Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:12]([C:13]3[CH:18]=[CH:17][N:16]=[CH:15][CH:14]=3)=[CH:11][N:10]([C:19]3[CH:24]=[CH:23][C:22](=[O:25])[NH:21][N:20]=3)[N:9]=2)=[CH:4][CH:3]=1.[NH2:26]C1C=C(C2C(C3C=CC(F)=CC=3)=NN(C3C=CC(=O)NN=3)C=2)C=CN=1>>[NH2:26][C:23]1[C:22](=[O:25])[NH:21][N:20]=[C:19]([N:10]2[CH:11]=[C:12]([C:13]3[CH:14]=[CH:15][N:16]=[CH:17][CH:18]=3)[C:8]([C:5]3[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=3)=[N:9]2)[CH:24]=1
Reactant: Nc1cc(-c2cn(-c3ccc(=O)[nH]n3)nc2-c2ccc(F)cc2)ccn1
Reactant: O=c1ccc(-n2cc(-c3ccncc3)c(-c3ccc(F)cc3)n2)n[nH]1
Product: Nc1cc(-n2cc(-c3ccncc3)c(-c3ccc(F)cc3)n2)n[nH]c1=O
Yield: 40 %

Procedure:
The reaction was carried out in the same manner as in Example 4 except for using 213 mg (0.64 mmol) of 3-(4-fluorophenyl)-1-(1,6-dihydro-6-oxopyridazin-3-yl)-4-(pyridin-4-yl)-1H-pyrazole obtained in Example 1-4) in place of 4-(2-aminopyridin-4-yl)-3-(4-fluorophenyl)-1-(1,6-dihydro-6-oxopyridazin-3-yl)-1H-pyrazole to obtain 90.3 mg of the title compound as a white powder. (Yield: 40%)
Reaction SMILES: [OH-:1].[Na+].[C:3]([CH2:5][C:6]1([CH3:18])[CH2:10][C:9]2[C:11]([CH3:17])=[CH:12][C:13]([CH3:16])=[C:14]([CH3:15])[C:8]=2[O:7]1)#N.Cl.[OH2:20]>CO>[CH3:18][C:6]1([CH2:5][C:3]([OH:20])=[O:1])[CH2:10][C:9]2[C:11]([CH3:17])=[CH:12][C:13]([CH3:16])=[C:14]([CH3:15])[C:8]=2[O:7]1
Reactant: Cc1cc(C)c2c(c1C)OC(C)(CC#N)C2
Reactant: [OH-]
Reactant: O
Agent: Cl
Agent: [Na+]
Solvent: CO
Product: Cc1cc(C)c2c(c1C)OC(C)(CC(=O)O)C2
Yield: 79.9 %

Procedure:
A solution of sodium hydroxide (12.0 g, 300 mmol) in water (30 ml) was added to a solution of 2-cyanomethyl-2,4,6,7-tetramethyl-2,3-dihydrobenzofuran (6.9 g, 32.1 mmol) in methanol (30 ml) and the mixture was heated under reflux for 18 hours. The reaction mixture was made weakly acidic with 6N hydrochloric acid and the product was extracted with ethyl acetate. The extract was washed with water, dried and concentrated. The residue was crystallized from ethyl acetate-hexane to obtain the desired compound (6.0 g, yield: 79.9%), m.p. 139°-140° C.
Reaction SMILES: C(O[CH:5]([O:12][CH2:13][O:14][C:15](=[O:17])[CH3:16])[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)(=O)C.C[Si](C)(C)[O:20][C:21]1[N:26]=[C:25]([O:27][Si](C)(C)C)[C:24]([F:32])=[CH:23][N:22]=1.C(=O)([O-])O.[Na+].O>C(#N)C>[C:15]([O:14][CH2:13][O:12][CH:5]([N:22]1[CH:23]=[C:24]([F:32])[C:25](=[O:27])[NH:26][C:21]1=[O:20])[C:6]1[CH:7]=[CH:8][CH:9]=[CH:10][CH:11]=1)(=[O:17])[CH3:16]
Reactant: C[Si](C)(C)Oc1ncc(F)c(O[Si](C)(C)C)n1
Reactant: CC(=O)OCOC(OC(C)=O)c1ccccc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CC#N
Solvent: O
Product: CC(=O)OCOC(c1ccccc1)n1cc(F)c(=O)[nH]c1=O
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 57.1 %

Procedure:
A solution of α-acetoxymethoxybenzyl alcohol acetate (1.43 g; 6 mmoles) prepared in Example I - 1 and 2,4-di-(trimethylsilyloxy)-5-fluoropyrimidine (1.37 g; 5 mmoles) in dry acetonitrile (25 ml) is cooled at 0° C. Stannic chloride (d=2.26; 0.58 ml; 5 mmoles) is added thereto, and the mixture is stirred at 0° C. for 30 minutes, then mixed with sodium hydrogencarbonate (2.52 g; 30 mmoles) and water (2.5 ml), and vigorously stirred at 0° C. The insoluble materials are filtered off and washed with acetonitrile and methylene chloride. The organic layer is washed with an aqueous saturated solution of sodium hydrogencarbonate and then with saturated brine, dried over magnesium sulfate, and evaporated. The residue is chromatographed on a column of silica gel and eluted with benzene-ethyl acetate (2:1). The eluate is recrystallized from ether to give the title compound (0.88 g; yield 57%). mp. 108°-109° C.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:11]=[C:10]2[C:6]([C:7](=[O:13])[C:8](=[O:12])[NH:9]2)=[CH:5][CH:4]=1.Br[CH2:15][CH2:16][CH:17]1[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]1>>[CH:17]1([CH2:16][CH2:15][N:9]2[C:10]3[C:6](=[CH:5][CH:4]=[C:3]([O:2][CH3:1])[CH:11]=3)[C:7](=[O:13])[C:8]2=[O:12])[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]1
Reactant: COc1ccc2c(c1)NC(=O)C2=O
Reactant: BrCCC1CCCCC1
Product: COc1ccc2c(c1)N(CCC1CCCCC1)C(=O)C2=O

Procedure:
The title compound was prepared as a red solid, using 6-methoxy-isatin prepared as described in Pavlidis et al. and 1-Bromo-2-cyclohexylethane following Method B. Pavlidis, V. H., et al., The Synthesis of a Novel Series of Substituted 2-Phenyl-4H-3,1-benzoxazin-4-ones, Synthetic Communications, 1994, 24:4, 533-548.
Reaction SMILES: CCO/[CH:4]=[C:5](/[CH:7]=O)\[CH3:6].[NH2:9][C:10]1[N:14]=[C:13]([SH:15])[NH:12][N:11]=1>>[CH3:6][C:5]1[CH:4]=[N:9][C:10]2[N:11]([N:12]=[C:13]([SH:15])[N:14]=2)[CH:7]=1
Reactant: Nc1n[nH]c(S)n1
Reactant: CCO/C=C(\C)C=O
Product: Cc1cnc2nc(S)nn2c1

Procedure:
The title compound was prepared from 3-ethoxymethacrolein and 3-amino-5-mercapto-1,2,4-triazole as previously described by M. Kunstlinger and E. Breitmaier in Synthesis, 1983, 44-47. 1H NMR (DMSO-d6) d 2.31 (s, 1H) 8.45 (s, 1H) 8.68 (s, 1H). MS (APCI) calcd for C6H6N4S: 166.21; found (M+H+) 167.0.
Reaction SMILES: [NH2:1][C:2]1[CH:11]=[CH:10][C:5]2[N:6]=[C:7]([SH:9])[S:8][C:4]=2[CH:3]=1.C(=O)CC[CH2:15][CH2:16][CH3:17].CO.[BH3-][C:22]#N.[Na+]>O.C(O)(=O)C>[CH3:22][CH:16]([CH3:15])[CH2:17][NH:1][C:2]1[CH:11]=[CH:10][C:5]2[N:6]=[C:7]([SH:9])[S:8][C:4]=2[CH:3]=1
Reactant: [BH3-]C#N
Reactant: Nc1ccc2nc(S)sc2c1
Reactant: CCCCCC=O
Agent: [Na+]
Solvent: O
Solvent: CC(=O)O
Solvent: CO
Product: CC(C)CNc1ccc2nc(S)sc2c1
Reaction time: 4 h
Yield: 55.9 %

Procedure:
Into a 500 ml round bottomed flask were added 6-amino-1,3-benzothiazole-2-thiol (5.0 g, 0.03 mol), hexanal (3.0 g, 0.03 mol), methanol (250 ml), glacial acetic acid (2.5 ml), water (1 ml), and NaCNBH3 (1.9 g, 0.03 mol). The mixture was stirred for 4 h, filtered, and the filtrate was concentrated to give light yellow solid. The solid was washed with water and triturated with diethyl ether to give 4.0 g (61%) of the title compound. 1H NMR (DMSO-d6) δ=0.88 (t, 6H), 1.79 (m, 1H), 2.77 (t, 2H), 6.64 (d, 1H), 6.72 (s, 1H), 6.99 (d, 2H); ESIMS: m/z 239 (M−H).
Reaction SMILES: [CH:1]1[CH2:6][CH2:5][CH:4]=[CH:3][CH:2]=1.[C:7]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])(=[O:10])C=C.[CH2:16]1COC[CH2:17]1>>[CH:2]12[CH2:17][CH2:16][CH:5]([CH:6]=[CH:1]1)[CH2:4][CH:3]2[C:7]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10]
Reactant: C1=CCCC=C1
Reactant: C=CC(=O)OC(C)(C)C
Reactant: C1CCOC1
Product: CC(C)(C)OC(=O)C1CC2C=CC1CC2
Reaction time: 24 h
Yield: 48 %

Procedure:
Cyclohexadiene (80g) and 154 g of t-butyl acrylate were dissolved in 500 g of THF solvent. After reacting at 50° C. for 24 hours, the solvent was removed by rotary evaporator. The residue was distilled under reduced pressure to obtain 112 g of t-butyl bicyclo[2,2,2]oct -5-ene-2-carboxylate as a mixture of endo and exo (yield: 48%).
Reaction SMILES: [CH2:1]([O:5][C:6]1[C:14]([C:15]2[NH:16][C:17](=[O:30])[C:18]3[C:19](=[C:21]([CH2:28][CH3:29])[N:22]([CH2:24][CH2:25][O:26][CH3:27])[N:23]=3)[N:20]=2)=[CH:13][C:9]([C:10]([OH:12])=O)=[CH:8][N:7]=1)[CH2:2][CH2:3][CH3:4].O.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.C(N(C(C)C)CC)(C)C.Cl.[CH3:64][NH:65][O:66][CH3:67]>ClCCl>[CH2:1]([O:5][C:6]1[C:14]([C:15]2[NH:16][C:17](=[O:30])[C:18]3[C:19](=[C:21]([CH2:28][CH3:29])[N:22]([CH2:24][CH2:25][O:26][CH3:27])[N:23]=3)[N:20]=2)=[CH:13][C:9]([C:10]([N:65]([O:66][CH3:67])[CH3:64])=[O:12])=[CH:8][N:7]=1)[CH2:2][CH2:3][CH3:4]
Reactant: CCCCOc1ncc(C(=O)O)cc1-c1nc2c(CC)n(CCOC)nc2c(=O)[nH]1
Reactant: CNOC
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Solvent: O
Product: CCCCOc1ncc(C(=O)N(C)OC)cc1-c1nc2c(CC)n(CCOC)nc2c(=O)[nH]1
Temperature: 25 °C
Reaction time: 14 h
Yield: 80.9 %

Procedure:
6-Butoxy-5-[3-ethyl-2-(2-methoxyethyl)-7-oxo-6,7-dihydro-2H-pyrazolo-[4,3-d]pyrimidin-5-yl]nicotinic acid (Example 3) (200 mg, 0.48 mmol) was dissolved in dichloromethane and 1-hydroxybenzotriazole hydrate (78 mg, 0.58 mmol) and 1-(3-dimethylaminopropyl)-3-ethyl-carbodiimide hydrochloride (120 mg, 0.58 mmol) were added followed by diisopropylethylamine (0.34 mL, 1.95 mmol). N,O-dimethylhydroxyl-amine hydrochloride (56.3 mg, 0.58 mmol) was added and the mixture stirred at room temperature for 14 h. A further 0.29 mmol of 1-hydroxybenzotriazole hydrate and 1-(3-dimethylaminopropyl)-3-ethyl-carbodiimide hydrochloride were added and the reaction stirred for a further 3 h. The reaction mixture was diluted with further dichloromethane, washed with water, dried (MgSO4) and concentrated. Purification by flash column chromatography (gradient elution from dichloromethane to 5% methanol:dichloromethane) gave the title compound (178 mg, 81%).
Reaction SMILES: C(OP(C#[N:10])(=O)OCC)C.[N:11]1[CH:16]=[CH:15][CH:14]=[C:13]([C:17]2[CH:22]=[CH:21][N:20]=[C:19]([NH:23][C:24]3[CH:25]=[C:26]([CH:30]=[CH:31][CH:32]=3)[C:27]([OH:29])=O)[N:18]=2)[CH:12]=1.[CH3:33][N:34]1[CH2:39][CH2:38][N:37]([CH2:40]C2C=CC(N)=CC=2)[CH2:36][CH2:35]1.C(N(CC)CC)C.C(=O)([O-])O.[Na+]>CN(C)C=O.O>[N:11]1[CH:16]=[CH:15][CH:14]=[C:13]([C:17]2[CH:22]=[CH:21][N:20]=[C:19]([NH:23][C:24]3[CH:25]=[C:26]([CH:30]=[CH:31][CH:32]=3)[C:27]([NH:10][CH2:40][N:37]3[CH2:36][CH2:35][N:34]([CH3:33])[CH2:39][CH2:38]3)=[O:29])[N:18]=2)[CH:12]=1
Reactant: CN1CCN(Cc2ccc(N)cc2)CC1
Reactant: CCOP(=O)(C#N)OCC
Reactant: O=C(O)c1cccc(Nc2nccc(-c3cccnc3)n2)c1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCN(CC)CC
Solvent: O
Solvent: CN(C)C=O
Product: CN1CCN(CNC(=O)c2cccc(Nc3nccc(-c4cccnc4)n3)c2)CC1
Temperature: 60 °C
Reaction time: 12 h

Procedure:
Diethylcyanophosphonate (Aldrich, Buchs, Switzerland; 0.50 mL, 3.0 mmol) is added to a stirred mixture of 3-[[4-(3-pyridinyl)-2-pyrimidinyl]amino]-benzoic acid (438 mg, 1.5 mmol), 4-[(4-methyl-1-piperazinyl)methyl]benzeneamine (308 mg, 1.5 mmol) and triethylamine (840 μL, 3.0 mmol) in 10 mL N,N-dimethylformamide at 10° C. After stirring for 12 hours at 60° C., the mixture is treated with an aqueous solution of sodium hydrogen carbonate and extracted three times with ethyl acetate. The combined extracts are washed with water, and the solvent is evaporated off under reduced pressure to give a residue. The residue is resuspended in water and filtered to afford the crude product which is recrystallised from tetrahydrofuran-ethyl acetate to give N-[3-[[4-(3-Pyridinyl)-2-pyrimidinyl]amino]-N-[(4-methyl-1-piperazinyl)-methyl]benzamide as a crystalline solid, m.p. 220-224° C.
Reaction SMILES: [CH3:1]/[C:2](/[NH2:6])=[CH:3]\[C:4]#[N:5].[C:7]([CH2:10][C:11](=O)[CH3:12])(=O)[CH3:8]>>[C:4]([C:3]1[C:2]([CH3:1])=[N:6][C:7]([CH3:8])=[CH:10][C:11]=1[CH3:12])#[N:5]
Reactant: CC(=O)CC(C)=O
Reactant: C/C(N)=C\C#N
Product: Cc1cc(C)c(C#N)c(C)n1

Procedure:
3-Cyano-2,4,6-trimethylpyridine was prepared from 3-aminocrotonitrile and acetylacetone following the procedure of Kato and Noda (Chem. Pharm. Bull. 24, 303, 1976).
Reaction SMILES: C([O:3][C:4]([C:6]1[CH:10]=[C:9]([CH3:11])[N:8]([CH2:12][C:13]2[CH:18]=[C:17]([Cl:19])[CH:16]=[CH:15][C:14]=2[O:20][CH2:21][C:22]2[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[CH:24][CH:23]=2)[N:7]=1)=[O:5])C.[Li+].[OH-].O>CCO>[CH3:11][C:9]1[NH:8][N:7]=[C:6]([C:4]([OH:5])=[O:3])[CH:10]=1.[Cl:19][C:17]1[CH:16]=[CH:15][C:14]([O:20][CH2:21][C:22]2[CH:23]=[CH:24][C:25]([O:28][CH3:29])=[CH:26][CH:27]=2)=[C:13]([CH:18]=1)[CH2:12][N:8]1[C:9]([CH3:11])=[CH:10][C:6]([C:4]([OH:5])=[O:3])=[N:7]1
Reactant: CCOC(=O)c1cc(C)n(Cc2cc(Cl)ccc2OCc2ccc(OC)cc2)n1
Agent: [Li+]
Agent: [OH-]
Solvent: CCO
Solvent: O
Product: COc1ccc(COc2ccc(Cl)cc2Cn2nc(C(=O)O)cc2C)cc1
Product: Cc1cc(C(=O)O)n[nH]1
Temperature: 100 °C

Procedure:
To a solution of 1-[5-chloro-2-(4-methoxy-benzyloxy)-benzyl]-5-methyl-1H-pyrazole-3-carboxylic acid ethyl ester, 13, 0.28 g (0.6 mmol) in EtOH (2 mL) was added a solution of LiOH (0.15 g in 0.5 ml H2O). The resulting mixture was heated at 100° C. on microwave for 10 minutes. The mixture was poured into water (20 mL) and extracted with EtOAc (3×15 mL). The organic layers were combined, washed with brine (30 mL), dried (MgSO4) and the volatiles removed in vacuo to yield 5-chloro-2-(4-methoxy-benzyloxy)-benzyl]-5-methyl-1H-pyrazole-3-carboxylic acid, 14 as a white solid.
Reaction SMILES: C([O:3][C:4]([C:6]1[C:7]([CH3:31])=[C:8]2[C:13]([NH:14][C:15]3[CH:20]=[CH:19][C:18]([O:21][C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=4)=[CH:17][CH:16]=3)=[C:12]([C:28]#[N:29])[CH:11]=[N:10][N:9]2[CH:30]=1)=O)C.CC(C[AlH]CC(C)C)C>C1COCC1>[OH:3][CH2:4][C:6]1[C:7]([CH3:31])=[C:8]2[C:13]([NH:14][C:15]3[CH:16]=[CH:17][C:18]([O:21][C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=4)=[CH:19][CH:20]=3)=[C:12]([C:28]#[N:29])[CH:11]=[N:10][N:9]2[CH:30]=1
Reactant: CCOC(=O)c1cn2ncc(C#N)c(Nc3ccc(Oc4ccccc4)cc3)c2c1C
Agent: CC(C)C[AlH]CC(C)C
Solvent: C1CCOC1
Product: Cc1c(CO)cn2ncc(C#N)c(Nc3ccc(Oc4ccccc4)cc3)c12
Temperature: -78 °C
Reaction time: 6 h
Yield: 89.1 %

Procedure:
To a solution of compound 3A (41 mg, 0.10 mmol) in THF (2 mL) at −78° C. was added DIBAL-H (1.5 M in toluene, 0.13 mL, 0.20 mmol). The reaction mixture was stirred for 6 h at −78° C., warmed to 0° C. and stirred for an additional 2 h. The reaction mixture was quenched by the addition of methanol (3 mL) and sat. aq. Na2CO3 (3 mL) and then poured onto dichloromethane (20 mL). The layers were separated, the aqueous phase was extracted with dichloromethane (2×15 mL), and the combined organic extracts were dried over MgSO4, filtered, and concentrated in vacuo. Purification via preparative HPLC (YMC S5 ODS 20×100 mm, eluting with 30-100% aqueous methanol over 15 min containing 0.1% TFA, 20 mL/min) afforded 33 mg (90% yield) of compound 3B as a yellow solid. HPLC: 100% at 3.98 min (retention time) (YMC S5 ODS column, 4.6×50 mm, eluting with 10-90% aqueous methanol over 4 min containing 0.2% phosphoric acid, 4 mL/min, monitoring at 220 nm). MS (ES): m/z 371.19 [M+H]+.
Reaction SMILES: C[O:2][C:3](=[O:27])[CH2:4][C:5]([NH:7][C:8]1[CH:13]=[C:12]([CH3:14])[C:11]([O:15][C:16]2[CH:21]=[CH:20][C:19]([OH:22])=[C:18]([CH:23]([CH3:25])[CH3:24])[CH:17]=2)=[C:10]([CH3:26])[CH:9]=1)=[O:6].[OH-].[K+]>CO.O>[OH:22][C:19]1[CH:20]=[CH:21][C:16]([O:15][C:11]2[C:10]([CH3:26])=[CH:9][C:8]([NH:7][C:5](=[O:6])[CH2:4][C:3]([OH:27])=[O:2])=[CH:13][C:12]=2[CH3:14])=[CH:17][C:18]=1[CH:23]([CH3:25])[CH3:24]
Reactant: COC(=O)CC(=O)Nc1cc(C)c(Oc2ccc(O)c(C(C)C)c2)c(C)c1
Agent: [K+]
Agent: [OH-]
Solvent: CO
Solvent: O
Product: Cc1cc(NC(=O)CC(=O)O)cc(C)c1Oc1ccc(O)c(C(C)C)c1
Temperature: 25 °C
Reaction time: 4 h

Procedure:
To a solution of N-[4-(4-hydroxy-3-isopropyl-phenoxy)-3,5-dimethyl-phenyl]-malonamic acid methyl ester (29 mg, 0.08 mmol) in a mixture of MeOH (1 mL) and H2O (1 mL) was added 3 N KOH (0.9 mmol, 0.3 mL). After stirring at RT for 4 h, H2O (10 mL) was added. The solution was washed with EtOAc (2×10 mL) and acidified with 1 N HCl. The aqueous solution was extracted with EtOAc (3×10 mL). The combined organic extracts were washed with brine, dried and concentrated to give the title compound of Step E and Example 1 (20 mg) as a white solid. MS (APCl−) Calc.: 357.1, Found: 356.1 (M−1).
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([C:9]2[C:13]3[CH2:14]N(C(OC(C)(C)C)=O)C[CH2:17][C:12]=3[NH:11][N:10]=2)[CH:5]=[CH:6][C:7]=1[F:8].O1CCC[C:27](=[O:31])C1.[F:32]C1C=C(F)C(F)=CC=1C(Cl)=O>>[F:32][C:5]1[CH:6]=[C:7]([F:8])[C:2]([F:1])=[CH:3][C:4]=1[C:9]1[C:13]2[CH2:14][CH2:27][O:31][CH2:17][C:12]=2[NH:11][N:10]=1
Reactant: O=C1CCCOC1
Reactant: O=C(Cl)c1cc(F)c(F)cc1F
Reactant: CC(C)(C)OC(=O)N1CCc2[nH]nc(-c3ccc(F)c(F)c3)c2C1
Product: Fc1cc(F)c(-c2n[nH]c3c2CCOC3)cc1F

Procedure:
Intermediate 16D was prepared according to the procedure for the synthesis of intermediate 15 by replacing 1-Boc-4-piperidone with dihydro-2H-pyran-3(4H)-one, and replacing 3,4-difluorobenzoyl chloride with 2,4,5-trifluorobenzoyl chloride. LCMS (+ESI) m/z=255 [M+H]+.
Reaction SMILES: [CH2:1]([NH:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1)[CH3:2].C(N(CC)CC)C.Br[CH2:18][CH2:19][CH2:20][C:21]([O:23][CH2:24][CH3:25])=[O:22]>C(OCC)(=O)C>[CH2:1]([N:3]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1)[CH2:18][CH2:19][CH2:20][C:21]([O:23][CH2:24][CH3:25])=[O:22])[CH3:2]
Reactant: CCOC(=O)CCCBr
Reactant: CCNc1ccccc1
Solvent: CCN(CC)CC
Solvent: CCOC(C)=O
Product: CCOC(=O)CCCN(CC)c1ccccc1
Temperature: 25 °C
Yield: 79.7 %

Procedure:
N-ethylaniline 5 (2.0 gm, 0.016 moles), triethylamine (5.0 ml, 0.036 moles), and ethyl 4-bromobutyrate (3.45 gm, 0.018 moles) were heated at 110° C. for 14 hours under argon. The mixture was cooled to room temperature, diluted with 50 ml ethyl acetate, washed with 50 ml water and 50 ml saturated NaCl, dried over MgSO4, filtered, and evaporated under reduced pressure to give crude ethyl 4-(ethylphenylamino)butanoate 6 (3.0 gm, 77% yield). 1H NMR (CDCl3) δ 7.2, 2H, m; 6.6; 3H, m; 4.15, 2H, q; 3.3, 4H, m; 2.38, 2H, t; 1.9, 2H, m; 1.25, 3H, t; 1.10, 3H, t.
Reaction SMILES: Cl.[N:2]([O-])=O.[Na+].Cl.C([O:10][C:11]1[CH:16]=[CH:15][C:14]([O:17]C(=O)C)=[CH:13][C:12]=1[CH2:21][CH2:22][C:23]1[CH:29]=[CH:28][C:26]([NH2:27])=[CH:25][CH:24]=1)(=O)C.C([O-])(=O)C.[Na+].[C:35]([CH2:37][C:38]([C:40]1[O:41][CH:42]=[CH:43][CH:44]=1)=[O:39])#[N:36]>C(O)C.O>[O:39]=[C:38]([C:40]1[O:41][CH:42]=[CH:43][CH:44]=1)[CH:37]([N:2]=[N:27][C:26]1[CH:25]=[CH:24][C:23]([CH2:22][CH2:21][C:12]2[CH:13]=[C:14]([OH:17])[CH:15]=[CH:16][C:11]=2[OH:10])=[CH:29][CH:28]=1)[C:35]#[N:36]
Reactant: O=N[O-]
Reactant: N#CCC(=O)c1ccco1
Reactant: CC(=O)Oc1ccc(OC(C)=O)c(CCc2ccc(N)cc2)c1
Agent: CC(=O)[O-]
Agent: Cl
Agent: [Na+]
Solvent: O
Solvent: CCO
Product: N#CC(N=Nc1ccc(CCc2cc(O)ccc2O)cc1)C(=O)c1ccco1
Temperature: 60 °C
Yield: 52 %

Procedure:
By utilizing 350 ml of water, 20 ml of 35% hydrochloric acid and 8 g of sodium nitrite, 35 g of 4-(2,5-bisacetoxyphenylethyl)aniline hydrochloride disclosed in Japanese Pat. Publication No. 444/63 was diazotized. Then, the mixture was neutralized with sodium acetate to adjust the pH of the solution to 6, and the mixture cooled with ice water was added dropwise at 5° C or less to liquid comprising of 13.5 g of 2-cyanoacetylfuran and 300 ml of ethanol. The resulting resinous substance was washed with water and decanted 2 times and then stirred in water, whereby crystals were formed. In 400 ml of ethanol, 40 g of the crude product obtained by filtering the crystals and drying the crystals was suspended. To the suspension, a liquid comprising 40 g of potassium hydroxide and 100 ml of water was added under vacuum, and the mixture heated for several minutes at 60° C, and then rapidly cooled. To the cooled mixture, 200 ml of a 35% hydrochloric acid aqueous solution was added to form crystals which were filtered, washed with water and recrystallized from 250 ml of ethanol to provide 19.5 g of the compound having a melting point of 175° to 178° C.
Reaction SMILES: Cl.Cl.[NH2:3][CH:4]1[CH:9]2[CH2:10][CH2:11][N:6]([CH2:7][CH2:8]2)[CH2:5]1.[O:12]1[CH:16]=[CH:15][CH:14]=[C:13]1[C:17]([NH:19][C:20](N)=[O:21])=[O:18].C(N(C(C)C)CC)(C)C.C([O-])(=O)CCC([O-])=O>N1C=CC=CC=1>[N:6]12[CH2:11][CH2:10][CH:9]([CH2:8][CH2:7]1)[CH:4]([NH:3][C:20]([NH:19][C:17]([C:13]1[O:12][CH:16]=[CH:15][CH:14]=1)=[O:18])=[O:21])[CH2:5]2
Reactant: NC1CN2CCC1CC2
Reactant: NC(=O)NC(=O)c1ccco1
Agent: Cl
Agent: O=C([O-])CCC(=O)[O-]
Solvent: c1ccncc1
Solvent: CCN(C(C)C)C(C)C
Product: O=C(NC(=O)c1ccco1)NC1CN2CCC1CC2

Procedure:
The above compound was prepared, following the procedure of Example 14b, from 3-aminoquinuclidine dihydrochloride (1.0 g, 5 mmol), 2-furoylurea (0.77 g, 5 mmol), and diisopropylethylamine (1.3 g, 10 mmol) in pyridine (20 ml). The product (0.58 g) was converted to the 1:1 succinate mp 156°-159° C.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]2[C:9]3([CH2:19][O:20][C:5]=2[CH:4]=1)[C:17]1[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=1)[NH:11][C:10]3=[O:18].CC1C2C=C3[C:33]4([C:41]5[C:36](=[CH:37]C=C[CH:40]=5)N[C:34]4=[O:42])COC3=CC=2ON=1.BrCC1CCOCC1.BrCC1OC(C(F)(F)F)=CC=1>>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]2[C:9]3([CH2:19][O:20][C:5]=2[CH:4]=1)[C:17]1[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=1)[N:11]([CH2:40][CH:41]1[CH2:36][CH2:37][O:42][CH2:34][CH2:33]1)[C:10]3=[O:18]
Reactant: COc1ccc2c(c1)OCC21C(=O)Nc2ccccc21
Reactant: Cc1noc2cc3c(cc12)C1(CO3)C(=O)Nc2ccccc21
Agent: BrCC1CCOCC1
Agent: FC(F)(F)c1ccc(CBr)o1
Product: COc1ccc2c(c1)OCC21C(=O)N(CC2CCOCC2)c2ccccc21

Procedure:
Following the procedure as described in EXAMPLE 9 and making non-critical variations using 6-methoxyspiro[1-benzofuran-3,3′-indol]-2′(1′H)-one to replace 3-methylspiro[furo[3,2-f][1,2]benzisoxazole-5,3′-indol]-2′(1′H)-one, and 4-(bromomethyl)tetrahydro-2H-pyran to replace 2-(bromomethyl)-5-(trifluoromethyl)furan, 6-methoxy-1′-(tetrahydro-2H-pyran-4-ylmethyl)spiro[1-benzofuran-3,3′-indol]-2′(1′H)-one was obtained (84%) as a colorless foam; 1H NMR (300 MHz, CDCl3) δ 7.31 (dd, J=7.5, 1.2 Hz, 1H), 7.15 (dd, J=7.5, 1.2 Hz, 1H), 7.04 (dd, J=7.5 Hz, 1H), 6.91 (d, J=7.8 Hz, 1H), 6.57 (d, J=8.4 Hz, 1H), 6.53 (d, J=2.4 Hz, 1H), 6.36 (dd, J=8.4, 2.4 Hz, 1H), 4.93 (d, J=9.0 Hz, 1H), 4.68 (d, J=9.0 Hz, 1H), 4.03-3.94 (m, 2H), 3.77 (s, 3H), 3.80-3.30 (m, 4H), 2.21-2.05 (m, 1H), 1.74-1.38 (m, 4H); 13C NMR (75 MHz, CDCl3) δ 177.8, 162.1, 161.5, 142.7, 132.6, 128.7, 123.9, 123.3, 123.2, 120.8, 108.5, 107.5, 96.6, 80.6, 67.4, 67.3, 57.5, 55.5, 46.0, 33.9, 30.8, 30.7; MS (ES+) m/z 366.4 (M+1).
Reaction SMILES: [NH2:1][C:2]1[C:3]2[N:10]=[N:9][N:8]([C@@H:11]3[O:17][C@H:16]([CH2:18][OH:19])[C@@H:14]([OH:15])[C@H:12]3[OH:13])[C:4]=2[N:5]=[CH:6][N:7]=1.C[Si](Cl)(C)C.[C:25](Cl)(=[O:32])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.N>N1C=CC=CC=1.O>[C:25]([NH:1][C:2]1[C:3]2[N:10]=[N:9][N:8]([C@@H:11]3[O:17][C@H:16]([CH2:18][OH:19])[C@@H:14]([OH:15])[C@H:12]3[OH:13])[C:4]=2[N:5]=[CH:6][N:7]=1)(=[O:32])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1
Reactant: Nc1ncnc2c1nnn2[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O
Reactant: O=C(Cl)c1ccccc1
Agent: C[Si](C)(C)Cl
Agent: N
Solvent: c1ccncc1
Solvent: O
Product: O=C(Nc1ncnc2c1nnn2[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O)c1ccccc1
Temperature: 25 °C
Reaction time: 4 h

Procedure:
100 mg (0.37 mmol) of 7-amino-3-β-D-ribofuranosyl-3H-1,2,3-triazolo[4,5-d]pyrimidine are initially introduced in 5 ml of dry pyridine. 0.47 ml (3.7 mmol) of trimethylsilyl chloride is added dropwise to this solution under an argon atmosphere. After the mixture has been stirred at room temperature for half an hour (monitoring by TLC), 0.25 ml (2.0 mmol) of benzoyl chloride is added dropwise, and this reaction mixture is stirred at room temperature for 4 hours. It is then cooled down to 0-5° C. and 1 ml of water is added followed, 5 min later, by 2 ml of aqueous ammonia (25%); this mixture is then stirred for a further 30 min. The solvent is stripped off and the residue is then evaporated with toluene. The residue is taken up in 15 ml of a saturated solution of NaHCO3, and this mixture is extracted one with 25 ml of methylene chloride and several times with ethyl acetate. The combined organic phases are dried using Na2SO4.