Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][CH:2]([C:4]1[N:8]=[C:7]([N:9]2[CH2:14][CH2:13][CH:12]([OH:15])[CH2:11][CH2:10]2)[O:6][N:5]=1)[CH3:3].C[N+]1([O-])CCOCC1.C([N+](CCC)(CCC)CCC)CC>ClCCl>[CH3:3][CH:2]([C:4]1[N:8]=[C:7]([N:9]2[CH2:10][CH2:11][C:12](=[O:15])[CH2:13][CH2:14]2)[O:6][N:5]=1)[CH3:1]
Reactant: CC(C)c1noc(N2CCC(O)CC2)n1
Agent: CCC[N+](CCC)(CCC)CCC
Agent: C[N+]1([O-])CCOCC1
Solvent: ClCCl
Product: CC(C)c1noc(N2CCC(=O)CC2)n1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
1-[3-(Propan-2-yl)-1,2,4-oxadiazol-5-yl]piperidin-4-ol (0.5 g) is dissolved in dichloromethane (75 mL) and 4 A molecular sieves (4 g) are added followed by N-methylmorpholine-N-oxide (1.52 g) and tetrapropylammonium perrhutenate (0.018 g) and the mixture is stirred at room temperature for 1 h. The reaction is then filtered through celite and the mother liquor washed with water (2×50 mL). The water layers are then combined and back extracted with dichloroemthane (100 mL). The dichloromethane layers are combined, dried over Na2SO4, filtered and concentrated to give the title compound. LC (method 20): tR=1.67 min; Mass spectrum (APCI): m/z=210 [M+H]+.
Reaction SMILES: [C@@H:1]1([N:9]2[C:18]3[N:17]=[CH:16][N:15]=[C:13](O)[C:12]=3[N:11]=[CH:10]2)[O:8][C@H:5]([CH2:6][OH:7])[C@@H:3]([OH:4])[CH2:2]1.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C.[N+:55]([C:58]1[CH:63]=[CH:62][CH:61]=[CH:60][C:59]=1[CH:64]([NH2:66])[CH3:65])([O-:57])=[O:56]>CN(C=O)C>[N+:55]([C:58]1[CH:63]=[CH:62][CH:61]=[CH:60][C:59]=1[CH:64]([NH:66][C:13]1[C:12]2[N:11]=[CH:10][N:9]([C:18]=2[N:17]=[CH:16][N:15]=1)[C@@H:1]1[O:8][C@H:5]([CH2:6][OH:7])[C@@H:3]([OH:4])[CH2:2]1)[CH3:65])([O-:57])=[O:56]
Reactant: OC[C@H]1O[C@@H](n2cnc3c(O)ncnc32)C[C@@H]1O
Reactant: CC(N)c1ccccc1[N+](=O)[O-]
Agent: CN(C)[P+](On1nnc2ccccc21)(N(C)C)N(C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: CC(Nc1ncnc2c1ncn2[C@H]1C[C@H](O)[C@@H](CO)O1)c1ccccc1[N+](=O)[O-]
Temperature: 25 °C
Reaction time: 64 h

Procedure:
To a suspension of 2′-deoxyinosine (100 mg, 0.4 mmol) and benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (BOP, 210 mg, 0.48 mmol) in anhydrous DMF (1 mL), N,N-diisopropylethylamine (100 μL, 0.6 mmol) was added followed by the addition of a solution of 1-(2-nitrophenyl)ethylamine (250 mg, 1.51 mmol) in DMF (1 mL). The reaction was stirred at room temperature for 64 hours. Silica gel 60 (1 g, 60-200 mesh) was added, and the mixture was evaporated in vacuo to dryness. The residue was purified by silica gel column chromatography to yield N6-[1-(2-nitrophenyl)ethyl]-2′-deoxyadenosine dA.19 (67 mg, 42%, 1:1 mixture of diastereomers) as a white foam.
Reaction SMILES: [OH:1][CH2:2][CH2:3][N:4]1[C:8](=[O:9])[C:7]2=[CH:10][CH:11]=[CH:12][CH:13]=[C:6]2[C:5]1=[O:14].[CH3:15][C:16]1[O:22]C(C)(C)O[C:18](=[O:19])[CH:17]=1>C1(C)C=CC=CC=1.C1(C)C=CC(S(O)(=O)=O)=CC=1>[C:18]([O:1][CH2:2][CH2:3][N:4]1[C:8](=[O:9])[C:7]2=[CH:10][CH:11]=[CH:12][CH:13]=[C:6]2[C:5]1=[O:14])(=[O:19])[CH2:17][C:16]([CH3:15])=[O:22]
Reactant: CC1=CC(=O)OC(C)(C)O1
Reactant: O=C1c2ccccc2C(=O)N1CCO
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: Cc1ccccc1
Product: CC(=O)CC(=O)OCCN1C(=O)c2ccccc2C1=O
Yield: 76.4 %

Procedure:
A solution of 10.0 g (52.3 mmol) of N-(2-hydroxyethyl)phthalimide, 8.84 ml (67.7 mmol) of 2,2,6-trimethyl-1,3-dioxen-4-one, and 10 mg of p-toluenesulfonic acid in 50 ml of toluene is heated at reflux under N2 for 4 hr. The solvent is removed under vacuum and the dark-colored residue is flash chromatographed on silica gel (1:1 hexane-EtOAc). The resulting product is recrystallized from EtOAc to give 11.0 g of 2-phthalimidoethyl acetoacetate.
Reaction SMILES: [NH2:1][C:2]1[C:7]2=[C:8]([C:18]3[CH:23]=[CH:22][C:21]([N+:24]([O-])=O)=[CH:20][CH:19]=3)[C:9](/[CH:11]=[CH:12]/[C:13]([O:15][CH2:16][CH3:17])=[O:14])=[CH:10][N:6]2[N:5]=[CH:4][N:3]=1>C(O)(=O)C.O=[Pt]=O>[NH2:1][C:2]1[C:7]2=[C:8]([C:18]3[CH:19]=[CH:20][C:21]([NH2:24])=[CH:22][CH:23]=3)[C:9]([CH2:11][CH2:12][C:13]([O:15][CH2:16][CH3:17])=[O:14])=[CH:10][N:6]2[N:5]=[CH:4][N:3]=1
Reactant: CCOC(=O)/C=C/c1cn2ncnc(N)c2c1-c1ccc([N+](=O)[O-])cc1
Agent: O=[Pt]=O
Solvent: CC(=O)O
Product: CCOC(=O)CCc1cn2ncnc(N)c2c1-c1ccc(N)cc1
Reaction time: 24 h
Yield: 90.4 %

Procedure:
A suspension of PtO2 (16 mg, 0.070 mmol) in acetic acid (0.5 ml) was added to a suspension of ethyl (2E)-3-[4-amino-5-(4-nitrophenyl)pyrrolo[2,1-f][1,2,4]triazin-6-yl]acrylate (144 mg, 0.408 mmol) in acetic acid (2 ml) under N2 atmosphere. The flask was evacuated and refilled with hydrogen gas (3×) and the reaction proceeded under a hydrogen atmosphere (1 atm) for 1 d. Additional PtO2 (50 mg, 0.22 mmol) in acetic acid (0.5 ml) was added and the reaction proceeded under H2 atmosphere for an additional 1 d. The reaction was filtered through a Celite pad and washed with MeOH. It was evaporated to dryness, diluted with EtOAc and washed with aqueous Na2CO3. The aqueous layer was back extracted with EtOAc (2×). Organic was dried (Na2SO4), filtered, and evaporated to dryness to afford the above compound as a yellow solid (120 mg, yield 90%). 1H-NMR (CD3OD) δ 7.70 (s, 1H), 7.47 (s, 1H), 7.12 (d, J=8.3 Hz, 2H), 6.84 (d, J=8.3 Hz, 2H), 4.06 (q, J=7.8 Hz, 2H), 2.82 (t, J=7.8 Hz, 2H), 2.48 (t, J=7.7 Hz, 2H), 1.18 (t, J=7.8 Hz, 3H); MS [M+H]+=326; LCMS RT=1.20 min.
Reaction SMILES: [C:1]([C:3]1[CH:4]=[C:5]([C:9]2[NH:13][C:12](=[O:14])[C:11]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[N:10]=2)[CH:6]=[CH:7][CH:8]=1)#[N:2].[H][H]>[Ni].CO>[NH2:2][CH2:1][C:3]1[CH:4]=[C:5]([C:9]2[NH:13][C:12](=[O:14])[C:11]([C:21]3[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=3)([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[N:10]=2)[CH:6]=[CH:7][CH:8]=1
Reactant: [H][H]
Reactant: N#Cc1cccc(C2=NC(c3ccccc3)(c3ccccc3)C(=O)N2)c1
Agent: [Ni]
Solvent: CO
Product: NCc1cccc(C2=NC(c3ccccc3)(c3ccccc3)C(=O)N2)c1
Reaction time: 8 h
Yield: 64.3 %

Procedure:
To a glass bomb was added 100 mg (0.296 mmol) of the compound of Example 2, the 3-cyanophenyl derivative, and 10 mg of freshly washed Raney nickel in 6 mL of a 5:1 MeOH:NH4OH(conc.) solution. The reaction vessel was charged with 50 psi hydrogen and shaken overnight. Upon completion the reaction was filtered through Celite and the solvent was evaporated in vacuo. Chromatography of the crude solid (Silica gel/Hexanes:Acetone 2:1) produced 65 mg (64%) of the desired amine as an off-white solid. LRMS m/z (ESI) 342.3 (M+H).
Reaction SMILES: [C:1]1([C:7](=[CH:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[Cl:18])[C:8]([OH:10])=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH3:19]O>>[CH3:19][O:9][C:8](=[O:10])[C:7]([C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1)=[CH:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[Cl:18]
Reactant: CO
Reactant: O=C(O)C(=Cc1ccccc1Cl)c1ccccc1
Product: COC(=O)C(=Cc1ccccc1Cl)c1ccccc1
Reaction time: 0.25 h

Procedure:
αPhenyl-2-chlorocinnamic acid (26.29 g (0.102 M) was dissolved in methanol (300 cc). Anhydrous HCl was bubbled through the reaction mixture with stirring for 15 minutes. The reaction mixture was refluxed for 2 hours, then HCl was bubbled through the reaction mixture for another 15 minutes. The reaction was stirred at reflux overnight. The methanol was removed in vacuo and the residue taken up in ether. The ether solution was washed with H2O, saturated NaHCO3 solution, and brine. It was then dried over MgSO4. The ether solution was concentrated in vacuo to yield an oil that quickly solidified to yield 27.13 g of product, mp 67-69° C.
Reaction SMILES: [B:1]1([CH2:10][CH2:11][CH2:12][CH2:13][Br:14])OC2C(=CC=CC=2)O1.[OH:15][C:16]([C:19]([OH:22])([CH3:21])[CH3:20])([CH3:18])[CH3:17]>C1COCC1>[Br:14][CH2:13][CH2:12][CH2:11][CH2:10][B:1]1[O:22][C:19]([CH3:21])([CH3:20])[C:16]([CH3:18])([CH3:17])[O:15]1
Reactant: CC(C)(O)C(C)(C)O
Reactant: BrCCCCB1Oc2ccccc2O1
Solvent: C1CCOC1
Product: CC1(C)OB(CCCCBr)OC1(C)C
Reaction time: 16 h
Yield: 97.4 %

Procedure:
After gently warming until melted, 4-bromo-1-butylboronic acid catechol ester (112.2 g, 0.44 mol, 1.0 equiv), while under a stream of nitrogen, was added to a 3-necked 500 mL round-bottomed flask, diluted with freshly distilled THF (150 mL, 3.0 M) and treated with pinacol (104.0 g, 0.88 mol, 2 equiv) in one portion. After stirring for 16 h under a nitrogen atmosphere the resulting solution was concentrated. The crude product was diluted with heptane (500 mL) and cooled in an ice-water bath. After 1 h, the precipitated catechol was removed by filtration and the remaining solution was filtered through a short pad of silica gel (500 g) wetted with heptane. After eluting with solutions of 5% ethyl acetate in heptane (700 mL) and 10% ethyl acetate in heptane (700 mL), the filtrate was concentrated to give 2-(4-bromobutyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane as a colorless oil (112.7 g, 97%). 1H NMR (CDCl3, 300 MHz) δ 3.38 (t, J=6.6 Hz, 2H), 1.90-1.78 (m, 2H), 1.58-1.44 (m, 2H), 1.26 (s, 12H), 0.78 (t, J=7.5 Hz, 2H); ESI-LCMS m/z calcd for C10H20BBrO2: expected 262.1. found 263.1 (M+H)+.
Reaction SMILES: Br[C:2]1[CH:17]=[CH:16][CH:15]=[C:14]([N+:18]([O-:20])=[O:19])[C:3]=1[O:4][CH2:5][CH2:6][O:7][CH:8]1[CH2:13][CH2:12][CH2:11][CH2:10][O:9]1.C(=O)([O-])O.[Na+].[CH:26]1([C:32]2[C:40]3[C:35](=[CH:36][C:37]([C:41]([O:43][CH3:44])=[O:42])=[CH:38][CH:39]=3)[NH:34][C:33]=2B2OC(C)(C)C(C)(C)O2)[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]1>COCCOC.O.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>[CH:26]1([C:32]2[C:40]3[C:35](=[CH:36][C:37]([C:41]([O:43][CH3:44])=[O:42])=[CH:38][CH:39]=3)[NH:34][C:33]=2[C:2]2[CH:17]=[CH:16][CH:15]=[C:14]([N+:18]([O-:20])=[O:19])[C:3]=2[O:4][CH2:5][CH2:6][O:7][CH:8]2[CH2:13][CH2:12][CH2:11][CH2:10][O:9]2)[CH2:27][CH2:28][CH2:29][CH2:30][CH2:31]1
Reactant: COC(=O)c1ccc2c(C3CCCCC3)c(B3OC(C)(C)C(C)(C)O3)[nH]c2c1
Reactant: O=[N+]([O-])c1cccc(Br)c1OCCOC1CCCCO1
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: [Na+]
Solvent: O
Solvent: COCCOC
Product: COC(=O)c1ccc2c(C3CCCCC3)c(-c3cccc([N+](=O)[O-])c3OCCOC3CCCCO3)[nH]c2c1
Temperature: 85 °C
Reaction time: 1 h
Yield: 77.4 %

Procedure:
To a solution of 2-[2-(2-bromo-6-nitrophenoxy)ethoxy]tetrahydropyran (12.30 g, 35.6 mmol) in 1,2-dimethoxyethane (150 ml) and water (75 ml) was added sodium hydrogen carbonate (9.74 g, 117.0 mmol) and tetrakis(triphenylphosphine)palladium (4.52 g, 3.91 mmol) and the mixture was heated at 85° C. for 15 min. Methyl 3-cyclohexyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole-6-carboxylate (16.40 g, 35.6 mmol) was added in 6 divided portions to the reaction mixture at 30 min intervals, and the mixture was stirred at the same temperature for 1 hr. The reaction mixture was allowed to cool to room temperature, water was added to the reaction mixture and the mixture was extracted with ethyl acetate. The organic layer was successively washed with saturated aqueous sodium hydrogen carbonate solution and saturated brine and dried over anhydrous magnesium sulfate. After filtration, the solvent was evaporated under reduced pressure, and the residue was purified by silica gel chromatography (hexane:ethyl acetate=3.5:1) to give methyl 3-cyclohexyl-2-{3-nitro-2-[2-(tetrahydropyran-2-yloxy)ethoxy]phenyl}-1H-indole-6-carboxylate (14.40 g, yield 77%).
Reaction SMILES: [Na][Na].O[CH:4]=[C:5]([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[C:6](=[O:16])[C:7]([C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)=[CH:8][OH:9].C1(CC(=O)CC2C=CC=CC=2)C=CC=CC=1.C(OCC)=O.C[O-].[Na+].CC(=O)C=C=C>>[C:10]1([C:7]2[C:6](=[O:16])[C:5]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)=[CH:4][O:9][CH:8]=2)[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1
Reactant: O=C(C(=CO)c1ccccc1)C(=CO)c1ccccc1
Agent: C=C=CC(C)=O
Agent: C[O-]
Agent: O=C(Cc1ccccc1)Cc1ccccc1
Solvent: CCOC=O
Product: O=c1c(-c2ccccc2)cocc1-c1ccccc1

Procedure:
Benary and Bitter, Ber. 61, 1058 (1928) taught the synthesis of an intermediate disodium salt of 1,5-dihydroxy-2,4-diphenyl-1,4-pentadien-3-one by the condensation of 1,3-diphenyl-2-propanone with ethyl formate in the presence of sodium methoxide. The intermediate pentadienone is neutralized with strong acid to form 3,5-diphenyl-4-pyrone. Reaction of the pyrone with ammonium acetate at an elevated temperature produces 3,5-diphenyl-4(1H)-pyridinone.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:29])[CH2:5][C:6]1[CH:11]=[C:10]([S:12][C:13]2[C:21]3[C:16](=[C:17]([F:23])[C:18]([Cl:22])=[CH:19][CH:20]=3)[NH:15][C:14]=2[CH3:24])[CH:9]=[CH:8][C:7]=1[C:25]([F:28])([F:27])[F:26])[CH3:2].I[C:31]1[CH:32]=[N:33][N:34]([CH2:36][CH2:37][CH3:38])[CH:35]=1>>[CH2:1]([O:3][C:4](=[O:29])[CH2:5][C:6]1[CH:11]=[C:10]([S:12][C:13]2[C:21]3[C:16](=[C:17]([F:23])[C:18]([Cl:22])=[CH:19][CH:20]=3)[N:15]([C:31]3[CH:32]=[N:33][N:34]([CH2:36][CH2:37][CH3:38])[CH:35]=3)[C:14]=2[CH3:24])[CH:9]=[CH:8][C:7]=1[C:25]([F:28])([F:26])[F:27])[CH3:2]
Reactant: CCOC(=O)Cc1cc(Sc2c(C)[nH]c3c(F)c(Cl)ccc23)ccc1C(F)(F)F
Reactant: CCCn1cc(I)cn1
Product: CCCn1cc(-n2c(C)c(Sc3ccc(C(F)(F)F)c(CC(=O)OCC)c3)c3ccc(Cl)c(F)c32)cn1

Procedure:
Prepared according to the procedure described in Example 55, Step 2 using the following starting materials: [5-(6-Chloro-7-fluoro-2-methyl-1H-indol-3-ylsulfanyl)-2-trifluoromethyl-phenyl]-acetic acid ethyl ester and 4-iodo-1-propyl-1H-pyrazole.
Reaction SMILES: [NH2:1][CH2:2][C:3]([N:5]([C:7]1[C:8]([Cl:27])=[C:9]([C:23]([Cl:26])=[CH:24][CH:25]=1)[CH2:10][O:11][C:12]1[C:20]2[N:19]=[C:18]([CH3:21])[N:17]([CH3:22])[C:16]=2[CH:15]=[CH:14][CH:13]=1)[CH3:6])=[O:4].[CH3:28][NH:29][C:30]([C:32]1[CH:42]=[CH:41][C:35]([CH:36]=[CH:37][C:38](O)=[O:39])=[CH:34][CH:33]=1)=[O:31].Cl.C(N=C=NCCCN(C)C)C.ON1C2C=CC=CC=2N=N1>O.CN(C)C=O>[Cl:27][C:8]1[C:7]([N:5]([CH3:6])[C:3](=[O:4])[CH2:2][NH:1][C:38](=[O:39])[CH:37]=[CH:36][C:35]2[CH:41]=[CH:42][C:32]([C:30](=[O:31])[NH:29][CH3:28])=[CH:33][CH:34]=2)=[CH:25][CH:24]=[C:23]([Cl:26])[C:9]=1[CH2:10][O:11][C:12]1[C:20]2[N:19]=[C:18]([CH3:21])[N:17]([CH3:22])[C:16]=2[CH:15]=[CH:14][CH:13]=1
Reactant: CNC(=O)c1ccc(C=CC(=O)O)cc1
Reactant: Cc1nc2c(OCc3c(Cl)ccc(N(C)C(=O)CN)c3Cl)cccc2n1C
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: O
Solvent: CN(C)C=O
Product: CNC(=O)c1ccc(C=CC(=O)NCC(=O)N(C)c2ccc(Cl)c(COc3cccc4c3nc(C)n4C)c2Cl)cc1
Temperature: 25 °C
Reaction time: 3 h
Yield: 82.9 %

Procedure:
To a mixture of 4-[3-(N-glycyl-N-methylamino)-2,6-dichlorobenzyloxy]-1,2-dimethyl-1H-benzimidazole (100 mg), 4-(methylcarbamoyl)cinnamic acid (55.4 mg) and dimethylformamide (1 ml) were added 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (61.2 mg) and 1-hydroxybenzotriazole (49.7 mg), and the mixture was stirred for 3 hours at ambient temperature. To the mixture was added water, and the mixture was extracted with dichloromethane. The separated organic layer was washed with saturated sodium bicarbonate solution and brine, dried over magnesium sulfate and evaporated in vacuo. The residue was purified by preparative thin layer chromatography (dichloromethane—methanol) to give 4-[2,6-dichloro-3-[N-methyl-N-[4-(methyl-carbamoyl)cinnamoylglycy]amino]benzyloxy]-1,2-dimethyl-1H-benzimidazole (121 mg).
Reaction SMILES: [Cl-].[K+].[Cl-].[Cl-].[Ca+2:5].[OH:6][P:7]([O-:10])([OH:9])=[O:8].[K+].Cl.[OH-].[K+]>O>[P:7]([O-:10])([O-:9])([O-:8])=[O:6].[Ca+2:5].[P:7]([O-:10])([O-:9])([O-:8])=[O:6].[Ca+2:5].[Ca+2:5]
Reactant: O=P([O-])(O)O
Agent: Cl
Agent: [Ca+2]
Agent: [Cl-]
Solvent: O
Product: O=P([O-])([O-])[O-]
Temperature: 22 °C
Reaction time: 48 h

Procedure:
Combine in a suitable vessel, 2.1M KCl (35 mL), 0.0175M CaCl2 (5 mL), 0.01M KH2PO4 (50mL), and de-ionized water (350 mL). A standard pH electrode equipped with a Standard Calomel Reference electrode is inserted and the temperature adjusted to 37° C. while purging of the solution of oxygen. Once the temperature and pH are stabilized, a solution of the crystal growth inhibitor to be test is then added. A typical inhibitor test concentration is 1×10−6 M. The solution is titrated to pH 7.4 with 0.05M KOH. The mixture is then treated with 5 mL's of a hydroxyapatite slurry. The hydroxyapatite slurry can be prepared by digesting Bio-Gel® HTP hydroxyapatite powder (100 g) in 1 L of distilled water the pH of which is adjusted to 2.5 by the addition of sufficient 6N HCl and subsequently heating the solution until all of the hydroxyapatite is dissolved (heating for several days may be necessary). The temperature of the solution is then maintained at about 22° C. while the pH is adjusted to 12 by the addition of a solution of 50% aqueous KOH. Once again the solution is heated and the resulting slurry is allowed to settle for two days before the supernatant is removed. 1.5 L of distilled water is added, the solution stirred, then after settling again for 2 days the supernatant is removed. This rinsing procedure is repeated six more time after which the pH of the solution is adjusted to neutrality using 2N HCl. The resulting slurry can be stored at 37° C. for eleven months.
Reaction SMILES: [NH2:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[C@@H:11]2[O:17][C@H:16]([CH2:18][OH:19])[C@H:14]([OH:15])[C@H:12]2[OH:13])=[C:4](Cl)[N:3]=1.[SH-:21].[Na+]>>[NH2:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[C@@H:11]2[O:17][C@H:16]([CH2:18][OH:19])[C@H:14]([OH:15])[C@H:12]2[OH:13])=[C:4]([SH:21])[N:3]=1
Reactant: Nc1nc(Cl)c2ncn([C@@H]3O[C@H](CO)[C@H](O)[C@H]3O)c2n1
Reactant: [SH-]
Agent: [Na+]
Product: Nc1nc(S)c2ncn([C@@H]3O[C@H](CO)[C@H](O)[C@H]3O)c2n1

Procedure:
2-Amino-6-chloro-9-(β-D-xylofuranosyl)purine as prepared by the Example 6, Method B, is treated with sodium hydrosulfide to give the title compound.
Reaction SMILES: CCC(C)[BH-](C(C)CC)C(C)CC.[Li+].[CH3:15][N:16]1[CH2:33][C:31]2=[C:32]3[C:27](=[C:28]([O:34][CH3:35])[CH:29]=[CH:30]2)[O:26][C@H:25]2[C@@:19]3([CH:20]=[CH:21][C:22]([CH2:24]2)=[O:23])[CH2:18][CH2:17]1.CO>C1COCC1.C(Cl)(Cl)Cl>[CH3:15][N:16]1[CH2:33][C:31]2=[C:32]3[C:27](=[C:28]([O:34][CH3:35])[CH:29]=[CH:30]2)[O:26][C@H:25]2[C@@:19]3([CH:20]=[CH:21][C@@H:22]([OH:23])[CH2:24]2)[CH2:18][CH2:17]1
Reactant: COc1ccc2c3c1O[C@@H]1CC(=O)C=C[C@]31CCN(C)C2
Agent: CCC(C)[BH-](C(C)CC)C(C)CC
Agent: [Li+]
Solvent: CO
Solvent: C1CCOC1
Solvent: ClC(Cl)Cl
Product: COc1ccc2c3c1O[C@@H]1C[C@H](O)C=C[C@]31CCN(C)C2
Temperature: -78 °C
Reaction time: 2 h

Procedure:
2 mmole (1N in tetrahydrofuran {THF}) of L-Selectride® (lithium tri-sec-butylborohydride, Aldrich) is charged into 8 ml THF and cooled to -78° C. 1 mmole of (+)-narwedine in 50 ml THF is added dropwise over a period of 30 minutes. After addition, the solution is stirred at -78° C. for 2 hours and then warmed to 0° C. 0.4 ml of methanol is added and the solution is warmed to 25° C. and stirred for 15 minutes. Solvent is then evaporated under vacuum to dryness to obtain a syrup. The syrup is dissolved in 0.5 ml CHCl3 and the solution is loaded into a SiO2 200-400 mesh, 6A, column. The column is eluted with a solvent mixture of CH2Cl2 /CH3OH 6:1 to obtain pure (+)-galanthamine.
Reaction SMILES: Cl.Cl.[NH:3]1[CH2:8][CH2:7][CH:6]([CH2:9][CH2:10][N:11]2[CH2:16][CH2:15][CH:14]([N:17]3[C:21]4[CH:22]=[CH:23][CH:24]=[CH:25][C:20]=4[NH:19][C:18]3=[O:26])[CH2:13][CH2:12]2)[CH2:5][CH2:4]1.[C:27](Cl)(=[O:34])[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1.C(N(C(C)C)CC)(C)C.N1CCCCC1>C(Cl)(Cl)Cl>[C:27]([N:3]1[CH2:8][CH2:7][CH:6]([CH2:9][CH2:10][N:11]2[CH2:16][CH2:15][CH:14]([N:17]3[C:21]4[CH:22]=[CH:23][CH:24]=[CH:25][C:20]=4[NH:19][C:18]3=[O:26])[CH2:13][CH2:12]2)[CH2:5][CH2:4]1)(=[O:34])[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1
Reactant: O=C(Cl)c1ccccc1
Reactant: O=c1[nH]c2ccccc2n1C1CCN(CCC2CCNCC2)CC1
Agent: Cl
Solvent: ClC(Cl)Cl
Solvent: CCN(C(C)C)C(C)C
Solvent: C1CCNCC1
Product: O=C(c1ccccc1)N1CCC(CCN2CCC(n3c(=O)[nH]c4ccccc43)CC2)CC1
Reaction time: 0.17 h
Yield: 65 %

Procedure:
To 20 mg of 1-[1-[2-(piperidin-4-yl)ethyl]piperidin-4-yl]-1,3-dihydro-2H-benzimidazol-2-one dihydrochloride which was synthesized in Production Example 1, 10 mg of benzoyl chloride, 27 mg of diisopropylethylamine and 2 ml of chloroform were added, and sonicated for 30 minutes. Then 20 mg of piperidine was added to the system followed by 10 minutes' standing. The resulting reaction mixture was concentrated, and the residue was purified on silica gel chromatography (chloroform/methanol=15/1) to provide 14 mg of the title compound as a colorless oil.
Reaction SMILES: C([O:3][C:4](=[O:24])/[CH:5]=[CH:6]/[CH:7]1[CH2:16][C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH2:9][N:8]1[C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])C>C(O)C.[Pd]>[C:20]([O:19][C:17]([N:8]1[CH:7]([CH2:6][CH2:5][C:4]([OH:24])=[O:3])[CH2:16][C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH2:9]1)=[O:18])([CH3:23])([CH3:21])[CH3:22]
Reactant: CCOC(=O)/C=C/C1Cc2ccccc2CN1C(=O)OC(C)(C)C
Agent: [Pd]
Solvent: CCO
Product: CC(C)(C)OC(=O)N1Cc2ccccc2CC1CCC(=O)O
Reaction time: 4 h
Yield: 95.9 %

Procedure:
A solution of (E)-tert-butyl 3-(3-ethoxy-3-oxoprop-1-enyl)-3,4-dihydroisoquinoline-2(1H)-carboxylate (8.7 g, 26.3 mmol) and Pd/C (cat) in ethanol (150 mL, 0.18 M) was evacuated to remove air then treated with hydrogen via a balloon. After stirring for 4 h, 3 M sodium hydroxide was added to adjust the solution to pH 11 and the mixture was stirred overnight. The resulting solution was filtered, concentrated, acidified to pH 2 and extracted with ethyl acetate. The organic layer was dried over MgSO4, filtered and concentrated to give 3-(2-(tert-butoxycarbonyl)-1,2,3,4-tetrahydroisoquinolin-3-yl)propanoic acid as a yellow oil (7.7 g, 96%). ESI MS found for C17H23NO4 m/z [328.4 (M+23)]. The crude product was used without further purification.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]([Cl:8])[CH:3]=1.[Cl:9][CH2:10][CH2:11][N:12]=[C:13]=[O:14]>C1(C)C=CC=CC=1>[Cl:9][CH2:10][CH2:11][NH:12][C:13]([NH:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]([Cl:8])[CH:3]=1)=[O:14]
Reactant: O=C=NCCCl
Reactant: Nc1ccnc(Cl)c1
Solvent: Cc1ccccc1
Product: O=C(NCCCl)Nc1ccnc(Cl)c1
Yield: 60.4 %

Procedure:
Using analogous reagents and reaction conditions as described in Example 1 above, 4-amino-2-chloro pyridine (3.0 g, 23.33 mmol) in toluene (30 mL) was reacted with 1-chloro-2-isocyanatoethane (3.69 g, 35.0 mmol) and purified by column chromatography on silica gel (1.5% methanol in DCM) to afford 3.3 g of the product (61% yield).
Reaction SMILES: [H-].[H-].[H-].[H-].[Li+].[Al+3].[CH2:7]([O:17][C:18]1[CH:23]=[CH:22][C:21]([C:24]2[CH:29]=[CH:28][C:27]([C:30](O)=[O:31])=[CH:26][CH:25]=2)=[CH:20][CH:19]=1)[CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16]>C(OCC)C>[OH:31][CH2:30][C:27]1[CH:26]=[CH:25][C:24]([C:21]2[CH:22]=[CH:23][C:18]([O:17][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16])=[CH:19][CH:20]=2)=[CH:29][CH:28]=1
Reactant: CCCCCCCCCCOc1ccc(-c2ccc(C(=O)O)cc2)cc1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: CCOCC
Product: CCCCCCCCCCOc1ccc(-c2ccc(CO)cc2)cc1

Procedure:
0.81 g (21.34 mmol) of LiAlH4 was introduced into 40 ml of diethyl ether and stirred. To the mixture was dropwise added a solution, prepared by introducing 1.71 g (5.06 mmol) of 4'-decyloxy-4-biphenylcarboxylic acid obtained in the first stage of Example 11 into 30 ml of diethyl ether, at room temperature over a period of 2 to 3 minutes, which was then continuously stirred for 5 days. After confirming the consumption of the raw material by TLC, to the resultant mixture was added 40 ml of water, and further added concentrated hydrochloric acid until the aqueous phase was approximately homogenized. The resultant solution was extracted with diethyl ether and dried, to obtain 4-hydroxymethyl-4'-decyloxybiphenyl.