Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]1([S:7](OC)=O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[H-].[K+].[CH3:13][C@H:14]1[C@H:19]([CH2:20][CH:21]=[CH2:22])[CH2:18][CH2:17][C:16](=[O:23])[CH2:15]1.Cl>C(COC)OC>[CH3:13][CH:14]1[CH2:15][C:16](=[O:23])[CH:17]([S:7][C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[CH2:18][CH:19]1[CH2:20][CH:21]=[CH2:22]
Reactant: C=CC[C@@H]1CCC(=O)C[C@H]1C
Reactant: COS(=O)c1ccccc1
Agent: Cl
Agent: [H-]
Agent: [K+]
Solvent: COCCOC
Product: C=CCC1CC(Sc2ccccc2)C(=O)CC1C
Temperature: 0 °C
Reaction time: 0.5 h

Procedure:
To a 0° C. mixture of 16.9 g. (0.109 mole) of methyl benzenesulfinate and 8.68 g. (0.217 mole) of potassium hydride in 100 ml. of dimethoxyethane was slowly added a solution of 15.0 g. (0.0987 mole) of trans-3-methyl-4-(2-propenyl)cyclohexanone in 50 ml. of dimethoxyethane. The reaction was stirred 30 minutes longer at 0° C. and then cautiously added to 500 ml. of ice-saturated sodium chloride and 45 ml. 6N hydrochloric acid. The quenched reaction mixture was extracted once with 300 ml. ether and once with 200 ml. dichloromethane. The organic extract was dried over magnesium sulfate and evaporated to give a quantitative yield of the title compound as a semisolid mixture of axial and equatorial sulfenates. Crystallization from ether yields 7.8 g. of pure axial sulfenate.
Reaction SMILES: [OH:1][CH:2]([CH2:17][OH:18])[CH2:3][NH:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16].[OH-].[K+].[OH:21][CH:22]([CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH3:32])[C:23](OC)=[O:24]>>[OH:1][CH:2]([CH2:17][OH:18])[CH2:3][N:4]([CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16])[C:23](=[O:24])[CH:22]([OH:21])[CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH3:32]
Reactant: CCCCCCC(O)C(=O)OC
Reactant: CCCCCCCCCCCCNCC(O)CO
Agent: [K+]
Agent: [OH-]
Product: CCCCCCCCCCCCN(CC(O)CO)C(=O)C(O)CCCCCC

Procedure:
N-(2,3-dihydroxypropyl)-N-dodecylamine (1.0 g, 0.0039 mole) and potassium hydroxide (0.01 g, 0.18 mmole) were heated to 85° C. under vacuum and methyl 2-hydroxyoctanoate (0.6718 g, 0.0039 mole) was added dropwise to the reaction. The reaction was heated under vacuum for 5 hours. A waxy off-white solid was obtained (crude yield=1.38 g). The waxy solid was recrystalized from hot hexane (yield=0.44 g).
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([S:8](Cl)(=[O:10])=[O:9])=[CH:4][CH:3]=1.[NH2:12][C:13]1[CH:14]=[C:15]([S:19]([NH2:22])(=[O:21])=[O:20])[CH:16]=[CH:17][CH:18]=1.CCN(C(C)C)C(C)C>C1COCC1>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([NH:12][C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([S:19](=[O:21])(=[O:20])[NH2:22])[CH:14]=2)(=[O:10])=[O:9])=[CH:4][CH:3]=1
Reactant: Nc1cccc(S(N)(=O)=O)c1
Reactant: O=S(=O)(Cl)c1ccc(Br)cc1
Solvent: C1CCOC1
Solvent: CCN(C(C)C)C(C)C
Product: NS(=O)(=O)c1cccc(NS(=O)(=O)c2ccc(Br)cc2)c1
Yield: 20.2 %

Procedure:
A solution of 4-bromobenzenesulfonyl chloride (1.34 g, 5.25 mmol), 3-aminobenzenesulfonamide (860 mg, 5.0 mmol) and DIPEA (1.29 g, 10 mmol) in THF (10 mL) was stirred overnight at room temperature. The solvent was then evaporated and the residue purified by chromatography on the SP4 (70 g Silica Isolute II, 0-100% EtOAc/hexane) to and the title compound obtained as a white solid (395 mg).
Reaction SMILES: [C:1]([C:3]1[CH:9]=[CH:8][C:6]([NH2:7])=[CH:5][C:4]=1[F:10])#[N:2].C([O-])([O-])=O.[Na+].[Na+].[NH2:17][OH:18].Cl>CCO.O>[NH2:7][C:6]1[CH:8]=[CH:9][C:3]([C:1](=[NH:2])[NH:17][OH:18])=[C:4]([F:10])[CH:5]=1
Reactant: NO
Reactant: N#Cc1ccc(N)cc1F
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CCO
Solvent: O
Product: N=C(NO)c1ccc(N)cc1F
Temperature: 60 °C
Yield: 60.3 %

Procedure:
4-cyano-3-fluoroaniline (10 g, 0.0735 mol) was dissolved in EtOH (36.7 ml) and water (7.3 ml), Na2CO3 (5.06 g, 0.65 eq) was added. The mixture was heated at 60° C. and a solution of NH2OH.HCl (5.615 g, 1.1 eq) in water (7.3 ml) was added slowly, the mixture was heated at 60° C. overnight. The mixture was cooled to 0° C., and the solid collected by filtration. Washed with water (7 ml), EtOH (7 ml), Et2O (20 ml) and dried to give 7.5 g of compound 139-1.
Reaction SMILES: ClC1C=C(C=CC=1)C(OO)=[O:6].[Cl:12][CH2:13][CH2:14][S:15]([CH2:17][C:18]([O:20][CH3:21])=[O:19])=[O:16]>>[Cl:12][CH2:13][CH2:14][S:15]([CH2:17][C:18]([O:20][CH3:21])=[O:19])(=[O:6])=[O:16]
Reactant: COC(=O)CS(=O)CCCl
Reactant: O=C(OO)c1cccc(Cl)c1
Product: COC(=O)CS(=O)(=O)CCCl

Procedure:
The title compound was prepared from 3-chloroperoxybenzoic acid and the title compound of Example 11 according to the procedure of Example 11 and identified by its NMR and IR spectra.
Reaction SMILES: [NH2:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([F:12])=[CH:9][CH:10]=2)[C:5]([C:13](=O)[CH3:14])=[CH:4][N:3]=1.Cl.[NH2:17][OH:18].CC([O-])=O.[Na+]>CO.O>[NH2:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([F:12])=[CH:9][CH:10]=2)[C:5]([C:13](=[N:17][OH:18])[CH3:14])=[CH:4][N:3]=1
Reactant: CC(=O)c1cnc(N)c2ccc(F)cc12
Reactant: NO
Agent: CC(=O)[O-]
Agent: Cl
Agent: [Na+]
Solvent: O
Solvent: CO
Product: CC(=NO)c1cnc(N)c2ccc(F)cc12
Yield: 87.3 %

Procedure:
1-(1-amino-6-fluoro-isoquinolin-4-yl)-ethanone (0.8 g, 1 eq), hydroxylamine hydrochloride (1.36 g, 5 eq), and NaOAc (1.6 g. 5 eq) in MeOH (70 mL) and H2O (70 mL) is stirred at RT over 3-day, then concentrated to remove MeOH, poured into Sat'd NaHCO3 aq. (300 mL), extracted by dichloromethane (3×150 mL), dried over Na2SO4, filtered, concentrated to give product 1-(1-amino-6-fluoro-isoquinolin-4-yl)-ethanone oxime (0.75 g, 87%). LC/MS m/z=220 [M+H]+.
Reaction SMILES: [BH4-].[Na+].[CH3:3][CH:4]1[CH2:12][C:11]2[C:6](=[C:7]([C:14]3[CH:19]=[CH:18][C:17]([C:20]([CH3:23])([CH3:22])[CH3:21])=[CH:16][CH:15]=3)[CH:8]=[CH:9][C:10]=2[CH3:13])[C:5]1=O.C1(C)C=CC=CC=1.S(=O)(=O)(O)O>CO>[CH3:3][C:4]1[CH2:12][C:11]2[C:6]([CH:5]=1)=[C:7]([C:14]1[CH:15]=[CH:16][C:17]([C:20]([CH3:23])([CH3:22])[CH3:21])=[CH:18][CH:19]=1)[CH:8]=[CH:9][C:10]=2[CH3:13]
Reactant: Cc1ccc(-c2ccc(C(C)(C)C)cc2)c2c1CC(C)C2=O
Agent: O=S(=O)(O)O
Agent: [BH4-]
Agent: [Na+]
Solvent: Cc1ccccc1
Solvent: CO
Product: CC1=Cc2c(-c3ccc(C(C)(C)C)cc3)ccc(C)c2C1
Temperature: 50 °C
Reaction time: 3 h

Procedure:
2.09 g (55.3 mmol) of sodium borohydride and 18.59 g (55.3 mmol) of 2,4-dimethyl-7-4′-tert-butylphenyl)-1-indanone (1d) together with 51 ml of toluene were placed in a reaction vessel. At 50° C., 9.8 ml of methanol were slowly added and the reaction mixture was stirred at 50° C. for 3 hours. After cooling to room temperature, 35 ml of 2N sulfuric acid were added and the mixture was stirred for 30 minutes. After phase separation, the organic phase was washed twice with a total of 60 ml of 2N sulfuric acid, most of the solvent was removed and the residue was taken up in 200 ml of toluene and admixed with 0.2 g of p-toluenesulfonic acid. Water was distilled off from this reaction mixture with the aid of a water separator by refluxing for 1.5 hours until the reaction was complete. The reaction mixture was washed once with 100 ml of saturated sodium hydrogen carbonate solution and dried over magnesium sulfate. After removal of the solvent, the residue was dried in an oil pump vacuum. This gave 16.8 g of the desired product (1e).
Reaction SMILES: [C:1](Cl)(=O)[C:2]([Cl:4])=[O:3].[CH3:7][N:8]([C:10]1C=[CH:17][CH:16]=[CH:15][C:11]=1C(O)=O)[CH3:9]>C(Cl)Cl>[CH3:7][N:8]([C:10]1[CH:11]=[CH:15][CH:16]=[CH:17][C:1]=1[C:2]([Cl:4])=[O:3])[CH3:9]
Reactant: O=C(Cl)C(=O)Cl
Reactant: CN(C)c1ccccc1C(=O)O
Solvent: ClCCl
Product: CN(C)c1ccccc1C(=O)Cl
Reaction time: 2.5 h

Procedure:
Oxalyl chloride (371 g) was added to a suspension prepared by adding 3.6 L of dry methylene chloride to 358 g of N,N-dimethylaminobenzoic acid. A vessel containing the resultant solution was dipped in an oil bath, and the solution was stirred for 2.5 hr while controlling the internal temperature at about 40° C. The solvent was removed by evaporation under the reduced pressure, and the residue was vacuum dried to give a crude product of N,N-dimethylaminobenzoic acid chloride.
Reaction SMILES: C([O:3][C:4](=[O:33])[CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][S:15][C:16]1[NH:17][C:18]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)=[C:19]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[N:20]=1)C.[OH-].[Na+]>C(O)C.O>[C:27]1([C:18]2[N:17]=[C:16]([S:15][CH2:14][CH2:13][CH2:12][CH2:11][CH2:10][CH2:9][CH2:8][CH2:7][CH2:6][CH2:5][C:4]([OH:33])=[O:3])[NH:20][C:19]=2[C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=1
Reactant: CCOC(=O)CCCCCCCCCCSc1nc(-c2ccccc2)c(-c2ccccc2)[nH]1
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CCO
Product: O=C(O)CCCCCCCCCCSc1nc(-c2ccccc2)c(-c2ccccc2)[nH]1
Yield: 69.2 %

Procedure:
To a solution of 6.0 g (0.013 mole) 11-(4,5-diphenyl-1H-imidazole-2-ylthio)undecanoic acid ethyl ester in 150 ml ethanol was added, dropwise, a solution of 6.0 g sodium hydroxide in 150 ml water. The reaction mixture was stirred at reflux under nitrogen for 3 hours. The solvent was concentrated to half the volume and the remaining solution was extracted with diethyl ether. This organic layer was discarded. The aqueous layer was acidified to pH=1.0 using 1N hydrochloric acid and then extracted with diethyl ether. The organic layer was dried over magnesium sulfate and the solvent removed under vacuum. The resulting solid was recrystallized from methanol and triturated with diethyl ether to give 4.10 g (0.009 mole) of the title compound as a white solid, mp=193°-195° C. 1HNMR(DMSO-d6): δ12.6(s,1H), 7.6-7.1(m,10H), 3.6(t,2H,J=7Hz), 2.3(t,2H,J=7Hz), 1.8-1.1(m,17H).
Reaction SMILES: [CH:1]1([C:6]2[CH:7]=[C:8]([CH:12]=[C:13]([O:15][CH3:16])[N:14]=2)[C:9]([OH:11])=O)[CH2:5][CH2:4][CH2:3][CH2:2]1.[CH2:17]([C:19]1[CH:20]=[C:21]([CH:26]=[C:27]([CH3:30])[C:28]=1[OH:29])[C:22]([NH:24]O)=[NH:23])[CH3:18].C1C=CC2N(O)N=NC=2C=1.C1CCC(N=C=NC2CCCCC2)CC1>C1COCC1>[CH:1]1([C:6]2[CH:7]=[C:8]([C:9]3[O:11][N:24]=[C:22]([C:21]4[CH:26]=[C:27]([CH3:30])[C:28]([OH:29])=[C:19]([CH2:17][CH3:18])[CH:20]=4)[N:23]=3)[CH:12]=[C:13]([O:15][CH3:16])[N:14]=2)[CH2:2][CH2:3][CH2:4][CH2:5]1
Reactant: COc1cc(C(=O)O)cc(C2CCCC2)n1
Reactant: CCc1cc(C(=N)NO)cc(C)c1O
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: On1nnc2ccccc21
Solvent: C1CCOC1
Product: CCc1cc(-c2noc(-c3cc(OC)nc(C4CCCC4)c3)n2)cc(C)c1O
Temperature: 25 °C
Reaction time: 18 h
Yield: 73.9 %

Procedure:
A solution of 2-cyclopentyl-6-methoxy-isonicotinic acid (21.0 g, 102 mmol), 3-ethyl-4,N-dihydroxy-5-methyl-benzamidine (20.0 g, 103 mmol) and HOBt (1.24 g, 9 mmol) in THF (200 mL) is cooled to 5° C. before a solution of DCC (20.0 g, 97 mmol) in THF (100 mL) is added dropwise. Upon complete addition, the mixture is stirred at rt for 18 h then at 75° C. for 48 h. The solvent is evaporated and the remaining residue is dissolved in TBME (200 mL). The precipitate that forms is removed, filtered off and washed with additional TBME (200 mL). The filtrate is washed with approximately 4% aq. NaHCO3 solution (100 mL) and water (100 mL) and concentrated. The crude product is recrystallised from hot acetonitrile (200 mL) to give 4-[5-(2-cyclopentyl-6-methoxy-pyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-2-ethyl-6-methyl-phenol (28.6 g) as a white solid; 1H NMR (CDCl3): δ1.33 (t, J=7.5 Hz, 3H), 1.70-1.80 (m, 2H), 1.84-1.96 (m, 4H), 2.05-2.16 (m, 2H), 2.36 (s, 3H), 2.74 (q, J=7.3 Hz, 2H), 3.25 (quint, J=7.5 Hz, 1H), 4.02 (s, 3H), 5.01 (s), 7.31 (s, 1H), 7.51 (s, 1H), 7.85 (s, 2H).
Reaction SMILES: [N+:1]([C:4]1[CH:12]=[C:11]2[C:7]([C:8](=[O:13])[NH:9][NH:10]2)=[CH:6][CH:5]=1)([O-:3])=[O:2].S(OC)(O[CH3:18])(=O)=O.C(=O)([O-])[O-].[Na+].[Na+]>CN(C=O)C.ClCCl>[CH3:18][N:9]1[C:8](=[O:13])[C:7]2[C:11](=[CH:12][C:4]([N+:1]([O-:3])=[O:2])=[CH:5][CH:6]=2)[NH:10]1
Reactant: COS(=O)(=O)OC
Reactant: O=c1[nH][nH]c2cc([N+](=O)[O-])ccc12
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: ClCCl
Product: Cn1[nH]c2cc([N+](=O)[O-])ccc2c1=O
Temperature: 60 °C

Procedure:
1.66 g (9.27 mmol) of 6-nitro-1,2-dihydro-3H-indazol-3-one were initially charged in 20 ml of DMF, and 1.75 ml (18.5 mmol, 2.0 eq.) of dimethyl sulphate were added. The reaction mixture was heated at 60° C. for 8 h and then diluted with dichloromethane and shaken with saturated aqueous sodium carbonate solution. The aqueous phase was washed three times each with dichloromethane and with ethyl acetate and the organic fractions were discarded. Using 4N aqueous hydrochloric acid, the aqueous phase was then carefully adjusted to pH 4.5 and extracted three times with ethyl acetate. These combined organic phases were dried over magnesium sulphate and concentrated under reduced pressure. The crude product was purified by flash chromatography (silica gel 50, mobile phase: gradient cyclohexane/ethyl acetate 1:1 to ethyl acetate/methanol 15:1), giving the title compound. Yield: 770 mg (43% of theory)
Reaction SMILES: [OH:1][C:2]([C:5]1[O:9][N:8]=[C:7]([CH:10]=[C:11]([C:14]#[N:15])[C:12]#[N:13])[CH:6]=1)([CH3:4])[CH3:3].[CH2:16]([Mg]Br)[CH3:17].Cl>O1CCOCC1.O1CCCC1.[Cu]I>[OH:1][C:2]([C:5]1[O:9][N:8]=[C:7]([CH:10]([CH:11]([C:12]#[N:13])[C:14]#[N:15])[CH2:16][CH3:17])[CH:6]=1)([CH3:4])[CH3:3]
Reactant: CC[Mg]Br
Reactant: CC(C)(O)c1cc(C=C(C#N)C#N)no1
Agent: [Cu]I
Agent: Cl
Solvent: C1CCOC1
Solvent: C1COCCO1
Product: CCC(c1cc(C(C)(C)O)on1)C(C#N)C#N
Reaction time: 1 h

Procedure:
1.02 g of {[5-(1-hydroxy-1-methylethyl)-isoxazol-3-yl]methylidene}malononitrile was dissolved in 50 ml of 1,4-dioxane. Thereto, 0.05 g of copper(I) iodide was added and ml of a 3 M solution of ethylmagnesium bromide in tetrahydrofuran was then added under ice-cooling. The mixture was stirred for 1 hour under ice-cooling. The reaction mixture was added to 0.1 M hydrochloric acid and then extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure. The residue was subjected to silica gel column chromatography to obtain 0.40 g of {1-[5-(1-hydroxy-1-methylethyl)-isoxazol-3-yl]propyl}malononitrile.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([C:8]#[C:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[NH:16][C:17]([NH2:19])=[O:18])[CH:5]=[CH:6][CH:7]=1>CC#N.CC#N.CC#N.Cl[Pd]Cl>[NH2:1][C:2]1[CH:3]=[C:4]([C:8]2[N:16]([C:17]([NH2:19])=[O:18])[C:11]3[C:10]([CH:9]=2)=[CH:15][CH:14]=[CH:13][CH:12]=3)[CH:5]=[CH:6][CH:7]=1
Reactant: NC(=O)Nc1ccccc1C#Cc1cccc(N)c1
Agent: Cl[Pd]Cl
Solvent: CC#N
Product: NC(=O)n1c(-c2cccc(N)c2)cc2ccccc21
Temperature: 90 °C
Reaction time: 3 h
Yield: 14.6 %

Procedure:
The mixture of 1-{2-[(3-aminophenyl)ethynyl]phenyl}urea (1.25 g, 5 mmol, 1 eq) in anhydrous CH3CN (35 mL) was bubbled with anhydrous nitrogen for about 15 minutes, followed by the addition of bis(acetonitrile)dichloropalladium (II) (259 mg, 0.2 eq). The resulting mixture was heated at 90° C. for 2 hours, then another batch of bis(acetonitrile)dichloropalladium (II) (259 mg, 0.2 eq) was added and the reaction was continued at 90° C. for 3 hours. The reaction mixture was then concentrated under reduced pressure to remove some of the acetonitrile solvent and the residue was taken into ethyl acetate. The organic solvent mixture was washed with water, brine, and dried with anhydrous sodium sulfate. The solvent mixture was filtered, the filtrate was isolated and concentrated, and the resulting solid residue was subject to a gradient column chromatography [from dichloromethane to MeOH-DCM (1:20)] to yield 2-(3-aminophenyl)-1H-indole-1-carboxamide as a yellow solid (184 mg).
Reaction SMILES: Br[C:2]1[CH:3]=[CH:4][C:5]([F:16])=[C:6]([C:8]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[O:9])[CH:7]=1.CC1(C)C(C)(C)OB([C:25]2[CH:26]=[C:27]3[C:31](=[CH:32][CH:33]=2)[NH:30][N:29]=[CH:28]3)O1.C(COC)OC.C(=O)([O-])[O-].[Na+].[Na+]>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C(O)C>[F:16][C:5]1[CH:4]=[CH:3][C:2]([C:25]2[CH:26]=[C:27]3[C:31](=[CH:32][CH:33]=2)[NH:30][N:29]=[CH:28]3)=[CH:7][C:6]=1[C:8]([C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)=[O:9]
Reactant: O=C(c1ccccc1)c1cc(Br)ccc1F
Reactant: CC1(C)OB(c2ccc3[nH]ncc3c2)OC1(C)C
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CCO
Solvent: COCCOC
Product: O=C(c1ccccc1)c1cc(-c2ccc3[nH]ncc3c2)ccc1F
Temperature: 150 °C
Yield: 60 %

Procedure:
The following reagents were mixed in no particular order and heated to 150° C. in a microwave for 1000 seconds: (5-bromo-2-fluorophenyl)(phenyl)methanone (from example 9, step 1) (278 mg, 1.0 mmol), 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indazole (486 mg, 2.0 mmol), dichlorobis(triphenyl-phosphine)palladium(II) (70 mg, 0.10 mmol), dimethoxyethane (2 mL), ethanol (1 mL) and a 2M aqueous solution of sodium carbonate (1 mL, 2.0 mmol). The reaction mixture was then filtered through a plug of celite, rinsed with methanol and concentrated to dryness. Purification from silica gel eluting with a 50% solution of ethyl acetate and hexanes affords [2-fluoro-5-(1H-indazol-5-yl)phenyl](phenyl)methanone (187 mg, 0.6 mmol) 1H NMR (400 MHz, DMSO-D6) δ ppm 13.1 (s, 1 H) 8.1 (s, 1 H) 8.1 (s, 1 H) 8.0 (m, J=5.9 Hz, 1 H) 7.8 (m, J=7.5 Hz, 3 H) 7.7 (m, 2 H) 7.6 (m, 3 H) 7.5 (dd, J=9.1, 9.1 Hz, 1 H)
Reaction SMILES: [NH2:1][CH:2]1[CH:6]([CH2:7][OH:8])[CH2:5][NH:4][CH2:3]1.[CH2:9]=O>>[CH:2]12[CH2:3][NH:4][CH2:5][CH:6]1[CH2:7][O:8][CH2:9][NH:1]2
Reactant: C=O
Reactant: NC1CNCC1CO
Product: C1NC2CNCC2CO1

Procedure:
3-Amino-4-hydroxymethyl-pyrrolidine is reacted with formaldehyde solution analogously to Example Pe).
Reaction SMILES: [OH:1][CH:2]1[CH2:7][CH2:6][NH:5][CH2:4][CH2:3]1.[CH:8]1([C:11]([CH:13](Br)[C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[F:20])=[O:12])[CH2:10][CH2:9]1.C(=O)([O-])[O-].[K+].[K+].O>CN(C)C=O>[CH:8]1([C:11]([CH:13]([N:5]2[CH2:6][CH2:7][CH:2]([OH:1])[CH2:3][CH2:4]2)[C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[F:20])=[O:12])[CH2:10][CH2:9]1
Reactant: OC1CCNCC1
Reactant: O=C(C1CC1)C(Br)c1ccccc1F
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: O=C(C1CC1)C(c1ccccc1F)N1CCC(O)CC1
Temperature: 25 °C
Reaction time: 2 h
Yield: 93.1 %

Procedure:
In 30 ml of dimethylformamide (DMF), 3.13 g (31 mmol) of 4-hydroxypiperidine were dissolved, followed by the addition of 7.94 g (31 mmol) of α-cyclopropylcarbonyl-2-fluorobenzylbromide and 4.7 g (34 mmol) of potassium carbonate. The resulting mixture was stirred at room temperature for 2 hours. Water was added to the reaction mixture, followed by extraction with toluene. The resulting organic layer was dried over anhydrous sodium sulfate. The solvent was concentrated by evaporation under reduced pressure. The residue was purified by chromatography on a silica gel column (eluting solvent: chloroform/methanol=19/1), whereby 8.00 g of the title compound were obtained as a brown oil (yield: 93%).
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([C:8]2[S:12][C:11]([N:13]3[CH2:18][CH2:17][O:16][CH2:15][CH2:14]3)=[N:10][C:9]=2[C:19]2[C:20]([F:37])=[C:21]([NH:25][S:26]([C:29]3[C:34]([F:35])=[CH:33][CH:32]=[CH:31][C:30]=3[F:36])(=[O:28])=[O:27])[CH:22]=[CH:23][CH:24]=2)[CH:5]=[CH:4][N:3]=1.[NH3:38].CO>>[NH2:38][C:2]1[N:7]=[C:6]([C:8]2[S:12][C:11]([N:13]3[CH2:18][CH2:17][O:16][CH2:15][CH2:14]3)=[N:10][C:9]=2[C:19]2[C:20]([F:37])=[C:21]([NH:25][S:26]([C:29]3[C:34]([F:35])=[CH:33][CH:32]=[CH:31][C:30]=3[F:36])(=[O:28])=[O:27])[CH:22]=[CH:23][CH:24]=2)[CH:5]=[CH:4][N:3]=1
Reactant: N
Reactant: O=S(=O)(Nc1cccc(-c2nc(N3CCOCC3)sc2-c2ccnc(Cl)n2)c1F)c1c(F)cccc1F
Solvent: CO
Product: Nc1nccc(-c2sc(N3CCOCC3)nc2-c2cccc(NS(=O)(=O)c3c(F)cccc3F)c2F)n1

Procedure:
Following a procedure analogous to the procedure described in Example 51, Step B using N-{3-[5-(2-chloro-4-pyrimidinyl)-2-(4-morpholinyl)-1,3-thiazol-4-yl]-2-fluorophenyl}-2,6-difluorobenzenesulfonamide (250 mg, 0.440 mmol) and ammonia in MeOH 7M (7 ml, 49.0 mmol) the title compound was obtained as a yellow solid (187 mg, 72% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 10.82 (br. s., 1H), 7.78 (d, J=5.3 Hz, 1H), 7.55-7.71 (m, 1H), 7.31-7.43 (m, 1H), 7.10-7.30 (m, 4H), 6.52 (s, 2H), 5.59 (d, J=5.2 Hz, 1H), 3.66 (t, J=4.3 Hz, 4H), 3.40 (d, J=4.5 Hz, 4H). MS (ESI): 549.1 [M+H]+.
Reaction SMILES: I[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([CH:8]=[C:9]([C:11]([NH:13][C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)=[O:12])[N:10]=2)[CH:7]=1.[C:20]1(B(O)O)[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.C(=O)([O-])[O-].[Na+].[Na+].C(#N)C>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.C1(C)C=CC=CC=1>[C:14]1([NH:13][C:11]([C:9]2[N:10]=[C:5]3[CH:4]=[CH:3][C:2]([C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=4)=[CH:7][N:6]3[CH:8]=2)=[O:12])[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1
Reactant: O=C(Nc1ccccc1)c1cn2cc(I)ccc2n1
Reactant: OB(O)c1ccccc1
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: CC#N
Solvent: Cc1ccccc1
Product: O=C(Nc1ccccc1)c1cn2cc(-c3ccccc3)ccc2n1
Yield: 65.2 %

Procedure:
0.391 g of 6-iodo-N-phenylimidazo[1,2-a]pyridine-2-carboxamide, 0.237 g of phenylboronic acid, 45 mg of tetrakis(triphenylphosphine)palladium, 4 ml of 2M aqueous sodium carbonate solution, 6 ml of acetonitrile and 6 ml of toluene are charged to a microwave tube. The mixture is heated for 20 minutes in the microwave device adjusted to 150° C. After cooling, the organic phase is separated, dried and evaporated. The residue is taken up in a mixture of dichloromethane and pentane. The solid is filtered off and then purified by triturating from methanol to give 0.22 g of N,6-diphenylimidazo[1,2-a]pyridine-2-carboxamide in the form of an ecru solid.
Reaction SMILES: [Br-].[CH2:2]([P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[CH2:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[Li]CCCC.[CH3:34][O:35][C:36]1[CH:43]=[CH:42][C:39]([CH:40]=O)=[CH:38][CH:37]=1>>[CH3:34][O:35][C:36]1[CH:43]=[CH:42][C:39]([CH:40]=[CH:2][CH2:3][C:4]2[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=2)=[CH:38][CH:37]=1
Reactant: COc1ccc(C=O)cc1
Reactant: c1ccc(CC[P+](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: [Br-]
Agent: [Li]CCCC
Product: COc1ccc(C=CCc2ccccc2)cc1
Yield: 85.9 %

Procedure:
Starting from phenethyltriphenylphosphonium bromide (3.16 g, 7.06 mmol, 1.0 equiv.), n-BuLi (1.6 M in hexanes, 4.4 mL, 7.06 mmol, 1.0 equiv.) and 4-methoxybenzaldehyde (1.44 g, 10.6 mmol, 1.5 equiv.), 1.36 g (86%) of the title compound as a light yellow oil was obtained after purification by flash chromatography on SiO2 (cyclohexane/EtOAc 99:1).
Reaction SMILES: Cl[CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([N+:12]([O-:14])=[O:13])[CH:7]=1.[CH3:15][NH2:16]>CO>[CH3:15][NH:16][CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([N+:12]([O-:14])=[O:13])[CH:7]=1
Reactant: O=[N+]([O-])c1cccc(OCCCCl)c1
Reactant: CN
Solvent: CO
Product: CNCCCOc1cccc([N+](=O)[O-])c1
Temperature: 100 °C
Yield: 50.6 %

Procedure:
The 1-(3-chloropropoxy)-3-nitrobenzene (1.00 g, 4.65 mmol) was dissolved in methanol (25 mL) and added to a 40 wt % aqueous solution of methylamine (50 mL) in a heavy-walled glass pressure-tube apparatus. The tube was sealed and the mixture was stirred and heated at 100° C. (oil bath temperature) for 4 h. After cooling, the mixture was concentrated by rotary evaporation. Saturated NaCl solution (25 mL) was added to the residue. The pH of the solution was adjusted to 6, and impurities were extracted with ether (3×15 mL). The aqueous layer was basified to pH 10 with 10% NaOH solution and extracted with chloroform (4×15 mL). The combined chloroform extracts were dried (Na2SO4), filtered, and concentrated by rotary evaporation to a residue that was dried briefly under high vacuum to give 493 mg (50.6%) of an oil.