Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [F:1][C:2]([F:17])([F:16])[C:3]1[CH:7]=[CH:6][N:5]([C:8]2[CH:13]=[CH:12][C:11]([O:14][CH3:15])=[CH:10][CH:9]=2)[N:4]=1.FC(F)(F)[C:20]([OH:22])=[O:21]>>[F:17][C:2]([F:1])([F:16])[C:3]1[CH:7]=[C:6]([C:20]([OH:22])=[O:21])[N:5]([C:8]2[CH:9]=[CH:10][C:11]([O:14][CH3:15])=[CH:12][CH:13]=2)[N:4]=1
Reactant: COc1ccc(-n2ccc(C(F)(F)F)n2)cc1
Reactant: O=C(O)C(F)(F)F
Product: COc1ccc(-n2nc(C(F)(F)F)cc2C(=O)O)cc1

Procedure:
3-Trifluoromethyl-1-(4-methoxyphenyl)-1H-pyrazole-5-(N-(2′-aminosulfonyl-[1,1′]-biphen-4-yl)carboxyamide: 3-Trifluoromethyl-1-(4-methoxyphenyl)-1H-pyrazole-5-(N-(2′-N-t-butylaminosulfonyl-[1,1′]-biphen-4-yl)carboxyamide (0.66 g) was dissolved in trifluoroacetic acid (20 mL) and heated at reflux for 30 min. The reaction was evaporated, then dissolved in ethyl acetate and washed with 1N sodium hydroxide solution (2×) and brine. This solution was dried and evaporated to 0.48 g of crude product. This material was made analytically pure by first subjecting it to flash chromatography with a 200 g column of silica gel and elution with 2:1 hexane:ethyl acetate and finally recrystallizing the homogeneous chromatography product from chloroform. There was obtained 0.262 g of the title compound; mp: 237.3; CHNSF: theory %C, 55.81, %H, 3.718, %N, 10.85, % S, 6.218, %F 11.03; found %C, 56.02, %H, 3.77, %N, 10.51, % S, 5.84, %F, 11.29.
Reaction SMILES: C(O[C:5](=[O:7])[CH3:6])(=O)C.Cl.[S:9]1[CH:13]=[C:12]([NH2:14])[N:11]=[CH:10]1.C(N(CC)CC)C>C(Cl)Cl.O>[S:9]1[CH:13]=[C:12]([NH:14][C:5](=[O:7])[CH3:6])[N:11]=[CH:10]1
Reactant: Nc1cscn1
Reactant: CC(=O)OC(C)=O
Agent: Cl
Solvent: O
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CC(=O)Nc1cscn1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
Acetic anhydride (153 mg, 1.50 mmol) was added to the solution of thiazol-4-amine hydrochloride from example 2.2 (100 mg, 1.0 mmol) and triethylamine (152 mg, 1.50 mmol) in DCM (5 mL). The solution was stirred for overnight at room temperature. The reaction mixture was diluted with water, washed with 0.1 M HCl (10 mL), NaHCO3 solution and brine. The combined organic layers were dried with Na2SO4, filtered and concentrated. The resulting mixture was deposited onto silica gel and loaded onto a silica gel column and eluted with EA/PE (1:2) to aim product (55 mg, 0.39 mmol, 38.7%).
Reaction SMILES: Br[CH2:2][C:3]([O:5][CH2:6][CH3:7])=[O:4].[F:8][C:9]1[CH:17]=[C:16]2[C:12]([C:13]([CH:18]3[CH2:23][CH2:22][NH:21][CH2:20][CH2:19]3)=[N:14][NH:15]2)=[CH:11][CH:10]=1.CCN(CC)CC>>[CH2:6]([O:5][C:3](=[O:4])[CH2:2][N:21]1[CH2:20][CH2:19][CH:18]([C:13]2[C:12]3[C:16](=[CH:17][C:9]([F:8])=[CH:10][CH:11]=3)[NH:15][N:14]=2)[CH2:23][CH2:22]1)[CH3:7]
Reactant: Fc1ccc2c(C3CCNCC3)n[nH]c2c1
Reactant: CCOC(=O)CBr
Solvent: CCN(CC)CC
Product: CCOC(=O)CN1CCC(c2n[nH]c3cc(F)ccc23)CC1
Temperature: 85 °C
Reaction time: 15 h
Yield: 33.3 %

Procedure:
To a suspension of ethyl 2-bromoacetate (0.55 g, 3.3 mmol) and 6-fluoro-3-piperidin-4-yl-1H-indazole (0.60 g, 2.7 mmol in 10 mL of acetonitrile) was added Et3N (1.4 g, 13.7 mmol) and the reaction mixture was stirred at 85° C. for 15 hours. The reaction mixture was cooled to ambient temperature and the solvent was removed in vacuo. The residue was redissolved in DCM (50 mL), washed with water, brine, dried over Na2SO4 and concentrated in vacuo. Purification by flash chromatography gave the title compound (0.29 g, 0.90 mmol) as a white solid. MS (ESI) m/z 306.9 (M+H+); HPLC (Novapak 150×3.9 mm C-18 column: mobile phase: 35-90% acetonitrile/water with 0.1% TFA, at 2 mL/min over 2 min.) t 1.54 min.
Reaction SMILES: [CH2:1]([C:3]1[O:4][C:5]2[CH:14]=[CH:13][C:12]([CH:15]([CH3:20])[C:16]([O:18][CH3:19])=[O:17])=[CH:11][C:6]=2[C:7](=[O:10])[C:8]=1[CH3:9])[CH3:2].S([O-])([O-])(=O)=O.[Ba+2].CC(C)=O.OS(O)(=O)=O.O=[Cr](=O)=O>C(O)C.[Pd].CC(C)=O>[CH2:1]([CH:3]1[CH:8]([CH3:9])[C:7](=[O:10])[C:6]2[CH:11]=[C:12]([CH:15]([CH3:20])[C:16]([O:18][CH3:19])=[O:17])[CH:13]=[CH:14][C:5]=2[O:4]1)[CH3:2]
Reactant: CCc1oc2ccc(C(C)C(=O)OC)cc2c(=O)c1C
Agent: O=[Cr](=O)=O
Agent: [Pd]
Agent: O=S(=O)(O)O
Solvent: CCO
Solvent: CC(C)=O
Product: CCC1Oc2ccc(C(C)C(=O)OC)cc2C(=O)C1C

Procedure:
Methyl 2-[2-ethyl-3-methyl-4-oxo-4H-1-benzopyran-6-yl]propionate (6.61 g) was taken up in dry ethanol (150 ml) and hydrogenated at 85 p.s.i. with 5% palladium on carbon (0.2 g) and 5% palladium on barium sulphate (0.49) for a total of 48 hours. The catalyst was removed by filtration (`Hyflo` supercel) and the ethanol removed in vacuo affording an oil. The oil was taken up in acetone (50 ml) and treated with a slight excess of Jones reagent. The excess oxidant was destroyed with methanol and the reaction mixture was dissolved in water (200 ml) and extracted with ether. The combined ethereal extracts were washed with water, dilute aqueous sodium bicarbonate solution and water, dried (MgSO4) and concentrated in vacuo to give the title compound as an oil--6 g.
Reaction SMILES: [H-].[H-].[H-].[H-].[Li+].[Al+3].[CH:7]([NH:9][CH2:10][C:11]([CH3:17])([CH3:16])[CH2:12][NH:13][CH:14]=O)=O>CCOCC>[CH3:7][NH:9][CH2:10][C:11]([CH3:17])([CH3:16])[CH2:12][NH:13][CH3:14]
Reactant: CC(C)(CNC=O)CNC=O
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: CCOCC
Product: CNCC(C)(C)CNC
Temperature: 25 °C
Reaction time: 20 h

Procedure:
To a mixture of 250 mL of ether and 10 g of LiAlH4 (95%) at 0° C., 9.88 g (62.5 mmol) N,N′-diformyl-2,2-dimethylpropane-1,3-diamine was added in small portions. After the addition, the reaction mixture was stirred at room temperature for 20 h. The mixture was then hydrolyzed with ether and water, the white solid removed by filtration through Celite, and the filtrate dried over anhydrous Na2SO4. After removal of the solvent, the product was obtained as a colorless oil. MS (m/e): 131 (M+).
Reaction SMILES: [OH:1][C@@H:2]1[C@H:6]([OH:7])[C@@H:5]([CH2:8][O:9][CH3:10])[O:4][C@H:3]1[N:11]1[CH:19]=[N:18][C:17]2[C:12]1=[N:13][C:14]([C:35]#[N:36])=[N:15][C:16]=2[NH:20][CH2:21][CH:22]([C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.N.[H][H]>C(O)C.[Pd]>[NH2:36][CH2:35][C:14]1[N:13]=[C:12]2[C:17]([N:18]=[CH:19][N:11]2[C@H:3]2[C@H:2]([OH:1])[C@H:6]([OH:7])[C@@H:5]([CH2:8][O:9][CH3:10])[O:4]2)=[C:16]([NH:20][CH2:21][CH:22]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=2)[N:15]=1
Reactant: [H][H]
Reactant: COC[C@H]1O[C@@H](n2cnc3c(NCC(c4ccccc4)c4ccccc4)nc(C#N)nc32)[C@H](O)[C@@H]1O
Agent: [Pd]
Agent: N
Solvent: CCO
Product: COC[C@H]1O[C@@H](n2cnc3c(NCC(c4ccccc4)c4ccccc4)nc(CN)nc32)[C@H](O)[C@@H]1O
Temperature: 25 °C
Reaction time: 24 h

Procedure:
A solution of 9-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(methoxymethyl)tetrahydro-2-furanyl]-6-[(2,2-diphenylethyl)amino]-9H-purine-2-carbonitrile (preparation 12) (2.15 g, 4.42 mmol) in ethanol (120 ml) saturated with ammonia gas was treated with 5% palladium on charcoal (1 g), pressurised to 1034 kPa (150 psi) with hydrogen in a sealed vessel and stirred at room temperature for 24 hr. The mixture was then filtered through Arbocel (trade mark) and the residue washed with ethanol. The solvent was removed under reduced pressure from the filtrate, the residue dissolved in ethanol and the solvent again removed under reduced pressure. A solid precipitated on re-evaporation which was then dissolved in hot ethanol (100 ml) and the solution cooled and filtered. The residue was washed with ethanol then diethyl ether and dried to give the title compound as an off white solid (1.05 g, 48%). The filtrate and washings were combined and the solvent removed under reduced pressure to give a residue which was then triturated with dichloromethane and a few drops of ethanol and filtered to afford a further portion of product (0.45 g). MS: 491 (MH+).
Reaction SMILES: Cl[C:2]1[C:3]2[N:10]([CH3:11])[C:9]([C:12]3[O:13][CH:14]=[CH:15][CH:16]=3)=[CH:8][C:4]=2[N:5]=[CH:6][N:7]=1.[CH3:17][C:18]1[CH:19]=[C:20]([CH:22]=[CH:23][C:24]=1[O:25][C:26]1[CH:27]=[N:28][C:29]([CH3:32])=[CH:30][CH:31]=1)[NH2:21].CN1CCCC1=O.C(=O)([O-])O.[Na+]>O>[O:13]1[CH:14]=[CH:15][CH:16]=[C:12]1[C:9]1[N:10]([CH3:11])[C:3]2[C:2]([NH:21][C:20]3[CH:22]=[CH:23][C:24]([O:25][C:26]4[CH:27]=[N:28][C:29]([CH3:32])=[CH:30][CH:31]=4)=[C:18]([CH3:17])[CH:19]=3)=[N:7][CH:6]=[N:5][C:4]=2[CH:8]=1
Reactant: Cc1ccc(Oc2ccc(N)cc2C)cn1
Reactant: Cn1c(-c2ccco2)cc2ncnc(Cl)c21
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O
Solvent: CN1CCCC1=O
Product: Cc1ccc(Oc2ccc(Nc3ncnc4cc(-c5ccco5)n(C)c34)cc2C)cn1
Temperature: 140 °C
Reaction time: 3.5 h
Yield: 64.8 %

Procedure:
A mixture of 4-chloro-6-(2-furyl)-5-methyl-5H-pyrrolo[3,2-d]pyrimidine (92 mg), 3-methyl-4-[(6-methylpyridin-3-yl)oxy]aniline (102 mg) and 1-methyl-2-pyrrolidinone (2.5 mL) was stirred at 140° C. for 3.5 hrs, poured into water (10 mL) and adjusted to pH 8 with saturated aqueous sodium hydrogen carbonate. The mixture was extracted with ethyl acetate (25 mL×2), and the organic layers were combined and dried over anhydrous magnesium sulfate. After concentration under reduced pressure, the residue was subjected to silica gel column chromatography (eluent, hexane:ethyl acetate=1:1→0:1). The object fraction was concentrated under reduced pressure. Diethyl ether was added to the residue, and the solid was collected by filtration and dried under reduced pressure at 60° C. to give the title compound (105 mg).
Reaction SMILES: [Cl:1][C:2]1[CH:15]=[CH:14][C:13]2[CH:12]3[CH2:16][C:5]([C:17](O)=[O:18])([C:6]4[C:11]3=[CH:10][CH:9]=[CH:8][CH:7]=4)[C:4]=2[CH:3]=1.S(Cl)(Cl)=O.[NH:24]1[CH2:34][CH2:33][CH:27]([C:28]([O:30][CH2:31][CH3:32])=[O:29])[CH2:26][CH2:25]1.Cl>C1(C)C=CC=CC=1.CN(C)C=O>[Cl:1][C:2]1[CH:15]=[CH:14][C:13]2[CH:12]3[CH2:16][C:5]([C:17]([N:24]4[CH2:25][CH2:26][CH:27]([C:28]([O:30][CH2:31][CH3:32])=[O:29])[CH2:33][CH2:34]4)=[O:18])([C:6]4[C:11]3=[CH:10][CH:9]=[CH:8][CH:7]=4)[C:4]=2[CH:3]=1
Reactant: CCOC(=O)C1CCNCC1
Reactant: O=C(O)C12CC(c3ccccc31)c1ccc(Cl)cc12
Agent: Cl
Solvent: Cc1ccccc1
Solvent: CN(C)C=O
Solvent: O=S(Cl)Cl
Product: CCOC(=O)C1CCN(C(=O)C23CC(c4ccccc42)c2ccc(Cl)cc23)CC1
Temperature: 25 °C
Reaction time: 16 h
Yield: 86.3 %

Procedure:
A suspension of (9RS,10RS)-2-chloro-9,10-dihydro-9,10-methano-9-anthracenecarboxylic acid (7.50 g, 27.7 mmol), prepared as described in Example 1j, in toluene (75 mL) was treated with thionyl chloride (4.12 g, 34.6 mmol) and N,N-dimethylformamide (2 drops). The mixture was heated to reflux for 3 h, then was cooled to room temperature and treated with ethyl isonipecotate (10.88 g, 69.25 mmol). The resulting thick slurry was stirred at room temperature for 16 h, then was poured into 1N hydrochloric acid (100 mL) and extracted with ethyl acetate (3×100 mL). The organic extracts were washed sequentially with 1N hydrochloric acid (100 mL), 10% aqueous sodium bicarbonate (100 mL) and brine (100 ml), combined, dried (MgSO4), filtered and evaporated to leave an amber oil which solidified on standing. The crystalline product was triturated with hexane (300 mL) and ether (25 mL), isolated by filtration, washed with hexane/ether (10:1, 50 mL) and air dried to afford the title compound (9.83 g, 23.9 mmol, 87%) as a white solid. 1H NMR (d6-DMSO): δ7.5 (br, 1H, H--C(1)), 7.35 (m, 3H), 7.01 (m, 3H), 4.5 (br, 1H), 4.43 (s, 1H, H--C(10)), 4.08 (q, J=7.0 Hz, 2H, CH2CH3), 3.6 (br, 1H), 3.2-2.55 (brm, 6H), 2.05-1.45 (brm, 5H), 1.19 (t, J=7.0 Hz, 3H, CH2CH3).
Reaction SMILES: [CH2:1]([C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=1Br)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH3:9].[Mg].[CH:18](=[O:24])[CH2:19][CH2:20][CH2:21][CH2:22][CH3:23].[Cl-].[NH4+]>O1CCCC1.C(Cl)(Cl)(Cl)Cl>[CH2:1]([C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=1[CH:18]([OH:24])[CH2:19][CH2:20][CH2:21][CH2:22][CH3:23])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH3:9]
Reactant: CCCCCC=O
Reactant: CCCCCCCCCc1ccccc1Br
Agent: [Cl-]
Agent: [Mg]
Agent: [NH4+]
Solvent: C1CCOC1
Solvent: ClC(Cl)(Cl)Cl
Product: CCCCCCCCCc1ccccc1C(O)CCCCC
Temperature: -70 °C
Reaction time: 1 h

Procedure:
A third of a solution of 11 g of 2-nonylbromobenzene [cf. EP-OL 0 123 543] in 15 ml of tetrahydrofuran is added to a mixture, stirred under an argon atmosphere, of 1.1 g of magnesium chips, 8 ml of tetrahydrofuran and 3 drops of carbon tetrachloride and the whole is heated at the boil, under reflux, for 30 minutes. The remainder of the solution of 2-nonylbromobenzene is then added dropwise over a period of 35 minutes and the reaction mixture is maintained under reflux for 2 hours. After dilution with 15 ml of tetrahydrofuran, the suspension is cooled to -10° C. and added in portions to a solution, cooled to -70° C., of 4.6 g of hexanal in 12 ml of tetrahydrofuran. After stirring for 1 hour at -70° C., 200 ml of saturated aqueous ammonium chloride solution are added to the reaction mixture, the organic layer is separated off and the aqueous layer is extracted three times with ether. The residue that remains after the combined ethereal extracts have been dried and concentrated by evaporation is purified by chromatography on silica gel with mixtures of petroleum ether with an increasing amount of methylene chloride, yielding the desired 1-(2-nonylphenyl)-1-hexanol in the form of a colourless oil. IR (CH2Cl2): 3600, 2960, 2925, 2855, 1465 cm-1.
Reaction SMILES: [CH3:1][N:2]1[CH2:7][CH2:6][CH:5]([C:8]2[NH:16][C:11]3=[N:12][CH:13]=[CH:14][CH:15]=[C:10]3[N:9]=2)[CH2:4][CH2:3]1.[CH2:17](Cl)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1>>[CH2:17]([N:16]1[C:11]2=[N:12][CH:13]=[CH:14][CH:15]=[C:10]2[N:9]=[C:8]1[CH:5]1[CH2:4][CH2:3][N:2]([CH3:1])[CH2:7][CH2:6]1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1
Reactant: CN1CCC(c2nc3cccnc3[nH]2)CC1
Reactant: ClCc1ccccc1
Product: CN1CCC(c2nc3cccnc3n2Cc2ccccc2)CC1

Procedure:
Operation is carried out similarly to the above description with the difference that 2-(1-methylpiperidin-4-yl)-3H-imidazo-[4,5-b] pyridine is reacted with benzylchloride to obtain 3-benzyl-2-(1-methylpiperidin-4-yl)-3H- imidazo-[4,5-b] pyridine which is isolated as fumarate melting at 205°-207° C. (ethyl alcohol).
Reaction SMILES: [H-].[Al+3].[Li+].[H-].[H-].[H-].[Cl:7][C:8]1[CH:13]=[CH:12][C:11]([CH:14]([CH3:18])[C:15](O)=[O:16])=[CH:10][CH:9]=1.O.[OH-].[Na+]>O1CCCC1>[Cl:7][C:8]1[CH:9]=[CH:10][C:11]([CH:14]([CH3:18])[CH2:15][OH:16])=[CH:12][CH:13]=1
Reactant: CC(C(=O)O)c1ccc(Cl)cc1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: O
Solvent: C1CCOC1
Product: CC(CO)c1ccc(Cl)cc1
Temperature: 25 °C
Reaction time: 16 h

Procedure:
To a suspension of 3.8 g (0.10 mole) of lithium aluminum hydride in 50 mL of tetrahydrofuran is added dropwise a solution of 18.4 g (0.10 mole) of 2-(4-chlorophenyl)propionic acid in 200 mL of tetrahydrofuran. This reaction mixture is allowed to stir at ambient temperature for a period of approximately 16 hours after which it is cooled by an ice/water bath. To the cooled reaction mixture are added in sequence 4 mL of water, 4 mL of a 10% aqueous solution of sodium hydroxide, and 12 mL of water. The mixture is then filtered, and the filter cake is washed with diethyl ether. The diethyl ether wash is combined with the filtrate, and the combination is dried over anhydrous magnesium sulfate. The solvents are then evaporated under reduced pressure, leaving 2-(4-chlorophenyl)propanol as a residue.
Reaction SMILES: [C:1]([O:4][C@H:5]1[CH2:24][CH2:23][C@@:22]2([CH3:25])[C@H:7]([CH2:8][CH2:9][C@@H:10]3[C@@H:21]2[CH2:20][CH2:19][C@@:18]2([CH3:26])[C:11]3=[CH:12][CH2:13][C@@H:14]2[C:15](=[O:17])[CH3:16])[CH2:6]1)(=[O:3])[CH3:2].C([O-])([O-])=O.[K+].[K+]>CO.O>[C:1]([O:4][C@H:5]1[CH2:24][CH2:23][C@@:22]2([CH3:25])[C@H:7]([CH2:8][CH2:9][C@@H:10]3[C@@H:21]2[CH2:20][CH2:19][C@@:18]2([CH3:26])[C:11]3=[CH:12][CH2:13][C@H:14]2[C:15](=[O:17])[CH3:16])[CH2:6]1)(=[O:3])[CH3:2]
Reactant: CC(=O)O[C@H]1CC[C@@]2(C)[C@H](CC[C@H]3C4=CC[C@H](C(C)=O)[C@@]4(C)CC[C@@H]32)C1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CO
Solvent: O
Product: CC(=O)O[C@H]1CC[C@@]2(C)[C@H](CC[C@H]3C4=CC[C@@H](C(C)=O)[C@@]4(C)CC[C@@H]32)C1

Procedure:
A solution of 10.0 g of 3β-acetoxy-5β-pregn-14-en-20-one (Bach, G. et al. Can. J. Chem. 1968, 46, 733) and K2CO3 (25.0 g) in MeOH/water (160 mL/80 mL) was stirred at room temperature for 2 hrs; the organic solvent was evaporated to dryness under reduced pressure and the aqueous suspension obtained was extracted with CH2Cl2 ; the organic layer was dried over anhydrous sodium sulfate and evaporated to dryness under reduced pressure; the crude 3β-acetoxy-5β,17α-pregn-14-en-20-one obtained was used for the next step without further purification. A solution of the crude intermediate and p-toluensulphonyl hydrazide (11.1 g) in AcOH (300 mL) was stirred at room temp. for 12 hrs. To this solution NaBH4 (7.8 g) was added portionwise; after 2 hrs the reaction mixture was poured in water/ice and the aqueous suspension obtained was extracted with AcOEt and neutralised with 0.1 N NaOH: the organic layer was dried over anhydrous sodium sulfate and evaporated to dryness under reduced pressure. The residue was purified by flash-chromatography (SiO2) using n-hexane/ethyl acetate 1/1 as eluant to give 7.0 g of 3β-acetoxy-5β,17α-pregn-14-ene as a white solid.
Reaction SMILES: [C:1]([C:5]1[CH:10]=[CH:9][C:8]([S:11]([NH:14][C:15]2[CH:16]=[C:17]([CH:21]=[C:22]([O:33][CH2:34][CH2:35][OH:36])[C:23]=2[O:24][C:25]2[CH:30]=[CH:29][CH:28]=[C:27]([O:31][CH3:32])[CH:26]=2)[C:18](O)=[O:19])(=[O:13])=[O:12])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[NH2:37][C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][C:39]=1[C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1>>[C:39]1([C:44]2[CH:45]=[CH:46][CH:47]=[CH:48][CH:49]=2)[CH:40]=[CH:41][CH:42]=[CH:43][C:38]=1[NH:37][C:18](=[O:19])[C:17]1[CH:21]=[C:22]([O:33][CH2:34][CH2:35][OH:36])[C:23]([O:24][C:25]2[CH:30]=[CH:29][CH:28]=[C:27]([O:31][CH3:32])[CH:26]=2)=[C:15]([NH:14][S:11]([C:8]2[CH:7]=[CH:6][C:5]([C:1]([CH3:3])([CH3:2])[CH3:4])=[CH:10][CH:9]=2)(=[O:13])=[O:12])[CH:16]=1
Reactant: COc1cccc(Oc2c(NS(=O)(=O)c3ccc(C(C)(C)C)cc3)cc(C(=O)O)cc2OCCO)c1
Reactant: Nc1ccccc1-c1ccccc1
Product: COc1cccc(Oc2c(NS(=O)(=O)c3ccc(C(C)(C)C)cc3)cc(C(=O)Nc3ccccc3-c3ccccc3)cc2OCCO)c1

Procedure:
Analogously to Example 74, by condensing 3-(4-tert-butyl-benzenesulphonylamino)-5-(2-hydroxy-ethoxy)-4-(3-methoxy-phenoxy)-benzoic acid with 2-aminobiphenyl there was obtained N-biphenyl-2-yl-3-(4-tert-butyl-benzenesulphonylamino)-5-(2-hydroxy-ethoxy)-4-(3-methoxy-phenoxy)-benzamide.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[N:4][C:5]2[N:6]([N:8]=[C:9]([C:11]([OH:13])=O)[CH:10]=2)[CH:7]=1.Br.[CH2:15]([C:17]1[S:18][C:19]2[CH2:25][CH2:24][NH:23][CH2:22][CH2:21][C:20]=2[N:26]=1)[CH3:16]>>[Br:1][C:2]1[CH:3]=[N:4][C:5]2[N:6]([N:8]=[C:9]([C:11]([N:23]3[CH2:24][CH2:25][C:19]4[S:18][C:17]([CH2:15][CH3:16])=[N:26][C:20]=4[CH2:21][CH2:22]3)=[O:13])[CH:10]=2)[CH:7]=1
Reactant: O=C(O)c1cc2ncc(Br)cn2n1
Reactant: CCc1nc2c(s1)CCNCC2
Agent: Br
Product: CCc1nc2c(s1)CCN(C(=O)c1cc3ncc(Br)cn3n1)CC2

Procedure:
The title compound was prepared in accordance with the general method of example 1 from 6-bromo-pyrazolo[1,5-A]pyrimidine-2-carboxylic acid and 2-ethyl-5,6,7,8-tetrahydro-4H-thiazolo[4,5-d]azepine hydrobromide. The reaction mixture was purified by HPLC chromatography and lyophilized. Yield: 24 mg (29% of theory). ESI-MS: m/z=406 (M+H)+; Rt(HPLC): 1.19 min. (Method J).
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([C:8]2[N:13]=[C:12]([C:14]([F:17])([F:16])[F:15])[CH:11]=[C:10]([C:18]3[CH:23]=[CH:22][C:21]([C:24]([F:27])([F:26])[F:25])=[CH:20][CH:19]=3)[N:9]=2)[CH:5]=[CH:6][CH:7]=1.[C:28]([NH:32][S:33]([C:36]1[CH:37]=[C:38](B(O)O)[CH:39]=[CH:40][CH:41]=1)(=[O:35])=[O:34])([CH3:31])([CH3:30])[CH3:29]>>[C:28]([NH:32][S:33]([C:36]1[CH:41]=[C:40]([C:2]2[CH:7]=[CH:6][CH:5]=[C:4]([C:8]3[N:13]=[C:12]([C:14]([F:16])([F:17])[F:15])[CH:11]=[C:10]([C:18]4[CH:19]=[CH:20][C:21]([C:24]([F:25])([F:27])[F:26])=[CH:22][CH:23]=4)[N:9]=3)[CH:3]=2)[CH:39]=[CH:38][CH:37]=1)(=[O:35])=[O:34])([CH3:31])([CH3:29])[CH3:30]
Reactant: FC(F)(F)c1ccc(-c2cc(C(F)(F)F)nc(-c3cccc(Br)c3)n2)cc1
Reactant: CC(C)(C)NS(=O)(=O)c1cccc(B(O)O)c1
Product: CC(C)(C)NS(=O)(=O)c1cccc(-c2cccc(-c3nc(-c4ccc(C(F)(F)F)cc4)cc(C(F)(F)F)n3)c2)c1

Procedure:
The title compound was prepared from 2-(3-bromo-phenyl)-4-trifluoromethyl-6-(4-trifluoromethyl-phenyl)-pyrimidine (example E.3) (0.45 g, 1.0 mmol) and commercially available 3-(tert.-butylsulfamoyl)-phenylboronic acid (0.31 g, 1.2 mmol) according to the general procedure VI. Obtained as a white solid (0.48 g, 83%). MS (ISP) 580.3 [(M+H)+]; mp 200° C.
Reaction SMILES: I[C:2]1[C:6]([C:7]2[CH:12]=[CH:11][N:10]=[C:9]([S:13][CH3:14])[N:8]=2)=[CH:5][N:4]([CH:15]2[CH2:20][CH2:19][CH2:18][CH2:17][O:16]2)[N:3]=1.CC1(C)C(C)(C)OB([C:29]2[CH:30]=[C:31]3[CH:37]=[CH:36][NH:35][C:32]3=[N:33][CH:34]=2)O1.C(=O)([O-])[O-].[Na+].[Na+]>CN(C=O)C>[CH3:14][S:13][C:9]1[N:8]=[C:7]([C:6]2[C:2]([C:29]3[CH:30]=[C:31]4[CH:37]=[CH:36][NH:35][C:32]4=[N:33][CH:34]=3)=[N:3][N:4]([CH:15]3[CH2:20][CH2:19][CH2:18][CH2:17][O:16]3)[CH:5]=2)[CH:12]=[CH:11][N:10]=1
Reactant: CSc1nccc(-c2cn(C3CCCCO3)nc2I)n1
Reactant: CC1(C)OB(c2cnc3[nH]ccc3c2)OC1(C)C
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CSc1nccc(-c2cn(C3CCCCO3)nc2-c2cnc3[nH]ccc3c2)n1
Temperature: 85 °C
Yield: 69 %

Procedure:
To a solution of 4-[3-Iodo-1-(tetrahydro-pyran-2-yl)-1H-pyrazol-4-yl]-2-methylsulfanyl-pyrimidine B (1.33 g, 3.3 mmol) and 5-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine (1 g, 4.1 mmol) in DMF (30 mL) was added a 2M solution of sodium carbonate (2 mL). The sodium carbonate appeared to come out of solution upon addition. The mixture was deoxygenated with a nitrogen bubbler for a few minutes. The palladium catalyst was added and nitrogen bubbling continued for a few minutes before the bubbler was removed. The mixture was heated at 85° C. for 18 hr. LCMS shows complete conversion to product. The mixture was dropped into saturated aqueous NaCl and the resulting solids collected by filtration and rinsed with water. The solids were dissolved in methanol/dichloromethane (1:9), dried over MgSO4 and reduced to minimum volume. The residue was purified on a short column of silica gel using a gradient of 0-50% ethyl acetate in dichloromethane as eluant to give 5-[4-(2-Methylsulfanyl-pyrimidin-4-yl)-1-(tetrahydro-pyran-2-yl)-1H-pyrazol-3-yl]-1H-pyrrolo[2,3-b]pyridine (C-1-1) (0.89 g, 69%) as a yellow solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 11.73 (br. s., 1H), 8.69 (s, 1H), 8.43 (d, J=5.31 Hz, 1H), 8.29 (d, J=2.02 Hz, 1H), 8.07 (d, J=2.02 Hz, 1H), 7.51 (t, J=3.03 Hz, 1H), 7.11 (d, J=5.31 Hz, 1H), 6.48 (dd, J=3.28, 1.77 Hz, 1H), 5.53 (dd, J=9.85, 2.27 Hz, 1H), 4.00 (br. d, J=13.39 Hz, 1H), 3.61-3.76 (br. m, 1H), 2.10-2.24 (br. m, 4H), 1.91-2.06 (br. m, 2H), 1.65-1.80 (br. m, 1H), 1.50-1.63 (br. m, 2H).
Reaction SMILES: [H-].[Na+].Br[C:4]1[CH:9]=[CH:8][C:7]([CH:10]([OH:15])[C:11]([F:14])([F:13])[F:12])=[CH:6][CH:5]=1.Br[CH:17]([CH2:22][CH:23]([CH3:25])[CH3:24])[C:18]([O:20][CH3:21])=[O:19].Cl>C1COCC1.C(OCC)C.C(OCC)(=O)C>[CH3:24][CH:23]([CH3:25])[CH2:22][CH:17]([O:15][CH:10]([C:7]1[CH:8]=[CH:9][CH:4]=[CH:5][CH:6]=1)[C:11]([F:14])([F:13])[F:12])[C:18]([O:20][CH3:21])=[O:19]
Reactant: COC(=O)C(Br)CC(C)C
Reactant: OC(c1ccc(Br)cc1)C(F)(F)F
Agent: Cl
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CCOCC
Solvent: CCOC(C)=O
Product: COC(=O)C(CC(C)C)OC(c1ccccc1)C(F)(F)F
Temperature: 0 °C
Reaction time: 0.75 h

Procedure:
Sodium hydride (60% W, 2.16 mmol, 87 mg) was suspended in dry THF and cooled to 0° C. A solution of 1-(4-bromophenyl)-2,2,2-trifluoroethanol from example 69 step 2 was added slowly and stirred at 0° C. over 0.75 h. A solution of methyl 2-bromo-4-methylpentanoate from example 69 step 1 was added and the mixture was allowed to warmed to r.t. and stirred overnight. The reaction was treated with 0.1 N aqueous hydrochloric acid, diluted with diethyl ether and ethyl acetate. The phases are separated and the organic layer was washed with 0.1N aqueous hydrochloric acid then brine and dried over magnesium sulfate. The volatiles were removed unde reduced pressure to yield methyl 4-methyl-2-(2,2,2-trifluoro-1-phenylethoxy)pentanoate that was used without further purification.