCCO
Reactant: COC(=O)c1ccccc1
Solvent: CC(C)OC(C)C
Product: NCCCCCCCCCCOC(=O)c1ccccc1
Yield: 90 %

Procedure:
In an argon atmosphere, a mixture of methyl benzoate (3.0 mmol), 10-aminodecan-1-ol (3.6 mmol), Zn4(OCOCF3)6O (1.25 mol % in terms of mole number) and diisopropyl ether (5.0 ml) was heated to reflux for 20 hours, and as a result, 10-aminodecyl benzoate was obtained at a yield of 90%. The yield of 10-benzoylaminodecyl benzoate was 7%.
Reaction SMILES: [OH:1][CH2:2][C@@H:3]([NH:8][C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])[CH2:4][CH:5]([CH3:7])[CH3:6].Cl[C:17]1[CH:18]=[CH:19][C:20]2[C:30]3[C:25](=[CH:26][N:27]=[CH:28][CH:29]=3)[CH:24]([C:31]([F:34])([F:33])[F:32])[O:23][C:21]=2[CH:22]=1>>[CH3:6][CH:5]([CH3:7])[CH2:4][C@H:3]([NH:8][C:9](=[O:15])[O:10][C:11]([CH3:13])([CH3:12])[CH3:14])[CH2:2][O:1][C:17]1[CH:18]=[CH:19][C:20]2[C:30]3[C:25](=[CH:26][N:27]=[CH:28][CH:29]=3)[CH:24]([C:31]([F:33])([F:34])[F:32])[O:23][C:21]=2[CH:22]=1
Reactant: CC(C)C[C@@H](CO)NC(=O)OC(C)(C)C
Reactant: FC(F)(F)C1Oc2cc(Cl)ccc2-c2ccncc21
Product: CC(C)C[C@@H](COc1ccc2c(c1)OC(C(F)(F)F)c1cnccc1-2)NC(=O)OC(C)(C)C
Yield: 49 %

Procedure:
Prepared as described in Example 8, Part C using (S)-tert-butyl (1-hydroxy-4-methylpentan-2-yl)carbamate and 8-chloro-5-(trifluoromethyl)-5H-chromeno[3,4-c]pyridine to afford tert-butyl ((2S)-4-methyl-1-((5-(trifluoromethyl)-5H-chromeno[3,4-c]pyridin-8-yl)oxy)pentan-2-yl)carbamate (0.28 g, 0.516 mmol, 49% yield) as a yellow solid. LCMS (ESI) m/e 467.2 [(M+H)+, calcd for C24H30F3N2O4 467.2]; LC/MS retention time (Method C): tR=2.19 min.