Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [OH-].[Na+].C([O:6][C:7]1[C:8]([CH3:32])=[C:9]2[C:14](=[C:15]([CH3:18])[C:16]=1[CH3:17])[O:13][C:12]([CH3:30])([CH2:19][O:20][C:21]1[CH:26]=[CH:25][C:24]([N+:27]([O-:29])=[O:28])=[CH:23][CH:22]=1)[CH2:11][C:10]2=[O:31])(=O)C.Br[CH2:34][C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36].Cl>O.C(O)C.CN(C)C=O>[C:38]([O:37][C:35]([CH2:34][O:6][C:7]1[C:8]([CH3:32])=[C:9]2[C:14](=[C:15]([CH3:18])[C:16]=1[CH3:17])[O:13][C:12]([CH3:30])([CH2:19][O:20][C:21]1[CH:26]=[CH:25][C:24]([N+:27]([O-:29])=[O:28])=[CH:23][CH:22]=1)[CH2:11][C:10]2=[O:31])=[O:36])([CH3:41])([CH3:40])[CH3:39]
Reactant: CC(=O)Oc1c(C)c(C)c2c(c1C)C(=O)CC(C)(COc1ccc([N+](=O)[O-])cc1)O2
Reactant: CC(C)(C)OC(=O)CBr
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CN(C)C=O
Solvent: CCO
Solvent: O
Product: Cc1c(C)c2c(c(C)c1OCC(=O)OC(C)(C)C)C(=O)CC(C)(COc1ccc([N+](=O)[O-])cc1)O2
Reaction time: 3 h

Procedure:
A mixture of 5.6 g of sodium hydroxide, 150 ml of ethanol and 20 ml of water was added dropwise to a mixture of 25 g of 6-acetoxy-2,5,7,8-tetramethyl-2-(4-nitrophenoxymethyl)chroman-4-one (prepared as described in Preparation 47), 30 ml of dimethylformamide and 150 ml of ethanol, whilst ice-cooling, and the reaction mixture was stirred for 3 hours. 18.3 g of t-butyl bromoacetate were then added. The reaction mixture was stirred for 1 hour at room temperature and then allowed to stand overnight. After this, the reaction mixture was poured into water, neutralized with a 10% w/v aqueous hydrogen chloride solution and extracted with benzene. This extract was washed with water and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography eluted with a 20:1 by volume mixture of benzene and ethyl acetate, to give the title compound.
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]([N:8]2[CH2:12][CH2:11][CH2:10][C@@H:9]2[CH2:13][N:14]2C(=O)C3C(=CC=CC=3)C2=O)[CH:5]=[CH:6][CH:7]=1.CO>C(O)C.O.NN.C(Cl)Cl>[CH3:1][C:2]1[CH:3]=[C:4]([N:8]2[CH2:12][CH2:11][CH2:10][C@@H:9]2[CH2:13][NH2:14])[CH:5]=[CH:6][CH:7]=1
Reactant: Cc1cccc(N2CCC[C@@H]2CN2C(=O)c3ccccc3C2=O)c1
Agent: NN
Solvent: O
Solvent: ClCCl
Solvent: CO
Product: Cc1cccc(N2CCC[C@@H]2CN)c1
Yield: 104.5 %

Procedure:
A solution of D6 (5.80 g, 0.018 mol) in ethanol (60 ml) and hydrazine hydrate (2 .eq., 2 ml) was heated at reflux for 1 h and cooled. The resulting precipitate was filtered and filtrate concentrated under reduced pressure to leave an oil. Chromatography on silica gel eluting with methanol in DCM (gradient elution, maximum 10%) afforded the product as an oil (3.58 g, 94%).
Reaction SMILES: F[C:2]1[CH:3]=[CH:4][C:5]([N+:9]([O-:11])=[O:10])=[C:6]([CH:8]=1)[NH2:7].[CH3:12][C@H:13]1[NH:18][CH2:17][C@@H:16]([CH2:19][N:20]([CH3:22])[CH3:21])[O:15][CH2:14]1.C(N(CC)CC)C.CN1C(=O)CCC1>C(Cl)Cl>[NH2:7][C:6]1[CH:8]=[C:2]([N:18]2[C@H:13]([CH3:12])[CH2:14][O:15][C@@H:16]([CH2:19][N:20]([CH3:21])[CH3:22])[CH2:17]2)[CH:3]=[CH:4][C:5]=1[N+:9]([O-:11])=[O:10]
Reactant: Nc1cc(F)ccc1[N+](=O)[O-]
Reactant: C[C@@H]1CO[C@H](CN(C)C)CN1
Solvent: ClCCl
Solvent: CN1CCCC1=O
Solvent: CCN(CC)CC
Product: C[C@@H]1CO[C@@H](CN(C)C)CN1c1ccc([N+](=O)[O-])c(N)c1
Temperature: 140 °C

Procedure:
A mixture of 5-fluoro-2-nitroaniline (1.1 equivalents), [((2S,5R)-5-methylmorpholin-2-yl)methyl]dimethylamine (1 equivalent), triethylamine (3 equivalents), and NMP was heated at 140° C. for 48 hours in a sealed high pressure vessel. The reaction mixture was cooled to 25° C. and dissolved in CH2Cl2. The solution was washed with water (2×) and dried (Na2SO4). Purification via chromatography on silicagel (10% MeOH in dichloromethane), afforded the desired product as a dark yellow foam. LC/MS m/z 295.2 (MH+) Rt 1.86 minutes.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[CH:10]=[C:9]([OH:12])[CH:8]=[CH:7]2.[N+:13]([C:16]1[CH:21]=[CH:20][C:19]([S:22](Cl)(=[O:24])=[O:23])=[CH:18][CH:17]=1)([O-:15])=[O:14].CC(O)=O>N1C=CC=CC=1.CCCCCC>[N+:13]([C:16]1[CH:17]=[CH:18][C:19]([S:22]([NH:1][C:2]2[CH:3]=[CH:4][CH:5]=[C:6]3[C:11]=2[CH:10]=[C:9]([OH:12])[CH:8]=[CH:7]3)(=[O:24])=[O:23])=[CH:20][CH:21]=1)([O-:15])=[O:14]
Reactant: Nc1cccc2ccc(O)cc12
Reactant: O=[N+]([O-])c1ccc(S(=O)(=O)Cl)cc1
Solvent: CC(=O)O
Solvent: c1ccncc1
Solvent: CCCCCC
Product: O=[N+]([O-])c1ccc(S(=O)(=O)Nc2cccc3ccc(O)cc23)cc1
Temperature: 0 °C
Yield: 46.5 %

Procedure:
A mixture of 8-amino-2-hydroxynapthalene (50 g, 0.3 mole) and 4-nitrobenzenesulfonyl chloride (55 g, 0.25 mole) in pyridine (500 ml) was heated under reflux for 2.5 hours then allowed to stand O/N. The mixture was poured in ice water and acidified with HOAc. The precipitated product was boiled in hexane and then recrystallized from ethyl acetate-hexane to give 40 g of green product (47%). This material was used in Part B.
Reaction SMILES: [F:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[C:5]([C:11]([O:13][CH3:14])=[O:12])[NH:6]2.[H-].[Na+].I[CH3:18].O>CN(C)C=O>[F:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[C:5]([C:11]([O:13][CH3:14])=[O:12])[N:6]2[CH3:18]
Reactant: CI
Reactant: COC(=O)c1cc2c(F)cccc2[nH]1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: COC(=O)c1cc2c(F)cccc2n1C
Yield: 105.2 %

Procedure:
To methyl 4-fluoro-1h-indole-2-carboxylate (1.211 mmol, 234 mg) in N,N-dimethylformamide (10 ml) at 0° C. was added sodium hydride (1.817 mmol, 72.7 mg). The reaction mixture was stirred for one hour at room temperature before iodomethane (1.817 mmol, 0.113 ml, 258 mg) was added. After stirring for three hours water was added and the product was extracted with dichloromethane and concentrated in vacuo to give methyl 4-fluoro-1-methyl-1H-indole-2-carboxylate (264 mg). The latter compound was dissolved in ethanol (5 ml). Then 2 N aqueous sodium hydroxide (5.84 mmol, 2.92 ml) and potassium hydroxide (1.168 mmol, 65.5 mg) were added and the reaction mixture was stirred at 80° C. over night. 2N Hydrochloric acid was added to the reaction mixture and extracted three times with ethyl acetate. The combined organic layers were washed with brine, dried (sodium sulfate) and concentrated to give 4-fluoro-1-methyl-1H-indole-2-carboxylic acid (189 mg).
Reaction SMILES: C[O:2][C:3](=[O:25])[C:4]1[CH:9]=[CH:8][C:7]([CH2:10][O:11][CH2:12][C:13]2[CH:14]=[N:15][CH:16]=[CH:17][CH:18]=2)=[CH:6][C:5]=1[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.[OH-].[Li+]>CO>[N:15]1[CH:16]=[CH:17][CH:18]=[C:13]([CH2:12][O:11][CH2:10][C:7]2[CH:8]=[CH:9][C:4]([C:3]([OH:25])=[O:2])=[C:5]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[CH:6]=2)[CH:14]=1
Reactant: COC(=O)c1ccc(COCc2cccnc2)cc1-c1ccccc1
Agent: [Li+]
Agent: [OH-]
Solvent: CO
Product: O=C(O)c1ccc(COCc2cccnc2)cc1-c1ccccc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 93.6 %

Procedure:
To a solution in methanol (5 mL) of [4-(3-pyridylmethyloxymethyl)-2-phenylbenzoic acid methyl ester (0.58 g), prepared as in Example 183A, was added saturated aqueous lithium hydroxide and the reaction mixture was stirred overnight at ambient temperature. The reaction mixture was warmed to 60° C. and stirred for 4 hours. The reaction mixture was concentrated in vacuo and the residue was taken up in water. The aqueous phase was taken to pH 5 with aqueous 3N HCl and extracted with chloroform. The organic phase was concentrated in vacuo to give 4-(3-pyridylmethyloxymethyl)-2-phenylbenzoic acid (0.52 g).
Reaction SMILES: C(OC1C=C([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([CH:21]([C:23]3[O:24][C:25]([CH3:28])=[N:26][N:27]=3)[OH:22])[CH:16]=2)C=CC=1)C1C=CC=CC=1.C(=O)C1C=CC=[C:32]([O:36]C)C=1.CN1NC=CO1>>[CH3:32][O:36][C:15]1[CH:16]=[C:17]([CH:21]([C:23]2[O:24][C:25]([CH3:28])=[N:26][N:27]=2)[OH:22])[CH:18]=[CH:19][CH:20]=1
Reactant: Cc1nnc(C(O)c2cccc(-c3cccc(OCc4ccccc4)c3)c2)o1
Reactant: COc1cccc(C=O)c1
Agent: CN1NC=CO1
Product: COc1cccc(C(O)c2nnc(C)o2)c1
Yield: 53.4 %

Procedure:
The synthesis was carried out analogous to the preparation of 77 using 79 (0.14 g, 1.03 mmol) and 63 (0.29 g, 3.45 mmol). Purification by flash column chromatography on silica gel gave compound 80 (0.12 g, 53.4% yield) as a viscous liquid.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[C:9]1[N:10]2[N:17]=[C:16]([CH3:18])[C:15]([NH2:19])=[C:11]2[O:12][C:13]=1[CH3:14].C(N(CC)CC)C.[C:27](Cl)(=[O:30])[CH2:28][CH3:29]>C(Cl)Cl>[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[C:9]1[N:10]2[N:17]=[C:16]([CH3:18])[C:15]([NH:19][C:27](=[O:30])[CH2:28][CH3:29])=[C:11]2[O:12][C:13]=1[CH3:14]
Reactant: Cc1nn2c(-c3ccc(Cl)cc3Cl)c(C)oc2c1N
Reactant: CCC(=O)Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CCC(=O)Nc1c(C)nn2c(-c3ccc(Cl)cc3Cl)c(C)oc12
Reaction time: 2 h

Procedure:
To a suspension of 3-(2,4-dichloro-phenyl)-2,6-dimethyl-pyrazolo[5,1-b]oxazol-7-ylamine (Intermediate ID) (500 mg, 1.503 mmol) in DCM (10 ml) under N2 is added triethylamine (0.461 ml, 3.31 mmol) followed by propionyl chloride (0.144 ml, 1.654 mmol) at 0° C. After 2 hr, the reaction mixture is diluted with DCM (50 ml) and washed with 1M HCl, NaHCO3, Brine, dried (MgSO4) and evaporated down to give a pink solid. This is then triturated with Et2O to give the title compound as an off white solid. MS: n/z 351.9[M+H]+
Reaction SMILES: [O-2].[La+3:2].[O-2].[O-2].[La+3].[N+]([O-])(O)=O.[C:10]([OH:15])(=[O:14])[C:11]([OH:13])=[O:12]>O>[C:10]([O-:15])(=[O:14])[C:11]([O-:13])=[O:12].[La+3:2].[C:10]([O-:15])(=[O:14])[C:11]([O-:13])=[O:12].[C:10]([O-:15])(=[O:14])[C:11]([O-:13])=[O:12].[La+3:2]
Reactant: O=C(O)C(=O)O
Agent: [La+3]
Agent: [O-2]
Solvent: O
Solvent: O=[N+]([O-])O
Product: O=C([O-])C(=O)[O-]
Temperature: 25 °C
Yield: 193.3 %

Procedure:
50 g (0.15 mol) of untreated lanthanum oxide (Fluka) were converted to the nitrates by adding 68.39 ml of concentrated nitric acid and 1.5 1 of demineralized water. During this, the solution was stirred and gently heated in order to speed up the dissolution process. After cooling the solution to room temperature, 84.27 g (0.67 mol, 1.5 equiv.) of oxalic acid, dissolved in 500 ml of demineralized water, were added with stirring and lanthanum oxalate was precipitated out. Decantation and filtration through a Buchner funnel were then carried out. The resulting white solid was dried overnight in a drying cabinet at 110° C. 78.43 g (0.145 mol, 94.3% of theory) of lanthanum oxalate were obtained. 2 g of the lanthanum oxalate were then calcined in air in a tubular furnace at 650° C. for 18 hours. After cooling to 50° C. in the stream of nitrogen, the prepared, white lanthanum oxide was transferred to a Schlenk tube filled with argon. A further 6 g of lanthanum oxalate were calcined to lanthanum oxide for 18 hours in the muffle furnace at 700° C., cooled in the desiccator and likewise stored in a Schlenk tube under argon.
Reaction SMILES: [F:1][C:2]([F:23])([F:22])[C:3]1[CH:17]=[C:16]([C:18]([F:21])([F:20])[F:19])[CH:15]=[CH:14][C:4]=1[CH2:5][N:6]1[CH2:11][CH2:10][CH:9]([CH:12]=O)[CH2:8][CH2:7]1.[O:24]=[C:25]1[CH2:29][CH2:28][CH2:27][N:26]1[CH2:30][CH2:31][CH2:32][NH:33][C:34]1[CH2:38][S:37][C:36](=[O:39])[N:35]=1.C([O-])(=O)C.[NH2+]1CCCCC1>CC(O)C>[F:23][C:2]([F:1])([F:22])[C:3]1[CH:17]=[C:16]([C:18]([F:21])([F:20])[F:19])[CH:15]=[CH:14][C:4]=1[CH2:5][N:6]1[CH2:11][CH2:10][CH:9](/[CH:12]=[C:38]2/[C:34]([NH:33][CH2:32][CH2:31][CH2:30][N:26]3[CH2:27][CH2:28][CH2:29][C:25]3=[O:24])=[N:35][C:36](=[O:39])[S:37]/2)[CH2:8][CH2:7]1
Reactant: O=C1N=C(NCCCN2CCCC2=O)CS1
Reactant: O=CC1CCN(Cc2ccc(C(F)(F)F)cc2C(F)(F)F)CC1
Agent: C1CC[NH2+]CC1
Agent: CC(=O)[O-]
Solvent: CC(C)O
Product: O=C1N=C(NCCCN2CCCC2=O)/C(=C/C2CCN(Cc3ccc(C(F)(F)F)cc3C(F)(F)F)CC2)S1
Temperature: 60 °C
Reaction time: 8 h
Yield: 53 %

Procedure:
To a solution of 1-[2,4-bis(trifluoromethyl)benzyl]piperidine-4-carbaldehyde (500 mg) in 2-propanol (10 mL) were added 4-([3-(2-oxopyrrolidin-1-yl)propyl]amino)thiazol-2(5H)-one (866 mg) and piperidinium acetate (107 mg). The reaction mixture was stirred at 60° C. overnight, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane) and recrystallized from ethyl acetate/heptane to give the title compound (439 mg).
Reaction SMILES: [C:1]([N:18]1[C:22]2[CH:23]=[CH:24][CH:25]=[CH:26][C:21]=2[N:20]=[N:19]1)(=[O:17])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14]CC.C(OC(C)(C)C)(=O)C>>[C:1]([N:18]1[C:22]2[CH:23]=[CH:24][CH:25]=[CH:26][C:21]=2[N:20]=[N:19]1)(=[O:17])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH3:14]
Reactant: CCCCCCCCCCCCCCCC(=O)n1nnc2ccccc21
Solvent: CC(=O)OC(C)(C)C
Product: CCCCCCCCCCCCCC(=O)n1nnc2ccccc21

Procedure:
1-hexadecanoylbenzotriazole, DSC 62.4° C. (recryst. from tert-butyl acetate).
Reaction SMILES: [Cl-].[Al+3].[Cl-].[Cl-].[H-].[Al+3].[Li+].[H-].[H-].[H-].[F:11][C:12]1[CH:42]=[CH:41][C:15]([C:16]([NH:18][C:19]2[C:20]([CH3:40])=[C:21]([CH3:39])[C:22]3[O:26][C:25]([CH3:27])=[C:24]([C:28]4[CH:33]=[CH:32][C:31]([CH:34]([CH3:36])[CH3:35])=[CH:30][CH:29]=4)[C:23]=3[C:37]=2[CH3:38])=O)=[CH:14][CH:13]=1.[OH-].[Na+]>O1CCCC1>[F:11][C:12]1[CH:13]=[CH:14][C:15]([CH2:16][NH:18][C:19]2[C:20]([CH3:40])=[C:21]([CH3:39])[C:22]3[O:26][C:25]([CH3:27])=[C:24]([C:28]4[CH:33]=[CH:32][C:31]([CH:34]([CH3:35])[CH3:36])=[CH:30][CH:29]=4)[C:23]=3[C:37]=2[CH3:38])=[CH:41][CH:42]=1
Reactant: Cc1oc2c(C)c(C)c(NC(=O)c3ccc(F)cc3)c(C)c2c1-c1ccc(C(C)C)cc1
Agent: [Al+3]
Agent: [Cl-]
Agent: [H-]
Solvent: C1CCOC1
Product: Cc1oc2c(C)c(C)c(NCc3ccc(F)cc3)c(C)c2c1-c1ccc(C(C)C)cc1
Temperature: 0 °C
Reaction time: 0.17 h
Yield: 53.7 %

Procedure:
To a suspension of aluminum chloride (807 mg, 6.05 mmol) in tetrahydrofuran (10 ml) was gradually added under ice cooling lithium aluminum hydride (230 mg, 6.05 mmol) and the resulting mixture was stirred at the same temperature for 10 minutes. To this mixture was added 4-fluoro-N-[3-(4-isopropylphenyl)-2,4,6,7-tetramethyl-1-benzofuran-5-yl]benzamide (0.52 g, 1.21 mmol) and the mixture was refluxed with heating for 3 hours. The reaction mixture was poured into ice water and neutralized with an 8 N aqueous solution of sodium hydroxide. The product was extracted twice with ethyl acetate. The combined organic layers were washed with water, dried on magnesium sulfate, filtered, and then concentrated under reduced pressure. The residue was crystallized from ethanol to obtain 0.27 g (54% yield) of the title compound. Melting point: 95-97° C.
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[C:7]([F:13])[CH:8]=[CH:9][C:10]=2[F:12])[N:5]=[C:4]([CH3:14])[CH:3]=1.[N-:15]=[N+:16]=[N-:17].[Na+]>CN(C)C=O>[N:15]([C:2]1[C:11]2[C:6](=[C:7]([F:13])[CH:8]=[CH:9][C:10]=2[F:12])[N:5]=[C:4]([CH3:14])[CH:3]=1)=[N+:16]=[N-:17]
Reactant: Cc1cc(Cl)c2c(F)ccc(F)c2n1
Reactant: [N-]=[N+]=[N-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: Cc1cc(N=[N+]=[N-])c2c(F)ccc(F)c2n1
Temperature: 0 °C
Yield: 64.6 %

Procedure:
4-Chloro-5,8-difluoro-2-methylquinoline (8.18 g) in dimethylformamide (80 ml) was treated with sodium azide (3.7 g) and the mixture heated for 20 h. The mixture was cooled, poured into ice/water and extracted with dichloromethane (2×200 ml). The organic phase was washed with water, dried (Na2SO4) and solvent removed at reduced pressure. The residue was column chromatographed (silica gel (5-20% diethyl ether in pentane) to give the title compound (5.45 g) as a colourless solid. (Method C). 1H NMR δ: 2.67 (3H, s), 7.29 (1H, m), 7.54 (1H, s), 7.58(1H, m).
Reaction SMILES: [CH3:1][C:2]([C:9]1[CH:14]=[CH:13][C:12]([OH:15])=[CH:11][CH:10]=1)([CH3:8])[C:3]([O:5][CH2:6][CH3:7])=[O:4].Br[CH2:17][C:18]1[C:19]([C:24]([O:26][CH2:27][CH3:28])=[O:25])=[CH:20][CH:21]=[CH:22][CH:23]=1>>[CH2:27]([O:26][C:24]([C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=1[CH2:17][O:15][C:12]1[CH:11]=[CH:10][C:9]([C:2]([CH3:1])([CH3:8])[C:3]([O:5][CH2:6][CH3:7])=[O:4])=[CH:14][CH:13]=1)=[O:25])[CH3:28]
Reactant: CCOC(=O)C(C)(C)c1ccc(O)cc1
Reactant: CCOC(=O)c1ccccc1CBr
Product: CCOC(=O)c1ccccc1COc1ccc(C(C)(C)C(=O)OCC)cc1

Procedure:
Reaction of ethyl α,α-dimethyl-p-hydroxyphenylacetate with ethyl α-bromo-o-toluate as described in Example 1b provides ethyl 4-(2-ethoxycarbonylbenzyloxy)-α,α-dimethylphenylacetate.
Reaction SMILES: [F:1][C:2]([F:15])([C:5]([F:14])([F:13])[C:6]([F:12])([F:11])[C:7]([F:10])([F:9])[F:8])[CH:3]=[CH2:4].[Cl:16][SiH:17]([Cl:19])[Cl:18]>C1(C)C(C)=CC=CC=1>[F:1][C:2]([F:15])([C:5]([F:13])([F:14])[C:6]([F:11])([F:12])[C:7]([F:9])([F:8])[F:10])[CH2:3][CH2:4][Si:17]([Cl:19])([Cl:18])[Cl:16]
Reactant: C=CC(F)(F)C(F)(F)C(F)(F)C(F)(F)F
Reactant: Cl[SiH](Cl)Cl
Solvent: Cc1ccccc1C
Product: FC(F)(F)C(F)(F)C(F)(F)C(F)(F)CC[Si](Cl)(Cl)Cl
Temperature: 140 °C
Reaction time: 0.13 h
Yield: 92 %

Procedure:
123 g (0.5 mol) of 3,3,4,4,5,5,6,6,6-nonafluorohexene and 76 g (0.5 mol) of trichlorosilane together with 0.34 g of CPC 072 (Pt(0)divinyltetramethyldisiloxane in xylene; concentration Pt:3,3,4,4,5,5,6,6,6-nonafluorohexene=1:20,000) are charged to a 250 ml laboratory steel autoclave. The autoclave is closed and heated to 140° C. in an oil bath over 70 minutes. The exothermic reaction begins after about 8 minutes, the reaction mixture rising to 165° C. It is subsequently cooled, the reactor is emptied, and short-path distillation gives 176 g (0.46 mol) of 3,3,4,4,5,5,6,6,6-nonafluorohexyltrichlorosilane (yield: 90%, purity: >98 area % GC-TCD).
Reaction SMILES: [C:1]([OH:11])(=[O:10])[C:2]1[CH:9]=[C:7]([OH:8])[CH:6]=[C:4]([OH:5])[CH:3]=1.S(=O)(=O)(O)O.[CH2:17](O)[CH3:18]>>[OH:5][C:4]1[CH:3]=[C:2]([CH:9]=[C:7]([OH:8])[CH:6]=1)[C:1]([O:11][CH2:17][CH3:18])=[O:10]
Reactant: CCO
Reactant: O=C(O)c1cc(O)cc(O)c1
Agent: O=S(=O)(O)O
Product: CCOC(=O)c1cc(O)cc(O)c1

Procedure:
308 g. of α-resorcylic acid were dissolved in 1000 ml of absolute ethanol and 25 ml of concentrated sulphuric acid were added. The reaction mixture was boiled under reflux for 20 hours. The ethanol was evaporated and the residue poured into water and extracted with ether. The etheral phase was washed with sodium bicarbonate solution and water and dried with magnesium sulphate. When the ether was evaporated, a crystallizing residue was obtained.
Reaction SMILES: O[CH2:2][C:3]1([CH2:14][OH:15])[O:10][C@@H:7]([O:8]C)[C@H:6]([OH:11])[C@@H:5]([OH:12])[C@H:4]1[OH:13]>S(=O)(=O)(O)O>[OH:15][CH2:14][C@@:3]12[CH2:2][O:8][C@@H:7]([O:10]1)[C@H:6]([OH:11])[C@@H:5]([OH:12])[C@H:4]2[OH:13]
Reactant: CO[C@@H]1OC(CO)(CO)[C@H](O)[C@H](O)[C@H]1O
Agent: O=S(=O)(O)O
Product: OC[C@@]12CO[C@@H](O1)[C@H](O)[C@@H](O)[C@H]2O
Temperature: 100 °C
Reaction time: 1.5 h
Yield: 39.6 %

Procedure:
Methyl 5-C-hydroxymethyl-α-L-arabino-hexopyranose (3) (59.0 g, 0.263 moles) is dissolved in 0.70M sulfuric acid (260 ml), and stirred at 100° C. for 90 minutes. The solution is cooled to room temperature and neutralized using an ion exchange resin (Amberlite IRA-400 (OH-). The resin is filtered off, and the filtrate is refluxed for 15 minutes with activated carbon (4.0 g). Carbon is removed with a glass fiber filter, and the filtrate is evaporated to dryness with ethanol. The white waxy residue is refluxed for 15 minutes with methanol (50 ml). The solution is stored overnight at 0° C. The product is filtered to yield 20.0g (39.6%) of 1,6-anhydro-5-C-hydroxymethyl-β-L-altropyranose (4).
Reaction SMILES: Cl[C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[N:5]=[C:4]([C:12]2[CH:13]=[N:14][CH:15]=[CH:16][CH:17]=2)[N:3]=1.[CH3:18][C:19]1[CH:25]=[C:24]([OH:26])[C:23]([CH3:27])=[CH:22][C:20]=1[NH2:21]>>[CH3:18][C:19]1[CH:25]=[C:24]([OH:26])[C:23]([CH3:27])=[CH:22][C:20]=1[NH:21][C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[N:5]=[C:4]([C:12]2[CH:13]=[N:14][CH:15]=[CH:16][CH:17]=2)[N:3]=1
Reactant: FC(F)(F)c1cc(Cl)nc(-c2cccnc2)n1
Reactant: Cc1cc(O)c(C)cc1N
Product: Cc1cc(Nc2cc(C(F)(F)F)nc(-c3cccnc3)n2)c(C)cc1O

Procedure:
The title compound was prepared from 4-chloro-2-(3-pyridinyl)-6-trifluoromethylpyrimidine (50 mg, 0.192 mmol) and 2,5-dimethyl-4-hydroxyaniline (40 mg, 0.288 mmol) similar to Example 190 and was isolated as a solid. 1H NMR (CDCl3): 9.51 (brs, 1H), 8.72 (d, J=8.4 Hz, 1H), 8.63 (d, J=3.6 Hz, 1H), 7.45 (dd, J=7.5, 3.5 Hz, 1H), 7.33 (s, 1H), 7.00 (s, 1H), 6.74 (s, 1H), 6.45 (brs, 1H), 2.25 (s, 3H), 2.16 (s, 3H).
Reaction SMILES: O.Cl.[NH:3]1[CH2:8][CH2:7][C:6](=[O:9])[CH2:5][CH2:4]1.Cl[CH2:11][C:12]#[N:13].C(N(C(C)C)CC)(C)C>O1CCCC1>[O:9]=[C:6]1[CH2:7][CH2:8][N:3]([CH2:11][C:12]#[N:13])[CH2:4][CH2:5]1
Reactant: N#CCCl
Reactant: O=C1CCNCC1
Agent: Cl
Solvent: CCN(C(C)C)C(C)C
Solvent: O
Solvent: C1CCOC1
Product: N#CCN1CCC(=O)CC1

Procedure:
A suspension of 25.0 g of 4-piperidinone monohydrochloride monohydrate, 11.5 ml of chloroacetonitrile and 57.0 ml of diisopropylethylamine in 250 ml of tetrahydrofuran was refluxed for 10 hours. After the reaction, an insoluble matter was filtered off. The filtrate was added with saturated aqueous sodium hydrogencarbonate solution and extracted with a mixture of ethyl acetate and methanol (10:1). The extract was dried, and the solvent was evaporated to give brown crystals. The crystals were washed with a mixture of ethyl acetate and n-heptane to give 15.7 g of pale brown crystals.
Reaction SMILES: [CH3:1][C:2]([CH3:4])=O.[C:5]([NH:9][NH2:10])([CH3:8])([CH3:7])[CH3:6].[OH-].[K+]>CCOCC>[C:5]([NH:9][N:10]=[C:2]([CH3:4])[CH3:1])([CH3:8])([CH3:7])[CH3:6]
Reactant: CC(C)(C)NN
Reactant: CC(C)=O
Agent: [K+]
Agent: [OH-]
Solvent: CCOCC
Product: CC(C)=NNC(C)(C)C

Procedure:
To 6.6 g of acetone, cooled in an ice bath, is added 5.0 g of tert-butylhydrazine. The mixture is stirred and then allowed to stand for several minutes. Ether and potassium hydroxide pellets are then added to the mixture. The mixture is stirred, and then the ethereal layer is separated from the mixture. Distillation of the ethereal layer yields the product acetone tert-butylhydrazone b.p. 132°-134° C.
Reaction SMILES: [CH3:1][O:2][CH:3]([O:6][CH3:7])[CH2:4][NH2:5].C(=O)([O-])[O-].[K+].[K+].[CH:14]1([CH2:19][CH2:20][CH2:21]I)[CH2:18][CH2:17][CH2:16][CH2:15]1>CN(C)C=O>[CH:14]1([CH2:19][CH2:20][CH2:21][NH:5][CH2:4][CH:3]([O:6][CH3:7])[O:2][CH3:1])[CH2:18][CH2:17][CH2:16][CH2:15]1
Reactant: ICCCC1CCCC1
Reactant: COC(CN)OC
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: COC(CNCCCC1CCCC1)OC
Temperature: 25 °C
Reaction time: 12 h
Yield: 89.2 %

Procedure:
A mixture of 2-aminoacetaldehyde dimethyl acetal (3.0 mL, 27.5 mmol), solid potassium carbonate (2.1 g, 15.2 mmol), and 3-cyclopentyl-1-iodopropane (3.3 g, 13.9 mmol) in anhydrous N,N-dimethylformamide was stirred for 12 hours at room temperature. The mixture was filtered, and the filtrate was partitioned between water and ethyl acetate. The organic layer was washed with brine, dried (Na2SO4) and concentrated to a crude oil. The crude was passed through a plug of silica gel with ethyl acetate to provide a yellow oil (2.67 g, 89%). H NMR (300 MHz, DMSO-d6) δ 4.35 (t, 1 H), 3.23 (s, 6 H), 2.54 (d, 2 H), 1.70 (m, 3 H), 1.51 (m, 6 H), 1.36 (m, 2 H), 1.27 (m, 2 H), 1.04 (m, 2 H).