Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][N:2]([CH3:24])[CH2:3][CH2:4][C:5]1[C:13]2[C:8](=[CH:9][CH:10]=[C:11]([NH:14][C:15]3[C:20]([N+:21]([O-])=O)=[CH:19][CH:18]=[CH:17][N:16]=3)[CH:12]=2)[NH:7][CH:6]=1>[Pd].C(O)C>[CH3:24][N:2]([CH3:1])[CH2:3][CH2:4][C:5]1[C:13]2[C:8](=[CH:9][CH:10]=[C:11]([NH:14][C:15]3[C:20]([NH2:21])=[CH:19][CH:18]=[CH:17][N:16]=3)[CH:12]=2)[NH:7][CH:6]=1
Reactant: CN(C)CCc1c[nH]c2ccc(Nc3ncccc3[N+](=O)[O-])cc12
Agent: [Pd]
Solvent: CCO
Product: CN(C)CCc1c[nH]c2ccc(Nc3ncccc3N)cc12
Reaction time: 2 h
Yield: 64.2 %

Procedure:
A mixture of 3-(2-dimethylaminoethyl)-5-(3-nitropyrid-2-ylamino)-1H-indole (1.27 g, 3.90 mmol), 10% Pd on carbon (200 mg), and absolute ethanol (20 mL) was shaken under a hydrogen atmosphere (3 atm) for 2 hours. The reaction mixture was filtered through diatomaceous earth, and the filtrate was evaporated under reduced pressure. The residue was column chromatographed using silica gel (approximately 40 g) and elution with absolute methanol to afford the title compound (0.74 g, 64%) as an off-white solid: mp., 196.0°-198.0° C. with effervescence; 13C NMR (DMSO-d6) δ145.3, 134.5, 133.6, 132.1, 131.0, 127.3, 122.6, 118.8, 116.1, 114.2, 112.1, 110.8, 108.6, 60.1, 45.2, 23.4; HRMS calculated for C17H21N5 295.1793, found 295.1810. Anal. calcd. for C17H21N5.0.4 C2H6O [ethanol]: C, 68.13; H, 7.52; N, 22.32. Found: C, 68.12; H, 7.19; N, 22.51.
Reaction SMILES: [OH:1][CH:2]1[C@@H:7]2[C:8]([CH2:11][OH:12])=[CH:9][CH2:10][C@@H:6]2[C:5]([C:13]([O:15][CH3:16])=[O:14])=[CH:4][O:3]1.[Cr](Cl)([O-])(=O)=O.[NH+]1C=CC=CC=1.CCCCCC.C(OC(=O)C)C>C(Cl)Cl>[CH:11]([C:8]1[C@H:7]2[CH:2]([OH:1])[O:3][CH:4]=[C:5]([C:13]([O:15][CH3:16])=[O:14])[C@H:6]2[CH2:10][CH:9]=1)=[O:12]
Reactant: COC(=O)C1=COC(O)[C@@H]2C(CO)=CC[C@H]12
Agent: O=[Cr](=O)([O-])Cl
Agent: c1cc[nH+]cc1
Solvent: ClCCl
Solvent: CCOC(C)=O
Solvent: CCCCCC
Product: COC(=O)C1=COC(O)[C@@H]2C(C=O)=CC[C@H]12
Reaction time: 3 h
Yield: 75.9 %

Procedure:
0.5 g (2.21 mmol) of methyl (4aS,7aS)-1-hydroxy-7-hydroxymethyl-1,4a, 5,7a-tetrahydrocyclopenta[c]pyran4carboxylate was dissolved in 10 ml of dried methylene chloride, then 0.954 g (4.42 mmol) of pyridiniumchlorochromate was added thereto. The reaction solution was stirred for 3 hours, filtered through cellite and then the filtrate was concentrated. The residue was subjected to silica gel column chromatography (eluent: n-hexane/ethylacetate=2/1, v/v) to obtain 0.376 g (Yield 76%) of methyl (4aS,7aS)-7-formyl-1-hydroxy-1,4a,5,7a-tetrahydrocyclopenta[c]pyran-4-carboxylate.
Reaction SMILES: C(O)(=O)C.[N:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[CH2:11][CH2:12][C:13]1[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[N:16]=[CH:15][CH:14]=1>C(O)C.[Pt]=O>[NH:5]1[CH2:10][CH2:9][CH2:8][CH2:7][CH:6]1[CH2:11][CH2:12][C:13]1[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[N:16]=[CH:15][CH:14]=1
Reactant: c1ccc(CCc2ccnc3ccccc23)nc1
Agent: O=[Pt]
Solvent: CC(=O)O
Solvent: CCO
Product: c1ccc2c(CCC3CCCCN3)ccnc2c1
Reaction time: 8 h

Procedure:
30 ml of a 10 N aqueous solution of acetic acid are added to a solution containing 7 g of 4-[2-(2-pyridyl)-ethyl]-quinoline in 700 ml of ethanol, then 1.4 g of 82% platinum oxide is added as catalyst. Hydrogenation is effected at 45° C. under a hydrogen pressure equal to the normal pressure (1 bar) for 24 hours, being careful to replace the catalyst used every eight hours by fresh catalyst. At the end of the 24 hours (the quantity of hydrogen absorbed is then 2.9 liters), the catalyst is removed by filtration, the ethanol is evaporated under reduced pressure and the residue is taken up with 200 ml of water. The aqueous phase is extracted with chloroform, then made alkaline with concentrated ammonia and extracted with methylene chloride. The methylene chloride phase is dried over magnesium sulfate and evaporated under reduced pressure. The oily residue (6.3 g) is fixed on a column containing 630 g of silica, then eluted with a 9/1 toluene-diethylamine mixture. 1.9 g are thus isolated of 4-[2-(2-piperidyl)-ethyl]-quinoline.
Reaction SMILES: [O-]S(S([O-])=O)=O.[Na+].[Na+].[Cl:9][C:10]1[CH:15]=[CH:14][C:13]([C:16]2[O:17][C:18]3[CH:28]=[C:27]([N:29]([C:34]4[CH:39]=[CH:38][C:37]([N+:40]([O-])=O)=[C:36]([C:43]#[N:44])[CH:35]=4)[S:30]([CH3:33])(=[O:32])=[O:31])[C:26]([CH:45]4[CH2:47][CH2:46]4)=[CH:25][C:19]=3[C:20]=2[C:21]([NH:23][CH3:24])=[O:22])=[CH:12][CH:11]=1>O.C1COCC1>[NH2:40][C:37]1[CH:38]=[CH:39][C:34]([N:29]([C:27]2[C:26]([CH:45]3[CH2:47][CH2:46]3)=[CH:25][C:19]3[C:20]([C:21]([NH:23][CH3:24])=[O:22])=[C:16]([C:13]4[CH:12]=[CH:11][C:10]([Cl:9])=[CH:15][CH:14]=4)[O:17][C:18]=3[CH:28]=2)[S:30]([CH3:33])(=[O:32])=[O:31])=[CH:35][C:36]=1[C:43]#[N:44]
Reactant: CNC(=O)c1c(-c2ccc(Cl)cc2)oc2cc(N(c3ccc([N+](=O)[O-])c(C#N)c3)S(C)(=O)=O)c(C3CC3)cc12
Agent: O=S([O-])S(=O)[O-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: O
Product: CNC(=O)c1c(-c2ccc(Cl)cc2)oc2cc(N(c3ccc(N)c(C#N)c3)S(C)(=O)=O)c(C3CC3)cc12
Reaction time: 8 h
Yield: 90.1 %

Procedure:
A solution of Na2S2O4 (4.98 g, 28.6 mmol) in water (50 mL) was added dropwise to a solution of 2-(4-chlorophenyl)-6-(N-(3-cyano-4-nitrophenyl)methylsulfonamido)-5-cyclopropyl-N-methylbenzofuran-3-carboxamide (2.70 g, 4.77 mmol) in THF at room temperature under N2. The mixture was stirred overnight. More water was added and then extracted with EtOAc. The combined extracts were washed with brine, dried over Na2SO4. Concentrated under reduced pressure, the crude residue was purified by chromatography on silica gel eluted with 0-15% EtOAc in DCM to give the product (2.3 g, 83%) as a white solid. LCMS (m/z, ES+)=535 (M+H+).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[CH:5]=[C:4]([Cl:11])[C:3]=1[N:12]1[CH:22]=[C:15]2[CH:16]=[N+:17]([O-])[CH:18]=[C:19]([F:20])[C:14]2=[N:13]1.P(Cl)(Cl)([Cl:25])=O>ClCCCl>[Cl:25][C:16]1[C:15]2=[CH:22][N:12]([C:3]3[C:2]([Cl:1])=[CH:7][C:6]([N+:8]([O-:10])=[O:9])=[CH:5][C:4]=3[Cl:11])[N:13]=[C:14]2[C:19]([F:20])=[CH:18][N:17]=1
Reactant: O=P(Cl)(Cl)Cl
Reactant: O=[N+]([O-])c1cc(Cl)c(-n2cc3c[n+]([O-])cc(F)c3n2)c(Cl)c1
Solvent: ClCCCl
Product: O=[N+]([O-])c1cc(Cl)c(-n2cc3c(Cl)ncc(F)c3n2)c(Cl)c1
Temperature: 70 °C
Yield: 40.2 %

Procedure:
2-(2,6-Dichloro-4-nitrophenyl)-7-fluoro-2H-pyrazolo[4,3-c]pyridine 5-oxide (4.20 g, 12.24 mmol) was suspended in DCE (60 mL), under an atmosphere of nitrogen and phosphorus oxychloride (3.61 mL, 39.2 mmol) was added. The reaction mixture was heated at 70° C. for 95 minutes. The resultant mixture was cooled to room temperature and was carefully quenched by the addition of 10% aqueous sodium carbonate solution. The layers were separated and the aqueous layer was extracted with DCM (×4). The combined organic layers were filtered to remove insoluble solids, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (0-50% ethyl acetate in cyclohexane) to afford the title compound as a pale yellow solid (1.78 g, 40% yield). 1H NMR (300 MHz, CDCl3): δ 8.43 (s, 2H), 8.37 (d, J=2.2 Hz, 1H), 8.03 (d, J=3.0 Hz, 1H).
Reaction SMILES: [CH3:1][N:2]([CH3:23])[C:3](=O)[CH2:4][C:5]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[NH:7][C:6]=1C1C(CC)=NOC=1C.[H-].[Al+3].[Li+].[H-].[H-].[H-]>O1CCCC1>[CH3:1][N:2]([CH2:3][CH2:4][C:5]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[NH:7][CH:6]=1)[CH3:23]
Reactant: CCc1noc(C)c1-c1[nH]c2ccccc2c1CC(=O)N(C)C
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Product: CN(C)CCc1c[nH]c2ccccc12
Temperature: 25 °C
Reaction time: 2 h

Procedure:
A solution of 4.7 g. (0.015 mole) of N,N-dimethyl-2-(3-ethyl-5-methyl-4-isoxazolyl)-3-indoleacetamide in 47 ml. of tetrahydrofuran under nitrogen is added dropwise to a suspension of 2.28 g. (0.06 mole) lithium aluminum hydride in 50 ml. tetrahydrofuran, while maintaining the reaction at room temperature. The mixture is stirred for 11/2 hours at room temperature, cooled in ice and quenched with 5 ml. water in 50 ml. tetrahydrofuran. The resulting solids are filtered and the filtrate dried over anhydrous magnesium sulfate, filtered and evaporated and the residue crystallized from ether to give 2-(3-ethyl-5-methyl)-4-isoxazolyl)-3-(dimethylaminoethyl)-indole; m.p. 118° to 120° C.
Reaction SMILES: [H-].[Na+].[CH3:3][O:4][C:5]1[CH:34]=[CH:33][C:8]([CH2:9][N:10]([CH2:24][C:25]2[CH:30]=[CH:29][C:28]([O:31][CH3:32])=[CH:27][CH:26]=2)[C:11]2[CH:16]=[C:15]([F:17])[C:14]([C:18]([CH3:22])([CH3:21])[CH2:19][OH:20])=[C:13]([F:23])[CH:12]=2)=[CH:7][CH:6]=1.I[CH2:36][CH3:37].[Cl-].[NH4+]>CN(C=O)C>[CH2:36]([O:20][CH2:19][C:18]([C:14]1[C:13]([F:23])=[CH:12][C:11]([N:10]([CH2:9][C:8]2[CH:7]=[CH:6][C:5]([O:4][CH3:3])=[CH:34][CH:33]=2)[CH2:24][C:25]2[CH:26]=[CH:27][C:28]([O:31][CH3:32])=[CH:29][CH:30]=2)=[CH:16][C:15]=1[F:17])([CH3:22])[CH3:21])[CH3:37]
Reactant: COc1ccc(CN(Cc2ccc(OC)cc2)c2cc(F)c(C(C)(C)CO)c(F)c2)cc1
Reactant: CCI
Agent: [Cl-]
Agent: [H-]
Agent: [NH4+]
Solvent: CN(C)C=O
Product: CCOCC(C)(C)c1c(F)cc(N(Cc2ccc(OC)cc2)Cc2ccc(OC)cc2)cc1F
Temperature: 25 °C
Reaction time: 14 h
Yield: 105 %

Procedure:
Sodium hydride (60%, oil, 1.726 g, 43.15 mmol) was added to a solution of 2-(4-(bis(4-methoxybenzyl)amino)-2,6-difluorophenyl)-2-methylpropan-1-ol (7.62 g, 17.26 mmol) and iodoethane (3.49 mL, 43.15 mmol) in DMF (30 mL) at 5° C., and the mixture was stirred at room temperature for 14 hr. To the reaction mixture was added aqueous ammonium chloride solution, and the mixture was extracted with ethyl acetate (×2). The organic layer was washed with brine, and dried over magnesium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (Diol, solvent gradient; 5→20% ethyl acetate/hexane) to give 4-(1-ethoxy-2-methylpropan-2-yl)-3,5-difluoro-N,N-bis(4-methoxybenzyl)aniline (8.51 g, 18.12 mmol, 105%) as a colorless oil.
Reaction SMILES: I([O-])(=O)(=O)=[O:2].[Na+].[CH:7]1([S:12][C:13]2[CH:14]=[C:15]([CH2:19][CH2:20][CH2:21][CH2:22][O:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][N:30]3[CH2:34][C@@H:33]([C:35]4[CH:46]=[CH:45][C:38]5[O:39][C:40]([CH3:44])([CH3:43])[O:41][CH2:42][C:37]=5[CH:36]=4)[O:32][C:31]3=[O:47])[CH:16]=[CH:17][CH:18]=2)[CH2:11][CH2:10][CH2:9][CH2:8]1>C(O)C.O>[CH:7]1([S:12]([C:13]2[CH:14]=[C:15]([CH2:19][CH2:20][CH2:21][CH2:22][O:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][N:30]3[CH2:34][C@@H:33]([C:35]4[CH:46]=[CH:45][C:38]5[O:39][C:40]([CH3:43])([CH3:44])[O:41][CH2:42][C:37]=5[CH:36]=4)[O:32][C:31]3=[O:47])[CH:16]=[CH:17][CH:18]=2)=[O:2])[CH2:8][CH2:9][CH2:10][CH2:11]1
Reactant: CC1(C)OCc2cc([C@@H]3CN(CCCCCCOCCCCc4cccc(SC5CCCC5)c4)C(=O)O3)ccc2O1
Reactant: [O-][I+3]([O-])([O-])[O-]
Agent: [Na+]
Solvent: O
Solvent: CCO
Product: CC1(C)OCc2cc([C@@H]3CN(CCCCCCOCCCCc4cccc(S(=O)C5CCCC5)c4)C(=O)O3)ccc2O1
Yield: 66.2 %

Procedure:
Sodium periodate (1.5 g) was added to a stirred solution of (5R)-3-(6-{4-[3-(cyclopentylthio)phenyl]butoxy}hexyl)-5-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)-1,3-oxazolidin-2-one (1.0 g) in ethanol (20 ml) and water (10 ml) at room temperature. After 2 h the solution was concentrated in-vacuo (ca 50% vol), diluted with water and extracted into dichloromethane. The extracts were dried (Na2SO4) and evaporated to dryness. The residual oil was purified on a biotage cartridge (40 g) using ethyl acetate as the eluent. The appropriate fractions were evaporated to give the title compound (0.68 g). LCMS RT=3.66 min
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[S:7]([C:10]1[CH:15]=[CH:14][C:13]([C:16](=O)[CH3:17])=[CH:12][CH:11]=1)(=[O:9])=[O:8].Cl.[NH2:20][O:21][CH2:22][CH2:23][O:24][C:25]1[CH:38]=[CH:37][C:28]([CH2:29][CH:30]2[S:34][C:33](=[O:35])[NH:32][C:31]2=[O:36])=[CH:27][CH:26]=1>>[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[S:7]([C:10]1[CH:15]=[CH:14][C:13]([C:16](=[N:20][O:21][CH2:22][CH2:23][O:24][C:25]2[CH:26]=[CH:27][C:28]([CH2:29][CH:30]3[S:34][C:33](=[O:35])[NH:32][C:31]3=[O:36])=[CH:37][CH:38]=2)[CH3:17])=[CH:12][CH:11]=1)(=[O:9])=[O:8]
Reactant: CC(=O)c1ccc(S(=O)(=O)c2ccccn2)cc1
Reactant: NOCCOc1ccc(CC2SC(=O)NC2=O)cc1
Agent: Cl
Product: CC(=NOCCOc1ccc(CC2SC(=O)NC2=O)cc1)c1ccc(S(=O)(=O)c2ccccn2)cc1
Yield: 61.3 %

Procedure:
Following a procedure similar to that described in Example 40(f), 150 mg of 4'-(2-pyridylsulfonyl)-acetophenone were reacted with 183 mg of 5-[4-(2-aminooxyethoxy)benzyl]thiazolidine-2,4-dione hydrochloride [prepared as described in Example 40(e)]. The reaction mixture was then concentrated by evaporation under reduced pressure, and the resulting residue was extracted with ethyl acetate. The extract was washed with water and the solvent was removed by distillation under reduced pressure. The residue was purified by column chromatography through silica gel, using a 2:98 by volume mixture of methanol and methylene chloride as the eluent, to give 185 mg of the title compound as a gum.
Reaction SMILES: [CH:1]1([Mg]Br)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[CH3:9][O:10][C:11]1[CH:12]=[C:13]([N:17]2[CH:21]=[C:20]([CH:22]=[O:23])[C:19]([CH3:24])=[N:18]2)[CH:14]=[CH:15][CH:16]=1>O1CCCC1>[CH:1]1([CH:22]([C:20]2[C:19]([CH3:24])=[N:18][N:17]([C:13]3[CH:14]=[CH:15][CH:16]=[C:11]([O:10][CH3:9])[CH:12]=3)[CH:21]=2)[OH:23])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: Br[Mg]C1CCCCC1
Reactant: COc1cccc(-n2cc(C=O)c(C)n2)c1
Solvent: C1CCOC1
Product: COc1cccc(-n2cc(C(O)C3CCCCC3)c(C)n2)c1
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 70 %

Procedure:
To a solution (15 mL) of in 1-(3-methoxyphenyl)-3-methyl-1H-pyrazole-4-carbaldehyde (0.62 g) synthesized in the above-mentioned (2) in tetrahydrofuran under ice-cooling was added dropwise cyclohexylmagnesium bromide (4.3 mL, 1M tetrahydrofuran solution). After the completion of the dropwise addition, the ice bath was removed, and the mixture was stirred at room temperature for 15 min. To the reaction mixture was added aqueous ammonium chloride solution, and the mixture was extracted with ethyl acetate. The extract was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate:hexane=1:2, volume ratio) to give the title object compound (0.60 g, 70%) as a pale-yellow oil.
Reaction SMILES: C[N:2]([CH3:7])[CH:3]=[CH:4][CH:5]=[O:6].Cl.[Cl:9][C:10]1[C:19]([Cl:20])=[CH:18][CH:17]=[CH:16][C:11]=1[C:12](=O)CN.CC[O-].[Na+].Cl>C(O)C>[CH:5]([C:4]1[C:12]([C:11]2[CH:16]=[CH:17][CH:18]=[C:19]([Cl:20])[C:10]=2[Cl:9])=[CH:7][NH:2][CH:3]=1)=[O:6]
Reactant: CN(C)C=CC=O
Reactant: NCC(=O)c1cccc(Cl)c1Cl
Agent: CC[O-]
Agent: Cl
Agent: [Na+]
Solvent: CCO
Product: O=Cc1c[nH]cc1-c1cccc(Cl)c1Cl
Temperature: 25 °C

Procedure:
5.4 g of 3-dimethylaminoacrolein, 3.2 g of 2,3-dichlorophenacylamine hydrochloride and 60 ml of ethanol are heated for 11/2 hours under reflux. Then a solution of sodium ethylate in ethanol (prepared from 1 g of sodium and 15 ml of ethanol) is added dropwise and the reaction mixture is heated under reflux for another 30 minutes. After it has cooled to room temperature, the reaction mixture is poured into ice/water and neutralised with hydrochloric acid. The precipitate is washed with water, dried in vacuo, and the dry residue is purified by column chromatography (silica gel; elution with a 4:1 mixture of toluene/ethyl acetate). M.p. 152°-154° C. IR (solid/KBr) in cm-1 : 1655 (CO). 1H-NMR (CDCL3) in ppm: 7.0 (broad s, 1H); 7.3 (m, 2H); 9.66 (s, 1H); 11,9 (s, 1H, H replaceable with D2O). Mass peak at 204. This substance is novel, has fungicidal activity, and falls within the ambit of the invention.
Reaction SMILES: [C:1]1(C(OC)=O)([C:7]([O:9][CH3:10])=[O:8])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[O-2].[Al+3].[O-2].[O-2].[Al+3]>CO>[CH:1]1([C:7]([O:9][CH3:10])=[O:8])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: COC(=O)C1(C(=O)OC)CCCCC1
Agent: [Al+3]
Agent: [O-2]
Solvent: CO
Product: COC(=O)C1CCCCC1
Yield: 316 %

Procedure:
Per hour a solution of 4.5 g of dimethyl 1,1-cyclohexanedicarboxylate in 4.5 g of methanol was passed at 275° C. over 5 g of aluminum oxide. The exit mixture obtained over 6 hours (36.5 g) was distilled to yield 10.1 g of methyl cyclohexanecarboxylate (53%, based on diester used) and 7.7 g of the starting material.
Reaction SMILES: C(OC(=O)[NH:7][C:8]1[CH:13]=[C:12]([CH3:14])[C:11]([N:15]([CH3:19])[CH2:16][CH2:17][CH3:18])=[CH:10][C:9]=1[NH:20][C:21](=O)[CH2:22][C:23]([C:25]1C=C[CH:28]=[C:27]([C:31]#[N:32])[CH:26]=1)=O)(C)(C)C.[C:35](O)([C:37](F)(F)F)=[O:36]>C(Cl)Cl>[CH3:14][C:12]1[C:11]([N:15]([CH3:19])[CH2:16][CH2:17][CH3:18])=[CH:10][C:9]2[N:20]=[C:21]([C:22]3[CH:28]=[C:27]([CH:26]=[CH:25][CH:23]=3)[C:31]#[N:32])[CH2:37][C:35](=[O:36])[NH:7][C:8]=2[CH:13]=1
Reactant: O=C(O)C(F)(F)F
Reactant: CCCN(C)c1cc(NC(=O)CC(=O)c2cccc(C#N)c2)c(NC(=O)OC(C)(C)C)cc1C
Solvent: ClCCl
Product: CCCN(C)c1cc2c(cc1C)NC(=O)CC(c1cccc(C#N)c1)=N2

Procedure:
The title compound was prepared from [2-[3-(3-cyano-phenyl)-3-oxo-propionylamino]-5-methyl-4-(methyl-propyl-amino)-phenyl]-carbamic acid tert-butyl ester (Example M79) (0.17 g, 0.37 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (74 mg, 58%).
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:17]=[CH:16][C:12]([C:13](O)=[O:14])=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.S(Cl)([Cl:20])=O>ClCCl.CN(C=O)C>[CH2:1]([O:8][C:9]1[CH:17]=[CH:16][C:12]([C:13]([Cl:20])=[O:14])=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=S(Cl)Cl
Reactant: O=C(O)c1ccc(OCc2ccccc2)cc1
Solvent: ClCCl
Solvent: CN(C)C=O
Product: O=C(Cl)c1ccc(OCc2ccccc2)cc1

Procedure:
To a mixture of 4-benzyloxybenzoic acid (2.28 g, 10 mmole) in 20 ml dried dichloromethane were added five drops of DMF and 2.5 ml thionyl chloride. The mixture was refluxed for three hours and evaporated under reduced pressure. Yield: 2.45 g=100%
Reaction SMILES: [H-].[Na+].[F:3][C:4]1[CH:23]=[CH:22][C:7]([CH2:8][N:9]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[C:12](=[O:19])[N:11]=[C:10]2[NH:20][CH3:21])=[CH:6][CH:5]=1.[CH3:24]I>CC(N(C)C)=O>[F:3][C:4]1[CH:5]=[CH:6][C:7]([CH2:8][N:9]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[C:12](=[O:19])[N:11]=[C:10]2[N:20]([CH3:24])[CH3:21])=[CH:22][CH:23]=1
Reactant: CI
Reactant: CNc1nc(=O)c2ccccc2n1Cc1ccc(F)cc1
Agent: [H-]
Agent: [Na+]
Solvent: CC(=O)N(C)C
Product: CN(C)c1nc(=O)c2ccccc2n1Cc1ccc(F)cc1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
To a suspension of 0.4 g. of sodium hydride in 25 ml. of dimethylacetamide is added 2.0 g. of 1-(4'-fluorobenzyl)-2-methylamino-quinazolin-4(1H)-one. The resulting mixture is stirred for 30 minutes at room temperature and there is then added 1.5 g. of methyliodide. The resulting mixture is stirred at room temperature for 3 days, poured over ice/water, extracted twice with methylene chloride, washed twice with water, dried and evaporated in vacuo. The residue is dissolved in methylene chloride and the methylene chloride exchanged for ether on a steam bath to obtain 1-(4'-fluorobenzyl)-2-dimethylamino-quinazolin-4(1H)-one, m.p. 160°-169°C.
Reaction SMILES: I[C:2]1[C:3](=[O:18])[NH:4][C:5](=[O:17])[N:6]([CH:16]=1)[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O.C(OC(=O)C)(=O)C.N1C=C[CH:29]=[CH:28][CH:27]=1>>[C:27]([C:2]1[C:3](=[O:18])[NH:4][C:5](=[O:17])[NH:6][CH:16]=1)#[C:28][CH3:29]
Reactant: O=c1[nH]c(=O)n([C@@H]2O[C@H](CO)[C@@H](O)[C@H]2O)cc1I
Reactant: c1ccncc1
Solvent: CC(=O)OC(C)=O
Product: CC#Cc1c[nH]c(=O)[nH]c1=O
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
A dry 250 mL round-bottomed flask was charged with 5-iodouridine (10 g, 27 mmol Aldrich), anhydrous pyridine (30 mL) and acetic anhydride (30mL). The reaction was stirred at room temperature for 30 minutes under a nitrogen atmosphere and the solvent removed in vacuo. The compound was diluted with toluene (2 ×50 mL) and the toluene removed in vacuo. The product was purified on a 75 g flash chromatography column which was eluted with 90:10 (v:v) CHC13 :MeOH. The appropriate fractions were combined and concentrated to give the title compound as a white foam. This was used directly in the next stage.
Reaction SMILES: [CH2:1]([Mg]Br)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12].Cl[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1Cl>>[CH2:1]([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1[CH2:12][CH2:11][CH2:10][CH2:9][CH2:8][CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2][CH3:1])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12]
Reactant: CCCCCCCCCCCC[Mg]Br
Reactant: Clc1ccccc1Cl
Product: CCCCCCCCCCCCc1ccccc1CCCCCCCCCCCC

Procedure:
1,2-Didodecylbenzene was synthesized with reference to the method described in “Synthesis”, 1993, pp. 387-390 from 1,2-dichlorobenzene and n-dodecylmagnesium bromide as follows.
Reaction SMILES: C([O:3][C:4]([C:6]1[C:7]([C:12]2[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=2)=[N:8][O:9][C:10]=1[CH3:11])=O)C.[H-].[Al+3].[Li+].[H-].[H-].[H-].O.[OH-].[Na+]>C1COCC1>[F:18][C:15]1[CH:14]=[CH:13][C:12]([C:7]2[C:6]([CH2:4][OH:3])=[C:10]([CH3:11])[O:9][N:8]=2)=[CH:17][CH:16]=1
Reactant: CCOC(=O)c1c(-c2ccc(F)cc2)noc1C
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: O
Solvent: C1CCOC1
Product: Cc1onc(-c2ccc(F)cc2)c1CO
Temperature: 25 °C
Reaction time: 3 h
Yield: 72.4 %

Procedure:
To a solution of 3-(4-fluoro-phenyl)-5-methyl-isoxazole-4-carboxylic acid ethyl ester (3.0 g, 12 mmol) (6.18 g, 25 mmol) in THF (320 mL) was added portionwise lithiumaluminiumhydride (528 mg, 14 mmol) at 0° C. and the reaction mixture was stirred at room temperature for 3 h. The mixture was then cooled to 0° C. and water (518 μL) added followed by sodium hydroxide (15% solution, 518 μL) and then again water (1.5 mL) and the mixture then stirred overnight at room temperature. The precipitate was then filtered off and washed with THF. The combined washings and filtrate were then evaporated. Purification by chromatography (SiO2, heptane:ethyl acetate=100:0 to 1:1) afforded the title compound (1.8 g, 71%) which was obtained as a white solid. MS: m/e=208.1 [M+H]+.
Reaction SMILES: C(O)(=O)C(C)(C)C.[CH3:8][C:9]1([CH3:29])[C:21]2[CH:20]=[C:19]([NH:22][C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[CH:18]=[CH:17][C:16]=2[C:15]2[C:10]1=[CH:11][CH:12]=[CH:13][CH:14]=2.C(=O)([O-])[O-].[K+].[K+].C([O-])([O-])=O.[Na+].[Na+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.ClCCl>[CH3:8][C:9]1([CH3:29])[C:21]2=[CH:20][C:19]3[NH:22][C:23]4[C:28]([C:18]=3[CH:17]=[C:16]2[C:15]2[C:10]1=[CH:11][CH:12]=[CH:13][CH:14]=2)=[CH:27][CH:26]=[CH:25][CH:24]=4
Reactant: CC1(C)c2ccccc2-c2ccc(Nc3ccccc3)cc21
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: CC(C)(C)C(=O)O
Solvent: ClCCl
Product: CC1(C)c2ccccc2-c2cc3c(cc21)[nH]c1ccccc13
Temperature: 120 °C
Reaction time: 9 h

Procedure:
35 ml of pivalic acid are added to 10 g of (9,9-dimethyl-9H-fluoren-2-yl)phenylamine (35 mmol), 0.4 g of palladium(II)acetate (1.78 mmol) and 0.5 g of potassium carbonate (3.62 mmol), and the mixture is stirred at 120° C. for 9 h. After this time, 0.4 g of palladium(II)acetate (1.78 mmol) is added, and the mixture is stirred at 120° C. for a further 9 h. 200 ml of dichloromethane and 0.1 M Na2CO3 solution are then added. The mixture is partitioned between water and dichloromethane, the aqueous phase is extracted three times with dichloromethane, and the combined organic phases are dried over Na2SO4 and evaporated in a rotary evaporator. The residue is recrystallised from toluene/heptane. The yield is 5 g (5 mmol, 50%).