Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: FC(F)(F)C(O)=O.FC(F)(F)C(O)=O.[O:15]([C:22]1[C:27]2[C:28]([NH:31][CH2:32][CH:33]3[CH2:38][CH2:37][NH:36][CH2:35][CH2:34]3)=[N:29][NH:30][C:26]=2[CH:25]=[CH:24][N:23]=1)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.Cl.Cl.Cl.[N:42]1[CH:47]=[CH:46][CH:45]=[CH:44][C:43]=1[C:48]1[S:49][C:50]([CH2:53]N2CCC(CN)CC2)=[CH:51][N:52]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.C[N+](C)(C)C>C(#N)C>[O:15]([C:22]1[C:27]2[C:28]([NH:31][CH2:32][CH:33]3[CH2:38][CH2:37][N:36]([CH2:53][C:50]4[S:49][C:48]([C:43]5[CH:44]=[CH:45][CH:46]=[CH:47][N:42]=5)=[N:52][CH:51]=4)[CH2:35][CH2:34]3)=[N:29][NH:30][C:26]=2[CH:25]=[CH:24][N:23]=1)[C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1
Reactant: c1ccc(Oc2nccc3[nH]nc(NCC4CCNCC4)c23)cc1
Reactant: NCC1CCN(Cc2cnc(-c3ccccn3)s2)CC1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: C[N+](C)(C)C
Agent: Cl
Solvent: O=C(O)C(F)(F)F
Solvent: CC#N
Product: c1ccc(Oc2nccc3[nH]nc(NCC4CCN(Cc5cnc(-c6ccccn6)s5)CC4)c23)cc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 16.7 %

Procedure:
A solution of the compound prepared in Example 436 (0.053 g) and the compound prepared in Example 214 (0.039 g) in acetonitrile (1 mL) was stirred at room temperature for 30 minutes. Tetramethylammoniumtriacetoxy borohydride (0.094 g) was added and stirring at room temperature continued for 1 hour. The reaction mixture was quenched with aqueous saturated sodium bicarbonate. After stirring at room temperature for 20 minutes, hopeful product was extracted with ethyl acetate, washed with aqueous saturated sodium bicarbonate, dried, evaporated in vacuo to an oil that was purified by column chromatography on silica gel (1-5% methanol in dichloromethane) to provide the title compound (0.008 g) with the following physical data.
Reaction SMILES: [C:1]1([C:7]2[N:11]=[C:10]([N:12]3[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]3)[S:9][N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(N(CC)CC)C.[C:25]([C:27]1[CH:28]=[C:29]([N:33]=[C:34]=[O:35])[CH:30]=[CH:31][CH:32]=1)#[N:26]>O1CCCC1>[C:25]([C:27]1[CH:28]=[C:29]([NH:33][C:34]([N:15]2[CH2:16][CH2:17][N:12]([C:10]3[S:9][N:8]=[C:7]([C:1]4[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=4)[N:11]=3)[CH2:13][CH2:14]2)=[O:35])[CH:30]=[CH:31][CH:32]=1)#[N:26]
Reactant: N#Cc1cccc(N=C=O)c1
Reactant: c1ccc(-c2nsc(N3CCNCC3)n2)cc1
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: N#Cc1cccc(NC(=O)N2CCN(c3nc(-c4ccccc4)ns3)CC2)c1
Temperature: 25 °C
Reaction time: 1 h
Yield: 64.3 %

Procedure:
To a solution of 1-(3-phenyl-1,2,4-thiadiazol-5-yl)piperazine (200 mg, 0.812 mmol) and triethylamine (0.113 ml, 0.812 mmol) in tetrahydrofuran (2 ml) was added 3-cyanophenyl isocyanate (176 mg, 1.22 mmol) at room temperature, and the mixture was stirred at room temperature for 1 hour. The solvent was distilled off under reduced pressure. The residue was purified by high performance liquid chromatography (YMC HPLC Column eluted with 10% to 100% Liquid A; Liquid A: a 0.1% solution of trifluoroacetic acid in acetonitrile; Liquid B: an aqueous 0.1% trifluoroacetic acid solution) and recrystallized from a mixed solvent of hexane and tetrahydrofuran to give 204 mg (64.4%) of the desired product as a solid.
Reaction SMILES: [C:1]([CH2:3][CH2:4][C:5]([OH:13])([P:9]([OH:12])([OH:11])=[O:10])[C:6]([OH:8])=[O:7])#[N:2].[H][H]>N.[Rh]>[NH2:2][CH2:1][CH2:3][CH2:4][C:5]([OH:13])([P:9]([OH:12])([OH:11])=[O:10])[C:6]([OH:8])=[O:7]
Reactant: N#CCCC(O)(C(=O)O)P(=O)(O)O
Reactant: [H][H]
Agent: [Rh]
Agent: N
Product: NCCCC(O)(C(=O)O)P(=O)(O)O

Procedure:
The hydrogenation of 4-cyano-2-hydroxy-2-phosphonobutanoic acid is carried out using the hydrogenation technique of Freifelder (J. Am. Chem. Soc., 82 2386 (1960)). The cyano compound (2.09 g; 0.01 mole) is placed in 20 ml of 10% methanolic ammonia. Rhodium on alumina (5%) catalyst (0.5 g) is added, and the mixture is hydrogenated at 40 PSI on a Parr apparatus for several hours (until uptake of hydrogen is complete). The catalyst is filtered of and the filtrate is evaporated dry. The residue treated with cation exchange resin in H+ form to convert the material to acid form. The solution containing it is evaporated to dryness under vacuum. The product is purified by dissolving the residue in water, adding ethanol to give a precipitate, and collecting the solids by filtration. Further purification is accomplished by again recrystallizing from water/ethanol.
Reaction SMILES: Br[C:2]1[C:10]2[C:9]([NH2:11])=[N:8][CH:7]=[N:6][C:5]=2[N:4]([CH:12]([CH3:14])[CH3:13])[CH:3]=1.CC1(C)C(C)(C)OB([C:23]2[CH:24]=[C:25]3[C:29](=[CH:30][CH:31]=2)[N:28]([C:32](=[O:44])[CH2:33][C:34]2[CH:39]=[CH:38][CH:37]=[C:36]([C:40]([F:43])([F:42])[F:41])[CH:35]=2)[CH2:27][CH2:26]3)O1.O1CCOCC1.C([O-])(O)=O.[Na+]>O.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>[CH3:13][CH:12]([N:4]1[C:5]2[N:6]=[CH:7][N:8]=[C:9]([NH2:11])[C:10]=2[C:2]([C:23]2[CH:24]=[C:25]3[C:29](=[CH:30][CH:31]=2)[N:28]([C:32](=[O:44])[CH2:33][C:34]2[CH:39]=[CH:38][CH:37]=[C:36]([C:40]([F:43])([F:41])[F:42])[CH:35]=2)[CH2:27][CH2:26]3)=[CH:3]1)[CH3:14]
Reactant: CC(C)n1cc(Br)c2c(N)ncnc21
Reactant: CC1(C)OB(c2ccc3c(c2)CCN3C(=O)Cc2cccc(C(F)(F)F)c2)OC1(C)C
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: C1COCCO1
Solvent: O
Product: CC(C)n1cc(-c2ccc3c(c2)CCN3C(=O)Cc2cccc(C(F)(F)F)c2)c2c(N)ncnc21
Temperature: 100 °C
Yield: 47.2 %

Procedure:
To 5-bromo-7-(1-methylethyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine (70 mg, 0.274 mmol) and 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-{[3-(trifluoromethyl)phenyl]acetyl}-2,3-dihydro-1H-indole (166 mg, 0.384 mmol) were added 1,4-Dioxane (2 mL) and saturated NaHCO3 (1 mL) in a 5 ml sealable vessel. The mixture was then bubbled with N2 gas for 5 minutes then added Pd(Ph3P)4 (317 mg, 0.274 mmol) and the vessel was capped. The reaction was then heated at 100° C. overnight. The reaction was then diluted with water (2 ml) then extracted with EtOAc (3×3 ml). The organics were then combined and washed with brine, dried over MgSO4, filtered and concentrated. The residue was dissolved in 3 mL of DMSO and then purified by HPLC: (HPLC condition: open-access Gilson using Trilution software with a Sunfire 5u C18(2) 100A. 50×30.00 mm 5 micron. 7.3-minute run (47 ml/min, 35% ACN/H2O, 0.1% TFA to 60% ACN/H2O, 0.1% TFA) with UV detection at 220 nm). Product fractions were combined and the volume was reduced to remove most of the MeCN. To the water left behind was added saturated NaHCO3 and the mixture was extracted with EtOAc (3×15 mL). The organics were combined wash with saturated NaCl solution, dried over MgSO4, filtered and concentrated. The product was transferred to a 40 mL vial with MeCN then water was added and the solution was freeze-dried to provide 7-(1-methylethyl)-5-(1-{[3-(trifluoromethyl)phenyl]acetyl}-2,3-dihydro-1H-indol-5-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine (62 mg, 47.1% yield) as a white solid. LC-MS (ES) m/z=480.5 [M+H]+. 1H NMR (400 MHz, DMSO-d6) δ 8.23 (s, 1H), 8.13 (d, J=8.34 Hz, 1H), 7.69 (s, 1H), 7.57-7.67 (m, 3H), 7.54 (s, 1H), 7.36 (s, 1H), 7.26 (d, J=8.08 Hz, 1H), 6.57 (br. s., 2H), 4.99 (quin, J=6.76 Hz, 1H), 4.28 (t, J=8.46 Hz, 2H), 4.04 (s, 2H), 3.23-3.28 (m, 2H), 1.47 (d, J=6.82 Hz, 6H).
Reaction SMILES: ON1C2C=CC=CC=2N=N1.ClCCl.CN(C=O)C.[CH3:19][S:20]([C:23]1[CH:24]=[C:25]([CH:29]=[CH:30][CH:31]=1)[C:26]([OH:28])=O)(=[O:22])=[O:21].[CH3:32][C:33]([CH3:54])([CH3:53])[CH2:34][CH2:35][NH:36][C:37](=[O:52])[C@H:38]([CH3:51])[CH2:39][C@H:40]([OH:50])[C@@H:41]([NH2:49])[CH2:42][C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1>CN(C=O)C.ClCCl>[CH2:42]([C@H:41]([NH:49][C:26](=[O:28])[C:25]1[CH:29]=[CH:30][CH:31]=[C:23]([S:20]([CH3:19])(=[O:21])=[O:22])[CH:24]=1)[C@@H:40]([OH:50])[CH2:39][C@H:38]([C:37](=[O:52])[NH:36][CH2:35][CH2:34][C:33]([CH3:32])([CH3:53])[CH3:54])[CH3:51])[C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1
Reactant: C[C@H](C[C@H](O)[C@@H](N)Cc1ccccc1)C(=O)NCCC(C)(C)C
Reactant: CS(=O)(=O)c1cccc(C(=O)O)c1
Agent: On1nnc2ccccc21
Solvent: ClCCl
Solvent: CN(C)C=O
Product: C[C@H](C[C@H](O)[C@H](Cc1ccccc1)NC(=O)c1cccc(S(C)(=O)=O)c1)C(=O)NCCC(C)(C)C
Temperature: 25 °C
Reaction time: 8 h
Yield: 48.7 %

Procedure:
N-Cyclohexylcarbodiimide-N′-methyl polystyrene (100 mg @ 1.70 mmol/g; ex. Novabiochem) was treated with dichloromethane (0.5 ml) followed by a solution of 1-hydroxybenzotriazole (22 mg, 0.14 mmol) in 4:1 dichloromethane/DMF (0.5 ml). 3-Methanesulfonyl benzoic acid (28 mg, 0.14 mmol) in DMF (0.5 ml) and (2R,4S,5S)-5-amino-4-hydroxy-2-methyl-6-phenylhexanoic acid (3,3-dimethylbutyl)-amide (D2) (30 mg, 0.094 mmol) in dichloromethane (0.5 ml) were then added and the mixture was stirred gently overnight at room temperature. It was then diluted with dichloromethane (0.5 ml) and treated with methylisocyanate polystyrene (100 mg @ 1.80 mmol/g; ex. Novabiochem) and tris-(2-aminoethyl)-amine polystyrene (100 mg @ 3.20 mmol/g; ex. Novabiochem), and the mixture was stirred gently for a further 1.5 h. It was then filtered and the spent resins were washed with DMF (1 ml) and dichloromethane (1 ml). The combined filtrates were evaporated to dryness and the residue was triturated with diethyl ether/hexane to afford the title compound (E1) as a white solid (23 mg, 49%).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[C:7]([O:9][CH3:10])[C:6]([C:11]([O:13][CH3:14])=[O:12])=[CH:5][C:4]=1[CH:15]([CH2:20][CH2:21][CH2:22][CH2:23][CH3:24])[CH2:16][C:17]([OH:19])=O.[C:25]([C:29]1[CH:35]=[CH:34][C:33]([C:36](=[O:38])[NH2:37])=[CH:32][C:30]=1[NH2:31])([CH3:28])([CH3:27])[CH3:26]>C(Cl)Cl.C(OCC)C>[C:25]([C:29]1[CH:35]=[CH:34][C:33]([C:36](=[O:38])[NH2:37])=[CH:32][C:30]=1[NH:31][C:17](=[O:19])[CH2:16][CH:15]([C:4]1[CH:5]=[C:6]([C:11]([O:13][CH3:14])=[O:12])[C:7]([O:9][CH3:10])=[CH:8][C:3]=1[O:2][CH3:1])[CH2:20][CH2:21][CH2:22][CH2:23][CH3:24])([CH3:28])([CH3:26])[CH3:27]
Reactant: CCCCCC(CC(=O)O)c1cc(C(=O)OC)c(OC)cc1OC
Reactant: CC(C)(C)c1ccc(C(N)=O)cc1N
Solvent: ClCCl
Solvent: CCOCC
Product: CCCCCC(CC(=O)Nc1cc(C(N)=O)ccc1C(C)(C)C)c1cc(C(=O)OC)c(OC)cc1OC

Procedure:
Following a similar procedure to that described in Example 44, but using 3-(2,4-dimethoxy-5-methoxycarbonylphenyl)octanoic acid (prepared as described in Preparation 37) and 2-t-butyl-5-carbamoylaniline (prepared as described in Preparation 38), the title compound was obtained as crystals, melting at 101°-103° C. (from methylene chloride-diethyl ether).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([O:17][CH2:18][C:19]2[C:24]([F:25])=[CH:23][CH:22]=[CH:21][C:20]=2[F:26])[C:5]2[N:6]([C:8]([C:12]([O:14]CC)=[O:13])=[C:9]([CH3:11])[N:10]=2)[CH:7]=1.[OH-].[Li+].Cl>C1COCC1.CO>[Br:1][C:2]1[CH:3]=[C:4]([O:17][CH2:18][C:19]2[C:20]([F:26])=[CH:21][CH:22]=[CH:23][C:24]=2[F:25])[C:5]2[N:6]([C:8]([C:12]([OH:14])=[O:13])=[C:9]([CH3:11])[N:10]=2)[CH:7]=1
Reactant: CCOC(=O)c1c(C)nc2c(OCc3c(F)cccc3F)cc(Br)cn12
Agent: Cl
Agent: [Li+]
Agent: [OH-]
Solvent: CO
Solvent: C1CCOC1
Product: Cc1nc2c(OCc3c(F)cccc3F)cc(Br)cn2c1C(=O)O
Temperature: 40 °C
Reaction time: 6 h

Procedure:
1.5 g of ethyl 6-bromo-8-[(2,6-difluorobenzyl)oxy]-2-methylimidazo[1,2-a]pyridine-3-carboxylate (Example 18A; 3.5 mmol, 1 equivalent) were dissolved in 72 ml of THF/methanol 5:1, 17.6 ml of 1N aqueous lithium hydroxide solution (17.6 mmol, 5 equivalents) were added and the mixture was warmed to 40° C. and stirred at this temperature for 6 h. Using 6 N aqueous hydrochloric acid, the mixture was then adjusted to pH 4 and concentrated under reduced pressure. Water was added to the solid formed and the solid was triturated, filtered off, washed with water and dried under reduced pressure. This gave 1.24 g of the title compound (88% of theory).
Reaction SMILES: [NH2:1][C:2]1[CH:15]=[C:14]([CH3:16])[CH:13]=[CH:12][C:3]=1[C:4]([C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)=[O:5].[CH3:17][C:18]([CH3:20])=O.[BH4-].[Na+]>C(O)(=O)C>[CH:18]([NH:1][C:2]1[CH:15]=[C:14]([CH3:16])[CH:13]=[CH:12][C:3]=1[C:4]([C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)=[O:5])([CH3:20])[CH3:17]
Reactant: Cc1ccc(C(=O)c2ccccc2)c(N)c1
Reactant: CC(C)=O
Agent: [BH4-]
Agent: [Na+]
Solvent: CC(=O)O
Product: Cc1ccc(C(=O)c2ccccc2)c(NC(C)C)c1
Temperature: 20 °C
Yield: 99 %

Procedure:
To a solution of 21.1 gms. of 2-amino-4-methylbenzophenone in 100 mls. of acetone is added 100 mls. of glacial acetic acid. The solution is cooled to 20° C. With stirring, and by portionwise addition, 10 gms. of sodium borohydride is added to the solution over a period of 70 minutes. After the addition, the solution is stirred for an additional 20 minutes at 20° C., and extracted with 100 mls. of chloroform and 50 mls. of water. The aqueous phase is extracted twice using 50 mls. of chloroform each time. All the chloroform solutions are then combined and treated with 150 mls. of 20% ammonium hydroxide. The chloroform phase is dried over magnesium sulphate, filtered and concentrated by distillation to a constant weight of 25 gms or a crude 99% yield of 2-(N-isopropylamino)-4-methylbenzophenone, providing an actual yield of pure material of at least 90%.
Reaction SMILES: [O:1]1[C:5]2([CH2:10][CH2:9][CH:8]([CH:11]=O)[CH2:7][CH2:6]2)[O:4][CH2:3][CH2:2]1.[CH2:13]1COCC1>>[CH:11]([CH:8]1[CH2:7][CH2:6][C:5]2([O:1][CH2:2][CH2:3][O:4]2)[CH2:10][CH2:9]1)=[CH2:13]
Reactant: C1CCOC1
Reactant: O=CC1CCC2(CC1)OCCO2
Product: C=CC1CCC2(CC1)OCCO2
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a flask containing triphenylphosphonium bromide-sodamide complex (20.04 g, 48.10 mmol) was added THF (100 mL). After stirring @ rt for 1 hour, the solution was bright yellow (with some ppt). The r×n mixture was cooled to 0° C. and a solution of 1,4-dioxaspiro[4.5]decane-8-carbaldehyde (693 mg, 4.07 mmol, prepared as described in Pearson, et al. in J. Org. Chem. 1997, 62(16), 5284-5292) in THF (20 mL) was added dropwise via syringe. After the complete addition, the reaction mixture turned light peach and was stirred, warming to rt overnight. The reaction was quenched cautiously with saturated aq NaHCO3 at 0° C. and allowed to warm to room temperature, followed by water and extraction with ether. The concentrated organic layers were purified by flash chrom (silica gel, ether, stains PAA). To avoid losing some material on the rotovap (seems volatile), the bath temperature was kept under 35° C.
Reaction SMILES: Br[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([CH:11]=[O:12])=[CH:9][N:10]=2)[CH:7]=1.[N:13]1[CH:18]=[C:17](B(O)O)[CH:16]=[N:15][CH:14]=1>>[N:13]1[CH:18]=[C:17]([C:2]2[CH:3]=[CH:4][C:5]3[N:6]([C:8]([CH:11]=[O:12])=[CH:9][N:10]=3)[CH:7]=2)[CH:16]=[N:15][CH:14]=1
Reactant: OB(O)c1cncnc1
Reactant: O=Cc1cnc2ccc(Br)cn12
Product: O=Cc1cnc2ccc(-c3cncnc3)cn12
Yield: 50 %

Procedure:
The title compound was prepared by following the procedure as described for Intermediate 1 using 6-bromoimidazo[1,2-a]pyridine-3-carbaldehyde and pyrimidin-5-ylboronic acid.
Reaction SMILES: [Cl:1][C:2]1[C:7]([CH3:8])=[C:6]([Cl:9])[CH:5]=[CH:4][C:3]=1[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.[Br:16]N1C(=O)CCC1=O>C(Cl)(Cl)(Cl)Cl>[Br:16][CH2:8][C:7]1[C:2]([Cl:1])=[C:3]([C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=2)[CH:4]=[CH:5][C:6]=1[Cl:9]
Reactant: O=C1CCC(=O)N1Br
Reactant: Cc1c(Cl)ccc(-c2ccccc2)c1Cl
Solvent: ClC(Cl)(Cl)Cl
Product: Clc1ccc(-c2ccccc2)c(Cl)c1CBr
Yield: 99.1 %

Procedure:
A stirred solution of 10.6 g (0.045 mole) of 2,4-dichloro-3-methyl[1,1'-biphenyl] and 8.0 g (0.045 mole) of N-bromosuccinimide in 100 ml of carbon tetrachloride was irradiated with a 250 watt infra-red lamp for 4 hours. The reaction mixture was allowed to reflux from the heat of the lamp during the 4 hour period. The reaction mixture was filtered and the filter cake was washed with one portion of 100 ml of carbon tetrachloride. The wash and filtrate were combined and washed with one portion of a saturated aqueous solution of sodium chloride. The organic layer was dried with magnesium sulfate, filtered and the filtrate concentrated under reduced pressure to give 14.1 g of 3-bromomethyl-2,4-dichloro[1,1'-biphenyl]. The nmr spectrum was consistent with the proposed structure.
Reaction SMILES: [CH2:1]([C:7]1[CH:8]=[C:9]([C:13]2[N:17]([CH3:18])[C:16]([C:19]([N:21]3[CH2:26][CH2:25][CH:24]([N:27]4[CH2:31][CH2:30][CH2:29][CH2:28]4)[CH2:23][CH2:22]3)=[O:20])=[C:15](I)[N:14]=2)[CH:10]=[CH:11][CH:12]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6].[CH3:33][O:34][C:35]([C:37]1[CH:42]=[CH:41][C:40](B(O)O)=[CH:39][CH:38]=1)=[O:36]>>[CH3:33][O:34][C:35](=[O:36])[C:37]1[CH:42]=[CH:41][C:40]([C:15]2[N:14]=[C:13]([C:9]3[CH:10]=[CH:11][CH:12]=[C:7]([CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH3:6])[CH:8]=3)[N:17]([CH3:18])[C:16]=2[C:19]([N:21]2[CH2:22][CH2:23][CH:24]([N:27]3[CH2:31][CH2:30][CH2:29][CH2:28]3)[CH2:25][CH2:26]2)=[O:20])=[CH:39][CH:38]=1
Reactant: CCCCCCc1cccc(-c2nc(I)c(C(=O)N3CCC(N4CCCC4)CC3)n2C)c1
Reactant: COC(=O)c1ccc(B(O)O)cc1
Product: CCCCCCc1cccc(-c2nc(-c3ccc(C(=O)OC)cc3)c(C(=O)N3CCC(N4CCCC4)CC3)n2C)c1

Procedure:
In analogy to the procedure described for example 7, [2-(3-hexyl-phenyl)-5-iodo-3-methyl-3H-imidazol-4-yl]-(4-pyrrolidin-1-yl-piperidin-1-yl)-methanone (example 2) was reacted with (4-methoxycarbonylphenyl)boronic acid to give the title compound as light brown oil. MS: 557.3 (MH+).
Reaction SMILES: FC(F)(F)S(O[C:7]1[C:11]2[C:12]([O:16][CH3:17])=[N:13][CH:14]=[CH:15][C:10]=2[N:9]([CH:18]2[CH2:23][CH2:22][O:21][CH2:20][CH2:19]2)[N:8]=1)(=O)=O.CC1(C)C(C)(C)OB([C:34]2[CH:35]=[C:36]([C:39]([O:41][CH3:42])=[O:40])[S:37][CH:38]=2)O1.C(=O)([O-])[O-].[Na+].[Na+].O>COCCOC.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>[CH3:17][O:16][C:12]1[C:11]2[C:7]([C:34]3[CH:35]=[C:36]([C:39]([O:41][CH3:42])=[O:40])[S:37][CH:38]=3)=[N:8][N:9]([CH:18]3[CH2:19][CH2:20][O:21][CH2:22][CH2:23]3)[C:10]=2[CH:15]=[CH:14][N:13]=1
Reactant: COc1nccc2c1c(OS(=O)(=O)C(F)(F)F)nn2C1CCOCC1
Reactant: COC(=O)c1cc(B2OC(C)(C)C(C)(C)O2)cs1
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: COCCOC
Solvent: O
Product: COC(=O)c1cc(-c2nn(C3CCOCC3)c3ccnc(OC)c23)cs1
Yield: 68.2 %

Procedure:
A solution of 4-methoxy-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazolo[4,3-c]pyridin-3-yl trifluoromethanesulfonate (250 mg) obtained in Step A of Example 15, methyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)thiophene-2-carboxylate (264 mg), tetrakis(triphenylphosphine)palladium(0) (76.0 mg) and 2M aqueous sodium carbonate solution (1.60 mL) in DME (15 mL) was heated overnight with reflux under nitrogen atmosphere. To the reaction mixture was added water, and the mixture was extracted with ethyl acetate. The organic layer was washed successively with water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (167 mg).
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([C:11]1[N:19]=[C:18]([NH:20][C@H:21]3[CH2:26][CH2:25][C@H:24]([NH:27][C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:23][CH2:22]3)[N:17]=[C:16]3[C:12]=1[N:13]=[CH:14][N:15]3[C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH2:6][CH2:5]2.[C:42](Cl)(=[O:51])[CH2:43][CH2:44][C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1.C(N(C(C)C)CC)(C)C>ClCCl>[O:51]=[C:42]([NH:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([C:11]1[N:19]=[C:18]([NH:20][C@H:21]3[CH2:26][CH2:25][C@H:24]([NH:27][C:28]([O:30][C:31]([CH3:33])([CH3:34])[CH3:32])=[O:29])[CH2:23][CH2:22]3)[N:17]=[C:16]3[C:12]=1[N:13]=[CH:14][N:15]3[C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH2:6][CH2:5]2)[CH2:43][CH2:44][C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1
Reactant: O=C(Cl)CCc1ccccc1
Reactant: CC(C)(C)OC(=O)N[C@H]1CC[C@H](Nc2nc(N3CCc4cc(N)ccc43)c3ncn(C(=O)OC(C)(C)C)c3n2)CC1
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: CC(C)(C)OC(=O)N[C@H]1CC[C@H](Nc2nc(N3CCc4cc(NC(=O)CCc5ccccc5)ccc43)c3ncn(C(=O)OC(C)(C)C)c3n2)CC1
Reaction time: 1 h

Procedure:
40 mg of product obtained in stage 4 of example 41 are mixed with 11.97 mg of hydrocinnamoyl chloride, 25 μl of diisopropylethylamine and 2 ml of dichloromethane. Stirring is carried out for 1 hour at ambient temperature, followed by washing with brine, drying over magnesium sulfate and evaporation to dryness.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH:29]=[C:30]([N:32]2[CH2:37][CH2:36][O:35][CH2:34][CH2:33]2)[CH:31]=1)[C:5]([NH:7][C:8]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[C:11]([O:18][C:19]2[CH:24]=[CH:23][N:22]=[C:21](S(C)(=O)=O)[N:20]=2)=[CH:10][CH:9]=1)=[O:6].[CH3:38][N:39]([CH3:45])[C@@H:40]1[CH2:44][CH2:43][NH:42][CH2:41]1>>[CH3:38][N:39]([CH3:45])[C@@H:40]1[CH2:44][CH2:43][N:42]([C:21]2[N:20]=[C:19]([O:18][C:11]3[C:12]4[C:17](=[CH:16][CH:15]=[CH:14][CH:13]=4)[C:8]([NH:7][C:5](=[O:6])[C:4]4[CH:29]=[C:30]([N:32]5[CH2:37][CH2:36][O:35][CH2:34][CH2:33]5)[CH:31]=[C:2]([F:1])[CH:3]=4)=[CH:9][CH:10]=3)[CH:24]=[CH:23][N:22]=2)[CH2:41]1
Reactant: CS(=O)(=O)c1nccc(Oc2ccc(NC(=O)c3cc(F)cc(N4CCOCC4)c3)c3ccccc23)n1
Reactant: CN(C)[C@@H]1CCNC1
Product: CN(C)[C@@H]1CCN(c2nccc(Oc3ccc(NC(=O)c4cc(F)cc(N5CCOCC5)c4)c4ccccc34)n2)C1

Procedure:
Compound is prepared from 3-fluoro-N-(4-{[2-(methylsulfonyl)pyrimidin-4-yl]oxy}-1-naphthyl)-5-morpholin-4-ylbenzamide and (R)—N,N-dimethylpyrrolidin-3-amine according to conditions described in general procedure C. Mp: 115-117° C.; 1H NMR (400 MHz, DMSO-d6) δ 1.70-2.10(m, 2 H), 2.13(s, 6H), 2.68-3.10 (m, 5 H), 3.25(t, J=4.4 Hz, 4 H), 3.74(t, J=4.8 Hz, 4 H), 6.15(bd, 1 H), 7.04(d, J=12.0 Hz, 1 H), 7.24(d, J=8.4 Hz, 1 H), 7.40-7.61(m, 5 H), 7.84(d, J=8.0 Hz, 1 H), 7.98(d, J=8.4 Hz, 1 H), 8.22(d, J=5.5 Hz, 1 H), 10.45(s, 1 H).
Reaction SMILES: [C:1]1(=[O:11])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3][CH2:2]1.CC(C)([O-])C.[K+].[N:18](OCCC(C)C)=[O:19]>C(OCC)C.C(O)(C)(C)C>[C:1]1(=[O:11])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3][C:2]1=[N:18][OH:19]
Reactant: O=C1CCCc2ccccc21
Reactant: CC(C)CCON=O
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: CCOCC
Solvent: CC(C)(C)O
Product: O=C1C(=NO)CCc2ccccc21
Temperature: 25 °C
Reaction time: 4 h
Yield: 71.9 %

Procedure:
Tetralone (25 g, 171 mmol) was added to a solution of potassium tert-butoxide (22 g, 196 mol) and isoamyl nitrite (26 g, 222 mmol) in diethyl ether (200 ml) and tert-butanol (200 ml). The solution was stirred at room temperature for 4 hours and then filtered to collect the potassium salt of the oxime. The solid was dissolved with 1 N aqueous hydrochloric acid (200 ml) and extracted with chloroform and dried over anhydrous magnesium sulfate. After removal of the solvent, the residue was washed with ethyl acetate, and dried to give 3,4-dihydro-[1,2]naphthoquinone 2-oxime (21.5 g, 123 mmol, 72%) as brown crystals.
Reaction SMILES: NC1[C:7]([CH2:8][CH2:9][C:10]2[N:18](Br)[C:13]3=[N:14][CH:15]=[CH:16][CH:17]=[C:12]3[N:11]=2)=[C:6](C)[CH:5]=[CH:4]N=1.[CH2:21]([O:28][C:29]1[CH:30]=[C:31](B(O)O)[CH:32]=[CH:33][CH:34]=1)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1>O1CCOCC1.C([O-])([O-])=O.[Na+].[Na+]>[CH2:21]([O:28][C:29]1[CH:30]=[C:31]([C:16]2[CH:17]=[C:12]3[N:11]=[C:10]([CH2:9][CH2:8][C:7]4[N:11]=[C:10]([NH2:18])[CH:9]=[C:5]([CH3:4])[CH:6]=4)[NH:18][C:13]3=[N:14][CH:15]=2)[CH:32]=[CH:33][CH:34]=1)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1
Reactant: Cc1ccnc(N)c1CCc1nc2cccnc2n1Br
Reactant: OB(O)c1cccc(OCc2ccccc2)c1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: C1COCCO1
Product: Cc1cc(N)nc(CCc2nc3cc(-c4cccc(OCc5ccccc5)c4)cnc3[nH]2)c1
Yield: 122 %

Procedure:
The title compound is synthesized according to General Procedure A. 150 mg of 2-[2-(2-amino-4-methylpyridinyl)ethyl]-bromo-3H-imidazo[4,5-b]pyridine in 7.5 ml dioxane, 1.36 ml Na2CO3 solution, 116 mg of 3-benzyloxyphenylboronic acid, 20 mg of PdCl2(PCy3)2, 120° C. for 48 h, 20 ml of CH2Cl2/H2O, 220 mg of crude title compound is purified by recrystallization from 6.0 ml isopropyl alcohol to yield 120 mg of the title compound. M.p. 181° C. ESI-MS: 436.3 (MH+). TLC: Rf=0.30 (dichloromethane/methanol 10:1).