Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH:1]1([C:4]2[C:13]3[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=3)[C:7]([N+:14]([O-])=O)=[CH:6][CH:5]=2)[CH2:3][CH2:2]1>C(O)C.[Pd]>[NH2:14][C:7]1[C:8]2[C:13](=[CH:12][CH:11]=[CH:10][CH:9]=2)[C:4]([CH:1]2[CH2:3][CH2:2]2)=[CH:5][CH:6]=1
Reactant: O=[N+]([O-])c1ccc(C2CC2)c2ccccc12
Agent: [Pd]
Solvent: CCO
Product: Nc1ccc(C2CC2)c2ccccc12
Reaction time: 8 h
Yield: 73.6 %

Procedure:
A solution of 1-cyclopropyl-4-nitro-naphthalene (5 g, 23 mmol) in ethanol (200 mL) was stirred under hydrogen in the presence of Pd/C (10% net, 1.8 g). The reaction mixture was shaken overnight, then filtered over celite. The solvent was evaporated, and the residue was purified by silica gel chromatography to yield 1-amino-4-cyclopropyl-naphthalene (3.1 g, 73%).
Reaction SMILES: [CH2:1]([N:3]([CH2:14][CH3:15])[C:4]1[CH:5]=[C:6]([CH:10]=[C:11]([CH3:13])[N:12]=1)[C:7]([OH:9])=O)[CH3:2].C([O:20][C:21](=[O:37])[CH2:22][CH2:23][C:24]1[C:29]([CH3:30])=[CH:28][C:27]([C:31](=[NH:34])[NH:32]O)=[CH:26][C:25]=1[CH2:35][CH3:36])(C)(C)C>>[CH2:14]([N:3]([CH2:1][CH3:2])[C:4]1[CH:5]=[C:6]([C:7]2[O:9][N:34]=[C:31]([C:27]3[CH:28]=[C:29]([CH3:30])[C:24]([CH2:23][CH2:22][C:21]([OH:37])=[O:20])=[C:25]([CH2:35][CH3:36])[CH:26]=3)[N:32]=2)[CH:10]=[C:11]([CH3:13])[N:12]=1)[CH3:15]
Reactant: CCc1cc(C(=N)NO)cc(C)c1CCC(=O)OC(C)(C)C
Reactant: CCN(CC)c1cc(C(=O)O)cc(C)n1
Product: CCc1cc(-c2noc(-c3cc(C)nc(N(CC)CC)c3)n2)cc(C)c1CCC(=O)O

Procedure:
The title compound is prepared in analogy to Example 8 starting from 2-(diethylamino)-6-methyl-isonicotinic acid and 3-[2-ethyl-4-(N-hydroxycarbamimidoyl)-6-methyl-phenyl]-propionic acid tert-butyl ester; LC-MS: tR=0.88 min; [M+1]+=423.17.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[CH:4][C:3]=1[C:9]1[C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[C:12](=[O:19])[N:11]([CH3:20])[C:10]=1[CH2:21][C:22]([O:24][CH3:25])=[O:23].[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[CH2:36](Br)[CH:37]=[CH2:38]>O1CCCC1>[CH3:1][C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[CH:4][C:3]=1[C:9]1[C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[C:12](=[O:19])[N:11]([CH3:20])[C:10]=1[CH:21]([CH2:38][CH:37]=[CH2:36])[C:22]([O:24][CH3:25])=[O:23]
Reactant: COC(=O)Cc1c(-c2ccc(C)cc2C)c2ccccc2c(=O)n1C
Reactant: C=CCBr
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Li+]
Solvent: C1CCOC1
Product: C=CCC(C(=O)OC)c1c(-c2ccc(C)cc2C)c2ccccc2c(=O)n1C
Temperature: 25 °C
Reaction time: 1 h

Procedure:
A solution of methyl 2-(4-(2,4-dimethylphenyl)-2-methyl-1-oxo-1,2-dihydroisoquinolin-3-yl)acetate (60 mg, 0.179 mmol) in tetrahydrofuran (THF) (2 mL) was treated with LiHMDS (0.358 mL, 0.358 mmol) and allyl bromide (0.232 mL, 2.68 mmol) at 0° C. The mixture was warmed to room temperature and stirred for 1 hour. The mixture was quenched with saturated NH4Cl solution and extracted with ethyl acetate. The combined extracts were washed with saturated NaHCO3 solution and brine, dried over Na2SO4, filtered and concentrated. The material was used crude in the next step (64 mg, 95%). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 8.44-8.54 (m, 1 H) 7.41-7.56 (m, 2 H) 7.06-7.19 (m, 2 H) 6.97-7.05 (m, 1 H) 6.80-6.91 (m, 1 H) 5.40-5.70 (m, 1 H) 4.85-5.06 (m, 2 H) 3.89-4.05 (m, 1 H) 3.68 (s, 3 H) 3.53 (s, 3 H) 2.91-3.06 (m, 1 H) 2.43-2.55 (m, 1 H) 2.41 (s, 3 H) 2.03 (s, 3 H). LC/MS (m/z) ES+=376 (M+1).
Reaction SMILES: F[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[N+:12]([O-:14])=[O:13])[NH:8][C:7](=[O:15])[N:6]([NH:16][S:17]([CH3:20])(=[O:19])=[O:18])[C:5]2=[O:21].[NH:22]1[CH2:26][CH2:25][C@H:24]([OH:27])[CH2:23]1>>[OH:27][C@H:24]1[CH2:25][CH2:26][N:22]([C:2]2[CH:3]=[C:4]3[C:9](=[CH:10][C:11]=2[N+:12]([O-:14])=[O:13])[NH:8][C:7](=[O:15])[N:6]([NH:16][S:17]([CH3:20])(=[O:19])=[O:18])[C:5]3=[O:21])[CH2:23]1
Reactant: O[C@H]1CCNC1
Reactant: CS(=O)(=O)Nn1c(=O)[nH]c2cc([N+](=O)[O-])c(F)cc2c1=O
Product: CS(=O)(=O)Nn1c(=O)[nH]c2cc([N+](=O)[O-])c(N3CC[C@H](O)C3)cc2c1=O
Yield: 69 %

Procedure:
N-(6-Fluoro-7-nitro-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)-methanesulfonamide (30 mg, 0.0943 mmol) is reacted with (S)-pyrrolidin-3-ol according to the GPA affording 25 mg (69%) of a red powder. Rt=3.11 min.
Reaction SMILES: [Br:1][C:2]1[C:3]([OH:19])=[N:4][N:5]2[C:10]=1[C:9]([CH3:11])=[N:8][N:7]=[C:6]2[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[F:18].C(=O)([O-])[O-].[Cs+].[Cs+].Cl.Cl[CH2:28][C:29]1[N:33]([CH3:34])[N:32]=[CH:31][N:30]=1>CN(C=O)C>[Br:1][C:2]1[C:3]([O:19][CH2:28][C:29]2[N:33]([CH3:34])[N:32]=[CH:31][N:30]=2)=[N:4][N:5]2[C:10]=1[C:9]([CH3:11])=[N:8][N:7]=[C:6]2[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[F:18]
Reactant: Cn1ncnc1CCl
Reactant: Cc1nnc(-c2ccccc2F)n2nc(O)c(Br)c12
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Product: Cc1nnc(-c2ccccc2F)n2nc(OCc3ncnn3C)c(Br)c12
Temperature: 25 °C
Reaction time: 72 h
Yield: 73.8 %

Procedure:
To a stirred solution of 3-bromo-7-(2-fluorophenyl)-2-hydroxy-4-methylpyrazolo[1,5-d][1,2,4]triazine (0.5636 g, 1.74 mmol) in anhydrous DMF (28 ml) was added cesium carbonate (2.1927 g, 6.73 mmol) and 5-chloromethyl-1-methyl-1H-[1,2,4]triazole hydrochloride (EP-A-421210) (0.3518 g, 2.09 mmol) and the mixture was stirred at room temperature under nitrogen for 3 days. The mixture was then filtered and the solid washed well with ethyl acetate. The filtrates were diluted to 150 ml with ethyl acetate and washed with saturated aqueous NH4Cl (75 ml). The aqueous layer was further extracted with ethyl acetate (100 ml), and the combined extracts were dried (NaSO4) and evaporated in vacuo. The residue was purified by flash chromatography (silica gel, 2% MeOH/CH2Cl2) to give 0.5367 g (74%) of the title compound as a yellow solid: 1H NMR (360 MHz, CDCl3) δ 3.01 (3H, s), 3.85 (3H, s), 5.49 (2H, s), 7.26 (1H, m), 7.37 (1H, td, J=7.6, 0.9 Hz), 7.62 (1H, m), 7.71 (1H, m), 7.86 (1H, s); MS (ES+) m/e 418/420 M+H]+.
Reaction SMILES: [CH3:1][C:2]1[N:6]([CH2:7][CH2:8][C:9]2[CH:14]=[CH:13][C:12]([N+:15]([O-])=O)=[CH:11][CH:10]=2)[C:5](=[O:18])[C:4]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[N:3]=1.O.O.Cl[Sn]Cl>C(O)C.O.N>[NH2:15][C:12]1[CH:11]=[CH:10][C:9]([CH2:8][CH2:7][N:6]2[C:5](=[O:18])[C:4]([C:19]3[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=3)([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[N:3]=[C:2]2[CH3:1])=[CH:14][CH:13]=1
Reactant: CC1=NC(c2ccccc2)(c2ccccc2)C(=O)N1CCc1ccc([N+](=O)[O-])cc1
Agent: Cl[Sn]Cl
Agent: N
Solvent: O
Solvent: CCO
Product: CC1=NC(c2ccccc2)(c2ccccc2)C(=O)N1CCc1ccc(N)cc1
Temperature: 50 °C
Yield: 97.4 %

Procedure:
A mixture of 2-methyl-3-[2-(4-nitro-phenyl)-ethyl]-5,5-diphenyl-3,5-dihydro-imidazol-4-one (205 mg, 0.5 mmol) and SnCl2.2H2O (591 mg, 2.6 mmol) in 10 mL ethanol is heated to 50° C. for 5 hours. The reaction mixture is cooled to room temperature, diluted with water and aqueous ammonia is added to reach pH 8-9. The mixture is filtered, the filtrate evaporated and the residue purified by flash chromatography. ISCO Companion CombiFlash, 12 g silica gel, methylene chloride/ethanol to yield 3-[2-(4-amino-phenyl)-ethyl]-2-methyl-5,5-diphenyl-3,5-dihydro-imidazol-4-one (180 mg, 85%). LC/MS at 254 nm; [M+H] 370; Rt 2.424 min.
Reaction SMILES: [CH2:1]([OH:3])[CH3:2].[H-].[Na+].Br[C:7]1[CH:8]=[C:9]([CH:30]=[CH:31][N:32]=1)[C:10]([NH:12][C:13]1[S:14][C:15]2[C:21]([N:22]3[CH2:27][CH2:26][O:25][CH2:24][CH2:23]3)=[CH:20][CH:19]=[C:18]([O:28][CH3:29])[C:16]=2[N:17]=1)=[O:11]>O1CCOCC1>[CH2:1]([O:3][C:7]1[CH:8]=[C:9]([CH:30]=[CH:31][N:32]=1)[C:10]([NH:12][C:13]1[S:14][C:15]2[C:21]([N:22]3[CH2:23][CH2:24][O:25][CH2:26][CH2:27]3)=[CH:20][CH:19]=[C:18]([O:28][CH3:29])[C:16]=2[N:17]=1)=[O:11])[CH3:2]
Reactant: CCO
Reactant: COc1ccc(N2CCOCC2)c2sc(NC(=O)c3ccnc(Br)c3)nc12
Agent: [H-]
Agent: [Na+]
Solvent: C1COCCO1
Product: CCOc1cc(C(=O)Nc2nc3c(OC)ccc(N4CCOCC4)c3s2)ccn1
Temperature: 50 °C
Yield: 44.4 %

Procedure:
To a stirred solution of 0.52 ml (8.90 mmol) ethanol in 30 ml dioxane at room temperature was added 486 mg (11.1 mmol) sodium hydride (55% dispersion in mineral oil) and the mixture heated at 50° C. for 30 minutes. 1.00 g (2.23 mmol) 2-bromo-N-(4-methoxy-7-morpholin-4-yl-benzothiazol-2-yl)-isonicotinamide was then added and the mixture heated at 115° C. for 72 h. The reaction mixture was then cooled to room temperature and concentrated in vacuo. The residue was resuspended in dichloromethane, and washed sequentially with water and saturated brine. The organic phase was then dried over sodium sulfate and concentrated in vacuo. The residue was resuspended in methanol and concentrated in vacuo to 2 ml, 20 ml ether added, and the resulting crystals were collected by filtration and dried in vacuo to afford 410 mg (44%) 2-ethoxy-N-(4-methoxy-7-morpholin-4-yl-benzothiazol-2-yl)-isonicotinamide as a light yellow crystalline solid.
Reaction SMILES: [Na].[O-]CC.[Na+].[CH2:6]([O:8][C:9]([CH2:11][C:12]([N:14]([CH2:22][CH3:23])[CH2:15][CH2:16][C:17]([O:19]CC)=O)=[O:13])=[O:10])[CH3:7]>C(O)C>[C:9]([CH:11]1[C:17](=[O:19])[CH2:16][CH2:15][N:14]([CH2:22][CH3:23])[C:12]1=[O:13])([O:8][CH2:6][CH3:7])=[O:10]
Reactant: CCOC(=O)CCN(CC)C(=O)CC(=O)OCC
Agent: CC[O-]
Agent: [Na+]
Agent: [Na]
Solvent: CCO
Product: CCOC(=O)C1C(=O)CCN(CC)C1=O
Yield: 71 %

Procedure:
5.8 g of metallic sodium was added to 300 ml of ethanol and they were reacted to obtain an ethanol solution containing sodium ethoxide. To this solution was added 62.2 g of ethyl N-ethoxycarbonylacetyl-3-ethylaminopropionate, and they were refluxed for 4 hours and allowed to cool. Ethanol was distilled off. Thereto were added ethyl acetate and a dilute aqueous hydrochloric acid solution and the resulting mixture was shaken. The organic layer was separated, water-washed, dried and concentrated to obtain 36.3 g of 3-carboethoxy-1-ethylpiperidine-2,4-dione as an oily matter with an yield of 71%.
Reaction SMILES: [Si:1]([O:8][C:9]([C:11]([F:35])([F:34])[C@@:12](C(=O)C1C=CC=CC=1)([C@@H:14]([CH:16]([C:18](=[O:25])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[OH:17])[OH:15])[OH:13])=[O:10])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].CC(C)([O-])C.[K+].C(O)(=O)C>O1CCCC1.C(OCC)(=O)C>[Si:1]([O:8][C:9]([C:11]([F:34])([F:35])[C@@H:12]([C@@H:14]([CH:16]([C:18](=[O:25])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[OH:17])[OH:15])[OH:13])=[O:10])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]
Reactant: CC(C)(C)[Si](C)(C)OC(=O)C(F)(F)[C@@](O)(C(=O)c1ccccc1)[C@H](O)C(O)C(=O)c1ccccc1
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: CC(=O)O
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: CC(C)(C)[Si](C)(C)OC(=O)C(F)(F)[C@H](O)[C@H](O)C(O)C(=O)c1ccccc1
Temperature: -78 °C
Reaction time: 0.25 h
Yield: 89.5 %

Procedure:
To a solution of 0.97 g (2.0 mmol) of 1-(t-butyldimethylsilyloxy)-3,5-bis(benzoyl)-2-deoxy-2,2-difluororibose in tetrahydrofuran (40 ml) cooled to -78° C. were added 4.0 ml of a 1M solution of potassium t-butoxide in tetrahydrofuran (4.0 mmol) dropwise. The reaction mixture was stirred 15 minutes at -78° C. and was then quenched with 0.45 ml glacial acetic acid (8.0 mmol). The reaction mixture was diluted with ethyl acetate (100 ml) and washed with brine (50 ml). The separated organic layer was dried with sodium sulfate and evaporated under reduced pressure. The resulting residue was chromatographed on silica gel and eluted with hexane containing 10-15% ethyl acetate. The product fractions were combined and concentrated under reduced pressure to yield 0.724 g (93%) of 1-(t-butyldimethylsilyloxy)-5-benzoyl-2-deoxy-2,2-difluororibose. Mass spec.: m/e=389=P+1, m/e=331=P-t-butyl.
Reaction SMILES: [OH:1][C:2]1[C:11]([CH3:12])=[CH:10][C:5]([C:6]([O:8]C)=O)=[CH:4][C:3]=1[CH3:13].[CH2:14]([CH2:16][NH2:17])[OH:15]>>[OH:15][CH2:14][CH2:16][NH:17][C:6](=[O:8])[C:5]1[CH:4]=[C:3]([CH3:13])[C:2]([OH:1])=[C:11]([CH3:12])[CH:10]=1
Reactant: NCCO
Reactant: COC(=O)c1cc(C)c(O)c(C)c1
Product: Cc1cc(C(=O)NCCO)cc(C)c1O

Procedure:
A 270 g quantity of methyl 4-hydroxy-3,5-dimethylbenzoate is heated in 300 ml of ethanolamine for 6 hours at a bath temperature of 160° C. while simultaneously removing the methanol which forms by distillation. The excess ethanolamine is removed under vacuum. The glassy product is ground, screened (1 mm screen), and dried thoroughly at 0.5 torr and 60° C. for a yield of 307 g.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]1[O:8][C:9]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14](I)[CH:13]=2)=[N:10][N:11]=1.[CH3:19][N:20](C)C=O>C(OCC)(=O)C.[C-]#N.[Zn+2].[C-]#N.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>[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]1[O:8][C:9]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([C:19]#[N:20])[CH:13]=2)=[N:10][N:11]=1
Reactant: CN(C)C=O
Reactant: Ic1cccc(-c2nnc(-c3ccccn3)o2)c1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: [C-]#N
Agent: [Zn+2]
Solvent: CCOC(C)=O
Product: N#Cc1cccc(-c2nnc(-c3ccccn3)o2)c1
Temperature: 80 °C
Yield: 30 %

Procedure:
Under an argon atmosphere, a mixture of 2-(2-pyridyl)-5-(3-iodophenyl)-1,3,4-oxadiazole (0.03 g, 0.08 mmol), zinc cyanide (0.01 g, 0.12 mmol), and Pd(PPh3)4 (9.1 mg, 0.01 mmol) in N,N-dimethylformamide (2ml) was heated at 80° C. for 2.5 hours. After cooling the reaction mixture was diluted with ethyl acetate and sequentially washed with water (3×50 mL) and brine (50 mL). The organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. Recrystallization of the crude product from 5% ethyl acetate in hexanes, afforded 5.8 mg (30%) of 2-(2-pyridyl)-5-(3-cyanophenyl)-1,3,4-oxadiazole.
Reaction SMILES: [N:1]1[C:5]2[CH:6]=[CH:7][C:8]([NH2:10])=[CH:9][C:4]=2[NH:3][CH:2]=1.[CH:11](=O)[CH2:12][CH2:13][CH3:14].[BH4-].[Na+]>>[CH2:11]([NH:10][C:8]1[CH:7]=[CH:6][C:5]2[NH:1][CH:2]=[N:3][C:4]=2[CH:9]=1)[CH2:12][CH2:13][CH3:14]
Reactant: CCCC=O
Reactant: Nc1ccc2nc[nH]c2c1
Agent: [BH4-]
Agent: [Na+]
Product: CCCCNc1ccc2[nH]cnc2c1

Procedure:
The compound was synthesized starting from benzimidazol-5-amine (399 mg; 3 mmol; 1 eq.), n-butanal (238 mg; 0.291 ml; 3.3 mmol; 1.1 eq.) and NaBH4 (228 mg; 6 mmol; 2 eq.) as described in method 3; Yield: 0.311 (54.9%); MS m/z: 190.4 [M+H]+; 1H-NMR (400 MHz, DMSO d6): δ 0.91 (t, 3H, 3J=7.5 Hz); 1.35-1.44 (m, 2H); 1.52-1.59 (m, 2H); 2.99 (t, 2H, 3J=7.1 Hz); 5.27 (br s, 1H); 6.53-6.55 (m, 2H); 7.25-7.27 (m, 1H); 7.84 (s, 1H); 11.83 (br s, 1H); HPLC (METHOD [A]): rt 7.51 min (95.9%)
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:20]=[CH:21][C:22]=1[Cl:23])[CH2:5][NH:6][C:7](=[O:19])[NH:8][C:9]1[S:10][CH:11]=[C:12]([C:14](OCC)=[O:15])[N:13]=1.B([O-])[O-].[Li+].[Li+].C1COCC1.O.O.O.O.O.O.O.O.O.O.S([O-])([O-])(=O)=O.[Na+].[Na+]>C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([CH:20]=[CH:21][C:22]=1[Cl:23])[CH2:5][NH:6][C:7]([NH:8][C:9]1[S:10][CH:11]=[C:12]([CH2:14][OH:15])[N:13]=1)=[O:19]
Reactant: CCOC(=O)c1csc(NC(=O)NCc2ccc(Cl)c(Cl)c2)n1
Agent: O=S(=O)([O-])[O-]
Agent: [Li+]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: O
Product: O=C(NCc1ccc(Cl)c(Cl)c1)Nc1nc(CO)cs1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To a suspension of Ethyl 2-(3-(3,4-dichlorobenzyl)ureido)thiazole-4-carboxylate Example 38 (172 mg, 460 μmol) in THF (8 ml) was added a solution of lithium boronate/THF (1 M, 0.7 ml, 700 μmol) at 0° C. Stirring was continued at 0° C. for 2 hours. After this time, TLC indicated complete conversion and to the reaction mixture was added sodium sulfate decahydrate (1.20 g, 3.72 mmol). While warming up to ambient temperature, the mixture was stirred for further 20 minutes. The solids were removed by filtration and the solvent was removed under reduced pressure. The crude material was purified by column chromatography (silica gel, ethyl acetate, methanol/ethyl acetate 1:40, 1:30, 1:20, 1:15), yielding the desired compound in 75% (115 mg, 346 μmol) as a white solid. 1H NMR (300 MHz, d6-DMSO) δ 4.32 (d, 2H), 4.37 (d, 2H), 5.10 (t, br, 1H), 6.71 (s, 1H), 7.18 (t, br, 1H), 7.27 (dd, 1H), 7.51 (d, 1H), 7.59 (d, 1H), 10.53 (s, br, 1H). MS (ES+): M/Z 332 and 334 (M+H).
Reaction SMILES: [CH3:1][N:2]([CH3:29])[C:3](=[O:28])[C:4]1[CH:9]=[CH:8][C:7]([C@H:10]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=2[CH3:27])[CH2:11][C:12]([C:14]2[CH:19]=[CH:18][N:17]=[C:16]([CH3:20])[CH:15]=2)=O)=[CH:6][CH:5]=1.Cl.[NH2:31][OH:32].C(=O)([O-])O.[Na+]>>[OH:32]/[N:31]=[C:12](/[C:14]1[CH:19]=[CH:18][N:17]=[C:16]([CH3:20])[CH:15]=1)\[CH2:11][C@H:10]([C:7]1[CH:8]=[CH:9][C:4]([C:3]([N:2]([CH3:29])[CH3:1])=[O:28])=[CH:5][CH:6]=1)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=1[CH3:27]
Reactant: NO
Reactant: Cc1cc(C(=O)C[C@H](c2ccc(C(=O)N(C)C)cc2)c2ccccc2C)ccn1
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Product: Cc1cc(/C(C[C@H](c2ccc(C(=O)N(C)C)cc2)c2ccccc2C)=N/O)ccn1

Procedure:
In analogy to example 132, step 6, from N,N-dimethyl-4-[(R)-3-(2-methyl-pyridin-4-yl)-3-oxo-1-o-tolyl-propyl]-benzamide and hydroxylamine hydrochloride in the presence of sodium hydrogencarbonate was prepared the title compound as a white foam, MS (ESI+): m/z=402.4 ([M+H]+).
Reaction SMILES: [Cl:1][C:2]1[CH:19]=[CH:18][C:5]([CH2:6][NH:7][C:8]2[C:13]([N+:14]([O-:16])=[O:15])=[CH:12][CH:11]=[C:10](Cl)[N:9]=2)=[CH:4][CH:3]=1.[C:20]([O:24][C:25](=[O:33])[N:26]([C@H:28]([C:30](=[O:32])[NH2:31])[CH3:29])[CH3:27])([CH3:23])([CH3:22])[CH3:21].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.C([O-])([O-])=O.[Cs+].[Cs+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O1CCOCC1>[C:20]([O:24][C:25](=[O:33])[N:26]([CH:28]([C:30](=[O:32])[NH:31][C:10]1[CH:11]=[CH:12][C:13]([N+:14]([O-:16])=[O:15])=[C:8]([NH:7][CH2:6][C:5]2[CH:18]=[CH:19][C:2]([Cl:1])=[CH:3][CH:4]=2)[N:9]=1)[CH3:29])[CH3:27])([CH3:21])([CH3:22])[CH3:23]
Reactant: C[C@@H](C(N)=O)N(C)C(=O)OC(C)(C)C
Reactant: O=[N+]([O-])c1ccc(Cl)nc1NCc1ccc(Cl)cc1
Agent: [Pd]
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Agent: O=C([O-])[O-]
Solvent: C1COCCO1
Product: CC(C(=O)Nc1ccc([N+](=O)[O-])c(NCc2ccc(Cl)cc2)n1)N(C)C(=O)OC(C)(C)C
Temperature: 90 °C
Yield: 57 %

Procedure:
(4-Chloro-benzyl)-(6-chloro-3-nitro-pyridin-2-yl)-amine (685 mg, 2.31 mmol), ((S)-1-carbamoyl-ethyl)-methyl-carbamic acid tert-butyl ester (Intermediate A1) (606 mg, 3.0 mmol), Pd2 dba3 (210 mg, 0.23 mmol), BINAP (286 mg, 0.46 mmol) and Cs2CO3 (1.5 g, 4.62 mmol) were added to 1,4-dioxane (15 mL). The mixture was evacuated and flushed with N2 three times and then heated at 90° C. for 2 hours. The mixture was cooled, diluted with EtOAc, filtered and concentrated in vacuo. The residue was purified by SiO2 chromatography (10-30% EtOAc/Petrol) to give {1-[6-(4-chloro-benzylamino)-5-nitro-pyridin-2-ylcarbamoyl]-ethyl}-methyl-carbamic acid tert-butyl ester (611 mg) as an orange foamy solid. MS: [M+H]+=464.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]=[C:9]=[S:10])=[CH:4][CH:3]=1.[CH3:11][C:12]([CH3:17])([CH3:16])[CH:13]([NH2:15])[CH3:14]>C1COCC1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]([NH:15][CH:13]([CH3:14])[C:12]([CH3:17])([CH3:16])[CH3:11])=[S:10])=[CH:4][CH:3]=1
Reactant: S=C=Nc1ccc(Cl)cc1
Reactant: CC(N)C(C)(C)C
Solvent: C1CCOC1
Product: CC(NC(=S)Nc1ccc(Cl)cc1)C(C)(C)C
Temperature: 25 °C
Reaction time: 8 h
Yield: 80.7 %

Procedure:
To a solution of 4-chloro-phenyl isothiocyanate (1.00 g, 5.90 mmol) in THF (20 mL) at room temperature was added (±) 3,3-dimethyl-2-aminobutane (1.03 mL, 7.66 mmol) and the reaction was stirred overnight at room temperature. The mixture was concentrated in vacuo and the resulting residue was triturated with diethyl ether and filtered to afford 1.29 g (81%) of 1-(4-chloro-phenyl)-3-(1,2,2-trimethylpropyl)-thiourea as a white solid which was used without further purification.
Reaction SMILES: F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.[Br:25][C:26]1[C:34]2[C:29](=[CH:30][CH:31]=[C:32]([C:35](O)=[O:36])[CH:33]=2)[N:28]([C:38]([C:51]2[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=2)([C:45]2[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=2)[C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)[N:27]=1.[NH2:57][C@@H:58]1[CH2:63][CH2:62][CH2:61][N:60]([C:64]([O:66][CH2:67][C:68]2[CH:73]=[CH:72][CH:71]=[CH:70][CH:69]=2)=[O:65])[CH2:59]1.C(N(C(C)C)CC)(C)C>CN(C=O)C>[Br:25][C:26]1[C:34]2[C:29](=[CH:30][CH:31]=[C:32]([C:35]([NH:57][C@@H:58]3[CH2:63][CH2:62][CH2:61][N:60]([C:64]([O:66][CH2:67][C:68]4[CH:73]=[CH:72][CH:71]=[CH:70][CH:69]=4)=[O:65])[CH2:59]3)=[O:36])[CH:33]=2)[N:28]([C:38]([C:45]2[CH:46]=[CH:47][CH:48]=[CH:49][CH:50]=2)([C:51]2[CH:52]=[CH:53][CH:54]=[CH:55][CH:56]=2)[C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)[N:27]=1
Reactant: N[C@@H]1CCCN(C(=O)OCc2ccccc2)C1
Reactant: O=C(O)c1ccc2c(c1)c(Br)nn2C(c1ccccc1)(c1ccccc1)c1ccccc1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: O=C(N[C@@H]1CCCN(C(=O)OCc2ccccc2)C1)c1ccc2c(c1)c(Br)nn2C(c1ccccc1)(c1ccccc1)c1ccccc1
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
2-(7-Aza-1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HATU) (3.1 mmol) was added to a suspension of 3-bromo-1-trityl-1H-indazole-5-carboxylic acid (1 g, 2.07 mmol) in DMF (5 mL) and was stirred at room temperature for 15 minutes. A solution of (R)-benzyl 3-aminopiperidine-1-carboxylate (500 mg, 2.13 mmol) in DMF (5 mL) was added to the reaction and followed by diisopropyl ethyl amine (DIEA) (0.72 mL). The mixture was stirred at room temperature for an additional 30 minutes. The reaction was quenched with water (50 mL) and extracted with ethyl acetate (3×100 mL). The extracts were combined, dried using anhydrous sodium sulfate, filtered, and concentrated in vacuo. The crude product was progressed to the next step without purification.
Reaction SMILES: [O:1]1[CH2:6][CH:5]=[C:4]([C:7]2[CH:12]=[CH:11][C:10]([N:13]3[CH2:17][C@H:16]([CH2:18][NH:19][C:20](=[O:22])[CH3:21])[O:15][C:14]3=[O:23])=[CH:9][C:8]=2[F:24])[CH2:3][CH2:2]1>CO.[Pd]>[O:1]1[CH2:6][CH2:5][CH:4]([C:7]2[CH:12]=[CH:11][C:10]([N:13]3[CH2:17][C@H:16]([CH2:18][NH:19][C:20](=[O:22])[CH3:21])[O:15][C:14]3=[O:23])=[CH:9][C:8]=2[F:24])[CH2:3][CH2:2]1
Reactant: CC(=O)NC[C@H]1CN(c2ccc(C3=CCOCC3)c(F)c2)C(=O)O1
Agent: [Pd]
Solvent: CO
Product: CC(=O)NC[C@H]1CN(c2ccc(C3CCOCC3)c(F)c2)C(=O)O1
Reaction time: 3 h

Procedure:
A mixture of (S)-(−)-N-[[3-[4-(3,6-dihydro-2H-pyran-4-yl)-3-fluorophenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide (EXAMPLE 47, 1.00 g) and 10% palladium-on-carbon (637 mg) in methanol (60 mL) is shaken on a Parr apparatus under a hydrogen atmosphere at 40 psi for three hours, the catalyst is removed by filtration through Celite and the filtrate is concentrated under reduced pressure to give the title compound, mp 191-192° C.
Reaction SMILES: [CH2:1](I)[CH3:2].[Cl:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[N:11]1[C:26]([C:27]2[CH:32]=[CH:31][C:30]([OH:33])=[CH:29][CH:28]=2)=[C:14]2[N:15]=[C:16]([CH3:25])[N:17]([CH2:20][C:21]([F:24])([F:23])[F:22])[C:18](=[O:19])[C:13]2=[N:12]1.C([O-])([O-])=O.[Cs+].[Cs+]>CN1C(=O)CCC1.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>[Cl:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[N:11]1[C:26]([C:27]2[CH:28]=[CH:29][C:30]([O:33][CH2:1][CH3:2])=[CH:31][CH:32]=2)=[C:14]2[N:15]=[C:16]([CH3:25])[N:17]([CH2:20][C:21]([F:24])([F:22])[F:23])[C:18](=[O:19])[C:13]2=[N:12]1
Reactant: CCI
Reactant: Cc1nc2c(-c3ccc(O)cc3)n(-c3ccccc3Cl)nc2c(=O)n1CC(F)(F)F
Agent: O=C(O)CC(O)(CC(=O)O)C(=O)O
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN1CCCC1=O
Product: CCOc1ccc(-c2c3nc(C)n(CC(F)(F)F)c(=O)c3nn2-c2ccccc2Cl)cc1
Temperature: 25 °C
Reaction time: 5 h

Procedure:
Ethyl iodide (88 μL, 1.1 mmol) was added to a mixture of 2-(2-chlorophenyl)-3-(4-hydroxyphenyl)-5-methyl-6-(2,2,2-trifluoroethyl)-2,6-dihydropyrazolo[4,3-d]pyrimidin-7-one (6A-1, 50 mg, 0.11 mmol), Cs2CO3 (55 mg, 0.17 mmol) in NMP (2 ml) at 85° C. The reaction mixture was stirred at this temperature for 5 h, cooled to room temperature, and diluted with 0.5 M citric acid. The aqueous solution was extracted with EtOAc (2×), and the combined organic extracts were washed with 1 M K2CO3, saturated aqueous NaCl, dried, and concentrated in vacuo. The crude residue was purified on a Chromatotron using 1 mm plates and 33% EtOAc/hexanes to give the desired product 7A-1 as an amorphous glass: MS (m/z) 435.4 (M+H)+; 1H NMR (400 MHz, CD2Cl2): δ 7.61–7.46 (m, 4H), 7.25–7.20 (m, 2H), 6.74–6.69 (m, 2H), 5.02 (q, J=7.1 Hz, 2H), 2.65 (s, 3H).