Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][CH:10]=1)[C:5]([OH:7])=[O:6].[C:11](N1C=CN=C1)(N1C=CN=C1)=[S:12].C(N(CC)CC)C.Cl>CCCCCCC.C(Cl)Cl>[N:1]([C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][CH:10]=1)[C:5]([OH:7])=[O:6])=[C:11]=[S:12]
Reactant: S=C(n1ccnc1)n1ccnc1
Reactant: Nc1cccc(C(=O)O)c1
Agent: Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Solvent: CCCCCCC
Product: O=C(O)c1cccc(N=C=S)c1
Temperature: -10 °C
Reaction time: 1 h
Yield: 93 %

Procedure:
3-aminobenzoic acid (5.00 g, 36.5 mmol) was added to a methylene chloride solution (51 mL) of thiocarbonyldiimidazole (7.8 g, 43.8 mmol) and triethylamine (5.6 mL, 40.2 mmol) at an internal temperature of at most 5° C., followed by stirring at −10° C. for one hour. The mixture was dropped to a separately prepared mixed solution of concentrated hydrochloric acid (11.6 mL, 133.0 mmol) and n-heptane (51 mL) as that the internal temperature became from 20° C. to 30° C., followed by stirring for one hour as it was. Then, the mixture was stirred under cooling with ice for 2 hours, and the obtained colorless solid was collected by filtration, washed with water (20 mL) four times and dried under reduced pressure to obtain 3-isothiocyanatobenzoic acid as a creamy solid (6.01 g, yield: 93%, HPLC purity: 99.8%).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH:8]=[C:7]([OH:12])[CH:6]=[CH:5]2.N1C=CN=C1.[Si:18](Cl)([C:21]([CH3:24])([CH3:23])[CH3:22])([CH3:20])[CH3:19].[SiH3]Cl>CN(C=O)C>[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH:8]=[C:7]([O:12][Si:18]([C:21]([CH3:24])([CH3:23])[CH3:22])([CH3:20])[CH3:19])[CH:6]=[CH:5]2
Reactant: Oc1ccc2cc(Br)ccc2c1
Reactant: CC(C)(C)[Si](C)(C)Cl
Agent: [SiH3]Cl
Agent: c1c[nH]cn1
Solvent: CN(C)C=O
Product: CC(C)(C)[Si](C)(C)Oc1ccc2cc(Br)ccc2c1
Reaction time: 24 h
Yield: 74.1 %

Procedure:
6-Bromo-2-naphthol (10 g, 44 mmol), imidazole (7.4 g, 110 mmol), and t-butyldimethylsilyl chloride (10 g, 66 mmol) were stirred in DMF (50 mL) at room temperature overnight. TLC analysis indicated incomplete reaction, so additional imidazole (0.6 g) and silyl chloride (1.3 g) were added, and stirring continued 1 day. After evaporation of DMF, the mixture was extracted with EtOAc and 5% aqueous KHSO4, dried (Na2SO4), and evaporated. The crude product was purified by silica gel chromatography, eluting with hexane, to yield a colorless solid (11 g). mp 62°-63° C. 1H NMR (300 MHz, CDCl3): 7.90 (d, 1H, J=l Hz), 7.62 (d, 1H, J=9 Hz), 7.55 (d, 1H, J=9 Hz), 7.46 (dd, 1H, J=9, 2 Hz), 7.14 (d, 1H, J=2 Hz), 7.08 (dd, 1H, J=9,2 Hz), 1.00 (s, 9H), 0.23 (s, 6H). MS(CH4): 365 (20%, M+C2H5, 1 Br isotope pattern), 337 (base, M+H, 1 Br isotope pattern).
Reaction SMILES: [N:1]1([C:11]([C:13]2[CH:17]=[C:16]([CH:18]3[CH2:23][CH2:22][NH:21][CH2:20][CH2:19]3)[S:15][CH:14]=2)=[O:12])[C@@H:10]2[C@@H:5]([CH2:6][CH2:7][CH2:8][CH2:9]2)[CH2:4][CH2:3][CH2:2]1.C(N(CC)CC)C.[CH3:31][S:32](Cl)(=[O:34])=[O:33]>ClCCl>[CH3:31][S:32]([N:21]1[CH2:20][CH2:19][CH:18]([C:16]2[S:15][CH:14]=[C:13]([C:11]([N:1]3[C@@H:10]4[C@@H:5]([CH2:6][CH2:7][CH2:8][CH2:9]4)[CH2:4][CH2:3][CH2:2]3)=[O:12])[CH:17]=2)[CH2:23][CH2:22]1)(=[O:34])=[O:33]
Reactant: O=C(c1csc(C2CCNCC2)c1)N1CCC[C@@H]2CCCC[C@@H]21
Reactant: CS(=O)(=O)Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CS(=O)(=O)N1CCC(c2cc(C(=O)N3CCC[C@@H]4CCCC[C@@H]43)cs2)CC1
Reaction time: 2 h
Yield: 44.7 %

Procedure:
cis-(Octahydro-quinolin-1-yl)-(5-piperidin-4-yl-thiophen-3-yl)-methanone (CC-033) (0.04 g, 0.12 mmol) was dissolved in dichloromethane (2 mL) and triethylamine (0.37 mmol). Methylsulphonyl chloride (0.25 mmol) was added and the mixture stirred for 2 hours and then the solvent removed by evaporation. The residue was purified by HPLC, eluting with 10%-98% acetonitrile in water (0.1% formic acid). The fractions containing the desired product were concentrated under vacuum to give the title compound as a colourless oil (0.022 g). LCMS m/z 411.11 min [M+H]+ RT=10.84 min (Analytical Method 2). 1H NMR (400 MHz, CHCl3-d): δ 7.2 (s, 1H), 6.9 (s, 1H), 4.6 (m, 1H), 3.9-3.6 (m, 3H), 3.1-2.7 (m, 2H), 2.7 (s, 3H), 2.1-1.1 (m, 19H).
Reaction SMILES: C[O:2][C:3](=O)[C:4]([CH3:11])([CH3:10])[CH2:5][CH2:6][C:7]([OH:9])=[O:8].CC(O)=O.O>C1COCC1>[OH:2][CH2:3][C:4]([CH3:11])([CH3:10])[CH2:5][CH2:6][C:7]([OH:9])=[O:8]
Reactant: COC(=O)C(C)(C)CCC(=O)O
Solvent: O
Solvent: CC(=O)O
Solvent: C1CCOC1
Product: CC(C)(CO)CCC(=O)O
Temperature: 10 °C
Reaction time: 1 h
Yield: 101.1 %

Procedure:
To a suspension of 2,2-dimethyl-pentanedioic acid 1-methyl ester (1.00 g, 5.75 mmol) in THF (3 mL), 1M LiBHEt3 in THF (38.0 ml, 38.0 mmol) is added dropwise maintaining the temperature below 10° C. under nitrogen. The mixture is stirred at 10° C. for 1 hour. To the mixture, 50% AcOH (4.6 mL) and H2O are added. The solution is extracted with AcOEt, and the organic layer is washed with H2O, dried over MgSO4, and concentrated under reduced pressure to give 5-hydroxy-4,4-dimethyl-pentanoic acid (850 mg, quant.); 1H NMR (400 MHz, chloroform-d) ppm 1.06 (s, 6H), 1.70 (t, 2H), 2.56 (t, 2H), 3.98 (s, 2H).
Reaction SMILES: [H-].[Na+].[O:3]=[C:4]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:6](=[O:13])[N:5]1[CH2:14][CH2:15][C:16]1[C:24]2[C:19](=[CH:20][CH:21]=[C:22]([CH2:25][NH:26][CH:27]=[O:28])[CH:23]=2)[NH:18][CH:17]=1.[CH3:29]I>CN(C)C=O.C(OCC)(=O)C>[OH2:3].[O:13]=[C:6]1[C:7]2[C:12](=[CH:11][CH:10]=[CH:9][CH:8]=2)[C:4](=[O:3])[N:5]1[CH2:14][CH2:15][C:16]1[C:24]2[C:19](=[CH:20][CH:21]=[C:22]([CH2:25][NH:26][CH:27]=[O:28])[CH:23]=2)[N:18]([CH3:29])[CH:17]=1.[O:13]=[C:6]1[C:7]2[C:12](=[CH:11][CH:10]=[CH:9][CH:8]=2)[C:4](=[O:3])[N:5]1[CH2:14][CH2:15][C:16]1[C:24]2[C:19](=[CH:20][CH:21]=[C:22]([CH2:25][NH:26][CH:27]=[O:28])[CH:23]=2)[N:18]([CH3:29])[CH:17]=1
Reactant: CI
Reactant: O=CNCc1ccc2[nH]cc(CCN3C(=O)c4ccccc4C3=O)c2c1
Agent: [H-]
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: Cn1cc(CCN2C(=O)c3ccccc3C2=O)c2cc(CNC=O)ccc21
Product: O
Reaction time: 0.5 h

Procedure:
Sodium hydride in oil (80%, 0.045 g) was added under nitrogen to a stirred solution of N-[[3-[2-(1,3-dihydro-1,3-dioxo-2H-isoindol-2-yl)ethyl]-1H-indol-5-yl]methyl]formamide (0.5 g) in dimethylformamide (20 ml) and stirring continued for 30 min. The solution was then treated with methyl iodide (0.2 ml). After 3 h, the solution was diluted with ethyl acetate (150 ml) washed with brine (10%, 3×50 ml), dried (sodium sulphate), filtered and evaporated to dryness giving a yellow solid which was crystallised from ethyl acetate to give the title compound (0.2 g) as an off-white solid m.p. 189°-191°.
Reaction SMILES: [OH:1][C:2]1([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[C:6](=[O:7])[C:5]([C:8]2[CH:13]=[CH:12][C:11]([C:14]([OH:16])=[O:15])=[CH:10][CH:9]=2)=[CH:4][O:3]1.[CH3:23]O>>[CH3:23][O:1][C:2]1([C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=2)[C:6](=[O:7])[C:5]([C:8]2[CH:9]=[CH:10][C:11]([C:14]([OH:16])=[O:15])=[CH:12][CH:13]=2)=[CH:4][O:3]1
Reactant: O=C(O)c1ccc(C2=COC(O)(c3ccccc3)C2=O)cc1
Reactant: CO
Product: COC1(c2ccccc2)OC=C(c2ccc(C(=O)O)cc2)C1=O
Reaction time: 17 h
Yield: 91.6 %

Procedure:
A solution of 1.50 g of 2-hydroxy-2-pheny-4-(4-carboxyphenyl)-3(2H)-furanone in 100 ml of methanol was heated under reflux with stirring for 17 hrs. THe reaction mixture was concentrated to a volume of 20 ml, seeded with the product and the precipitate was collected after standing at 0° C. for 3 days. The precipitate was collected, washed with cold methanol and ether and dried at 0° C. for 4 hrs. to give 1.42 g (91.6%) of 2-methoxy-2-phenyl-4-(4-caboxyphenyl)-3(2H)-furanone as colorless crystals, m.p. 212°-214° C.
Reaction SMILES: C(OC(NC(=NC(OCC1C=CC=CC=1)=O)SC)=O)C1C=CC=CC=1.O.Br.Br.N1C2=NC=CC([NH:38][C:39](=[O:52])[C:40]3[CH:45]=[CH:44][C:43]([C@H](N)C)=[CH:42][C:41]=3[N+:49]([O-:51])=[O:50])=C2C=N1.C(N(CC)CC)C>CO>[N+:49]([C:41]1[CH:42]=[CH:43][CH:44]=[CH:45][C:40]=1[C:39]([NH2:38])=[O:52])([O-:51])=[O:50]
Reactant: C[C@@H](N)c1ccc(C(=O)Nc2ccnc3[nH]ncc23)c([N+](=O)[O-])c1
Agent: Br
Agent: CSC(=NC(=O)OCc1ccccc1)NC(=O)OCc1ccccc1
Solvent: CCN(CC)CC
Solvent: CO
Solvent: O
Product: NC(=O)c1ccccc1[N+](=O)[O-]
Temperature: 40 °C
Reaction time: 7.5 h

Procedure:
N,N'-dibenzyloxycarbonyl-S-methylisothiourea (215 mg) was added to a mixture of (R)-N-(1H-pyrazolo[3,4-b]pyridin-4-yl)-4-(1-aminoethyl)-2-nitrobenzamide dihydrobromide monohydrate (224 mg), triethylamine (0.25 ml) and methanol (5 ml) at room temperature, and the mixture was stirred at room temperature for 14 hours and at 40° C. for 7.5 hours. After the reaction, the reaction mixture was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography to give 166 mg of (R)-N-(1H-pyrazolo[3,4-b]pyridin-4-yl)-4-(1-(2',3'-dibenzyloxycarbonyl)guanidinoethyl))-2-nitrobenzamide as a pale-yellow oil.
Reaction SMILES: [Cl:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:14][CH2:15][CH2:16][CH2:17][N:18]3[CH2:22][CH2:21][CH2:20][CH2:19]3)=[C:9]([C:12]#[N:13])[CH:10]=2)[N:5]=[CH:4][CH:3]=1.[NH2:23][C:24]1[CH:25]=[C:26]2[C:30](=[CH:31][CH:32]=1)[NH:29][C:28]([CH3:33])=[CH:27]2>>[ClH:1].[C:12]([C:9]1[CH:10]=[C:11]2[C:6](=[CH:7][C:8]=1[O:14][CH2:15][CH2:16][CH2:17][N:18]1[CH2:22][CH2:21][CH2:20][CH2:19]1)[N:5]=[CH:4][CH:3]=[C:2]2[NH:23][C:24]1[CH:25]=[C:26]2[C:30](=[CH:31][CH:32]=1)[NH:29][C:28]([CH3:33])=[CH:27]2)#[N:13]
Reactant: Cc1cc2cc(N)ccc2[nH]1
Reactant: N#Cc1cc2c(Cl)ccnc2cc1OCCCN1CCCC1
Product: Cc1cc2cc(Nc3ccnc4cc(OCCCN5CCCC5)c(C#N)cc34)ccc2[nH]1
Product: Cl
Yield: 39.6 %

Procedure:
Using an analogous procedure to that described in Example 33, 4-chloro-6-cyano-7-(3-(pyrrolidin-1-yl)propoxy)quinoline (100 mg), (prepared as described for the starting material in Example 11), was reacted with 5-amino-2-methylindole (51 mg) to give 6-cyano-4-(2-methylindol-5-ylamino)-7-(3-(pyrrolidin-1-yl)propoxy)quinoline hydrochloride (58 mg, 37%).
Reaction SMILES: C([O:8][C:9]1[CH:14]=[C:13]([O:15]CC2C=CC=CC=2)[C:12]([C:23]2[N:27]([CH2:28][CH2:29][CH2:30][O:31][CH3:32])[N:26]=[N:25][N:24]=2)=[CH:11][C:10]=1[C:33]1[CH:38]=[CH:37][CH:36]=[C:35]([C:39]([OH:41])=O)[CH:34]=1)C1C=CC=CC=1.[NH2:42][CH2:43][CH2:44][CH:45]1[CH2:49][CH2:48][CH2:47][N:46]1[CH3:50]>>[CH3:50][N:46]1[CH2:47][CH2:48][CH2:49][CH:45]1[CH2:44][CH2:43][NH:42][C:39]([C:35]1[CH:34]=[C:33]([C:10]2[CH:11]=[C:12]([C:23]3[N:27]([CH2:28][CH2:29][CH2:30][O:31][CH3:32])[N:26]=[N:25][N:24]=3)[C:13]([OH:15])=[CH:14][C:9]=2[OH:8])[CH:38]=[CH:37][CH:36]=1)=[O:41]
Reactant: COCCCn1nnnc1-c1cc(-c2cccc(C(=O)O)c2)c(OCc2ccccc2)cc1OCc1ccccc1
Reactant: CN1CCCC1CCN
Product: COCCCn1nnnc1-c1cc(-c2cccc(C(=O)NCCC3CCCN3C)c2)c(O)cc1O

Procedure:
This product was synthesized using 2′,4′-bis-benzyloxy-5′-[1-(3-methoxy-propyl)-1H-tetrazol-5-yl]-biphenyl-3-carboxylic acid and 2-(2-aminoethyl)-1-methylpyrrolidine as described in general procedure D. LCMS: 481 [M+H].
Reaction SMILES: C(NC1CCCCC1)(C)C.C([Li])CCC.[CH3:16][O:17][C:18](=[O:28])[CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=1[O:26][CH3:27].[Cl:29][C:30]1[N:35]=[C:34]([Cl:36])[C:33]([CH2:37]I)=[CH:32][N:31]=1>O1CCCC1.C(OCC)(=O)C>[CH3:16][O:17][C:18](=[O:28])[CH:19]([C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=1[O:26][CH3:27])[CH2:37][C:33]1[C:34]([Cl:36])=[N:35][C:30]([Cl:29])=[N:31][CH:32]=1
Reactant: COC(=O)Cc1ccccc1OC
Reactant: Clc1ncc(CI)c(Cl)n1
Agent: CC(C)NC1CCCCC1
Agent: [Li]CCCC
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: COC(=O)C(Cc1cnc(Cl)nc1Cl)c1ccccc1OC
Temperature: -78 °C
Reaction time: 0.5 h

Procedure:
To a solution of N-isopropylcyclohexylamine (1.44 g, 10.0 mmol) (Aldrich) in dry tetrahydrofuran (20 mL) was added n-butyllithium (2.5 M in hexanes, 4.0 mL, 10.0 mmol) (Aldrich) at −78° C. under argon. After 30 minutes, a solution of 2-methoxyphenylacetic acid methyl ester (1.8 g, 10.0 mmol) (TCI-US) in tetrahydrofuran (5 mL) was added by injection via a syringe and the reaction mixture was stirred at −78° C. for another 30 minutes. To the reaction mixture was added a solution of 2,4-dichloro-5-iodomethyl-pyrimidine (1.45 g, 5.0 mmol) (from Example 1c supra) in tetrahydrofuran (5 mL) at −78° C. and the reaction mixture was stirred at the same temperature for 1 hour then slowly allowed to warm up to −30° C. and stirred for 10 minutes. The reaction mixture was diluted with ethyl acetate (100 mL) and successively washed with saturated aqueous ammonium chloride solution (100 mL), water (50 mL) and brine (50 mL), dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by flash column chromatography to give 3-(2,4-dichloro-pyrimidin-5-yl)-2-(2-methoxy-phenyl)-propionic acid methyl ester as a yellow oil. (Yield 1.40 g, 82.3%).
Reaction SMILES: [C:1]([NH:5][C:6](=[O:13])[C:7](=O)[C:8]([CH3:11])([CH3:10])[CH3:9])([CH3:4])([CH3:3])[CH3:2].[C:14]1([C@@H:20]([NH2:22])[CH3:21])[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.O>C1(C)C=CC=CC=1>[C:1]([NH:5][C:6](=[O:13])[C:7](=[N:22][C@H:20]([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[CH3:21])[C:8]([CH3:11])([CH3:10])[CH3:9])([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(C)(C)NC(=O)C(=O)C(C)(C)C
Reactant: C[C@H](N)c1ccccc1
Solvent: Cc1ccccc1
Solvent: O
Product: C[C@H](N=C(C(=O)NC(C)(C)C)C(C)(C)C)c1ccccc1
Yield: 79.6 %

Procedure:
A solution of 30.0 g (162 mmol) of N-tert-butyl-3,3-dimethyl-2-oxo-butyramide (D. Seyferth, R. C. Hui, Tetrahedron Lett. 1984, 25, 5251) and 50 g (413 mmol) of (S)-1-phenylethylamine in 150 ml of toluene was boiled under reflux on a water separator for 20 hours. Subsequently, the solvent and excess amine were removed in a vacuum. The residue was treated with 200 ml of hexane at 0° C. and stirred. After filtration of the suspension and concentration in a vacuum the residual oil was distilled. There were obtained 37.2 g (80%) of (S)-N-tert-butyl-3,3-dimethyl-2-(1-phenylethylimino)-butyramide of boiling point 140° C. at 0.3 mbar. [α]=-40.7 (c=1.0, CHCl3).
Reaction SMILES: Cl[C:2]1[N:7]=[CH:6][N:5]=[C:4]([NH:8][CH2:9][C@@H:10]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[NH:11][C:12]([O:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[O:13])[C:3]=1[CH2:29][CH3:30].[NH:31]1[CH2:36][CH2:35][CH:34]([C:37]([O:39][CH3:40])=[O:38])[CH2:33][CH2:32]1.C(NCC)(C)C.C(=O)(O)[O-].[Na+]>C(OCC)(=O)C.O>[CH2:29]([C:3]1[C:4]([NH:8][CH2:9][C@@H:10]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[NH:11][C:12]([O:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[O:13])=[N:5][CH:6]=[N:7][C:2]=1[N:31]1[CH2:36][CH2:35][CH:34]([C:37]([O:39][CH3:40])=[O:38])[CH2:33][CH2:32]1)[CH3:30]
Reactant: COC(=O)C1CCNCC1
Reactant: CCc1c(Cl)ncnc1NC[C@H](NC(=O)OCc1ccccc1)C(=O)OC(C)(C)C
Agent: CCNC(C)C
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: O
Product: CCc1c(NC[C@H](NC(=O)OCc2ccccc2)C(=O)OC(C)(C)C)ncnc1N1CCC(C(=O)OC)CC1
Temperature: 25 °C
Yield: 17 %

Procedure:
A mixture of 1.2 g (2.8 mmoles) of (1,1-dimethylethyl) 3-[(6-chloro-5-ethyl-4-pyrimidinyl)amino]-N-[(phenyl methoxy)carbonyl]alaninate, 5 ml of methyl 4-piperidinylcarboxylate and 1 ml of isopropylethylamine is heated between 110 and 120° C. for 4 hours. After cooling down to ambient temperature, the reaction medium is taken up in ethyl acetate, water and a saturated solution of sodium bicarbonate. The organic phase is separated, dried over magnesium sulphate then concentrated to dryness under vacuum. The residue is chromatographed on silicagel with a gradient of pure heptane to pure ethyl acetate. 260 mg (Yield=17%) of expected product is obtained in the form of an oil.
Reaction SMILES: C([O:3]P([CH2:9][C:10]1[S:11][CH:12]=[C:13]([CH:15]2[CH2:18][CH2:17][CH2:16]2)[N:14]=1)(=O)OCC)C.[N+:19]([C:22]1[CH:23]=[C:24]([CH:27]=[CH:28][CH:29]=1)[CH:25]=O)([O-:21])=[O:20].CO.C(=O)([O-])[O-].[K+:36].[K+]>CO.C(OCC)(=O)C>[OH-:3].[K+:36].[CH:15]1([C:13]2[N:14]=[C:10](/[CH:9]=[CH:25]/[C:24]3[CH:27]=[CH:28][CH:29]=[C:22]([N+:19]([O-:21])=[O:20])[CH:23]=3)[S:11][CH:12]=2)[CH2:16][CH2:17][CH2:18]1
Reactant: O=Cc1cccc([N+](=O)[O-])c1
Reactant: CCOP(=O)(Cc1nc(C2CCC2)cs1)OCC
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CO
Solvent: CCOC(C)=O
Product: O=[N+]([O-])c1cccc(/C=C/c2nc(C3CCC3)cs2)c1
Product: [OH-]
Reaction time: 8 h
Yield: 96.1 %

Procedure:
A 1-L round-bottom flask was charged with 28.0 g (0.0968 mol) of crude compound of Example 2, 15.21 g (0.1006 mol) of 3-nitrobenzaldehyde and 400 mL of methanol. The mixture was stirred until a solution was obtained. To this solution was added 40.13 g (0.2903 mol) of powdered potassium carbonate under vigorous stirring and stirring was continued overnight at room temperature. The compound of Example 2 was no longer detectable at this time (TLC, Merck silica gel 60, F-254; 95:5 ethyl acetate methanol). During the reaction time additional solids had precipitated from the solution. The suspension was concentrated at 30° C. bath temperature and 10 torr until a volume of about 200 mL of methanol was removed. To the resulting residue was added 200 mL of water and the mixture was stirred at room temperature for one hour. The solids were collected by filtration under reduced pressure using a sintered-glass funnel of medium porosity. The filter cake was washed with 2×100 mL of water and dried for 16 hours at 30° C. and 10 torr over potassium hydroxide flakes to afford 26.63 g of crude [E]-4-cyclobutyl-2-[2-(3-nitrophenyl)ethenyl]thiazole as a mustard-colored powder (TLC, Merck silica gel 60, F-254; 95:5 ethyl acetate-methanol); 96.1% yield based on crude compound of Example 2 used, 96.76% pure (HPLC).
Reaction SMILES: [Si:1]([O:8][CH:9]1[CH:14]2[CH2:15][O:16][N:17]=[C:13]2[CH2:12][CH:11]([O:18][Si:19]([C:22]([CH3:25])([CH3:24])[CH3:23])([CH3:21])[CH3:20])[CH:10]1[OH:26])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].C(N(CC)CC)C.[C:34](Cl)(=[O:36])[CH3:35]>C(Cl)Cl.CN(C)C1C=CN=CC=1.C(OCC)C>[C:34]([O:26][CH:10]1[CH:9]([O:8][Si:1]([C:4]([CH3:7])([CH3:5])[CH3:6])([CH3:3])[CH3:2])[CH:14]2[CH2:15][O:16][N:17]=[C:13]2[CH2:12][CH:11]1[O:18][Si:19]([C:22]([CH3:25])([CH3:24])[CH3:23])([CH3:20])[CH3:21])(=[O:36])[CH3:35]
Reactant: CC(=O)Cl
Reactant: CC(C)(C)[Si](C)(C)OC1CC2=NOCC2C(O[Si](C)(C)C(C)(C)C)C1O
Agent: CN(C)c1ccncc1
Solvent: CCN(CC)CC
Solvent: CCOCC
Solvent: ClCCl
Product: CC(=O)OC1C(O[Si](C)(C)C(C)(C)C)CC2=NOCC2C1O[Si](C)(C)C(C)(C)C
Temperature: 25 °C
Reaction time: 8 h
Yield: 80.1 %

Procedure:
4,6-Bis(tert-butyldimethylsilyloxy)-5-hydroxy-3,3a,4,5,6,7-hexahydro-2,1-benzoisooxazole (401 mg) was dissolved in 20 ml of methylene chloride. Five milliliters of triethylamine and 0.5 g of 4-dimethylaminopyridine were added, and 100 mg of acetyl chloride was then added, followed by stirring the mixture overnight at room temperature. The reaction mixture was diluted with diethyl ether, and washed with dilute hydrochloric acid, a sodium hydrogen carbonate aqueous solution and a sodium chloride aqueous solution in sequence. The organic layer was dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography to give 355 mg of 5-acetoxy-4,6-bis(tert-butyldimethylsilyloxy)-3,3a,4,5,6,7-hexahydro-2,1-benzoisooxazole having the following property (yield 80%).
Reaction SMILES: [CH2:1]([N:8]1[CH2:12][CH2:11][CH:10]([OH:13])[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:14][C:15]1[N:24]([C:25]2[CH:30]=[CH:29][C:28](O)=[CH:27][CH:26]=2)[C:23](=[O:32])[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[N:16]=1>>[CH2:1]([N:8]1[CH2:12][CH2:11][CH:10]([O:13][C:28]2[CH:27]=[CH:26][C:25]([N:24]3[C:23](=[O:32])[C:22]4[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=4)[N:16]=[C:15]3[CH3:14])=[CH:30][CH:29]=2)[CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: OC1CCN(Cc2ccccc2)C1
Reactant: Cc1nc2ccccc2c(=O)n1-c1ccc(O)cc1
Product: Cc1nc2ccccc2c(=O)n1-c1ccc(OC2CCN(Cc3ccccc3)C2)cc1

Procedure:
1-benzyl-3-pyrrolidinol and 2-methyl-3-(4-hydroxyphenyl)-4-(3H) quinazolinone synthesized according to Example 1-(1) and -(2) were etherated by the Mitsunobu reaction according to Example 117-(2), and the target compound was thus obtained.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[CH:10]=[C:9]([C:11]([NH:13][C@@H:14]([CH2:18][C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=3)[C:15](O)=[O:16])=[O:12])[NH:8][C:5]2=[CH:6][N:7]=1.Cl.[CH3:27][O:28][CH2:29][CH2:30][O:31][CH:32]1[CH2:37][CH2:36][NH:35][CH2:34][CH2:33]1>>[F:25][C:22]1[CH:21]=[CH:20][C:19]([CH2:18][C@H:14]([NH:13][C:11]([C:9]2[NH:8][C:5]3=[CH:6][N:7]=[C:2]([Cl:1])[CH:3]=[C:4]3[CH:10]=2)=[O:12])[C:15]([N:35]2[CH2:36][CH2:37][CH:32]([O:31][CH2:30][CH2:29][O:28][CH3:27])[CH2:33][CH2:34]2)=[O:16])=[CH:24][CH:23]=1
Reactant: O=C(N[C@@H](Cc1ccc(F)cc1)C(=O)O)c1cc2cc(Cl)ncc2[nH]1
Reactant: COCCOC1CCNCC1
Agent: Cl
Product: COCCOC1CCN(C(=O)[C@H](Cc2ccc(F)cc2)NC(=O)c2cc3cc(Cl)ncc3[nH]2)CC1

Procedure:
The title compound was prepared according to EXAMPLE 229 from 2-(S)-[(5-chloro-1H-pyrrolo[2,3-c]pyridine-2-carbonyl)amino]-3-(4-fluorophenyl)propionic acid (EXAMPLE 228) and 4-(2-methoxyethoxy)piperidine hydrochloride (Preparation 82). Purification by chromatography using dichloromethane/methanol (95:5) as the eluent gave the title compound as an off-white powder. m/z (ES+) 503.26 [M+H]+; RT=3.3 min.
Reaction SMILES: [CH:1]1([CH:6]([N:10]2[CH:14]=[C:13]([C:15]3[C:16]4[CH:23]=[CH:22][N:21](COCC[Si](C)(C)C)[C:17]=4[N:18]=[CH:19][N:20]=3)[CH:12]=[N:11]2)[CH2:7][C:8]#[CH:9])[CH2:5][CH2:4][CH2:3][CH2:2]1.[C:32]([OH:38])([C:34]([F:37])([F:36])[F:35])=[O:33]>C(Cl)Cl>[F:35][C:34]([F:37])([F:36])[C:32]([OH:38])=[O:33].[CH:1]1([CH:6]([N:10]2[CH:14]=[C:13]([C:15]3[C:16]4[CH:23]=[CH:22][NH:21][C:17]=4[N:18]=[CH:19][N:20]=3)[CH:12]=[N:11]2)[CH2:7][C:8]#[CH:9])[CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: C#CCC(C1CCCC1)n1cc(-c2ncnc3c2ccn3COCC[Si](C)(C)C)cn1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: C#CCC(C1CCCC1)n1cc(-c2ncnc3[nH]ccc23)cn1
Reaction time: 1 h
Yield: 60 %

Procedure:
A solution of 4-[1-(1-cyclopentylbut-3-yn-1-yl)-1H-pyrazol-4-yl]-7-[2-(trimethylsilyl)-ethoxy]methyl-7H-pyrrolo[2,3-d]pyrimidine (52 mg, 0.12 mmol) in DCM (3 mL) and TFA (1 mL) was stirred for 2 hours. The solvents were removed in vacuo. The resulting residue was dissolved in THF (3 mL) and 6N NaOH (2 mL) was added. After stirring for 1 hour, the mixture was partitioned between water and ethyl acetate. The organic layer was dried over sodium sulfate and the solvent was removed in vacuo. Purification via preparative-HPLC/MS (C18 eluting with a gradient of H2O and ACN containing 0.1% TFA) afforded product (30 mg, 60%).
Reaction SMILES: C1(C)C=CC(S(O)(=O)=O)=CC=1.[C:12]1([CH:19]=[CH:18][C:16]([OH:17])=CC=1)O.COCN[C:24](=[O:27])[CH:25]=[CH2:26]>CC(OCCOC)=O>[C:24]([O:17][CH2:16][CH2:18][CH2:19][CH3:12])(=[O:27])[CH:25]=[CH2:26]
Reactant: Oc1ccc(O)cc1
Reactant: C=CC(=O)NCOC
Agent: COCCOC(C)=O
Agent: Cc1ccc(S(=O)(=O)O)cc1
Product: C=CC(=O)OCCCC

Procedure:
The polymer was dissolved in 250 g methyl glycol acetate and, after the addition of 800 mg p-toluene-sulfonic acid and 80 mg hydroquinone, mixed with 77 g N-methoxymethyl-acrylamide, sensitized as described in Example 1, and used for the production of a relief image.
Reaction SMILES: Br[CH2:2][CH2:3][CH2:4][CH2:5][C:6]#[N:7].[C:8]([C:12]1[CH:13]=[C:14]([OH:22])[CH:15]=[C:16]([C:18]([CH3:21])([CH3:20])[CH3:19])[CH:17]=1)([CH3:11])([CH3:10])[CH3:9]>>[C:18]([C:16]1[CH:15]=[C:14]([CH:13]=[C:12]([C:8]([CH3:11])([CH3:10])[CH3:9])[CH:17]=1)[O:22][CH2:2][CH2:3][CH2:4][CH2:5][C:6]#[N:7])([CH3:21])([CH3:20])[CH3:19]
Reactant: N#CCCCCBr
Reactant: CC(C)(C)c1cc(O)cc(C(C)(C)C)c1
Product: CC(C)(C)c1cc(OCCCCC#N)cc(C(C)(C)C)c1
Yield: 61.9 %

Procedure:
Using the method of Example 1, 17.8 g (0.11 mole) of 5-bromo-pentanenitrile was reacted with 20.6 g (0.10 mole) of 3,5-di-t-butylphenol to give 17.8 g of white crystalline 5-(3,5-di-t-butylphenoxy)pentanenitrile, m.p. 61°-64° C. Analysis: Calculated for: C19H29NO: %C, 79.4; , %H, 10.2; %N, 4.9; Found: %C, 79.0; %H, 10.3; %N, 5.1.