Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[CH:4][C:5]([N+:19]([O-:21])=[O:20])=[C:6](/[CH:8]=[C:9](/[C:12]2[CH:13]=[N:14][C:15]([CH3:18])=[CH:16][CH:17]=2)\[C:10]#[N:11])[CH:7]=1.[BH4-].[Na+]>C1COCC1.CO.O>[CH3:1][C:2]1[CH:3]=[CH:4][C:5]([N+:19]([O-:21])=[O:20])=[C:6]([CH2:8][CH:9]([C:12]2[CH:13]=[N:14][C:15]([CH3:18])=[CH:16][CH:17]=2)[C:10]#[N:11])[CH:7]=1
Reactant: Cc1ccc([N+](=O)[O-])c(/C=C(\C#N)c2ccc(C)nc2)c1
Agent: [BH4-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CO
Solvent: O
Product: Cc1ccc([N+](=O)[O-])c(CC(C#N)c2ccc(C)nc2)c1
Temperature: 0 °C
Reaction time: 2 h
Yield: 91.9 %

Procedure:
To a cooled solution of (Z)-3-(5-methyl-2-nitrophenyl)-2-(6-methylpyridin-3-yl)acrylonitrile (6.5 g, 0.0232 mol) in THF (44 mL) and MeOH (135 mL) was added sodium borohydride (1.7 g, 0.0465 mol) at 0° C. under nitrogen atmosphere. After the addition, the reaction mixture was stirred for 2 h at 0° C. After completion of reaction (monitored by TLC), the reaction mixture was diluted with water (100 mL), and extracted with EtOAc (3×150 mL). The organic layer was dried over anhydrous sodium sulfate, and solvent was removed under reduced pressure to obtain product as a yellow colored solid (6 g, 91.7% yield).
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([NH:11][C:12]2[S:13][C:14]([CH3:17])=[N:15][N:16]=2)(=[O:10])=[O:9])=[CH:4][CH:3]=1.[C:18](Cl)(=[O:28])[CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH3:27].Cl>N1C=CC=CC=1>[CH3:17][C:14]1[S:13][C:12]([NH:11][S:8]([C:5]2[CH:6]=[CH:7][C:2]([NH:1][C:18](=[O:28])[CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH3:27])=[CH:3][CH:4]=2)(=[O:10])=[O:9])=[N:16][N:15]=1
Reactant: Cc1nnc(NS(=O)(=O)c2ccc(N)cc2)s1
Reactant: CCCCCCCCCC(=O)Cl
Agent: Cl
Solvent: c1ccncc1
Product: CCCCCCCCCC(=O)Nc1ccc(S(=O)(=O)Nc2nnc(C)s2)cc1
Temperature: 95 °C
Reaction time: 1 h
Yield: 94.6 %

Procedure:
Compound 105 (250 mg, 0.93 mmol) was suspended in pyridine (0.5 mL). Decanoyl chloride (141 mg, 0.74 mmol) was added slowly at 0° C. The reaction mixture was then heated to 95° C. and was stirred for 1 h. The reaction mixture was then added to aqueous 3 N HCl solution (5 mL) and the mixture extracted with ethyl acetate (3×10 mL). The organic extracts were washed with water (3×20 mL), brine (3×20 mL), dried over anhydrous Na2SO4, and filtered. Evaporation of the solvent left a residue which was crystallized from hexanes and ethyl acetate (1:2) to give the product (297 mg, 0.70 mmol, 95%) as a solid, mp 141-142° C.; 1H NMR (500 MHz, DMSO) δ 0.82 (3, t, J=7.0 Hz), 1.10-1.30 (12, m), 1.54-1.63 (2, m), 2.32 (2, t, J=7.0 Hz), 2.45 (3, s), 8.25 (2, d, J=8.0 Hz), 8.28 (2, d, J=8.0 Hz), 10.25 (1, s), 13.87 (1, s); 13C NMR (125 MHz, DMSO) δ 13.9, 16.0, 22.1, 24.9, 28.5, 28.6, 28.8, 28.9, 31.2, 36.4, 118.5, 126.8, 135.5, 142.7, 154.1, 167.6, 171.7; MS (LCQ, ESI+) Calculated for C19H29N4O3S2 425.2. found 425.1 (M+H)+; HRMS (FAB+, m/z) Calculated for C19H29N4O3S2 425.1681. found 425.1678 (M+H)+.
Reaction SMILES: [CH3:1][C:2](=[CH2:5])[C:3]#[CH:4].C(N(CC)CC)C.[CH3:13][C:14]1([CH3:33])[O:19][C:18]2[CH:20]=[CH:21][CH:22]=[C:23](OS(C(F)(F)F)(=O)=O)[C:17]=2[C:16](=[O:32])[O:15]1.P(=O)(O)(O)O>CN(C)C=O.O>[CH3:13][C:14]1([CH3:33])[O:19][C:18]2[CH:20]=[CH:21][CH:22]=[C:23]([C:4]#[C:3][C:2]([CH3:5])=[CH2:1])[C:17]=2[C:16](=[O:32])[O:15]1
Reactant: C#CC(=C)C
Reactant: CC1(C)OC(=O)c2c(cccc2OS(=O)(=O)C(F)(F)F)O1
Agent: O=P(O)(O)O
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Solvent: O
Product: C=C(C)C#Cc1cccc2c1C(=O)OC(C)(C)O2
Temperature: 115 °C
Reaction time: 0.25 h
Yield: 62.8 %

Procedure:
0.64 g (0.92 mmol) of bistriphenylphosphinepalladium dichloride, 4.4ml (46 mmol) of 3-methyl-3-buten-1-yne and 24ml of triethylamine are added under nitrogen to a solution of 15.0 g (46 mmol) of 2,2-dimethyl-5-trifluoromethylsulfonyloxy-4H(1,3)benzodioxin-4-one in 150 ml of dimethylformamide. The mixture is heated at 115° C. for 0.5 h, a further 6.6 ml of 3-methyl-3-buten-1-yne are then added at this temperature in the course of 1 h and the reaction solution is subsequently stirred for 15 min. After cooling, it is poured into 500 ml of water containing phosphoric acid (pH 3) at 0° C. and extracted with methyl tert-butyl ether, and the combined organic phases are carefully washed with water and saturated sodium chloride solution, dried over sodium sulfate and concentrated. 14 g of a dark oil remain, which is chromatographed on silica gel using n-hexane/ethyl acetate. 7.0 g of colorless crystals are obtained, m.p. 60° C. (cf. Table 1, No. 1.009).
Reaction SMILES: [O:1]1[CH2:5][CH:2]1[CH2:3]Cl.[OH:6][C:7]1[C:16]2[O:15][C:14]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)=[C:13]([CH3:23])[C:12](=[O:24])[C:11]=2[CH:10]=[CH:9][CH:8]=1.[OH-].[Na+].O>C(O)C>[O:1]1[CH2:5][CH:2]1[CH2:3][O:6][C:7]1[C:16]2[O:15][C:14]([C:17]3[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=3)=[C:13]([CH3:23])[C:12](=[O:24])[C:11]=2[CH:10]=[CH:9][CH:8]=1
Reactant: ClCC1CO1
Reactant: Cc1c(-c2ccccc2)oc2c(O)cccc2c1=O
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CCO
Product: Cc1c(-c2ccccc2)oc2c(OCC3CO3)cccc2c1=O
Reaction time: 6 h

Procedure:
7 ml of 2,3-epoxypropyl chloride was added dropwise at 20°-25° C. to a stirred mixture of 5 g of 8-hydroxy-3-methyl-4-oxo-2-phenyl-4H-1-benzopyran and 9.7 ml of 2N aqueous sodium hydroxide solution in 10 ml of ethanol. After 6 hours at 20°-25° C., the reaction mixture was poured into 100 ml of water and the precipitate which formed was collected by suction filtration. After drying and purifying by flash chromatography on silica gel (eluant petroleum ether: ethyl acetate (65:35), there was obtained 4.45 g of the title compound, m.p. 128°-129° C.
Reaction SMILES: [CH3:1][C:2]1[N:11]([C:12]2[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=2)[C:10](=[O:19])[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]=1.[C:20]([O:24][C:25]([N:27]1[CH2:32][CH2:31][CH:30](O)[CH2:29][CH2:28]1)=[O:26])([CH3:23])([CH3:22])[CH3:21].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CCOC(/N=N/C(OCC)=O)=O>O1CCCC1>[C:20]([O:24][C:25]([N:27]1[CH2:32][CH2:31][CH:30]([O:18][C:15]2[CH:16]=[CH:17][C:12]([N:11]3[C:10](=[O:19])[C:9]4[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=4)[N:3]=[C:2]3[CH3:1])=[CH:13][CH:14]=2)[CH2:29][CH2:28]1)=[O:26])([CH3:23])([CH3:21])[CH3:22]
Reactant: Cc1nc2ccccc2c(=O)n1-c1ccc(O)cc1
Reactant: CC(C)(C)OC(=O)N1CCC(O)CC1
Agent: CCOC(=O)/N=N/C(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: Cc1nc2ccccc2c(=O)n1-c1ccc(OC2CCN(C(=O)OC(C)(C)C)CC2)cc1
Temperature: 25 °C
Reaction time: 48 h

Procedure:
2-methyl-3-(4-hydroxyphenyl)-4(3H)quinazolinone synthesized according to Example 1-(1) and -(2) (1.0 g, 3.96 mmol), N-(t-butoxycarbonyl)-4-piperidinol (956 mg, 4.75 mmol) and triphenylphosphine (1.56 g, 5.94 mmol) were dissolved in dry tetrahydrofuran (2 mL) in a current of nitrogen, and cooled on an ice bath. Diethylazodicarboxylate (1.17 mL, 5.94 mmol) was dripped in at 0° C., and stirred at room temperature for 48 hours. The solvent was distilled off under reduced pressure, ether was added, the solid precipitate was filtered off, and the filtrate was concentrated. The residue was purified by silica gel column chromatography (hexane/ethyl acetate=7/3), and the target substance (1.1 g, 64%) was obtained as a light brown solid.
Reaction SMILES: [C:1]([C:3]1[CH:4]=[C:5]([CH:10]=[C:11]([CH3:13])[N:12]=1)[C:6](OC)=[O:7])#[N:2].[BH4-].[Na+]>CO.C1COCC1>[OH:7][CH2:6][C:5]1[CH:10]=[C:11]([CH3:13])[N:12]=[C:3]([C:1]#[N:2])[CH:4]=1
Reactant: COC(=O)c1cc(C)nc(C#N)c1
Agent: [BH4-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CO
Product: Cc1cc(CO)cc(C#N)n1
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 40.5 %

Procedure:
To a stirring solution of 1.3 g (7.33 mmol) of methyl 2-cyano-6-methylisonicotinate in 25 mL of MeOH and 5 mL of THF at 0° C. was added 823 mg (21.7 mmol) of NaBH4. After 2 h the ice bath was removed and stirring was continued with warming to r.t. and after a further 15 min. 1.06 g of NaBH4 was added. After another 15 min., the solution was concentrated, and EtOAc was added. The pH was adjusted to 7 with 1N HCl, and the layers were separated. The aqueous layer was extracted with EtOAc (2×), and the combined extracts were washed with brine (50 mL), dried over Na2SO4, filtered, and concentrated. Purification by flash silica gel chromatography (2-3) % MeOH/CHCl3 provided 440 mg of 4-(hydroxymethyl)-6-methylpicolinonitrile in 40% yield as a colorless solid.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12](=[O:13])[NH:11][NH:10][C:9]2=[O:14])=[CH:4][CH:3]=1.[OH-].[Na+].[Cl:17][C:18]([Cl:22])([Cl:21])[S:19]Cl>O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[C:9](=[O:14])[N:10]([S:19][C:18]([Cl:22])([Cl:21])[Cl:17])[N:11]([S:19][C:18]([Cl:22])([Cl:21])[Cl:17])[C:12]2=[O:13])=[CH:6][CH:7]=1
Reactant: ClSC(Cl)(Cl)Cl
Reactant: O=c1[nH][nH]c(=O)n1-c1ccc(Cl)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: O=c1n(-c2ccc(Cl)cc2)c(=O)n(SC(Cl)(Cl)Cl)n1SC(Cl)(Cl)Cl

Procedure:
To a solution of 42.2g (0.2 mole) 4-(4-chlorophenyl)urazole in 200 ml water was added a solution of 16g (0.4 mole) sodium hydroxide in 20 ml water. A mixture of 74.4g (0.4 mole) trichloromethylsulfenyl chloride and 3g of an emulsifier solution (as in example 1) in 50 ml water was added dropwise to the above basic solution while keeping the reaction mixture at 0° C. The reactants were mixed so that the reaction mixture was kept at a pH greater than 7. The precipitate that was formed was collected on a filter and the filter cake was washed with water. After drying, triturating with ethyl ether, and recrystallizing from benzene-cyclohexane (1:1, by volume) there was obtained 42g (64%) of 4-(4-chlorophenyl)-1, 2-bis(trichloromethylthio)urazole having a melting point of 169° C.
Reaction SMILES: C(OC([N:8]1[CH2:30][CH2:29][C:11]2[N:12]=[C:13]([N:23]3[CH2:27][CH2:26][CH2:25][CH:24]3[CH3:28])[N:14]=[C:15]([C:16]3[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=3)[C:10]=2[CH2:9]1)=O)(C)(C)C.[ClH:31]>CCOCC.O1CCOCC1>[ClH:31].[F:22][C:19]1[CH:18]=[CH:17][C:16]([C:15]2[C:10]3[CH2:9][NH:8][CH2:30][CH2:29][C:11]=3[N:12]=[C:13]([N:23]3[CH2:27][CH2:26][CH2:25][CH:24]3[CH3:28])[N:14]=2)=[CH:21][CH:20]=1
Reactant: CC1CCCN1c1nc2c(c(-c3ccc(F)cc3)n1)CN(C(=O)OC(C)(C)C)CC2
Agent: Cl
Solvent: CCOCC
Solvent: C1COCCO1
Product: CC1CCCN1c1nc2c(c(-c3ccc(F)cc3)n1)CNCC2
Reaction time: 16 h
Yield: 76 %

Procedure:
To a solution of 4-(4-fluoro-phenyl)-2-(2-methyl-pyrrolidin-1-yl)-7,8-dihydro-5H-pyrido[4,3-d]pyrimidine-6-carboxylic acid tert-butyl ester (0.193 g, 0.47 mmol) in Et2O (2 mL) was added 4 M HCl in dioxane (2.5 mL). After 16 h, the mixture was concentrated and the residue was triturated with Et2O to give the title compound (0.124 g, 76%) as a white solid. MS (ESI): mass calcd. for C18H21FN4, 312.4; m/z found, 313.4 [M+H]+. 1H NMR (DMSO-d6): 9.54 (m, 2H), 7.64 (dd, J=8.5, 5.5, 2H), 7.37 (t, J=8.8, 2H), 4.23-4.04 (m, 3H), 3.58-3.36 (m, 4H), 3.03-2.95 (m, 2H), 2.08-1.96 (m, 2H), 1.93-1.85 (m, 1H), 1.71-1.64 (m, 1H), 1.21 (d, J=6.3, 3H).
Reaction SMILES: [C:1]([O:5][C:6]([N:8]([CH3:14])[CH2:9][CH2:10][C:11]([OH:13])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.[CH3:16][NH:17][O:18][CH3:19].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)CC)C>CN(C=O)C>[CH3:19][O:18][N:17]([CH3:16])[C:11](=[O:13])[CH2:10][CH2:9][N:8]([CH3:14])[C:6](=[O:7])[O:5][C:1]([CH3:2])([CH3:3])[CH3:4]
Reactant: CNOC
Reactant: CN(CCC(=O)O)C(=O)OC(C)(C)C
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: Cl
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: CON(C)C(=O)CCN(C)C(=O)OC(C)(C)C
Temperature: 25 °C
Yield: 99 %

Procedure:
To a stirred solution of 3-[(tert-butoxycarbonyl)(methyl)amino]-propanoic acid (5.0 g, 24.6 mmol), N,O-dimethylhydroxylamine hydrochloride (3.1 g, 32.0 mmol) and HBTU (11.2 g, 29.5 mmol) in DMF (50 mL) at 0° C. was added triethylamine (10.2 mL, 73.8 mmol). The mixture was stirred at room temperature over night and the solvent was removed under reduced pressure. The residue was taken up in ethyl acetate (300 mL), washed with water (100 mL) and 0.6 N NaOH solution (100 mL). The aqueous phases were back extracted with ethyl acetate (100 mL). The combined organic phases were dried over sodium sulfate, filtered and concentrated. The residue was purified by column chromatography on silica gel (120 g column, 0% ethyl acetate in hexanes to 100% ethyl acetate in hexanes) to give product (6.0 g, 99%). 1H NMR (CDCl3) 3.69 (s, 3H), 3.52 (t, J=6.2 Hz, 2H), 3.18 (s, 3H), 2.88 (s, 3H), 2.66 (brs, 2H), 1.45 (s, 9H); MS EI m/z 269 (M+Na)+.
Reaction SMILES: [CH:1]([O:4][CH2:5][CH2:6][NH:7][C:8]1[CH:30]=[CH:29][C:11]([C:12]([N:14]2[CH2:19][CH2:18][N:17]([CH2:20][CH2:21][C:22]3[CH:27]=[CH:26][C:25]([Cl:28])=[CH:24][CH:23]=3)[CH2:16][CH2:15]2)=[O:13])=[CH:10][CH:9]=1)([CH3:3])[CH3:2].C([O-])([O-])=O.[K+].[K+].[CH2:37]([O:44][C:45]([Cl:47])=[O:46])[C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1>C1(C)C=CC=CC=1>[ClH:28].[ClH:47].[CH:1]([O:4][CH2:5][CH2:6][N:7]([C:45]([O:44][CH2:37][C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1)=[O:46])[C:8]1[CH:30]=[CH:29][C:11]([C:12]([N:14]2[CH2:15][CH2:16][N:17]([CH2:20][CH2:21][C:22]3[CH:27]=[CH:26][C:25]([Cl:28])=[CH:24][CH:23]=3)[CH2:18][CH2:19]2)=[O:13])=[CH:10][CH:9]=1)([CH3:3])[CH3:2]
Reactant: CC(C)OCCNc1ccc(C(=O)N2CCN(CCc3ccc(Cl)cc3)CC2)cc1
Reactant: O=C(Cl)OCc1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: Cc1ccccc1
Product: CC(C)OCCN(C(=O)OCc1ccccc1)c1ccc(C(=O)N2CCN(CCc3ccc(Cl)cc3)CC2)cc1
Product: Cl
Temperature: 25 °C
Reaction time: 0.17 h

Procedure:
1.2 g of 1-{4-[N-(2-isopropyloxyethyl)amino]benzoyl}-4-[2-(4-chlorophenyl)ethyl]piperazine are dissolved in 15 ml of toluene, and 1.1 g of potash are added. The mixture is stirred for 10 minutes at RT and then 1.9 g of chloroformic acid benzyl ester in 4 ml of toluene are added dropwise thereto. The mixture is stirred overnight at RT and concentrated by evaporation, the residue is partitioned between dichloromethane and water, and the mixture is concentrated by evaporation and chromatographed over silica gel (eluant: dichloromethane/acetone 9:1). Treatment with alcoholic hydrochloric acid yields 1-{4-[N-(2-isopropyloxyethyl)benzyloxycarbonylamino]benzoyl}-4-[2-(4-chlorophenyl)ethyl]piperazine hydrochloride having a melting point of 135°-137°.
Reaction SMILES: [CH2:1]([N:8](C)[CH2:9][CH:10]([C:12]1[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=1)[OH:11])C1C=CC=CC=1>C(OCC)(=O)C.CO.[C].[Pd]>[F:18][C:15]1[CH:14]=[CH:13][C:12]([CH:10]([OH:11])[CH2:9][NH:8][CH3:1])=[CH:17][CH:16]=1
Reactant: CN(Cc1ccccc1)CC(O)c1ccc(F)cc1
Agent: [Pd]
Solvent: CO
Solvent: CCOC(C)=O
Product: CNCC(O)c1ccc(F)cc1
Yield: 72.4 %

Procedure:
2-(Benzyl-methyl-amino)-1-(4-fluorophenyl)-ethanol (54.6 g) and 10% palladium-carbon (5.8 g) was stirred in ethyl acetate-methanol (3:1) (800 mL) at 50° C. under hydrogen atmosphere for three hours. The catalyst was removed by filtration, and the filtrate was concentrated. After solidifying with an ether-hexane solvent, and the title compound (25.8 g) was obtained as a colorless solid.
Reaction SMILES: [CH3:1][CH:2]([N:4]1[C:12](/[CH:13]=[CH:14]/[C@H:15]([OH:24])[CH2:16][C@H:17]([OH:23])[CH2:18][C:19]([O:21]C)=[O:20])=[C:11]([C:25]2[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=2)[C:10]2[C:5]1=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH3:3].[OH-].[Na+:33]>C(#N)C.O>[CH3:3][CH:2]([N:4]1[C:12](/[CH:13]=[CH:14]/[CH:15]([OH:24])[CH2:16][CH:17]([OH:23])[CH2:18][C:19]([O-:21])=[O:20])=[C:11]([C:25]2[CH:26]=[CH:27][C:28]([F:31])=[CH:29][CH:30]=2)[C:10]2[CH:9]=[CH:8][CH:7]=[CH:6][C:5]1=2)[CH3:1].[Na+:33]
Reactant: COC(=O)C[C@@H](O)C[C@@H](O)/C=C/c1c(-c2ccc(F)cc2)c2ccccc2n1C(C)C
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CC#N
Product: CC(C)n1c(/C=C/C(O)CC(O)CC(=O)[O-])c(-c2ccc(F)cc2)c2ccccc21
Temperature: 40 °C
Reaction time: 2 h
Yield: 83 %

Procedure:
Fluvastatin methyl ester (3.01 g) was dissolved in acetonitrile (60 ml) by heating and a solution of NaOH (0.28 g) in water (0.75 ml) was added at about 50° C. The mixture was stirred at about 40° C. for 2 h, cooled to room temperature and stirred for another h. The product was isolated by filtration under nitrogen, washed with acetonitrile (40 ml) and dried at 50° C. in a vacuum oven for 24 h to obtain 2.52 g (82.2%) of fluvastatin sodium crystal Form I.
Reaction SMILES: [C:1]1([CH:7]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[O:8][CH:9]2[CH2:14][CH2:13][N:12]([CH2:15][CH2:16][CH2:17][NH2:18])[CH2:11][CH2:10]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH2:25]([O:27][C:28](=[O:45])[C:29]([CH3:44])([CH3:43])[NH:30][C:31]([C:33]1[N:41]=[C:40]2[N:35]([N:36]=[C:37](Cl)[CH:38]=[CH:39]2)[N:34]=1)=[O:32])[CH3:26].C(N(C(C)C)C(C)C)C.C(=O)(O)[O-].[Na+].[C:60]([OH:67])(=[O:66])/[CH:61]=[CH:62]/[C:63]([OH:65])=[O:64]>CN(C)C=O.C(O)C>[C:60]([OH:67])(=[O:66])/[CH:61]=[CH:62]/[C:63]([OH:65])=[O:64].[CH2:25]([O:27][C:28](=[O:45])[C:29]([CH3:44])([CH3:43])[NH:30][C:31]([C:33]1[N:41]=[C:40]2[N:35]([N:36]=[C:37]([NH:18][CH2:17][CH2:16][CH2:15][N:12]3[CH2:13][CH2:14][CH:9]([O:8][CH:7]([C:1]4[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=4)[C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=4)[CH2:10][CH2:11]3)[CH:38]=[CH:39]2)[N:34]=1)=[O:32])[CH3:26]
Reactant: NCCCN1CCC(OC(c2ccccc2)c2ccccc2)CC1
Reactant: CCOC(=O)C(C)(C)NC(=O)c1nc2ccc(Cl)nn2n1
Agent: O=C(O)/C=C/C(=O)O
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: CCO
Solvent: CCN(C(C)C)C(C)C
Product: CCOC(=O)C(C)(C)NC(=O)c1nc2ccc(NCCCN3CCC(OC(c4ccccc4)c4ccccc4)CC3)nn2n1
Temperature: 70 °C
Reaction time: 16 h
Yield: 88.8 %

Procedure:
1.56 g of 4-(diphenylmethoxy)-1-piperidinepropanamine and 1.50 g of N-(6-chloro[1,2,4]triazolo[1,5-b]pyridazine-2-carbonyl)-2,2-dimethylglycine ethyl ester were dissolved in 20 ml of N,N-dimethylformamide; 1.65 ml of N-ethyldiisopropylamine was added, followed by stirring at 70° C. for 16 hours. After cooling, aqueous sodium bicarbonate was added, followed by extraction with ethyl acetate; the extract was washed with saturated saline, dried over magnesium sulfate and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography and eluted with ethyl acetate:methanol:triethylamine (50:5:1). The desired fraction was collected and concentrated; 880 mg of the oily substance obtained was dissolved in 5 ml of ethanol, followed by the addition of 170 mg of fumaric acid and concentration; the resulting concentrate was powdered by the addition of ethyl ether, washed with ethyl ether, collected by filtration and dried to yield 931 mg of the title compound.
Reaction SMILES: C([N:8]1[C:20]2[C:19]([O:21][CH2:22][CH2:23]Br)=[C:18]3[N:25](C(OC(C)(C)C)=O)[C:26]4[CH:27]=[CH:28][C:29]([Cl:32])=[CH:30][C:31]=4[C:17]3=[CH:16][C:15]=2[C:14]2[C:9]1=[CH:10][CH:11]=[C:12]([Cl:40])[CH:13]=2)(OC(C)(C)C)=O.[NH:41]1[CH:45]=[CH:44][N:43]=[N:42]1>>[N:41]1[N:42]([CH2:23][CH2:22][O:21][C:19]2[C:18]3[NH:25][C:26]4[C:31](=[CH:30][C:29]([Cl:32])=[CH:28][CH:27]=4)[C:17]=3[CH:16]=[C:15]3[C:14]4[CH:13]=[C:12]([Cl:40])[CH:11]=[CH:10][C:9]=4[NH:8][C:20]=23)[N:43]=[CH:44][CH:45]=1
Reactant: CC(C)(C)OC(=O)n1c2ccc(Cl)cc2c2cc3c4cc(Cl)ccc4n(C(=O)OC(C)(C)C)c3c(OCCBr)c21
Reactant: c1c[nH]nn1
Product: Clc1ccc2[nH]c3c(OCCn4nccn4)c4[nH]c5ccc(Cl)cc5c4cc3c2c1
Yield: 70 %

Procedure:
The title compound was prepared in a manner analogous to Example 70 except the staring material is 5,7-diBOC-2,10-dichloro-6-(2-bromoethoxy)indolo[2,3-b]carbazole and the reagent is 1,2,3-triazole. 1H-NMR (400 MHz, DMSO-d6) δ ppm 11.29 (s, 2H), 8.70 (s, 1H), 8.16 (d, J=2.0 Hz, 2H), 7.88 (s, 2H), 7.51 (d, J=8.8 Hz, 2H), 7.37 (dd, J=8.4, 2.0 Hz, 2H), 4.98 (t, J=6.4 Hz, 2H), 4.71 (t, J=6.0 Hz, 2H); MS (ESI) m/z 434.0 (M−H)−; MS (ESI) m/z 436.0 (M+H)+
Reaction SMILES: [CH3:1][C:2]([CH3:48])([C:39]1[CH:44]=[C:43]([CH2:45][CH3:46])[CH:42]=[CH:41][C:40]=1[OH:47])[CH2:3][N:4]1[C:9](=[O:10])[N:8]([CH2:11][C:12]([C:15]2[CH:20]=[C:19]([CH2:21][CH3:22])[CH:18]=[CH:17][C:16]=2[OH:23])([CH3:14])[CH3:13])[C:7](=[O:24])[N:6]([CH2:25][C:26]([C:29]2[CH:34]=[C:33]([CH2:35][CH3:36])[CH:32]=[CH:31][C:30]=2[OH:37])([CH3:28])[CH3:27])[C:5]1=[O:38].[C:49]1([CH3:59])[CH:54]=CC(S(O)(=O)=O)=C[CH:50]=1.[CH3:60][C:61](=[CH2:63])[CH3:62]>C1(C)C=CC=CC=1.C(OCC)(=O)C>[CH3:14][C:12]([CH3:13])([C:15]1[CH:20]=[C:19]([CH2:21][CH3:22])[CH:18]=[C:17]([C:49]([CH3:50])([CH3:54])[CH3:59])[C:16]=1[OH:23])[CH2:11][N:8]1[C:7](=[O:24])[N:6]([CH2:25][C:26]([C:29]2[CH:34]=[C:33]([CH2:35][CH3:36])[CH:32]=[C:31]([C:61]([CH3:62])([CH3:60])[CH3:63])[C:30]=2[OH:37])([CH3:27])[CH3:28])[C:5](=[O:38])[N:4]([CH2:3][C:2]([C:39]2[CH:44]=[C:43]([CH2:45][CH3:46])[CH:42]=[C:41]([C:2]([CH3:39])([CH3:3])[CH3:1])[C:40]=2[OH:47])([CH3:1])[CH3:48])[C:9]1=[O:10]
Reactant: Cc1ccc(S(=O)(=O)O)cc1
Reactant: C=C(C)C
Reactant: CCc1ccc(O)c(C(C)(C)Cn2c(=O)n(CC(C)(C)c3cc(CC)ccc3O)c(=O)n(CC(C)(C)c3cc(CC)ccc3O)c2=O)c1
Solvent: CCOC(C)=O
Solvent: Cc1ccccc1
Product: CCc1cc(C(C)(C)C)c(O)c(C(C)(C)Cn2c(=O)n(CC(C)(C)c3cc(CC)cc(C(C)(C)C)c3O)c(=O)n(CC(C)(C)c3cc(CC)cc(C(C)(C)C)c3O)c2=O)c1
Temperature: 90 °C

Procedure:
To a 100 ml 3-neck round bottom flask is charged 8.9 g product of Example 4 in 30 ml toluene. To this is added 0.8 g p-toluenesulfonic acid. Isobutylene is passed through the solution while warming to 90° C. When TLC shows the reaction to be complete, the contents are diluted with an equal volume of ethyl acetate and washed 2 times with 50 ml of 5% sodium bicarbonate. The organic layer is dried, and stripped under vacuum. The residue is purified by dry column chromatography to give 3.3 g white solids. Further purification by precipitation from a water/methanol solution gives 2.4 g of product.
Reaction SMILES: N[C:2]1[CH:11]=[C:10]2[C:5]([C:6](=[O:37])[NH:7][C:8](=[O:36])[N:9]2[CH2:12][CH2:13][CH2:14][CH2:15][N:16]2[CH2:21][CH2:20][CH:19]([O:22][CH:23]([C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)[C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[CH2:18][CH2:17]2)=[CH:4][CH:3]=1.[C:38](O)(=O)C.C=O.[C:44]([BH3-])#[N:45].[Na+]>CO>[CH3:38][N:45]([CH3:44])[C:2]1[CH:11]=[C:10]2[C:5]([C:6](=[O:37])[NH:7][C:8](=[O:36])[N:9]2[CH2:12][CH2:13][CH2:14][CH2:15][N:16]2[CH2:17][CH2:18][CH:19]([O:22][CH:23]([C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)[C:24]3[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=3)[CH2:20][CH2:21]2)=[CH:4][CH:3]=1
Reactant: [BH3-]C#N
Reactant: CC(=O)O
Reactant: Nc1ccc2c(=O)[nH]c(=O)n(CCCCN3CCC(OC(c4ccccc4)c4ccccc4)CC3)c2c1
Agent: C=O
Agent: [Na+]
Solvent: CO
Product: CN(C)c1ccc2c(=O)[nH]c(=O)n(CCCCN3CCC(OC(c4ccccc4)c4ccccc4)CC3)c2c1
Reaction time: 1 h
Yield: 72 %

Procedure:
7-Amino-2,4-dioxo-1-[4-(4-diphenylmethoxypiperidino)butyl]-1,2,3,4-tetrahydroquinazoline (500 mg) obtained in Example 39 was suspended in methanol (5.00 ml), and to this mixture acetic acid (0.5 ml) and 37% formaldehyde (0.5 ml) were added and the mixture was stirred for 1 hour. A solution of sodium cyanoborohydride (94.5 mg) in methanol (2.0 ml) was added dropwise and the mixture was stirred at room temperature for 21 hours. The reaction mixture was concentrated under reduced pressure, diluted with ethyl acetate, washed with water, dried (Na2SO4) and then the solvent was distilled off under reduced pressure. The residue was subjected to a column chromatography on a silica gel to give the title compound (378 mg, 72%) from a fraction eluted with n-hexane-ethyl acetate (5:1,v/v). Recrystallization from ethyl acetate-ethyl ether yielded a yellow crystal having a melting point of 203 to 204° C.