Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([C:7]2[O:8][CH:9]=[CH:10][N:11]=2)[CH:2]=1.Br[C:13]1[N:18]=[C:17]([C:19]2[N:24]=[CH:23][CH:22]=[CH:21][N:20]=2)[CH:16]=[CH:15][CH:14]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([C:7]2[O:8][C:9]([C:13]3[N:18]=[C:17]([C:19]4[N:20]=[CH:21][CH:22]=[CH:23][N:24]=4)[CH:16]=[CH:15][CH:14]=3)=[CH:10][N:11]=2)[CH:2]=1
Reactant: Brc1cccc(-c2ncccn2)n1
Reactant: c1cncc(-c2ncco2)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: c1cnc(-c2cccc(-c3cnc(-c4cccnc4)o3)n2)nc1
Temperature: 120 °C
Reaction time: 16 h

Procedure:
Under argon, 130 mg (0.88 mmol) of 2-(3-pyridinyl)oxazole (Hel. Chim. Acta 1962, 42, 375-381), 175 mg (0.74 mmol) of 2-(6-bromo-2-pyridyl)pyrimidine, 11 mg (0.02 mmol) of [(t-Bu)2P(OH)]2PdCl2 (POPd) and 205 mg (1.48 mmol) of potassium carbonate were initially charged in 5 ml of N,N-dimethylformamide, and the mixture was stirred at 120° C. for 16 hours. For work-up, the reaction mixture was concentrated under reduced pressure and the crude product that remained was purified by chromatography on silica gel (mobile phase: dichloromethane/methanol). This gave 126 mg (54% of theory) of 2-{6-[2-(pyridin-3-yl)-1,3-oxazol-5-yl]pyridin-2-yl}pyrimidine.
Reaction SMILES: CS[C:3]1[NH:12][C:11](=[O:13])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[N:4]=1.NC1C(C)=CC=CC=1>C(O)C>[N:4]1[C:5]2[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=2)[C:11](=[O:13])[NH:12][CH:3]=1
Reactant: CSc1nc2ccccc2c(=O)[nH]1
Solvent: CCO
Solvent: Cc1ccccc1N
Product: O=c1[nH]cnc2ccccc12
Reaction time: 4 h
Yield: 140.8 %

Procedure:
2-Methylthio-4-quinazolone (10.0 g, 0.052 mol) was fused with o-toluidine (8.35 g, 0.078 mol) at 160°. After 4 hours, the solid was treated with ethanol, and filtered to give 2-methylphenylamino)-4-quinazolone (10.7 g, 82%) m.p. 278°-280°.
Reaction SMILES: CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C.[ClH:34].[N:35]12[CH2:42][CH2:41][CH:38]([CH2:39][CH2:40]1)[C@@H:37]([NH:43][C:44]([C:46]1[S:47][C:48]3[C:54]([C:55]4[CH:56]=[C:57]([CH:61]=[CH:62][CH:63]=4)[C:58]([OH:60])=O)=[CH:53][CH:52]=[CH:51][C:49]=3[CH:50]=1)=[O:45])[CH2:36]2.[NH:64]1[CH2:69][CH2:68][O:67][CH2:66][CH2:65]1>CN(C=O)C>[ClH:34].[N:35]12[CH2:40][CH2:39][CH:38]([CH2:41][CH2:42]1)[C@@H:37]([NH:43][C:44]([C:46]1[S:47][C:48]3[C:54]([C:55]4[CH:63]=[CH:62][CH:61]=[C:57]([C:58]([N:64]5[CH2:69][CH2:68][O:67][CH2:66][CH2:65]5)=[O:60])[CH:56]=4)=[CH:53][CH:52]=[CH:51][C:49]=3[CH:50]=1)=[O:45])[CH2:36]2
Reactant: O=C(O)c1cccc(-c2cccc3cc(C(=O)N[C@H]4CN5CCC4CC5)sc23)c1
Reactant: C1COCCN1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: Cl
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: O=C(N[C@H]1CN2CCC1CC2)c1cc2cccc(-c3cccc(C(=O)N4CCOCC4)c3)c2s1
Temperature: 25 °C
Reaction time: 18 h

Procedure:
103 mg (0.27 mmol) of HATU and 70.8 μl (0.41 mmol) of N,N-diisopropylethylamine are added to a solution of 50 mg (0.11 mmol) of 3-(2-{[(3R)-1-azabicyclo[2.2.2]oct-3-ylamino]carbonyl}-1-benzothien-7-yl)benzoic acid hydrochloride (Example 75) and 19.7 μl (0.23 mmol) of morpholine in 0.5 ml of DMF at 0° C. The mixture is stirred at room temperature for 18 h. After purification by preparative HPLC, the product fractions are concentrated and, after addition of a 3:1 mixture of acetonitrile and 1N hydrochloric acid, again concentrated. Drying under high vacuum results in 43 mg (74% of theory) of the title compound.
Reaction SMILES: Cl[CH2:2][CH2:3][O:4][C:5]1[CH:14]=[C:13]2[C:8]([C:9]([O:15][C:16]3[C:17]([C:26]([O:28][CH2:29][CH2:30][CH3:31])=[O:27])=[CH:18][C:19]4[C:24]([CH:25]=3)=[CH:23][CH:22]=[CH:21][CH:20]=4)=[CH:10][CH:11]=[N:12]2)=[CH:7][C:6]=1[O:32][CH3:33].C(=O)([O-])[O-].[K+].[K+].[NH:40]1[CH2:45][CH2:44][O:43][CH2:42][CH2:41]1.O>CN(C)C=O>[CH3:33][O:32][C:6]1[CH:7]=[C:8]2[C:13](=[CH:14][C:5]=1[O:4][CH2:3][CH2:2][N:40]1[CH2:45][CH2:44][O:43][CH2:42][CH2:41]1)[N:12]=[CH:11][CH:10]=[C:9]2[O:15][C:16]1[C:17]([C:26]([O:28][CH2:29][CH2:30][CH3:31])=[O:27])=[CH:18][C:19]2[C:24]([CH:25]=1)=[CH:23][CH:22]=[CH:21][CH:20]=2
Reactant: C1COCCN1
Reactant: CCCOC(=O)c1cc2ccccc2cc1Oc1ccnc2cc(OCCCl)c(OC)cc12
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: CCCOC(=O)c1cc2ccccc2cc1Oc1ccnc2cc(OCCN3CCOCC3)c(OC)cc12
Temperature: 60 °C
Reaction time: 48 h
Yield: 59 %

Procedure:
Propyl 3-[7-(2-chloro-ethoxy)-6-methoxy-quinolin-4-yloxy]-naphthalene-2-carboxylate (compound 322) (80 mg) was dissolved in N,N-dimethylformamide (2 ml) to prepare a solution. Potassium carbonate (484 mg) and morpholine (0.15 ml) were added to the solution, and the mixture was stirred at 60° C. for 2 days. The reaction solution was cooled to room temperature, water was then added thereto, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was then washed with saturated brine and was dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by thin layer chromatography using hexane-acetone to give the title compound (52 mg, yield 59%).
Reaction SMILES: [CH3:1][C:2]1[C:7]([CH3:8])=[CH:6][C:5]([CH3:9])=[CH:4][C:3]=1[O:10][CH3:11].[Cl:12][S:13](O)(=[O:15])=[O:14]>C(Cl)Cl>[CH3:11][O:10][C:3]1[CH:4]=[C:5]([CH3:9])[C:6]([S:13]([Cl:12])(=[O:15])=[O:14])=[C:7]([CH3:8])[C:2]=1[CH3:1]
Reactant: O=S(=O)(O)Cl
Reactant: COc1cc(C)cc(C)c1C
Solvent: ClCCl
Product: COc1cc(C)c(S(=O)(=O)Cl)c(C)c1C
Temperature: 0 °C

Procedure:
In 500 ml of methylenchloride was dissolved 4.5 g of 2,3,5-trimethylanisole, and after cooling at -5°~-10° C., a solution (400 ml) of 6.0 ml of chlorosulfonic acid in methylene chloride was added dropwise to the mixture. The reaction mixture was kept at room temperature and then poured into ice-5% aqueous NaHCO3. The methylene chloride layer was washed with water and dried over anhydrous magnesium sulfate. The solvent was distilled off and the residue was crystallized from n-hexane and filtered.
Reaction SMILES: [CH2:1]([C:4]1[C:5]([NH:7][C:8](=[O:10])[CH:9]=1)=[O:6])[CH2:2][CH3:3].[CH:11]12[CH2:18][CH2:17][CH:14]([CH:15]=[CH:16]1)[CH2:13][CH:12]2[C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20].[CH:26]12[CH2:33][CH2:32][CH:29]([CH:30]=[CH:31]1)[CH2:28][CH:27]2[C:34]([O:36][CH2:37][CH2:38]CO)=[O:35].N(C(C)(C)C#N)=NC(C)(C)C#N>O1CCCC1>[CH2:1]([C:4]1[C:5]([NH:7][C:8](=[O:10])[CH:9]=1)=[O:6])[CH2:2][CH3:3].[CH:11]12[CH2:18][CH2:17][CH:14]([CH:15]=[CH:16]1)[CH2:13][CH:12]2[C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20].[CH:26]12[CH2:33][CH2:32][CH:29]([CH:30]=[CH:31]1)[CH2:28][CH:27]2[C:34]([O:36][CH2:37][CH2:38][OH:6])=[O:35]
Reactant: O=C(OCCCO)C1CC2C=CC1CC2
Agent: CC(C)(C#N)N=NC(C)(C)C#N
Agent: CC(C)(C)OC(=O)C1CC2C=CC1CC2
Agent: CCCC1=CC(=O)NC1=O
Solvent: C1CCOC1
Product: O=C(OCCO)C1CC2C=CC1CC2

Procedure:
Propyl maleimide (1 mol.), t-butyl bicyclo[2,2,2]oct-5-ene-2-carboxylate (0.5 mol.) and 3-hydroxypropyl bicyclo[2,2,2]oct-5-ene-2-carboxylate (0.5 mol) were dissolved in 50 g to 300 g of tetrahydrofuran (THF), 2 g to 15 g of 2,2′-azobisisobutyronitrile (AIBN) was added thereto, and the resulting solution was reacted at a temperature between 60° C. and 70° C. in a nitrogen atmosphere for 10 hours. After a high molecular weight was achieved by the reaction, the resultant product was precipitated in an ethyl ether or hexane solvent. The gathered precipitate was dried, and the desired poly(propyl maleimide/t-butyl bicyclo[2,2,2]oct-5-ene-2-carboxylate/2-hydroxyethyl bicyclo[2,2,2]oct-5-ene-2-carboxylate) polymer was obtained at a yield of about 78%.
Reaction SMILES: [OH:1][CH2:2][CH:3]1[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10][CH2:9][CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1.Br[CH:16]([CH3:18])[CH3:17]>O>[CH:3]1([CH2:2][O:1][CH:16]([CH3:18])[CH3:17])[CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14]1
Reactant: OCC1CCCCCCCCCCC1
Reactant: CC(C)Br
Solvent: O
Product: CC(C)OCC1CCCCCCCCCCC1

Procedure:
According to the disclosure of Example 1, 99 g of hydroxymethylcyclododecane was first converted into the sodium alcoholate. 74 g (0.6 mol) of 2-bromopropane was added dropwise to the boiling suspension, and then the mixture was heated for 30 hours under reflux. The reaction mixture was poured into water, the organic phase was washed with water, dried over Na2SO4, and then distilled.
Reaction SMILES: O.O.C1(C)C=CC=CC=1NC1NC2C=C(CC([NH:22][C:23]3[CH:28]=[CH:27][C:26]([C@H:29]([CH3:34])[CH2:30][C:31]([OH:33])=[O:32])=[CH:25][CH:24]=3)=O)C=CC=2N=1.C([O-])=O.[NH4+].[CH2:40](O)[CH3:41]>[Pd]>[NH2:22][C:23]1[CH:24]=[CH:25][C:26]([C@H:29]([CH3:34])[CH2:30][C:31]([O:33][CH2:40][CH3:41])=[O:32])=[CH:27][CH:28]=1
Reactant: CCO
Reactant: Cc1ccccc1Nc1nc2ccc(CC(=O)Nc3ccc([C@H](C)CC(=O)O)cc3)cc2[nH]1
Agent: [Pd]
Agent: O=C[O-]
Agent: [NH4+]
Solvent: O
Product: CCOC(=O)C[C@@H](C)c1ccc(N)cc1
Temperature: 50 °C

Procedure:
A solution of ethyl 3(R)-(4-nitrophenyl)butanoate (4.0 g, Reference Example 2) in ethanol (100 mL) was treated with ammonium formate (about 15 g). The reaction mixture was immersed in an oil-bath in a single neck flask, the solution was heated to 50° C., then treated with palladium on charcoal (about 1 g, 5%) to give an immediate visible effervescence. The mixture was kept at 50° C. with stirring for about an hour, then filtered through filter-aid. The filtrate was evaporated and the residue was partitioned between tert-butyl methyl ether and water. The organic phase was dried then evaporated to give the title compound (2.8 g) as a light brown gum.
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][CH2:9][C:10]1[C:19]2[C:14](=[CH:15][C:16]([O:22][CH3:23])=[C:17]([O:20][CH3:21])[CH:18]=2)[C:13]([CH2:24][C:25](O)=[O:26])=[CH:12][N:11]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:28]([NH:35][CH3:36])[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1>>[C:1]([O:5][C:6](=[O:7])[NH:8][CH2:9][C:10]1[C:19]2[C:14](=[CH:15][C:16]([O:22][CH3:23])=[C:17]([O:20][CH3:21])[CH:18]=2)[C:13]([CH2:24][C:25](=[O:26])[N:35]([CH2:28][C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[CH3:36])=[CH:12][N:11]=1)([CH3:3])([CH3:4])[CH3:2]
Reactant: COc1cc2c(CC(=O)O)cnc(CNC(=O)OC(C)(C)C)c2cc1OC
Reactant: CNCc1ccccc1
Product: COc1cc2c(CC(=O)N(C)Cc3ccccc3)cnc(CNC(=O)OC(C)(C)C)c2cc1OC

Procedure:
As described in Example 1, 83 mg of [1-(tert-butoxycarbonylamino-methyl)-6,7-dimethoxy-isoquinolin-4-yl]-acetic acid was coupled with benzyl-methyl-amine to give 69 mg of {4-[(benzyl-methyl-carbamoyl)-methyl]-6,7-dimethoxy-isoquinolin-1-ylmethyl}-carbamic acid tert-butyl ester. MS: APCI (M+H) calc'd for C27H33N3O5+H 480.6; found 480.0.
Reaction SMILES: [Si]([O:18][C:19]1[CH:20]=[C:21]([C@:26]([NH:45][C:46]([NH:48][CH2:49][C:50]([F:53])([F:52])[F:51])=[O:47])([C:34]2[CH:39]=[CH:38][C:37]([F:40])=[C:36]([C:41]([F:44])([F:43])[F:42])[CH:35]=2)[CH2:27][C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[CH:22]=[C:23]([F:25])[CH:24]=1)(C(C)(C)C)(C1C=CC=CC=1)C1C=CC=CC=1.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1.C(Cl)Cl>[F:40][C:37]1[CH:38]=[CH:39][C:34]([C@@:26]([NH:45][C:46]([NH:48][CH2:49][C:50]([F:51])([F:52])[F:53])=[O:47])([C:21]2[CH:20]=[C:19]([OH:18])[CH:24]=[C:23]([F:25])[CH:22]=2)[CH2:27][C:28]2[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=2)=[CH:35][C:36]=1[C:41]([F:44])([F:42])[F:43]
Reactant: CC(C)(C)[Si](Oc1cc(F)cc([C@](Cc2ccccc2)(NC(=O)NCC(F)(F)F)c2ccc(F)c(C(F)(F)F)c2)c1)(c1ccccc1)c1ccccc1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: C1CCOC1
Solvent: ClCCl
Product: O=C(NCC(F)(F)F)N[C@@](Cc1ccccc1)(c1cc(O)cc(F)c1)c1ccc(F)c(C(F)(F)F)c1
Temperature: 25 °C
Reaction time: 0.75 h
Yield: 78.9 %

Procedure:
To a solution of (R)-1-(1-(3-(tert-butyldiphenylsilyloxy)-5-fluorophenyl)-1-(4-fluoro-3-(trifluoromethyl)phenyl)-2-phenylethyl)-3-(2,2,2-trifluoroethyl)urea (85 mg, 0.11 mmol) in THF (1.5 mL) was added TBAF (1.0 M in THF, 0.12 mL, 0.12 mmol). The resulting mixture was stirred at room temperature for 45 min. The reaction was diluted with CH2Cl2 and washed with sat. NH4Cl, H2O and sat. NaCl, dried over Na2SO4, filtered and concentrated. The resulting residue was purified by flash chromatography (silica gel, hexanes/EtOAc) to give (R)-1-(1-(4-fluoro-3-(trifluoromethyl)phenyl)-1-(3-fluoro-5-hydroxyphenyl)-2-phenylethyl)-3-(2,2,2-trifluoroethyl)urea (Example 254, 45 mg, yield 77%). LCMS: RT=2.0 min [M+H] 519.1 (Phenomenex Luna C18 column, 4.6×30 mm eluting with 10-90% MeOH/H2O over 2 minutes containing 0.1% TFA; 5 mL/min, monitoring at 220 nm). 1H NMR (400 MHz, CDCl3) δ ppm 7.20-7.27 (3H, m), 7.09-7.18 (3H, m), 6.72 (1H, d, J=9.60 Hz), 6.66 (3H, d, J=7.07 Hz), 6.57 (1H, s), 3.73-3.78 (1H, m), 3.65-3:71 (1H, m), 3.63 (1H, d, J=8.59 Hz), 3.47-3.58 (1H, m).
Reaction SMILES: [F:1][C:2]1[CH:10]=[CH:9][C:8]([F:11])=[C:7]2[C:3]=1[C:4](=[O:35])[N:5]([CH2:27][C:28]1[CH:33]=[CH:32][C:31]([F:34])=[CH:30][CH:29]=1)[CH:6]2[CH2:12][CH2:13][C:14](NC1C=CC(C(F)(F)F)=CN=1)=[O:15].[CH2:36]([O:38][C:39](=[O:47])[CH2:40][C:41]1[N:42]=[C:43]([NH2:46])[S:44][CH:45]=1)[CH3:37]>>[CH2:36]([O:38][C:39](=[O:47])[CH2:40][C:41]1[N:42]=[C:43]([NH:46][C:14](=[O:15])[CH2:13][CH2:12][CH:6]2[C:7]3[C:3](=[C:2]([F:1])[CH:10]=[CH:9][C:8]=3[F:11])[C:4](=[O:35])[N:5]2[CH2:27][C:28]2[CH:29]=[CH:30][C:31]([F:34])=[CH:32][CH:33]=2)[S:44][CH:45]=1)[CH3:37]
Reactant: O=C(CCC1c2c(F)ccc(F)c2C(=O)N1Cc1ccc(F)cc1)Nc1ccc(C(F)(F)F)cn1
Reactant: CCOC(=O)Cc1csc(N)n1
Product: CCOC(=O)Cc1csc(NC(=O)CCC2c3c(F)ccc(F)c3C(=O)N2Cc2ccc(F)cc2)n1

Procedure:
The product from Example 18, Part A (100 mg, 0.29 mmol) and (2-amino-4-thiazolyl)acetic acid ethyl ester was converted to the title compound in a manner analogous to the method described in Example 7, Part E without crystallization (70 mg, 47%).
Reaction SMILES: Cl[C:2]([O:4][CH2:5][CH3:6])=[O:3].[NH2:7][C:8]1[CH:9]=[C:10]([CH:26]=[CH:27][C:28]=1[F:29])[NH:11][C:12]1[C:21]2[C:16](=[CH:17][C:18]([O:24][CH3:25])=[C:19]([O:22][CH3:23])[CH:20]=2)[N:15]=[CH:14][N:13]=1.C(N(CC)CC)C>C(Cl)Cl>[F:29][C:28]1[CH:27]=[CH:26][C:10]([NH:11][C:12]2[C:21]3[C:16](=[CH:17][C:18]([O:24][CH3:25])=[C:19]([O:22][CH3:23])[CH:20]=3)[N:15]=[CH:14][N:13]=2)=[CH:9][C:8]=1[NH:7][C:2]([O:4][CH2:5][CH3:6])=[O:3]
Reactant: COc1cc2ncnc(Nc3ccc(F)c(N)c3)c2cc1OC
Reactant: CCOC(=O)Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CCOC(=O)Nc1cc(Nc2ncnc3cc(OC)c(OC)cc23)ccc1F
Temperature: 25 °C
Reaction time: 18 h
Yield: 19 %

Procedure:
Ethyl chloroformate (0.058 ml) was added to a suspension of 4-(3-amino-4-fluoroanilino)-6,7-dimethoxyquinazoline (159 mg) and triethylamine (0.14 ml) in dry methylene chloride (3.5 ml) and the resulting mixture was stirred at ambient temperature for 18 hours. Methylene chloride (100 ml) was added and the mixture was washed with water and brine, dried over magnesium sulphate, filtered and evaporated to dryness. The residue was purified by silica column chromatography, eluting with 2% methanol in methylene chloride to yield the title compound as a solid (38 mg, 19%); NMR: 1.23 (t, 3H), 3.91 (s, 3H), 3.94 (s, 3H), 4.12 (m, 2H), 7.16 (s, 1H), 7.21 (m, 1H), 7.57 (m, 1H), 7.83 (s, 1H), 8.0 (m, 1H), 8.42 (s, 1H), 9.28 (s, 1H), 9.49 (s, 1H); m/s: M+H+ 387.
Reaction SMILES: [CH2:1]([Si:3](Cl)([CH2:6][CH3:7])[CH2:4][CH3:5])[CH3:2].N1C=CN=C1.[O:14]1[CH:18]=[CH:17][CH:16]=[C:15]1[C@@H:19]1[NH:22][C:21](=[O:23])[C@@:20]1([OH:25])[CH3:24].C(OCC)(=O)C.CCCCC>CN(C=O)C>[O:14]1[CH:18]=[CH:17][CH:16]=[C:15]1[C@@H:19]1[NH:22][C:21](=[O:23])[C@@:20]1([O:25][Si:3]([CH2:6][CH3:7])([CH2:4][CH3:5])[CH2:1][CH3:2])[CH3:24]
Reactant: C[C@]1(O)C(=O)N[C@H]1c1ccco1
Reactant: CC[Si](Cl)(CC)CC
Agent: c1c[nH]cn1
Solvent: CN(C)C=O
Solvent: CCCCC
Solvent: CCOC(C)=O
Product: CC[Si](CC)(CC)O[C@@]1(C)C(=O)N[C@H]1c1ccco1
Yield: 67 %

Procedure:
Triethyl silyl chloride (0.316 g, 2.1 mmol) and imidazole (0.100 g, 1.5 mmol) were added to a stirred solution of (3R,4R)-4-(furan-2-yl)-3-hydroxy-3-methyl-azetidin-2-one (0.167 g, 1.0 mmol) in DMF (6.0 ml) at 25° C. under argon atmosphere. The reaction solution was quenched after 4 h with a saturated NH4Cl aqueous solution and extracted with ethyl acetate. The organic phase was dried and concentrated under reduced pressure. Chromatography of the residue (SiO2, ethyl acetate/n-pentane, 1:2) afforded 0.190 g (0.67 mmol 67%) of (3R,4S)-4-(furan-2-yl)-3-triethylsilyloxy-3-methyl-azetidin-2-one: [α]D20=+42.8 (c 1.04, CHCl3); IR (CDCl3, cm−1): 3600–3000, 3413, 2957, 1768, 1458, 1377, 1012; 1H NMR (CDCl3): δ=0.65 (m, 6H, 3 CH2), 0.95 (t, 9H, 3 Me), 1.19 (s, 3H, Me), 4.54 (s, 1H), 6.27 (d, 1H, 2-furyl), 6.28 (m, 1H, 2-furyl), 6.72 (b, 1H, NH), 7.40 (m, 1H, 2-furyl); 13H NMR (CDCl3): δ=5.71 (CH2), 6.73 (Me), 19.3 (Me), 61.0 (CH), 89.1(C), 108.1 (CH), 110.5 (CH), 142.7 (CH), 150.9 (C), 171.5 (C).
Reaction SMILES: Cl[C:2]1[CH:16]=[CH:15][C:14]([N+:17]([O-:19])=[O:18])=[CH:13][C:3]=1[C:4]([C:6]1[CH:11]=[CH:10][C:9]([Cl:12])=[CH:8][CH:7]=1)=[O:5].[CH3:20][CH:21]1[CH2:26][CH2:25][CH2:24][CH2:23][NH:22]1.C(=O)([O-])[O-].[Ca+2]>C(O)C>[CH3:20][CH:21]1[CH2:26][CH2:25][CH2:24][CH2:23][N:22]1[C:2]1[CH:16]=[CH:15][C:14]([N+:17]([O-:19])=[O:18])=[CH:13][C:3]=1[C:4]([C:6]1[CH:11]=[CH:10][C:9]([Cl:12])=[CH:8][CH:7]=1)=[O:5]
Reactant: CC1CCCCN1
Reactant: O=C(c1ccc(Cl)cc1)c1cc([N+](=O)[O-])ccc1Cl
Agent: O=C([O-])[O-]
Agent: [Ca+2]
Solvent: CCO
Product: CC1CCCCN1c1ccc([N+](=O)[O-])cc1C(=O)c1ccc(Cl)cc1
Yield: 40.6 %

Procedure:
Proceeding as indicated in example 2, from 0.035 mole (10.4 g) of 2,4'-dichloro-5-nitro-benzophenone, 0.07 mole (7 cm3) of 2-methylpiperidine and 0.035 mole (5 g) of calcium carbonate in ethanol, 5.1 g (Yield: 40%) of the expected product are obtained after recrystallization in ethanol. M.P. 142° C.
Reaction SMILES: [CH3:1][C:2]([C:5]1[CH:10]=[CH:9][C:8]([N:11]([S:15]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)(=[O:17])=[O:16])[C:12](=[O:14])[CH3:13])=[C:7]([O:24][CH3:25])[CH:6]=1)(O)[CH3:3].C(=O)([O-])O.[Na+]>C(Cl)Cl.FC(F)(F)C(O)=O.C([SiH](CC)CC)C>[CH3:25][O:24][C:7]1[CH:6]=[C:5]([CH:2]([CH3:1])[CH3:3])[CH:10]=[CH:9][C:8]=1[N:11]([S:15]([C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1)(=[O:16])=[O:17])[C:12](=[O:14])[CH3:13]
Reactant: COc1cc(C(C)(C)O)ccc1N(C(C)=O)S(=O)(=O)c1ccccc1
Agent: CC[SiH](CC)CC
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: COc1cc(C(C)C)ccc1N(C(C)=O)S(=O)(=O)c1ccccc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 97.5 %

Procedure:
To a solution of 1-methyl-1-[4-(N-acetyl-phenylsulfonylamino)-3-methoxyphenyl]ethanol (2.50 g; prepared in Reference Example 39.) in methylene chloride (10 ml), trifluoroacetic acid (10 ml) and triethylsilane (3.3 ml) were added at 0° C. The mixture was stirred for 1 hour at room temperature. The reaction mixture was added to saturated sodium hydrogencarbonate carefully The mixture was extracted with ethyl acetate. The organic layer was washed, dried over and concentrated. The residue was purified on silica gel column chromatography (hexane:AcOEt=3:1) to give the title compound (2.33 g) having the following physical data.
Reaction SMILES: O.[NH2:2][C:3]1[CH:8]=[C:7]([OH:9])[N:6]=[C:5]([SH:10])[N:4]=1.[Cl:11][C:12]1[CH:13]=[C:14]([CH:17]=[CH:18][CH:19]=1)[CH2:15]Cl>>[NH2:2][C:3]1[N:4]=[C:5]([S:10][CH2:15][C:14]2[CH:17]=[CH:18][CH:19]=[C:12]([Cl:11])[CH:13]=2)[NH:6][C:7](=[O:9])[CH:8]=1
Reactant: Nc1cc(O)nc(S)n1
Reactant: ClCc1cccc(Cl)c1
Solvent: O
Product: Nc1cc(=O)[nH]c(SCc2cccc(Cl)c2)n1

Procedure:
The subtitle compound was prepared according to the procedure of Example 1 step i) treating 4-amino-6-hydroxy-2-mercaptopyrimidine monohydrate (10.00 g) with 3-chlorobenzyl chloride (9.98 g) to afford the subtitle compound as a white solid. Yield: 15.00 g.
Reaction SMILES: C([O:3][C:4](=[O:14])[C:5]([C:7]1[CH:11]=[C:10]([Br:12])[S:9][C:8]=1[Br:13])=[O:6])C.Cl>CC(C)=O.O>[Br:13][C:8]1[S:9][C:10]([Br:12])=[CH:11][C:7]=1[C:5](=[O:6])[C:4]([OH:14])=[O:3]
Reactant: CCOC(=O)C(=O)c1cc(Br)sc1Br
Agent: Cl
Solvent: O
Solvent: CC(C)=O
Product: O=C(O)C(=O)c1cc(Br)sc1Br

Procedure:
(2,5-Dibromothiophen-3-yl)-oxo-acetic acid ethyl ester (1.71 g, 5.0 mmol) was dissolved in 15 ml acetone and 2 ml water, then treated with 15 ml concentrated HCl at reflux for 2 hours. The reaction mixture was then poured into 100 ml water, and extracted into 100 ml of dichloromethane. The organic layer was dried over Na2SO4 and concentrated under vacuum to yield crude (2,5-dibromothiophen-3-yl)-oxo-acetic acid which was used without further purification.
Reaction SMILES: [F:1][C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[C:4]([N+:9]([O-:11])=[O:10])[CH:3]=1.[Br:12][CH2:13][CH2:14][C:15](Cl)=[O:16].C(N(C(C)C)CC)(C)C.C(Cl)Cl>O>[N+:9]([C:4]1[CH:3]=[C:2]([F:1])[CH:8]=[CH:7][C:5]=1[NH:6][C:15](=[O:16])[CH2:14][CH2:13][Br:12])([O-:11])=[O:10]
Reactant: Nc1ccc(F)cc1[N+](=O)[O-]
Reactant: O=C(Cl)CCBr
Solvent: O
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: O=C(CCBr)Nc1ccc(F)cc1[N+](=O)[O-]
Reaction time: 48 h
Yield: 101.1 %

Procedure:
A mixture of 7.8 gm of 4-fluoro-2-nitroaniline, 8.57 gm of 3-bromo propionylchloride (added at a temperature of 0° C. over a period of 0.3 hours), 6.5 gm of diisopropylethylamine and 150 ml CH2Cl2 was kept for 48 hours at 20-25° C. Water (300 ml) was added and the mixture was extracted with CH2C2. The CH2Cl2 extract was collected, washed with water (2×20 ml) and desiccated wtih Na2SO4. The crude product (14.7 gm) obtained after removal of solvents was used without further purification. A sample of this crude material (14.79 gm) exhibited the following data. M+/z of 292.
Reaction SMILES: [Br:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6]Br)=[CH:4][CH:3]=1.[C:10]1([CH:16]2[CH2:21][CH2:20][CH2:19]CN2)[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.C(=O)([O-])[O-].[K+].[K+].[C:28](#[N:30])C>>[Br:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6][N:30]2[CH2:19][CH2:20][CH2:21][CH:16]([C:10]3[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=3)[CH2:28]2)=[CH:4][CH:3]=1
Reactant: CC#N
Reactant: c1ccc(C2CCCCN2)cc1
Reactant: BrCc1ccc(Br)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Product: Brc1ccc(CN2CCCC(c3ccccc3)C2)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 54 %

Procedure:
5.632 g of 4-Bromobenzyl bromide and 2.422 g of 2-Phenylpiperidine (Array) in 50 mL of acetonitrile were stirred at room temperature and 6.229 g of potassium carbonate was added. The reaction was stirred at room temperature overnight. The solution was filtered through Celite and concentrated in vacuo to afford a brown solid. Purification was done by flash chromatography to afford product. Wt:0.908 g, 54% yield.
Reaction SMILES: [C:1]([O:7][CH2:8][CH3:9])(=[O:6])[CH2:2][C:3]([CH3:5])=[O:4].[CH2:10]([C:16]1[CH:23]=[CH:22][C:19]([CH:20]=O)=[CH:18][CH:17]=1)[CH2:11][CH2:12][CH2:13][CH2:14][CH3:15]>N1CCCCC1>[CH2:10]([C:16]1[CH:23]=[CH:22][C:19](/[CH:20]=[C:2](/[C:3](=[O:4])[CH3:5])\[C:1]([O:7][CH2:8][CH3:9])=[O:6])=[CH:18][CH:17]=1)[CH2:11][CH2:12][CH2:13][CH2:14][CH3:15]
Reactant: CCCCCCc1ccc(C=O)cc1
Reactant: CCOC(=O)CC(C)=O
Solvent: C1CCNCC1
Product: CCCCCCc1ccc(/C=C(/C(C)=O)C(=O)OCC)cc1
Temperature: 70 °C
Reaction time: 96 h

Procedure:
Ethyl acetoacetate (3.9g, 0.03 moles), parahexylbenzaldehyde (3.8g, 0.02 moles) and piperidine (3 drops) were stirred at room temperature for 20 hrs. and then stirred for 4 days at 70° C. Products A and B were separated and purified by silica gel chromatography. Structure assignments were supported by NMR, infrared and uv spectra and elemental analysis (302.4).