Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([NH:10][C:11]2[N:16]=[CH:15][C:14]([C:17]([NH:20][C:21](=O)[CH3:22])([CH3:19])[CH3:18])=[CH:13][CH:12]=2)[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=1.Cl.[OH-].[Na+].O>C1COCC1>[Br:1][C:2]1[CH:3]=[C:4]([NH:10][C:11]2[CH:12]=[CH:13][C:14]([C:17]([NH:20][CH2:21][CH3:22])([CH3:19])[CH3:18])=[CH:15][N:16]=2)[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=1
Reactant: CC(=O)NC(C)(C)c1ccc(Nc2cc(Br)cn(C)c2=O)nc1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: C1CCOC1
Product: CCNC(C)(C)c1ccc(Nc2cc(Br)cn(C)c2=O)nc1
Temperature: 25 °C
Yield: 18.2 %

Procedure:
N-(2-(6-(5-bromo-1-methyl-2-oxo-1,2-dihydropyridin-3-ylamino)pyridin-3-yl)propan-2-yl)acetamide (417 mg, 1.1 mmol) was dissolved in THF (40 ml). This solution was refluxed and 10 M borane dimethyl sulfide complex (165 μl, 1.65 mmol) was added slowly to the refluxing mixture. The reaction mixture was refluxed for 2.5 hr. Next, 0.5 ml 6 M hydrochloric acid solution was added and after stirring at reflux for 5 min it was cooled to room temperature. Next 3M sodium hydroxide solution was added, followed by water and the material was extracted with ethyl acetate. It was washed with brine, dried over sodium sulfate, filtered and concentrated. The crude was purified by silica gel chromatography 0-10% MeOH in DCM to give 5-Bromo-3-[5-(1-ethylamino-1-methyl-ethyl)-pyridin-2-ylamino]-1-methyl-1H-pyridin-2-one (73 mg, 18%). 1H NMR (300 MHz, DMSO-d6) δ ppm 1.14 (t, J=7.18 Hz, 3 H) 1.70 (s, 6 H) 2.67 (m, 2 H) 3.52 (s, 3 H) 7.44 (d, J=9.06 Hz, 1 H) 7.58 (d, J=2.27 Hz, 1 H) 7.86 (dd, J=8.69, 2.64 Hz, 1 H) 8.45 (d, J=2.64 Hz, 1 H) 8.73 (d, J=2.64 Hz, 1 H) 8.76-8.88 (m, 1 H) 8.99 (s, 1 H).
Reaction SMILES: [NH2:1][C:2]1[CH:23]=[CH:22][C:5]2[N:6]([CH:9]3[CH2:14][CH2:13][N:12](C(OC(C)(C)C)=O)[CH2:11][CH2:10]3)[CH:7]=[N:8][C:4]=2[CH:3]=1.FC(F)(F)C(O)=O>ClCCl>[NH:12]1[CH2:11][CH2:10][CH:9]([N:6]2[C:5]3[CH:22]=[CH:23][C:2]([NH2:1])=[CH:3][C:4]=3[N:8]=[CH:7]2)[CH2:14][CH2:13]1
Reactant: CC(C)(C)OC(=O)N1CCC(n2cnc3cc(N)ccc32)CC1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: Nc1ccc2c(c1)ncn2C1CCNCC1
Yield: 128.5 %

Procedure:
tert-Butyl 4-(5-amino-1H-benzo[d]imidazol-1-yl)piperidine-1-carboxylate (3.75 mmol, 1.187 g) was stirred in dichloromethane (5 mL)/trifluoroacetic acid (5 mL) for 1 hour at room temperature. The reaction was concentrated under vacuum and passed down an SCX column to afford the title compound (1.042 g). MS (ESI) m/z 217.1 [M+H]+
Reaction SMILES: [CH2:1]([N:8]1[CH2:13][CH:12]=[C:11]([C:14]2[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=2)[CH:10]([CH2:21][OH:22])[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O>C1(C)C=CC=CC=1>[CH2:1]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[CH:15]=[CH:16][C:17]([F:20])=[CH:18][CH:19]=2)[CH:10]([CH2:21][OH:22])[CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: OCC1CN(Cc2ccccc2)CC=C1c1ccc(F)cc1
Solvent: Cc1ccccc1
Solvent: O
Product: OCC1CN(Cc2ccccc2)CCC1c1ccc(F)cc1
Temperature: 80 °C
Reaction time: 4 h
Yield: 22.3 %

Procedure:
58 ml (203 mmol) of sodium dihydrido-bis-(2-methoxy-ethoxy)aluminate (70% in toluene) were added dropwise under argon at room temperature while stirring to a solution of 17.4 g (58.5 mmol) of (RS)-[1-benzyl-4-(4-fluoro-phenyl)-1,2,3,6-tetrahydro-pyridin-3-yl]-methanol in 580 ml of absolute toluene. Subsequently, the mixture was stirred at 80° C. for 4 hours. 100 ml of water were added dropwise to the reaction mixture at room temperature, with working-up thereafter being carried out by extraction with water and ethyl acetate. The crude product was chromatographed on silica gel with hexane and ethyl acetate as the eluent. There were obtained 3.90 g (44% of theory) of (3RS,4SR)-[1-benzyl-4-(4-fluoro-phenyl)-piperidin-3-yl]-methanol; MS: 300 (M+H)+.
Reaction SMILES: [F:1][C:2]([F:32])([F:31])[C:3]1[CH:26]=[C:25]([C:27]([F:30])([F:29])[F:28])[CH:24]=[CH:23][C:4]=1[CH2:5][N:6]1[C:14]2[C:9](=[CH:10][C:11]([CH:15]=[C:16]3[S:20][C:19](=[O:21])[NH:18][C:17]3=[O:22])=[CH:12][CH:13]=2)[CH:8]=[N:7]1.[C:33]([O:37][C:38](=[O:49])[NH:39][C:40]1([CH2:46][CH2:47]O)[CH2:45][CH2:44][O:43][CH2:42][CH2:41]1)([CH3:36])([CH3:35])[CH3:34]>>[C:33]([O:37][C:38](=[O:49])[NH:39][C:40]1([CH2:46][CH2:47][N:18]2[C:17](=[O:22])[C:16](=[CH:15][C:11]3[CH:10]=[C:9]4[C:14](=[CH:13][CH:12]=3)[N:6]([CH2:5][C:4]3[CH:23]=[CH:24][C:25]([C:27]([F:29])([F:28])[F:30])=[CH:26][C:3]=3[C:2]([F:31])([F:1])[F:32])[N:7]=[CH:8]4)[S:20][C:19]2=[O:21])[CH2:45][CH2:44][O:43][CH2:42][CH2:41]1)([CH3:36])([CH3:35])[CH3:34]
Reactant: CC(C)(C)OC(=O)NC1(CCO)CCOCC1
Reactant: O=C1NC(=O)C(=Cc2ccc3c(cnn3Cc3ccc(C(F)(F)F)cc3C(F)(F)F)c2)S1
Product: CC(C)(C)OC(=O)NC1(CCN2C(=O)SC(=Cc3ccc4c(cnn4Cc4ccc(C(F)(F)F)cc4C(F)(F)F)c3)C2=O)CCOCC1

Procedure:
[4-(2-{5-[1-(2,4-Bis-trifluoromethylbenzyl)-1H-indazol-5-ylmethylene]-2,4-dioxothiazolidin-3-yl}ethyl)tetrahydro-2H-pyran-4-yl]carbamic acid tert-butyl ester was prepared from 5-[1-(2,4-bis-trifluoromethylbenzyl)-1H-indazol-5-ylmethylene]thiazolidine-2,4-dione (from Example 6) and ([4-(2-hydroxyethyl)tetrahydro-2H-pyran-4-yl]carbamic acid tert-butyl ester following General Procedure J.
Reaction SMILES: [CH2:1]([O:8][C:9]1[C:14](=[O:15])[CH:13]=[CH:12]O[C:10]=1[CH3:16])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[F:17][CH:18]([F:21])[CH2:19][NH2:20].Cl.C(N(CC)CC)C>N1C=CC=CC=1>[CH2:1]([O:8][C:9]1[C:14](=[O:15])[CH:13]=[CH:12][N:20]([CH2:19][CH:18]([F:21])[F:17])[C:10]=1[CH3:16])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: Cc1occc(=O)c1OCc1ccccc1
Reactant: NCC(F)F
Agent: Cl
Solvent: CCN(CC)CC
Solvent: c1ccncc1
Product: Cc1c(OCc2ccccc2)c(=O)ccn1CC(F)F
Temperature: 110 °C
Yield: 60.3 %

Procedure:
3-(Benzyloxy)-2-methyl-4H-pyran-4-one (432 mg, 2.0 mmol) was mixed with 2,2-difluoroethylamine (655 mg, 8.0 mmol) and triethylamine hydrochloride (1.10 g, 8.0 mmol) in pyridine (6 mL) in a sealed vial. The reaction mixture was heated at 110° C. for overnight. The solid was filtered and washed with ethyl acetate. The filtrate was concentrated under reduced pressure and the residue was mixed with water, and then extracted with ethyl acetate. The organic layer was washed with water and brine. The product was purified by column chromatography on silica gel with 5% methanol in ethyl acetate as eluant to give 3-(benzyloxy)-1-(2,2-difluoroethyl)-2-methylpyridin-4(1H)-one (337 mg) as pale-yellow solid. Yield=60%; 1H NMR (MeOD-D4, 90 MHz) δ (ppm): 7.66 (d, J=7.1 Hz, 1H), 7.16-7.55 (m, 5H), 6.46 (d, J=7.1 Hz, 1H), 5.55 (t, J=55.0 Hz, 1H), 4.45 (t, J=14.8 Hz, 1H) and 2.20 (s, 3H); MS m/z 280 [M+1]+.
Reaction SMILES: [C:1]([C:3]1[CH:8]=[CH:7][N:6]=[CH:5][CH:4]=1)#[N:2].[Na].[CH3:10][N:11]([C:13](=O)[C:14]1[CH:19]=[CH:18][N:17]=[CH:16][CH:15]=1)[NH2:12]>CO>[CH3:10][N:11]1[C:13]([C:14]2[CH:19]=[CH:18][N:17]=[CH:16][CH:15]=2)=[N:2][C:1]([C:3]2[CH:8]=[CH:7][N:6]=[CH:5][CH:4]=2)=[N:12]1
Reactant: CN(N)C(=O)c1ccncc1
Reactant: N#Cc1ccncc1
Agent: [Na]
Solvent: CO
Product: Cn1nc(-c2ccncc2)nc1-c1ccncc1
Reaction time: 0.5 h

Procedure:
To a solution of 4-cyanopyridine (4.1 grams, 0.04 mole) in methanol (60 ml.) is added sodium (0.2 grams). The resulting solution is allowed to stand at room temperature for 1/2 hour and is then added to a solution of N-methylisonicotinic acid hydrazide (6 grams, 0.04 mole) in methanol (80 ml.). The solution is refluxed for 3 hours and is then concentrated until a solid separates out of solution. The solid is collected by filtration and, upon recrystallization from ethanol, 1-methyl-3,5-di(4-pyridyl)-1,2,4-triazole is obtained, m.p. 168°-170°C.
Reaction SMILES: CN(C)C=O.CS([C:10]1[N:15]=[C:14]([CH3:16])[C:13]([C:17]([O:19][CH2:20][CH2:21][C:22]([CH3:26])=[C:23]([F:25])[F:24])=[O:18])=[CH:12][N:11]=1)(=O)=O.[CH2:27]([NH:31][CH3:32])[CH2:28][CH2:29][CH3:30]>O>[CH2:27]([N:31]([C:10]1[N:15]=[C:14]([CH3:16])[C:13]([C:17]([O:19][CH2:20][CH2:21][C:22]([CH3:26])=[C:23]([F:25])[F:24])=[O:18])=[CH:12][N:11]=1)[CH3:32])[CH2:28][CH2:29][CH3:30]
Reactant: CCCCNC
Reactant: CC(CCOC(=O)c1cnc(S(C)(=O)=O)nc1C)=C(F)F
Solvent: CN(C)C=O
Solvent: O
Product: CCCCN(C)c1ncc(C(=O)OCCC(C)=C(F)F)c(C)n1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 78.3 %

Procedure:
To 3 ml of N,N-dimethylformamide were dissolved 0.50 g (1.6 mmol) of 4,4-difluoro-3-methyl-3-butenyl 2-methanesulfonyl-4-methylpyrimidine-5-carboxylate, followed by the addition of 0.28 g (3.2 mmol) of N-butyl-N-methylamine and stirring at room temperature for 30 minutes. The reaction liquid was then poured in water and extracted with diethyl ether. The organic layer was washed with water and a saturated saline solution in this order, followed by drying over anhydrous magnesium sulfate and concentration under reduced pressure. The residue was purified with silica gel column chromatography (ethyl acetate ether:hexane=1:7) to obtain 0.41 g (yield: 80%) of 4,4-difluoro-3-methyl-3-butenyl 2-(N-butyl-N-methylamino)-4-methylpyrimidine-5-carboxylate.
Reaction SMILES: N1CCCCC1.C(O)=O.CC1(C)[O:18][C:16](=[O:17])[CH2:15][C:13](=O)O1.C(=O)[C:21]1[CH:30]=[CH:29][C:26]([O:27][CH3:28])=[C:23]([O:24][CH3:25])[CH:22]=1>>[CH3:25][O:24][C:23]1[CH:22]=[C:21]([CH2:13][CH2:15][C:16]([OH:18])=[O:17])[CH:30]=[CH:29][C:26]=1[O:27][CH3:28]
Reactant: CC1(C)OC(=O)CC(=O)O1
Reactant: COc1ccc(C=O)cc1OC
Solvent: O=CO
Solvent: C1CCNCC1
Product: COc1ccc(CCC(=O)O)cc1OC

Procedure:
After dropping 20.4 g (23.7 ml, 0.24 mol) of piperidine to 27.6 g (22.6 ml, 0.6 mol) of formic acid under stirring and cooling, 7.2 g (0.05 mol) of Meldrum's acid and 8.3 g (0.05 mol) of veratraldehyde were added to the above mixture, then the procedure of Example 35 was followed.
Reaction SMILES: [NH2:1][C:2]1[CH:12]=[CH:11][C:5]([CH2:6][CH2:7][C:8]([OH:10])=[O:9])=[CH:4][CH:3]=1.B(F)(F)F.[CH3:17][CH2:18]OCC.C(=O)([O-])[O-].[Na+].[Na+]>C(O)C>[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][CH2:7][C:8]([O:10][CH2:17][CH3:18])=[O:9])=[CH:11][CH:12]=1
Reactant: Nc1ccc(CCC(=O)O)cc1
Reactant: CCOCC
Agent: FB(F)F
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CCO
Product: CCOC(=O)CCc1ccc(N)cc1

Procedure:
A solution of 10.0 g. p-aminohydrocinnamic acid in 100 ml. of absolute ethanol containing 16 ml. of boron trifluoride etherate is heated to reflux for 48 hours. The solution is then cooled, poured into 5% aqueous sodium carbonate, and extracted with methylene chloride. Evaporation of the organic extracts yields ethyl p-aminohydrocinnamate.
Reaction SMILES: F[C:2](F)(F)C(O)=O.[NH2:8][C@H:9]1[CH2:15][CH:14]=[CH:13][CH2:12][N:11]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[C:10]1=[O:22].C(OC(N[C@@H](CCC=C)C(O)=O)=O)(C)(C)C>>[NH2:8][C@H:9]1[CH2:15][CH2:14][CH:13]=[CH:12][CH2:2][N:11]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[C:10]1=[O:22]
Reactant: N[C@H]1CC=CCN(c2ccccc2)C1=O
Reactant: O=C(O)C(F)(F)F
Agent: C=CCC[C@H](NC(=O)OC(C)(C)C)C(=O)O
Agent: N[C@H]1CC/C=C\CN(c2ccccc2)C1=O
Product: N[C@H]1CCC=CCN(c2ccccc2)C1=O

Procedure:
(S,Z)-3-Amino-1-phenyl-1,4,5,8-tetrahydroazocin-2 (3H)-one (175 mg, 0.692 mmol) was synthesized as described for the preparation of Intermediate 52 using (S)-2-(tert-butoxycarbonylamino)hex-5-enoic acid in step A. Anal. Calcd. for C13H16N2O m/z 216.2. found: 217.0 (M+H)+.
Reaction SMILES: [CH3:1][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][CH2:8][CH:9]2[C:12]([OH:14])=O)=[CH:4][CH:3]=1.[CH3:15][N:16]([CH3:34])[C:17]1[CH:22]=[CH:21][C:20]([CH2:23][NH:24][C:25]2[CH:30]=[CH:29][C:28]([CH:31]([CH3:33])[CH3:32])=[CH:27][CH:26]=2)=[CH:19][CH:18]=1>>[CH3:15][N:16]([CH3:34])[C:17]1[CH:18]=[CH:19][C:20]([CH2:23][N:24]([C:25]2[CH:30]=[CH:29][C:28]([CH:31]([CH3:32])[CH3:33])=[CH:27][CH:26]=2)[C:12]([CH:9]2[C:10]3[C:5](=[CH:4][CH:3]=[C:2]([CH3:1])[CH:11]=3)[CH2:6][CH2:7][CH2:8]2)=[O:14])=[CH:21][CH:22]=1
Reactant: CC(C)c1ccc(NCc2ccc(N(C)C)cc2)cc1
Reactant: Cc1ccc2c(c1)C(C(=O)O)CCC2
Product: Cc1ccc2c(c1)C(C(=O)N(Cc1ccc(N(C)C)cc1)c1ccc(C(C)C)cc1)CCC2
Yield: 23.1 %

Procedure:
By the reaction and treatment in the same manner as in Example 12 using 7-methyl-1,2,3,4-tetrahydronaphthalene-1-carboxylic acid (1.0 g) and [(4-dimethylaminophenyl)methyl](4-isopropylphenyl) amine (1.40 g) as starting materials, N-[(4-dimethylaminophenyl)methyl]-N-(4-isopropylphenyl)-7-methyl-1,2,3,4-tetrahydronaphthalene-1-carboxamide (0.53 g) was obtained.
Reaction SMILES: [OH:1][C:2]1[C:10]2[CH:9]=[C:8]([C:11]3[O:15][N:14]=[C:13]([CH3:16])[N:12]=3)[O:7][C:6]=2[CH:5]=[CH:4][CH:3]=1.S(C1C=CC([N+]([O-])=O)=CC=1)(O[CH2:21][C@H:22]1[O:24][CH2:23]1)(=O)=O>>[CH2:21]([O:1][C:2]1[C:10]2[CH:9]=[C:8]([C:11]3[O:15][N:14]=[C:13]([CH3:16])[N:12]=3)[O:7][C:6]=2[CH:5]=[CH:4][CH:3]=1)[C@H:22]1[O:24][CH2:23]1
Reactant: O=[N+]([O-])c1ccc(S(=O)(=O)OC[C@@H]2CO2)cc1
Reactant: Cc1noc(-c2cc3c(O)cccc3o2)n1
Product: Cc1noc(-c2cc3c(OC[C@@H]4CO4)cccc3o2)n1
Yield: 28.3 %

Procedure:
By the reactions in the same manner as in Starting Material Synthesis Example 1 using 5-(4-hydroxybenzo(b)furan-2-yl)-3-methyl-1,2,4-oxadiazole (3.3 g) and (S)-glycidyl nosylate (3.7 g), the title compound (1.1 g) was obtained as white crystals.
Reaction SMILES: [CH2:1]([O:8][C:9]([CH2:11][N:12]1[CH:15](SC)[CH2:14][C:13]1=[O:18])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Cl:19]Cl>C(Cl)Cl.C(Cl)(Cl)(Cl)Cl>[CH2:1]([O:8][C:9]([CH2:11][N:12]1[CH:15]([Cl:19])[CH2:14][C:13]1=[O:18])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CSC1CC(=O)N1CC(=O)OCc1ccccc1
Reactant: ClCl
Solvent: ClC(Cl)(Cl)Cl
Solvent: ClCCl
Product: O=C(CN1C(=O)CC1Cl)OCc1ccccc1
Yield: 104.6 %

Procedure:
1-Benzyloxycarbonylmethyl-4-methylthioazetidin-2-one (2.65 g) was dissolved in methylene dichloride (50 ml) and the solution was stirred and ice cooled while a solution of chlorine (0.71 g) in carbon tetrachloride (7 ml) was added in one portion. The mixture was stirred for 3 minutes and then the solvent was evaporated under reduced pressure to yield 1-benzyloxycarbonylmethyl-4-chloroazetidin-2-one as a pale yellow oil (2.65 g).
Reaction SMILES: [C:1]1([C:7]([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)=[CH:8][CH:9]2[CH2:14][CH2:13][N:12]([C:15](=O)[CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][C:24]3[CH:25]=[N:26][CH:27]=[CH:28][CH:29]=3)[CH2:11][CH2:10]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[H-].COCCO[Al+]OCCOC.[Na+].[H-].CCCCCC>C1(C)C=CC=CC=1>[C:31]1([C:7]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)=[CH:8][CH:9]2[CH2:10][CH2:11][N:12]([CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][C:24]3[CH:25]=[N:26][CH:27]=[CH:28][CH:29]=3)[CH2:13][CH2:14]2)[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=1
Reactant: O=C(CCCCCCCCc1cccnc1)N1CCC(C=C(c2ccccc2)c2ccccc2)CC1
Agent: COCCO[Al+]OCCOC
Agent: [H-]
Agent: [Na+]
Solvent: Cc1ccccc1
Solvent: CCCCCC
Product: C(=C(c1ccccc1)c1ccccc1)C1CCN(CCCCCCCCCc2cccnc2)CC1

Procedure:
The title compound was prepared in a manner similar to that employed for the compound of Example 16 starting with 6.5 g of 4-(2,2-diphenylethenyl)-1-[1-oxo-9-(3-pyridinyl)nonyl]piperidine and 7.7 mL of a 3.5M solution of sodium bis(2-methoxyethoxy)aluminum hydride in toluene. The analytically pure base was obtained from hexane, mp 51°-53° C. Analysis Calculated for C33H42N2 : C. 84.93; H, 9.07; N, 6.00. Found: C, 85.20; H, 9.00; N, 6.05. Evaporation of the hexane filtrates provided 5.9 g of crude product, which was dissolved in 25 mL of hot methanol and treated with 1.47 g of fumaric acid. The methanol was removed by distillation while adding acetone and the resulting solids were recovered and recrystallized from methanol/acetone to give 6.7 g (85%) of pure fumarate salt of 3-[9-[4-(2,2-diphenylethenyl)-1-piperidinyl]nonyl]pyridine, mp 125°-127° C. Analysis Calculated for C33H42N2.C4H4O4 : C, 76.26; H, 7.96; N, 4.81. Found: C, 76.54; H, 7.92; N, 4.90.
Reaction SMILES: [CH2:1]([O:8][C:9](=[O:27])[NH:10][C:11]([CH3:26])([C:13]1[NH:14][C:15](=[O:25])[CH:16]=[C:17]([C:19]2[CH:24]=[CH:23][N:22]=[CH:21][N:20]=2)[N:18]=1)[CH3:12])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Li+].[CH3:30]OS(OC)(=O)=O.O>O1CCOCC1>[CH2:1]([O:8][C:9](=[O:27])[NH:10][C:11]([CH3:12])([C:13]1[N:14]([CH3:30])[C:15](=[O:25])[CH:16]=[C:17]([C:19]2[CH:24]=[CH:23][N:22]=[CH:21][N:20]=2)[N:18]=1)[CH3:26])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: COS(=O)(=O)OC
Reactant: CC(C)(NC(=O)OCc1ccccc1)c1nc(-c2ccncn2)cc(=O)[nH]1
Agent: [H-]
Agent: [Li+]
Solvent: C1COCCO1
Solvent: O
Product: Cn1c(C(C)(C)NC(=O)OCc2ccccc2)nc(-c2ccncn2)cc1=O
Temperature: 40 °C
Reaction time: 0.75 h
Yield: 11 %

Procedure:
To a suspension of 0.13 g (0.36 mmol) of [1-Methyl-1-(6-oxo-1,6-dihydro-[4,4′]bipyrimidinyl-2-yl)-ethyl]-carbamic acid benzyl ester in 1.5 mL of anhydrous dioxane was added 0.003 g (0.39 mmol) of lithium hydride. The resulting mixture was allowed to stir at 40° C. for 45 minutes. After cooling down to room temperature, 0.058 g (0.46 mmol) of dimethylsulfate was added and reaction mixture was heated at 60° C. for 12 h. After cooling to 0° C., water was added and the mixture extracted with ethyl acetate. The extracts were washed with a saturated aqueous solution of sodium chloride, dried and evaporated. The residue was purified on preparative thin layer chromatography eluting with a mixture of dichloromethane/methanol/aqueous ammonia solution (29%) in the proportions 95/5/0.5 to afford 0.015 g (11%) of the desired compound as a colorless oil.
Reaction SMILES: [C:1]1([CH:7]=[N+]=[N-])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CSC.[C:13]1([CH:19]=[CH:20][C:21]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)=[O:22])[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1>ClCCl.C([O-])(=O)C.[Rh+2].C([O-])(=O)C>[C:21]([CH:20]1[CH:7]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[CH:19]1[C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1)(=[O:22])[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1
Reactant: O=C(C=Cc1ccccc1)c1ccccc1
Reactant: [N-]=[N+]=Cc1ccccc1
Agent: [Rh+2]
Agent: CC(=O)[O-]
Solvent: ClCCl
Solvent: CSC
Product: O=C(c1ccccc1)C1C(c2ccccc2)C1c1ccccc1

Procedure:
Phenyl diazomethane (prepared as in Example 36, 0.5 mmol in 3 ml of t-butyl methyl ether) was added to a stirred solution of dimethylsulphide (7.3 ml; 0.1 mmol), rhodium (II) acetate (2 mg; 0.005 mmol) and chalcone (103 mg; 0.5 mmol) in dichloromethane (2 ml) at room temperature over a period of 24 hours. After the addition was complete the solvent was removed in vacuo and the residue was chromatographed over silica [eluent dichloromethane:petrol (2:3)], to give the title compound as a 4:1 mixture of trans:cis cyclopropanes as a yellowy solid (58 mg; 39%).
Reaction SMILES: C1CCN2C(=NCCC2)CC1.[CH2:12]([CH:14]([CH2:27][CH3:28])[CH2:15][O:16][C:17](=[O:26])[C:18]1[CH:23]=[CH:22][C:21]([CH2:24]Br)=[CH:20][CH:19]=1)[CH3:13].[CH3:29][O:30][C:31]1[CH:45]=[C:44]([O:46][CH3:47])[CH:43]=[CH:42][C:32]=1[CH2:33][N:34]1[C:38](=[O:39])[CH2:37][NH:36][S:35]1(=[O:41])=[O:40]>C(Cl)Cl>[CH2:12]([CH:14]([CH2:27][CH3:28])[CH2:15][O:16][C:17](=[O:26])[C:18]1[CH:23]=[CH:22][C:21]([CH2:24][N:36]2[CH2:37][C:38](=[O:39])[N:34]([CH2:33][C:32]3[CH:42]=[CH:43][C:44]([O:46][CH3:47])=[CH:45][C:31]=3[O:30][CH3:29])[S:35]2(=[O:40])=[O:41])=[CH:20][CH:19]=1)[CH3:13]
Reactant: CCC(CC)COC(=O)c1ccc(CBr)cc1
Reactant: COc1ccc(CN2C(=O)CNS2(=O)=O)c(OC)c1
Solvent: ClCCl
Solvent: C1CCC2=NCCCN2CC1
Product: CCC(CC)COC(=O)c1ccc(CN2CC(=O)N(Cc3ccc(OC)cc3OC)S2(=O)=O)cc1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
DBU (127 mg, 0.836 mmol) is added slowly to a suspension of the title B compound, 4-bromomethyl-benzoic acid 2-ethyl-butyl ester (250 mg, 0.836 mmol) and the title B compound in Example 9, 2-(2,4-dimethoxybenzyl)-1,1-dioxo-1,2,5-thiadiazolidin-3-one (240 mg, 0.836 mmol) in 10 mL of CH2Cl2 at RT. The resulting solution is stirred at RT overnight. The solvent is evaporated under reduced pressure and the residue is chromatographed on silica gel with EtOAc/hexane (gradient 60-40) to afford 4-[5-(2,4-dimethoxy-benzyl)-1,1,4-trioxo1,2,5-thiadiazolidin-2-ylmethyl]-benzoic acid 2-ethyl-butyl ester as a white solid.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[C:9]1[S:10][C:11]2[C:12](=O)[NH:13][CH:14]=[CH:15][C:16]=2[N:17]=1.P(Br)(Br)([Br:21])=O>CC#N>[Br:21][C:12]1[C:11]2[S:10][C:9]([C:3]3[C:4]([F:8])=[CH:5][CH:6]=[CH:7][C:2]=3[Cl:1])=[N:17][C:16]=2[CH:15]=[CH:14][N:13]=1
Reactant: O=P(Br)(Br)Br
Reactant: O=c1[nH]ccc2nc(-c3c(F)cccc3Cl)sc12
Solvent: CC#N
Product: Fc1cccc(Cl)c1-c1nc2ccnc(Br)c2s1
Temperature: 100 °C
Yield: 58.2 %

Procedure:
To a stirred solution of 2-(2-chloro-6-fluorophenyl)thiazolo[5,4-c]pyridin-4(5H)-one (0.30 g, 1.1 mmol) in MeCN (50 mL), was added POBr3 (0.92 g, 3.2 mmol). The mixture was heated at 100° C. for 2 hours and then cooled to room temperature. The reaction was quenched with ice and extracted with EtOAc (3×20 mL). The combined organic extract was washed with saturated NaHCO3 solution (100 mL) and brine (100 mL), dried over Na2SO4 and concentrated under reduced pressure. The residue was purified by silica gel column chromatography eluting with a 0-10% gradient of EtOAc in petroleum ether to give the desired product as a white solid (0.22 g, 60% yield). 1H NMR (500 MHz, DMSO-d6): δ 8.59 (d, J=5.5 Hz, 1H), 8.27 (d, J=5.5 Hz, 1H), 7.76-7.68 (m, 3H). LCMS (ESI) m/z: 342.9 [M+H+].
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([CH:18]=[C:19]([N+:21]([O-])=O)[CH:20]=1)[C:5]([NH:7][CH2:8][CH2:9][O:10][CH2:11][CH2:12][O:13][CH2:14][CH2:15][O:16][CH3:17])=[O:6].Cl>CCO.O.[Fe]>[NH2:21][C:19]1[CH:18]=[C:4]([CH:3]=[C:2]([Br:1])[CH:20]=1)[C:5]([NH:7][CH2:8][CH2:9][O:10][CH2:11][CH2:12][O:13][CH2:14][CH2:15][O:16][CH3:17])=[O:6]
Reactant: COCCOCCOCCNC(=O)c1cc(Br)cc([N+](=O)[O-])c1
Agent: [Fe]
Agent: Cl
Solvent: CCO
Solvent: O
Product: COCCOCCOCCNC(=O)c1cc(N)cc(Br)c1
Temperature: 75 °C

Procedure:
Iron powder (5.90 g, 106 mmol) was added to a solution of the product from step (i) above (8.24 g, 20.43 mmol) and concentrated HCl (2 mL, 23.40 mmol) in EtOH (65 mL) and water (15 mL). The mixture was heat at 75° C. (block temperature) for 1 h. Then, the reaction was cooled to rt, before being diluted with water (30 mL), filtered and concentrated in vacuo. The residue was basified (NaHCO3) then partitioned between EtOAc (350 mL) and water (275 mL). The organic layer was dried (MgSO4), filtered and concentrated in vacuo to afford an orange oil that was purified by chromatography on silica gel (220 g column, 0-5% MeOH in DCM) to afford the sub-title compound (5.25 g) as an orange oil.
Reaction SMILES: [Cl-].[Na+].C([Al](CCCCCCCC)CCCCCCCC)CCCCCCC.[Cl:28][Si](Cl)(Cl)Cl.[CH2:33]([Si:41](CCCCCCCC)([CH2:50][CH2:51][CH2:52][CH2:53][CH2:54][CH2:55][CH2:56][CH3:57])[CH2:42][CH2:43][CH2:44][CH2:45][CH2:46][CH2:47][CH2:48][CH3:49])[CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH3:40]>>[CH2:33]([Si:41]([CH2:50][CH2:51][CH2:52][CH2:53][CH2:54][CH2:55][CH2:56][CH3:57])([CH2:42][CH2:43][CH2:44][CH2:45][CH2:46][CH2:47][CH2:48][CH3:49])[Cl:28])[CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH3:40]
Reactant: Cl[Si](Cl)(Cl)Cl
Reactant: CCCCCCCC[Si](CCCCCCCC)(CCCCCCCC)CCCCCCCC
Agent: CCCCCCCC[Al](CCCCCCCC)CCCCCCCC
Agent: [Cl-]
Agent: [Na+]
Product: CCCCCCCC[Si](Cl)(CCCCCCCC)CCCCCCCC

Procedure:
Utilizing the apparatus of Examples 1-5, 50 millimoles of sodium chloride, 100 millimoles of tri-n-octylaluminum, and 73 millimoles of tetrachlorosilane were reacted for 4 hours at 180° C. The analysis utilized in Examples 1-5 revealed that 62.9 mole percent tetraoctylsilane and 6.8 mole percent trioctylchlorosilane were produced based on tetrachlorosilane as the limiting reagent.