Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[N:3]=[CH:4][CH:5]=[C:6]2[CH:10]=[C:9]([CH:11]=[O:12])[NH:8][C:7]=12.[C:13]1([Mg]Br)[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.CCOCC.[NH4+].[Cl-]>C1COCC1>[Cl:1][C:2]1[N:3]=[CH:4][CH:5]=[C:6]2[CH:10]=[C:9]([CH:11]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[OH:12])[NH:8][C:7]=12
Reactant: O=Cc1cc2ccnc(Cl)c2[nH]1
Reactant: Br[Mg]c1ccccc1
Agent: [Cl-]
Agent: [NH4+]
Solvent: CCOCC
Solvent: C1CCOC1
Product: OC(c1ccccc1)c1cc2ccnc(Cl)c2[nH]1
Reaction time: 2 h
Yield: 67 %

Procedure:
To a solution of 7-chloro-1H-pyrrolo[2,3-c]pyridine-2-carboxaldehyde (Example 138) (1.0 g, 5.5 mmol) in THF (27.7 mL) was added 3.0 M phenylmagnesium bromide in Et2O (3.8 mL, 11.3 mmol) at −78° C. under a nitrogen atmosphere. After stirring for ca. 2 h, additional 3.0 M phenylmagnesium bromide in Et2O (0.92 mL, 2.7 mmol) was added. The reaction mixture was stirred for another 1.5 h. The reaction mixture was poured into a saturated NH4Cl solution and extracted with EtOAc (3×). The combined organic extracts were washed with saturated NaCl, and dried over Na2SO4. Filtration and concentration provided the crude material, which was purified by flash chromatography to provide (7-chloro-1H-pyrrolo[2,3-c]pyridin-2-yl)(phenyl)methanol (0.97 g, 67%) as an off-white solid: 1H NMR (300 MHz, CD3OD) δ5.99 (1H, s), 6.42 (1H, s), 7.25-7.48 (6H, m), 7.82 (1H, d, J=5.4 Hz); ESI MS m/z 259 [C14H11ClN2O+H]+; HPLC (Method A) >99% (AUC), tR=13.8 min.
Reaction SMILES: [OH:1][C:2]1[C:3](=[O:20])[CH:4]=[C:5]([CH2:8][NH:9][S:10]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[CH3:19])(=[O:12])=[O:11])[O:6][CH:7]=1.[OH:21][C:22]1C(=O)C=C(CNS(C2C=CC=CC=2)(=O)=O)OC=1CO>>[OH:1][C:2]1[C:3](=[O:20])[CH:4]=[C:5]([CH2:8][NH:9][S:10]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[CH3:19])(=[O:12])=[O:11])[O:6][C:7]=1[CH2:22][OH:21]
Reactant: Cc1ccccc1S(=O)(=O)NCc1cc(=O)c(O)co1
Reactant: O=c1cc(CNS(=O)(=O)c2ccccc2)oc(CO)c1O
Product: Cc1ccccc1S(=O)(=O)NCc1cc(=O)c(O)c(CO)o1
Yield: 62.78 %

Procedure:
N-(5-Hydroxy-6-hydroxymethyl-4-oxo-4H-pyran-2-ylmethyl)-2-methyl-benzenesulfonamide (9-02) (9.0 g, 62.78%) was synthesized as a white solid from N-(5-hydroxy-4-oxo-4H-pyran-2-ylmethyl)-2-methyl-benzenesulfonamide (8-02) (13.0 g, 44.06 mmol) following the procedure described for N-(5-hydroxy-6-hydroxymethyl-4-oxo-4H-pyran-2-ylmethyl)-benzenesulfonamide (9-01).
Reaction SMILES: [NH:1]1[C:5]([C:6]2[CH:11]=[CH:10][C:9]([NH:12][C:13]([CH:15]3[CH:19]([C:20]4[CH:25]=[CH:24][CH:23]=[C:22]([Cl:26])[C:21]=4[CH3:27])[C:18]([C:30]4[CH:35]=[CH:34][C:33]([Cl:36])=[CH:32][C:31]=4[F:37])([C:28]#[N:29])[CH:17]([CH2:38][C:39]([CH3:42])([CH3:41])[CH3:40])[NH:16]3)=[O:14])=[CH:8][CH:7]=2)=[N:4][N:3]=[N:2]1.[C:43](=O)(O)[O-].[Na+].S(OC)(OC)(=O)=O>CC(C)=O>[CH3:43][N:4]1[C:5]([C:6]2[CH:7]=[CH:8][C:9]([NH:12][C:13]([CH:15]3[CH:19]([C:20]4[CH:25]=[CH:24][CH:23]=[C:22]([Cl:26])[C:21]=4[CH3:27])[C:18]([C:30]4[CH:35]=[CH:34][C:33]([Cl:36])=[CH:32][C:31]=4[F:37])([C:28]#[N:29])[CH:17]([CH2:38][C:39]([CH3:42])([CH3:41])[CH3:40])[NH:16]3)=[O:14])=[CH:10][CH:11]=2)=[N:1][N:2]=[N:3]1
Reactant: O=C([O-])O
Reactant: Cc1c(Cl)cccc1C1C(C(=O)Nc2ccc(-c3nnn[nH]3)cc2)NC(CC(C)(C)C)C1(C#N)c1ccc(Cl)cc1F
Agent: [Na+]
Solvent: CC(C)=O
Solvent: COS(=O)(=O)OC
Product: Cc1c(Cl)cccc1C1C(C(=O)Nc2ccc(-c3nnnn3C)cc2)NC(CC(C)(C)C)C1(C#N)c1ccc(Cl)cc1F
Temperature: 25 °C
Reaction time: 5 h
Yield: 9.2 %

Procedure:
To a stirred solution of rac (2R,3R,4R,5S)-4-(4-Chloro-2-fluoro-phenyl)-3-(3-chloro-2-methyl-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carboxylic acid [4-(1H-tetrazol-5-yl)-phenyl]-amide (32 mg, 0.0524 mmol) in acetone (5 mL), sodium bicarbonate (45 mg, 0.6 mmol) and dimethyl sulfate (0.11 mmol) was added and the mixture was stirred at rt for 5 hrs. The solvent was removed and the residue was suspended in 3 mL of methylene chloride. The mixture was filtered and the filtrate was loaded on a silica gel column. Eluting with 35-70% EtOAc/Hexanes on an ISCO machine gave the desired product (3 mg) and the other regioisomer (18 mg).
Reaction SMILES: [Br:1][C:2]1[C:3]([O:19][CH3:20])=[C:4]([NH:12][C:13](=[O:18])[C:14]([CH3:17])([CH3:16])[CH3:15])[C:5]([C:10]#[N:11])=[C:6]([CH3:9])[C:7]=1I.[N+:21]([C:24]1[CH:25]=[C:26](B(O)O)[CH:27]=[CH:28][CH:29]=1)([O-:23])=[O:22].P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C(OCC)(=O)C.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>[Br:1][C:2]1[C:3]([O:19][CH3:20])=[C:4]([NH:12][C:13](=[O:18])[C:14]([CH3:17])([CH3:16])[CH3:15])[C:5]([C:10]#[N:11])=[C:6]([CH3:9])[C:7]=1[C:28]1[CH:27]=[CH:26][CH:25]=[C:24]([N+:21]([O-:23])=[O:22])[CH:29]=1
Reactant: COc1c(Br)c(I)c(C)c(C#N)c1NC(=O)C(C)(C)C
Reactant: O=[N+]([O-])c1cccc(B(O)O)c1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=P([O-])([O-])[O-]
Agent: [K+]
Solvent: CCOC(C)=O
Product: COc1c(Br)c(-c2cccc([N+](=O)[O-])c2)c(C)c(C#N)c1NC(=O)C(C)(C)C
Temperature: 95 °C
Reaction time: 4 h
Yield: 67.5 %

Procedure:
N-(3-Bromo-6-cyano-4-iodo-2-methoxy-5-methylphenyl)-2,2-dimethylpropionamide (I-6) (965 mg, 2.14 mmol), 3-nitrophenylboronic acid (375 mg, 2.25 mmol), tripotassium phosphate (74-85%, 1.23 g, 4.28 mmol) and tetrakis(triphenylphosphine)palladium(0) (247 mg, 0.214 mmol) were added to a 50-ml eggplant-type flask, followed by purging with nitrogen. N,N-Dimethylformamide (20 ml) was injected into it with a syringe, followed by stirring at 95° C. for 4 hours. After cooling, the reaction liquid was diluted with ethyl acetate, successively washed with saturated brine (×3), 1 N hydrochloric acid, saturated brine, an aqueous saturated sodium hydrogencarbonate solution and saturated brine, dried on anhydrous magnesium sulfate, then the solvent was concentrated under reduced pressure to obtain a pale brown residue. The resulting residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=6:1→4:1) to obtain the entitled compound (645 mg, 68%) as a pale yellow solid.
Reaction SMILES: [N:1]1([CH2:7][CH2:8][CH2:9][OH:10])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[H-].[Na+].[CH2:13]([O:20][C:21]1[CH:26]=[CH:25][C:24]([C:27]2[CH:32]=[C:31](Cl)[N:30]=[N:29][C:28]=2[CH2:34][CH2:35][CH2:36][CH3:37])=[CH:23][CH:22]=1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.O>C1COCC1>[CH2:13]([O:20][C:21]1[CH:26]=[CH:25][C:24]([C:27]2[CH:32]=[C:31]([O:10][CH2:9][CH2:8][CH2:7][N:1]3[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]3)[N:30]=[N:29][C:28]=2[CH2:34][CH2:35][CH2:36][CH3:37])=[CH:23][CH:22]=1)[C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1
Reactant: CCCCc1nnc(Cl)cc1-c1ccc(OCc2ccccc2)cc1
Reactant: OCCCN1CCCCC1
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: C1CCOC1
Product: CCCCc1nnc(OCCCN2CCCCC2)cc1-c1ccc(OCc2ccccc2)cc1
Reaction time: 0.17 h

Procedure:
To a stirred solution of 3-piperidin-1-yl-propan-1-ol (0.85 mmol, 121 mg) in THF at room temperature, NaH (1.2 mmol, 29 mg) was added and stirring continued for 10 min then 4-(4-benzyloxy-phenyl)-3-butyl-6-chloro-pyridazine (Example 1, 0.42 mmol, 150 mg) was added. The resulting mixture was stirred at 50-55° C. over night, poured into water and extracted with ethyl acetate. The organic layer was washed with water, brine dried (Na2SO4) filtered and concentrated under reduced pressure. The product was purified by column chromatography using 10% methanolic solution of ammonia (2.0 M ammonia in methanol) in DCM to get 4-(4-Benzyloxy-phenyl)-3-butyl-6-(3-piperidin-1-yl-propoxy)-pyridazine.
Reaction SMILES: [CH:1]1([S:7]([N:10]2[C:18]3[C:13](=[CH:14][C:15]([N+:19]([O-])=O)=[CH:16][CH:17]=3)[C:12]([C:22]3[CH2:23][CH2:24][N:25]([CH3:28])[CH2:26][CH:27]=3)=[CH:11]2)(=[O:9])=[O:8])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1>C(O)C.[Pd]>[NH2:19][C:15]1[CH:14]=[C:13]2[C:18](=[CH:17][CH:16]=1)[N:10]([S:7]([CH:1]1[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1)(=[O:9])=[O:8])[CH:11]=[C:12]2[C:22]1[CH2:23][CH2:24][N:25]([CH3:28])[CH2:26][CH:27]=1
Reactant: CN1CC=C(c2cn(S(=O)(=O)C3CCCCC3)c3ccc([N+](=O)[O-])cc23)CC1
Agent: [Pd]
Solvent: CCO
Product: CN1CC=C(c2cn(S(=O)(=O)C3CCCCC3)c3ccc(N)cc23)CC1
Reaction time: 20 h
Yield: 40.2 %

Procedure:
200 mg of 50% Pd/C with a humidity of 5% were added to a solution of 403 mg (1 mMol) of 1-cyclohexanesulfonyl-3-(1-methyl-1,2,3,6-tetrahydropyridine-4-yl)-5-nitro-1H-indole in 200 ml of ethanol. The resulting suspension was hydrogenized at 25 psi of overpressure for 20 hours. Then the catalyst was filtered and evaporated to drying. The resulting crude was purified by chromatography and 150 mg (40%) of the mentioned compound were obtained as a solid cream.
Reaction SMILES: [CH3:1][C:2]1([CH3:26])[CH2:6][C:5]2[CH:7]=[CH:8][CH:9]=[C:10]([CH2:11][NH:12][C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=3[O:19][C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[C:4]=2[O:3]1.[F:27][CH2:28][C:29](Cl)=[O:30]>C(Cl)Cl>[CH3:1][C:2]1([CH3:26])[CH2:6][C:5]2[CH:7]=[CH:8][CH:9]=[C:10]([CH2:11][N:12]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=3[O:19][C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[C:29](=[O:30])[CH2:28][F:27])[C:4]=2[O:3]1
Reactant: O=C(Cl)CF
Reactant: CC1(C)Cc2cccc(CNc3ccccc3Oc3ccccc3)c2O1
Solvent: ClCCl
Product: CC1(C)Cc2cccc(CN(C(=O)CF)c3ccccc3Oc3ccccc3)c2O1
Temperature: 0 °C
Reaction time: 1 h
Yield: 72.3 %

Procedure:
To a solution of N-(2,2,-Dimethyl-2,3-dihydrobenzofuran-7-ylmethyl)-N-(2-phenoxy phenyl)amine (0.20 g, 0.58 mmol) dissolved in DCM (2 mL) was added TEA (0.24 g, 2.32 mmol, 0.32 mL). The reaction was cooled to 0° C. and fluoroacetyl chloride (0.11 g, 1.16 mmol, 0.08 mL) was added. The mixture was stirred at room temperature for 1 h. The solvents were removed in vacuo, the residue quenched with water (10 mL), extracted with DCM (2×20 mL), dried over MgSO4, filtered and solvents removed in vacuo. The crude material was purified by silica gel chromatography eluting with DCM (A) and MeOH (B) (1% B, 80 g, 2 CV, 60 mL/min) to afford 170 mg (72%) of N-(2,2,-Dimethyl-2,3-dihydrobenzofuran-7-ylmethyl)-2-Fluoro-N-(2-phenoxy phenyl)acetamide as a pale yellow oil.
Reaction SMILES: [OH-].[Ca+2].[OH-].Cl.[C:5]([OH:17])(=[O:16])[CH:6]([CH:8]([CH2:12][C:13]([OH:15])=[O:14])[C:9]([OH:11])=[O:10])O>O>[CH2:12]([C:13]([OH:15])=[O:14])/[C:8](/[C:9]([OH:11])=[O:10])=[CH:6]\[C:5]([OH:17])=[O:16]
Reactant: O=C(O)CC(C(=O)O)C(O)C(=O)O
Agent: Cl
Agent: [Ca+2]
Agent: [OH-]
Solvent: O
Product: O=C(O)/C=C(\CC(=O)O)C(=O)O
Temperature: 75 °C
Reaction time: 2 h
Yield: 60 %

Procedure:
Thirty one grams (0.1 mole) of product prepared as in Example I-B is mixed with 200 mls water. Thirty grams (0.4 mole) calcium hydroxide is added slowly while the pH of the reaction medium is maintained at 10-10.5 and the temperature is kept between 70° and 75° C. After the addition of calcium hydroxide is complete, the reaction mixture is stirred at 75° C. for an additional two hours and then cooled. 90 grams of a 20% by weight hydrochloric acid solution is added slowly to a pH of 1.3 and the resulting solution is then filtered. The filtrate is evaporated to dryness in vacuo and the residue extracted with acetone. The acetone extract is filtered and 19.5 grams of product consisting of 53.5% (60% yield) transaconitic acid and 5.8% of a mixture of lactones of isocitric acid and alloisocitric acid.
Reaction SMILES: [CH2:1]([O:4][C:5]([NH:7][CH2:8][CH:9]([CH2:13][NH:14][C:15]([O:17][CH2:18][CH:19]=[CH2:20])=[O:16])[CH:10]([OH:12])[CH3:11])=[O:6])[CH:2]=[CH2:3].N1C=CN=C1.[Si:26](Cl)([C:29]([CH3:32])([CH3:31])[CH3:30])([CH3:28])[CH3:27]>CN(C)C=O.C(OCC)(=O)C>[CH2:18]([O:17][C:15]([NH:14][CH2:13][CH:9]([CH2:8][NH:7][C:5]([O:4][CH2:1][CH:2]=[CH2:3])=[O:6])[CH:10]([O:12][Si:26]([C:29]([CH3:32])([CH3:31])[CH3:30])([CH3:28])[CH3:27])[CH3:11])=[O:16])[CH:19]=[CH2:20]
Reactant: CC(C)(C)[Si](C)(C)Cl
Reactant: C=CCOC(=O)NCC(CNC(=O)OCC=C)C(C)O
Agent: c1c[nH]cn1
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: C=CCOC(=O)NCC(CNC(=O)OCC=C)C(C)O[Si](C)(C)C(C)(C)C
Reaction time: 14 h
Yield: 91.6 %

Procedure:
To a stirred solution of 1-allyloxycarbonylamino-2-(N-allyloxycarbonylaminomethyl)butan-3-ol (90.00 g) in N,N-dimethylformamide (800 ml) were added imidazole (85.51 g) and t-butyldimethylsilyl chloride (61.53 g). The resulting mixture was allowed to stand at ambient temperature for 14 hours. The mixture was diluted with ethyl acetate (2.4 l), washed successively with water (1.6 l) and brine (1 l), and dried over magnesium sulfate. Removal of the solvents gave a residue, which was chromatographed on silica gel (1 l) eluting with a mixture of n-hexane and ethyl acetate (9:1-7:3, V/V) to give 1-allyloxycarbonylamino-2-(N-allyloxycarbonylaminomethyl)-3-(t-butyldimethylsilyloxy)butane (115.40 g).
Reaction SMILES: [OH:1][CH2:2][CH2:3][N:4]1[CH2:8][CH2:7][NH:6][C:5]1=[O:9].C(O[Cl:15])(C)(C)C>CO>[Cl:15][N:6]1[CH2:7][CH2:8][N:4]([CH2:3][CH2:2][OH:1])[C:5]1=[O:9]
Reactant: CC(C)(C)OCl
Reactant: O=C1NCCN1CCO
Solvent: CO
Product: O=C1N(Cl)CCN1CCO
Reaction time: 1.5 h
Yield: 60.3 %

Procedure:
A solution of 1-(2-hydroxyethyl)imidazolidin-2-one (418 mg, 3.2 mmol) in MeOH (6 ml) was cooled to 0° C. tert-Butylhypochlorite (450 ul, 4 mmol) was added. The resulting solution was stirred for 90 min and then concentrated under reduced pressure. The crude material was purified by column chromatography (0 to 12% methanol in dichloromethane) to give a white solid (317 mg, 1.93 mmol, 60%). 1H NMR (400 MHz, D2O) δ 3.28-3.31 (t, J=5.3 Hz, 2H), 3.47-3.51 (m, 2H), 3.56-3.59 (m, 2H), 3.62-3.64 (t, J=5.3 Hz, 2H). 13C NMR (100 MHz, D2O) δ 43.31, 46.6, 51.9, 58.3, 163.9. LRMS (ESI/APCI) m/z 165 [M+H]+.
Reaction SMILES: [NH:1]1[CH:5]=[CH:4][N:3]=[C:2]1[CH2:6][N:7]([CH2:14][C:15]1[CH:28]=[CH:27][C:18]([C:19]([NH:21][CH2:22][CH2:23][CH2:24][CH2:25][NH2:26])=[O:20])=[CH:17][CH:16]=1)[CH2:8][C:9]1[NH:10][CH:11]=[CH:12][N:13]=1.[F:29][C:30]([F:40])([F:39])[C:31]1[CH:38]=[CH:37][CH:36]=[CH:35][C:32]=1[CH:33]=O.C(OC)(OC)OC.[BH4-].[Na+]>CO>[CH:36]1[CH:35]=[C:32]([CH2:33][NH:26][CH2:25][CH2:24][CH2:23][CH2:22][NH:21][C:19]([C:18]2[CH:27]=[CH:28][C:15]([CH2:14][N:7]([CH2:8][C:9]3[NH:13][CH:12]=[CH:11][N:10]=3)[CH2:6][C:2]3[NH:3][CH:4]=[CH:5][N:1]=3)=[CH:16][CH:17]=2)=[O:20])[C:31]([C:30]([F:29])([F:39])[F:40])=[CH:38][CH:37]=1
Reactant: O=Cc1ccccc1C(F)(F)F
Reactant: NCCCCNC(=O)c1ccc(CN(Cc2ncc[nH]2)Cc2ncc[nH]2)cc1
Agent: [BH4-]
Agent: [Na+]
Solvent: COC(OC)OC
Solvent: CO
Product: O=C(NCCCCNCc1ccccc1C(F)(F)F)c1ccc(CN(Cc2ncc[nH]2)Cc2ncc[nH]2)cc1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
The compound (50.6 mg) obtained in Example 3-2 was dissolved in anhydrous methanol (2.0 ml) and added with 2-trifluoromethylbenzaldehyde (manufactured by Tokyo Kasei Kogyo Co., Ltd.) (0.0260 ml) and trimethyl orthoformate (0.0430 ml), followed by stirring at room temperature for 30 minutes. Then, the solution was added with sodium borohydride (14.8 mg), followed by stirring at room temperature for 15 minutes. After completion of the reaction, the solvent was distilled off. The residue was dissolved in chloroform and washed with a 1 mol/l sodium hydroxide aqueous solution and saturated saline solution, followed by drying with anhydrous magnesium sulfate. The solvent was distilled off and the residue was then treated with hydrochloric acid. Subsequently, the residue was purified through silica gel column chromatography (chloroform/methanol/water), thereby obtaining hydrochloride (57.1 mg) of the subject compound as a white solid.
Reaction SMILES: Cl[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([C:8]([F:11])([F:10])[F:9])[N:3]=1.C([Sn](CCCC)(CCCC)[C:17]1[N:21]2[CH:22]=[CH:23][C:24]([C:26]([F:29])([F:28])[F:27])=[N:25][C:20]2=[N:19][CH:18]=1)CCC>>[F:28][C:26]([F:27])([F:29])[C:24]1[CH:23]=[CH:22][N:21]2[C:17]([C:2]3[CH:7]=[CH:6][CH:5]=[C:4]([C:8]([F:11])([F:10])[F:9])[N:3]=3)=[CH:18][N:19]=[C:20]2[N:25]=1
Reactant: CCCC[Sn](CCCC)(CCCC)c1cnc2nc(C(F)(F)F)ccn12
Reactant: FC(F)(F)c1cccc(Cl)n1
Product: FC(F)(F)c1cccc(-c2cnc3nc(C(F)(F)F)ccn23)n1
Yield: 14 %

Procedure:
2-Chloro-6-trifluoromethylpyridine (385 mg, 2.1 mmol) was coupled to 3-tributylstannyl-7-trifluoromethylimidazo[1,2-α]pyrimidine (1.4 mmol) by the method of Example 1 to give 7-trifluoromethyl-3-(6-trifluoromethyl-pyridin-2-yl)imidazo[1,2-α]pyrimidine (65 mg) as a white solid: δH (360 MHz, DMSO) 7.89 (2H, d, J 7.4), 8.27 (1H, t, J 7.9), 8.46 (1H, d, J 7.4), 9.01 (1H, s), 10.26 (1H, d, J 7.4); m/z (ES+) 333 (M++H).
Reaction SMILES: [O:1]=[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[C:4]([CH2:18][N:19]([C:27]2[N:35]=[CH:34][N:33]=[C:32]3[C:28]=2[N:29]=[CH:30][N:31]3C(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)C(=O)OC(C)(C)C)[O:3]1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[N:35]1[C:27]([NH:19][CH2:18][C:4]2[O:3][C:2](=[O:1])[C:11]3[C:6]([C:5]=2[C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=2)=[CH:7][CH:8]=[CH:9][CH:10]=3)=[C:28]2[C:32]([NH:31][CH:30]=[N:29]2)=[N:33][CH:34]=1
Reactant: CC(C)(C)OC(=O)N(Cc1oc(=O)c2ccccc2c1-c1ccccc1)c1ncnc2c1ncn2C(c1ccccc1)(c1ccccc1)c1ccccc1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: O=c1oc(CNc2ncnc3[nH]cnc23)c(-c2ccccc2)c2ccccc12

Procedure:
tert-Butyl (1-oxo-4-phenyl-1H-isochromen-3-yl)methyl(9-trityl-9H-purin-6-yl)carbamate (80 mg, 0.112 mmol) was dissolved in DCM (0.7 ml) and TFA (1 mL) at RT for 45 min. Solvent was then removed and the crude was straightforward purified by Preparative HPLC (method 1) to the title compound (17 mg, 40.9%).
Reaction SMILES: [CH:1]([Si:3]([CH:8]=[CH2:9])([CH:6]=[CH2:7])[CH:4]=[CH2:5])=[CH2:2].[CH3:10][SiH:11]([CH3:16])[O:12][SiH:13]([CH3:15])[CH3:14]>>[CH:1]([Si:3]([CH:8]=[CH2:9])([CH:6]=[CH2:7])[CH2:4][CH2:5][Si:11]([CH3:16])([CH3:10])[O:12][Si:13]([CH2:9][CH2:8][Si:3]([CH:6]=[CH2:7])([CH:4]=[CH2:5])[CH:1]=[CH2:2])([CH3:15])[CH3:14])=[CH2:2]
Reactant: C=C[Si](C=C)(C=C)C=C
Reactant: C[SiH](C)O[SiH](C)C
Product: C=C[Si](C=C)(C=C)CC[Si](C)(C)O[Si](C)(C)CC[Si](C=C)(C=C)C=C
Temperature: 70 °C
Yield: 28.8 %

Procedure:
To the 25 ml round bottomed flask equipped with a reflex condenser was charged 10.17 g of tetravinylsilane (75 mmol), 1 g of 1,1,3,3-tetramethyldisiloxane (7.5 mmol) and 10 μL of platinumdivinylmethyldisiloxane (5% Pt). The mixture was stirred and heated at 70° C. until it turned light yellow. (Scheme 5) . From this mixture, 0.88 g (29% yield) of 1,3 -di- [2 - (trivinylsilyl)ethyl ]-1,1,3,3-tetramethyldisiloxane (7) was isolated by distillation at 115° C and 0.1 nun Hg. 1H NMR 300 MHz, CDCl3 :δ6 6.22** (AXY,JAX =18 Hz, JAY =2 HZ, Z.Z H) , 6.20** (AXY, JAX =18 HZ, JAY =2 HZ), 6.15 (AXY,JAX =18HZ, JAY =2 HZ), 6.12 (AXY,JAX =7 HZ, JAY =2 HZ), 6.11(AXY, JAX = 7 HZ, JAY =2 Hz), 6,08* (AXY,JAX =7 Hz, JAY =2 Hz), 6.07** (AXY,JAX =7HZ,JAY=HZ), 5.82** (AXY,JAX =18 HZ, JAY =7 Hz), 5.80* (AXY,JAX =18 HZ, JAY =7 HZ), 5.79 (AXY,JAX =18 Hz, JAY =7 HZ), 5.76** (AXY,JAX =18 Hz, JAY=7HZ), 5.75* (AXY,JAX=18 Hz, JAY=7 Hz), 1.09* (d, 0.1 H), 1.07(d,l.5 H), 0.67 (m 1.2 H), 0.47 (m 1.2 (H), 0.12, (m, 0.1 H), 0.08, (s, 1H), 0.06, (s, 1 H) , 0.05 (s, 5 H) . 13C NMR 75 MHz, CDCl3 : δ135.089,, (CH); 134,628, (CH); 134,4, (CH2); 10.137, (CH 2); 6.869,, (CH); 4.21,, (CH2); 4.131, (CH2); 1.347,, (CH3); -0.34, (CH3) . 29Si NMR 99.4 MHz, CDCl3 with Cr (acac)3 δ-18.12, 8.00. IR (neat liquid on NaC1): cm-1 3180 (w) , 3050 (s) , 3010 (m) , 2960(s) , 2910(m) , 2880(m) , 2790(w) , 1610(m) , 1400(s) , 1250(s), 1130(s), 1050(s), 1010(s), 955(s), 840(s), 800(m), 770(s) , 730(s) , 625(w) , 550(m) , 525(m). C20H/38Si4O calc. C 59.04, H 9.41, Si 27.61, 0 3.96; found C 57.76, H 9.02. ##STR11##
Reaction SMILES: [CH:1]([NH:4][C:5]1[C:6]([N:11]2[CH2:16][CH2:15][N:14]([C:17]([C:19]3[CH:27]=[CH:26][C:22]([C:23]([OH:25])=O)=[CH:21][CH:20]=3)=[O:18])[CH2:13][CH2:12]2)=[N:7][CH:8]=[CH:9][CH:10]=1)([CH3:3])[CH3:2].[CH2:28]([NH:30][CH2:31][CH2:32][OH:33])[CH3:29]>>[CH2:28]([N:30]([CH2:31][CH2:32][OH:33])[C:23]([C:22]1[CH:21]=[CH:20][C:19]([C:17]([N:14]2[CH2:13][CH2:12][N:11]([C:6]3[C:5]([NH:4][CH:1]([CH3:3])[CH3:2])=[CH:10][CH:9]=[CH:8][N:7]=3)[CH2:16][CH2:15]2)=[O:18])=[CH:27][CH:26]=1)=[O:25])[CH3:29]
Reactant: CC(C)Nc1cccnc1N1CCN(C(=O)c2ccc(C(=O)O)cc2)CC1
Reactant: CCNCCO
Product: CCN(CCO)C(=O)c1ccc(C(=O)N2CCN(c3ncccc3NC(C)C)CC2)cc1
Yield: 86 %

Procedure:
By the same procedure as described in the example 1, synthesis was carried out starting with 4-[1-[3-(isopropylamino)-2-pyridyl]piperazin-4-yl-carbonyl]benzoic acid and using 2-(ethylamino)ethanol. Then, the product was recrystallized using ethyl acetate and petroleum ether, filtered and dried to give the desired compound as white crystal.
Reaction SMILES: [CH:1]1([CH2:10][C:11]([O:13][CH2:14][CH3:15])=[O:12])[CH:9]2[CH:4]([CH2:5][CH2:6][CH2:7][CH2:8]2)[CH2:3][NH:2]1.[C:16]1([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[C:17]([C:22](O)=[O:23])=[CH:18][CH:19]=[CH:20][CH:21]=1>>[C:16]1([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[C:17]([C:22]([N:2]2[CH2:3][CH:4]3[CH:9]([CH2:8][CH2:7][CH2:6][CH2:5]3)[CH:1]2[CH2:10][C:11]([O:13][CH2:14][CH3:15])=[O:12])=[O:23])=[CH:18][CH:19]=[CH:20][CH:21]=1
Reactant: CCOC(=O)CC1NCC2CCCCC21
Reactant: O=C(O)c1ccccc1-c1ccccc1
Product: CCOC(=O)CC1C2CCCCC2CN1C(=O)c1ccccc1-c1ccccc1

Procedure:
Ethyl 2-(2-(biphenylcarbonyl)octahydro-1H-isoindol-1-yl)acetate was prepared according to general procedure A using ethyl 2-(octahydro-1H-isoindol-1-yl)acetate and biphenyl-2-carboxylic acid.
Reaction SMILES: [C:1]([O:5][C:6](=[O:20])[NH:7][C:8]1[CH:13]=[C:12](F)[C:11]([C:15]#[N:16])=[CH:10][C:9]=1[N+:17]([O-:19])=[O:18])([CH3:4])([CH3:3])[CH3:2].[CH3:21][NH:22][CH3:23]>CS(C)=O>[C:1]([O:5][C:6](=[O:20])[NH:7][C:8]1[CH:13]=[C:12]([N:22]([CH3:23])[CH3:21])[C:11]([C:15]#[N:16])=[CH:10][C:9]=1[N+:17]([O-:19])=[O:18])([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(C)(C)OC(=O)Nc1cc(F)c(C#N)cc1[N+](=O)[O-]
Reactant: CNC
Solvent: CS(C)=O
Product: CN(C)c1cc(NC(=O)OC(C)(C)C)c([N+](=O)[O-])cc1C#N

Procedure:
The title compound was prepared from (4-cyano-5-fluoro-2-nitro-phenyl)-carbamic acid tert-butyl ester (Example B9) (2.0 g, 7.11 mmol) and dimethylamine (6.3 ml, 33% in EtOH, 35.0 mmol) in DMSO (30 mL) at RT according to the general procedure C. Obtained as a yellow solid (1.87 g, 86%).
Reaction SMILES: S(S([O-])=O)([O-])=O.[Na+].[Na+].[NH2:9][C:10]1[N:15]=[C:14]([OH:16])[C:13]([N+]([O-])=O)=[C:12]([NH:20][C:21]([CH2:29][CH3:30])([CH2:27][CH3:28])[C:22](=[N:25]O)[CH2:23][OH:24])[N:11]=1>[OH-].[Na+]>[NH2:9][C:10]1[N:15]=[C:14]([OH:16])[C:13]2[N:25]=[C:22]([CH2:23][OH:24])[C:21]([CH2:29][CH3:30])([CH2:27][CH3:28])[NH:20][C:12]=2[N:11]=1
Reactant: CCC(CC)(Nc1nc(N)nc(O)c1[N+](=O)[O-])C(CO)=NO
Agent: O=S([O-])S(=O)[O-]
Agent: [Na+]
Agent: [OH-]
Product: CCC1(CC)Nc2nc(N)nc(O)c2N=C1CO
Yield: 2.8 %

Procedure:
Sodium dithionite was added portionwise to a warm solution of 2-amino-4-hydroxy-6-(1,1-diethyl-3-hydroxy-2-hydroxyiminopropylamino)-5-nitropyrimidine (450 mg) in 0.1M sodium hydroxide until the colour changed from red to very pale yellow. A solid product was not obtained either on cooling or on adjusting the pH. In order to separate the product from inorganic material the solution was evaporated and the product extracted with ethanol and the inorganic material was filtered off. This extraction was repeated and the combined extracts were evaporated to dryness in vacuo. The residue was dissolved in the minimum quantity of water and placed on a column of Amberlite (C.G.50) ion exchange resin (2.5×28 cm.). Elution with water gave two main fluorescent bands. Evaporation of solution containing the first band gave the 6-carboxaldehyde derivative of the title compound (10 mg., 3%) as a bright orange powder. The second band gave the 7,8-dihydropteridine (160 mg., 44.5%) as a yellow powder.