Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: N[C:2]1[CH:11]=[CH:10][C:9]2[C:8]([CH3:13])([CH3:12])[CH2:7][CH2:6][C:5]([CH3:15])([CH3:14])[C:4]=2[CH:3]=1.C=O.[C:18]([BH3-])#[N:19].[Na+].[C:22](O)(=O)C>C(#N)C>[CH3:22][N:19]([CH3:18])[C:2]1[CH:11]=[CH:10][C:9]2[C:8]([CH3:13])([CH3:12])[CH2:7][CH2:6][C:5]([CH3:15])([CH3:14])[C:4]=2[CH:3]=1
Reactant: CC(=O)O
Reactant: [BH3-]C#N
Reactant: CC1(C)CCC(C)(C)c2cc(N)ccc21
Agent: C=O
Agent: [Na+]
Solvent: CC#N
Product: CN(C)c1ccc2c(c1)C(C)(C)CCC2(C)C
Temperature: 25 °C
Reaction time: 2 h
Yield: 70 %

Procedure:
To a solution of 2-amino-5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalene (70.10 g, 0.345 mol) and formaldehyde (280 mL, 10 eq) in 2 L of acetonitrile cooled to 0° C. was added sodium cyanoborohydride (65 g, 3 eq.) in portions while maintaining the temperature between 10–20° C. Glacial acetic acid was added to adjust the pH to 7. The reaction was stirred for 2 hrs at room temperature and the resulting mixture was partitioned between 1N NaOH and EtOAc, the organic phase was washed with water and brine, dried over sodium sulfate, filtered and evaporated. Chromatography on silica gel (hexanes/EtOAc 95:5) gave 54.90 g (70%, 2 steps) of 2-dimethylamino-5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-naphthalene. 1H-NMR (300 MHz, CDCl3): 1.25 (s, 6 H), 1.29 (s, 6 H), 1.66 (s, 4 H), 2.91 (s, 6 H), 6.62 (dd, J=3.0 Hz, J=8.7 Hz, 1 H), 6.67 (d, J=2.7 Hz, 1 H), 7.19 (d, J=8.7 Hz, 1 H).
Reaction SMILES: C([O:4][CH2:5][CH2:6][CH2:7][CH2:8][N:9]1[C:14]2=[N:15][C:16]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)=[C:17]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[N:18]=[C:13]2[CH2:12][CH2:11][CH2:10]1)(=O)C.[OH-].[Li+]>C1COCC1.O.CCOC(C)=O>[C:19]1([C:17]2[N:18]=[C:13]3[CH2:12][CH2:11][CH2:10][N:9]([CH2:8][CH2:7][CH2:6][CH2:5][OH:4])[C:14]3=[N:15][C:16]=2[C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1
Reactant: CC(=O)OCCCCN1CCCc2nc(-c3ccccc3)c(-c3ccccc3)nc21
Agent: [Li+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Solvent: O
Product: OCCCCN1CCCc2nc(-c3ccccc3)c(-c3ccccc3)nc21

Procedure:
To a solution of 4-(2,3-diphenyl-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)butyl acetate (step 2) (410 mg, 1.021 mmol) in THF (6 ml) and water (3 ml) was added lithium hydroxide (56.9 mg, 2.375 mmol) and the mixture was heated at reflux for 18 h. The reaction mixture was diluted with EtOAc and the combined organic extracts were washed with water (2×), brine, dried (MgSO4), filtered and concentrated in vacuo to afford the title compound;
Reaction SMILES: [CH2:1]([C@H:8]([NH:30][C:31](=[O:50])[C@H:32]([CH:47]([CH3:49])[CH3:48])[NH:33][C:34]([N:36]([CH2:38][C:39]1[N:40]=[C:41]([CH:44]([CH3:46])[CH3:45])[S:42][CH:43]=1)[CH3:37])=[O:35])[CH2:9][C@H:10]([OH:29])[C@@H:11]([NH:19][C:20]([O:22][CH2:23][C:24]1[S:28][CH:27]=[N:26][CH:25]=1)=[O:21])[CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:51]([S:55][CH2:56][CH2:57][CH2:58][CH3:59])[CH2:52][CH2:53][CH3:54].C(OOC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1>C(#N)C.C(OCC)(=O)C>[CH2:1]([C@H:8]([NH:30][C:31](=[O:50])[C@H:32]([CH:47]([CH3:49])[CH3:48])[NH:33][C:34]([N:36]([CH2:38][C:39]1[N:40]=[C:41]([CH:44]([CH3:45])[CH3:46])[S:42][CH:43]=1)[CH3:37])=[O:35])[CH2:9][C@H:10]([O:29][CH:51]([S:55][CH2:56][CH2:57][CH2:58][CH3:59])[CH2:52][CH2:53][CH3:54])[C@@H:11]([NH:19][C:20]([O:22][CH2:23][C:24]1[S:28][CH:27]=[N:26][CH:25]=1)=[O:21])[CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CC(C)c1nc(CN(C)C(=O)N[C@H](C(=O)N[C@@H](Cc2ccccc2)C[C@H](O)[C@H](Cc2ccccc2)NC(=O)OCc2cncs2)C(C)C)cs1
Reactant: CCCCSCCCC
Agent: O=C(OOC(=O)c1ccccc1)c1ccccc1
Solvent: CCOC(C)=O
Solvent: CC#N
Product: CCCCSC(CCC)O[C@@H](C[C@H](Cc1ccccc1)NC(=O)[C@@H](NC(=O)N(C)Cc1csc(C(C)C)n1)C(C)C)[C@H](Cc1ccccc1)NC(=O)OCc1cncs1
Temperature: 0 °C
Reaction time: 1 h
Yield: 68 %

Procedure:
To a solution of the compound of Example 1 (3.0 g, 4.2 mmol) and butyl sulfide (18 mL) in acetonitrile (24 mL) at 0° C. was added benzoyl peroxide (2.0 g) in three portions over 3 hours, and the reaction was stirred at 0° C. for 1 hour and then at room temperature for 1 hour. Additional benzoyl peroxide (4.0 g) was added in two portions over 2 hours at room temperature. The reaction was diluted with ethyl acetate and washed with 10% Na2CO3 and brine. The organic phase was dried over MgSO4, filtered and evaporated. The concentrate was chromatographed on silica gel eluting with a gradient starting with 50% ethyl acetate in chloroform and ending with ethyl acetate to give the title compound (2.43 g, 68% yield).
Reaction SMILES: [CH:1]([O:4][C:5]1[CH:6]=[CH:7][C:8]([O:11][C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([CH:18]=[C:19]3[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]3)[CH:13]=2)=[N:9][CH:10]=1)([CH3:3])[CH3:2].[N:25]1[CH:30]=[CH:29][CH:28]=[C:27]([NH:31][C:32](=O)[O:33]C2C=CC=CC=2)[N:26]=1.C(N(CC)CC)C>CS(C)=O.O>[CH:1]([O:4][C:5]1[CH:6]=[CH:7][C:8]([O:11][C:12]2[CH:13]=[C:14]([CH:15]=[CH:16][CH:17]=2)[CH:18]=[C:19]2[CH2:20][CH2:21][N:22]([C:32]([NH:31][C:27]3[N:26]=[N:25][CH:30]=[CH:29][CH:28]=3)=[O:33])[CH2:23][CH2:24]2)=[N:9][CH:10]=1)([CH3:3])[CH3:2]
Reactant: O=C(Nc1cccnn1)Oc1ccccc1
Reactant: CC(C)Oc1ccc(Oc2cccc(C=C3CCNCC3)c2)nc1
Solvent: CS(C)=O
Solvent: CCN(CC)CC
Solvent: O
Product: CC(C)Oc1ccc(Oc2cccc(C=C3CCN(C(=O)Nc4cccnn4)CC3)c2)nc1
Temperature: 25 °C
Reaction time: 12 h
Yield: 53.1 %

Procedure:
To a solution of 5-isopropoxy-2-(3-(piperidin-4-ylidenemethyl)phenoxy)pyridine (0.18 g, 0.55 mmol) in DMSO (3 mL) was added phenyl pyridazin-3-ylcarbamate (0.118 g, 0.55 mmol) followed by triethylamine (0.235 mL, 1.692 mmol). The resulting mixture was stirred at RT for 12 h. The reaction mixture was diluted with water and extracted with EtOAc. The organic extract was dried over Na2SO4 and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (30% acetone, 70% hexane) to give the title compound (0.13 g, 52.6%). 1H NMR (500 MHz, CDCl3): δ 8.80 (s, 1H), 8.30 (s, 1H), 7.86 (d, J=3 Hz, 1H), 7.40 (m, 1H), 7.31 (t, J=8 Hz, 1H), 7.28 (m, 1H), 6.93 (m, 3H), 6.86 (d, J=8.5 Hz, 1H), 6.40 (s, 1H), 4.45 (q, J=6 Hz, 1H), 3.67 (m, 2H), 3.57 (m, 2H), 2.6 (m, 2H), 2.46 (m, 2H), 1.33 (d, J=6 Hz, 6H). 13C NMR (125 MHz, CDCl3): δ 157.33, 156.57, 155.18, 150.69, 138.70, 137.37, 135.54, 129.41, 128.33, 128.03, 125.0, 124.58, 120.63, 118.43, 112.45, 71.65, 45.64, 44.62, 35.75, 29.13, 21.96; m/z (446.2, M+ H+); HPLC: 98.5%.
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([N+:14]([O-:16])=[O:15])=[C:7]([C:11]([OH:13])=O)[NH:8]2)=[CH:4][CH:3]=1.Cl.[CH3:18][NH:19][O:20][CH3:21].CCN=C=NCCCN(C)C>CN(C=O)C.C(OCC)C>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([N+:14]([O-:16])=[O:15])=[C:7]([C:11]([N:19]([O:20][CH3:21])[CH3:18])=[O:13])[NH:8]2)=[CH:4][CH:3]=1
Reactant: CNOC
Reactant: O=C(O)c1[nH]c2cc(Cl)ccc2c1[N+](=O)[O-]
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Solvent: CCOCC
Solvent: CN(C)C=O
Product: CON(C)C(=O)c1[nH]c2cc(Cl)ccc2c1[N+](=O)[O-]
Reaction time: 4 h
Yield: 55.9 %

Procedure:
To a mixture of 6-chloro-3-nitroindole-2-carboxylic acid (step 1, 2.35 g, 9.77 mmol) and N,O-dimethylhydroxylamine hydrochloride (3.81 g, 39.1 mmol) in DMF (50 ml) was added dropwise a dimethylformamide (15 ml) solution of WSC (5.61 g, 29.3 mmol) over 10 min. After stirring for 4 h the mixture was diluted with diethyl ether (200 ml) and washed with water (100 ml×4). The organic extract was dried (MgSO4) and solvent removed by evaporation. The crude product was recystallized from ethyl acetate to afford 1.55 g (56%) of the title compound.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([S:8]([OH:11])(=[O:10])=[O:9])[CH:5]=[CH:6][CH:7]=1.O.O.O.C([O-])(=O)C.[Na+].[CH3:20][C:21]1[CH:28]=[C:27]([CH3:29])[CH:26]=[C:25]([CH3:30])[C:22]=1[CH2:23]Cl.Cl>O.C(#N)C>[CH3:20][C:21]1[CH:28]=[C:27]([CH3:29])[CH:26]=[C:25]([CH3:30])[C:22]=1[CH2:23][NH:1][C:2]1[CH:3]=[C:4]([S:8]([OH:11])(=[O:9])=[O:10])[CH:5]=[CH:6][CH:7]=1
Reactant: Nc1cccc(S(=O)(=O)O)c1
Reactant: Cc1cc(C)c(CCl)c(C)c1
Agent: CC(=O)[O-]
Agent: Cl
Agent: [Na+]
Solvent: O
Solvent: CC#N
Product: Cc1cc(C)c(CNc2cccc(S(=O)(=O)O)c2)c(C)c1
Reaction time: 0.33 h
Yield: 40.7 %

Procedure:
A mixture of 52.0 g (0.30 mole) of 3-aminobenzenesulfonic acid, 83.0 g (0.61 mole) of sodium acetate trihydrate, 33.7 g (0.20 mole) of 2,4,6-trimethylbenzyl chloride, 225 ml of water and 150 ml of acetonitrile was refluxed for 4 hrs, then acidified by the dropwise addition of 40 ml of conc. HCl over 30 minutes during which time approximately 100 ml of acetonitrile was distilled off. The resulting mixture was vacuum filtered while hot (80° C.) and a grayish-white powder obtained which was then slurried in 300 ml of hot (65° C.) water for 20 minutes and vacuum filtered. The slurrying process was repeated with water and then with 300 ml of boiling methanol for 20 minutes. Vacuum filtration followed by drying in vacuo at about 60° C. afforded 24.85 g (40.7% yield) of purified 3-(((2,4,6-trimethylphenyl)methyl)amino)benzenesulfonic acid as a white powder having a melting point greater than 275° C.
Reaction SMILES: [F:1][C:2]1[CH:19]=[CH:18][C:5]2[C:6]([CH:9]3[CH2:14][CH2:13][N:12]([CH2:15][CH2:16][NH2:17])[CH2:11][CH2:10]3)=[N:7][O:8][C:4]=2[CH:3]=1.[F:20][C:21]1[CH:29]=[CH:28][CH:27]=[C:23]([C:24](O)=[O:25])[C:22]=1[C:30](O)=[O:31].C1(N=C=NC2CCCCC2)CCCCC1>ClCCl>[F:1][C:2]1[CH:19]=[CH:18][C:5]2[C:6]([CH:9]3[CH2:14][CH2:13][N:12]([CH2:15][CH2:16][N:17]4[C:30](=[O:31])[C:22]5=[C:21]([F:20])[CH:29]=[CH:28][CH:27]=[C:23]5[C:24]4=[O:25])[CH2:11][CH2:10]3)=[N:7][O:8][C:4]=2[CH:3]=1
Reactant: O=C(O)c1cccc(F)c1C(=O)O
Reactant: NCCN1CCC(c2noc3cc(F)ccc23)CC1
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Solvent: ClCCl
Product: O=C1c2cccc(F)c2C(=O)N1CCN1CCC(c2noc3cc(F)ccc23)CC1
Temperature: 25 °C
Reaction time: 18 h

Procedure:
A mixture of 2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]ethylamine (2.37 gm, 8.98 mmoles), 3-fluorophthalic acid (1.82 in, 9.9 moles) and dicyclohexylcarbodiimide (DCC, 5.5 gm, 26.7 mmoles, 2.6 eq) in dichloromethane (DCM, 250 ml) was stirred at room temperature for 18 hrs. The solids were filtered off. The organic solution was concentrated down. The residue was purified on a flash chromatography column (SiO2, 50 in; eluted with 1% CH3OH:99% DCM, 1.4 liter; 2-6% CH3OH:DCM, liter). The desired product thus obtained weighed 2.64 gm (71%) as an off-white solid. Recrystallization from hot ethanol gave 1.41 gm of white crystals, m.p.=142°-143° C.
Reaction SMILES: [C:1]([C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[C:9](=[O:13])[CH2:8][CH2:7][C:6]2([CH3:15])[CH3:14])#[CH:2].I[C:17]1[CH:27]=[CH:26][C:20]([C:21]([O:23][CH2:24][CH3:25])=[O:22])=[CH:19][CH:18]=1>C(N(CC)CC)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH3:14][C:6]1([CH3:15])[C:5]2[CH:4]=[C:3]([C:1]#[C:2][C:17]3[CH:27]=[CH:26][C:20]([C:21]([O:23][CH2:24][CH3:25])=[O:22])=[CH:19][CH:18]=3)[CH:12]=[CH:11][C:10]=2[C:9](=[O:13])[CH2:8][CH2:7]1
Reactant: CCOC(=O)c1ccc(I)cc1
Reactant: C#Cc1ccc2c(c1)C(C)(C)CCC2=O
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Solvent: CCN(CC)CC
Product: CCOC(=O)c1ccc(C#Cc2ccc3c(c2)C(C)(C)CCC3=O)cc1
Temperature: 25 °C
Reaction time: 18 h

Procedure:
To a solution of 8.8 g (47.8 mmol) of 6-ethynyl-1,2,3,4-tetrahydro-4,4-dimethylnaphthalen-1-one (Compound K) flushed for 15 minutes with a stream of argon, and 13.2 g (47.8 mmol) of ethyl 4-iodobenzoate in 200 ml of triethylamine was added 1.1 g (1.6 mmol) of bis(triphenylphosphine)palladium(II) chloride and 0.30 g (1.6 mmol) of cuprous iodide. The solution mixture was flushed with argon for 5 minutes and then stirred at ambient temperature for 18 hours. The reaction mixture was filtered through Celite and the filtrate concentrated in vacuo. Purification by flash chromatography (silica, 10% EtOAc-hexane) yielded the title compound as a white solid.
Reaction SMILES: [NH:1]1[CH2:5][CH2:4][CH2:3][C:2]1=[O:6].[H-].[Na+].Br[CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[C:13]([I:17])[CH:12]=1>CN(C=O)C.O>[I:17][C:13]1[CH:12]=[C:11]([CH:16]=[CH:15][CH:14]=1)[CH2:10][N:1]1[CH2:5][CH2:4][CH2:3][C:2]1=[O:6]
Reactant: O=C1CCCN1
Reactant: BrCc1cccc(I)c1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: O=C1CCCN1Cc1cccc(I)c1
Temperature: 0 °C
Yield: 107.2 %

Procedure:
To a stirred solution of pyrrolidin-2-one (1.55 mL, 20.2 mmol) in DMF (25 mL) at 0° C. under N2 was added NaH (60% dispersion in mineral oil, 808 mg, 20.2 mmol) portion-wise over 10 min. The reaction mixture was maintained at 0° C. for 30 min and was then treated with 1-(bromomethyl)-3-iodobenzene (5.00 g, 17.0 mmol) over 10 min and afterwards was warmed to RT for 2 hr. The resulting mixture was diluted with water (100 mL) and extracted with DCM (2×100 mL). The combined organic extracts were washed with water (100 mL) and with brine (100 mL) and evaporated in vacuo to afford 1-(3-iodobenzyl)pyrrolidin-2-one as a yellow oil (5.49 g, 100%); Rt 1.85 min (Method 2, acidic); m/z 302 (M+H)+, (ES+).
Reaction SMILES: [F:1][C:2]([F:20])([F:19])[C:3]([C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][CH:13]([CH3:18])[CH2:12]2)([OH:8])[C:4]([F:7])([F:6])[F:5].Br[CH2:22][CH2:23][C:24]1[N:25]=[C:26]([C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)[O:27][C:28]=1[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1>CN(C=O)C>[C:35]1([C:26]2[O:27][C:28]([C:29]3[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=3)=[C:24]([CH2:23][CH2:22][N:14]3[C:15]4[C:11](=[CH:10][C:9]([C:3]([OH:8])([C:2]([F:1])([F:19])[F:20])[C:4]([F:7])([F:6])[F:5])=[CH:17][CH:16]=4)[CH2:12][CH:13]3[CH3:18])[N:25]=2)[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1
Reactant: BrCCc1nc(-c2ccccc2)oc1-c1ccccc1
Reactant: CC1Cc2cc(C(O)(C(F)(F)F)C(F)(F)F)ccc2N1
Solvent: CN(C)C=O
Product: CC1Cc2cc(C(O)(C(F)(F)F)C(F)(F)F)ccc2N1CCc1nc(-c2ccccc2)oc1-c1ccccc1
Yield: 21 %

Procedure:
A solution of 100 mg (0.33 mmol) of 1,1,1,3,3,3-hexafluoro-2-(2-methyl-2,3-dihydro-1H-indol-5-yl)-propan-2-ol (example 51.1) and 4-(2-bromo-ethyl)-2,5-diphenyl-oxazole in 0.5 mL of DMF was stirred at 80° C. overnight. Distribution of the mixture between a saturated aqueous solution of NH4Cl and Et2O, drying of the combined organic phases over Na2SO4 and column chromatography on silica gel with n-heptane/EtOAc 4:1 yielded 39 mg (21%) of 2-{1-[2-(2,5-diphenyl-oxazol-4-yl)-ethyl]-2-methyl-2,3-dihydro-1H-indol-5-yl}-1,1,1,3,3,3-hexafluoro-propan-2-ol, light yellow gum, MS: 547 (MH+).
Reaction SMILES: [Cl:1][C:2]1[CH:19]=[C:18]([O:20][CH3:21])[C:17]([CH3:22])=[CH:16][C:3]=1[CH2:4][N:5]1C(=O)C2C(=CC=CC=2)C1=O.O.NN>CO>[Cl:1][C:2]1[CH:19]=[C:18]([O:20][CH3:21])[C:17]([CH3:22])=[CH:16][C:3]=1[CH2:4][NH2:5]
Reactant: COc1cc(Cl)c(CN2C(=O)c3ccccc3C2=O)cc1C
Agent: NN
Solvent: O
Solvent: CO
Product: COc1cc(Cl)c(CN)cc1C
Yield: 127.3 %

Procedure:
2-(2-Chloro-4-methoxy-5-methylbenzyl)isoindoline-1,3-dione (174 mg, 0.55 mmol) was dissolved in MeOH (30 ml) and hydrazine hydrate (111 mg, 2.21 mmol) and then heated under reflux for 1 hour. The solvent was removed in vacuo and the precipitate was filtered off. The filtrate was evaporated to give a residue, which was chromatographed on a column of silica gel eluting with MeOH-DCM (1:10) to give the title compound (130 mg, 100%) as white solid. 1H NMR (270 MHz, DMSO-d6) δ ppm 2.12 (3H, s), 3.38 (2H, br s), 3.69 (2H, s), 3.78 (3H, s), 6.94 (1H, s), 7.29 (1H, s). MS (ESI) m/z 169 (M+H—NH2)+
Reaction SMILES: [C:1]([C:3]1[C:11]2[C:6](=[N:7][C:8]([CH3:12])=[CH:9][CH:10]=2)[N:5]([CH:13]2[C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[CH2:15][CH2:14]2)[C:4]=1/[CH:22]=[CH:23]/[C:24]([NH:26][CH:27]1[CH2:32][CH2:31][O:30][C:29](C)(C)[CH2:28]1)=[O:25])#[N:2].[C:35](C1C2C(=NC(C)=CC=2)N(C2C3C(=CC=CC=3)CC2)C=1/C=C/C(O)=O)#N.CNC1CCOCC1>>[C:1]([C:3]1[C:11]2[C:6](=[N:7][C:8]([CH3:12])=[CH:9][CH:10]=2)[N:5]([CH:13]2[C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[CH2:15][CH2:14]2)[C:4]=1/[CH:22]=[CH:23]/[C:24]([N:26]([CH3:35])[CH:27]1[CH2:28][CH2:29][O:30][CH2:31][CH2:32]1)=[O:25])#[N:2]
Reactant: Cc1ccc2c(C#N)c(/C=C/C(=O)O)n(C3CCc4ccccc43)c2n1
Reactant: Cc1ccc2c(C#N)c(/C=C/C(=O)NC3CCOC(C)(C)C3)n(C3CCc4ccccc43)c2n1
Agent: CNC1CCOCC1
Product: Cc1ccc2c(C#N)c(/C=C/C(=O)N(C)C3CCOCC3)n(C3CCc4ccccc43)c2n1

Procedure:
In the same manner described in (4) of Example 2, (E)-3-[3-cyano-1-(2,3-dihydro-iH-inden-1-yl)-6-methyl-1H-pyrrolo[2,3-b]pyridin-2-yl]-N-methyl-N-tetrahydro-2H-pyran-4-yl-2-propenamide was synthesized from (E)-3-[3-cyano-1-(2,3-dihydro-1H-inden-1-yl)-6-methyl-1H-pyrrolo[2,3-b]pyridin-2-yl]-2-propenoic acid and N-methyltetrahydro-2H-pyran-4-ylamine.
Reaction SMILES: Cl.[CH3:2][NH:3][O:4][CH3:5].C(N(CC)CC)C.[Cl:13][C:14]1[N:19]=[CH:18][C:17]([C:20](Cl)=[O:21])=[CH:16][CH:15]=1>ClCCl>[Cl:13][C:14]1[N:19]=[CH:18][C:17]([C:20]([N:3]([O:4][CH3:5])[CH3:2])=[O:21])=[CH:16][CH:15]=1
Reactant: CNOC
Reactant: O=C(Cl)c1ccc(Cl)nc1
Agent: Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CON(C)C(=O)c1ccc(Cl)nc1
Temperature: 25 °C
Reaction time: 12 h

Procedure:
To a 1000-mL round-bottom flask containing N,O-dimethylhydroxylamine hydrochloride (12.0 g, 123 mmol) and triethylamine (40.0 g, 395 mmol) was added a solution of 6-chloropyridine-3-carbonyl chloride (17.6 g, 100 mmol, Intermediate 4, step a) in dichloromethane (100 mL) dropwise. The resulting mixture was stirred for 12 hours at room temperature and filtered. The filtrate was concentrated under vacuum to give the title compound as a yellow oil.
Reaction SMILES: [C:1]([O:6]CC[N:9]=C=O)(=[O:5])[C:2](C)=[CH2:3].[C:12]([O:15][CH2:16][CH3:17])(=[O:14])C>>[C:1]([OH:6])(=[O:5])[CH:2]=[CH2:3].[NH2:9][C:12]([O:15][CH2:16][CH3:17])=[O:14]
Reactant: C=C(C)C(=O)OCCN=C=O
Reactant: CCOC(C)=O
Product: C=CC(=O)O
Product: CCOC(N)=O
Reaction time: 6 h

Procedure:
Next, to a 100-mL round-bottom flask, 8.00 g of the polyester polyol, 2.15 g of methacryloyloxyethyl isocyanate, and 10.0 g of ethyl acetate were charged, and a reaction was conducted under stirring for six hours. The reaction mixture was filtered through a 0.2-μm membrane filter to remove the catalyst. An ethyl acetate solution of a target urethane acrylate with an NCO conversion rate of 95% was obtained. The residual ratio of the catalyst in the ethyl acetate solution was below the detection limit (5 ppm).
Reaction SMILES: C([O:3][C:4](=O)[CH:5]([O:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[C:6](OCC)=[O:7])C.[C:19]1([C:25]([O:27][Si](C)(C)C)=[CH2:26])[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.N#N>CCCCCC.C(OCC)(=O)C>[OH:7][C:6]1[CH:26]=[C:25]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[O:27][C:4](=[O:3])[C:5]=1[O:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1
Reactant: C=C(O[Si](C)(C)C)c1ccccc1
Reactant: CCOC(=O)C(Oc1ccccc1)C(=O)OCC
Agent: N#N
Solvent: CCCCCC
Solvent: CCOC(C)=O
Product: O=c1oc(-c2ccccc2)cc(O)c1Oc1ccccc1
Temperature: 100 °C
Yield: 18.3 %

Procedure:
To a pressure reactor was added 2-phenoxypropanedioicacid diethylester 8.11 g (0.032 moles) and 1-phenyl-1-(trimethylsilyloxy)ethylene 12.35 g (0.064 moles). The vessel was pressurized to 600 psi with N2. The mixture was heated at 100° C. for 8 hours then an additional 63.5 hours at 147°-154° C. The vessel was cooled to room temperature and rinsed with ethyl acetate. Crude flash chromatography (hexane/ethyl acetate 1/1) afforded partially purified material which was then flashed on silica gel using hexane/ethyl acetate 95/5-40/60 as eluents. The resulting solid was recrystallized from diethyl ether and ethyl acetate to afford 1.64 g (18%) of the title compound (mp=215°-219° C.). 1H NMR (400 MHz, DMSO-d6) δ 6.90 (s, 1 H), 6.95 (dd, 2 H), 7.02 (t, 1 H), 7.28-7.33 (m, 2 H), 7.52-7.56 (m, 3 H), 7.80-7.856 (m, 2 H), 12.0 (bs, 1 H).
Reaction SMILES: C([N:8](C(OC(C)(C)C)=O)[C@H:9]1[CH2:13][C@@H:12]([N:14]2[CH:22]=[N:21][C:20]3[C:15]2=[N:16][C:17]([Cl:24])=[N:18][C:19]=3[Cl:23])[CH:11]=[CH:10]1)(OC(C)(C)C)=O.[CH2:32]([C:34]1[CH:38]=[N:37]N[N:35]=1)[CH3:33]>>[Cl:24][C:17]1[N:16]=[C:15]2[C:20]([N:21]=[CH:22][N:14]2[C@@H:12]2[CH2:13][C@H:9]([N:8]3[N:35]=[C:34]([CH2:32][CH3:33])[CH:38]=[N:37]3)[CH:10]=[CH:11]2)=[C:19]([Cl:23])[N:18]=1
Reactant: CCc1cn[nH]n1
Reactant: CC(C)(C)OC(=O)N(C(=O)OC(C)(C)C)[C@@H]1C=C[C@H](n2cnc3c(Cl)nc(Cl)nc32)C1
Product: CCc1cnn([C@@H]2C=C[C@H](n3cnc4c(Cl)nc(Cl)nc43)C2)n1

Procedure:
The title compound is prepared analogously to di-Boc-[(1S,4R)-4-(2,6-dichloro-purin-9-yl)-cyclopent-2-enyl]-amine (AA3) by replacing di-t-butyliminodicarboxylate with 4-ethyl-2H-[1,2,3]triazole.
Reaction SMILES: [CH2:1]([CH2:3][NH2:4])[OH:2].CC(C)([O-])C.[K+].F[C:12]1[CH:17]=[CH:16][C:15]([C:18]2[NH:22][N:21]=[C:20]([C:23]([F:26])([F:25])[F:24])[CH:19]=2)=[CH:14][CH:13]=1.O>CS(C)=O>[F:26][C:23]([F:24])([F:25])[C:20]1[NH:21][N:22]=[C:18]([C:15]2[CH:16]=[CH:17][C:12]([O:2][CH2:1][CH2:3][NH2:4])=[CH:13][CH:14]=2)[CH:19]=1
Reactant: Fc1ccc(-c2cc(C(F)(F)F)n[nH]2)cc1
Reactant: NCCO
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: O
Solvent: CS(C)=O
Product: NCCOc1ccc(-c2cc(C(F)(F)F)[nH]n2)cc1
Temperature: 65 °C
Yield: 34.3 %

Procedure:
In a flame-dried, round-bottomed flask, ethanolamine (836 mg, 13.7 mmol) was dissolved in dimethylsulfoxide (2.7 ml), and potassium tert-butoxide (95%, 1.54 g, 13.7 mmol) was added to the solution. This mixture was stirred at about 65° C. for about ten minutes, and then 5-(4-fluoro-phenyl)-3-trifluoromethyl-1H-pyrazole (630 mg, 2.74 mmol) was added. The dark-colored solution was heated to about 85° C. for about eighteen hours, and was then allowed to cool to room temperature. Water was added, and the resulting tan-colored solid was collected by filtration. This crude product was purified by column chromatography (5% methanol/dichloromethane to 20% methanol/dichloromethane) to afford the product as a white solid (255 mg, 25% yield). LRMS ([M+H]+)=272.2.
Reaction SMILES: C(N1C=CN=C1)(N1C=CN=C1)=O.[C:13]([CH:16]1[CH2:20][CH2:19][CH:18]([C:21]2[NH:29][C:28]3[C:27](=[O:30])[N:26]([CH2:31][CH2:32][CH3:33])[C:25](=[O:34])[N:24]([CH2:35][CH2:36][CH3:37])[C:23]=3[N:22]=2)[CH2:17]1)(O)=[O:14].[NH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][C:44]#[N:45]>ClCCl.O1CCCC1>[C:39]([CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][NH:45][C:13]([CH:16]1[CH2:20][CH2:19][CH:18]([C:21]2[NH:29][C:28]3[C:27](=[O:30])[N:26]([CH2:31][CH2:32][CH3:33])[C:25](=[O:34])[N:24]([CH2:35][CH2:36][CH3:37])[C:23]=3[N:22]=2)[CH2:17]1)=[O:14])#[N:38]
Reactant: CCCn1c(=O)c2[nH]c(C3CCC(C(=O)O)C3)nc2n(CCC)c1=O
Reactant: N#CCCCCCN
Agent: O=C(n1ccnc1)n1ccnc1
Solvent: C1CCOC1
Solvent: ClCCl
Product: CCCn1c(=O)c2[nH]c(C3CCC(C(=O)NCCCCCC#N)C3)nc2n(CCC)c1=O
Temperature: 25 °C
Reaction time: 0.58 h

Procedure:
0.3 g (1.9 mmol) of carbonyldiimidazole are added to a suspension of 0.67 g (1.9 mmol) of 8-(3-carboxycyclopentyl)-1,3-dipropyl-7H-purine-2,6-dione in 20 ml of dichloromethane and 1 ml of tetrahydrofuran and the mixture is stirred for 35 minutes at ambient temperature. After the addition of 0.21 g (1.9 mmol) of 6-aminocapronitrile the mixture is stirred for a further 24 hours, acidified and washed with water. The organic phase is concentrated by evaporation, the residue is taken up in 5% sodium bicarbonate solution and this solution is extracted with dichloromethane. After drying and evaporation of the organic extracts the title compound is obtained in the form of crystals which, are purified with a mixture of dichloromethane/methanol in the ratio 95:5. 0.67 g (79.8% of theory) of the title compound are obtained in the form of colourless crystals.