Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br[C:2]1[CH:3]=[CH:4][C:5]2[N:9]=[CH:8][N:7]([C:10]3[CH:15]=[CH:14][C:13]([F:16])=[CH:12][CH:11]=3)[C:6]=2[CH:17]=1.[F:18][C:19]([F:35])([F:34])[C:20]1[CH:25]=[CH:24][C:23]([N:26]2[C:30](B(O)O)=[CH:29][CH:28]=[N:27]2)=[CH:22][CH:21]=1>>[F:16][C:13]1[CH:14]=[CH:15][C:10]([N:7]2[C:6]3[CH:17]=[C:2]([C:30]4[N:26]([C:23]5[CH:22]=[CH:21][C:20]([C:19]([F:18])([F:34])[F:35])=[CH:25][CH:24]=5)[N:27]=[CH:28][CH:29]=4)[CH:3]=[CH:4][C:5]=3[N:9]=[CH:8]2)=[CH:11][CH:12]=1
Reactant: OB(O)c1ccnn1-c1ccc(C(F)(F)F)cc1
Reactant: Fc1ccc(-n2cnc3ccc(Br)cc32)cc1
Product: Fc1ccc(-n2cnc3ccc(-c4ccnn4-c4ccc(C(F)(F)F)cc4)cc32)cc1

Procedure:
The title compound, yellow solid (45 mg, 31%), MS (ISP) m/z=423.5 [(M+H)+], mp 167° C., was prepared in accordance with the general method of example 1 from 6-bromo-1-(4-fluoro-phenyl)-1H-benzo[d]imidazole (intermediate G) (100 mg, 344 μmol) and 1-(4-trifluoromethyl-phenyl)-1H-pyrazol-5-ylboronic acid (intermediate C) (96.7 mg, 378 μmol).
Reaction SMILES: C(OC(=O)[NH:7][CH:8]1[CH2:13][CH2:12][CH2:11][CH:10]([NH:14][C:15]([C:17]2[C:25]3[C:20](=[N:21][CH:22]=[C:23]([C:26]4[C:34]5[C:29](=[CH:30][C:31]([Cl:35])=[CH:32][CH:33]=5)[N:28]([CH3:36])[N:27]=4)[N:24]=3)[NH:19][CH:18]=2)=[O:16])[CH2:9]1)(C)(C)C.C(O)(C(F)(F)F)=O>ClCCl.CO>[NH2:7][CH:8]1[CH2:13][CH2:12][CH2:11][CH:10]([NH:14][C:15]([C:17]2[C:25]3[C:20](=[N:21][CH:22]=[C:23]([C:26]4[C:34]5[C:29](=[CH:30][C:31]([Cl:35])=[CH:32][CH:33]=5)[N:28]([CH3:36])[N:27]=4)[N:24]=3)[NH:19][CH:18]=2)=[O:16])[CH2:9]1
Reactant: Cn1nc(-c2cnc3[nH]cc(C(=O)NC4CCCC(NC(=O)OC(C)(C)C)C4)c3n2)c2ccc(Cl)cc21
Solvent: CO
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: Cn1nc(-c2cnc3[nH]cc(C(=O)NC4CCCC(N)C4)c3n2)c2ccc(Cl)cc21
Reaction time: 18 h

Procedure:
The more polar, diastereomer A of (3-{[2-(6-chloro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carbonyl]-amino}-cyclohexyl)-carbamic acid tert-butyl ester (53 mg, 101 μmol) was dissolved in dichloromethane (5 mL) and treated with TFA (1.19 g, 803 μL, 10.4 mmol), the light yellow solution became a bright red-orange solution, stirring continued for 18 h at room temperature. Solvents were evaporated and the residue dissolved in dichloromethane/MeOH, adsorbed on silica gel and purified by chromatography (25 g column, 50 μm from Thomson, 0-10% MeOH containing 10% ammonium hydroxide in dichloromethane, 10 min gradient) to give an off white solid that was sonicated in MeOH and allowed to stand to promote complete solid formation. The solid was separated by decanting the mother liquor and dried under high vacuum to give 2-(6-chloro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (3-amino-cyclohexyl)-amide (diastereomer A) (27 mg, 63%) as an off-white solid. MS (M+H)+=424; 1H NMR (DMSO-d6) δ: 9.05 (s, 1H), 8.38-8.49 (m, 2H), 8.06 (d, J=7.9 Hz, 1H), 7.99 (s, 1H), 7.33 (d, J=10.2 Hz, 1H), 4.16 (s, 3H), 3.91 (d, J=4.2 Hz, 1H), 3.32 (br. s., 1H), 3.15 (s, 1H), 2.22 (d, J=11.0 Hz, 1H), 2.04 (d, J=11.7 Hz, 1H), 1.79 (br. s., 1H), 0.98-1.24 (m, 3H).
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][CH:9]1[CH2:17][C:16]2[C:11](=[CH:12][CH:13]=[C:14](OS(C(F)(F)F)(=O)=O)[CH:15]=2)[CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:26][C:27]1[CH:32]=[CH:31][C:30](/[CH:33]=[CH:34]/B(O)O)=[CH:29][CH:28]=1.C(=O)([O-])[O-].[Na+].[Na+].[Cl-].[Li+]>CCOCC.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C(O)C.C1(C)C=CC=CC=1>[C:1]([O:5][C:6]([NH:8][CH:9]1[CH2:17][C:16]2[C:11](=[CH:12][CH:13]=[C:14](/[CH:34]=[CH:33]/[C:30]3[CH:31]=[CH:32][C:27]([CH3:26])=[CH:28][CH:29]=3)[CH:15]=2)[CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(C)(C)OC(=O)NC1Cc2ccc(OS(=O)(=O)C(F)(F)F)cc2C1
Reactant: Cc1ccc(/C=C/B(O)O)cc1
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: [Cl-]
Solvent: CCOCC
Solvent: CCO
Solvent: Cc1ccccc1
Product: Cc1ccc(/C=C/c2ccc3c(c2)CC(NC(=O)OC(C)(C)C)C3)cc1
Yield: 78.3 %

Procedure:
2-(tert-butoxycarbonylamino)-5-trifluoromethanesulfonyloxyindan (260 mg, 0.69 mmol), (E)-2-(4-methylphenyl)ethenylboronic acid (180 mg), toluene (7 ml), Pd(PPh3)4 (30 mg, 0.026 mmol), 2M sodium carbonate (0.99 ml), ethanol (3.0 ml), and lithium chloride (64 mg, 1.5 mmol) were heated to reflux for 5 hours. The reaction mixture was diluted with ether, washed with water, dried, and then the solvent was distilled off under reduced pressure. The residue obtained was purified by silica gel chromatography (hexane:ethyl acetate=4:1) to obtain the title compound (190 mg, 0.54 mmol) having the following physical properties;
Reaction SMILES: [OH-].[Na+].C[O:4][C:5]([C:7]1[S:8][C:9]([Br:15])=[CH:10][C:11]=1[N+:12]([O-:14])=[O:13])=[O:6]>C1COCC1.CO>[Br:15][C:9]1[S:8][C:7]([C:5]([OH:6])=[O:4])=[C:11]([N+:12]([O-:14])=[O:13])[CH:10]=1
Reactant: COC(=O)c1sc(Br)cc1[N+](=O)[O-]
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CO
Product: O=C(O)c1sc(Br)cc1[N+](=O)[O-]
Temperature: 25 °C
Reaction time: 1 h

Procedure:
1N sodium hydroxide solution (4 mL) was added to a solution of 5-bromo-3-nitrothiophene-2-carboxylic acid methyl ester (975 mg) in 1:1 THF/methanol (4 mL) and the solution was stirred at room temperature for 1 h. The solution was partitioned between water and ethyl acetate. The aqueous phase was brought to pH 1 with 2N HCl, extracted with ethyl acetate, dried over magnesium sulfate and concentrated. The product with the molecular weight of 252.04 (C5H2BrNO4S) was obtained in this way; MS (ESI): 252 and 254 (M+H+).
Reaction SMILES: [NH2:1][CH2:2][C:3]1[CH:4]=[C:5]([C:9]2[CH:10]=[C:11]([C:19]([NH:21][C:22]3[CH:23]=[C:24](/[CH:29]=[CH:30]/[C:31]([O:33]CC)=[O:32])[CH:25]=[CH:26][C:27]=3[F:28])=[O:20])[C:12]3[C:17]([CH:18]=2)=[CH:16][CH:15]=[CH:14][CH:13]=3)[CH:6]=[CH:7][CH:8]=1.O[Li].O>>[NH2:1][CH2:2][C:3]1[CH:4]=[C:5]([C:9]2[CH:10]=[C:11]([C:19]([NH:21][C:22]3[CH:23]=[C:24](/[CH:29]=[CH:30]/[C:31]([OH:33])=[O:32])[CH:25]=[CH:26][C:27]=3[F:28])=[O:20])[C:12]3[C:17]([CH:18]=2)=[CH:16][CH:15]=[CH:14][CH:13]=3)[CH:6]=[CH:7][CH:8]=1
Reactant: CCOC(=O)/C=C/c1ccc(F)c(NC(=O)c2cc(-c3cccc(CN)c3)cc3ccccc23)c1
Agent: [Li]O
Solvent: O
Product: NCc1cccc(-c2cc(C(=O)Nc3cc(/C=C/C(=O)O)ccc3F)c3ccccc3c2)c1

Procedure:
Compound 17d was synthesized from 16d (1 g crude) and LiOH.H2O (8.94 mmol) using the procedure according to Method E described above.
Reaction SMILES: [CH:1]1([NH:4][C:5]([C:7]2[N:8]=[N:9][N:10]([C:14]3[CH:19]=[CH:18][C:17]([C:20]([NH:22][CH2:23][CH3:24])=[O:21])=[CH:16][CH:15]=3)[C:11]=2[CH2:12][OH:13])=[O:6])[CH2:3][CH2:2]1.[F:25][C:26]1[CH:27]=[C:28](O)[CH:29]=[CH:30][CH:31]=1.C(P(CCCC)CCCC)CCC.C1CCN(C(N=NC(N2CCCCC2)=O)=O)CC1>C1COCC1.O>[CH:1]1([NH:4][C:5]([C:7]2[N:8]=[N:9][N:10]([C:14]3[CH:19]=[CH:18][C:17]([C:20]([NH:22][CH2:23][CH3:24])=[O:21])=[CH:16][CH:15]=3)[C:11]=2[CH2:12][O:13][C:30]2[CH:29]=[CH:28][CH:27]=[C:26]([F:25])[CH:31]=2)=[O:6])[CH2:2][CH2:3]1
Reactant: CCNC(=O)c1ccc(-n2nnc(C(=O)NC3CC3)c2CO)cc1
Reactant: Oc1cccc(F)c1
Agent: CCCCP(CCCC)CCCC
Agent: O=C(N=NC(=O)N1CCCCC1)N1CCCCC1
Solvent: O
Solvent: C1CCOC1
Product: CCNC(=O)c1ccc(-n2nnc(C(=O)NC3CC3)c2COc2cccc(F)c2)cc1
Temperature: 25 °C
Reaction time: 6 h
Yield: 70.1 %

Procedure:
To a solution of N-cyclopropyl-1-{4-[(ethylamino)carbonyl]phenyl}-5-(hydroxymethyl)-1H-1,2,3-triazole-4-carboxamide (200 mg) obtained in Example 112 in THF (4 ml) were added 3-fluorophenol (68 mg), tributylphosphine (182 μM) and ADDP (184 mg), and the mixture was stirred at room temperature for 6 hr. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate and washed with saturated brine. The organic layer was dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column (ethyl acetate/hexane=1/1 to 2/1) and recrystallized from ethyl acetate/hexane to give the title compound as a colorless powder (180 mg).
Reaction SMILES: [NH2:1][C:2]1[CH:20]=[CH:19][C:5]([C:6]([N:8]2[C:14]3[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=3[CH2:12][CH2:11][CH2:10][CH2:9]2)=[O:7])=[CH:4][CH:3]=1.[C:21]1(=[O:27])[O:26][C:24](=[O:25])[CH2:23][CH2:22]1>ClCCl>[C:24]([CH2:23][CH2:22][C:21]([NH:1][C:2]1[CH:20]=[CH:19][C:5]([C:6]([N:8]2[C:14]3[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=3[CH2:12][CH2:11][CH2:10][CH2:9]2)=[O:7])=[CH:4][CH:3]=1)=[O:27])([OH:26])=[O:25]
Reactant: O=C1CCC(=O)O1
Reactant: Nc1ccc(C(=O)N2CCCCc3ccccc32)cc1
Solvent: ClCCl
Product: O=C(O)CCC(=O)Nc1ccc(C(=O)N2CCCCc3ccccc32)cc1
Temperature: 25 °C
Reaction time: 4.5 h
Yield: 87.5 %

Procedure:
To a solution of 1-(4-aminobenzoyl)-2,3,4,5-tetrahydro-1H-benzazepine (3.0 g) in dichloromethane (50 ml) is added succinic anhydride (1.4 g) and the mixture is stirred at room temperature for 4.5 hours. The reaction mixture is evaporated under reduced pressure in order to remove the solvent therefrom, and the resulting crystal is recrystallized from ethyl acetate to give 1-[4-(3-carboxypropionylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine (3.61 g) as colorless needles, m.p. 192° C.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:11]2[CH2:15][O:14][C:13](=[O:16])[C:12]=2[C:17]([N:19]2[CH2:24][CH2:23][O:22][CH2:21][CH2:20]2)=[O:18])[CH:6]=[CH:7][C:8]=1[O:9][CH3:10].[Cl:25][C:26]1[CH:33]=[CH:32][C:29]([CH:30]=O)=[CH:28][CH:27]=1>N1CCCCC1.C(O)C>[Cl:25][C:26]1[CH:33]=[CH:32][C:29]([CH:30]=[C:15]2[O:14][C:13](=[O:16])[C:12]([C:17]([N:19]3[CH2:20][CH2:21][O:22][CH2:23][CH2:24]3)=[O:18])=[C:11]2[C:5]2[CH:6]=[CH:7][C:8]([O:9][CH3:10])=[C:3]([O:2][CH3:1])[CH:4]=2)=[CH:28][CH:27]=1
Reactant: O=Cc1ccc(Cl)cc1
Reactant: COc1ccc(C2=C(C(=O)N3CCOCC3)C(=O)OC2)cc1OC
Solvent: CCO
Solvent: C1CCNCC1
Product: COc1ccc(C2=C(C(=O)N3CCOCC3)C(=O)OC2=Cc2ccc(Cl)cc2)cc1OC

Procedure:
4-(3,4-Dimethoxyphenyl)-2-oxo-2,5-dihydrofurane-3-carboxylic acid morpholide (1.00 g, 3 mmol) and 4-chlorobenzaldehyde (0.42 g, 3 mmol) were refluxed with ethanol (15 ml) and a small amount of piperidine (3 drops) for 3 h, then the reaction mixture was concentrated. The residue was dissolved in ethyl acetate (5 ml), petrol ether (2.5 ml) was added and the solution was applied onto a flash chromatography column (silica gel, 30 g). The column was eluted with ethyl acetate/petrol ether (2:1). The fractions containing the compound with the Rf (ethyl acetate/petrol ether, 2:1): 0.32 were collected and concentrated. 5-(4-Chlorobenzylidene)-4-(3,4-dimethoxyphenyl)-2-oxo-2,5-dihydro-furane-3-carboxylic acid morpholide was precipitated by addition of petrol ether.
Reaction SMILES: [CH3:1][S:2]([O:5][C:6]1[CH:11]=[C:10]([C:12]([F:15])([F:14])[F:13])[CH:9]=[CH:8][C:7]=1[CH:16]=[CH2:17])(=[O:4])=[O:3].C(=O)([O-])O.[Na+].[Cl:23][CH2:24][C:25](=[O:30])[C:26](Cl)=[N:27][OH:28]>C(#N)C>[CH3:1][S:2]([O:5][C:6]1[CH:11]=[C:10]([C:12]([F:13])([F:14])[F:15])[CH:9]=[CH:8][C:7]=1[CH:16]1[O:28][N:27]=[C:26]([C:25](=[O:30])[CH2:24][Cl:23])[CH2:17]1)(=[O:4])=[O:3]
Reactant: O=C(CCl)C(Cl)=NO
Reactant: C=Cc1ccc(C(F)(F)F)cc1OS(C)(=O)=O
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CC#N
Product: CS(=O)(=O)Oc1cc(C(F)(F)F)ccc1C1CC(C(=O)CCl)=NO1
Temperature: 25 °C
Reaction time: 1 h
Yield: 89.6 %

Procedure:
To a solution of 5-(trifluoromethyl)-2-vinylphenyl methanesulphonate (1.05 g) in acetonitrile (10 ml) were added sodium hydrogencarbonate (2.55 g) and 3-chloro-N-hydroxy-2-oxopropanimidoyl chloride (0.60 g) at room temperature under argon. The reaction mixture was stirred at room temperature for one hour. The solids were filtered off with suction and the filtrate was concentrated under reduced pressure. The residue was stirred with heptane to obtain 2-[3-(chloroacetyl)-4,5-dihydro-1,2-oxazol-5-yl]-5-(trifluoromethyl)phenyl methanesulphonate (1.33 g, 86% pure, 75%).
Reaction SMILES: [CH3:1][C:2]1[O:6][N:5]=[C:4]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[C:3]=1[C:13]1[N:14]=[C:15]2[CH:20]=[CH:19][C:18]([NH2:21])=[CH:17][N:16]2[CH:22]=1.[CH:23]1([C:26](O)=[O:27])[CH2:25][CH2:24]1>>[CH3:1][C:2]1[O:6][N:5]=[C:4]([C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=2)[C:3]=1[C:13]1[N:14]=[C:15]2[CH:20]=[CH:19][C:18]([NH:21][C:26]([CH:23]3[CH2:25][CH2:24]3)=[O:27])=[CH:17][N:16]2[CH:22]=1
Reactant: Cc1onc(-c2ccccc2)c1-c1cn2cc(N)ccc2n1
Reactant: O=C(O)C1CC1
Product: Cc1onc(-c2ccccc2)c1-c1cn2cc(NC(=O)C3CC3)ccc2n1
Yield: 79 %

Procedure:
As described for Example 56, 2-(5-methyl-3-phenyl-isoxazol-4-yl)-imidazo[1,2-a]pyridin-6-ylamine (64 mg, 0.2 mmol) was converted, using cyclopropancarboxylic acid instead of cyclopropylacetic acid, to the title compound (57 mg, 79%) which was obtained as a light brown solid. MS: m/e=359.1 [M+H]+.
Reaction SMILES: Cl[C:2]1[CH:3]=[CH:4][N:5]2[C:10]([C:11]=1[CH3:12])=[C:9]([CH:13]1[CH2:15][CH2:14]1)[CH:8]=[C:7]([C:16]([O:18][CH3:19])=[O:17])[C:6]2=[O:20].[F:21][C:22]1[CH:28]=[C:27](B2OC(C)(C)C(C)(C)O2)[CH:26]=[CH:25][C:23]=1[NH2:24]>>[NH2:24][C:23]1[CH:25]=[CH:26][C:27]([C:2]2[CH:3]=[CH:4][N:5]3[C:10]([C:11]=2[CH3:12])=[C:9]([CH:13]2[CH2:15][CH2:14]2)[CH:8]=[C:7]([C:16]([O:18][CH3:19])=[O:17])[C:6]3=[O:20])=[CH:28][C:22]=1[F:21]
Reactant: COC(=O)c1cc(C2CC2)c2c(C)c(Cl)ccn2c1=O
Reactant: CC1(C)OB(c2ccc(N)c(F)c2)OC1(C)C
Product: COC(=O)c1cc(C2CC2)c2c(C)c(-c3ccc(N)c(F)c3)ccn2c1=O
Yield: 76.7 %

Procedure:
Methyl 8-(4-amino-3-fluoro-phenyl)-1-cyclopropyl-9-methyl-4-oxo-4H-quinolizine-3-carboxylate was prepared according to General Procedure A using methyl 8-chloro-1-cyclopropyl-9-methyl-4-oxo-4H-quinolizine-3-carboxylate (200 mg, 0.68 mmol) and 2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (195 mg, 0.82 mmol). Purification by flash silica column chromatography (CH2Cl2:MeOH) (1:0 to 9:1) afforded the title compound as a yellow solid (191 mg, 76%). ESI-MS m/z: 367 (M+H)+.
Reaction SMILES: [CH3:1][O:2][C:3]1[N:8]=[C:7]2[C:9]([C:13]3[N:29](S(C4C=CC(C)=CC=4)(=O)=O)[C:16]4=[N:17][CH:18]=[CH:19][C:20]([CH2:21][O:22][C:23]5[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=5)=[C:15]4[CH:14]=3)=[CH:10][N:11]([CH3:12])[C:6]2=[CH:5][C:4]=1[O:40][CH3:41].[OH-].[K+]>>[CH3:1][O:2][C:3]1[N:8]=[C:7]2[C:9]([C:13]3[NH:29][C:16]4=[N:17][CH:18]=[CH:19][C:20]([CH2:21][O:22][C:23]5[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=5)=[C:15]4[CH:14]=3)=[CH:10][N:11]([CH3:12])[C:6]2=[CH:5][C:4]=1[O:40][CH3:41]
Reactant: COc1cc2c(nc1OC)c(-c1cc3c(COc4ccccc4)ccnc3n1S(=O)(=O)c1ccc(C)cc1)cn2C
Agent: [K+]
Agent: [OH-]
Product: COc1cc2c(nc1OC)c(-c1cc3c(COc4ccccc4)ccnc3[nH]1)cn2C
Yield: 93.1 %

Procedure:
The product is prepared by following the procedure described in example 34 stage (k), starting with 0.140 g of 5,6-dimethoxy-1-methyl-3-[4-phenoxymethyl-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-1H-pyrrolo[3,2-b]pyridine instead of the cyclopropyl-[2-(5,6-dimethoxy-1-methyl-1H-pyrrolo[3,2-b]pyridin-3-yl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-4-ylmethyl]amine used in example 34 stage (k) and 1.2 cm3 of 5N potassium hydroxide. 0.095 g of 5,6-dimethoxy-1-methyl-3-(4-phenoxymethyl-1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-pyrrolo[3,2-b]pyridine is obtained with the following characteristics:
Reaction SMILES: [CH2:1]([C:3]1(O)[C:11]2[C:6](=[CH:7][C:8]([F:12])=[CH:9][CH:10]=2)[CH2:5][CH2:4]1)[CH3:2].[CH2:14]([O:21][C:22](=[O:33])[NH:23][C:24]1[CH:25]=[CH:26][CH:27]=[C:28]2[C:32]=1[NH:31][CH:30]=[CH:29]2)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1>>[CH2:14]([O:21][C:22](=[O:33])[NH:23][C:24]1[CH:25]=[CH:26][CH:27]=[C:28]2[C:32]=1[NH:31][CH:30]=[C:29]2[C:3]1([CH2:1][CH3:2])[C:11]2[C:6](=[CH:7][C:8]([F:12])=[CH:9][CH:10]=2)[CH2:5][CH2:4]1)[C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1
Reactant: O=C(Nc1cccc2cc[nH]c12)OCc1ccccc1
Reactant: CCC1(O)CCc2cc(F)ccc21
Product: CCC1(c2c[nH]c3c(NC(=O)OCc4ccccc4)cccc23)CCc2cc(F)ccc21

Procedure:
Utilizing 1-ethyl-5-fluoro-indan-1-ol and (1H-indol-7-yl)-carbamic acid benzyl ester, the tide compound is prepared as in example 1. 7.78 g (100%). LC-MS m/z 249.1 (M++1)
Reaction SMILES: Cl.[NH2:2][C@H:3]1[CH2:6][C@H:5]([N:7]2[C:11]3=[N:12][CH:13]=[CH:14][N:15]=[C:10]3[N:9]([CH:16]3[CH2:18][CH2:17]3)[C:8]2=[O:19])[CH2:4]1.Cl[C:21]1[O:22][C:23]2[CH:29]=[CH:28][CH:27]=[CH:26][C:24]=2[N:25]=1.C(NC(C)C)(C)C>CS(C)=O>[O:22]1[C:23]2[CH:29]=[CH:28][CH:27]=[CH:26][C:24]=2[N:25]=[C:21]1[NH:2][C@H:3]1[CH2:6][C@H:5]([N:7]2[C:11]3=[N:12][CH:13]=[CH:14][N:15]=[C:10]3[N:9]([CH:16]3[CH2:17][CH2:18]3)[C:8]2=[O:19])[CH2:4]1
Reactant: N[C@H]1C[C@H](n2c(=O)n(C3CC3)c3nccnc32)C1
Reactant: Clc1nc2ccccc2o1
Agent: Cl
Solvent: CC(C)NC(C)C
Solvent: CS(C)=O
Product: O=c1n(C2CC2)c2nccnc2n1[C@H]1C[C@H](Nc2nc3ccccc3o2)C1

Procedure:
A glass microwave reaction vessel was charged with 1-(trans-3-aminocyclobutyl)-3-cyclopropyl-1H-imidazo[4,5-b]pyrazin-2(3H)-one hydrochloride (Intermediate 79, 0.1099 g, 0.390 mmol), 2-chlorobenzoxazole (0.088 ml, 0.768 mmol, Sigma-Aldrich Chemical Company, Inc.), and diisopropylamine (0.204 ml, 1.170 mmol, Sigma-Aldrich Chemical Company, Inc.) in DMSO. The reaction was heated to 90° C. for 24 h The crude product was purified by reverse-phase preparative HPLC using a Phenomenex Gemini column, 10 micron, C18, 110 Å, 100×50 mm, 0.1% TFA in CH3CN/H2O, gradient 10% to 909% over 15 min. LCMS showed product was not isolated at ≧95% purity. The crude product was adsorbed onto a plug of silica gel and chromatographed through a Biotage SNAP HP-silica gel column (25 g), eluting with a gradient of % to 5% MeOH in CH2Cl2, to provide the title compound (0.0590 g, 0.163 mmol, 42.4% yield). LCMS showed product peak at 1.604 min (m+1=362.9). 1H NMR (400 MHz, DMSO-d6) δ ppm 0.96-1.02 (m, 2 H) 1.02-1.09 (m, 2 H) 2.52-2.58 (m, 1 H) 2.91-3.01 (m, 1 H) 3.18-3.30 (m, 2 H) 4.46-4.59 (m, 1 H) 5.11-5.23 (m, 1 H) 6.99 (td, J=7.73, 1.37 Hz, 1 H) 7.12 (td, J=7.63, 1.17 Hz, 1 H) 7.27 (dd, J=7.73, 0.68 Hz, 1 H) 7.36 (dd, J=7.82, 0.59 Hz, 1 H) 7.94-7.98 (m, 1 H) 7.99-8.02 (m, 1 H) 8.42 (d, J=6.46 Hz, 1 H)
Reaction SMILES: [NH2:1][CH:2]1[C:6](=[O:7])[N:5]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH2:4][CH:3]1[C:14]([O:16][CH2:17][CH3:18])=[O:15].C(N(CC)CC)C.[CH:26]1[C:35]2[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=2)[CH:29]=[CH:28][C:27]=1[C:36](Cl)=[O:37]>C(Cl)Cl>[CH:26]1[C:35]2[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=2)[CH:29]=[CH:28][C:27]=1[C:36]([NH:1][C@H:2]1[C:6](=[O:7])[N:5]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH2:4][C@H:3]1[C:14]([O:16][CH2:17][CH3:18])=[O:15])=[O:37]
Reactant: O=C(Cl)c1ccc2ccccc2c1
Reactant: CCOC(=O)C1CN(c2ccccc2)C(=O)C1N
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CCOC(=O)[C@@H]1CN(c2ccccc2)C(=O)[C@@H]1NC(=O)c1ccc2ccccc2c1
Temperature: 25 °C
Reaction time: 12 h
Yield: 100.2 %

Procedure:
To a solution of the aminopyrrolidinone of Example S (1.54 g, 6.2 mmol) and triethylamine (1.3 ml, 9.3 mmol) in CH2Cl2 (10 ml) was added a solution of 2-naphthoyl chloride (1.18 g, 6.2 mmol) in CH2Cl2 (7 ml) dropwise via syringe. After stirring for 12 h at room temperature the reaction mixture was evaporated in vacuo to give a residue which was chromatographed on silica gel eluting with EtOH/CH2Cl2 (2%-5%) to give the title compound (2.5 g, 100%) as a colorless solid. Anal calcd for C24H22N2O4 : C, 71.63; H, 5.51; N, 6.96. Found C, 71.31; H, 5.45; N, 6.73. MS calcd for C24H22N2O4 402; found 402.
Reaction SMILES: [CH:1]1[CH:2]=[CH:3][N:4]2[CH2:10][C:9]3[CH:11]=[CH:12][CH:13]=[CH:14][C:8]=3[N:7]([C:15]([C:17]3[CH:22]=[CH:21][C:20](B4OC(C)(C)C(C)(C)O4)=[C:19]([CH3:32])[CH:18]=3)=[O:16])[CH2:6][C:5]=12.FC(F)(F)S(O[C:39]1[CH:44]([CH3:45])[CH2:43][CH2:42][CH2:41][C:40]=1[CH3:46])(=O)=O>>[CH:1]1[CH:2]=[CH:3][N:4]2[CH2:10][C:9]3[CH:11]=[CH:12][CH:13]=[CH:14][C:8]=3[N:7]([C:15]([C:17]3[CH:22]=[CH:21][C:20]([C:39]4[CH:44]([CH3:45])[CH2:43][CH2:42][CH2:41][C:40]=4[CH3:46])=[C:19]([CH3:32])[CH:18]=3)=[O:16])[CH2:6][C:5]=12
Reactant: CC1=C(OS(=O)(=O)C(F)(F)F)C(C)CCC1
Reactant: Cc1cc(C(=O)N2Cc3cccn3Cc3ccccc32)ccc1B1OC(C)(C)C(C)(C)O1
Product: CC1=C(c2ccc(C(=O)N3Cc4cccn4Cc4ccccc43)cc2C)C(C)CCC1

Procedure:
(10,11-Dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-10-yl)-[3-methyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-methanone of Example 2, Step B (0.500 g, 1.17 mmol) and 2,6-dimethyl-cyclohex-1-en-1-yl trifluoromethanesulfonate (0.401 g, 1.29 mmol) were reacted in the manner of Example 2, Step C. Purification by flash column chromatography on silica gel, eluting with 30% ethyl acetate in hexane, followed by recrystallization from petroleum ether (−20° C.) afforded the title compound as white crystals, m.p. 133–135° C.
Reaction SMILES: [I:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=1.Br[CH2:10][CH2:11][OH:12].C([O-])([O-])=O.[K+].[K+].O>CC(C)=O>[I:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH2:10][CH2:11][OH:12])=[CH:4][CH:3]=1
Reactant: Oc1ccc(I)cc1
Reactant: OCCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Solvent: O
Product: OCCOc1ccc(I)cc1

Procedure:
A suspension of 11 g (50 mmol) 4-iodophenol, 3.88 mL (55 mmol) 2-bromoethanol and 8.3 g (60 mmol) K2CO3 in 60 mL acetone is refluxed for 24 h. The solvent is eliminated i.vac., the residue is combined with water, exhaustively extracted with EtOAc and the organic phase is dried over Na2SO4. After the desiccant and solvent have been eliminated the residue is purified by chromatography on silica gel (cyc/EtOAc 7:3).
Reaction SMILES: N.COC([O:6][C:7]1[CH:26]=[CH:25][C:10]([C:11]([O:13][C:14]2[CH:24]=[CH:23][C:17]3[CH:18]=[CH:19][C:20](=[O:22])[O:21][C:16]=3[CH:15]=2)=[O:12])=[CH:9][CH:8]=1)=O>C(O)C>[OH:6][C:7]1[CH:8]=[CH:9][C:10]([C:11]([O:13][C:14]2[CH:24]=[CH:23][C:17]3[CH:18]=[CH:19][C:20](=[O:22])[O:21][C:16]=3[CH:15]=2)=[O:12])=[CH:25][CH:26]=1
Reactant: COC(=O)Oc1ccc(C(=O)Oc2ccc3ccc(=O)oc3c2)cc1
Agent: N
Solvent: CCO
Product: O=C(Oc1ccc2ccc(=O)oc2c1)c1ccc(O)cc1
Reaction time: 2 h
Yield: 93.9 %

Procedure:
50 ml of saturated ethanolic ammonia solution is added dropwise to a solution of 12.2 g of 2-oxo-2H-1-benzopyran-7-yl 4-methoxycarbonyloxybenzoate in 200 ml of ethanol. The reaction mixture is stirred for two hours, evaporated down and taken up in 100 ml diethyl ether. This solution is washed with water, dried, filtered to remove inorganic material and the filtrate evaporated down. The residue is purified by column chromatography on silica gel using hexane/ethyl acetate (1/1 v/v) as eluent and recrystallisation from acetonitrile to yield 9.5 g of 2-oxo-2H-1-benzopyran-7-yl 4-hydroxybenzoate.
Reaction SMILES: [C:1]1([C:7]2([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[CH2:12][CH2:11][C:10](=O)[CH2:9][CH2:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1>O1CCCC1>[C:1]1([C:7]2([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[CH2:12][CH2:11][C:10]([CH2:6][CH2:1][CH2:2][CH3:3])=[CH:9][CH2:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: O=C1CCC(c2ccccc2)(c2ccccc2)CC1
Solvent: C1CCOC1
Product: CCCCC1=CCC(c2ccccc2)(c2ccccc2)CC1
Temperature: 25 °C
Yield: 105.2 %

Procedure:
4,4-Diphenylcyclohexanone 54.0 g was dissolved with stirring in tetrahydrofuran 700 ml, which was purified by dehydration, under nitrogen sealing and cooled with dry ice acetone. Then, a solution 200 ml of n-butyl lithium (1.6 mole/liter) in hexane was added dropwise for two hours. Two hours after adding, the ice bath was removed and the mixture was slowly heated to room temperature for four hours. The finish of the reaction was confirmed by liquid chromatography, then a saturated ammonium chloride aqueous solution 300 ml was poured into the reaction solution and the mixture was extracted with toluene 700 ml. The solution was washed with an aqueous solution of sodium chloride and toluene was removed with a rotary evaporator. Then, the residue was dissolved in toluene 400 ml, an ion exchange resin (Amberlist 15E, manufactured by ORGANO Co, Ltd.) 2.8 g was mixed, and the mixture was heated under reflux for three hours. The ion exchange resin was filtered off, toluene was removed with a rotary evapotator, the residue was dissolved in toluene/heptane 1/4 (v/v) and the solution was purified with a silica gel column to obtain 4,4-diphenyl-1-butylcyclohexene (containing 4,4-diphenyl-1-butylidenecyclohexane) 32.97 g.