Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br[C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([Br:12])[CH:8]=2)[CH:3]=1.[C:13]1([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[C:14](B(O)O)=[CH:15][CH:16]=[CH:17][CH:18]=1.C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1>[C:13]1([C:22]2[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=2)[CH:14]=[CH:15][CH:16]=[CH:17][C:18]=1[C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([Br:12])[CH:8]=2)[CH:3]=1
Reactant: Brc1ccc2cc(Br)ccc2c1
Reactant: OB(O)c1ccccc1-c1ccccc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: Cc1ccccc1
Product: Brc1ccc2cc(-c3ccccc3-c3ccccc3)ccc2c1
Yield: 57.8 %

Procedure:
The procedure of Synthesis Example 1 was repeated except that 2-naphthalene boronic acid in place of phenylboronic acid was used, and then 7.5 g of 1-bromo-4-(naphthalene-2-yl)naphthalene of white crystal was obtained (yield: 43%). Synthesis Example 3 (Synthesis of 2-(biphenyl-2-yl)-6-bromonaphthelene) 15 g of 2,6-dibromonaphthalene on the market, 12.5 g of 2-biphenylboronic acid and 1.8 g of tetrakis(triphenylphophine)palladium were mixed, followed by argon displacement. After adding 250 ml of toluene and 90 ml of 2M sodium carbonate aqueous solution thereto, it was refluxed on heating for 7 hours. After standing to cool, the organic layer was extracted by toluene, and then it was washed by water and saturated salt water. Subsequently the organic layer was dried by using sodium sulfate anhydride, and then the solvent was removed by distillation. The product was refined through a silica gel chromatography and then 10.9 g of 2-(biphenyl-2-yl)-6-bromonaphthalene of white crystal was obtained (yield: 58%).
Reaction SMILES: [NH2:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][C:6]([CH3:12])=[N:7]2.[CH3:13][O:14][C:15]1[CH:16]=[C:17]([CH:20]=[CH:21][CH:22]=1)[CH:18]=O.C(O)(=O)C.O>C1(C)C=CC=CC=1>[CH3:13][O:14][C:15]1[CH:16]=[C:17]([CH:18]=[N:1][C:2]2[C:3]3[CH:4]=[CH:5][C:6]([CH3:12])=[N:7][C:8]=3[CH:9]=[CH:10][CH:11]=2)[CH:20]=[CH:21][CH:22]=1
Reactant: Cc1ccc2c(N)cccc2n1
Reactant: COc1cccc(C=O)c1
Solvent: CC(=O)O
Solvent: O
Solvent: Cc1ccccc1
Product: COc1cccc(C=Nc2cccc3nc(C)ccc23)c1
Yield: 102.7 %

Procedure:
To 1.17 g (7.4 mmol) 5-amino-2-methylquinolin and 1 g (7.4 mmol) 3-methoxybenzaldehyde in 39 ml toluene are added 1 ml acetic acid. The mixture is heated over 3 hours under reflux while water is trapped in a Dean Stark apparatus. The solvent is evaporated and the residue is two times azeotrophed with small portions of toluene. 2.1 g of [(3-methoxyphenyl)methylene]-2-methylquinolin-5-amine are obtained as product. 0.31 ml (3.6 mmol) 1,1,1-trifluoroepoxypropane in 17 ml THF and are cooled to −104° C. and 1.59 ml of a 2.5 M n-butyl lithium solution in hexane are added over 3 hours while the temperature does not exceed −99° C. 10 Minutes after complete addition 1.5 g (5.4 mmol) [(3-methoxyphenyl)methylene]-2-methylquinolin-5-amine in 5 ml THF are added over 0.5 hours while the temperature temperature does not exceed −99° C. After 0.5 hours at −100° C. 4 ml diethyl ether are added and the reaction mixture is warmed to 20° C. over one hour. The reaction was quenched by addition of saturated ammonium chloride solution. The phases were separated and the aqueous layer was extracted twice with diethyl ether, the combined organic phases washed with brine, dried over sodium sulphate and then evaporated. Flash chromatography on silica gel (aceton in hexane 30 to 40%) yields 800 mg of the desired epoxide.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([N:11]2[C:20]3[C:15](=[CH:16][C:17]([F:22])=[C:18]([Cl:21])[N:19]=3)[C:14](=[O:23])[C:13]([C:24]([O:26]CC)=[O:25])=[CH:12]2)[C:5]([F:10])=[C:6]([F:9])[C:7]=1[F:8].C(O)(=O)C.ClC(Cl)C>CO.[Pd]>[NH2:1][C:2]1[CH:3]=[C:4]([N:11]2[C:20]3[C:15](=[CH:16][C:17]([F:22])=[C:18]([Cl:21])[N:19]=3)[C:14](=[O:23])[C:13]([C:24]([OH:26])=[O:25])=[CH:12]2)[C:5]([F:10])=[C:6]([F:9])[C:7]=1[F:8]
Reactant: CCOC(=O)c1cn(-c2cc(N)c(F)c(F)c2F)c2nc(Cl)c(F)cc2c1=O
Agent: [Pd]
Solvent: CC(=O)O
Solvent: CC(Cl)Cl
Solvent: CO
Product: Nc1cc(-n2cc(C(=O)O)c(=O)c3cc(F)c(Cl)nc32)c(F)c(F)c1F
Temperature: 25 °C
Reaction time: 8 h
Yield: 28.6 %

Procedure:
Ethyl 1-(3-amino-4,5,6-trifluorophenyl)-7-chloro-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylate (600 mg) was dissolved in 30 ml of methanol, 10 ml of acetic acid, and 30 ml of dichloroethane, to which was added 100 mg of 10% palladium on carbon. Under a hydrogen atmosphere, the solution was stirred overnight at room temperature. The catalyst was removed by a membrane filter and the filtrate was concentrated in vacua. To the residue were added 4 ml of acetic acid and 1 ml of hydrochloric acid. The solution was heated at 100° C. and stirred overnight. The reaction solution was concentrated in vacua whereupon diethyl ether was added to the residue. The solid was collected by filtration and washed with diethyl ether to give 160 mg of the title compound.
Reaction SMILES: C([N:8]1[CH2:12][C@@H:11]([CH3:13])[C@H:10]([C:14]2[NH:15][C:16](=[O:28])[C:17]3[CH:22]=[N:21][N:20]([CH:23]4[CH2:27][CH2:26][CH2:25][CH2:24]4)[C:18]=3[N:19]=2)[CH2:9]1)C1C=CC=CC=1.[ClH:29]>C(O)C.[OH-].[Pd+2].[OH-]>[CH:23]1([N:20]2[C:18]3[N:19]=[C:14]([C@H:10]4[C@H:11]([CH3:13])[CH2:12][NH:8][CH2:9]4)[NH:15][C:16](=[O:28])[C:17]=3[CH:22]=[N:21]2)[CH2:27][CH2:26][CH2:25][CH2:24]1.[ClH:29]
Reactant: C[C@@H]1CN(Cc2ccccc2)C[C@H]1c1nc2c(cnn2C2CCCC2)c(=O)[nH]1
Agent: [Pd+2]
Agent: Cl
Agent: [OH-]
Solvent: CCO
Product: C[C@@H]1CNC[C@H]1c1nc2c(cnn2C2CCCC2)c(=O)[nH]1
Reaction time: 4 h

Procedure:
A solution of 6-[(3S,4S)-1-benzyl-4-methylpyrrolidin-3-yl]-1-cyclopentyl-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one (9.25 g) in ethanol 100 mL was added to a Parr bottle. 2 mL of concentrated HCl followed by 3 g of palladium hydroxide was added. The reaction mixture was placed on a hydrogenator under 45 psi of H2 gas for 4 h. The reaction mixture was filtered through Celite and concentrated to provide the title compound as an HCl salt. 400 MHz 1H NMR (CDCl3) δ 8.00 (s, 1H), 5.14-5.10 (m, 1H), 4.89-3.84 (m, 1H), 3.72-3.67 (m, 1H), 3.38-3.31 (m, 1H), 3.03-2.98 (m, 1H), 2.85-2.81 (m, 1H), 2.08-1.85 (m, 7H), 1.69-1.61 (m, 2H), 1.19-1.10 (m, 3H). MS: (M+H m/z=288.2).
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:21])[CH2:5][CH:6]([N:10]1[C:14]2[CH:15]=[C:16]([CH3:19])[CH:17]=[CH:18][C:13]=2[NH:12][C:11]1=[O:20])[CH2:7][CH2:8][CH3:9])[CH3:2].C([O-])([O-])=O.[K+].[K+].[CH3:28][N:29]1[C:37]2[C:32](=[C:33]([CH3:38])[CH:34]=[CH:35][CH:36]=2)[C:31]([CH2:39][N+](C)(C)C)=[CH:30]1.[I-]>CN(C=O)C.C(OCC)(=O)C>[CH2:1]([O:3][C:4](=[O:21])[CH2:5][CH:6]([N:10]1[C:14]2[CH:15]=[C:16]([CH3:19])[CH:17]=[CH:18][C:13]=2[N:12]([CH2:39][C:31]2[C:32]3[C:37](=[CH:36][CH:35]=[CH:34][C:33]=3[CH3:38])[N:29]([CH3:28])[CH:30]=2)[C:11]1=[O:20])[CH2:7][CH2:8][CH3:9])[CH3:2]
Reactant: Cc1cccc2c1c(C[N+](C)(C)C)cn2C
Reactant: CCCC(CC(=O)OCC)n1c(=O)[nH]c2ccc(C)cc21
Agent: O=C([O-])[O-]
Agent: [I-]
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: CCCC(CC(=O)OCC)n1c(=O)n(Cc2cn(C)c3cccc(C)c23)c2ccc(C)cc21
Temperature: 80 °C

Procedure:
To a solution of 3-(6-Methyl-2-oxo-2,3-dihydro-benzimidazol-1-yl)-hexanoic acid ethyl ester (50 mg, 0.17 mmol) in DMF (2 mL) were added K2CO3 (71 mg, 0.52 mmol) and (1,4-Dimethyl-1H-indol-3-ylmethyl)-trimethyl-ammonium; iodide (90 mg, 0.26 mmol). The reaction mixture was heated to 80° C. for 16 h. The reaction mixture was then diluted with ethyl acetate and washed with water (×4). The organic phase was then dried over Na2SO4 and concentrated. The resulting residue was purified by silica gel prep TLC using 4:1 Hexanes:ethyl acetate as an eluent to afford 35 mg of the desired product as oil. LCMS (ESMS): m/z 448.82 (M+H+).
Reaction SMILES: [H-].[Na+].[CH3:3][C:4]1[S:5][C:6]([CH:9]([NH:12][C:13]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH2:10][OH:11])=[CH:7][N:8]=1.Cl[C:33]1[C:37]2[CH:38]=[C:39]([Cl:42])[CH:40]=[CH:41][C:36]=2[O:35][N:34]=1.O>CN(C)C=O.C(OCC)(=O)C>[Cl:42][C:39]1[CH:40]=[CH:41][C:36]2[O:35][N:34]=[C:33]([O:11][CH2:10][CH:9]([C:6]3[S:5][C:4]([CH3:3])=[N:8][CH:7]=3)[NH:12][C:13]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)([C:20]3[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=3)[C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[C:37]=2[CH:38]=1
Reactant: Clc1ccc2onc(Cl)c2c1
Reactant: Cc1ncc(C(CO)NC(c2ccccc2)(c2ccccc2)c2ccccc2)s1
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: Cc1ncc(C(COc2noc3ccc(Cl)cc23)NC(c2ccccc2)(c2ccccc2)c2ccccc2)s1

Procedure:
To a solution of 0.24 g of 60% sodium hydride in 10 ml of N,N-dimethylformamide are dropwise added 2.0 g of 2-(2-methyl-1,3-thiazol-5-yl)-2-tritylaminoethanol, a solution of 10 ml of N,N-dimethylformamide at room temperature, and the temperature is gradually elevated to 80° C. after which 1.03 g of 3,5-dichloro-1,2-benzoisoxazole is added. They are subjected to reaction at the same temperature for one hour. After cooling, water and ethyl acetate are added, and the crystals precipitated are collected by filtration. The organic layer of the filtrate is separated, washed with a saturated saline solution and dried over anhydrous magnesium sulfate, after which the solvent is removed by distillation under reduced pressure. The crystals obtained are combined with the crystals previously collected by filtration to obtain 1.81 g of colorless, crystalline 5-chloro-3-[2-(2-methyl-1,3-thiazol-5-yl)-2-tritylaminoethoxy]-1,2-benzoisoxazole.
Reaction SMILES: [CH2:1]([N:3]([C:29](=O)[C:30]1[CH:35]=[CH:34][C:33]([OH:36])=[CH:32][CH:31]=1)[C:4]1[CH:9]=[C:8]([O:10][CH3:11])[CH:7]=[CH:6][C:5]=1[CH:12]1[CH2:21][CH2:20][C:19]2[CH:18]=[C:17]([O:22]C(=O)C(C)(C)C)[CH:16]=[CH:15][C:14]=2[CH2:13]1)[CH3:2].Cl[CH2:39][C:40]([N:42]1[CH2:47][CH2:46][O:45][CH2:44][CH2:43]1)=O>>[CH2:1]([N:3]([CH2:29][C:30]1[CH:31]=[CH:32][C:33]([O:36][CH2:39][CH2:40][N:42]2[CH2:47][CH2:46][O:45][CH2:44][CH2:43]2)=[CH:34][CH:35]=1)[C:4]1[CH:9]=[C:8]([O:10][CH3:11])[CH:7]=[CH:6][C:5]=1[CH:12]1[CH2:21][CH2:20][C:19]2[CH:18]=[C:17]([OH:22])[CH:16]=[CH:15][C:14]=2[CH2:13]1)[CH3:2]
Reactant: CCN(C(=O)c1ccc(O)cc1)c1cc(OC)ccc1C1CCc2cc(OC(=O)C(C)(C)C)ccc2C1
Reactant: O=C(CCl)N1CCOCC1
Product: CCN(Cc1ccc(OCCN2CCOCC2)cc1)c1cc(OC)ccc1C1CCc2cc(O)ccc2C1
Yield: 93.7 %

Procedure:
Synthesized from pivalic acid 6-{2-[ethyl(4-hydroxybenzoyl)amino]-4-methoxyphenyl}-5,6,7,8-tetrahydronaphthalen-2-yl ester (29 mg) and 2-chloro-1-morpholin-4-ylethanone (19 mg) according to an analogous synthetic method to Example 404 and purified by LC-MS, the title compound (28 mg) was obtained.
Reaction SMILES: [Cl:1][C:2]1[N:3]=[C:4]([N:22]2[CH2:27][CH2:26][O:25][CH2:24][CH2:23]2)[C:5]2[S:10][C:9]([CH2:11][N:12]3[CH2:15][C:14]4([CH2:20][CH2:19][N:18](C)[CH2:17][CH2:16]4)[CH2:13]3)=[CH:8][C:6]=2[N:7]=1.C(OC(N1CCC2(CNC2)CC1)=O)(C)(C)C.[C:44]([O:48][C:49]([N:51]1[CH2:76][CH2:75][C:54]2([CH2:57][N:56]([CH2:58][C:59]3[S:67][C:66]4[C:65]([N:68]5[CH2:73][CH2:72][O:71][CH2:70][CH2:69]5)=[N:64][C:63]([Cl:74])=[N:62][C:61]=4[CH:60]=3)[CH2:55]2)[CH2:53][CH2:52]1)=[O:50])([CH3:47])([CH3:46])[CH3:45]>>[C:44]([O:48][C:49]([N:51]1[CH2:52][CH2:53][C:54]2([CH2:57][N:56]([CH2:58][C:59]3[S:67][C:66]4[C:65]([N:68]5[CH2:69][CH2:70][O:71][CH2:72][CH2:73]5)=[N:64][C:63]([Cl:74])=[N:62][C:61]=4[CH:60]=3)[CH2:55]2)[CH2:75][CH2:76]1)=[O:50])([CH3:47])([CH3:45])[CH3:46].[Cl:1][C:2]1[N:3]=[C:4]([N:22]2[CH2:27][CH2:26][O:25][CH2:24][CH2:23]2)[C:5]2[S:10][C:9]([CH2:11][N:12]3[CH2:13][C:14]4([CH2:20][CH2:19][NH:18][CH2:17][CH2:16]4)[CH2:15]3)=[CH:8][C:6]=2[N:7]=1
Reactant: CN1CCC2(CC1)CN(Cc1cc3nc(Cl)nc(N4CCOCC4)c3s1)C2
Agent: CC(C)(C)OC(=O)N1CCC2(CC1)CN(Cc1cc3nc(Cl)nc(N4CCOCC4)c3s1)C2
Agent: CC(C)(C)OC(=O)N1CCC2(CC1)CNC2
Product: Clc1nc(N2CCOCC2)c2sc(CN3CC4(CCNCC4)C3)cc2n1
Yield: 58 %

Procedure:
2-(2-Chloro-4-morpholin-4-yl-thieno[3,2-d]pyrimidin-6-ylmethyl)-2,7-diaza-spiro[3.5]nonane-7-carboxylic acid tert-butyl ester was prepared according to the method used in the preparation of 2-chloro-6-(7-methyl-2,7-diaza-spiro[3.5]non-2-ylmethyl)-4-morpholin-4-yl-thieno[3,2-d]pyrimidine using 2,7-diaza-spiro[3.5]-nonane-7-carboxylic acid tert-butyl ester in place of 7-methyl-2,7-diaza-spiro[3.5]nonane. 2-(2-chloro-4-morpholin-4-yl-thieno[3,2-d]pyrimidin-6-ylmethyl)-2,7-diaza-spiro[3.5]nonane-7-carboxylic acid tert-butyl ester was subsequently BOC-deprotected to give the title compound as a pale yellow oil (287 mg, 58%).
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6](=[O:11])[CH2:5]2.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[CH2:22]([N:24]([CH2:40][CH3:41])[CH2:25][CH2:26][NH:27][C:28]([C:30]1[N:35]=[C:34]2[CH2:36][O:37][C:38](=O)[C:33]2=[CH:32][CH:31]=1)=[O:29])[CH3:23].Cl>C1COCC1.O1CCOCC1>[CH2:40]([N:24]([CH2:22][CH3:23])[CH2:25][CH2:26][NH:27][C:28]([C:30]1[N:35]=[C:34]2[CH2:36][O:37][C:38](=[C:5]3[C:4]4[C:8](=[CH:9][CH:10]=[C:2]([F:1])[CH:3]=4)[NH:7][C:6]3=[O:11])[C:33]2=[CH:32][CH:31]=1)=[O:29])[CH3:41]
Reactant: O=C1Cc2cc(F)ccc2N1
Reactant: CCN(CC)CCNC(=O)c1ccc2c(n1)COC2=O
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: Cl
Agent: [Li+]
Solvent: C1CCOC1
Solvent: C1COCCO1
Product: CCN(CC)CCNC(=O)c1ccc2c(n1)COC2=C1C(=O)Nc2ccc(F)cc21
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 49.7 %

Procedure:
A solution of 5-fluoro-1,3-dihydro-indol-2-one (76 mg, 0.46 mmol) in THF (3 mL) is treated with a solution of lithium bis(trimethylsilyl)amide (1.2 mL of a 1M solution in THF, 1.2 mmol) dropwise. The resulting solution is stirred at room temperature for 10 min. A solution of 5-oxo-5,7-dihydro-furo[3,4-b]pyridine-2-carboxylic acid (2-diethylamino-ethyl)-amide (70 mg, 0.25 mmol) in THF (2 mL) is added dropwise to the reaction mixture. The resulting solution is stirred for 4 h and is poured into a cold 4M HCl solution in dioxane (3 mL) at 0° C. The resulting mixture is stirred at room temperature overnight. The reaction mixture is concentrated to partially remove the dioxane and is then partitioned between EtOAc and saturated aqueous NaHCO3 solution. The organic phase is collected and the aqueous phase is extracted with additional EtOAc. The combined organic extracts are dried (Na2SO4), filtered and concentrated. The residue is purified by chromatography (silica gel, MeOH-Chloroform). The product containing fraction are concentrated and the residue is treated with EtOAc-hexane (1:1). The solid is collected by filtration to give the title compound as an orange solid (51 mg, 49%).
Reaction SMILES: [CH2:1]([O:11][C:12]1[CH:17]=[CH:16][C:15]([C:18]#[C:19][C:20]2[CH:25]=[CH:24][C:23]([OH:26])=[CH:22][CH:21]=2)=[CH:14][CH:13]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH3:10].[F:27][C:28]([F:56])([C:52]([F:55])([F:54])[F:53])[C:29]([F:51])([F:50])[C:30]([F:49])([F:48])[O:31][C:32]([F:47])([F:46])[C:33]([F:45])([F:44])[O:34][C:35]([F:43])([F:42])[CH2:36][O:37][CH2:38][CH2:39][CH2:40]Br>>[CH2:1]([O:11][C:12]1[CH:13]=[CH:14][C:15]([C:18]#[C:19][C:20]2[CH:25]=[CH:24][C:23]([O:26][CH2:40][CH2:39][CH2:38][O:37][CH2:36][C:35]([O:34][C:33]([F:44])([F:45])[C:32]([F:46])([F:47])[O:31][C:30]([F:48])([F:49])[C:29]([F:50])([F:51])[C:28]([F:27])([F:56])[C:52]([F:55])([F:54])[F:53])([F:43])[F:42])=[CH:22][CH:21]=2)=[CH:16][CH:17]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH3:10]
Reactant: CCCCCCCCCCOc1ccc(C#Cc2ccc(O)cc2)cc1
Reactant: FC(F)(COCCCBr)OC(F)(F)C(F)(F)OC(F)(F)C(F)(F)C(F)(F)C(F)(F)F
Product: CCCCCCCCCCOc1ccc(C#Cc2ccc(OCCCOCC(F)(F)OC(F)(F)C(F)(F)OC(F)(F)C(F)(F)C(F)(F)C(F)(F)F)cc2)cc1

Procedure:
The title compound was prepared essentially as in Example 1 by combining 4-decyloxy-4'-hydroxytolane (1.5 g, 4.3 mmol, prepared essentially as described in EP 641850) with 3-(2-(2-(nonafluorobutoxy)tetrafluoroethoxy)-2,2-difluoroethoxy)propyl bromide (2.6 g, 4.7 mmol). The reaction mixture was quenched with water, and the resulting crude product was further purified by recrystallization from ethanol, followed by Kugelrohr distillation (200-220° C. at 0.5 torr), to provide a yield of 2.64 g.
Reaction SMILES: N1(C2C(C(N[C@H]3CCC[C@@H]3NC3C=NC(C(F)(F)F)=CN=3)=O)=NC=CC=2)CCCCC1.Cl.[F:33][C:34]([F:49])([F:48])[C:35]1[N:36]=[CH:37][C:38]([NH:41][C@H:42]2[CH2:46][CH2:45][CH2:44][C@@H:43]2[NH2:47])=[N:39][CH:40]=1.[F:50][C:51]1[C:52]([N:61]2[N:65]=[CH:64][CH:63]=[N:62]2)=[C:53]([CH:57]=[C:58]([F:60])[CH:59]=1)[C:54](O)=[O:55]>>[F:50][C:51]1[C:52]([N:61]2[N:65]=[CH:64][CH:63]=[N:62]2)=[C:53]([CH:57]=[C:58]([F:60])[CH:59]=1)[C:54]([NH:47][C@H:43]1[CH2:44][CH2:45][CH2:46][C@@H:42]1[NH:41][C:38]1[CH:37]=[N:36][C:35]([C:34]([F:33])([F:48])[F:49])=[CH:40][N:39]=1)=[O:55]
Reactant: O=C(O)c1cc(F)cc(F)c1-n1nccn1
Reactant: N[C@H]1CCC[C@@H]1Nc1cnc(C(F)(F)F)cn1
Agent: Cl
Agent: O=C(N[C@H]1CCC[C@@H]1Nc1cnc(C(F)(F)F)cn1)c1ncccc1N1CCCCC1
Product: O=C(N[C@H]1CCC[C@@H]1Nc1cnc(C(F)(F)F)cn1)c1cc(F)cc(F)c1-n1nccn1

Procedure:
Prepared according to the procedure for 3-(piperidin-1-yl)-N-[(1S,2S)-2-{[5-(trifluoromethyl)pyrazin-2-yl]amino}cyclopentyl]pyridine-2-carboxamide (Example 51) from (1S,2S)-1-N-[5-(trifluoromethyl)pyrazin-2-yl]cyclopentane-1,2-diamine hydrochloride (Intermediate 14; 75 mg, 0.27 mmol) and 3,5-difluoro-2-(2H-1,2,3-triazol-2-yl)benzoic acid (Intermediate 40a; 60 mg, 0.27 mmol) except this was purified only by column chromatography (silica, 40-100% ethyl acetate/petrol) to afford the title compound.
Reaction SMILES: F[C:2]1[CH:14]=[CH:13][C:5]([C:6]([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7])=[CH:4][CH:3]=1.[N:15]1([CH2:21][CH2:22][NH2:23])[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]1>C(OCC)(=O)C>[N:15]1([CH2:21][CH2:22][NH:23][C:2]2[CH:14]=[CH:13][C:5]([C:6]([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7])=[CH:4][CH:3]=2)[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]1
Reactant: CC(C)(C)OC(=O)c1ccc(F)cc1
Reactant: NCCN1CCCCC1
Solvent: CCOC(C)=O
Product: CC(C)(C)OC(=O)c1ccc(NCCN2CCCCC2)cc1
Yield: 64.5 %

Procedure:
tert-Butyl 4-fluorobenzoate 185 (0.502 g, 2.55 mmol) and 2-(piperidin-1-yl)ethanamine 186 (1.46 mL, 10.21 mmol) were stirred neat at 120° C. overnight then diluted with ethyl acetate, washed with saturated aqueous sodium bicarbonate (1×), brine (1×), dried over magnesium sulfate and evaporated to give 187 (0.501 g, 64%). 1H NMR: (DMSO) δ (ppm): 400 MHz, (DMSO) d (ppm): 7.59 (d, J=8.8 Hz, 2H), 6.55 (d, J=8.8 Hz, 2H), 6.24 (t, J=5.1 Hz, 1H), 4.11 (m, 2H), 3.21 to 3.13 (m, 6H), 2.44 (t, J=7.1 Hz, 2H), 2.37 (m, 2H), 1.49 (s, 9H), 1.47 to 1.38 (m, 2H). MS: 304.22 (calc), 249.1 (M-tBu).
Reaction SMILES: [NH:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6]([O:8][CH2:9][CH3:10])=[O:7].[C:11](Cl)(=[O:17])[CH2:12][CH2:13][CH2:14][CH2:15][CH3:16]>>[C:11]([C:4]1[CH:3]=[C:2]([C:6]([O:8][CH2:9][CH3:10])=[O:7])[NH:1][CH:5]=1)(=[O:17])[CH2:12][CH2:13][CH2:14][CH2:15][CH3:16]
Reactant: CCOC(=O)c1ccc[nH]1
Reactant: CCCCCC(=O)Cl
Product: CCCCCC(=O)c1c[nH]c(C(=O)OCC)c1
Yield: 81.6 %

Procedure:
Starting with 2.0 g of ethyl pyrrole carboxylate (14 mmol) and 4.5 ml (30 mmol) of hexanoylchloride and following a procedure analogous to the one described above, 2.71 g (80% yield) of the desired product is obtained. 1H NMR (δ ppm, CDCl3): 10.70 (s, br, 1H, NH); 7.57 (dd, J=1.61, 3.35 Hz, 1H, α-pyrrolic); 7.29 (dd, J=1.61, 2.48, 1H ; β-pyrrolic); 4.32 (q, 2H, J=7.12 Hz, CO2Et); 2.74 (t, 2H, J=7.54, α-CO CH2); 1.68 (m, 2H, β-CO CH2); 1.34 (t, 3H, J=7.12, CO2Et); 1.31 (m, 4H, γ,δ-CO CH2); 0.87 (m, 3H, CH3). 13C NMR (CDCl3): 196.57; 161.32; 126.74; 126.65; 123.93; 114.91; 60.87; 39.60; 31.44; 24.28; 22.35; 14.17; 13.77. Exact mass calculated for C13H20NO3 (M+H)=238.144319, found=238.143749.
Reaction SMILES: [N:1]1[CH:2]=[C:3]([C:10]([OH:12])=O)[N:4]2[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=12.S(Cl)(Cl)=O.[CH3:17][C:18]1[C:26]2[C:25]([NH2:27])=[CH:24][CH:23]=[CH:22][C:21]=2[N:20]([CH2:28][C:29]2[CH:34]=[CH:33][CH:32]=[C:31]([CH3:35])[N:30]=2)[N:19]=1>>[CH3:17][C:18]1[C:26]2[C:21](=[CH:22][CH:23]=[CH:24][C:25]=2[NH:27][C:10]([C:3]2[N:4]3[CH:9]=[CH:8][CH:7]=[CH:6][C:5]3=[N:1][CH:2]=2)=[O:12])[N:20]([CH2:28][C:29]2[CH:34]=[CH:33][CH:32]=[C:31]([CH3:35])[N:30]=2)[N:19]=1
Reactant: Cc1cccc(Cn2nc(C)c3c(N)cccc32)n1
Reactant: O=C(O)c1cnc2ccccn12
Solvent: O=S(Cl)Cl
Product: Cc1cccc(Cn2nc(C)c3c(NC(=O)c4cnc5ccccn45)cccc32)n1
Temperature: 25 °C
Reaction time: 1 h
Yield: 31.9 %

Procedure:
Imidazo[1,2-a]pyridine-3-carboxylic acid (62 mg, 0.38 mmol) was dissolved neat in thionyl chloride (112 mL, 1.5 mmol). The reaction mixture was stirred at ambient temperature for 1 hour before concentrating and drying under high vacuum for 16 hours. The resulting solid was dissolved in tetrahydrofuran (2 mL). 3-Methyl-1-((6-methylpyridin-2-yl)methyl)-1H-indazol-4-amine (97 mg, 0.38 mmol) was added and the reaction was stirred at 70° C. in a sand bath for 6 hours. The mixture was concentrated and partitioned between ethyl acetate and saturated sodium bicarbonate. The ethyl acetate layer was washed with water and brine before drying over sodium sulfate and concentrating. Preparative Thin Layer Chromatography (Silica, 1 mm) of the crude material, eluting with 10% MeOH/DCM, gave N-(3-methyl-1-((6-methylpyridin-2-yl)methyl)-1H-indazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide (48 mg) in a band with Rf=0.6. MS m/z 397.3 (M+1, APCI+).
Reaction SMILES: C([NH:5][S:6]([C:9]1[CH:14]=[CH:13][C:12]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]3[CH2:22][C:23](=[O:39])[NH:24][C:25]4[CH:31]=[C:30]([C:32]([F:35])([F:34])[F:33])[C:29]([N:36]([CH3:38])[CH3:37])=[CH:28][C:26]=4[N:27]=3)[CH:16]=2)=[CH:11][CH:10]=1)(=[O:8])=[O:7])(C)(C)C.C(O)(C(F)(F)F)=O>>[CH3:37][N:36]([CH3:38])[C:29]1[C:30]([C:32]([F:35])([F:33])[F:34])=[CH:31][C:25]2[NH:24][C:23](=[O:39])[CH2:22][C:21]([C:17]3[CH:16]=[C:15]([C:12]4[CH:11]=[CH:10][C:9]([S:6]([NH2:5])(=[O:7])=[O:8])=[CH:14][CH:13]=4)[CH:20]=[CH:19][CH:18]=3)=[N:27][C:26]=2[CH:28]=1
Reactant: CN(C)c1cc2c(cc1C(F)(F)F)NC(=O)CC(c1cccc(-c3ccc(S(=O)(=O)NC(C)(C)C)cc3)c1)=N2
Solvent: O=C(O)C(F)(F)F
Product: CN(C)c1cc2c(cc1C(F)(F)F)NC(=O)CC(c1cccc(-c3ccc(S(N)(=O)=O)cc3)c1)=N2

Procedure:
) The title compound was prepared from the above described 3′-(8-dimethylamino-4-oxo-7-trifluoromethyl-4,5-dihydro-3H-benzo[b][1,4]diazepin-2-yl)-biphenyl-4-sulfonic acid tert-butylamide (132 mg) and TFA (3 mL) according to the general procedure I step 2. Obtained as a white solid (55 mg, 22%). MS (ISP) 501.4 [(M−H)−]; mp 246° C. (dec).
Reaction SMILES: [C:1]([C:3]1[CH:35]=[CH:34][C:6]([O:7][C:8]2[C:13]([NH:14][S:15]([C:18]3[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=3)(=[O:17])=[O:16])=[CH:12][CH:11]=[C:10]([O:25][C:26]3[CH:31]=[CH:30][C:29]([C:32]#[N:33])=[CH:28][CH:27]=3)[N:9]=2)=[CH:5][CH:4]=1)#[N:2]>C(O)C>[CH2:6]([O:7][C:1]([C:3]1[CH:35]=[CH:34][C:6]([O:7][C:8]2[C:13]([NH:14][S:15]([C:18]3[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=3)(=[O:17])=[O:16])=[CH:12][CH:11]=[C:10]([O:25][C:26]3[CH:31]=[CH:30][C:29]([C:32]([O:25][CH2:10][CH3:11])=[NH:33])=[CH:28][CH:27]=3)[N:9]=2)=[CH:5][CH:4]=1)=[NH:2])[CH3:5]
Reactant: N#Cc1ccc(Oc2ccc(NS(=O)(=O)c3ccc(F)cc3)c(Oc3ccc(C#N)cc3)n2)cc1
Solvent: CCO
Product: CCOC(=N)c1ccc(Oc2ccc(NS(=O)(=O)c3ccc(F)cc3)c(Oc3ccc(C(=N)OCC)cc3)n2)cc1
Reaction time: 8 h
Yield: 260.7 %

Procedure:
2,6-Bis-(4-cyano-phenoxy)-3-(4-fluorobenzene-sulphonamido)-pyridine 0.3 g (0.61 mmol) was added to 70 ml of ethanol (saturated with HCl gas at −25° C.) and the reaction mixture was kept in a tight vessel at room temperature overnight. The reaction mixture was concentrated under reduced pressure to afford 0.46 g of the crude product which was taken for the next step without purification. Percentage purity: 51.1%, (M+1)=578.1+1.