Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([C:3]1[C:8](=[O:9])[NH:7][C:6]([CH3:10])=[C:5]([C:11]2[CH:12]=[N:13][CH:14]=[C:15]([C:17]([OH:19])=O)[CH:16]=2)[CH:4]=1)[CH3:2].[NH2:20][CH2:21][CH2:22][C:23]1[CH:31]=[CH:30][C:26]([C:27]([OH:29])=[O:28])=[CH:25][CH:24]=1>>[CH2:1]([C:3]1[C:8](=[O:9])[NH:7][C:6]([CH3:10])=[C:5]([C:11]2[CH:12]=[N:13][CH:14]=[C:15]([C:17]([NH:20][CH2:21][CH2:22][C:23]3[CH:31]=[CH:30][C:26]([C:27]([OH:29])=[O:28])=[CH:25][CH:24]=3)=[O:19])[CH:16]=2)[CH:4]=1)[CH3:2]
Reactant: NCCc1ccc(C(=O)O)cc1
Reactant: CCc1cc(-c2cncc(C(=O)O)c2)c(C)[nH]c1=O
Product: CCc1cc(-c2cncc(C(=O)NCCc3ccc(C(=O)O)cc3)c2)c(C)[nH]c1=O

Procedure:
Method 1, Example 205 is substantially repeated except for utilizing 5′-ethyl-2′-methyl-6′-oxo-1′,6′-dihydro-[3,3′]bipyridinyl-5-carboxylic acid and 4-(2-amino-ethyl)-benzoic acid to afford the title compound. MS: m/e=406 (M+H).
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.Br[CH:8]([CH3:14])[C:9]([O:11][CH2:12][CH3:13])=[O:10]>C1C=CC=CC=1>[O:4]1[CH2:5][CH2:6][N:1]([CH:8]([CH3:14])[C:9]([O:11][CH2:12][CH3:13])=[O:10])[CH2:2][CH2:3]1
Reactant: C1COCCN1
Reactant: CCOC(=O)C(C)Br
Solvent: c1ccccc1
Product: CCOC(=O)C(C)N1CCOCC1
Yield: 85.2 %

Procedure:
3.5 g (40 mmole) of morpholine were added to a mixture of 3.6 g (20 mmole) of ethyl 2-bromopropionate and 50 ml of dry benzene, and then the mixture was heated under reflux for 7 hours. At the end of this time, the reaction mixture was filtered, the filtrate was concentrated by evaporation under reduced pressure, and the residue was dissolved in chloroform. The resulting solution was washed with water, dried, and concentrated by evaporation under reduced pressure, to give 3.19 g of ethyl 2-morpholinopropionate. 10 ml of methanol and 10 ml of a concentrated aqueous solution of ammonium hydroxide were then added to 3.1 g (16.6 mmole) of this ethyl 2-morpholinopropionate, and the resulting mixture was heated under reflux for 28 hours. At the end of this time, the reaction mixture was concentrated by evaporation under reduced pressure, and the residue was dried by heating it under reduced pressure, to give 2-morpholinopropionamide as a precipitate.
Reaction SMILES: COC1C=CC(P2(SP(C3C=CC(OC)=CC=3)(=S)S2)=[S:10])=CC=1.[C:23]([C:26](=[N:36][O:37][CH:38]([CH3:40])[CH3:39])[C:27]([N:31]1[CH:35]=[N:34][CH:33]=[N:32]1)=[N:28][O:29][CH3:30])(=O)[NH2:24].C(OC(C)C)(C)C>O1CCCC1>[CH:38]([O:37][N:36]=[C:26]([C:23](=[S:10])[NH2:24])[C:27]([N:31]1[CH:35]=[N:34][CH:33]=[N:32]1)=[N:28][O:29][CH3:30])([CH3:40])[CH3:39]
Reactant: CON=C(C(=NOC(C)C)C(N)=O)n1cncn1
Reactant: COc1ccc(P2(=S)SP(=S)(c3ccc(OC)cc3)S2)cc1
Solvent: C1CCOC1
Solvent: CC(C)OC(C)C
Product: CON=C(C(=NOC(C)C)C(N)=S)n1cncn1
Temperature: 40 °C
Reaction time: 2 h
Yield: 57.8 %

Procedure:
0.77 g (1.9 mmol) of Lawesson's reagent was added, at room temperature, to a tetrahydrofuran (8 ml) solution containing 0.40 g (1.6 mmol) of 1-(2-carbamoyl-2-isopropoxyimino-1-methoxyiminoethyl)-1H-1,2,4-triazole, followed by stirring at 40° C. for 2 hours and then at 60° C. for 3 hours. The reaction mixture was cooled to room temperature. Thereto was added diisopropyl ether. The mixture was washed with water and an aqueous saturated sodium chloride solution and dried over anhydrous sodium sulfate. The solvent was distilled off. The resulting residue was purified by silica gel column chromatography (elutant:ethyl acetate/hexane=1/2) to obtain 0.25 g (yield: 58%) of a title compound as a yellow powder.
Reaction SMILES: [CH2:1]([N:8]1[CH:12]=[C:11](/[CH:13]=[CH:14]/[C:15]2[N:20]([CH2:21][CH2:22][CH3:23])[C:19](=[O:24])[N:18]([CH2:25][CH2:26][CH3:27])[C:17](=[O:28])[C:16]=2[N+:29]([O-])=O)[CH:10]=[N:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Sn](Cl)Cl.Cl>>[CH2:1]([N:8]1[CH:12]=[C:11]([C:13]2[NH:29][C:16]3[C:17](=[O:28])[N:18]([CH2:25][CH2:26][CH3:27])[C:19](=[O:24])[N:20]([CH2:21][CH2:22][CH3:23])[C:15]=3[CH:14]=2)[CH:10]=[N:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CCCn1c(/C=C/c2cnn(Cc3ccccc3)c2)c([N+](=O)[O-])c(=O)n(CCC)c1=O
Agent: Cl
Agent: Cl[Sn]Cl
Product: CCCn1c(=O)c2[nH]c(-c3cnn(Cc4ccccc4)c3)cc2n(CCC)c1=O

Procedure:
To a solution of 6-{(1E)-2-[1-benzylpyrazol-4-yl]vinyl}-5-nitro-1,3-dipropyl-1,3-dihydropyrimidine-2,4-dione prepared in Example 18 (0.24 g, 0.57 mmol) in N,N′-dimethyl formamide (4 ml) was added tin (II) chloride (1.07 g, 5.7 mmol). The reaction mixture was heated to 150° for 2 hours. After cooling to room temperature 2N HCl (6 ml) was added and a light brown precipitate formed and was removed by filtration and washed with water (5 ml). The precipitate (0,025 g) was dissolved in DMSO (0.5 ml) and purified using preparative HPLC to yield 6-[1-benzylpyrazol-4-yl]-1,3-dipropyl-1,3-dihydropyrrolo[3,2-d]pyrimidine-2,4-dione, (0.009 g, M+1=392.2)
Reaction SMILES: [C:1]([OH:6])(=O)[C@H:2]([CH3:4])[OH:3].O.ON1C2C=CC=CC=2N=N1.Cl.CN(CCCN=C=NCC)C.C(N(CC)CC)C.[CH3:37][C@H:38]1[NH:43][CH2:42][CH2:41][N:40]([C:44]2[N:45]([CH2:66][C:67]([F:70])([F:69])[F:68])[C:46]3[C:51]([N:52]=2)=[C:50]([N:53]2[CH2:58][CH2:57][O:56][CH2:55][CH2:54]2)[N:49]=[C:48]([C:59]2[CH:60]=[N:61][C:62]([NH2:65])=[N:63][CH:64]=2)[N:47]=3)[CH2:39]1>C(Cl)Cl.CO.CN(C)C=O.C(Cl)Cl>[NH2:65][C:62]1[N:63]=[CH:64][C:59]([C:48]2[N:47]=[C:46]3[C:51]([N:52]=[C:44]([N:40]4[CH2:41][CH2:42][N:43]([C:1](=[O:6])[C@@H:2]([OH:3])[CH3:4])[C@H:38]([CH3:37])[CH2:39]4)[N:45]3[CH2:66][C:67]([F:69])([F:68])[F:70])=[C:50]([N:53]3[CH2:54][CH2:55][O:56][CH2:57][CH2:58]3)[N:49]=2)=[CH:60][N:61]=1
Reactant: C[C@H](O)C(=O)O
Reactant: C[C@@H]1CN(c2nc3c(N4CCOCC4)nc(-c4cnc(N)nc4)nc3n2CC(F)(F)F)CCN1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Solvent: O
Product: C[C@H](O)C(=O)N1CCN(c2nc3c(N4CCOCC4)nc(-c4cnc(N)nc4)nc3n2CC(F)(F)F)C[C@H]1C
Reaction time: 120 h
Yield: 36.3 %

Procedure:
L-Lactic acid (48.2 μl, 0.55 mmol), 1-hydroxybenzotriazole monohydrate (42.0 mg, 0.27 mmol), 1-(dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (105.1 mg, 0.55 mmol), and triethylamine (76.4 μl, 0.55 mmol) were added to a methylene chloride (3.0 ml)-N,N-dimethylformamide (3.0 ml) mixture solution of 5-{8-[(3R)-3-methylpiperazin-1-yl]-6-morpholin-4-yl-9-(2,2,2-trifluoroethyl)-9H-purin-2-yl}pyrimidin-2-amine (131.1 mg, 0.27 mmol) at room temperature. The resulting mixture was stirred for 5 days followed by the addition of L-lactic acid (48.2 μl, 0.55 mmol), 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride (105.1 mg, 0.55 mmol), and triethylamine (76.4 μl, 0.55 mmol). The resulting mixture was stirred for 1 day and then the reaction mixture was poured into methylene chloride-methanol (10:1), washed with saturated aqueous sodium hydrogen carbonate solution, and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure and the resulting residue was purified by preparative thin layer silica gel chromatography (methylene chloride:methanol=10:1) to give the title compound (53.9 mg, 36%) as a pale yellow solid.
Reaction SMILES: [Br:1][C:2]1[CH:15]=[CH:14][C:5]([O:6][Si:7]([C:10]([CH3:13])([CH3:12])[CH3:11])([CH3:9])[CH3:8])=[CH:4][C:3]=1[CH3:16].[Br:17]N1C(=O)CCC1=O.N(C(C)(C)C#N)=NC(C)(C)C#N>C(OCC)(=O)C>[Br:1][C:2]1[CH:15]=[CH:14][C:5]([O:6][Si:7]([C:10]([CH3:11])([CH3:12])[CH3:13])([CH3:8])[CH3:9])=[CH:4][C:3]=1[CH2:16][Br:17]
Reactant: Cc1cc(O[Si](C)(C)C(C)(C)C)ccc1Br
Reactant: O=C1CCC(=O)N1Br
Agent: CC(C)(C#N)N=NC(C)(C)C#N
Solvent: CCOC(C)=O
Product: CC(C)(C)[Si](C)(C)Oc1ccc(Br)c(CBr)c1
Yield: 30.1 %

Procedure:
To a solution of (4-bromo-3-methylphenoxy)(tert-butyl)dimethylsilane (6.97 g) and N-bromosuccinimide (6.21 g) in ethyl acetate (100 mL) was added 2,2′-azobis(isobutyronitrile) (383 mg), and the mixture was refluxed for 17 hr. The mixture was washed with saturated aqueous sodium hydrogen carbonate solution and saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure and the residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (2.65 g) as a colorless oil.
Reaction SMILES: [C:1]([OH:20])(=O)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8]/[CH:9]=[CH:10]\[CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18].C(Cl)(=O)C([Cl:24])=O>CCCCCC>[C:1]([Cl:24])(=[O:20])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8]/[CH:9]=[CH:10]\[CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18]
Reactant: O=C(Cl)C(=O)Cl
Reactant: CCCCCCCC/C=C\CCCCCCCC(=O)O
Solvent: CCCCCC
Product: CCCCCCCC/C=C\CCCCCCCC(=O)Cl
Reaction time: 1.5 h

Procedure:
A 1.0 g portion of oleic acid was dissolved in 10 ml of hexane. A 2.0 ml portion of oxalyl chloride was added and this mixture was stirred under dry conditions for 1.5 hours, then evaporated in vacuo, giving the desired compound as a colorless oil.
Reaction SMILES: [CH3:1][C:2]1([CH3:16])[O:14][C:6]2=[CH:7][C:8]3[C:9]([CH:13]=[C:5]2[CH:4]2O[CH:3]12)=[N:10][O:11][N:12]=3.[C-:17]#[N:18].C([Al+]CC)C.[OH-].[Na+]>C1(C)C=CC=CC=1>[C:17]([C:4]1[C:5]2[C:6](=[CH:7][C:8]3[C:9]([CH:13]=2)=[N:10][O:11][N:12]=3)[O:14][C:2]([CH3:16])([CH3:1])[CH:3]=1)#[N:18]
Reactant: CC1(C)Oc2cc3nonc3cc2C2OC21
Reactant: [C-]#N
Agent: CC[Al+]CC
Agent: [Na+]
Agent: [OH-]
Solvent: Cc1ccccc1
Product: CC1(C)C=C(C#N)c2cc3nonc3cc2O1
Temperature: 0 °C

Procedure:
To a mixture of 3.9 g of 7,8-dihydro-6,6-dimethyl-7,8-epoxy-6H-pyrano[2,3-f]benzo-2,1,3-oxadiazole and 80 ml of toluene was added dropwise 90 ml of a 1.0M solution of diethyl-aluminum cyanide in toluene with stirring under ice-cooling, followed by stirring at room temperature for 2 hours. The reaction mixture was poured into ice-water, and 2N NaOH was added thereto. The mixture was extracted with methylene chloride, and the organic layer was washed with water and dried. The solvent was removed by distillation, and the residue was purified by silica gel column chromatography (developing solution: CH2Cl2) to obtain 2.9 g of 8-cyano-6,6-dimethyl-6H-pyrano[2,3-f]benzo-2,1,3-oxadiazole represented by formula shown below.
Reaction SMILES: [N:1]([C:4]1[CH:5]=[CH:6][C:7]([CH3:30])=[C:8]([C:10]([C:12]2[CH:17]=[CH:16][C:15]([NH:18][C:19]3[CH:24]=[CH:23][C:22](C(F)(F)F)=[CH:21][CH:20]=3)=[CH:14][C:13]=2[Cl:29])=[O:11])[CH:9]=1)=[N+:2]=[N-:3].N[C:32]1C=CC(C)=C(C(C2C=CC(NC3C=C(C)C=CC=3)=CC=2Cl)=O)C=1>>[N:1]([C:4]1[CH:5]=[CH:6][C:7]([CH3:30])=[C:8]([C:10]([C:12]2[CH:17]=[CH:16][C:15]([NH:18][C:19]3[CH:20]=[C:21]([CH3:32])[CH:22]=[CH:23][CH:24]=3)=[CH:14][C:13]=2[Cl:29])=[O:11])[CH:9]=1)=[N+:2]=[N-:3]
Reactant: Cc1cccc(Nc2ccc(C(=O)c3cc(N)ccc3C)c(Cl)c2)c1
Reactant: Cc1ccc(N=[N+]=[N-])cc1C(=O)c1ccc(Nc2ccc(C(F)(F)F)cc2)cc1Cl
Product: Cc1cccc(Nc2ccc(C(=O)c3cc(N=[N+]=[N-])ccc3C)c(Cl)c2)c1

Procedure:
The reaction was carried out similarly as described in the preparation of compound 416, using compound 464 (1.17 mmol). The crude product was purified by flash chromatography using EtOAc/petroleum ether (40-60) 1:9 and 1:6 as the eluent to afford the title compound as yellow syrup.
Reaction SMILES: [C:1]([C:5]1[CH:12]=[CH:11][C:8]([CH:9]=O)=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[CH2:13]([NH2:21])[CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.[BH4-].[Na+]>CO.Cl>[C:1]([C:5]1[CH:12]=[CH:11][C:8]([CH2:9][NH:21][CH2:13][CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(C)(C)c1ccc(C=O)cc1
Reactant: NCCc1ccccc1
Agent: Cl
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Product: CC(C)(C)c1ccc(CNCCc2ccccc2)cc1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 91.1 %

Procedure:
0.65 ml of 4-tert-butylbenzaldehyde (3.7 mmol) and 0.32 ml of phenethylamine (2.5 mmol) were dissolved in 7.5 ml methanol at rt, and after stirring for 30 min at rt, were refluxed for 2¼ h. After cooling down to rt, 142 mg (3.7 mmol) of sodium borohydride were added and after stirring for 15 min at rt, the reaction mixture was then refluxed for 3.5 h. After cooling down to rt, the reaction mixture was treated with 6 drops 1 N HCl and concentrated in vacuo. The residue was diluted with water/EtOAc. After separation of the organic phase, the aqueous phase was extracted with EtOAc and the combined organic phases were washed with brine, dried with magnesium sulfate, filtered off and concentrated in vacuo. The residue was purified by column chromatography (40 g silica gel; EtOAc/heptane 1:2) to give 609 mg of colorless oil (91%). MS (ISP) 268.3 (M+H)+.
Reaction SMILES: [K].[CH3:2][C:3]1[CH:4]=[C:5]([SH:10])[CH:6]=[C:7]([CH3:9])[CH:8]=1.F[C:12]1[CH:17]=[CH:16][C:15]([N+:18]([O-:20])=[O:19])=[CH:14][CH:13]=1>CN1CCCC1=O>[CH3:9][C:7]1[CH:6]=[C:5]([S:10][C:12]2[CH:17]=[CH:16][C:15]([N+:18]([O-:20])=[O:19])=[CH:14][CH:13]=2)[CH:4]=[C:3]([CH3:2])[CH:8]=1
Reactant: O=[N+]([O-])c1ccc(F)cc1
Reactant: Cc1cc(C)cc(S)c1
Agent: [K]
Solvent: CN1CCCC1=O
Product: Cc1cc(C)cc(Sc2ccc([N+](=O)[O-])cc2)c1
Temperature: 160 °C
Reaction time: 5 h
Yield: 63.3 %

Procedure:
0.25 g (0.0014 mol) of 3,5-dimethylthiophenol potassium salt were dissolved in 5 ml of 1-methyl-2-pyrrolidone, treated with 0.19 g (0.00134 mol) of 1-fluoro-4-nitrobenzene and a spatula tip of Cu powder and stirred at 160° C. for about 5 hrs. Thereafter, the solvent was removed by distillation, the residue was partitioned in water/ethyl acetate and the organic phase was washed with sat. sodium chloride solution and dried over MgSO4. After filtration and removal of the solvent the residue was chromatographed on silica gel with ethyl acetate/hexane 1:15. There was obtained 0.22 g (62%) of 1,3-dimethyl-5-(4-nitrophenylsulphanyl)-benzene as a viscous, yellow oil. MS (EI): me/e=259 (C14H13NO2S+).
Reaction SMILES: [CH2:1]([C@@H:8]1[C@@H:16]([OH:17])[C@H:15]([CH3:18])[O:14][C:13](=[O:19])[C@@H:12]([NH:20][C:21]([C:23]2[C:28]([OH:29])=[C:27]([O:30][CH3:31])[CH:26]=[CH:25][N:24]=2)=[O:22])[CH2:11][O:10][C:9]1=[O:32])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].[I-].[Na+].[C:41]([O:44][CH2:45]Br)(=[O:43])[CH3:42]>CC(C)=O.C(OCC)(=O)C.O>[C:41]([O:44][CH2:45][O:29][C:28]1[C:23]([C:21]([NH:20][C@H:12]2[CH2:11][O:10][C:9](=[O:32])[C@H:8]([CH2:1][C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=3)[C@@H:16]([OH:17])[C@H:15]([CH3:18])[O:14][C:13]2=[O:19])=[O:22])=[N:24][CH:25]=[CH:26][C:27]=1[O:30][CH3:31])(=[O:43])[CH3:42]
Reactant: COc1ccnc(C(=O)N[C@H]2COC(=O)[C@H](Cc3ccccc3)[C@@H](O)[C@H](C)OC2=O)c1O
Reactant: CC(=O)OCBr
Agent: O=C([O-])[O-]
Agent: [I-]
Agent: [K+]
Solvent: O
Solvent: CC(C)=O
Solvent: CCOC(C)=O
Product: COc1ccnc(C(=O)N[C@H]2COC(=O)[C@H](Cc3ccccc3)[C@@H](O)[C@H](C)OC2=O)c1OCOC(C)=O
Temperature: 2.5 °C
Reaction time: 0.33 h
Yield: 90.3 %

Procedure:
To a solution of Compound 1 (40 g, 90.09 mmol) in dry acetone (360 mL) was added powdered potassium carbonate (14.92 g, 108 mmol) in three portions over 5 min, the mixture stirred at 0-5° C. for 20 min and sodium iodide (2.697 g, 18 mmol) was added. Bromomethyl acetate (16.54 g, 108.11 mmol) was then added dropwise over 15 min using an addition funnel, the mixture stirred at 0-5° C. for 1 h then at RT for 3 hours. The mixture was diluted with ethyl acetate (700 mL) and water (200 mL), the organic phase rinsed with water (×2), brine. (×2), dried over sodium sulfate and concentrated in vacuo to give a solid, which was passed through silica gel (1:1 hexanes/acetone) to give 42 g of Compound 3. (M+1)+=517. Spectral data were consistent with the assigned structure.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[CH:4][C:5]2[N:9]=[C:8](C(Cl)(Cl)Cl)[N:7]([C:14]3[CH:19]=[CH:18][N:17]=[C:16]([NH2:20])[N:15]=3)[C:6]=2[CH:21]=1.[F:22][C:23]([F:27])([F:26])[CH2:24][OH:25].C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C)C=O>[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[N:9]=[C:8]([O:25][CH2:24][C:23]([F:27])([F:26])[F:22])[N:7]([C:14]3[CH:19]=[CH:18][N:17]=[C:16]([NH2:20])[N:15]=3)[C:6]=2[CH:21]=1
Reactant: OCC(F)(F)F
Reactant: Nc1nccc(-n2c(C(Cl)(Cl)Cl)nc3ccc(Br)cc32)n1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Product: Nc1nccc(-n2c(OCC(F)(F)F)nc3ccc(Br)cc32)n1
Yield: 54.5 %

Procedure:
A mixture of 4-[6-bromo-2-(trichloromethyl)-1H-1,3-benzodiazol-1-yl]pyrimidin-2-amine (500 mg, 1.23 mmol), 2,2,2-trifluoroethan-1-ol (500 mg, 5.00 mmol) and cesium carbonate (2.5 g, 7.67 mmol) in N,N-dimethylformamide (5 mL) placed in a 10-mL sealed tube maintained under nitrogen was irradiated with microwave radiation at 70° C. for 2 hr. The residue was purified on a C18 column (acetonitrile/water, 5:95-80:20) to yield 260 mg (46%) of 4-[6-bromo-2-(2,2,2-trifluoroethoxy)-1H-1,3-benzodiazol-1-yl]pyrimidin-2-amine as a yellow solid. LC-MS: m/z=+388 (M+H)+.
Reaction SMILES: Br[CH2:2][C:3](=[N:7][C:8]1[CH:21]=[CH:20][C:19]([N+:22]([O-:24])=[O:23])=[CH:18][C:9]=1[C:10]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)=[O:11])[O:4][CH2:5][CH3:6].CN(C)C=O.[N-:30]=[N+:31]=[N-:32].[Na+].C(OCC)(=O)C>O>[N:30]([CH2:2][C:3](=[N:7][C:8]1[CH:21]=[CH:20][C:19]([N+:22]([O-:24])=[O:23])=[CH:18][C:9]=1[C:10]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)=[O:11])[O:4][CH2:5][CH3:6])=[N+:31]=[N-:32]
Reactant: [N-]=[N+]=[N-]
Reactant: CCOC(CBr)=Nc1ccc([N+](=O)[O-])cc1C(=O)c1ccccc1
Agent: [Na+]
Solvent: O
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: CCOC(CN=[N+]=[N-])=Nc1ccc([N+](=O)[O-])cc1C(=O)c1ccccc1
Reaction time: 0.67 h

Procedure:
To a solution of 3.3 parts of 2-(2-bromo-1-ethoxyethylideneamino)-5-nitrobenzophenone produced in Step (1) in 15 parts by volume of dimethylformamide is added 0.5 part of sodium azide at a room temperature with stirring. After the stirring is continued for further 40 minutes. Ethyl acetate and water are added to the reaction mixture and shaken well. The ethyl acetate layer separated is washed with water and dried over anhydrous sodium sulfate. Evaporation of the solvent gives 2-(2-azido-1-ethoxyethylideneamino)-5-nitrobenzophenone as an oily substance. The product shows an absorption band at 2077 cm-1 due to N3 in an infrared absorption spectrum.
Reaction SMILES: Cl[C:2]1[C:17]([N+:18]([O-:20])=[O:19])=[CH:16][C:15]([N+:21]([O-:23])=[O:22])=[CH:14][C:3]=1[C:4]([NH:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][OH:13])=[O:5].CC[N:26]([CH2:29][CH3:30])CC.N1CC1>CCOC(C)=O>[N:26]1([C:2]2[C:17]([N+:18]([O-:20])=[O:19])=[CH:16][C:15]([N+:21]([O-:23])=[O:22])=[CH:14][C:3]=2[C:4]([NH:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][OH:13])=[O:5])[CH2:29][CH2:30]1
Reactant: CCN(CC)CC
Reactant: O=C(NCCCCCCO)c1cc([N+](=O)[O-])cc([N+](=O)[O-])c1Cl
Agent: C1CN1
Solvent: CCOC(C)=O
Product: O=C(NCCCCCCO)c1cc([N+](=O)[O-])cc([N+](=O)[O-])c1N1CC1
Yield: 84.3 %

Procedure:
A solution of 2-chloro-N-(6-hydroxyhexyl)-3,5-dinitrobenzamide (16) [for preparation see Example 14 below] (118 mg, 0.34 mmol) and Et3N (200 mg) in EtOAc (200 mL) was treated with aziridine (100 mg) at room temperature for 3 h. The mixture was diluted with EtOAc and washed three times with water, after dry, concentrated under reduced pressure until about 20 mL, the yellow solid was collected and gave 101 mg product (84%); 1H NMR [(CD3)2SO] δ 8.74 (d, J=2.8 Hz, 1 H), 8.63 (m, 1 H), 8.29 (d, J=2.8 Hz, 1 H), 4.31 (m, 1 H), 3.39 (m, 2 H), 3.25 (m, 2 H), 2.37 (s, 4 H), 1.56 (m, 2 H), 1.43 (m, 2 H), 1.33 (m, 4 H). Anal. (C15H20N4O6) C, H, N.
Reaction SMILES: [CH3:1][S:2]([OH:5])(=[O:4])=[O:3].ClC1N2C=CC=CC2=NC=1COC1C=CC([C:24]2[C:25](=[O:39])[C:26]([CH3:38])([CH3:37])[O:27][C:28]=2[C:29]2[CH:34]=[CH:33][C:32]([O:35][CH3:36])=[CH:31][CH:30]=2)=CC=1>C(Cl)Cl.C(OCC)C>[CH3:1][S:2]([OH:5])(=[O:4])=[O:3].[CH3:36][O:35][C:32]1[CH:31]=[CH:30][C:29]([C:28]2[O:27][C:26]([CH3:37])([CH3:38])[C:25](=[O:39])[CH:24]=2)=[CH:34][CH:33]=1
Reactant: COc1ccc(C2=C(c3ccc(OCc4nc5ccccn5c4Cl)cc3)C(=O)C(C)(C)O2)cc1
Agent: CS(=O)(=O)O
Solvent: CCOCC
Solvent: ClCCl
Product: COc1ccc(C2=CC(=O)C(C)(C)O2)cc1
Temperature: 25 °C
Reaction time: 4 h
Yield: 159.1 %

Procedure:
Methanesulfonic acid (50.5 mg, 0.52 mmol) was added to a solution of 4-(4-((3-chloroimidazo[1,2-a]pyridin-2-yl)methoxy)phenyl)-5-(4-methoxyphenyl)-2,2-dimethylfuran-3(2H)-one (250 mg, 0.52 mmol) in DCM (2.5 ml) and diethyl ether (25 mL) at RT under an atmosphere of nitrogen. The reaction mixture was stirred at RT for 4 h upon which the compound was filtered, washed with 20% DCM in diethyl ether and dried in vacuo to afford 4-(4-(3-chloroimidazo[1,2-a]pyridin-2-yl)methoxy)phenyl)-5-(4-methoxyphenyl)-2,2-dimethylfuran-3(2H)-one methanesulfonate (260 mg, 86%) as white solid. 1H NMR: 500 MHz, DMSO-d6: δ 8.55 (d, 1H), 8.0 (s, 1H), 7.65 (Ar, 3H), 7.3-6.85 (Ar, 7H), 5.2 (s, 2H), 3.85 (s, 3H), 2.15 (s, 3H) 1.25 (s, 6H), HPLC: (98.8%, Condition-A).
Reaction SMILES: [C:1]1([S:7]([N:10]2[C:14]3=[N:15][CH:16]=[C:17]([O:19][CH3:20])[CH:18]=[C:13]3[CH:12]=[CH:11]2)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C([N-]C(C)C)(C)C.[Li+].C([Li])CCC.CCCCCC.C(NC(C)C)(C)C.[O:47]1[CH2:51][CH2:50][CH2:49][CH:48]1[CH2:52][CH:53]=[O:54]>O1CCCC1>[C:1]1([S:7]([N:10]2[C:14]3=[N:15][CH:16]=[C:17]([O:19][CH3:20])[CH:18]=[C:13]3[CH:12]=[C:11]2[CH:53]([OH:54])[CH2:52][CH:48]2[CH2:49][CH2:50][CH2:51][O:47]2)(=[O:8])=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: COc1cnc2c(ccn2S(=O)(=O)c2ccccc2)c1
Reactant: O=CCC1CCCO1
Agent: CC(C)[N-]C(C)C
Agent: [Li+]
Agent: [Li]CCCC
Solvent: CC(C)NC(C)C
Solvent: C1CCOC1
Solvent: CCCCCC
Product: COc1cnc2c(c1)cc(C(O)CC1CCCO1)n2S(=O)(=O)c1ccccc1
Temperature: -78 °C
Reaction time: 0.08 h
Yield: 29.9 %

Procedure:
To a solution of 1-benzenesulfonyl-5-methoxy-1H-pyrrolo[2,3-b]pyridine (prepared as in Example 10, 6 g, 20.8 mmol) in dry tetrahydrofuran (40 mL) at −78° C. was added freshly prepared lithium diisopropylamide [prepared by adding 1.6 M n-butyllithium in n-hexane (19.5 mL, 31.2 mmol) to a 0° C. solution of diisopropylamine (4.7 mL, 32.8 mmol) in dry tetrahydrofuran (20 mL)] dropwise. The mixture was stirred at −78° C. for 5 min and then treated with (tetrahydro-furan-2-yl)-acetaldehyde (3.5 g, 30.7 mmol) dropwise. The resulting mixture was stirred at −78° C. for 1 h and quenched with brine. The mixture was extracted with ethyl acetate (2×200 mL), washed with brine, dried over anhydrous sodium sulfate and concentrated in vacuo. Purification by flash silica gel chromatography (silica gel from QingDao, 200-300 mesh, glass column from Shanghai SD company, 25% ethyl acetate/hexanes) afforded 1-(1-benzenesulfonyl-5-methoxy-1H-pyrrolo[2,3-b]pyridin-2-yl)-2-(tetrahydro-furan-2-yl)-ethanol (2.5 g, 30%) as a white solid: LC/MS m/e calcd for C21H22N2O5S [M+H]+ 403.47, observed 403.2.
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[NH:10][C:9]([CH2:11][CH2:12][CH3:13])=[N:8][C:7]=1[C:14]([OH:17])([CH3:16])[CH3:15])=[O:5])[CH3:2].[C:18]1([C:24]([C:50]2[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=2)([C:44]2[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=2)[N:25]2[C:29]([C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=3[C:36]3[CH:41]=[CH:40][C:39]([CH2:42]Br)=[CH:38][CH:37]=3)=[N:28][N:27]=[N:26]2)[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.C(=O)([O-])[O-].[K+].[K+]>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.CC(C)=O>[CH2:1]([O:3][C:4]([C:6]1[N:10]([CH2:42][C:39]2[CH:38]=[CH:37][C:36]([C:31]3[CH:32]=[CH:33][CH:34]=[CH:35][C:30]=3[C:29]3[N:25]([C:24]([C:50]4[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=4)([C:44]4[CH:45]=[CH:46][CH:47]=[CH:48][CH:49]=4)[C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)[N:26]=[N:27][N:28]=3)=[CH:41][CH:40]=2)[C:9]([CH2:11][CH2:12][CH3:13])=[N:8][C:7]=1[C:14]([OH:17])([CH3:15])[CH3:16])=[O:5])[CH3:2]
Reactant: BrCc1ccc(-c2ccccc2-c2nnnn2C(c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Reactant: CCCc1nc(C(C)(C)O)c(C(=O)OCC)[nH]1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: O=C([O-])[O-]
Agent: [Br-]
Solvent: CC(C)=O
Product: CCCc1nc(C(C)(C)O)c(C(=O)OCC)n1Cc1ccc(-c2ccccc2-c2nnnn2C(c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Yield: 93.9 %

Procedure:
4-(1-Hydroxy-1-methylethyl)-2-propyl-1H-imidazole-5-carboxylic acid ethyl ester (100 g), N-(triphenylmethyl)-5-(4′-bromomethyl biphenyl-2-yl)tetrazole (250 g), potassium carbonate (170 g) & tetra butyl ammonium bromide (15 g) in acetone (2.5 L) were refluxed for 10-16 hours. Progress of reaction was monitor by HPLC. After completion of reaction, reaction mass was cooled and filtered to remove the salts. Inorganic salts were washed with acetone (300 mL). Acetone from combine the filtrate and washings was distilled. The residue obtained was crystallized in acetonitrile to get ethyl-4-(1-hydroxy-1-methylethyl)-2-propyl-1-{4-[2-(trityltetrazol-5-yl)phenyl]phenyl}methylimidazole-5-carboxylate (280 g).