Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C(O[C:6]([NH:8][C@@H:9]([C:18](=[O:20])[NH2:19])[CH2:10][CH2:11][C:12]([O:14][CH:15]([CH3:17])[CH3:16])=[O:13])=[O:7])(C)(C)C.FC(F)(F)C(O)=O.[C:28]([O:32][C:33]([NH:35][C@H:36](C(O)=O)[CH2:37][O:38][CH2:39][C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1)=[O:34])([CH3:31])([CH3:30])[CH3:29]>>[C:28]([O:32][C:33]([NH:35][C@H:36]([C:6]([NH:8][C@@H:9]([C:18](=[O:20])[NH2:19])[CH2:10][CH2:11][C:12]([O:14][CH:15]([CH3:16])[CH3:17])=[O:13])=[O:7])[CH2:37][O:38][CH2:39][C:40]1[CH:41]=[CH:42][CH:43]=[CH:44][CH:45]=1)=[O:34])([CH3:31])([CH3:29])[CH3:30]
Reactant: CC(C)OC(=O)CC[C@@H](NC(=O)OC(C)(C)C)C(N)=O
Reactant: CC(C)(C)OC(=O)N[C@@H](COCc1ccccc1)C(=O)O
Solvent: O=C(O)C(F)(F)F
Product: CC(C)OC(=O)CC[C@@H](NC(=O)[C@H](COCc1ccccc1)NC(=O)OC(C)(C)C)C(N)=O

Procedure:
Isopropyl t-butyloxycarbonyl-D-isoglutaminate (176 mg, 0.61 mmol) was treated with trifluoroacetic acid (1 ml) at room temperature for 20 minutes. Trifluoroacetic acid was evaporated and the residue was washed thoroughly with a mixture of diethyl ether-petroleum ether (1:1) and dried in a desiccator over sodium hydroxide pellets. The resulting trifluoroacetic acid salt was dissolved in acetonitrile (10 ml) together with triethylamine (0.19 ml). To this solution was added t-butyloxycarbonyl-O-benzyl-L-serine HOSuc ester (274 mg, 0.7 mmol), and the mixture was allowed to react for 15 hours at room temperature. The solvent was evaporated and the residue was dissolved in ethyl acetate (20 ml). The solution was washed successively with a 5% aqueous sodium bicarbonate solution, 1 N hydrochloric acid and water, dried over anhydrous sodium sulfate, and evaporated. The residue was crystallized by addition of petroleum ether and the resulting crystals were filtered to obtain isopropyl t-butyloxycarbonyl-O-benzyl-L-seryl-D-isoglutaminate (243 mg). Melting point, 98°-99° C. [α]D22 +2.0° (c 0.5, DMF). Rf2 =0.50; Rf3 =0.78.
Reaction SMILES: [Na].C(OC(=O)[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1[O:17][S:18]([NH:21]C(OCC1C=CC=CC=1)=O)(=[O:20])=[O:19])C1C=CC=CC=1.Cl.[H][H]>CO.[Pd]>[C:12]1([O:17][S:18](=[O:19])(=[O:20])[NH2:21])[CH:11]=[CH:16][CH:15]=[CH:14][CH:13]=1
Reactant: [H][H]
Reactant: O=C(NS(=O)(=O)Oc1ccccc1C(=O)OCc1ccccc1)OCc1ccccc1
Agent: [Pd]
Agent: Cl
Agent: [Na]
Solvent: CO
Product: NS(=O)(=O)Oc1ccccc1
Yield: 39 %

Procedure:
The 2-(benzyloxycarbonylaminosulfonyloxy)benzoic acid benzyl ester sodium salt prepared above, [35.3 g (0.076 mole)] was suspended in 500 ml of methanol was mixed with 6.2 ml of concentrated hydrochloric acid and 2 g of 5% palladium on carbon wetted with 50 ml methanol. The mixture was hydrogenated with hydrogen gas for 4 hr and filtered. The filtrate was concentrated to an oil. The oil was suspended in THF and filtered to remove some solids. The clear filtrate was concentrated and mixed with 1,1,1-trichloroethanol to precipitate the product as 8.82 g of light purple solid obtained after filtration. The purple solid was dissolved in THF and the solution was treated with charcoal, filtered and concentrated. The solid was recrystallized from 1,1,1-trichloroethane to give 6.5 g of white solid (39%), mp 139°-140° C.
Reaction SMILES: [CH3:1][CH:2]1[N:15]2[C:6]([CH2:7][O:8][C:9]3[C:14]2=[CH:13][C:12]([N+:16]([O-])=O)=[C:11]([O:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH:10]=3)=[N:5][NH:4][C:3]1=[O:26]>CO.[Ni]>[NH2:16][C:12]1[CH:13]=[C:14]2[C:9](=[CH:10][C:11]=1[O:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[O:8][CH2:7][C:6]1[N:15]2[CH:2]([CH3:1])[C:3](=[O:26])[NH:4][N:5]=1
Reactant: CC1C(=O)NN=C2COc3cc(Oc4ccccc4)c([N+](=O)[O-])cc3N21
Agent: [Ni]
Solvent: CO
Product: CC1C(=O)NN=C2COc3cc(Oc4ccccc4)c(N)cc3N21
Temperature: 25 °C
Reaction time: 8 h

Procedure:
A mixture of 4-methyl-6-nitro-7-phenoxy-2,10-dihydro-9-oxa-1,2,4a-triaza-phenanthren-3-one (0.090 g, 0.25 mmol) and Raney Ni (0.030 g) in MeOH (5 mL) was stirred overnight under an atmosphere of H2 (30 psi) at ambient temperature. The reaction mixture was filtered and the filtrate was concentrated in vacuo to give 6-amino-4-methyl-7-phenoxy-2,10-dihydro-9-oxa-1,2,4a-triaza-phenanthren-3-one as a colorless oil (0.090 g, crude), which was used in next step without further purification. LC/MS (Table 1, Method 2) Rt=0.938 min; MS m/z: 325 [M+H]+
Reaction SMILES: [O:1]1[C:5]2([CH2:10][CH2:9][C:8](=O)[CH2:7][CH2:6]2)[O:4][CH2:3][CH2:2]1.[CH2:12]([NH:19][CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)(O)[O-]>ClCCl>[CH2:20]([N:19]([CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[CH:8]1[CH2:9][CH2:10][C:5]2([O:4][CH2:3][CH2:2][O:1]2)[CH2:6][CH2:7]1)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.[CH2:20]([N:19]([CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[CH:8]1[CH2:9][CH2:10][C:5]2([O:4][CH2:3][CH2:2][O:1]2)[CH2:6][CH2:7]1)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1
Reactant: O=C1CCC2(CC1)OCCO2
Reactant: c1ccc(CNCc2ccccc2)cc1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Product: c1ccc(CN(Cc2ccccc2)C2CCC3(CC2)OCCO3)cc1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To a solution of 1,4-dioxaspiro[4.5]decan-8-one (25 g, 0.16 mol) in 1,2-dichloroetrane (396 mL) was added dibenzylamine (32.3 mL, 0.16 mol) under nitrogen atmosphere and the resulting solution was stirred for 2 hours at room temperature. Then sodium triacetoxyborohydride (55.4 g, 0.25 mol) was added portionwise and the reaction mixture was stirred at room temperature overnight. A mixture of bicarbonate and dichloromethane (1:1) was added to the reaction mixture and it was stirred for half an hour, then the organic phase was extracted and washed with bicarbonate and brine, dried, filtered and the organic solvent was evaporated under reduced pressure. The resulting oil was precipitated with hexane obtaining a white solid as a title compound (80%), which was used in the next step without further manipulation.
Reaction SMILES: Cl.[CH2:2]([C:6]1[CH:11]=[CH:10][C:9]([C:12]#[C:13][C:14]2[CH:34]=[CH:33][C:17]([CH2:18][NH:19][C:20]3[CH:32]=[CH:31][C:23]4[O:24][C:25]([CH3:30])([CH3:29])[O:26][C:27](=[O:28])[C:22]=4[CH:21]=3)=[CH:16][CH:15]=2)=[CH:8][CH:7]=1)[CH2:3][CH2:4][CH3:5].[C:35]1([C:44]2[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=2)[CH:40]=[CH:39][C:38]([C:41](Cl)=[O:42])=[CH:37][CH:36]=1>>[CH2:2]([C:6]1[CH:7]=[CH:8][C:9]([C:12]#[C:13][C:14]2[CH:34]=[CH:33][C:17]([CH2:18][N:19]([C:20]3[CH:32]=[CH:31][C:23]4[O:24][C:25]([CH3:30])([CH3:29])[O:26][C:27](=[O:28])[C:22]=4[CH:21]=3)[C:41]([C:38]3[CH:39]=[CH:40][C:35]([C:44]4[CH:45]=[CH:46][CH:47]=[CH:48][CH:49]=4)=[CH:36][CH:37]=3)=[O:42])=[CH:16][CH:15]=2)=[CH:10][CH:11]=1)[CH2:3][CH2:4][CH3:5]
Reactant: O=C(Cl)c1ccc(-c2ccccc2)cc1
Reactant: CCCCc1ccc(C#Cc2ccc(CNc3ccc4c(c3)C(=O)OC(C)(C)O4)cc2)cc1
Agent: Cl
Product: CCCCc1ccc(C#Cc2ccc(CN(C(=O)c3ccc(-c4ccccc4)cc3)c3ccc4c(c3)C(=O)OC(C)(C)O4)cc2)cc1

Procedure:
The titled compound was prepared following the procedure J using 6-({4-[(4-butylphenyl)ethynyl]benzyl}amino)-2,2-dimethyl-4H-1,3-benzodioxin-4-one hydrochloride and biphenyl-4-carbonyl chloride as a pale yellow oil (43%). 1H NMR (CDCl3, 300 MHz) δ 7.72 (brs, 1H), 7.53-7.27 (m, 15H), 7.17 (d, J=8.3 Hz, 2H), 6.98 (brd, J=8.7 Hz, 1H), 6.73 (d, J=8.7 Hz, 1H), 5.15 (s, 2H), 2.63 (t, J=7.5 Hz, 2H), 1.67 (s, 6H), 1.61 (m, 2H), 1.37 (m, 2H), 0.94 (t, J=7.2 Hz, 3H). HPLC, Rt: 6.07 min (Purity: 99.8%).
Reaction SMILES: I[C:2]1[C:3]([NH2:12])=[N:4][CH:5]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:7]=1.[CH2:13]([Si:15]([CH2:23][CH3:24])([CH2:21][CH3:22])[C:16]#[C:17][CH2:18][CH2:19][OH:20])[CH3:14].[Cl-].[Li+].C(=O)([O-])[O-].[Na+].[Na+]>CN(C=O)C.ClCCl.[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].O.CCOC(C)=O.CCOCC>[CH2:23]([Si:15]([CH2:13][CH3:14])([CH2:21][CH3:22])[C:16]1[NH:12][C:3]2=[N:4][CH:5]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:7]=[C:2]2[C:17]=1[CH2:18][CH2:19][OH:20])[CH3:24]
Reactant: CC[Si](C#CCCO)(CC)CC
Reactant: Nc1ncc(C(F)(F)F)cc1I
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: O=C([O-])[O-]
Solvent: ClCCl
Solvent: CCOC(C)=O
Solvent: O
Product: CC[Si](CC)(CC)c1[nH]c2ncc(C(F)(F)F)cc2c1CCO
Temperature: 100 °C
Reaction time: 15 h

Procedure:
A mixture of 3-iodo-5-(trifluoromethyl)pyridin-2-amine (13 g, 45.1 mmole), 4-(triethylsilyl)but-3-in-1-ol (12.4 g, 67.7 mmole), 1,1′-bis(diphenylphosphino)ferrocene-palladium(II) dichloride dichloromethane (1.78 g, 2.26 mmole), lithium chloride (1.86 g, 45.1 mmole) and sodium carbonate (9.54 g, 90.3 mmole) in DMF (460 ml) was stirred under nitrogen for 15 hours at 100° C. The reaction mixture was cooled to RT, 2 l of EtOAc/ether (1:1) were added, and the mixture was poured into 2 l of H2O. The two-phase suspension was filtered through filter earth. After separating the phases the aqueous phase was extracted with EtOAc (2×1 l). The organic phases were combined and washed with H2O and with saturated NaCl solution and dried over MgSO4. After filtering the drying agent the solvents were removed on a rotary evaporator. The residue was purified by column chromatography (tert.-butyl methyl ether/n-hexane=2:3). The mixed fraction thereby obtained was taken up 4 times, each time with 20 ml of dichloromethane and suction filtered from the white crystalline solid. The first three fractionated precipitates were combined: 2-(2-(triethylsilyl)-5-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)ethanol was obtained (3.8 g, 24.4%).
Reaction SMILES: [CH3:1][O:2][C:3](=[O:15])[C:4](=O)[CH:5]=[CH:6][C:7]1[CH:12]=[CH:11][C:10]([Br:13])=[CH:9][CH:8]=1.Cl.[Cl:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=1[NH:24][NH2:25]>C(O)(=O)C>[CH3:1][O:2][C:3]([C:4]1[CH2:5][CH:6]([C:7]2[CH:12]=[CH:11][C:10]([Br:13])=[CH:9][CH:8]=2)[N:24]([C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=2[Cl:17])[N:25]=1)=[O:15]
Reactant: NNc1ccccc1Cl
Reactant: COC(=O)C(=O)C=Cc1ccc(Br)cc1
Agent: Cl
Solvent: CC(=O)O
Product: COC(=O)C1=NN(c2ccccc2Cl)C(c2ccc(Br)cc2)C1
Temperature: 125 °C
Reaction time: 4 h
Yield: 95.6 %

Procedure:
4-(4-Bromo-phenyl)-2-oxo-3-butenoic acid methyl ester (13.5 g, 50.2 mmol) prepared in Step 2 and 2-chlorophenylhydrazine hydrochloride (9.9 g, 55.2 mmol) were added to acetic acid (200.0 mL). The reaction mixture was stirred at 125° C. for 4 hours, concentrated under reduced pressure, and then ethyl acetate was added thereto. The reaction mixture was washed with a saturated solution of sodium hydrogen carbonate, dried on anhydrous magnesium sulfate, and then concentrated under reduced pressure to give a yellow liquid residue. The resulting residue was purified by silica gel column chromatography (eluent: ethyl acetate/n-hexane=1/5) to give 18.9 g of the titled compound as a brown liquid.
Reaction SMILES: [CH3:1][S:2](Cl)(=[O:4])=[O:3].[NH2:6][C:7]1[CH:20]=[CH:19][C:10]([C:11]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[O:12])=[CH:9][CH:8]=1.N1C=CC=CC=1.Cl>O>[C:11]([C:10]1[CH:9]=[CH:8][C:7]([NH:6][S:2]([CH3:1])(=[O:4])=[O:3])=[CH:20][CH:19]=1)(=[O:12])[C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1
Reactant: CS(=O)(=O)Cl
Reactant: Nc1ccc(C(=O)c2ccccc2)cc1
Agent: Cl
Solvent: c1ccncc1
Solvent: O
Product: CS(=O)(=O)Nc1ccc(C(=O)c2ccccc2)cc1
Temperature: 90 °C
Reaction time: 4 h
Yield: 83 %

Procedure:
Methanesulfonyl chloride (35.0 g., 0.305 mole) is added dropwise over a 20 min. period with stirring to a solution of 4-aminobenzophenone (60.2 g., 0.305 mole) in 475 ml. of pyridine cooled at 0°-10°C. After the addition is completed, stirring at 0°-10°C. is continued for 4 hrs., and then for an additional 12 hrs. at room temperature. The solution is then heated to 90°C. for 1 hr., allowed to cool, poured into 1.0.1. of water, and then acidified with concentrated hydrochloric acid to pH 1.0. The precipitate which forms is collected on a filter, washed with water, and recrystallized from isopropanol without previous drying to give 70.0 g. (83% yield), m.p. 145-147°C.
Reaction SMILES: [CH3:1][C:2]1([CH3:27])[CH2:15][CH2:14][C:13]([CH3:17])([CH3:16])[C:12]2[CH:11]=[C:10]3[C:5]([CH:6]=[CH:7][C:8]([C:18]4[CH:26]=[CH:25][C:21]([C:22](O)=[O:23])=[CH:20][CH:19]=4)=[CH:9]3)=[CH:4][C:3]1=2.[H-].[H-].[H-].[H-].[Li+].[Al+3].[Na].C(C(C(C([O-])=O)O)O)([O-])=O.[K+].[K+]>C1COCC1>[CH3:1][C:2]1([CH3:27])[CH2:15][CH2:14][C:13]([CH3:16])([CH3:17])[C:12]2[CH:11]=[C:10]3[C:5]([CH:6]=[CH:7][C:8]([C:18]4[CH:26]=[CH:25][C:21]([CH2:22][OH:23])=[CH:20][CH:19]=4)=[CH:9]3)=[CH:4][C:3]1=2
Reactant: CC1(C)CCC(C)(C)c2cc3cc(-c4ccc(C(=O)O)cc4)ccc3cc21
Agent: O=C([O-])C(O)C(O)C(=O)[O-]
Agent: [Al+3]
Agent: [H-]
Solvent: C1CCOC1
Product: CC1(C)CCC(C)(C)c2cc3cc(-c4ccc(CO)cc4)ccc3cc21
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 58.4 %

Procedure:
300 mg (0.83 mmole) of p-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-anthracenyl) benzoic acid obtained in Example III above are dissolved in THF. 48 mg (1.25 mmoles) of LiAlH4 are added and the mixture is stirred initially for 15 minutes at ambient temperature and then for 10 minutes at reflux. The mixture is then left to stand until its temperature returns to ambient temperature. 28 μl of a saturated solution of sodium and potassium tartrate are then added. The mixture is then filtered and the THF is evaporated. The resulting residue is taken up in hexane and the precipitate that forms is filtered, yielding 167 mg (57% yield) of the expected alcohol which melts at 131° C.
Reaction SMILES: Cl[CH2:2][C:3]([NH:5][C:6]1[C:11]([F:12])=[CH:10][CH:9]=[CH:8][C:7]=1[SH:13])=[O:4].[OH-].[Na+]>>[F:12][C:11]1[C:6]2[NH:5][C:3](=[O:4])[CH2:2][S:13][C:7]=2[CH:8]=[CH:9][CH:10]=1
Reactant: O=C(CCl)Nc1c(F)cccc1S
Agent: [Na+]
Agent: [OH-]
Product: O=C1CSc2cccc(F)c2N1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
2-Chloroacetylamino-3-fluorothiophenol (2.0 g) was added to 2 N aqueous sodium hydroxide solution (25 ml), followed by stirring at room temperature (25° C.) for 3 hours. The precipitated crystals were filtered, washed with water and dried to obtain 1.5 g of the objective, 5-fluoro-2,3-dihydro-1,4-benzothiazine-3-one (m.p. 190°-191° C.).
Reaction SMILES: C[CH:2]([CH:6]1[C:10]2=[C:11]([S:20][C:21]3[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][CH:22]=3)[C:12]3[C:13](Br)=[CH:14][C:15]([F:18])=[CH:16][C:17]=3[N:9]2[CH2:8][CH2:7]1)[C:3]([O-:5])=[O:4].C([Sn](CCCC)(CCCC)[C:33]1[S:34][CH:35]=[CH:36][C:37]=1[CH3:38])CCC>>[Cl:27][C:24]1[CH:23]=[CH:22][C:21]([S:20][C:11]2[C:12]3[C:13]([C:33]4[S:34][CH:35]=[CH:36][C:37]=4[CH3:38])=[CH:14][C:15]([F:18])=[CH:16][C:17]=3[N:9]3[CH2:8][CH2:7][CH:6]([CH2:2][C:3]([OH:5])=[O:4])[C:10]=23)=[CH:26][CH:25]=1
Reactant: CCCC[Sn](CCCC)(CCCC)c1sccc1C
Reactant: CC(C(=O)[O-])C1CCn2c1c(Sc1ccc(Cl)cc1)c1c(Br)cc(F)cc12
Product: Cc1ccsc1-c1cc(F)cc2c1c(Sc1ccc(Cl)cc1)c1n2CCC1CC(=O)O

Procedure:
Starting from (+/−)-methyl{8-bromo-9-[(4-chlorophenyl)thio]-6-fluoro-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl}acetate and tributyl(3-methylthien-2-yl)stannane, the title compound was synthesized following the procedures described in Example 42 and Step 10 of Example 7.
Reaction SMILES: [NH2:1][C:2]1[N:7]=[C:6](OS(C2C(C)=CC(C)=CC=2C)(=O)=O)[C:5]([CH2:21][C:22]2[CH:40]=[CH:39][C:25]([CH2:26][N:27]3[CH2:31][CH2:30][CH2:29][C@@H:28]3[C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])=[CH:24][C:23]=2[O:41][CH3:42])=[C:4]([CH3:43])[N:3]=1.[NH2:44][C@@H:45]([CH2:49][CH2:50][CH3:51])[CH2:46][CH2:47][OH:48]>>[NH2:1][C:2]1[N:7]=[C:6]([NH:44][C@@H:45]([CH2:49][CH2:50][CH3:51])[CH2:46][CH2:47][OH:48])[C:5]([CH2:21][C:22]2[CH:40]=[CH:39][C:25]([CH2:26][N:27]3[CH2:31][CH2:30][CH2:29][C@@H:28]3[C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])=[CH:24][C:23]=2[O:41][CH3:42])=[C:4]([CH3:43])[N:3]=1
Reactant: COc1cc(CN2CCC[C@@H]2C(=O)OC(C)(C)C)ccc1Cc1c(C)nc(N)nc1OS(=O)(=O)c1c(C)cc(C)cc1C
Reactant: CCC[C@H](N)CCO
Product: CCC[C@@H](CCO)Nc1nc(N)nc(C)c1Cc1ccc(CN2CCC[C@@H]2C(=O)OC(C)(C)C)cc1OC

Procedure:
The sub-title compound was synthesized by the method of example 1 step (viii) from the product of step (i) (234 mg) and (s)-3-aminohexan-1-ol (X mg). The sub-title compound (70 mg) was obtained as a colourless amorphous solid; LC-MS: m/z 528.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[N:4][C:5]([N:8]2[CH2:13][CH2:12][CH:11]([C@H:14]3[CH2:16][C@H:15]3[CH2:17][CH2:18][OH:19])[CH2:10][CH2:9]2)=[N:6][CH:7]=1.[N:20]1([C:24](=[O:34])[CH2:25][C:26]2[CH:31]=[CH:30][C:29](O)=[CH:28][C:27]=2[CH3:33])[CH2:23][CH2:22][CH2:21]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C>C1(C)C=CC=CC=1.C(OCC)(=O)C>[N:20]1([C:24](=[O:34])[CH2:25][C:26]2[CH:31]=[CH:30][C:29]([O:19][CH2:18][CH2:17][C@@H:15]3[CH2:16][C@@H:14]3[CH:11]3[CH2:12][CH2:13][N:8]([C:5]4[N:6]=[CH:7][C:2]([Cl:1])=[CH:3][N:4]=4)[CH2:9][CH2:10]3)=[CH:28][C:27]=2[CH3:33])[CH2:23][CH2:22][CH2:21]1
Reactant: Cc1cc(O)ccc1CC(=O)N1CCC1
Reactant: OCC[C@@H]1C[C@@H]1C1CCN(c2ncc(Cl)cn2)CC1
Agent: CC(C)OC(=O)/N=N/C(=O)OC(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CCOC(C)=O
Solvent: Cc1ccccc1
Product: Cc1cc(OCC[C@@H]2C[C@@H]2C2CCN(c3ncc(Cl)cn3)CC2)ccc1CC(=O)N1CCC1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
2-{(1S,2R)-2-[1-(5-chloropyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethanol (50 mg, 0.177 mmol) was dissolved in toluene (1 ml) and 1-(azetidin-1-yl)-2-(4-hydroxy-2-methylphenyl)ethanone (36.4 mg, 0.177 mmol), triphenylphosphine (55.8 mg, 0.213 mmol), and DIAD (41.4 μl, 0.213 mmol) added and the mixture stirred at RT overnight. The mixture was diluted with ethyl acetate (20 mL), washed with brine (10 ml), dried over MgSO4, filtered and the solvent removed in vacuo. The residue was purified by chromatography on silica gel, Biotage 25M, eluting with a gradient eluant of 0-100% EtOAc/Hexane to afford afford the title compound. LC/MS (m/z): 469 (M+H)+. GPR119 Human EC50: 0.73 nM.
Reaction SMILES: [C:1]([O:7][CH2:8][N:9]1[CH:13]=[C:12]([C:14]2[CH:19]=[C:18]([O:20][C:21]3[C:22]([CH3:30])=[N:23][C:24]([N+:27]([O-])=O)=[CH:25][CH:26]=3)[CH:17]=[CH:16][N:15]=2)[N:11]=[N:10]1)(=[O:6])[C:2]([CH3:5])([CH3:4])[CH3:3]>CCOC(C)=O.[Pd]>[C:1]([O:7][CH2:8][N:9]1[CH:13]=[C:12]([C:14]2[CH:19]=[C:18]([O:20][C:21]3[C:22]([CH3:30])=[N:23][C:24]([NH2:27])=[CH:25][CH:26]=3)[CH:17]=[CH:16][N:15]=2)[N:11]=[N:10]1)(=[O:6])[C:2]([CH3:5])([CH3:4])[CH3:3]
Reactant: Cc1nc([N+](=O)[O-])ccc1Oc1ccnc(-c2cn(COC(=O)C(C)(C)C)nn2)c1
Agent: [Pd]
Solvent: CCOC(C)=O
Product: Cc1nc(N)ccc1Oc1ccnc(-c2cn(COC(=O)C(C)(C)C)nn2)c1
Temperature: 25 °C
Reaction time: 24 h
Yield: 95.8 %

Procedure:
A solution of (4-(4-((2-methyl-6-nitropyridin-3-yl)oxy)pyridin-2-yl)-1H-1,2,3-triazol-1-yl)methyl pivalate (0.27 g, 0.655 mmol) in EtOAc (5 mL) was treated with 10% Pd/C (50% wet, 0.070 g, 0.066 mmol) and the mixture was stirred under hydrogen (1 atm) at RT for 24 h. The mixture was filtered through diatomaceous earth and the filter cake was washed with EtOAc. The combined filtrates were evaporated to dryness to give (4-(4-((6-amino-2-methylpyridin-3-yl)oxy)pyridin-2-yl)-1H-1,2,3-triazol-1-yl)methyl pivalate (0.24 g, 96%) as colorless foam. 1H NMR (400 MHz, DMSO-d6): δ 8.67 (s, 1H), 8.45 (d, J=5.7 Hz, 1H), 7.35 (d, J=2.5 Hz, 1H), 7.23 (d, J=8.7 Hz, 1H), 6.86 (dd, J=5.7, 2.6 Hz, 1H), 6.38-6.35 (m, 3H); 5.99 (s, 2H), 2.06 (s, 3H), 1.11 (s, 9H); MS (ESI) m/z: 383.2 (M+H+).
Reaction SMILES: Cl.[Cl:2][CH2:3][CH2:4][CH2:5][CH:6]([C:18]1[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=1)[C:7]([NH:9][NH:10]C(OC(C)(C)C)=O)=[O:8]>C(OCC)(=O)C>[ClH:2].[Cl:2][CH2:3][CH2:4][CH2:5][CH:6]([C:18]1[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=1)[C:7]([NH:9][NH2:10])=[O:8]
Reactant: CC(C)(C)OC(=O)NNC(=O)C(CCCCl)c1ccc(F)cc1
Agent: Cl
Solvent: CCOC(C)=O
Product: NNC(=O)C(CCCCl)c1ccc(F)cc1
Temperature: 25 °C
Reaction time: 4 h
Yield: 162.3 %

Procedure:
A solution of 4 N hydrochloric acid in ethyl acetate (2 mL) was added to a solution of tert-butyl N′-[5-chloro-2-(4-fluorophenyl)pentanoyl]hydrazinecarboxylate (517 mg) in ethyl acetate (2 mL), and the reaction solution was stirred at room temperature for four hours. The reaction solution was concentrated under reduced pressure to obtain 342 mg of the title compound. The property values of the compound are as follows.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:9]2[C:10]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH:6]=[CH:7][CH:8]=1>[Fe](Cl)(Cl)Cl.C(Cl)Cl>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]2[C:20]3[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=3)[C:10]3[C:9](=[CH:14][CH:13]=[CH:12][CH:11]=3)[C:5]=2[CH:4]=1
Reactant: COc1cccc(-c2ccccc2-c2ccccc2)c1
Agent: Cl[Fe](Cl)Cl
Solvent: ClCCl
Product: COc1ccc2c3ccccc3c3ccccc3c2c1
Reaction time: 1 h
Yield: 59.9 %

Procedure:
23.4 g of 3-methoxy[1,1′:2′,1″]terphenyl, 146 g of iron (III) chloride and 200 mL of methylene chloride were placed in a flask, and stirred for one hour while deaerating with argon. The reaction solution was subjected to filtration, followed by washing with an excessive amount of acetone. The resulting solid was dissolved in heated toluene. Insoluble substances were filtered out, followed by crystallization with cooling. The resulting crystal was collected by filtration to obtain 13.9 g (yield: 60%) of 2-methoxytriphenylene.
Reaction SMILES: [OH:1][C:2]1[C:3]([OH:18])=[N:4][C:5]2[C:6]([N:17]=1)=[C:7]1[C:12](=[CH:13][CH:14]=2)[N:11]=[C:10]([CH3:15])[C:9]([CH3:16])=[N:8]1.[N+:19]([O-])([O-:21])=[O:20].[K+].[OH-].[Na+]>S(=O)(=O)(O)O>[OH:1][C:2]1[C:3]([OH:18])=[N:4][C:5]2[C:6]([N:17]=1)=[C:7]1[C:12](=[C:13]([N+:19]([O-:21])=[O:20])[CH:14]=2)[N:11]=[C:10]([CH3:15])[C:9]([CH3:16])=[N:8]1
Reactant: Cc1nc2ccc3nc(O)c(O)nc3c2nc1C
Reactant: O=[N+]([O-])[O-]
Agent: O=S(=O)(O)O
Agent: [K+]
Agent: [Na+]
Product: Cc1nc2c([N+](=O)[O-])cc3nc(O)c(O)nc3c2nc1C
Reaction time: 24 h
Yield: 33 %

Procedure:
To a solution of 0,45 g (1,9 mmol) 2,3-dihydroxy-8,9-dimethylpyrazino(2,3-f)quinoxaline in 30 ml concentrated sulfuric acid was added at 0° C. 384 mg (3,8 mmol) potassium nitrate. Stirring was continued at 0° C. for 30 min. and at 25° C. for 24 h. The reaction mixture was poured into 150 ml icewater. The solution was added 10N sodium hydroxide to pH 7, and then extracted with ethyl acetate (5×100 ml). The combined and dried ethyl acetate phases were evaporated to give 0,18 g (33%) 2,3-dihydroxy-8,9-dimethyl-6-nitropyrazino(2,3-f)quinoxaline, m.p. >300° C. NMR (DMSO-d6): 8.07 (1H,s), 2.77 (3H,s), 2.73 (3H,s).
Reaction SMILES: [Cl:1][C:2]1[N:3]=[C:4](Cl)[C:5]2[S:10][CH:9]=[C:8]([CH3:11])[C:6]=2[N:7]=1.[C:13]([NH2:17])([CH3:16])([CH3:15])[CH3:14].O>CN(C=O)C>[C:13]([NH:17][C:4]1[C:5]2[S:10][CH:9]=[C:8]([CH3:11])[C:6]=2[N:7]=[C:2]([Cl:1])[N:3]=1)([CH3:16])([CH3:15])[CH3:14]
Reactant: Cc1csc2c(Cl)nc(Cl)nc12
Reactant: CC(C)(C)N
Solvent: CN(C)C=O
Solvent: O
Product: Cc1csc2c(NC(C)(C)C)nc(Cl)nc12
Reaction time: 3 h
Yield: 91.3 %

Procedure:
In 3 ml of DMF was dissolved 300 mg (1.4 mmol) of 2,4-dichloro-7-methylthieno[3,2-d]pyrimidine, and after 150 mg (2.1 mmol) of t-butylamine was added to the resulting solution, the mixture was stirred for 3 hours. Water was added to the reaction mixture, and crystals thus precipitated were filtered to give 327 mg (yield: 93.4%) of the title compound.
Reaction SMILES: N[C:2]1[C:7]([C:8]#[N:9])=[N:6][C:5]([C:10]2[CH:15]=[C:14]([C:16]([F:19])([F:18])[F:17])[CH:13]=[C:12]([C:20]([F:23])([F:22])[F:21])[CH:11]=2)=[C:4]([CH3:24])[N:3]=1.C(=O)(O)O.[NH2:29][C:30]([NH2:32])=[NH:31]>CN(C)C(=O)C>[NH2:31][C:30]1[N:32]=[C:8]([NH2:9])[C:7]2[C:2](=[N:3][C:4]([CH3:24])=[C:5]([C:10]3[CH:15]=[C:14]([C:16]([F:19])([F:18])[F:17])[CH:13]=[C:12]([C:20]([F:22])([F:21])[F:23])[CH:11]=3)[N:6]=2)[N:29]=1
Reactant: N=C(N)N
Reactant: Cc1nc(N)c(C#N)nc1-c1cc(C(F)(F)F)cc(C(F)(F)F)c1
Agent: O=C(O)O
Solvent: CC(=O)N(C)C
Product: Cc1nc2nc(N)nc(N)c2nc1-c1cc(C(F)(F)F)cc(C(F)(F)F)c1

Procedure:
This compound is prepared in a manner analogous to that of Step B of Example 4, using 1.1 grams (0.003 mole) of 2-amino-3-cyano-5-[3,5di(trifluoromethyl)phenyl]-6-methylpyrazine and 1.3 grams (0.007 mole) of guanidine carbonate in 10 mL of N,N-dimethylacetamide, yielding 2,4-diamino-6-[3,5-di(trifluoromethyl)phenyl]-7-methylpteridine.