Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:10]=[C:11]([CH:17]=[CH:18][C:19]=1[O:20][CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[CH:12]=[CH:13][N+:14]([O-:16])=[O:15])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[N+:28]([O-])([OH:30])=[O:29]>CC(O)=O>[CH2:21]([O:20][C:19]1[C:9]([O:8][CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)=[CH:10][C:11](/[CH:12]=[CH:13]/[N+:14]([O-:16])=[O:15])=[C:17]([N+:28]([O-:30])=[O:29])[CH:18]=1)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1
Reactant: O=[N+]([O-])C=Cc1ccc(OCc2ccccc2)c(OCc2ccccc2)c1
Reactant: O=[N+]([O-])O
Solvent: CC(=O)O
Product: O=[N+]([O-])/C=C/c1cc(OCc2ccccc2)c(OCc2ccccc2)cc1[N+](=O)[O-]
Temperature: 20 °C
Reaction time: 3 h
Yield: 93 %

Procedure:
3,4-Dibenzyloxy -β-nitrostyrene (12) (67.2 g; 0.186 mol) is dispersed in 1.5 L CH3CO2H. HNO3 (d 1.42) is added until the temperature reaches 40° C. The mixture is cooled to 20° C., and the remainder of the 375 mL HNO3 is added without further cooling. After stirring at 23° C. for three hours, the reaction mixture is poured onto 2 kg of ice, and filtered. The yellow powder is washed well with H2O. Recrystallization from CH3CO2H affords 70.3 g (93%) of (13) as yellow needles; mp 162°-164° C.
Reaction SMILES: Cl[C:2]1[CH:10]=[N:9][CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].[Cl:11][C:12]1[CH:17]=[CH:16][C:15]([C:18](=[O:29])[CH2:19]C(C2C=CC(Cl)=CC=2)=O)=[CH:14][CH:13]=1>>[Cl:11][C:12]1[CH:17]=[CH:16][C:15]([C:18](=[O:29])[CH2:19][C:2]2[CH:10]=[N:9][CH:8]=[CH:7][C:3]=2[C:4]([OH:6])=[O:5])=[CH:14][CH:13]=1
Reactant: O=C(O)c1ccncc1Cl
Reactant: O=C(CC(=O)c1ccc(Cl)cc1)c1ccc(Cl)cc1
Product: O=C(Cc1cnccc1C(=O)O)c1ccc(Cl)cc1

Procedure:
3-[2-(4-Chlorophenyl)-2-oxoethyl]-isonicotinic acid (above) was prepared by Method H using 3-chloro-isonicotinic acid and 1,3-bis-(4-chlorophenyl)-propane-1,3-dione.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([OH:11])=O)=[CH:4][CH:3]=1.[C:12](N1C=CN=C1)([N:14]1C=CN=[CH:15]1)=O.C(N(CC)CC)C.Cl.CNC>ClCCl>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([N:14]([CH3:15])[CH3:12])=[O:11])=[CH:4][CH:3]=1
Reactant: O=C(O)Cc1ccc(Br)cc1
Reactant: O=C(n1ccnc1)n1ccnc1
Agent: CNC
Agent: Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CN(C)C(=O)Cc1ccc(Br)cc1
Reaction time: 1 h
Yield: 63.4 %

Procedure:
A solution of 4-bromophenylacetic acid (960 mg, 4.49 mmol) in dichloromethane (30 ml) was treated in one portion with solid 1,1′-carbonyldiimidazole (730 mg, 4.5 mmol) at 20° C. with stirring under argon. This mixture was allowed to stir at room temperature for 15 minutes. Triethylamine (0.63 ml) was then added followed by dimethylamine hydrochloride (367 mg, 4.5 mmol) and the stirring continued for 1 hour. Most of the solvent was removed under reduced pressure and the residue added to a 20 g isolute silica sep-pak column and eluted from 0-50% ethyl acetate in petroleum ether to give the title compound as a colourless solid (689 mg, 64%).
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([C@@H:15]([O:18][Si:19]([C:22]([CH3:25])([CH3:24])[CH3:23])([CH3:21])[CH3:20])[CH2:16]Br)=[CH:11][C:10]=1[CH2:26][O:27][Si:28]([C:31]([CH3:34])([CH3:33])[CH3:32])([CH3:30])[CH3:29])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:35][C:36]([CH3:49])([CH3:48])[CH2:37][C:38]1[CH:39]=[C:40]([CH:45]=[CH:46][CH:47]=1)[C:41]([O:43][CH3:44])=[O:42]>CCN(CC)CC>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([C@@H:15]([O:18][Si:19]([C:22]([CH3:25])([CH3:24])[CH3:23])([CH3:21])[CH3:20])[CH2:16][NH:35][C:36]([CH3:49])([CH3:48])[CH2:37][C:38]2[CH:39]=[C:40]([CH:45]=[CH:46][CH:47]=2)[C:41]([O:43][CH3:44])=[O:42])=[CH:11][C:10]=1[CH2:26][O:27][Si:28]([C:31]([CH3:34])([CH3:33])[CH3:32])([CH3:30])[CH3:29])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: COC(=O)c1cccc(CC(C)(C)N)c1
Reactant: CC(C)(C)[Si](C)(C)OCc1cc([C@H](CBr)O[Si](C)(C)C(C)(C)C)ccc1OCc1ccccc1
Solvent: CCN(CC)CC
Product: COC(=O)c1cccc(CC(C)(C)NC[C@H](O[Si](C)(C)C(C)(C)C)c2ccc(OCc3ccccc3)c(CO[Si](C)(C)C(C)(C)C)c2)c1
Yield: 36.5 %

Procedure:
Intermediate 6 (1.6 g, 2.89 mmol) and Intermediate 19 (900 mg, 4.3 mmol) were heated neat at 95° C. for 3 days. The reaction mixture was cooled then chromatography (3:1 Hexanes/EtOAc, 0.1% Et3N) afforded the title compound (730 mg, 37%). ES/MS calcd. for C40H62NO5Si2+ 692.4. found m/z=692.4 (M+H)+.
Reaction SMILES: [BH4-].[Na+].[OH:3][C:4](=[CH:17][C:18]1[CH:23]=[CH:22][N:21]=[CH:20][N:19]=1)[C:5]([CH3:16])([CH3:15])[O:6][C:7]1[CH:14]=[CH:13][C:10]([C:11]#[N:12])=[CH:9][CH:8]=1>C(O)C>[OH:3][CH:4]([CH2:17][C:18]1[CH:23]=[CH:22][N:21]=[CH:20][N:19]=1)[C:5]([CH3:15])([CH3:16])[O:6][C:7]1[CH:8]=[CH:9][C:10]([C:11]#[N:12])=[CH:13][CH:14]=1
Reactant: CC(C)(Oc1ccc(C#N)cc1)C(O)=Cc1ccncn1
Agent: [BH4-]
Agent: [Na+]
Solvent: CCO
Product: CC(C)(Oc1ccc(C#N)cc1)C(O)Cc1ccncn1
Temperature: 20 °C
Reaction time: 16 h
Yield: 73959.8 %

Procedure:
0.013 mg of sodium borohydride was added to a solution of 0.098 mg of 4-[2-hydroxy-1,1-dimethyl-3-(4-pyrimidinyl)-2-propenyloxy]benzonitrile in 3 ml of ethanol and the solution was stirred at 20° C. for 16 hours. The solvent was removed by evaporation and the residue was partitioned between ethyl acetate and water. The organic phase was evaporated and the residue was chromatographed on silica gel using ethyl acetate for the elution. There was obtained 0.073 g of 4-[2-hydroxy-1,1-dimethyl-3-(4-pyrimidinyl)propoxy]benzonitrile in the form of a white solid of melting point 96°-98° C.
Reaction SMILES: O[Li].O.C[O:5][C:6](=[O:26])[CH2:7][CH2:8][C:9]1[C:10](=[O:25])[N:11]([CH2:14][C:15]2[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][C:16]=2[O:23][CH3:24])[CH2:12][CH:13]=1.Cl>C1COCC1>[CH3:24][O:23][C:16]1[CH:17]=[C:18]([O:21][CH3:22])[CH:19]=[CH:20][C:15]=1[CH2:14][N:11]1[CH2:12][CH:13]=[C:9]([CH2:8][CH2:7][C:6]([OH:26])=[O:5])[C:10]1=[O:25]
Reactant: COC(=O)CCC1=CCN(Cc2ccc(OC)cc2OC)C1=O
Agent: Cl
Agent: [Li]O
Solvent: C1CCOC1
Solvent: O
Product: COc1ccc(CN2CC=C(CCC(=O)O)C2=O)c(OC)c1
Temperature: 0 °C
Reaction time: 2 h
Yield: 79 %

Procedure:
10.8 mg of LiOH.H2O solution (0.25 mmol) was added to 0.86 ml of THF solution containing 55 mg of 3-[1-(2,4-dimethoxy benzyl)-2-oxo-2,5-dihydro-1H-pyrrol-3-yl]-propionic acid methyl ester (0.17 mmol) in a dropwise manner at 0° C. The reaction mixture was stirred for 2 hrs at 0° C. and 5% HCl was added to pH 1. Then the mixture was extracted three times with 10 ml of ethyl acetate, the organic layer was washed with 15 ml of saturated NaCl solution, dried over anhydrous MgSO4, filtered and concentrated in vacuo. The resulting compound was purified with Silica gel column chromatography with a solvent mixture mixed with methanol and chloroform (1:9) as an eluant to give 41 mg of 3-[1-(2,4-dimethoxy-benzyl)-2-oxo-2,5-dihydro-1H-pyrrol-3-yl]-propionic acid (16f) (yield: 80%).
Reaction SMILES: [C:1]([NH:4][C:5]1[CH:14]=[C:13]2[C:8]([NH:9][C:10](=[O:22])[C:11](=[O:21])[N:12]2[CH2:15][CH:16]([CH2:19][CH3:20])[CH2:17][CH3:18])=[CH:7][CH:6]=1)(=[O:3])[CH3:2].[N+:23]([O-])([O-:25])=[O:24].[K+]>S(=O)(=O)(O)O>[C:1]([NH:4][C:5]1[CH:14]=[C:13]2[C:8]([NH:9][C:10](=[O:22])[C:11](=[O:21])[N:12]2[CH2:15][CH:16]([CH2:19][CH3:20])[CH2:17][CH3:18])=[CH:7][C:6]=1[N+:23]([O-:25])=[O:24])(=[O:3])[CH3:2]
Reactant: CCC(CC)Cn1c(=O)c(=O)[nH]c2ccc(NC(C)=O)cc21
Reactant: O=[N+]([O-])[O-]
Agent: O=S(=O)(O)O
Agent: [K+]
Product: CCC(CC)Cn1c(=O)c(=O)[nH]c2cc([N+](=O)[O-])c(NC(C)=O)cc21
Temperature: 0 °C
Reaction time: 1 h
Yield: 74.7 %

Procedure:
21.0 g (69.2 mmol) of 7-acetamido-1-(2-ethylbutyl)-2,3(1H,4H)-quinoxalinedione were dissolved in 250 ml of concentrated sulfuric acid and, at 0°-5° C., 7.0 g (69.2 mmol) of potassium nitrate were added a little at a time. The mixture was stirred for 1 h and a further 3.5 g (34.6 mmol) of potassium nitrate were added, and the mixture was stirred at room temperature for 16 h. It was then poured into ice-water, and the precipitate was filtered off with suction and dried to yield 18.0 g (75%) of the product, which was immediately processed further.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]([CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([C:23]2[CH2:27][CH2:26][CH2:25][CH:24]=2)[CH:18]=1)[C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:7])([CH3:4])([CH3:3])[CH3:2]>C(OCC)(=O)C.[C].[Pd]>[C:11]([O:10][C:9]([N:8]([CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([CH:23]2[CH2:24][CH2:25][CH2:26][CH2:27]2)[CH:18]=1)[C:6](=[O:7])[O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:15])([CH3:12])([CH3:13])[CH3:14]
Reactant: CC(C)(C)OC(=O)N(Cc1cccc(C2=CCCC2)c1)C(=O)OC(C)(C)C
Agent: [Pd]
Solvent: CCOC(C)=O
Product: CC(C)(C)OC(=O)N(Cc1cccc(C2CCCC2)c1)C(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 2 h
Yield: 95 %

Procedure:
Tert-butyl N-tert-butoxycarbonyl-N-{[3-(cyclopenten-1-yl)phenyl]methyl}carbamate (4.92 g) was dissolved in ethyl acetate (150 mL). To the solution, 10% palladium-carbon (0.50 g) was added, and the mixture was then stirred at room temperature for 2 hours under a hydrogen atmosphere. The reaction solution was filtered through celite. The filtrate was concentrated under reduced pressure to obtain the title compound (4.70 g).
Reaction SMILES: [C:1]([O:4][CH2:5][C:6]([C:9]1[CH:14]=[C:13]([NH:15][C:16]2[S:17][CH:18]=[CH:19][N:20]=2)[CH:12]=[C:11]([C:21]([CH3:24])([CH3:23])[CH3:22])[C:10]=1[OH:25])([CH3:8])[CH3:7])(=[O:3])[CH3:2].[C:26](OC(=O)C)(=[O:28])[CH3:27]>>[C:1]([O:4][CH2:5][C:6]([C:9]1[CH:14]=[C:13]([N:15]([C:26](=[O:28])[CH3:27])[C:16]2[S:17][CH:18]=[CH:19][N:20]=2)[CH:12]=[C:11]([C:21]([CH3:24])([CH3:23])[CH3:22])[C:10]=1[OH:25])([CH3:8])[CH3:7])(=[O:3])[CH3:2]
Reactant: CC(=O)OCC(C)(C)c1cc(Nc2nccs2)cc(C(C)(C)C)c1O
Reactant: CC(=O)OC(C)=O
Product: CC(=O)OCC(C)(C)c1cc(N(C(C)=O)c2nccs2)cc(C(C)(C)C)c1O
Temperature: 100 °C

Procedure:
A mixture consisting of 0.50 g of Compound 13 (prepared in Example 13) and 6 ml of acetic anhydride was heated at 100° C. for 1 hour. The reaction mixture was then cooled to ambient temperature and concentrated. The resulting crude product was purified by silica gel column chromatography (diethyl ether-hexane=1:2) to give 0.50 g of the desired compound as a colorless solid. The structure and physical properties of this product compound are shown in Table 2.
Reaction SMILES: Br[CH2:2][C:3]1[N:4]([CH3:28])[C:5]2[C:10]([N:11]=1)=[C:9]([N:12]1[CH2:17][CH2:16][O:15][CH2:14][CH2:13]1)[N:8]=[C:7]([N:18]1[C:22]3[CH:23]=[CH:24][CH:25]=[CH:26][C:21]=3[N:20]=[C:19]1[CH3:27])[N:6]=2.[C:29]1([CH:35]([NH2:37])[CH3:36])[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1>>[CH3:28][N:4]1[C:3]([CH2:2][NH:37][CH:35]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[CH3:36])=[N:11][C:10]2[C:5]1=[N:6][C:7]([N:18]1[C:22]3[CH:23]=[CH:24][CH:25]=[CH:26][C:21]=3[N:20]=[C:19]1[CH3:27])=[N:8][C:9]=2[N:12]1[CH2:17][CH2:16][O:15][CH2:14][CH2:13]1
Reactant: CC(N)c1ccccc1
Reactant: Cc1nc2ccccc2n1-c1nc(N2CCOCC2)c2nc(CBr)n(C)c2n1
Product: Cc1nc2ccccc2n1-c1nc(N2CCOCC2)c2nc(CNC(C)c3ccccc3)n(C)c2n1

Procedure:
4-(8-(bromomethyl)-9-methyl-2-(2-methyl-1H-benzo[d]imidazol-1-yl)-9H-purin-6-yl)morpholine (50 mg) was reacted with 1-phenylethanamine via General Procedure E to give 10.8 mg of 279 following reverse phase purification. MS (Q1) 483.2 (M)+
Reaction SMILES: [CH2:1]=[CH:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[Cl:9][SiH:10]([Cl:12])[Cl:11].CS(O)(=O)=O>[Pt].C1(C)C=CC=CC=1>[CH2:1]([Si:10]([Cl:12])([Cl:11])[Cl:9])[CH2:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1
Reactant: C=Cc1ccccc1
Reactant: Cl[SiH](Cl)Cl
Agent: [Pt]
Agent: CS(=O)(=O)O
Solvent: Cc1ccccc1
Product: Cl[Si](Cl)(Cl)CCc1ccccc1
Yield: 8.7 %

Procedure:
Reaction between styrene and trichlorosilane with platinum catalyst in the presence of a trimethylsilyl ester of methanesulfonic acid. 518 mg Styrene and 694 mg trichlorosilane were introduced into a glass tube, and 42 mg of a trimethylsilyl ester of methanesulfonic acid were added. 2.5 mg Of a toluene solution of a 0-valent platinum complex of divinylsiloxane (0.04 wt % platinum content) were added. The tube was sealed with Teflon tape and a rubber septum and placed in a 50° C. oil bath where it was heated for 30 minutes. After cooling, the tube contents were analyzed by gas chromatography revealing a styrene conversion of 11% and a phenethyltrichlorosilane yield of 8.7%. The ratio between the phenethyltrichlorosilane and the (α-methylbenzyl)trichlorosilane was 390:1.
Reaction SMILES: [C:1]([C:6]1[C:18]([CH3:19])=[CH:17][C:9]2[N:10]([CH3:16])[C:11]([CH:13](Cl)Cl)=[N:12][C:8]=2[CH:7]=1)(=[O:5])[CH2:2][CH2:3][CH3:4].C([O-])(=[O:22])C.[Na+]>C(O)C>[C:1]([C:6]1[C:18]([CH3:19])=[CH:17][C:9]2[N:10]([CH3:16])[C:11]([CH:13]=[O:22])=[N:12][C:8]=2[CH:7]=1)(=[O:5])[CH2:2][CH2:3][CH3:4]
Reactant: CCCC(=O)c1cc2nc(C(Cl)Cl)n(C)c2cc1C
Reactant: CC(=O)[O-]
Agent: [Na+]
Solvent: CCO
Product: CCCC(=O)c1cc2nc(C=O)n(C)c2cc1C

Procedure:
2.0 g of 5-butyryl-2-dichloromethyl-1,6-dimethylbenzimidazole are dissolved in 100 ml of ethanol. 50 ml of a 4 N sodium acetate solution are added and the solution is refluxed for 5 hours. The solution is evaporated to dryness under reduced pressure and recrystallised from ethyl acetate/cyclohexane. 5-butyryl-1,6-dimethylbenzimidazole-2-carboxaldehyde having a melting point of 116°-118° is obtained.
Reaction SMILES: [C:1]([O-:4])([O-])=O.[K+].[K+].CI.[Br:9][C:10]1[CH:11]=[C:12](O)[CH:13]=[N:14][C:15]=1[Cl:16]>CN(C=O)C.O>[Br:9][C:10]1[C:15]([Cl:16])=[N:14][CH:13]=[C:12]([O:4][CH3:1])[CH:11]=1
Reactant: Oc1cnc(Cl)c(Br)c1
Reactant: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Solvent: CI
Product: COc1cnc(Cl)c(Br)c1
Temperature: 45 °C
Reaction time: 8 h

Procedure:
K2CO3 (0.50 g, 3.6 mmol) followed by methyl iodide (0.20 mL, 2.9 mmol) were added to a stirred mixture of 5-bromo-6-chloropyridin-3-ol (Asymchem Laboratories, Inc., Morrisville, N.C.) (0.50 g, 2.4 mmol) in DMF (3.00 mL) and the mixture was sealed and heated at 45° C. for 4 h and then allowed to stand at room temperature overnight. The resulting mixture was diluted with water and the precipitate was collected and dried to give the product as a tan solid. LCMS (API-ES) m/z 223 (M+H)+; 1H NMR (400 MHz, CDCl3) δ 8.04 (s, 1H) 7.49 (d, J=1.37 Hz, 1H) 3.86 (s, 3H).
Reaction SMILES: [N+:1]([O-:4])(O)=[O:2].S(=O)(=O)(O)O.[Br:10][CH2:11][CH2:12][C:13]1[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[NH:16][C:15](=[O:23])[CH:14]=1>>[Br:10][CH2:11][CH2:12][C:13]1[C:22]2[C:17](=[CH:18][CH:19]=[C:20]([N+:1]([O-:4])=[O:2])[CH:21]=2)[NH:16][C:15](=[O:23])[CH:14]=1
Reactant: O=c1cc(CCBr)c2ccccc2[nH]1
Reactant: O=[N+]([O-])O
Agent: O=S(=O)(O)O
Product: O=c1cc(CCBr)c2cc([N+](=O)[O-])ccc2[nH]1
Temperature: 45 °C
Reaction time: 0.75 h

Procedure:
To a mixture of nitric acid (60%) (21 ml) and concentrated sulfuric acid (14 ml) was added 4-(2-bromoethyl)-2(1H)-quinolinone (II-2) (3.5 g, 13.9 mmol) under ice-cooling and then the mixture was stirred at 45 ° C. (bath temperature) for 45 minutes.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:35]=[CH:34][C:6]([CH2:7][O:8][C:9]2[C:10]([C:18]3[CH:23]=[CH:22][C:21]([C:24]4[CH:25]=[N:26][C:27]([C:30](=[O:33])[NH:31][CH3:32])=[CH:28][CH:29]=4)=[CH:20][CH:19]=3)=[N:11][N:12]([CH3:17])[C:13]=2[C:14]([OH:16])=O)=[CH:5][CH:4]=1.[CH3:36][O:37][C:38]1[CH:66]=[C:65]([O:67][CH3:68])[CH:64]=[CH:63][C:39]=1[CH2:40][NH:41][C:42]1[CH:43]=[C:44]2[C:48](=[CH:49][C:50]=1[NH2:51])[CH2:47][N:46]([CH2:52][C:53]1[CH:58]=[CH:57][C:56]([O:59][CH3:60])=[CH:55][C:54]=1[O:61][CH3:62])[CH2:45]2.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C>CN(C)C=O.C(OCC)(=O)C>[CH3:62][O:61][C:54]1[CH:55]=[C:56]([O:59][CH3:60])[CH:57]=[CH:58][C:53]=1[CH2:52][N:46]1[CH2:47][C:48]2[C:44](=[CH:43][C:42]([NH:41][CH2:40][C:39]3[CH:63]=[CH:64][C:65]([O:67][CH3:68])=[CH:66][C:38]=3[O:37][CH3:36])=[C:50]([NH:51][C:14]([C:13]3[N:12]([CH3:17])[N:11]=[C:10]([C:18]4[CH:19]=[CH:20][C:21]([C:24]5[CH:29]=[CH:28][C:27]([C:30]([NH:31][CH3:32])=[O:33])=[N:26][CH:25]=5)=[CH:22][CH:23]=4)[C:9]=3[O:8][CH2:7][C:6]3[CH:34]=[CH:35][C:3]([O:2][CH3:1])=[CH:4][CH:5]=3)=[O:16])[CH:49]=2)[CH2:45]1
Reactant: CNC(=O)c1ccc(-c2ccc(-c3nn(C)c(C(=O)O)c3OCc3ccc(OC)cc3)cc2)cn1
Reactant: COc1ccc(CNc2cc3c(cc2N)CN(Cc2ccc(OC)cc2OC)C3)c(OC)c1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: CNC(=O)c1ccc(-c2ccc(-c3nn(C)c(C(=O)Nc4cc5c(cc4NCc4ccc(OC)cc4OC)CN(Cc4ccc(OC)cc4OC)C5)c3OCc3ccc(OC)cc3)cc2)cn1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To a solution of 4-(4-methoxybenzyloxy)-1-methyl-3-(4-(6-(methylcarbamoyl)pyridin-3-yl)phenyl)-1H-pyrazole-5-carboxylic acid T-13 (304 mg, 0.64 mmol) in N,N-dimethylformamide (4 mL) were added N5,2-bis(2,4-dimethoxybenzyl)isoindoline-5,6-diamine T-04 (347 mg, 0.77 mmol), HATU (318 mg, 0.84 mmol) and diisopropylethylamine (0.34 mL, 2.0 mmol). The reaction mixture was stirred at room temperature for 2 hours. The crude product was diluted with ethyl acetate. The organic layer was washed with water and saturated brine. The organic layer was dried over sodium sulfate. Solvent was evaporated under reduced pressure. The crude product was purified by flash chromatography to afford the desired 5-(4-(5-(2-(2,4-dimethoxybenzyl)-6-(2,4-dimethoxybenzylamino)isoindolin-5-ylcarbamoyl)-4-(4-methoxybenzyloxy)-1-methyl-1H-pyrazol-3-yl)phenyl)-N-methylpicolinamide T-14 (410 mg, 0.45 mmol).
Reaction SMILES: C(O)(C(F)(F)F)=O.[S:8]1[C:12]2[CH:13]=[C:14]([NH:17][CH2:18][CH2:19][C:20]3[CH:25]=[CH:24][C:23]([C:26]([F:29])([F:28])[F:27])=[CH:22][CH:21]=3)[CH:15]=[CH:16][C:11]=2[N:10]=[CH:9]1.[CH3:30][O:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=1[CH2:38][C:39](O)=[O:40]>>[S:8]1[C:12]2[CH:13]=[C:14]([N:17]([CH2:18][CH2:19][C:20]3[CH:25]=[CH:24][C:23]([C:26]([F:27])([F:28])[F:29])=[CH:22][CH:21]=3)[C:39](=[O:40])[CH2:38][C:33]3[CH:34]=[CH:35][CH:36]=[CH:37][C:32]=3[O:31][CH3:30])[CH:15]=[CH:16][C:11]=2[N:10]=[CH:9]1
Reactant: COc1ccccc1CC(=O)O
Reactant: FC(F)(F)c1ccc(CCNc2ccc3ncsc3c2)cc1
Solvent: O=C(O)C(F)(F)F
Product: COc1ccccc1CC(=O)N(CCc1ccc(C(F)(F)F)cc1)c1ccc2ncsc2c1

Procedure:
In analogy to example 33, step 2, without TFA addition, benzothiazol-6-yl-[2-(4-trifluoromethyl-phenyl)-ethyl]-amine was coupled to (2-methoxy-phenyl)-acetic acid (commercially available) to provide the title compound. MS m/e: 471.0 [M+H]+.
Reaction SMILES: [CH3:1][C:2]([OH:11])([CH2:4][CH2:5][CH:6]=[CH:7][C:8]([CH3:10])=[CH2:9])[CH3:3].[C:12](OC(C)=C)(=[O:14])[CH3:13]>CCCCCC.C1(C)C=CC(S(O)(=O)=O)=CC=1>[C:12]([O:11][C:2]([CH3:1])([CH2:4][CH2:5][CH:6]=[CH:7][C:8]([CH3:10])=[CH2:9])[CH3:3])(=[O:14])[CH3:13]
Reactant: C=C(C)OC(C)=O
Reactant: C=C(C)C=CCCC(C)(C)O
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: CCCCCC
Product: C=C(C)C=CCCC(C)(C)OC(C)=O
Yield: 39.9 %

Procedure:
6.7 g of 2,7-dimethyl-5,7-octadien-2-ol, 13 g of isopropenyl acetate and 0.1 g of p-toluenesulphonic acid are heated at reflux for 3 hours in a three-necked flask provided with a thermometer, stirrer and reflux condenser. The mixture is taken up in 100 ml of hexane and washed with a saturated sodium bicarbonate solution and with water. The solvent is distilled off and the residue fractionally distilled. There are obtained 3.4 g of 2,7-dimethyl-5,7-octadien-2-ol acetate of boiling point 60° C/0.2 mm Hg; nD20 = 1.4675; d420 = 0.9077. The yield is 40% of theory.
Reaction SMILES: C(OC1C=C(C=CC=1)CN(C1C=CC(C#N)=CC=1)N1C=NN=C1)C1C=CC=CC=1.[H-].[Na+].[C:32]([C:34]1[CH:39]=[CH:38][C:37]([NH:40][N:41]2[CH:45]=[N:44][N:43]=[CH:42]2)=[CH:36][CH:35]=1)#[N:33].[C:46]([O:54][C:55]1[CH:56]=[C:57]([CH:60]=[CH:61][C:62]=1[Cl:63])[CH2:58]Br)(=[O:53])[C:47]1[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=1>CN(C=O)C.CCOC(C)=O>[C:46]([O:54][C:55]1[CH:56]=[C:57]([CH:60]=[CH:61][C:62]=1[Cl:63])[CH2:58][N:40]([C:37]1[CH:36]=[CH:35][C:34]([C:32]#[N:33])=[CH:39][CH:38]=1)[N:41]1[CH:42]=[N:43][N:44]=[CH:45]1)(=[O:53])[C:47]1[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=1
Reactant: O=C(Oc1cc(CBr)ccc1Cl)c1ccccc1
Reactant: N#Cc1ccc(Nn2cnnc2)cc1
Agent: N#Cc1ccc(N(Cc2cccc(OCc3ccccc3)c2)n2cnnc2)cc1
Agent: [H-]
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: N#Cc1ccc(N(Cc2ccc(Cl)c(OC(=O)c3ccccc3)c2)n2cnnc2)cc1
Yield: 82.5 %

Procedure:
The title compound was prepared by adapting the method for 4-[(3-benzyloxybenzyl)(4-cyanophenyl)amino]-4H-[1,2,4]triazole using NaH (60% dispersion in oil, 0.20 g, 5.0 mmol), 4-[(4-cyanophenyl)amino]-4H-[1,2,4]triazole (0.926 g, 5.0 mmol) and 3-benzoyloxy-4-chlorobenzyl bromide (1.63 g, 5.0 mmol) in anhydrous DMF (20 mL) to give 4-[(3-benzoyloxy-4-chlorobenzyl)(4-cyanophenyl)amino]-4H-[1,2,4]triazole as a white solid (1.773 g, 82%) after chromatography [SiO2, EtOAc (100%)]; δH (400 MHz, CDCl3) 4.93 (s, 2H), 6.66 (AA′BB′, 2H), 7.06 (dd, J=8.2, 2.0, 1H), 7.27 (d, J=2.0, 1H), 7.45 (d, J=8.2, 1H), 7.47-7.58 (m, 4H), 7.60-7.69 (m, 1H), 8.16-8.21 (m, 2H), 8.24 (s, 2H); LRMS (FAB+) m/z (rel. intensity) 430.1 (100, [M+H]+).
Reaction SMILES: CN(C=O)C.[OH:6][C:7]1[CH:8]=[C:9]([CH:12]=[C:13]([O:15][CH3:16])[CH:14]=1)[CH:10]=[O:11].N1C=CN=C1.Cl[Si:23]([CH:30]([CH3:32])[CH3:31])([CH:27]([CH3:29])[CH3:28])[CH:24]([CH3:26])[CH3:25]>C(OCC)(=O)C.O>[CH3:16][O:15][C:13]1[CH:12]=[C:9]([CH:8]=[C:7]([O:6][Si:23]([CH:30]([CH3:32])[CH3:31])([CH:27]([CH3:29])[CH3:28])[CH:24]([CH3:26])[CH3:25])[CH:14]=1)[CH:10]=[O:11]
Reactant: COc1cc(O)cc(C=O)c1
Reactant: CC(C)[Si](Cl)(C(C)C)C(C)C
Agent: c1c[nH]cn1
Solvent: CCOC(C)=O
Solvent: O
Solvent: CN(C)C=O
Product: COc1cc(C=O)cc(O[Si](C(C)C)(C(C)C)C(C)C)c1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
To a 50 ml DMF solution containing 2.8 g of 3-hydroxy-5-methoxybenzaldehyde [CAS No. 57179-35-8] there were added 2.5 g of imidazole and 5.9 ml of chlorotriisopropylsilane. The mixture was stirred at room temperature for 14 hours and 30 minutes. Water was added to the reaction mixture and extraction was performed with ethyl acetate. The organic layer was washed with ice-cooled 1N hydrochloric acid, water and saturated brine and then dried over anhydrous magnesium sulfate. The desiccating agent was filtered off and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate-heptane) to give the title compound (5.7 g) as a light yellow oil.
Reaction SMILES: C([O:4][CH2:5][CH:6]=[C:7]([CH3:9])[CH3:8])(=O)C.[CH3:10][C:11]([CH3:15])=[CH:12][CH:13]=O.C(O)(=O)C1C=CC=CC=1>>[CH3:10][C:11](=[CH:12][CH2:13][CH2:9][C:7](=[CH:6][CH:5]=[O:4])[CH3:8])[CH3:15]
Reactant: CC(=O)OCC=C(C)C
Reactant: CC(C)=CC=O
Agent: O=C(O)c1ccccc1
Product: CC(C)=CCCC(C)=CC=O
Yield: 48 %

Procedure:
60 parts of prenyl acetate, 40 parts of 3,3-dimethylacrolein and 2 parts of benzoic acid are heated together for five hours 30 minutes at 140° C and the product is worked up. 11.1 parts of citral is obtained having a boiling point of 104° C. at 12 mm in a yield of 48% at a conversion of 32% (based on 3,3-dimethylacrolein).