Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([CH2:3][N:4]1[C:12]2[CH2:11][C:10]([F:14])([F:13])[CH2:9][CH2:8][C:7]=2[CH:6]=[C:5]1[C:15]([O:17][CH2:18][CH3:19])=[O:16])#[N:2].[BH4-].[Na+]>C(O)C>[NH2:2][CH2:1][CH2:3][N:4]1[C:12]2[CH2:11][C:10]([F:14])([F:13])[CH2:9][CH2:8][C:7]=2[CH:6]=[C:5]1[C:15]([O:17][CH2:18][CH3:19])=[O:16]
Reactant: CCOC(=O)c1cc2c(n1CC#N)CC(F)(F)CC2
Agent: [BH4-]
Agent: [Na+]
Solvent: CCO
Product: CCOC(=O)c1cc2c(n1CCN)CC(F)(F)CC2
Temperature: 25 °C
Reaction time: 24 h
Yield: 20.9 %

Procedure:
Into a 100-mL round-bottom flask was placed a solution of 113m (3.3 g, 12.30 mmol, 1.00 equiv) in ethanol (30 mL) and NiCl2.6H2O (3.2 g, 13.45 mmol, 1.10 equiv), followed by the addition of NaBH4 (1.4 g, 37.01 mmol, 3.00 equiv) in several batches at 0° C. (FIG. 14). The resulting solution was stirred at room temperature for 24 h. The solids were filtered out and the filtrate was concentrated under vacuum. The resulting solution was diluted with 30 mL of ethyl acetate and washed with 1×30 mL of hydrogen chloride (2/V). The solution was adjusted to pH=9 with saturated aqueous sodium bicarbonate and extracted with 2×30 mL of ethyl acetate. The combined organic layers were dried over anhydrous sodium sulfate and concentrated under vacuum to afford 0.7 g (21%) of 113n as a light yellow oil.
Reaction SMILES: Br[C:2]1[N:7]=[C:6]([Cl:8])[C:5](/[CH:9]=[CH:10]/[O:11][CH2:12][CH3:13])=[CH:4][CH:3]=1.[F:14][C:15]1[CH:20]=[CH:19][C:18]([C:21]2[O:22][C:23]3[CH:33]=[C:32]([N:34]([CH3:39])[S:35]([CH3:38])(=[O:37])=[O:36])[C:31](B4OC(C)(C)C(C)(C)O4)=[CH:30][C:24]=3[C:25]=2[C:26]([NH:28][CH3:29])=[O:27])=[CH:17][CH:16]=1.C(=O)([O-])[O-].[Cs+].[Cs+].O1CCOCC1>O>[Cl:8][C:6]1[N:7]=[C:2]([C:31]2[C:32]([N:34]([CH3:39])[S:35]([CH3:38])(=[O:37])=[O:36])=[CH:33][C:23]3[O:22][C:21]([C:18]4[CH:19]=[CH:20][C:15]([F:14])=[CH:16][CH:17]=4)=[C:25]([C:26]([NH:28][CH3:29])=[O:27])[C:24]=3[CH:30]=2)[CH:3]=[CH:4][C:5]=1/[CH:9]=[CH:10]/[O:11][CH2:12][CH3:13]
Reactant: CCO/C=C/c1ccc(Br)nc1Cl
Reactant: CNC(=O)c1c(-c2ccc(F)cc2)oc2cc(N(C)S(C)(=O)=O)c(B3OC(C)(C)C(C)(C)O3)cc12
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: O
Solvent: C1COCCO1
Product: CCO/C=C/c1ccc(-c2cc3c(C(=O)NC)c(-c4ccc(F)cc4)oc3cc2N(C)S(C)(=O)=O)nc1Cl
Temperature: 60 °C

Procedure:
To a mixture of (E)-6-bromo-2-chloro-3-(2-ethoxyvinyl)pyridine (3.37 g, 12.84 mmol), 2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzofuran-3-carboxamide (6.45 g, 12.84 mmol), cesium carbonate (10.46 g, 32.1 mmol), and 1,1′ Bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (0.524 g, 0.642 mmol) was added 1,4-Dioxane (83 mL) followed by H2O (8.34 mL). A steady stream of N2 was bubbled through the reaction mixture for 7 minutes then the mixture was heated to 60° C. for 16 h. The mixture was cooled to ambient temperature, diluted with EtOAc, and washed successively with H2O (1×) and brine (1×). The organic layer was dried over MgSO4, filtered, and concentrated in vacuo. The solid residue was triturated with EtOAc and further purified by silica gel column chromatography using a gradient of 0-30% EtOAc/CH2Cl2 as eluent. Further purification by silica gel column chromatography with a gradient of 0-100% EtOAc/Hexanes as eluent provided the title compound as a tan solid. 1H NMR δ (ppm) (CHCl3-d): 8.03˜7.97 (3H, m), 7.79 (1H, d, J=7.96 Hz), 7.69 (1H, s), 7.52 (1H, d, J=7.50 Hz), 7.28˜7.00 (2H, m), 7.11 (1H, d, J=13.00 Hz), 6.12 (1H, d, J=13.00 Hz), 5.91 (1H, br s), 4.04 (2H, q, J=7.04 Hz), 3.24 (3H, s), 3.03 (3H, d, J=4.87 Hz), 2.89 (3H, s), 1.44 (3H, t, J=7.00). MS (M+H): 557.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([C:9]2[N:14]3[N:15]=[C:16]([CH3:19])[C:17](I)=[C:13]3[N:12]=[C:11]([N:20]3[CH2:24][CH2:23][CH2:22][C@H:21]3[CH2:25][OH:26])[CH:10]=2)[CH:5]=[CH:6][C:7]=1[F:8].[CH2:27]([O:29][C:30]1[CH:35]=[CH:34][C:33](B(O)O)=[CH:32][CH:31]=1)[CH3:28].C1(C)C=CC=CC=1.C([O-])(O)=O.[Na+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C(O)C>[F:1][C:2]1[CH:3]=[C:4]([C:9]2[N:14]3[N:15]=[C:16]([CH3:19])[C:17]([C:33]4[CH:34]=[CH:35][C:30]([O:29][CH2:27][CH3:28])=[CH:31][CH:32]=4)=[C:13]3[N:12]=[C:11]([N:20]3[CH2:24][CH2:23][CH2:22][C@H:21]3[CH2:25][OH:26])[CH:10]=2)[CH:5]=[CH:6][C:7]=1[F:8]
Reactant: CCOc1ccc(B(O)O)cc1
Reactant: Cc1nn2c(-c3ccc(F)c(F)c3)cc(N3CCC[C@H]3CO)nc2c1I
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCO
Solvent: Cc1ccccc1
Product: CCOc1ccc(-c2c(C)nn3c(-c4ccc(F)c(F)c4)cc(N4CCC[C@H]4CO)nc23)cc1
Temperature: 85 °C
Reaction time: 6 h
Yield: 75 %

Procedure:
(S)-(1-(7-(3,4-Difluorophenyl)-3-iodo-2-methylpyrazolo[1,5-a]pyrimidin-5-yl)pyrrolidin-2-yl)methanol (27 mg), 4-ethoxyphenylboronic acid (16 mg) and tetrakis(triphenylphosphine)palladium (10 mg) are added to toluene (8 mL), ethanol (3 mL) and 1 N NaHCO3 aqueous solution (1.5 mL) and stirred at 85° C. for 6 hours under argon atmosphere. After cooling to room temperature, the reaction solvent is removed by distillation under reduced pressure. The remainder is extracted with ethyl acetate and water. The organic layer is washed with brine and dehydrated with anhydrous MgSO4. The dehydrated organic layer is distilled under reduced pressure, concentrated and purified by column chromatography to yield the target compound (20 mg).
Reaction SMILES: Cl.Cl.Cl.[NH:4]([C:8]1[S:9][CH:10]=[C:11]([CH2:13][S:14][CH2:15][CH2:16][NH:17][C:18](=[NH:22])[C:19](=[NH:21])[NH2:20])[N:12]=1)[C:5]([NH2:7])=[NH:6].C(Cl)Cl.[S:26](N1C(=O)C2=CC=CC=C2C1=O)N1C(=O)C2=CC=CC=C2C1=O.[OH-].[Na+]>C(N(CC)CC)C>[NH2:21][C:19]1[C:18]([NH:17][CH2:16][CH2:15][S:14][CH2:13][C:11]2[N:12]=[C:8]([NH:4][C:5]([NH2:7])=[NH:6])[S:9][CH:10]=2)=[N:22][S:26][N:20]=1
Reactant: N=C(N)Nc1nc(CSCCNC(=N)C(=N)N)cs1
Reactant: O=C1c2ccccc2C(=O)N1SN1C(=O)c2ccccc2C1=O
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: N=C(N)Nc1nc(CSCCNc2nsnc2N)cs1
Reaction time: 1 h
Yield: 53.9 %

Procedure:
A mixture of crude N-{2-[(2-guanidinothiazol-4-yl)methylthio]ethyl}ethanediimidamide trihydrochloride (5.65 g, 13.7 mmoles) [prepared in Step A], 50 ml of CH2Cl2 and 5.7 ml of triethylamine was treated with N,N'-thiobisphthalimide (DMF solvate) (5.44 g; 13.7 mmoles) and stirred for one hour to give a thick suspension. The mixture was treated with 40 ml of 2N NaOH and the solvents were decanted from the gum-like material which had separated. The gum was washed with 40 ml of 2N NaOH, water, and then dissolved in methanol and concentrated to give 3.0 g of crude product. The product was purified by flash chromatography on 90 g of silica gel (230-400 mesh) using ethyl acetate-methanol (97:3) as the eluent to give 2.44 g (54%) of the title compound. Treatment of the product in 35 ml of acetone with one equivalent of cyclohexylsulfamic acid gave the salt which was then recrystallized from 95 % aqueous ethanol to give the title compound as its cyclohexylsulfamate salt, mp. 171°-173.5° C.
Reaction SMILES: Br[CH2:2][CH2:3][C:4]#[C:5][Si:6]([CH3:9])([CH3:8])[CH3:7].[F:10][C:11]1[CH:19]=[CH:18][C:14]2[NH:15][N:16]=[N:17][C:13]=2[CH:12]=1.[OH-].[Na+]>>[F:10][C:11]1[CH:19]=[CH:18][C:14]2=[N:15][N:16]([CH2:2][CH2:3][C:4]#[C:5][Si:6]([CH3:9])([CH3:8])[CH3:7])[N:17]=[C:13]2[CH:12]=1
Reactant: Fc1ccc2[nH]nnc2c1
Reactant: C[Si](C)(C)C#CCCBr
Agent: [Na+]
Agent: [OH-]
Product: C[Si](C)(C)C#CCCn1nc2ccc(F)cc2n1
Temperature: 100 °C
Yield: 100 %

Procedure:
(4-Bromo-but-1-ynyl)-trimethyl-silane (294 mg, 1.43 mmol) was added to a solution of 5-fluoro-1H-benzo[d][1,2,3]triazole (187 mg, 1.36 mmol) in a solution of NaOH (2N, 955 μL). The reaction mixture was heated at 100° C. for 14 hours, then it was cooled down and was extracted with DCM. The organic phase was washed with water, brine, dried over MgSO4, filtered and evaporated to yield 355 mg (1.36 mmol) 5-fluoro-2-(4-trimethylsilanyl-but-3-ynyl)-2H-benzo[d][1,2,3]triazole including the two others isomers.
Reaction SMILES: [NH:1]1[CH2:4][CH:3]([N:5]2[CH2:10][CH2:9][N:8]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:7][CH:6]2[C:18](=[O:20])[NH2:19])[CH2:2]1.CCN(CC)CC.[C:28](Cl)(=[O:31])[CH:29]=[CH2:30]>C(Cl)Cl>[C:28]([N:1]1[CH2:4][CH:3]([N:5]2[CH2:10][CH2:9][N:8]([C:11]([O:13][C:14]([CH3:15])([CH3:16])[CH3:17])=[O:12])[CH2:7][CH:6]2[C:18](=[O:20])[NH2:19])[CH2:2]1)(=[O:31])[CH:29]=[CH2:30]
Reactant: CC(C)(C)OC(=O)N1CCN(C2CNC2)C(C(N)=O)C1
Reactant: C=CC(=O)Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: C=CC(=O)N1CC(N2CCN(C(=O)OC(C)(C)C)CC2C(N)=O)C1
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 46.6 %

Procedure:
To a solution of tert-butyl 4-(azetidin-3-yl)-3-carbamoylpiperazine-1-carboxylate (640 mg, 2.22 mmol) and Et3N (463 mg, 4.58 mmol) in DCM (10 mL) at 0° C., acryloyl chloride (248 mg, 2.74 mmol) was added dropwise and the resulting mixture was stirred at RT for 1.5 h. The mixture was partitioned between dichloromethane and saturated NaHCO3 solution. The organic layer was washed with saturated brine, dried over Na2SO4 and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel (dichloromethane/methanol=50:1) to afford the desired product (350 mg, 47% yield).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[C:9]1[C:22](=[O:23])[N:21]([CH3:24])[C:12]2[N:13]=[C:14](S(C)(=O)=O)[N:15]=[CH:16][C:11]=2[CH:10]=1.[CH3:25][O:26][C:27]1[CH:33]=[CH:32][C:30]([NH2:31])=[CH:29][CH:28]=1>>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[C:9]1[C:22](=[O:23])[N:21]([CH3:24])[C:12]2[N:13]=[C:14]([NH:31][C:30]3[CH:32]=[CH:33][C:27]([O:26][CH3:25])=[CH:28][CH:29]=3)[N:15]=[CH:16][C:11]=2[CH:10]=1
Reactant: COc1ccc(N)cc1
Reactant: Cn1c(=O)c(-c2c(Cl)cccc2Cl)cc2cnc(S(C)(=O)=O)nc21
Product: COc1ccc(Nc2ncc3cc(-c4c(Cl)cccc4Cl)c(=O)n(C)c3n2)cc1
Temperature: 180 °C

Procedure:
A mixture of 0.113 g (0.29 mmol) of 6-(2,6-dichlorophenyl)-2-methanesulfonyl-8-methyl-8H-pyrido[2,3-d]pyrimidin-7-one of Example 39 and 0.50 g (4.10 mmol) of 4-methoxyaniline was heated, with stirring, in a 180° C. oil bath. The resulting solution was heated for 10 minutes. Much of the excess aniline was evaporated at reduced pressure. The remainder was dissolved in 2 mL of ethyl acetate. The crystals that separated from the dark solution were filtered and washed with 2 mL of ethyl acetate, wt 0.102 g.
Reaction SMILES: [C:1]([C:4]1[CH:5]=[C:6]([CH:35]=[CH:36][CH:37]=1)[C:7]([C:9]1[CH:10]=[CH:11][C:12]([O:20][CH2:21][CH2:22][CH2:23][CH2:24]/[CH:25]=[CH:26]/[C:27]2[CH:32]=[CH:31][C:30]([O:33][CH3:34])=[CH:29][CH:28]=2)=[C:13]([CH:19]=1)[O:14][CH2:15][C:16]([OH:18])=[O:17])=[O:8])([OH:3])=[O:2].[BH4-].[Na+]>O1CCOCC1.O>[C:1]([C:4]1[CH:5]=[C:6]([CH:7]([C:9]2[CH:10]=[CH:11][C:12]([O:20][CH2:21][CH2:22][CH2:23][CH2:24]/[CH:25]=[CH:26]/[C:27]3[CH:28]=[CH:29][C:30]([O:33][CH3:34])=[CH:31][CH:32]=3)=[C:13]([CH:19]=2)[O:14][CH2:15][C:16]([OH:18])=[O:17])[OH:8])[CH:35]=[CH:36][CH:37]=1)([OH:3])=[O:2]
Reactant: COc1ccc(/C=C/CCCCOc2ccc(C(=O)c3cccc(C(=O)O)c3)cc2OCC(=O)O)cc1
Agent: [BH4-]
Agent: [Na+]
Solvent: O
Solvent: C1COCCO1
Product: COc1ccc(/C=C/CCCCOc2ccc(C(O)c3cccc(C(=O)O)c3)cc2OCC(=O)O)cc1
Yield: 89.6 %

Procedure:
Under the conditions of example 5A, 100 mg of 5-(3-carboxybenzoyl)-2-[6-(4-methoxyphenyl)-(5E)-5-hexenyloxy]-phenoxy acetic acid is reacted with 31 mg of sodium borohydride in 5 ml of dioxane and 0.5 ml of water and worked up (>pH 3-4). 90 mg of the title compound is obtained as colorless oil.
Reaction SMILES: [Cl:1][C:2]1[N:7]=[C:6]([NH:8][C:9]2[CH:17]=[CH:16][CH:15]=[CH:14][C:10]=2[C:11]([OH:13])=[O:12])[C:5]([Cl:18])=[CH:4][N:3]=1.[CH3:19][Si](C=[N+]=[N-])(C)C>C(Cl)Cl.CO.C(OCC)C>[Cl:1][C:2]1[N:7]=[C:6]([NH:8][C:9]2[CH:17]=[CH:16][CH:15]=[CH:14][C:10]=2[C:11]([O:13][CH3:19])=[O:12])[C:5]([Cl:18])=[CH:4][N:3]=1
Reactant: O=C(O)c1ccccc1Nc1nc(Cl)ncc1Cl
Reactant: C[Si](C)(C)C=[N+]=[N-]
Solvent: CO
Solvent: CCOCC
Solvent: ClCCl
Product: COC(=O)c1ccccc1Nc1nc(Cl)ncc1Cl
Reaction time: 0.5 h

Procedure:
To a solution of 2-(2,5-dichloropyrimidin-4-ylamino)benzoic acid (300 mg, 1.1 mmol) in DCM/MeOH (10/5 mL) is added trimethylsilyl diazomethane in ethyl ether solution (2.0 M, 2 mL). The mixture is stirred for 30 min and concentrated to afford methyl 2-(2,5-dichloropyrimidin-4-ylamino)benzoate as yellow solid.
Reaction SMILES: [Cl:1][C:2]1[C:7]([CH2:8][O:9][CH2:10][CH3:11])=[CH:6][C:5]([N+:12]([O-])=O)=[C:4]([F:15])[CH:3]=1.[H][H]>C(O)(=O)C.[Pt]>[Cl:1][C:2]1[C:7]([CH2:8][O:9][CH2:10][CH3:11])=[CH:6][C:5]([NH2:12])=[C:4]([F:15])[CH:3]=1
Reactant: [H][H]
Reactant: CCOCc1cc([N+](=O)[O-])c(F)cc1Cl
Agent: [Pt]
Solvent: CC(=O)O
Product: CCOCc1cc(N)c(F)cc1Cl

Procedure:
A solution of 4-chloro-5-ethoxymethyl-2-fluoronitrobenzene (0.9 g, 0.0039 mole) in glacial acetic acid (50 ml) was added to a 250 ml Parr bottle containing platinum IV oxide (0.3 g) under a nitrogen atmosphere. The Parr bottle was placed on a Parr hydrogenation apparatus and charged with hydrogen. The reaction mixture was allowed to shake until hydrogen absorption ceased. The catalyst was removed by vacuum filtration. The 4-chloro-5-ethoxymethyl-2-fluoroaniline produced was used in the next step in acetic acid solution without being isolated.
Reaction SMILES: [NH:1]=[C:2]1[NH:6][C:5]([C:11]([F:14])([F:13])[F:12])([C:7]([F:10])([F:9])[F:8])[C:4](=[C:15]([F:20])[C:16]([F:19])([F:18])[F:17])[S:3]1.C(N(CC)CC)C.[C:28]([C:30]1[CH:38]=[CH:37][C:33]([C:34](Cl)=[O:35])=[CH:32][CH:31]=1)#[N:29]>C1(C)C=CC=CC=1.ClCCl>[C:28]([C:30]1[CH:38]=[CH:37][C:33]([C:34]([NH:1][C:2]2[S:3][C:4](=[C:15]([F:20])[C:16]([F:17])([F:18])[F:19])[C:5]([C:7]([F:10])([F:9])[F:8])([C:11]([F:12])([F:13])[F:14])[N:6]=2)=[O:35])=[CH:32][CH:31]=1)#[N:29]
Reactant: N=C1NC(C(F)(F)F)(C(F)(F)F)C(=C(F)C(F)(F)F)S1
Reactant: N#Cc1ccc(C(=O)Cl)cc1
Solvent: ClCCl
Solvent: Cc1ccccc1
Solvent: CCN(CC)CC
Product: N#Cc1ccc(C(=O)NC2=NC(C(F)(F)F)(C(F)(F)F)C(=C(F)C(F)(F)F)S2)cc1
Temperature: 103 °C
Reaction time: 3 h

Procedure:
In toluene (40 ml) were dissolved 2-imino-4,4-bis(trifluoromethyl)-5-(tetrafluoroethylidene)-1,3-thiazolidine (2.0 g) and triethylamine (1.0 ml), and a solution of 4-cyanobenzoyl chloride (1.2 g) dissolved in a mixed solution of toluene (10 ml) and dichloromethane (2 ml) was gradually added thereto under cooling and the mixture was stirred at 103° C. for 3 hours.
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6]([CH3:8])[C:5]([S:9][CH2:10][C:11]([F:14])([F:13])[F:12])=[CH:4][C:3]=1[N:15]1[C:19]([NH:20][CH3:21])=[CH:18][C:17]([O:22][C:23]([F:38])([F:37])[CH:24]([F:36])[O:25][C:26]([F:35])([F:34])[C:27]([F:33])([F:32])[C:28]([F:31])([F:30])[F:29])=[N:16]1.ClC1C=CC=C(C(OO)=[O:47])C=1>C(Cl)(Cl)Cl>[F:1][C:2]1[CH:7]=[C:6]([CH3:8])[C:5]([S:9]([CH2:10][C:11]([F:14])([F:13])[F:12])=[O:47])=[CH:4][C:3]=1[N:15]1[C:19]([NH:20][CH3:21])=[CH:18][C:17]([O:22][C:23]([F:38])([F:37])[CH:24]([F:36])[O:25][C:26]([F:34])([F:35])[C:27]([F:32])([F:33])[C:28]([F:30])([F:31])[F:29])=[N:16]1
Reactant: CNc1cc(OC(F)(F)C(F)OC(F)(F)C(F)(F)C(F)(F)F)nn1-c1cc(SCC(F)(F)F)c(C)cc1F
Reactant: O=C(OO)c1cccc(Cl)c1
Solvent: ClC(Cl)Cl
Product: CNc1cc(OC(F)(F)C(F)OC(F)(F)C(F)(F)C(F)(F)F)nn1-c1cc(S(=O)CC(F)(F)F)c(C)cc1F
Reaction time: 1 h
Yield: 77.9 %

Procedure:
0.15 g of 1-{2-fluoro-4-methyl-5-(2,2,2-trifluoroethylthio)phenyl}-5-methylamino-3-{1,1,2-trifluoro-2-(heptafluoropropoxy)ethoxy}pyrazole was dissolved in 10 mL of chloroform, and 73 mg of m-chloroperbenzoic acid (purity: 75%) was added under cooling with ice. After stirring for one hour under cooling with ice, the solution was washed with an aqueous sodium thiosulfate solution and then washed with an aqueous sodium hydrogen carbonate solution, and then dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the obtained residue was purified by column chromatography (developing solvent ethyl acetate:hexane=1:2) to obtain 0.12 g of 1-{2-fluoro-4-methyl-5-(2,2,2-trifluoroethylsulfinyl)phenyl}-5-methylamino-3-{1,1,2-trifluoro-2-(heptafluoropropoxy)ethoxy}pyrazole.
Reaction SMILES: [CH:1]([NH:14][CH2:15][CH2:16][CH2:17][C:18]([O:20][CH2:21][CH3:22])=[O:19])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(C(C)C)C(C)C)C.[Cl:32][C:33]1[CH:34]=[CH:35][C:36]([O:42][CH3:43])=[C:37]([CH:41]=1)[C:38](Cl)=[O:39].CS(C)=O>C1C=CC=CC=1>[Cl:32][C:33]1[CH:34]=[CH:35][C:36]([O:42][CH3:43])=[C:37]([CH:41]=1)[C:38]([N:14]([CH:1]([C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)[CH2:15][CH2:16][CH2:17][C:18]([O:20][CH2:21][CH3:22])=[O:19])=[O:39]
Reactant: COc1ccc(Cl)cc1C(=O)Cl
Reactant: CCOC(=O)CCCNC(c1ccccc1)c1ccccc1
Solvent: CCN(C(C)C)C(C)C
Solvent: CS(C)=O
Solvent: c1ccccc1
Product: CCOC(=O)CCCN(C(=O)c1cc(Cl)ccc1OC)C(c1ccccc1)c1ccccc1
Yield: 99 %

Procedure:
Analogously to Example 19, 8.9 g of ethyl 4-benzhydrylaminobutyrate and 4.3 g of ethyl diisopropylamine are dissolved in 80 ml of benzene and reacted with a solution of 6.8 g of 5-chloro-2-methoxybenzoic acid chloride in 20 ml of benzene. As reaction product one obtains 13.8 g (99% of theory) of ethyl N-(5-chloro-2-methoxybenzoyl)-4-benzhydrylaminobutyrate as a viscous non-distillable oil. The saponification of this ester yields 11.1 g (85.6% of theory) of N-(5-chloro-2-methoxybenzoyl)-4-benzhydrylaminobutyric acid (M.P. 176° to 178°).
Reaction SMILES: [Br-].[Br:2][CH2:3][P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.CC([O-])(C)C.[K+].[CH2:29]1[CH2:42][O:41][C:31]([CH3:40])([CH2:32][CH:33]=[CH:34][C:35]([CH3:39])=[CH:36][CH:37]=O)[O:30]1.O>O1CCCC1>[CH2:29]1[CH2:42][O:41][C:31]([CH3:40])([CH2:32][CH:33]=[CH:34][C:35]([CH3:39])=[CH:36][CH:37]=[CH:3][Br:2])[O:30]1
Reactant: CC(C=CCC1(C)OCCO1)=CC=O
Reactant: BrC[P+](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: CC(C)(C)[O-]
Agent: [Br-]
Agent: [K+]
Solvent: C1CCOC1
Solvent: O
Product: CC(C=CCC1(C)OCCO1)=CC=CBr
Temperature: -70 °C
Reaction time: 0.5 h
Yield: 70.4 %

Procedure:
Anhydrous tetrahydrofuran (22 cc) and bromomethyltriphenylphosphonium bromide (1.7 g, 3.9 mmol) are introduced into a 50-cc round-bottomed flask. This is cooled to -70° C. and potassium tert-butylate (0.44 g) is then added over 10 minutes. The mixture is stirred for 1 hour 30 minutes and 7,7-ethylenedioxy-3-methyl-2,4-octadienal (0.5 g) is then added in solution in tetrahydrofuran (3 cc) over 10 minutes. The temperature is allowed to rise to 10° C. and stirring is then performed for 2 hours 20 minutes. Water (12 cc) is quickly added and stirring is then performed for 15 minutes. After extraction, the organic phases are dried over magnesium sulphate. After evaporation of the solvents, the product obtained is placed in a mortar and is taken up with petroleum ether; the triphenylphosphine oxide which precipitates is ground until white and is then separated by filtration. After evaporation of the petroleum ether, 8,8-ethylenedioxy-1-bromo-4-methyl-1,3,5-nonatriene (0.49 g) is obtained, its characteristics being as follows:
Reaction SMILES: [NH2:1][C:2]([CH3:11])([CH2:5][CH2:6][C:7]([F:10])([F:9])[F:8])[C:3]#[N:4].C(=O)([O-])[O-].[K+].[K+].Cl[C:19]([O:21][CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)=[O:20]>O1CCCC1.O>[C:3]([C:2]([NH:1][C:19](=[O:20])[O:21][CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)([CH2:5][CH2:6][C:7]([F:8])([F:9])[F:10])[CH3:11])#[N:4]
Reactant: CC(N)(C#N)CCC(F)(F)F
Reactant: O=C(Cl)OCc1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: C1CCOC1
Product: CC(C#N)(CCC(F)(F)F)NC(=O)OCc1ccccc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 70.9 %

Procedure:
8.7 g (52.36 mmol) of rac-2-amino-5,5,5-trifluoro-2-methylpentanonitrile from Example 60A were initially charged in 128 ml of tetrahydrofuran/water=9/1, and 22.43 g (162.3 mmol) of potassium carbonate were added. At 0° C., 8.93 g (52.36 mmol) of benzyl chloroformate were added dropwise. Then the mixture was allowed to warm up gradually to room temperature and stirred at room temperature overnight. The supernatant solvent was decanted off, the residue was twice stirred with 100 ml each time of tetrahydrofuran, and then the supernatant solvent was decanted off each time. The combined organic phases were concentrated and the crude product was purified by means of silica gel chromatography (eluent:cyclohexane/ethyl acetate gradient 9/1 to 4/1). 11.14 g of the title compound were obtained (68% of theory).
Reaction SMILES: Cl.[C@@H:2]1([N:10]2[CH:17]=[CH:16][C:14]([NH2:15])=[N:13][C:11]2=[O:12])[O:9][C@H:6]([CH2:7][OH:8])[C@@H:4]([OH:5])[CH2:3]1.C[Si](Cl)(C)C.[C:23]1([CH3:33])[CH:28]=[CH:27][C:26]([S:29](Cl)(=[O:31])=[O:30])=[CH:25][CH:24]=1.ClCCl>N1C=CC=CC=1>[C:23]1([CH3:33])[CH:28]=[CH:27][C:26]([S:29]([NH:15][C:14]2[CH:16]=[CH:17][N:10]([C@@H:2]3[O:9][C@H:6]([CH2:7][OH:8])[C@@H:4]([OH:5])[CH2:3]3)[C:11](=[O:12])[N:13]=2)(=[O:31])=[O:30])=[CH:25][CH:24]=1
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Reactant: Nc1ccn([C@H]2C[C@H](O)[C@@H](CO)O2)c(=O)n1
Agent: C[Si](C)(C)Cl
Agent: Cl
Solvent: ClCCl
Solvent: c1ccncc1
Product: Cc1ccc(S(=O)(=O)Nc2ccn([C@H]3C[C@H](O)[C@@H](CO)O3)c(=O)n2)cc1
Reaction time: 8 h

Procedure:
2'-deoxycytidine hydrochloride (1.32 g, 5 mmol) is allowed to react for 1 hour with trimethylsilyl chloride (2.5 ml, 20 mmol) in anhydrous pyridine (20 ml) while stirring. The reaction mixture is then concentrated by evaporation to a volume of ca. 15 ml while excluding moisture and p-toluenesulfonyl chloride (1.9 g, 10 mmol) is added. The well-sealed reaction vessel is stored overnight at 60° C. in a drying cupboard. Examination of the mixture by thin-layer chromatography shows a complete conversion of the starting materials. The reaction volume is increased by addition of dichloromethane (50 ml) and the organic phase is extracted by shaking with a saturated aqueous sodium bicarbonate solution (60 ml). The aqueous layer is extracted twice with dichloromethane (20 ml). The combined extracts are concentrated in a water jet vacuum and made up to a volume of ca. 15 ml with pyridine. Concentrated aqueous ammonia solution (15 ml) is added to this and the progress of the desilylation is monitored by thin layer chromatography. The reaction is quantitative after 4 hours. The reaction mixture is then concentrated under reduced pressure and the crude product, 4-N-p-toluenesulfonyl-2'-deoxycytidine obtained is concentrated by coevaporation with anhydrous pyridine (3×20 ml) and subsequently dissolved again in absolute pyridine (20 ml). 4,4'-dimethoxytrityl chloride (1.70 g, 5 mmol) is added. The tritylation reaction is observed by thin layer chromatography and is completed within 2 hours. The reaction mixture is partitioned between dichloromethane (50 ml) and 0.5M aqueous sodium bicarbonate solution (50 ml). The aqueous layer is additionally extracted with dichloromethane (2×50 ml) and the organic extracts are dried over anhydrous sodium sulfate and concentrated. Pure 5'-O-dimethoxytrityl-4-N-p-toluenesulfonyl-2'-deoxycytidine is obtained after chromatographic purification on a silica gel column with dichloromethane/methanol as the eluting agent. The product is dissolved in benzene (20 ml), frozen and lyophilized in an oil-pump vacuum. The pure product is isolated as a white solid substance. 2.520 g, 73.7% yield