Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([N:4]1[CH2:9][CH:8]2[C:6]([C:10]3[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=3)([CH2:7]2)[CH2:5]1)(=[O:3])[CH3:2].[N+:16]([O-])([OH:18])=[O:17]>S(=O)(=O)(O)O>[C:1]([N:4]1[CH2:9][CH:8]2[C:6]([C:10]3[CH:15]=[CH:14][C:13]([N+:16]([O-:18])=[O:17])=[CH:12][CH:11]=3)([CH2:7]2)[CH2:5]1)(=[O:3])[CH3:2]
Reactant: CC(=O)N1CC2CC2(c2ccccc2)C1
Reactant: O=[N+]([O-])O
Agent: O=S(=O)(O)O
Product: CC(=O)N1CC2CC2(c2ccc([N+](=O)[O-])cc2)C1
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
To a suspension of 3-acetyl-1-phenyl-3-azabicyclo[3.1.0]hexane in concentrated sulfuric acid is added concentrated nitric acid during 15 minutes at 0°-10° C. The resulting mixture is stirred at room temperature for 15 minutes and then poured onto ice. The product, 3-acetyl-1-(p-nitrophenyl)-3-azabicyclo[3.1.0]hexane, is collected by filtration.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH:12]=[C:11]([C:14]2[C:22]3[S:21][C:20]([NH:23][C:24]([C:26]4[CH:31]=[CH:30][N:29]=[C:28]([CH3:32])[CH:27]=4)=[O:25])=[N:19][C:18]=3[C:17]([O:33][CH3:34])=[CH:16][CH:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C1COCC1>CO.[Pd]>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[C:22]3[S:21][C:20]([NH:23][C:24]([C:26]4[CH:31]=[CH:30][N:29]=[C:28]([CH3:32])[CH:27]=4)=[O:25])=[N:19][C:18]=3[C:17]([O:33][CH3:34])=[CH:16][CH:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: COc1ccc(C2=CCN(C(=O)OC(C)(C)C)CC2)c2sc(NC(=O)c3ccnc(C)c3)nc12
Agent: [Pd]
Solvent: CO
Solvent: C1CCOC1
Product: COc1ccc(C2CCN(C(=O)OC(C)(C)C)CC2)c2sc(NC(=O)c3ccnc(C)c3)nc12
Reaction time: 10 h
Yield: 50.1 %

Procedure:
To a solution of 0.30 g (0.62 mMol) of 4-{4-methoxy-2-[(2-methyl-pyridine-4-carbonyl)-amino]-benzothiazol-7-yl}-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester in 15.0 ml of methanol and 15.0 ml THF 160.0 mg of Pd/C (10%) were added. The reaction mixture was hydrogenated at 60° C. for 10 h, then filtered and evaporated to dryness in vacuo. The residue was triturated in diethyl ether to yield 0.15 g (53%) 4-{4-methoxy-2-[(2-methyl-pyridine-4-carbonyl)-amino]-benzothiazol-7-yl}-piperidine-1-carboxylic acid tert-butyl ester as a white solid. F.p.: 155-157° C.
Reaction SMILES: [NH2:1][C:2]1[C:20]([Cl:21])=[CH:19][C:5]([C:6]([NH:8][CH2:9][C:10]2([OH:18])[CH:15]3[CH2:16][CH2:17][N:12]([CH2:13][CH2:14]3)[CH2:11]2)=O)=[C:4]([O:22][CH3:23])[CH:3]=1.P12(SP3(SP(SP(S3)(S1)=S)(=S)S2)=S)=[S:25].[S-2].[K+].[K+]>>[NH2:1][C:2]1[C:20]([Cl:21])=[CH:19][C:5]([C:6]([NH:8][CH2:9][C:10]2([OH:18])[CH:15]3[CH2:16][CH2:17][N:12]([CH2:13][CH2:14]3)[CH2:11]2)=[S:25])=[C:4]([O:22][CH3:23])[CH:3]=1
Reactant: COc1cc(N)c(Cl)cc1C(=O)NCC1(O)CN2CCC1CC2
Reactant: S=P12SP3(=S)SP(=S)(S1)SP(=S)(S2)S3
Agent: [K+]
Agent: [S-2]
Product: COc1cc(N)c(Cl)cc1C(=S)NCC1(O)CN2CCC1CC2

Procedure:
4-Amino-5-chloro-N-(3-hydroxy-1-azabicyclo[2.2.2]octan-3-ylmethyl)2-methoxybenzamide is reacted with phosphorus pentasulfide and potassium sulfide using methods known to those skilled in the art to obtain the title compound.
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:13](=[O:14])[N:12]3[CH:15]=[CH:16][S:17][C:11]3=[N:10][C:9]=2[CH3:18])=[CH:4][CH:3]=1.[CH2:19](Br)[CH3:20].[H-].[Na+]>CN(C=O)C.C(OCC)(=O)C>[CH2:19]([O:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[C:13](=[O:14])[N:12]3[CH:15]=[CH:16][S:17][C:11]3=[N:10][C:9]=2[CH3:18])=[CH:6][CH:7]=1)[CH3:20]
Reactant: CCBr
Reactant: Cc1nc2sccn2c(=O)c1-c1ccc(O)cc1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: CCOc1ccc(-c2c(C)nc3sccn3c2=O)cc1
Temperature: 80 °C

Procedure:
To a solution of Step 1 intermediate (250 mg, 0.967 mmol) in DMF (4 ml) was added ethyl bromide (0.147 g, 1.355 mmol) and NaH (0.053 g, 1.355 mmol) and heated to 80° C. for 15.0 h. After completion of the reaction, the mixture was diluted with ethyl acetate, washed with water, brine, dried over anhydrous Na2SO4 to afford 300 mg of the desired compound as a white solid; 1H NMR (300 MHz, DMSO-d6) δ 1.34 (t, J=6.6 Hz, 3H), 2.17 (s, 3H), 4.05 (q, J=6.6 Hz, 2H), 6.93-6.96 (m, 2H), 7.17-7.20 (m, 2H), 7.50 (d, J=4.5 Hz, 1H), 7.98 (d, J=4.8 Hz, 1H); ESI-MS (m/z) 311.28 (M+H)+.
Reaction SMILES: [CH3:1][C:2]1[N:11]=[C:10](O)[C:9]2[CH2:8][CH2:7][CH2:6][C:5]([CH3:19])([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[C:4]=2[N:3]=1.P(Cl)(Cl)([Cl:22])=O>>[Cl:22][C:10]1[C:9]2[CH2:8][CH2:7][CH2:6][C:5]([CH3:19])([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[C:4]=2[N:3]=[C:2]([CH3:1])[N:11]=1
Reactant: Cc1nc(O)c2c(n1)C(C)(c1ccccc1)CCC2
Reactant: O=P(Cl)(Cl)Cl
Product: Cc1nc(Cl)c2c(n1)C(C)(c1ccccc1)CCC2

Procedure:
A mixture of 2,8-dimethyl-8-phenyl-5,6,7,8-tetrahydro-quinazolin-4-ol (4 g, 16 mmol) and 25 mL of phosphorous oxychloride was heated under reflux for 2 hours, concentrated under reduced pressure and ice, water and dichloromethane were added. The mixture was basified with aqueous sodium carbonate and the organic layer was dried (sodium sulfate) and evaporated to afford 4.4 g of 4-chloro-2,8-dimethyl-8-phenyl-5,6,7,8-tetrahydroquinazoline as an oil.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([CH2:8][NH:9][C:10](=[O:15])[C:11]([F:14])([F:13])[F:12])[CH:5]=[CH:6][CH:7]=1.O1C(C2C=C(N[C:28]3[N:33]=[C:32]([C:34]4[C:35]([C:43]5[CH:44]=[C:45]([NH:49][C:50](=[O:57])[CH2:51][C:52]6[S:53][CH:54]=[CH:55][CH:56]=6)[CH:46]=[CH:47][CH:48]=5)=[N:36][N:37]5[CH:42]=[CH:41][CH:40]=[CH:39][C:38]=45)[CH:31]=[CH:30][N:29]=3)C=CC=2)=CN=C1>CC(O)C.Cl.C(Cl)Cl>[F:14][C:11]([F:12])([F:13])[C:10]([NH:9][CH2:8][C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([NH:1][C:28]2[N:33]=[C:32]([C:34]3[C:35]([C:43]4[CH:48]=[CH:47][CH:46]=[C:45]([NH:49][C:50](=[O:57])[CH2:51][C:52]5[S:53][CH:54]=[CH:55][CH:56]=5)[CH:44]=4)=[N:36][N:37]4[CH:42]=[CH:41][CH:40]=[CH:39][C:38]=34)[CH:31]=[CH:30][N:29]=2)[CH:3]=1)=[O:15]
Reactant: Nc1cccc(CNC(=O)C(F)(F)F)c1
Reactant: O=C(Cc1cccs1)Nc1cccc(-c2nn3ccccc3c2-c2ccnc(Nc3cccc(-c4cnco4)c3)n2)c1
Agent: Cl
Solvent: CC(C)O
Solvent: ClCCl
Product: O=C(Cc1cccs1)Nc1cccc(-c2nn3ccccc3c2-c2ccnc(Nc3cccc(CNC(=O)C(F)(F)F)c3)n2)c1
Temperature: 180 °C
Yield: 67 %

Procedure:
A suspension of N-[(3-aminophenyl)methyl]-2,2,2-trifluoroacetamide (46 mg, 0.21 mmol) and N-{3-[3-(2-chloro-4-pyrimidinyl)pyrazolo[1,5-a]pyridin-2-yl]phenyl}-2-(2-thienyl)acetamide (75 mg, 0.17 mmol) (see Example 2, Step B) in i-PrOH (3 mL) was acidified with 2 drops of 12 N HCl and heated in a microwave for 15 min. at 180° C. The reaction mixture was then diluted with DCM, washed with saturated aqueous NaHCO3, dried over Na2SO4, and adsorbed onto silica gel. The crude product was purified by column chromatography to generate the title compound in 67% yield. 1H NMR (400 MHz, CDCl3) δ 8.51 (d, J=6.8 Hz, 1H), 8.31 (d, J=9.1 Hz, 1H), 8.22 (d, J=5.2 Hz, 1H), 7.72-7.75 (m, 2H), 7.63 (s, 1H), 7.46 (d, J=8.3 Hz, 1H), 7.26-7.38 (m, 7H), 7.04 (s, 1H), 6.94 (m, 1H), 6.63 (d, J=5.4 Hz, 1H), 4.48 (d, J=5.7 Hz, 2H), 3.96 (s, 2H). ES-LC/MS m/z=628 [M+H]+.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:12]2[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][CH:13]=2)[C:9]([OH:11])=[O:10])=[CH:4][CH:3]=1.[CH3:19]O>Cl>[CH3:19][O:10][C:9](=[O:11])[CH:8]([C:12]1[CH:13]=[CH:14][C:15]([Cl:18])=[CH:16][CH:17]=1)[C:5]1[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=1
Reactant: O=C(O)C(c1ccc(Cl)cc1)c1ccc(Cl)cc1
Reactant: CO
Agent: Cl
Product: COC(=O)C(c1ccc(Cl)cc1)c1ccc(Cl)cc1
Yield: 78 %

Procedure:
Bis-(4-chloro-phenyl)-acetic acid (4.33 g, 15.4 mmol) was suspended in anhydrous methanol (20 mL) and concentrated hydrochloric acid (5 drops) was added. After 1 day the reaction was quenched by the addition of saturated sodium bicarbonate solution, then the organic solvent was removed in vacuo. The residue was partitioned between ethyl acetate and 50% saturated potassium carbonate solution. The organic phase was washed with brine, dried (MgSO4), filtered and concentrated to give a residue which was purified by column chromatography (SiO2), eluting with 10% ethyl acetate/petrol, to afford the title compound as a colourless oil (3.57 g, 78%); LCMS (PS-B3) Rt 3.79 min, No Ionisation. 1H NMR (CDCl3) δ 3.74 (3H, s), 4.96 (1H, s), 7.20-7.23 (4H, m), 7.28-7.32 (4H, m).
Reaction SMILES: [C:1]1([OH:7])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(Cl)(Cl)=O.[OH-].[Na+].[C:14](=O)([O:22]C1C=CC=CC=1)[O:15][C:16]1C=CC=CC=1>C(N(CC)CC)C.C(Cl)Cl.O.C(Cl)(Cl)Cl>[C:14]([O:15][CH3:16])(=[O:22])[C:2]1[C:1](=[CH:6][CH:5]=[CH:4][CH:3]=1)[OH:7]
Reactant: Oc1ccccc1
Reactant: O=C(Oc1ccccc1)Oc1ccccc1
Agent: O=C(Cl)Cl
Agent: [Na+]
Agent: [OH-]
Solvent: ClCCl
Solvent: ClC(Cl)Cl
Solvent: O
Product: COC(=O)c1ccccc1O

Procedure:
A classical preparation of diaryl carbonates involves the reaction of a hydroxy aromatic compound such as phenol with phosgene gas in a two phase reaction system comprising water, an acid acceptor such as sodium hydroxide and a solvent such as methylene chloride or chloroform. Typical interfacial conditions used to prepare diphenyl carbonate (DPC) utilize water and methylene chloride phases, sodium hydroxide as a pH control measure and triethylamine as a catalyst. Under such conditions it is possible to convert phenol to DPC in essentially quantitative yield. However, application of these same conditions to methyl salicylate results in only modest conversion of this ester-substituted phenol to the corresponding diaryl carbonate. Even the use of as much as 20 percent excess phosgene does not result in conversion of more than 70 to 75% of methyl salicylate to the bis methyl salicyl carbonate.
Reaction SMILES: Cl[CH2:2][CH2:3][CH2:4][CH2:5][N:6]1[C:11]2=[CH:12][C:13]3[C:14]([NH:22][C:23]4[CH:28]=[CH:27][C:26]([F:29])=[C:25]([Cl:30])[CH:24]=4)=[C:15]([C:20]#[N:21])[CH:16]=[N:17][C:18]=3[CH:19]=[C:10]2[O:9][CH2:8][CH2:7]1.[I-].[Na+].[CH3:33][NH:34][CH3:35].O1CCCC1.C(=O)(O)[O-].[Na+]>CN(C)C=O.[I-].C([N+](CCCC)(CCCC)CCCC)CCC.C(OCC)(=O)C>[Cl:30][C:25]1[CH:24]=[C:23]([CH:28]=[CH:27][C:26]=1[F:29])[NH:22][C:14]1[C:13]2[CH:12]=[C:11]3[N:6]([CH2:5][CH2:4][CH2:3][CH2:2][N:34]([CH3:35])[CH3:33])[CH2:7][CH2:8][O:9][C:10]3=[CH:19][C:18]=2[N:17]=[CH:16][C:15]=1[C:20]#[N:21]
Reactant: N#Cc1cnc2cc3c(cc2c1Nc1ccc(F)c(Cl)c1)N(CCCCCl)CCO3
Reactant: CNC
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: O=C([O-])O
Agent: [I-]
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: CN(C)CCCCN1CCOc2cc3ncc(C#N)c(Nc4ccc(F)c(Cl)c4)c3cc21
Temperature: 45 °C
Yield: 58 %

Procedure:
An amount of 1-(4-chlorobutyl)-9-(3-chloro-4-fluoroanilino)-2,3-dihydro-1H-[1,4]oxazino[3,2-g]quinoline-8-carbonitrile (150 mg, 0.34 mmol) was stirred in N,N-dimethylformamide (1.5 ml), and to this were added sodium iodide (76 mg, 0.51 mmol), tetrabutyl ammonium iodide (25.9 mg, 0.07 mmol), and dimethylamine in tetrahydrofuran (2M) (5.4 mL, 10.8 mmol). The mixture was heated at 45° C. for 4 hours, cooled to room temperature, and stirred with ethyl acetate and saturated sodium bicarbonate solution. After separation of the layers, the organic layer was dried over sodium sulfate and evaporated to an oil. Purification was performed by preparative thin layer chromatography (60% acetone in methanol) to give a yellow solid (89 mg, 58% yield), m.p. 105° C.; 1H NMR (DMSO-d6) δ 9.50-9.00 (bs, 1H), 8.20 (s, 1H), 7.33 (t, 1H), 7.26 (dd, 1H), 7.23 (s, 1H), 7.07 (m, 2H), 4.30 t, 2H), 3.37 (m, 4H), 2.18 (t, 2H), 2.06 (s, 6H), 1.55 (m, 2H), 1.40 (m, 2H); HRMS (EI) m/z 453.1736 (M+1).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([O:9][CH3:10])=[CH:5][C:4]=1[C:11](C1C=CC=CC=1)=[C:12]([N:17]=[N+]=[N-])[C:13]([O:15][CH3:16])=[O:14]>C1(C)C(C)=CC=CC=1>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([O:9][CH3:10])=[C:5]2[C:4]=1[CH:11]=[C:12]([C:13]([O:15][CH3:16])=[O:14])[NH:17]2
Reactant: COC(=O)C(N=[N+]=[N-])=C(c1ccccc1)c1cc(OC)ccc1OC
Solvent: Cc1ccccc1C
Product: COC(=O)c1cc2c(OC)ccc(OC)c2[nH]1
Yield: 62.8 %

Procedure:
A solution of 1.5 g (6.84 mmol) of the above-obtained methyl 2,5-dimethoxyphenyl-α-azidocinnamate in 300 ml of xylene was refluxed for 4 hours. After distilling off xylene, the residue was recrystallized from methanol to provide 1.01 g of the title compound (74.7%).
Reaction SMILES: ClC(Cl)(F)F.F[O:7][C:8]([O:11]F)([F:10])[F:9].[Br:13][C:14]([F:18])=[C:15]([F:17])[F:16]>N#N>[Br:13][C:14]1([F:18])[C:15]([F:17])([F:16])[O:11][C:8]([F:10])([F:9])[O:7]1
Reactant: FOC(F)(F)OF
Reactant: FC(F)=C(F)Br
Agent: FC(F)(Cl)Cl
Agent: N#N
Product: FC1(F)OC(F)(F)C(F)(Br)O1
Temperature: -70 °C

Procedure:
Into a multineck glass reactor equipped with: magnetic entrainment mechanical stirrer, reflux cooler, thermocouple, inner plunging pipes for introducing the reagents, and maintained at a temperature of -70° C., there were simultaneously fed--after having introduced 75 ml of dichlorodifluoromethane--0.75 l of bis(fluoroxy)difluoromethane at a flowrate of 0.375 l/h diluted with N2 (0.5 l/h) and bromotrifluoroethylene (5.4 g/h) for 2 hours.
Reaction SMILES: ClC1C=CC=C(C(OO)=[O:9])C=1.[CH2:12]1[O:35][C:15]2([CH2:32][CH2:31][C:30]3[C:29]4[C@H:20]([C@H:21]5[C@@:25]([CH2:27][CH:28]=4)([CH3:26])[C@@H:24]([OH:33])[CH2:23][CH2:22]5)[C@@H:19]([CH3:34])[CH2:18][C:17]=3[CH2:16]2)[O:14][CH2:13]1>C(Cl)Cl.C(=O)([O-])O.[Na+]>[CH2:13]1[O:14][C:15]2([CH2:32][CH2:31][C@:30]34[O:9][C@:17]3([CH2:18][C@H:19]([CH3:34])[C@@H:20]3[C:29]4=[CH:28][CH2:27][C@@:25]4([CH3:26])[C@H:21]3[CH2:22][CH2:23][C@@H:24]4[OH:33])[CH2:16]2)[O:35][CH2:12]1
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: C[C@H]1CC2=C(CCC3(C2)OCCO3)C2=CC[C@]3(C)[C@@H](O)CC[C@H]3[C@@H]21
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Product: C[C@H]1C[C@@]23CC4(CC[C@@]2(O3)C2=CC[C@]3(C)[C@@H](O)CC[C@H]3[C@@H]21)OCCO4
Temperature: -35 °C
Reaction time: 1 h
Yield: 38.2 %

Procedure:
11.6 g of solid sodium hydrogen carbonate and 15.8 g of m-chloroperbenzoic acid were added consecutively scoopwise at -35° C. to a cooled solution of 22 g of 17β-hydroxy-7β-methyloestr-5(10),9(11)-dien-3-one-3-ethyleneacetal in 350 ml of methylene dichloride. After being stirred for 1 hour at -35° C., the reaction mixture was diluted with a saturated sodium hydrogen carbonate solution followed by extraction with methylene dichloride. The organic layer was washed with 0.2M sulphite solution and with water until neutral, dried on sodium sulphate, filtered and evaporated to dryness in vacuo. After purification by chromatography through silica gel, 8.8 g of 5α,10α-epoxy-17β-hydroxy-7β-methyloestr-9(11)-en-3-one-3-ethyleneacetal were obtained.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]([C@H:10]([CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[C:11](O)=[O:12])[CH3:9])=[O:7])([CH3:4])([CH3:3])[CH3:2].C(=O)([O-])O.[NH4+].O.O[N:28]1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC>CN(C)C=O.C(OCC)(=O)C>[C:1]([O:5][C:6](=[O:7])[N:8]([C@@H:10]([C:11](=[O:12])[NH2:28])[CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[CH3:9])([CH3:4])([CH3:3])[CH3:2]
Reactant: CN(C(=O)OC(C)(C)C)[C@H](Cc1ccccc1)C(=O)O
Reactant: On1nnc2ccccc21
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: O=C([O-])O
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Solvent: O
Product: CN(C(=O)OC(C)(C)C)[C@H](Cc1ccccc1)C(N)=O
Temperature: 25 °C
Reaction time: 16 h
Yield: 70.2 %

Procedure:
A solution of (2R)-2-(N-tert-butoxycarbonyl-N-methylamino)-3-phenylpropionic acid (4.00 g, 14.32 mmol) in N,N-dimethylformamide (10 ml) was cooled to 0° C. Ammonium hydrogen carbonate (5.66 g, 71.60 mmol) was added as a solid. 1-Hydroxybenzotriazole hydrate (1.94 g, 14.32 mmol) and successively N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (2.75 g, 14.32 mmol) were added. The suspension was stirred for 16 h, while warming up to room temperature. The reaction mixture was diluted with ethyl acetate (150 ml) and extracted with saturated sodium chloride solution/water (200 ml/300 ml). The aqueous phase was extracted with ethyl acetate (3×100 ml). The combined organic layers were washed with saturated sodium hydrogen carbonate solution and dried over magnesium sulfate. The solvent was removed in vacuo. The crude product was purified by flash-chromatography on silica (70 g), using ethyl acetate/heptane as eluent, to give 2.80 g of N-((1R)-1-carbamoyl-2-phenylethyl)-N-methylcarbamic acid tert.-butylester.
Reaction SMILES: I[C:2]1[CH:7]=[CH:6][C:5]([NH2:8])=[C:4]([CH3:9])[CH:3]=1.[C:10]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)#[CH:11].C(N)CCC>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.CCOCC.[Cu]I>[CH3:9][C:4]1[CH:3]=[C:2]([C:11]#[C:10][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH:7]=[CH:6][C:5]=1[NH2:8]
Reactant: C#Cc1ccccc1
Reactant: Cc1cc(I)ccc1N
Agent: [Cu]I
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: CCOCC
Solvent: CCCCN
Product: Cc1cc(C#Cc2ccccc2)ccc1N

Procedure:
4-iodo-2-methylbenzenamine 24 (233 mg, 1 mmol) on reaction with ethynyl benzene (25a, 102 mg, 1 mmol) by employing Sonagashira coupling conditions using Pd(PPh3)4 (69.3 mg, 0.06 equiv) as catalyst, CuI (22.8 mg, 0.12 equiv) as cocatalyst, butyl amine (261 mg, 3 equiv) as base and ether as solvent and kept the reaction for 6 h. After completion of the reaction as indicated by TLC and the reaction mixture is extracted into ether (4×25 mL) from the aqueous layer and concentrated in vacuo. The compound was further purified by column chromatography using 60-120 silica gel (ethyl acetate/hexane, 1:9) to obtain 2-methyl-4-(phenylethynyl)benzenamine compounds (26a) as pure product. Anthranilic acid (27, 137 mg, 1 mmol) on reaction with acetic anhydride at 150° C. and reflux for 30 min, after completion of reaction aqueous sodium bicarbonate solution is added and extracted in ethyl acetate (4×25 mL) from the aqueous layer and concentrated in vacuo afforded 2-methyl 4H-benzo[d][1,3]oxazin-4-one compound (28) as pure product. To a stirred solution of 2-methyl-4-(phenylethynyl)benzenamine (26a, 207 mg, 1 mmol) with 2-methyl-4H-benzo[d][1,3]oxazin-4-one (28, 161 mg, 1 mmol) in acetic acid and reflux for 8 h. After completion of the reaction as indicated by TLC, the reaction mixture was quenched with NaHCO3 and extracted in ethyl acetate (4×25 mL) from the ice cold aqueous layer and dried over anhydrous Na2SO4 afforded 2-methyl-3-(2-methyl-4-(phenylethynyl)phenyl)quinazolin-4(3H)-one (29a). Reaction of 2-methyl-3-(2-methyl-4-(phenylethynyl)phenyl)quinazolin-4(3H)-one (29a, 350 mg, 1 mmol) with 2,5-dihydroxy benzaldehyde (30c, 138 mg, 1 mmol) was taken in acetic acid Then the resulting mixture was stirred under reflux conditions for 8 h and then the reaction mixture was quenched with NaHCO3 and extracted in ethyl acetate (4×25 mL) from the ice cold aqueous layer and dried over anhydrous Na2SO4. The resulting product (4c) was purified by column chromatography employing EtOAc/Hexane as an eluent.
Reaction SMILES: [CH2:1]([C:3]1[C:8](=[O:9])[NH:7][C:6]([CH3:10])=[C:5]([C:11]2[O:15][C:14]([C:16]([OH:18])=O)=[CH:13][CH:12]=2)[CH:4]=1)[CH3:2].[CH3:19][CH:20]1[CH2:22][NH:21]1>>[CH2:1]([C:3]1[C:8](=[O:9])[NH:7][C:6]([CH3:10])=[C:5]([C:11]2[O:15][C:14]([C:16]([N:21]3[CH2:22][CH:20]3[CH3:19])=[O:18])=[CH:13][CH:12]=2)[CH:4]=1)[CH3:2]
Reactant: CC1CN1
Reactant: CCc1cc(-c2ccc(C(=O)O)o2)c(C)[nH]c1=O
Product: CCc1cc(-c2ccc(C(=O)N3CC3C)o2)c(C)[nH]c1=O
Yield: 81 %

Procedure:
Method 1, Example 205 is substantially repeated except for utilizing 5-(5-ethyl-2-methyl-6-oxo-1,6-dihydropyridin-3-yl)furan-2-carboxylic acid and 2-methylaziridine to give the title compound (81% yield). LC/MS: RT 2.02 min; m/e 287 (M+H).
Reaction SMILES: [Br:1][C:2]1[N:7]=[C:6]2[N:8]([CH2:12][C:13]3[CH:18]=[CH:17][C:16]([C:19]([OH:21])=[O:20])=[CH:15][C:14]=3[Cl:22])[C:9]([CH3:11])=[N:10][C:5]2=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].[CH:29](I)([CH3:31])[CH3:30].O>CN(C)C=O.C(OCC)(=O)C>[Br:1][C:2]1[N:7]=[C:6]2[N:8]([CH2:12][C:13]3[CH:18]=[CH:17][C:16]([C:19]([O:21][CH:29]([CH3:31])[CH3:30])=[O:20])=[CH:15][C:14]=3[Cl:22])[C:9]([CH3:11])=[N:10][C:5]2=[CH:4][CH:3]=1
Reactant: Cc1nc2ccc(Br)nc2n1Cc1ccc(C(=O)O)cc1Cl
Reactant: CC(C)I
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Solvent: CCOC(C)=O
Product: Cc1nc2ccc(Br)nc2n1Cc1ccc(C(=O)OC(C)C)cc1Cl
Temperature: 25 °C
Reaction time: 24 h
Yield: 88.7 %

Procedure:
To a solution of 5-bromo-3-(2-chloro-4-carboxybenzyl)-2-methyl-3H-imidazo[4,5-b]pyridine (400 mg) in N,N-dimethylformamide (4 ml) were successively added potassium carbonate (218 mg) and isopropyl iodide (197 mg), and the mixture was stirred at room temperature for 24 hr. Water and ethyl acetate were added for partitioning. The organic layer was successively washed with water and saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. Hexane was added to the residue and the mixture was heated and allowed to cool. The precipitated crystals were collected by filtration. The crystals were dried under reduced pressure and by heating to give the objective compound (394 mg) as gray-brown crystals.
Reaction SMILES: Br[C:2]1[CH:7]=[C:6]([NH2:8])[N:5]2[N:9]=[C:10]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)[N:11]=[C:4]2[CH:3]=1.[C:18]1([CH3:27])[CH:23]=[CH:22][C:21](B(O)O)=[CH:20][CH:19]=1.C([O-])([O-])=O.[Na+].[Na+].[OH-].[Na+]>COCCOC.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O>[C:12]1([CH:10]2[N:11]=[C:4]3[CH:3]=[C:2]([C:21]4[CH:22]=[CH:23][C:18]([CH3:27])=[CH:19][CH:20]=4)[CH:7]=[C:6]([NH2:8])[N:5]3[NH:9]2)[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1
Reactant: Nc1cc(Br)cc2nc(-c3ccccc3)nn12
Reactant: Cc1ccc(B(O)O)cc1
Agent: [Pd]
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O
Solvent: COCCOC
Product: Cc1ccc(C2=CC3=NC(c4ccccc4)NN3C(N)=C2)cc1
Temperature: 90 °C
Yield: 72.8 %

Procedure:
A mixture of 30 mg (0.1 mmol) 7-bromo-2-phenyl-[1,2,4]triazolo[1,5-a]pyridin-5-ylamine, 15.5 mg (0.11 mmol) p-tolyl-boronic acid, and 0.1 ml aqueous 2M Na2CO3 in 0.5 ml 1,2-dimethoxyethane was treated with 6 mg (0.01 mmol) tetrakis-(triphenylphosphine)-palladium(0) and heated to 90° C. for 15 h. Water was added and the mixture was adjusted to pH=12 with 2M NaOH and extracted with ethylacetate. The organic phases were dried with Na2SO4 and concentrated under reduced pressure yielding 22 mg (71%) 2-phenyl-7-p-tolyl-3H-[1,2,4]triazolo[1,5-a]pyridin-5-ylamine, MS m/e (%): 300 (M+, 100).
Reaction SMILES: [F:1][C:2]([F:23])([F:22])[C:3]1[CH:4]=[C:5]([C:13]2[CH:18]=[C:17]([F:19])[C:16]([F:20])=[C:15]([F:21])[CH:14]=2)[C:6]2[NH:10][C:9](=O)[NH:8][C:7]=2[CH:12]=1.O=P(Cl)(Cl)[Cl:26]>>[Cl:26][C:9]1[NH:8][C:7]2[CH:12]=[C:3]([C:2]([F:23])([F:22])[F:1])[CH:4]=[C:5]([C:13]3[CH:18]=[C:17]([F:19])[C:16]([F:20])=[C:15]([F:21])[CH:14]=3)[C:6]=2[N:10]=1
Reactant: O=P(Cl)(Cl)Cl
Reactant: O=c1[nH]c2cc(C(F)(F)F)cc(-c3cc(F)c(F)c(F)c3)c2[nH]1
Product: Fc1cc(-c2cc(C(F)(F)F)cc3[nH]c(Cl)nc23)cc(F)c1F

Procedure:
The benzoimidazol-2-one from step (a) above (1.1 g, 3.3 mmol) reacted with POCl3 under the conditions of Example 1c to give the title compound as a white solid. MS (ESI, pos. ion) m/z: 350 (M+1).