Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([O:3][CH2:4][CH2:5][S:6][C:7]1[CH:12]=[C:11]([CH3:13])[C:10](Br)=[C:9]([CH3:15])[CH:8]=1)[CH3:2].[CH:16]([C:18]1[CH:19]=[C:20](B(O)O)[CH:21]=[CH:22][CH:23]=1)=[O:17]>C(=O)([O-])[O-].[Na+].[Na+].C(O)C.C1(C)C=CC=CC=1.[Cl-].[Na+].O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:1]([O:3][CH2:4][CH2:5][S:6][C:7]1[CH:12]=[C:11]([CH3:13])[C:10]([C:22]2[CH:21]=[CH:20][CH:19]=[C:18]([CH:16]=[O:17])[CH:23]=2)=[C:9]([CH3:15])[CH:8]=1)[CH3:2]
Reactant: O=Cc1cccc(B(O)O)c1
Reactant: CCOCCSc1cc(C)c(Br)c(C)c1
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: CCO
Solvent: Cc1ccccc1
Solvent: O
Product: CCOCCSc1cc(C)c(-c2cccc(C=O)c2)c(C)c1
Temperature: 80 °C
Reaction time: 16 h
Yield: 38.2 %

Procedure:
2-[(4-Bromo-3,5-dimethylphenyl)thio]ethyl ethyl ether (2.41 g, 8.33 mmol) and (3-formylphenyl)boronic acid (1.37 g, 9.16 mmol) were dissolved in a mixture of 2 M aqueous sodium carbonate solution (24 mL), ethanol (8 mL) and toluene (24 mL), the air was substituted with argon gas, and tetrakis(triphenylphosphine)palladium(0) (0.48 g, 0.42 mmol) was added. The reaction mixture was stirred under an argon atmosphere at 80° C. for 16 hr. After cooling the reaction mixture, saturated brine was added and the mixture was extracted with diethyl ether. The organic layer was dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate=10/1-hexane/ethyl acetate=5/1) to give the title compound (1.00 g, yield 38%) as a colorless oil.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[O:12][C:13]1[CH:18]=[CH:17][C:16]([C:19](=[O:34])[NH:20][CH:21]3[CH2:26][CH2:25][CH:24]([C:27]4[CH:32]=[CH:31][C:30]([Cl:33])=[CH:29][CH:28]=4)[CH2:23][CH2:22]3)=[CH:15][CH:14]=1)[O:8][CH2:7][CH2:6][CH:5]2[C:35]([OH:37])=[O:36].C[O-].[Na+:40].CO>C1COCC1.CO>[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[O:12][C:13]1[CH:14]=[CH:15][C:16]([C:19](=[O:34])[NH:20][CH:21]3[CH2:22][CH2:23][CH:24]([C:27]4[CH:28]=[CH:29][C:30]([Cl:33])=[CH:31][CH:32]=4)[CH2:25][CH2:26]3)=[CH:17][CH:18]=1)[O:8][CH2:7][CH2:6][CH:5]2[C:35]([O-:37])=[O:36].[Na+:40]
Reactant: O=C(NC1CCC(c2ccc(Cl)cc2)CC1)c1ccc(Oc2cc3c(cc2Cl)C(C(=O)O)CCO3)cc1
Agent: C[O-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CO
Product: O=C(NC1CCC(c2ccc(Cl)cc2)CC1)c1ccc(Oc2cc3c(cc2Cl)C(C(=O)[O-])CCO3)cc1
Yield: 100 %

Procedure:
To a suspension of 6-chloro-7-(4-(4-(4-chlorophenyl)cyclohexylcarbamoyl)phenoxy)chroman-4-carboxylic acid (0.045 g, 0.0833 mmol) in 1:1 THF/methanol (5 ml) was added 0.5M sodium methanolate in methanol (0.170 ml, 0.0849 mmol), and the reaction was stirred for 3 weeks, then concentrated to yield 47 mg of the title compound (100% yield). MS (apci) m/z=562.1 (M-Na+2H).
Reaction SMILES: [CH2:1]([O:5][C:6]1[CH:11]=[CH:10][C:9]([O:12][CH2:13][CH2:14][CH3:15])=[CH:8][CH:7]=1)[CH:2]1[O:4][CH2:3]1.[NH2:16][CH2:17][CH2:18][NH:19][C:20]1[N:21]([CH3:30])[C:22](=[O:29])[N:23]([CH3:28])[C:24](=[O:27])[C:25]=1[CH3:26]>>[CH2:13]([O:12][C:9]1[CH:10]=[CH:11][C:6]([O:5][CH2:1][CH:2]([OH:4])[CH2:3][NH:16][CH2:17][CH2:18][NH:19][C:20]2[N:21]([CH3:30])[C:22](=[O:29])[N:23]([CH3:28])[C:24](=[O:27])[C:25]=2[CH3:26])=[CH:7][CH:8]=1)[CH2:14][CH3:15]
Reactant: Cc1c(NCCN)n(C)c(=O)n(C)c1=O
Reactant: CCCOc1ccc(OCC2CO2)cc1
Product: CCCOc1ccc(OCC(O)CNCCNc2c(C)c(=O)n(C)c(=O)n2C)cc1
Yield: 32 %

Procedure:
This compound is obtained in a manner analogous to that described in Example 5 by reacting 4-propoxyphenyl glycidyl ether with 4-(2-aminoethylamino)-1,3,5-trimethylpyrimidine-2,6(1H,3H)-dione. It is obtained in a yield of 32% of theory in the form of colorless crystals which, after recrystallization from methanol, melt at 121°-123° C.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][C:4]([C:7]2[CH:8]=[C:9]([NH:13][C:14]3[CH:19]=[CH:18][C:17]([C:20]#[N:21])=[CH:16][C:15]=3[NH2:22])[CH:10]=[CH:11][CH:12]=2)=[N:3][CH:2]=1.[CH:23](O)=O>>[C:20]([C:17]1[CH:18]=[CH:19][C:14]2[N:13]([C:9]3[CH:10]=[CH:11][CH:12]=[C:7]([C:4]4[CH:5]=[CH:6][N:1]=[CH:2][N:3]=4)[CH:8]=3)[CH:23]=[N:22][C:15]=2[CH:16]=1)#[N:21]
Reactant: N#Cc1ccc(Nc2cccc(-c3ccncn3)c2)c(N)c1
Reactant: O=CO
Product: N#Cc1ccc2c(c1)ncn2-c1cccc(-c2ccncn2)c1
Temperature: 110 °C
Reaction time: 1 h

Procedure:
A mixture of (39) (3.0 g, 10 mmol) and HCO2H (20 ml) was stirred at 110° C. for 1 hr. The mixture was concentrated in vacuo. The residue was partitioned between a 5% aqueous NaHCO3 solution and CH2Cl2. The organic phase was dried over MgSO4 and the solvent was removed by evaporation. The residue was triturated with ethyl acetate to afford crystalline (40). (2.6 g, 85%).
Reaction SMILES: C(O)(C(F)(F)F)=[O:2].O1C[CH:10]([N:12]2[CH2:17][CH2:16][N:15]([C:18]3[CH:23]=[CH:22][C:21]([C:24]4[CH:25]=[C:26]([O:33][C@@H:34]([C@H:36]5[CH2:40][NH:39][C:38](=[O:41])[CH2:37]5)[CH3:35])[C:27]5[S:31][CH:30]=[N:29][C:28]=5[CH:32]=4)=[CH:20][CH:19]=3)[CH2:14][CH2:13]2)[CH2:9]1.CCN(CC)CC.C(OC(=O)C)(=O)C>C(Cl)Cl>[C:10]([N:12]1[CH2:13][CH2:14][N:15]([C:18]2[CH:23]=[CH:22][C:21]([C:24]3[CH:25]=[C:26]([O:33][C@@H:34]([C@H:36]4[CH2:40][NH:39][C:38](=[O:41])[CH2:37]4)[CH3:35])[C:27]4[S:31][CH:30]=[N:29][C:28]=4[CH:32]=3)=[CH:20][CH:19]=2)[CH2:16][CH2:17]1)(=[O:2])[CH3:9]
Reactant: O=C(O)C(F)(F)F
Reactant: C[C@@H](Oc1cc(-c2ccc(N3CCN(C4COC4)CC3)cc2)cc2ncsc12)[C@H]1CNC(=O)C1
Solvent: CCN(CC)CC
Solvent: ClCCl
Solvent: CC(=O)OC(C)=O
Product: CC(=O)N1CCN(c2ccc(-c3cc(O[C@H](C)[C@H]4CNC(=O)C4)c4scnc4c3)cc2)CC1
Reaction time: 4 h

Procedure:
The crude TFA salt of 4.27 (0.058 mmol) was suspended in DCM (1 mL) and Et3N (60 μL, 0.43 mmol) was added followed by acetic anhydride (6.5 μL, 0.069 mmol). The resulting mixture was stirred 4 h and was partitioned between EtOAc and water. The aqueous layer was acidified with aqueous HCl. The phases were separated, and the aqueous phase was extracted with EtOAc. The combined organic phase was dried over Na2SO4, filtered, and concentrated. The crude product was purified by silica gel chromatography (0-20% MeOH in DCM) to afford (R)-4-((R)-1-((5-(4-(4-acetylpiperazin-1-yl)phenyl)benzo[d]thiazol-7-yl)oxy)ethyl)pyrrolidin-2-one (4.31).
Reaction SMILES: Cl[C:2]1[C:7]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)=[CH:6][N:5]2[N:14]=[CH:15][CH:16]=[C:4]2[N:3]=1.[CH:17]([C:19]1[CH:24]=[CH:23][C:22](B(O)O)=[CH:21][CH:20]=1)=[O:18].C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.O.ClCCl.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[C:8]1([C:7]2[C:2]([C:22]3[CH:23]=[CH:24][C:19]([CH:17]=[O:18])=[CH:20][CH:21]=3)=[N:3][C:4]3[N:5]([N:14]=[CH:15][CH:16]=3)[CH:6]=2)[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1
Reactant: Clc1nc2ccnn2cc1-c1ccccc1
Reactant: O=Cc1ccc(B(O)O)cc1
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: O=C([O-])[O-]
Solvent: ClCCl
Solvent: COCCOC
Solvent: O
Product: O=Cc1ccc(-c2nc3ccnn3cc2-c2ccccc2)cc1
Temperature: 80 °C

Procedure:
To a mixture of 300 mg of the mixture from step 3 and 360 mg 4-formylphenylboronic acid in 9 ml 1,2-dimethoxyethane are added 1.8 ml of a 10% w/w sodium carbonate solution and 36 mg dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium (II) and the resulting mixture is heated to 80° C. under an inert gas atmosphere for 18 h. The work up is performed by diluting the reaction mixture with water and dichloromethane, separating the phases and extraction of the aqueous phase with dichloromethane. The combined organic layers are dried over sodium sulphate, evaporated and the residue is purified by chromatography on silica gel (dichloromethane/methanol). The product is crystallized from ethyl acetate.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:21]=[C:20]([O:22][CH3:23])[CH:19]=[CH:18][C:4]=1[CH2:5][N:6]1[C:9](=[O:10])[C@H:8]([N:11]=[N+]=[N-])[C@@H:7]1[C:14]([O:16][CH3:17])=[O:15].[H][H]>[Pd].C(O)C>[CH3:1][O:2][C:3]1[CH:21]=[C:20]([O:22][CH3:23])[CH:19]=[CH:18][C:4]=1[CH2:5][N:6]1[C:9](=[O:10])[C@H:8]([NH2:11])[C@@H:7]1[C:14]([O:16][CH3:17])=[O:15]
Reactant: COC(=O)[C@H]1[C@@H](N=[N+]=[N-])C(=O)N1Cc1ccc(OC)cc1OC
Reactant: [H][H]
Agent: [Pd]
Solvent: CCO
Product: COC(=O)[C@H]1[C@@H](N)C(=O)N1Cc1ccc(OC)cc1OC
Reaction time: 2 h

Procedure:
A mixture containing 10.0 g (0.0312 mole) of methyl cis-1-(2,4-dimethoxybenzyl)-3-azido-4-oxoazetidine-2-carboxylate, 1.0 g of 10% palladium on carbon, and 200 ml of ethanol is hydrogenated for 2 hrs at 40°-45° and 60 psi of hydrogen. The reaction mixture is allowed to cool to 25° and is filtered through filter-aid. After removing the solvents in vacuo a clear, yellow gum of the title product is obtained.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[C:6]([CH:8]([CH3:10])[CH3:9])[CH:5]=[CH:4][C:3]=1[N:11]([CH2:31][CH3:32])[C:12]1[N:17]=[C:16]([C:18]([N:20]2[CH2:25][CH2:24][C:23]3(OCC[O:26]3)[CH2:22][CH2:21]2)=[O:19])[CH:15]=[C:14]([CH3:30])[N:13]=1.Cl.[OH-].[Na+]>C1COCC1>[Br:1][C:2]1[CH:7]=[C:6]([CH:8]([CH3:10])[CH3:9])[CH:5]=[CH:4][C:3]=1[N:11]([CH2:31][CH3:32])[C:12]1[N:17]=[C:16]([C:18]([N:20]2[CH2:25][CH2:24][C:23](=[O:26])[CH2:22][CH2:21]2)=[O:19])[CH:15]=[C:14]([CH3:30])[N:13]=1
Reactant: CCN(c1nc(C)cc(C(=O)N2CCC3(CC2)OCCO3)n1)c1ccc(C(C)C)cc1Br
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Product: CCN(c1nc(C)cc(C(=O)N2CCC(=O)CC2)n1)c1ccc(C(C)C)cc1Br
Yield: 101.2 %

Procedure:
A solution-of N-(2-bromo-4-(1-methylethyl)phenyl)-N-ethyl-4-((4,4-ethylenedioxypiperidino)carbonyl)-6-methylpyrimidinamine (260 mg) in a mixture of a 1N HCl solution (2.5 mL) and THF (2.5 mL) was stirred at reflux temperature for 20 h. The reaction mixture was poured into a 1N NaOH solution, and extracted three times with ethyl acetate. The combined organic layers were dried over MgSO4, filtered and concentrated in vacuo to give the title product as a yellow oil (240 mg, 100% yield, Rf 0.75): NMR (CDCl3, 300 MHz): 7.5 (s, 1H), 7.2 (d, 1H, J=8), 7.1 (d, 1H, J=8), 6.8 (br s, 1H), 4.3-4.1 (m, 1H), 3.95-3.85 (m, 1H), 3.75-3.6 (m, 1H), 3.55-3.4 (m, 1H), 2.95-2.85 (m, 1H), 2.6-2.3 (m, 4H), 2.0-1.6 (m, 2H), 1.4-1.15 (m, 12H); CI-HRMS: Calcd (C22H27BrN4O2): 459.1396 (M+H); Found: 459.1386.
Reaction SMILES: [CH3:1][S:2](Cl)(=[O:4])=[O:3].[NH2:6][C:7]1[C:12]([C:13]([O:15][CH2:16][CH3:17])=[O:14])=[CH:11][C:10]([N:18]2[CH2:23][CH2:22][C@H:21]([NH:24][C:25]([C:27]3[NH:28][C:29]([CH3:34])=[C:30]([Cl:33])[C:31]=3[Cl:32])=[O:26])[C@H:20]([O:35][CH3:36])[CH2:19]2)=[N:9][CH:8]=1>N1C=CC=CC=1>[Cl:32][C:31]1[C:30]([Cl:33])=[C:29]([CH3:34])[NH:28][C:27]=1[C:25]([NH:24][C@H:21]1[CH2:22][CH2:23][N:18]([C:10]2[CH:11]=[C:12]([C:7]([NH:6][S:2]([CH3:1])(=[O:4])=[O:3])=[CH:8][N:9]=2)[C:13]([O:15][CH2:16][CH3:17])=[O:14])[CH2:19][C@H:20]1[O:35][CH3:36])=[O:26]
Reactant: CCOC(=O)c1cc(N2CC[C@H](NC(=O)c3[nH]c(C)c(Cl)c3Cl)[C@H](OC)C2)ncc1N
Reactant: CS(=O)(=O)Cl
Solvent: c1ccncc1
Product: CCOC(=O)c1cc(N2CC[C@H](NC(=O)c3[nH]c(C)c(Cl)c3Cl)[C@H](OC)C2)ncc1NS(C)(=O)=O
Reaction time: 1 h
Yield: 82.1 %

Procedure:
Methanesulfonyl chloride (16 μl, 21 mmol) was added to 66 mg (0.14 mmol) of Cis(±)-ethyl 5-amino-2-(4-{[(3,4-dichloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-methoxypiperidin-1-yl)isonicotinate (Example 194) in 3 ml pyridine. After stirring for 1 h, 5 μl more methanesulfonyl chloride was added. Stirred at room temperature overnight. Solvent was removed, and the residue was partitioned between EtOAc and Na2CO3 (aqueous). The EtOAc was separated and washed with water and brine. Drying (MgSO4) and removal of solvent gave 63 mg of product. MS (ES)(MH+): 534 for C21H27Cl2N5O6S, NMR (d6-DMSO): 1.4 (t, 3H), 1.8 (m, 2H) 2.2 (s, 3H), 2.9 (s, 3H), 3.1-3.2 (m, 2H), 3.3-3.5 (m), 3.6 (m, 1H), 4.2-4.3 (m, 2H), 4.4 (q, 2H), 4.7 (m, 1H), 7.1 (s, 1H), 7.2 (d, 1H), 8.2 (s, 1H), 12.2 (s, 1H).
Reaction SMILES: [NH2:1][C:2]1[CH:21]=[CH:20][C:19]([C:22]([F:25])([F:24])[F:23])=[CH:18][C:3]=1[C:4]([NH:6][CH2:7][C:8]([NH:10][CH2:11][CH:12]1[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]1)=[O:9])=[O:5].[Cl:26][C:27]1[CH:34]=[CH:33][C:30]([CH2:31]Cl)=[C:29]([N+:35]([O-])=O)[CH:28]=1.C(#N)C>C(Cl)(Cl)Cl>[NH2:1][C:2]1[CH:21]=[CH:20][C:19]([C:22]([F:25])([F:23])[F:24])=[CH:18][C:3]=1[C:4]([NH:6][CH2:7][C:8]([NH:10][CH2:11][CH:12]1[CH2:13][CH2:14][N:15]([CH2:31][C:30]2[CH:33]=[CH:34][C:27]([Cl:26])=[CH:28][C:29]=2[NH2:35])[CH2:16][CH2:17]1)=[O:9])=[O:5]
Reactant: Nc1ccc(C(F)(F)F)cc1C(=O)NCC(=O)NCC1CCNCC1
Reactant: O=[N+]([O-])c1cc(Cl)ccc1CCl
Solvent: ClC(Cl)Cl
Solvent: CC#N
Product: Nc1cc(Cl)ccc1CN1CCC(CNC(=O)CNC(=O)c2cc(C(F)(F)F)ccc2N)CC1
Temperature: 50 °C
Reaction time: 8 h

Procedure:
A mixture of 4-[{N-(2-amino-5-trifluoromethylbenzoyl)glycyl}aminomethyl]piperidine (0.050 mmol), 4-chloro-2-nitrobenzyl chloride (0.050 mmol), piperidinomethylpolystyrene (60 mg), acetonitrile (1.0 mL) and chloroform (0.7 mL) was stirred overnight at 50° C. The reaction mixture was cooled, loaded onto Variant™ SCX column and washed with 50% CHCl3/CH3OH (10 mL) and CH3OH (10 mL). Product was eluted using 2 N NH3 in CH3OH (5 mL) and concentrated. To the resulting material was added ethanol (3 mL) and 10% Pd—C (15 mg), and the mixture was stirred under H2 at room temperature for 1.5 h. Filtration, concentration, and preparative TLC afforded 4-[{N-(2-amino-5-trifluoromethylbenzoyl)glycyl}aminomethyl]-1-(2-amino-4-chlorobenzyl)piperidine (Compound No. 1919) (5.1 mg, 14%): The purity was determined by RPLC/MS (90%); 1H NMR (400 MHz, CDCl3) δ1.09-1.32 (m, 4H), 1.41-1.59 (m, 1H), 1.66 (d, J=12.5 Hz, 2H), 1.88 (t, J=11.5 Hz, 2H), 2.82 (d, J=11.5 Hz, 2H), 3.17 (t, J=6.5 Hz, 2H), 3.42 (s, 2H), 4.05 (d, J=5.5 Hz, 2H), 4.85 (br s, 1H), 5.92 (br s, 2H), 6.25-6.36 (m, 1H), 6.55-6.66 (m, 1H), 6.70 (d, J=8.5 Hz, 1H), 6.85 (d, J=8.5 Hz, 1H), 7.26 (s, 1H), 7.42 (d, J=8.5 Hz, 1H), 7.68 (s, 1H); ESI/MS m/e 498.2 (M++H, C23H27ClF3N5O3).
Reaction SMILES: I[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][C:9]=2[N+:11]([O-:13])=[O:12])[N:4]([CH2:14][C:15]2[CH:19]=[CH:18][N:17]([CH3:20])[N:16]=2)[N:3]=1.B(O)(O)O.F[C:26]([K])=[C:27](F)F.C(N(CC)CC)C>C1COCC1.CC(O)C.CCOC(C)=O>[CH3:20][N:17]1[CH:18]=[CH:19][C:15]([CH2:14][N:4]2[C:5]3[C:10](=[C:9]([N+:11]([O-:13])=[O:12])[CH:8]=[CH:7][CH:6]=3)[C:2]([CH:26]=[CH2:27])=[N:3]2)=[N:16]1
Reactant: FC(F)=C(F)[K]
Reactant: Cn1ccc(Cn2nc(I)c3c([N+](=O)[O-])cccc32)n1
Agent: OB(O)O
Solvent: CC(C)O
Solvent: CCOC(C)=O
Solvent: CCN(CC)CC
Product: C=Cc1nn(Cc2ccn(C)n2)c2cccc([N+](=O)[O-])c12
Temperature: 80 °C
Yield: 62.6 %

Procedure:
To 3-iodo-1-((1-methyl-1H-pyrazol-3-yl)methyl)-4-nitro-1H-indazole (5.11 g, 13.3 mmol) in THF/IPA (10 mL/30 mL) was added trifluorovinylpotassium borate (3.57 g, 26.7 mmol), 1,1′-bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (0.545 g, 0.667 mmol) and triethylamine (5.58 mL, 40.0 mmol). The reaction mixture was heated to 80° C. for 16 hours. The reaction mixture was diluted with EtOAc (100 mL), washed with H2O and brine. The organic phase was concentrated under reduced pressure and the residue was purified by silica gel chromatography (hexanes/EtOAc 5:1) to provide the product (2.36 g).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][CH:10]=1)[C:5](Cl)=[O:6].[C:11]([O:15][C:16]([N:18]1[C:26]2[C:21](=[CH:22][C:23]([NH:27][C:28]([NH:30][CH2:31][C:32]3[CH:37]=[C:36]([F:38])[CH:35]=[CH:34][C:33]=3[F:39])=[O:29])=[CH:24][CH:25]=2)[C:20]([NH2:40])=[N:19]1)=[O:17])([CH3:14])([CH3:13])[CH3:12].N1C=CC=CC=1>CN(C)C1C=CN=CC=1.O1CCOCC1>[Cl:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][CH:10]=1)[C:5]([NH:40][C:20]1[C:21]2[C:26](=[CH:25][CH:24]=[C:23]([NH:27][C:28]([NH:30][CH2:31][C:32]3[CH:37]=[C:36]([F:38])[CH:35]=[CH:34][C:33]=3[F:39])=[O:29])[CH:22]=2)[N:18]([C:16]([O:15][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:17])[N:19]=1)=[O:6]
Reactant: CC(C)(C)OC(=O)n1nc(N)c2cc(NC(=O)NCc3cc(F)ccc3F)ccc21
Reactant: O=C(Cl)c1cccc(Cl)c1
Agent: CN(C)c1ccncc1
Solvent: c1ccncc1
Solvent: C1COCCO1
Product: CC(C)(C)OC(=O)n1nc(NC(=O)c2cccc(Cl)c2)c2cc(NC(=O)NCc3cc(F)ccc3F)ccc21
Temperature: 90 °C
Reaction time: 24 h
Yield: 34 %

Procedure:
7.1 93 mg of 3-chlorobenzoyl chloride are added to a mixture of 200 mg of tert-butyl-3-amino-5-[3-(2,5-difluorobenzyl)ureido]indazole-1-carboxylate (0.48 mmol, preparation analogous to Example 1.1), 2.0 ml of pyridine, 8 mg of 4-(dimethylamino)pyridine and 100 μl of dioxane, and the mixture is stirred at 90° C. for 24 hours. After cooling, the batch is evaporated, and the residue is purified by column chromatography on silica gel (eluent:heptane/EA 3:2), giving 90 mg of tert-butyl 3-(3-chlorobenzoylamino)-5-[3-(2,5-difluorobenzyl)ureido]indazole-1-carboxylate (34%), MS-FAB (M+H+)=556.
Reaction SMILES: [CH3:1][C:2]1[O:6][C:5]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)=[N:4][C:3]=1[CH2:13][C:14]#[N:15].C([O-])(=O)C.[Na+].[H][H]>[Co]>[CH3:1][C:2]1[O:6][C:5]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)=[N:4][C:3]=1[CH2:13][CH2:14][NH2:15]
Reactant: Cc1oc(-c2ccccc2)nc1CC#N
Reactant: [H][H]
Agent: [Co]
Agent: CC(=O)[O-]
Agent: [Na+]
Product: Cc1oc(-c2ccccc2)nc1CCN
Yield: 103.3 %

Procedure:
This example was run in an analogous manner as example 5 but using 6.00 g (30 mmol) of (5-Methyl-2-phenyl-oxazol-4-yl)-acetonitrile in the presence of 0.60 g of wet Raney Cobalt catalyst (Johnson Matthey 8B0022, wet, ca. 50 weight %) in the presence of 50 mg of sodium acetate as modifier in a 185 mL autoclave at 70° C. under 9 bar of hydrogen pressure for 1.5 h. Removal of the catalyst by filtration, evaporation of the solvents and drying (50° C./10 mbar/2 h) afforded 6.27 g of 2-(5-Methyl-2-phenyl-oxazol-4-yl)-ethylamine with a purity of 89.3% (HPLC area %).
Reaction SMILES: [CH2:1]([O:8][C:9](=[O:28])[NH:10][CH:11]([C:16]1[CH:20]=[C:19]([CH:21](OCC)[O:22]CC)[O:18][N:17]=1)[CH2:12][CH:13]([CH3:15])[CH3:14])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([O-])(O)=O.[Na+]>OS(O)(=O)=O.CC(C)=O>[CH2:1]([O:8][C:9](=[O:28])[NH:10][CH:11]([C:16]1[CH:20]=[C:19]([CH:21]=[O:22])[O:18][N:17]=1)[CH2:12][CH:13]([CH3:15])[CH3:14])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CCOC(OCC)c1cc(C(CC(C)C)NC(=O)OCc2ccccc2)no1
Agent: O=C([O-])O
Agent: O=S(=O)(O)O
Agent: [Na+]
Solvent: CC(C)=O
Product: CC(C)CC(NC(=O)OCc1ccccc1)c1cc(C=O)on1
Temperature: 25 °C
Yield: 53.6 %

Procedure:
A stirred mixture of [1-(5-diethoxymethyl-isoxazol-3-yl)-3-methyl-butyl]-carbamic acid benzyl ester (920 mg, 2.4 mmol), acetone (50 ml) and H2SO4 (10 drops) was heated to reflux. After 35 min. the mixture was cooled to room temperature, neutralized with solid NaHCO3 and concentrated under reduced pressure. The resulting paste was taken up in EtOAc; washed with water and brine; dried over Na2SO4; filtered; and concentrated under reduced pressure to give a light yellow oil. Purification by Flash 40(small) chromatography eluting with 1:3 EtOAc/hexane gave 407 mg of the title compound as a light yellow oil. MS [M+1]+ 317.
Reaction SMILES: [N:1]1[CH:2]=[C:3]([CH2:10][C:11]([O:13]CC)=O)[N:4]2[CH2:9][CH2:8][CH2:7][CH2:6][C:5]=12.[NH3:16]>CO>[N:1]1[CH:2]=[C:3]([CH2:10][C:11]([NH2:16])=[O:13])[N:4]2[CH2:9][CH2:8][CH2:7][CH2:6][C:5]=12
Reactant: N
Reactant: CCOC(=O)Cc1cnc2n1CCCC2
Solvent: CO
Product: NC(=O)Cc1cnc2n1CCCC2
Temperature: 25 °C

Procedure:
Hydrogenate a mixture 2-(imidazo[1,2-a]pyridin-3-yl)acetamide (0.64 gm) and 0.158 gm platinum oxide in 200 mL ethanol saturated with hydrogen chloride at 60 p.s.i. for 2 hours at room temperature. Filter the reaction mixture and concentrate the filtrate under reduced pressure to provide 0.58 gm ethyl 2-(5,6,7,8-tetrahydroimidazo[1,2-a]pyridin-3-yl)acetate. Heat a solution of this ester in 40 mL 2 M ammonia in methanol in a sealed tube at 100° C. for 2 hours. Cool the reaction mixture to room temperature and concentrate under reduced pressure to a volume of about 5 mL. Dilute with ethyl acetate and filter the resulting solid to provide the title compound.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([C:12]2[O:13][C:14]3[CH:20]=[CH:19][C:18](Br)=[CH:17][C:15]=3[N:16]=2)[CH:7]=[CH:8][C:9]=1[O:10][CH3:11])([O-:3])=[O:2].[F:22][C:23]([F:34])([F:33])[C:24]1[CH:29]=[CH:28][C:27](B(O)O)=[CH:26][CH:25]=1>>[N+:1]([C:4]1[CH:5]=[C:6]([C:12]2[O:13][C:14]3[CH:20]=[CH:19][C:18]([C:27]4[CH:28]=[CH:29][C:24]([C:23]([F:34])([F:33])[F:22])=[CH:25][CH:26]=4)=[CH:17][C:15]=3[N:16]=2)[CH:7]=[CH:8][C:9]=1[O:10][CH3:11])([O-:3])=[O:2]
Reactant: COc1ccc(-c2nc3cc(Br)ccc3o2)cc1[N+](=O)[O-]
Reactant: OB(O)c1ccc(C(F)(F)F)cc1
Product: COc1ccc(-c2nc3cc(-c4ccc(C(F)(F)F)cc4)ccc3o2)cc1[N+](=O)[O-]

Procedure:
Prepared by the method of Example 15d), from 2-(3-nitro-4-methoxyphenyl)-5-bromobenzoxazole (200 mg, 0.57 mmol) and 4-trifluoromethylphenylboronic acid (161 mg, 0.85 mmol) the subtitle compound was obtained (204 mg, 58%). 1H NMR (DMSO) δ 8.64(d, 1H), 8.46(dd, 1H), 8.16(d, 1H), 7.97(d, 2H), 7.92(d, 1H), 7.85–7.78(m, 3H), 7.63(d, 1H), 4.05(s, 3H).
Reaction SMILES: O=[C:2]([NH:7][CH2:8][C:9](=O)[O:10][CH2:11][CH2:12][CH2:13][CH:14]=[CH2:15])[C:3]([O:5][CH3:6])=[O:4].N1C=CC=CC=1.O(S(C(F)(F)F)(=O)=O)S(C(F)(F)F)(=O)=O>ClCCl>[O:10]1[C:9]2=[CH:8][N:7]=[C:2]([C:3]([O:5][CH3:6])=[O:4])[CH:15]=[C:14]2[CH2:13][CH2:12][CH2:11]1
Reactant: C=CCCCOC(=O)CNC(=O)C(=O)OC
Agent: O=S(=O)(OS(=O)(=O)C(F)(F)F)C(F)(F)F
Solvent: ClCCl
Solvent: c1ccncc1
Product: COC(=O)c1cc2c(cn1)OCCC2
Temperature: 25 °C

Procedure:
Methyl 2-oxo-2-((2-oxo-2-(pent-4-en-1-yloxy)ethyl)amino)acetate (42.5 g, 1 eq) and dichloromethane (DCM) (425 mL) were added to a vessel with stirring followed by the addition of pyridine (17.6 g, 1.2 eq). Tf2O (78.5 g, 1.5 eq) was added over 45 min to the mixture maintaining an internal temperature of ˜25° C. The mixture was stirred for 6 h at which point the reaction was carefully quenched by the addition of 20 wt % aqueous NaOAc (255 mL) to form a biphasic solution. The aqueous layer was extracted with DCM (85 mL). The combined organic layers were washed first with water (127.5 mL) and 10 wt % citric acid solution (170 mL). 6N HCl (127.5 mL) was added to the mixture to form a biphasic mixture. The two layers were separated and the organic layer was extracted with 6 N HCl (85 mL). The acidic aqueous layers were combined and DCM (127.5 mL) was added. While maintaining the temperature below 25° C., 28 wt % aqueous NH4OH was slowly added until the pH of the aqueous layer reached 3-5. The two layers were separated and the aqueous layer was extracted with DCM (85 mL). The combined organic layers were washed with water (85 mL). The organic solution was concentrated under reduced pressure to provide the title compound as an oil which solidified on standing. 1H NMR (400 MHz, CDCl3) δ ppm 8.17 (s, 1H), 7.80-7.86 (m, 1H), 4.26 (t, J=5.19 Hz, 2H), 3.92 (s, 3H), 2.79 (t, J=6.44 Hz, 2H), 1.97-2.09 (m, 2H); 13C NMR (75 MHz, CDCl3) δ ppm 165.11, 154.25, 138.95, 138.64, 130.06, 126.13, 65.55, 51.99, 23.57, 20.67; HRMS (M+Na) m/z, calcd for C10H11NO3Na, 216.0637; found, 216.0643.
Reaction SMILES: [O:1]=[CH:2][C@@H:3]([C@H:5]([C@@H:7]([C@@H:9](CO)[OH:10])[OH:8])[OH:6])[OH:4]>C(O)C>[CH2:2]([OH:1])[C@@H:3]([C@H:5]([C@@H:7]([CH2:9][OH:10])[OH:8])[OH:6])[OH:4]
Reactant: O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO
Solvent: CCO
Product: OC[C@@H](O)[C@H](O)[C@@H](O)CO

Procedure:
As illustrated in FIG. 2, addition of glucose and ethanol resulted in the production of an significantly increased amount of xylitol, so that a considerable effect of their addition was observed. In the case where no carbon source was added, D-arabitol was oxidized substantially completely to D-xylulose. Even in the reaction without addition of any carbon source, prevention of pH at the time of reaction from decreasing by addition of calcium carbonate resulted in a slight increase in the yield of xylitol, more particularly 1.23% (w/v) xylitol was produced in 24 hours' reaction. However, a portion of D-xylulose remained unreacted, no further increase in yield did occur. In contrast, with addition of a carbon source, D-xylulose was reduced to xylitol substantially completely, and at the point in time of 24 hours, xylitol was produced and accumulated in a yield as high as 5.24% (w/v) (98% based on D-arabitol).