Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl[C:2]1[N:7]=[CH:6][C:5]([C:8]2[CH:9]=[CH:10][C:11](=[O:15])[N:12]([CH3:14])[N:13]=2)=[CH:4][CH:3]=1.[OH:16][CH:17]1[CH2:22][CH2:21][N:20]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:19][CH2:18]1>C1(C)C=CC=CC=1>[C:26]([O:25][C:23]([N:20]1[CH2:21][CH2:22][CH:17]([O:16][C:2]2[CH:3]=[CH:4][C:5]([C:8]3[CH:9]=[CH:10][C:11](=[O:15])[N:12]([CH3:14])[N:13]=3)=[CH:6][N:7]=2)[CH2:18][CH2:19]1)=[O:24])([CH3:29])([CH3:27])[CH3:28]
Reactant: CC(C)(C)OC(=O)N1CCC(O)CC1
Reactant: Cn1nc(-c2ccc(Cl)nc2)ccc1=O
Solvent: Cc1ccccc1
Product: Cn1nc(-c2ccc(OC3CCN(C(=O)OC(C)(C)C)CC3)nc2)ccc1=O
Temperature: 80 °C
Reaction time: 8 h

Procedure:
To 6-(6-chloro-pyridin-3-yl)-2-methyl-2H-pyridazin-3-one (3 g, 13.6 mmol) in toluene (50 mL) was added 4-hydroxy-boc-piperidine (2.7 g, 13.6 mmol) and 1M KtOBu (16.3 mL, 16.3 mmol). After overnight stirring at 80° C., the reaction was concentrated, partitioned between dichloromethane/1N sodium carbonate, washed with water/brine, dried over sodium sulfate, and concentrated. The product was purified by column chromatography (99:1 dichloromethane:methanol) to obtain 2.7 g (51%); MS m/z 387 (M+H).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][CH2:10][C:11]2[S:12][C:13]3[N:14]=[C:15]([NH2:26])[N:16]=[C:17]([N:20]4[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]4)[C:18]=3[N:19]=2)=[CH:4][CH:3]=1.[Cl:27][C:28]1[CH:38]=[CH:37][C:31]([O:32][CH2:33][C:34](O)=[O:35])=[CH:30][CH:29]=1>>[NH2:26][C:15]1[N:16]=[C:17]([N:20]2[CH2:21][CH2:22][N:23]([C:34](=[O:35])[CH2:33][O:32][C:31]3[CH:37]=[CH:38][C:28]([Cl:27])=[CH:29][CH:30]=3)[CH2:24][CH2:25]2)[C:18]2[N:19]=[C:11]([CH2:10][CH2:9][CH2:8][C:5]3[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=3)[S:12][C:13]=2[N:14]=1
Reactant: Nc1nc(N2CCNCC2)c2nc(CCCc3ccc(F)cc3)sc2n1
Reactant: O=C(O)COc1ccc(Cl)cc1
Product: Nc1nc(N2CCN(C(=O)COc3ccc(Cl)cc3)CC2)c2nc(CCCc3ccc(F)cc3)sc2n1
Yield: 33 %

Procedure:
This compound was prepared from 2-(3-(4-fluorophenyl)propyl)-7-(piperazin-1-yl)thiazolo[5,4-d]pyrimidin-5-amine using 4-chlorophenoxyacetic acid in a yield of 33%, according to the procedure for the synthesis of example 50.
Reaction SMILES: [CH:1](=[C:8]1/[CH2:9][CH2:10][C@H:11]([C:18]([N:20]2[CH2:25][CH2:24][N:23]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[CH2:22][CH2:21]2)=[O:19])[C@@H:12]([C:14]([O:16]C)=[O:15])[CH2:13]/1)/[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O1CCCC1.[OH-].[Li+].O.OO>>[CH:1](=[C:8]1/[CH2:9][CH2:10][C@H:11]([C:18]([N:20]2[CH2:21][CH2:22][N:23]([C:26]3[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=3)[CH2:24][CH2:25]2)=[O:19])[C@@H:12]([C:14]([OH:16])=[O:15])[CH2:13]/1)/[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: COC(=O)[C@H]1C/C(=C/c2ccccc2)CC[C@@H]1C(=O)N1CCN(c2ccccc2)CC1
Agent: OO
Agent: [Li+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: O
Product: O=C(O)[C@H]1C/C(=C/c2ccccc2)CC[C@@H]1C(=O)N1CCN(c2ccccc2)CC1
Temperature: 25 °C
Reaction time: 17 h

Procedure:
To a stirred solution of methyl(1S,2S,5E)-5-benzylidene-2-[(4-phenylpiperazin-1-yl)carbonyl]cyclohexanecarboxylate (116 mg, 0.000277 mol) in tetrahydrofuran (6.0 mL, 0.074 mol) at rt was added a solution of lithium hydroxide (102 mg, 0.00416 mol) in water (2.0 mL, 0.11 mol). The resulting cloudy solution was stirred at rt for 17 h. LCMS showed that there was only 40% conversion. The reaction mixture was cooled to 0° C., hydrogen peroxide (0.113 mL, 0.00111 mol) was then added. The reaction mixture was stirred at 0° C. for 2 h. LCMS showed that there was little change. The reaction mixture was then stirred at rt over the weekend. LCMS showed the reaction was done. The reaction was quenched with 10% Na2S2O3 (10 mL), acidified with 1 N HCl (5 mL) to pH=4, extracted with EtOAc (2×). The combined organic layers were washed with brine, dried over magnesium sulfate, filtered and concentrated in vacuo to give the desired product as a colorless solid. (112 mg, 100% in yield). MS (ESI): (M+H)+=405.1.
Reaction SMILES: [CH2:1](Cl)[CH:2]=[CH2:3].[CH:5]1([O:10][C:11]2[CH:12]=[C:13]([CH2:19][C:20]([NH:22][C:23]3[CH:28]=[C:27]([Cl:29])[CH:26]=[CH:25][C:24]=3[OH:30])=[O:21])[CH:14]=[CH:15][C:16]=2[O:17][CH3:18])[CH2:9][CH2:8][CH2:7][CH2:6]1>C(O)C.[OH-].[Na+].CO.O>[CH:5]1([O:10][C:11]2[CH:12]=[C:13]([CH2:19][C:20]([NH:22][C:23]3[CH:28]=[C:27]([Cl:29])[CH:26]=[CH:25][C:24]=3[O:30][CH2:3][CH:2]=[CH2:1])=[O:21])[CH:14]=[CH:15][C:16]=2[O:17][CH3:18])[CH2:9][CH2:8][CH2:7][CH2:6]1
Reactant: C=CCCl
Reactant: COc1ccc(CC(=O)Nc2cc(Cl)ccc2O)cc1OC1CCCC1
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Solvent: O
Solvent: CO
Product: C=CCOc1ccc(Cl)cc1NC(=O)Cc1ccc(OC)c(OC2CCCC2)c1
Yield: 64.6 %

Procedure:
In this step, allyl chloride (23.3 grams, 0.31 mol) was added to a stirred solution of N-(3-cyclopentyloxy-4-methoxyphenylacetyl)-2-hydroxy-5-chloroaniline (78 grams, 0.21 mol) in ethanol (600 millilters) and 1N NaOH in methanol (213 milliters). The mixture was heated under reflux for 8 hours and then diluted with water and extracted twice with ethyl acetate. Evaporation of the ethyl acetate and crystallization of the residue from methanol gave 56.4 grams (65%) of the title compound, mp 75°-76.5°.
Reaction SMILES: C([O:4][C:5]1[CH:6]=[C:7]([CH:20]=[CH:21][CH:22]=1)[O:8][CH2:9]/[CH:10]=[C:11](\[CH3:19])/[CH:12](OCC)[O:13]CC)(=O)C.[OH-].[Na+]>CO>[OH:4][C:5]1[CH:6]=[C:7]([CH:20]=[CH:21][CH:22]=1)[O:8][CH2:9]/[CH:10]=[C:11](\[CH3:19])/[CH:12]=[O:13]
Reactant: CCOC(OCC)/C(C)=C/COc1cccc(OC(C)=O)c1
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: C/C(C=O)=C\COc1cccc(O)c1
Reaction time: 2 h

Procedure:
A solution of 10.32 g resorcinol monoacetate in 40 ml sieve dried dimethyl formamide is stirred at ambient temperature under nitrogen as 18.7 g of solid potassium carbonate is added. After 5 minutes, a solution of 16.08 g (E)-4-bromo-1,1-diethoxy-2-methyl-2-butene in 40 ml sieve dried dimethyl formamide is added in dropwise fashion over a 30 minute period. During this addition, the solution becomes dark brown. After the addition is completed, the reaction mixture is stirred for 21/2 hours at room temperature and is then poured into 700 ml 10% potassium carbonate at 0° C. The mixture is extracted with two 200 ml portions of diethylether and the extracts are combined and washed with four 200 ml portions of distilled water. Anhydrous magnesium sulfate and activated charcoal are added to the solution and it is allowed to stand for 30 minutes and is then filtered. The golden filtrate is evaporated to dryness to yield 11.36 g of dark yellow brown oil which is (E)-4(3-acetoxyphenoxy)-1,1-diethoxy-2-methyl-2-butene which is dissolved in 150 ml methanol and stirred under nitrogen as 50 ml 5% aqueous sodium hydroxide solution is added and stirred for about two hours. The reaction mixture is placed in a rotary evaporator and the methanol removed. The remaining mixture is diluted to 200 ml and extracted with 200 ml diethylether. The ether solution is evaporated to dryness. The solution is dried over magnesium sulfate and treated with activated charcoal and filtered to yield a bright yellow solution. The solution is evaporated and yields 3.41 g of yellow oily residue which is taken up in 30 ml of a 1:5 water-acetone mixture and stirred under nitrogen as 0.5 g p-tolunesulfonic acid monohydrate is added. After about 30 minutes, the solution is evaporated to dryness and 25 ml water and 25 ml ethyl acetate are added and the residue separated. The ethyl acetate phase is dried over magnesium sulfate, treated with activated charcoal and filtered and the filtrate evaporated to dryness to yield 2.5 g yellow, oily solid residue. The residue is extracted in 50 ml diethylether and the diethylether solution concentrated to yield a yellow solid which is purified by recrystallization from a methanol-water mixture to yield about 1.0 g light yellow solid product, m.p. 136°-38° C. Elemental Analysis. Calculated: C,68.74; H,6.29. Found: C,68.75; H,6.36.
Reaction SMILES: [C:1]([C:5]1[CH:25]=[CH:24][C:8]([C:9]([NH:11][C:12]2[CH:20]=[CH:19][C:18]([N+:21]([O-:23])=[O:22])=[CH:17][C:13]=2[C:14]([OH:16])=[O:15])=O)=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].C(Cl)(=O)C(Cl)=O>C(Cl)Cl.CN(C)C=O>[N+:21]([C:18]1[CH:19]=[CH:20][C:12]2[N:11]=[C:9]([C:8]3[CH:24]=[CH:25][C:5]([C:1]([CH3:2])([CH3:4])[CH3:3])=[CH:6][CH:7]=3)[O:16][C:14](=[O:15])[C:13]=2[CH:17]=1)([O-:23])=[O:22]
Reactant: CC(C)(C)c1ccc(C(=O)Nc2ccc([N+](=O)[O-])cc2C(=O)O)cc1
Agent: O=C(Cl)C(=O)Cl
Solvent: ClCCl
Solvent: CN(C)C=O
Product: CC(C)(C)c1ccc(-c2nc3ccc([N+](=O)[O-])cc3c(=O)o2)cc1
Reaction time: 2 h
Yield: 93.9 %

Procedure:
To a suspension of 2-(4-tert-butylbenzoylamino)-5-nitrobenzoic acid (37.1 g, 108 mmol) and N,N-dimethylformamide (0.4 mL, 5.4 mmol) in methylene chloride (200 mL) was added oxalyl chloride (10.4 mL, 119 mmol) in a dropwise manner. After stirring for 2 h, the mixture was filtered and the small amount of black solid was discarded. The filtrate was concentrated in vacuo to give 32.9 g (94%) of the title compound as a light brown solid; mp 159-61° C.
Reaction SMILES: C(OC([N:8]1[C:12]2=[CH:13][N:14]=[C:15]([N:17]3[CH:21]=[N:20][CH:19]=[N:18]3)[CH:16]=[C:11]2[C:10]([CH:22]=[CH:23][C:24]([O:26][CH2:27][CH3:28])=[O:25])=[CH:9]1)=O)(C)(C)C.[H][H]>[Pd].C(O)C>[N:17]1([C:15]2[CH:16]=[C:11]3[CH:10]([CH2:22][CH2:23][C:24]([O:26][CH2:27][CH3:28])=[O:25])[CH2:9][NH:8][C:12]3=[CH:13][N:14]=2)[CH:21]=[N:20][CH:19]=[N:18]1
Reactant: [H][H]
Reactant: CCOC(=O)C=Cc1cn(C(=O)OC(C)(C)C)c2cnc(-n3cncn3)cc12
Agent: [Pd]
Solvent: CCO
Product: CCOC(=O)CCC1CNc2cnc(-n3cncn3)cc21

Procedure:
Ethyl 3-[1-tert-butyloxycarbonyl-5-(1,2,4-triazol-1-yl)pyrrolo[2,3-c]pyridin-3-yl]prop-2-enoate (0.29 g) was hydrogenated over palladium on carbon (10%, 0.435 g) in ethanol (50 mL) at 50 psi of hydrogen for 75 min. The catalyst was removed by filtration and the solvent evaporated in vacuo to give the title compound. (0.24 g) as a colourless solid. This was used without further purification in the next step.
Reaction SMILES: [CH:1]([C:3]1[CH:4]=[C:5]([C:9]2[CH:14]=[CH:13][C:12]([C:15]([NH2:17])=[O:16])=[CH:11][C:10]=2[CH3:18])[CH:6]=[CH:7][CH:8]=1)=O.[ClH:19].[CH3:20][C:21]1([CH3:29])[CH2:26][CH2:25][CH:24]([CH2:27][NH2:28])[CH2:23][CH2:22]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].O>C(O)(=O)C.CO>[ClH:19].[CH3:20][C:21]1([CH3:29])[CH2:26][CH2:25][CH:24]([CH2:27][NH:28][CH2:1][C:3]2[CH:4]=[C:5]([C:9]3[CH:14]=[CH:13][C:12]([C:15]([NH2:17])=[O:16])=[CH:11][C:10]=3[CH3:18])[CH:6]=[CH:7][CH:8]=2)[CH2:23][CH2:22]1
Reactant: Cc1cc(C(N)=O)ccc1-c1cccc(C=O)c1
Reactant: CC1(C)CCC(CN)CC1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: Cl
Agent: [Na+]
Solvent: CO
Solvent: O
Solvent: CC(=O)O
Product: Cc1cc(C(N)=O)ccc1-c1cccc(CNCC2CCC(C)(C)CC2)c1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
A mixture of 3′-formyl-2-methyl-4-biphenylcarboxamide (0.15 g, 0.63 mmol; Ex. IX-23), 4,4-dimethylcyclohexylmethylamine hydrochloride (0.28 g, 1.6 mmol; Ex III-1) and acetic acid (4 drops) in methanol was stirred at room temperature for 30 min. Sodium triacetoxyborohydride (0.34 g, 1.6 mmol) was added in one portion and the mixture was stirred at room temperature for 72 hr. Water (10 mL) was added and the mixture was stirred at room temperature for 2 hr. The mixture was concentrated in vacuo to remove the methanol and the residue was taken up in a mixture of ethyl acetate and 5% Na2CO3 (aq). The aqueous phase was extracted with ethyl acetate. The combined organic phase was washed with brine, silica gel was added and the mixture was concentrated in vacuo.
Reaction SMILES: Cl.[CH3:2][NH:3][C:4]([N:6]1[CH2:11][CH2:10][NH:9][CH2:8][CH2:7]1)=[O:5].C([O-])([O-])=O.[K+].[K+].[C:18]([O:22][C:23](=[O:27])[CH:24](Br)[CH3:25])([CH3:21])([CH3:20])[CH3:19]>C(#N)C>[CH3:2][NH:3][C:4]([N:6]1[CH2:11][CH2:10][N:9]([CH2:25][CH2:24][C:23]([O:22][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:27])[CH2:8][CH2:7]1)=[O:5]
Reactant: CNC(=O)N1CCNCC1
Reactant: CC(Br)C(=O)OC(C)(C)C
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: CNC(=O)N1CCN(CCC(=O)OC(C)(C)C)CC1
Temperature: 25 °C

Procedure:
To a suspension of N-methylpiperazine-1-carboxamide hydrochloride (6 g, 33.52 mmol) and K2CO3 (9.26 g, 67.0 mmol) in acetonitrile (100 mL) was added bromopropionic acid tert-butyl ester (8.4 g, 40.2 mmol). The reaction mixture was stirred at reflux for 12 h, cooled to room temperature and partitioned in ethyl acetate (200 mL) and water (100 mL). Organic layer was separated, dried (MgSO4), and concentrated to give tert-butyl 3-(4-(methylcarbamoyl)piperazin-1-yl)propanoate as an oil which was dissolved in a mixture of dichloromethane (100 mL) and TFA (trifluoroacetic acid) (20 mL) and then stirred overnight. The volatiles were removed under vacuum. The residue was dissolved in methanol, 1N hydrogen chloride in ether was added, and then the solution was concentrated to give 3-(4-(methylcarbamoyl)piperazin-1-yl)propanoic acid as a solid. LCMS 216 (M+1)
Reaction SMILES: [CH2:1]([CH:4]1[C:8]([OH:10])([CH3:9])[CH:7]=[CH:6][C:5]1=[O:11])[CH:2]=[CH2:3].[C:12](OC(=O)C)(=[O:14])[CH3:13]>C1(C)C=CC(S(O)(=O)=O)=CC=1>[C:12]([O:10][C:8]1([CH3:9])[CH:7]=[CH:6][C:5](=[O:11])[CH:4]1[CH2:1][CH:2]=[CH2:3])(=[O:14])[CH3:13]
Reactant: C=CCC1C(=O)C=CC1(C)O
Reactant: CC(=O)OC(C)=O
Agent: Cc1ccc(S(=O)(=O)O)cc1
Product: C=CCC1C(=O)C=CC1(C)OC(C)=O
Reaction time: 2 h
Yield: 95.9 %

Procedure:
Into the same flask as used in Example 1, 2-allyl-3-hydroxy-3-methyl-4-cyclopentenone (152 g), p-toluenesulfonic acid (1 g) and acetic anhydride (320 g) were charged, and stirring was continued for 2 hours at 100° C. After completion of the reaction, acetic anhydride was removed under reduced pressure, and the residue was extracted with toluene. The toluene layer was washed with 1% aqueous sodium carbonate solution and water in order and concentrated to give dl-3-acetoxy-2-allyl-3-methyl-4-cyclopentenone (186 g). Yield, 96%. B.P., 72°-75° C./0.2-0.3 mmHg.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([CH3:17])[CH:5]=[C:6]2[C:10]=1[NH:9][C:8]([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][N:12]=1)=[CH:7]2.[S:18]1[CH:22]=[CH:21][CH:20]=[C:19]1[S:23](Cl)(=[O:25])=[O:24]>>[CH3:17][C:4]1[CH:5]=[C:6]2[C:10](=[C:2]([NH:1][S:23]([C:19]3[S:18][CH:22]=[CH:21][CH:20]=3)(=[O:25])=[O:24])[CH:3]=1)[NH:9][C:8]([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][N:12]=1)=[CH:7]2
Reactant: Cc1cc(N)c2[nH]c(-c3ccccn3)cc2c1
Reactant: O=S(=O)(Cl)c1cccs1
Product: Cc1cc(NS(=O)(=O)c2cccs2)c2[nH]c(-c3ccccn3)cc2c1

Procedure:
7-Amino-5-methyl-2-(pyridin-2-yl)-1H-indole prepared in Step A of Example 1 and 2-thiophenesulfonylchloride were reacted according to the same procedure as Example 22 to give the title compound.
Reaction SMILES: [N:1]([CH2:4][C:5]([OH:7])=[O:6])=[N+:2]=[N-:3].[C:8]([C:10]([O:12][CH2:13][CH3:14])=[O:11])#[N:9]>>[CH2:13]([O:12][C:10]([C:8]1[N:1]([CH2:4][C:5]([OH:7])=[O:6])[N:2]=[N:3][N:9]=1)=[O:11])[CH3:14]
Reactant: [N-]=[N+]=NCC(=O)O
Reactant: CCOC(=O)C#N
Product: CCOC(=O)c1nnnn1CC(=O)O
Temperature: 110 °C

Procedure:
A mixture of azidoacetic acid (5.0 grams, 50 mmol.) and ethyl cyanoformate (15.0 grams, 150 millimoles,) was heated at 110°C. for 8.5 hours. The reaction mixture was cooled; crystalline product separated which was filtered and washed with toluene. The filtrate was concentrated under vacuum, and the remaining oil was cooled and seeded with a crystal of the product to give a second crop. The yield of the title product was 5.1 grams (51 percent, assuming pure starting materials), m.p. (both crops) 144°-147°C. The analysis was as follows:
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([C:8]2[CH:13]=[CH:12][N:11]=[C:10](Cl)[N:9]=2)[N:5]=[CH:4][N:3]=1.[Cl:15][C:16]1[CH:17]=[C:18]([CH:20]=[CH:21][CH:22]=1)[NH2:19].[CH3:23][O:24][CH2:25][CH:26]([NH2:28])[CH3:27]>O1CCCC1>[Cl:15][C:16]1[CH:17]=[C:18]([NH:19][C:2]2[N:7]=[C:6]([C:8]3[CH:13]=[CH:12][N:11]=[C:10]([NH:28][CH:26]([CH3:27])[CH2:25][O:24][CH3:23])[N:9]=3)[N:5]=[CH:4][N:3]=2)[CH:20]=[CH:21][CH:22]=1
Reactant: Nc1cccc(Cl)c1
Reactant: Clc1nccc(-c2ncnc(Cl)n2)n1
Reactant: COCC(C)N
Solvent: C1CCOC1
Product: COCC(C)Nc1nccc(-c2ncnc(Nc3cccc(Cl)c3)n2)n1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
To a solution of 2-chloro-4-(2-chloro-4-pyrimidinyl)-1,3,5-triazine (i.e., the product of Step B) (25 mg, 0.11 mmol) in tetrahydrofuran (1.0 mL) was added 3-chloroaniline (0.1 mL). The resulting mixture was stirred at room temperature for 3 h to generate a yellow suspension. To this suspension was added 1-methoxy-2-propylamine (0.2 mL), and the resulting mixture was refluxed for 5 h. The solution was concentrated and purified using column chromatography on silica gel eluted with 70% ethyl acetate in hexanes to give 30 mg of the title compound as a yellow solid.
Reaction SMILES: [NH2:1][CH2:2][CH2:3][CH2:4][NH:5][C:6]1[N:7]=[C:8]([NH:17][C:18]2[CH:23]=[CH:22][CH:21]=[C:20]([CH3:24])[CH:19]=2)[C:9]2[C:15](=[O:16])[NH:14][CH:13]=[CH:12][C:10]=2[N:11]=1.NCCCN[C:30]([C@@H:32]1[CH2:36][S:35][C:34](=[O:37])[NH:33]1)=[O:31]>>[CH3:24][C:20]1[CH:19]=[C:18]([NH:17][C:8]2[C:9]3[C:15](=[O:16])[NH:14][CH:13]=[CH:12][C:10]=3[N:11]=[C:6]([NH:5][CH2:4][CH2:3][CH2:2][NH:1][C:30]([C@@H:32]3[CH2:36][S:35][C:34](=[O:37])[NH:33]3)=[O:31])[N:7]=2)[CH:23]=[CH:22][CH:21]=1
Reactant: NCCCNC(=O)[C@@H]1CSC(=O)N1
Reactant: Cc1cccc(Nc2nc(NCCCN)nc3cc[nH]c(=O)c23)c1
Product: Cc1cccc(Nc2nc(NCCCNC(=O)[C@@H]3CSC(=O)N3)nc3cc[nH]c(=O)c23)c1

Procedure:
The compound was prepared from 2-[(3-aminopropyl)amino]-4-[(3-methylphenyl)amino]pyrido[4,3-d]pyrimidin-5(6H)-one and (4R)—N-(3-aminopropyl)-2-oxo-1,3-thiazolidine-4-carboxamide using the procedure similar to that described for Example
Reaction SMILES: [CH3:1][N:2]([CH2:4][CH:5]1[CH2:14][CH2:13][C:12]2[CH:11]=[C:10]([NH:15][C:16]([C:18]3[CH:23]=[CH:22][C:21]([C:24]4[CH:29]=[CH:28][C:27]([CH:30]=[O:31])=[CH:26][CH:25]=4)=[CH:20][CH:19]=3)=[O:17])[CH:9]=[CH:8][C:7]=2[CH2:6]1)[CH3:3].[BH4-].[Na+].C(OCC)(=O)C>O1CCCC1CO>[CH3:3][N:2]([CH2:4][CH:5]1[CH2:14][CH2:13][C:12]2[CH:11]=[C:10]([NH:15][C:16]([C:18]3[CH:23]=[CH:22][C:21]([C:24]4[CH:25]=[CH:26][C:27]([CH2:30][OH:31])=[CH:28][CH:29]=4)=[CH:20][CH:19]=3)=[O:17])[CH:9]=[CH:8][C:7]=2[CH2:6]1)[CH3:1]
Reactant: CN(C)CC1CCc2cc(NC(=O)c3ccc(-c4ccc(C=O)cc4)cc3)ccc2C1
Agent: [BH4-]
Agent: [Na+]
Solvent: OCC1CCCO1
Solvent: CCOC(C)=O
Product: CN(C)CC1CCc2cc(NC(=O)c3ccc(-c4ccc(CO)cc4)cc3)ccc2C1
Reaction time: 2 h
Yield: 85.7 %

Procedure:
N-[6-[(N,N-Dimethylamino)methyl]-5,6,7,8-tetrahydro-2-naphthalenyl]-4′-formyl[1,1′-biphenyl]-4-carboxamide (100 mg, 0.242 mmol) was dissolved in tetrahydrofuran-methanol (1:1) solution (2.4 ml), then sodium borohydride (18.3 mg, 0.485 mmol) was added, which was stirred for 2 hours. Ethyl acetate was added to the reaction mixture, which was washed with saturated aqueous sodium chloride solution, dried using anhydrous magnesium sulfate, and the solvent was distilled out under reduced pressure. The residue was pulverized using ether-n-hexane, to give the titled compound (86 mg) as a white powder.
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][C:6]([O:10][CH2:11][CH2:12][CH2:13]Cl)=[CH:7][CH:8]=2)[CH:3]=[CH:2]1.[OH:15][C:16]1([C:22]2[CH:23]=[N:24][C:25]3[C:30]([CH:31]=2)=[CH:29][CH:28]=[CH:27][CH:26]=3)[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]1>>[NH:1]1[C:9]2[C:4](=[CH:5][C:6]([O:10][CH2:11][CH2:12][CH2:13][N:19]3[CH2:20][CH2:21][C:16]([OH:15])([C:22]4[CH:23]=[N:24][C:25]5[C:30]([CH:31]=4)=[CH:29][CH:28]=[CH:27][CH:26]=5)[CH2:17][CH2:18]3)=[CH:7][CH:8]=2)[CH:3]=[CH:2]1
Reactant: ClCCCOc1ccc2[nH]ccc2c1
Reactant: OC1(c2cnc3ccccc3c2)CCNCC1
Product: OC1(c2cnc3ccccc3c2)CCN(CCCOc2ccc3[nH]ccc3c2)CC1
Yield: 45.6 %

Procedure:
Beginning with 0.275 gm (1.3 mMol) 3-chloropropyl indol-5-yl ether and 0.300 gm (1.3 mMol) 4-hydroxy-4-(quinolin-3-yl)piperidine, 0.238 gm (45%) of the title compound were recovered as an off-white solid.
Reaction SMILES: [CH:1]([CH:3]1[C:7]([CH3:9])([CH3:8])[CH2:6][CH2:5][C:4]1([CH3:11])[CH3:10])=[O:2].CC(C)=[O:14].OS(O)(=O)=O.O=[Cr](=O)=O.O.C(OCC)(=O)C>CC(C)=O.C(O)(C)C>[CH3:8][C:7]1([CH3:9])[CH2:6][CH2:5][C:4]([CH3:11])([CH3:10])[CH:3]1[C:1]([OH:14])=[O:2]
Reactant: CC(C)=O
Reactant: CC1(C)CCC(C)(C)C1C=O
Agent: O=[Cr](=O)=O
Agent: O=S(=O)(O)O
Solvent: CC(C)O
Solvent: CCOC(C)=O
Solvent: O
Product: CC1(C)CCC(C)(C)C1C(=O)O
Temperature: 25 °C
Reaction time: 4 h
Yield: 92 %

Procedure:
2.47 g of 1-formyl-2,2,5,5-tetramethylcyclopentane was dissolved in 26 ml of acetone, and 5.2 ml of Jones' reagent was added thereto with ice cooling. After stirring at room temperature for 4 hours, 26 ml of water, 26 ml of ethyl acetate and 2.6 ml of isopropyl alcohol were added thereto, and the mixture was stirred at room temperature for 30 minutes, and the resulting layers were separated. The organic layer was washed with water and aqueous saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and subjected to filtration. The filtrate was concentrated under reduced pressure, whereby 2.51 g of 2,2,5,5-tetramethylcyclopentanecarboxylic acid was obtained. Yield 92%.
Reaction SMILES: [CH3:1][N:2]([CH3:15])[CH2:3][CH2:4][C:5]1[CH:13]=[CH:12][C:11]([NH2:14])=[C:10]2[C:6]=1[CH:7]=[N:8][NH:9]2.[CH3:16][S:17]([Cl:20])(=[O:19])=[O:18]>CN(C)C=O.O1CCCC1>[ClH:20].[CH3:15][N:2]([CH3:1])[CH2:3][CH2:4][C:5]1[CH:13]=[CH:12][C:11]([NH:14][S:17]([CH3:16])(=[O:19])=[O:18])=[C:10]2[C:6]=1[CH:7]=[N:8][NH:9]2
Reactant: CS(=O)(=O)Cl
Reactant: CN(C)CCc1ccc(N)c2[nH]ncc12
Solvent: C1CCOC1
Solvent: CN(C)C=O
Product: CN(C)CCc1ccc(NS(C)(=O)=O)c2[nH]ncc12
Product: Cl
Temperature: 0 °C
Reaction time: 14 h

Procedure:
At 0° C., 1.2 g of N,N-dimethyl-N-[2-(7-amino-1H-indazol-4-yl)ethyl]amine in 10 ml of dimethylformamide and 5 ml of tetrahydrofuran is combined with 0.91 ml of methanesulfonyl chloride The mixture is agitated for 2 hours at 0° C. and for 14 hours at room temperature. The product is chromatographed on silica gel with methanol/dichloromethane 1:1 and treated with ethereal hydrochloric acid, obtaining, after recrystallization from methanol/diethyl ether, 550 mg of N-[4-(2-dimethylamino-ethyl)-1H-indazol-7-yl]methanesulfonamide, hydrochloride, mp 203°-205° C.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C:11]2[CH2:15][C:14]([C:20]3[CH:25]=[C:24]([Cl:26])[C:23]([Cl:27])=[C:22]([Cl:28])[CH:21]=3)([C:16]([F:19])([F:18])[F:17])[O:13][N:12]=2)[CH:5]=[CH:6][C:7]=1[CH2:8][NH:9][CH3:10].[CH2:29]([S:31][CH2:32][C:33]([OH:35])=O)[CH3:30].Cl.CN(C)CCCN=C=NCC>ClCCl>[Cl:1][C:2]1[CH:3]=[C:4]([C:11]2[CH2:15][C:14]([C:20]3[CH:25]=[C:24]([Cl:26])[C:23]([Cl:27])=[C:22]([Cl:28])[CH:21]=3)([C:16]([F:19])([F:17])[F:18])[O:13][N:12]=2)[CH:5]=[CH:6][C:7]=1[CH2:8][N:9]([CH3:10])[C:33](=[O:35])[CH2:32][S:31][CH2:29][CH3:30]
Reactant: CNCc1ccc(C2=NOC(c3cc(Cl)c(Cl)c(Cl)c3)(C(F)(F)F)C2)cc1Cl
Reactant: CCSCC(=O)O
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Solvent: ClCCl
Product: CCSCC(=O)N(C)Cc1ccc(C2=NOC(c3cc(Cl)c(Cl)c(Cl)c3)(C(F)(F)F)C2)cc1Cl

Procedure:
To a solution of 0.10 g of 3-[3-chloro-4-[N-(methyl)aminomethyl]phenyl]-5-(3,4,5-trichlorophenyl)-5-trifluoromethyl-4,5-dihydroisoxazole and 0.038 g of (ethylthio)acetic acid in 3 mL of dichloromethane, 0.089 g of 1-[3-(dimethylamino) propyl]-3-ethylcarbodiimide hydrochloride was added and the resultant mixture was stirred at room temperature for 3 hours. After the completion of the reaction, the reaction mixture was washed with water (5 mL×1) and then dehydrated and dried over saturated saline and anhydrous sodium sulfate in this order, and then the solvent was distilled off under reduced pressure. The resultant residue was purified by preparative medium pressure liquid chromatography eluting with ethyl acetate-hexane (a gradient from 1:5 to 1:3) using a medium pressure preparative apparatus (trade name: YFLC-Wprep; manufactured by Yamazen Corporation) to obtain 0.083 g of the objective substance as a colorless resinoid.