Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: O[CH2:2][C:3]1([C:6]2[C:11]([O:12][CH2:13][O:14][CH3:15])=[CH:10][CH:9]=[CH:8][C:7]=2[OH:16])[CH2:5][CH2:4]1.O1CCCC1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C>>[CH3:15][O:14][CH2:13][O:12][C:11]1[C:6]2[C:3]3([CH2:2][O:16][C:7]=2[CH:8]=[CH:9][CH:10]=1)[CH2:4][CH2:5]3
Reactant: COCOc1cccc(O)c1C1(CO)CC1
Agent: CC(C)OC(=O)/N=N/C(=O)OC(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: COCOc1cccc2c1C1(CC1)CO2
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 68.7 %

Procedure:
To a solution of 2-[1-(hydroxymethyl)cyclopropyl]-3-{[(methyloxy)methyl]oxy}phenol (Intermediate 83, 190 mg) in dry tetrahydrofuran (10 ml) triphenylphosphine (333 mg, 1.271 mmol) was added and the reaction mixture was stirred until complete dissolution of PPh3. DIAD (0.198 ml, 1.017 mmol) was then added dropwise and the reaction mixture was stirred for 30 minutes at room temperature The solvent was removed under reduced pressure. The residue was purified by flash chromatography (Biotage system) on silica gel using a 25 g SNAP column and cyclohexane to cyclohexane/ethyl acetate 9:1 as eluents affording the title compound as a light yellow oil (120 mg).
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[N:7]=[CH:8][C:9]2[NH:10][C:11]3[C:16]([C:17]=2[C:18]=1[CH2:19][O:20][CH3:21])=[CH:15][CH:14]=[CH:13][CH:12]=3)=[O:5])[CH3:2].[Br:22]Br>C(Cl)(Cl)Cl>[CH2:1]([O:3][C:4]([C:6]1[N:7]=[CH:8][C:9]2[NH:10][C:11]3[C:16]([C:17]=2[C:18]=1[CH2:19][O:20][CH3:21])=[CH:15][C:14]([Br:22])=[CH:13][CH:12]=3)=[O:5])[CH3:2]
Reactant: CCOC(=O)c1ncc2[nH]c3ccccc3c2c1COC
Reactant: BrBr
Solvent: ClC(Cl)Cl
Product: CCOC(=O)c1ncc2[nH]c3ccc(Br)cc3c2c1COC
Temperature: 0 °C
Reaction time: 2 h

Procedure:
A solution of 284 mg of 4-methoxymethyl-beta-carboline-3-carboxylic-acid-ethylester in 13 ml of chloroform is cooled to -30° C. and is dropwise mixed with 0.05 ml bromine in 1 ml of chloroform. This mixture is stirred for 2 h at -20° C. to -10° C., is poured into ice-cold 10% sodium hydrogen sulfite solution and extracted with methylene chloride. The crystallization in ethyl acetate yields 240 mg of 6-bromo-4-methoxymethyl-beta-carboline-3-carboxylic-acid-ethylester with a m.p. 207°-209° C.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([CH2:9][CH2:10][OH:11])=[CH:5][CH:4]=1.Cl[C:13]1[CH:23]=[C:17]2[N:18]([CH3:22])[CH2:19][CH2:20][CH2:21][N:16]2[C:15](=[O:24])[N:14]=1.[H-].[Na+]>CS(C)=O>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([CH2:9][CH2:10][O:11][C:13]2[CH:23]=[C:17]3[N:18]([CH3:22])[CH2:19][CH2:20][CH2:21][N:16]3[C:15](=[O:24])[N:14]=2)=[CH:5][CH:4]=1
Reactant: CN1CCCn2c1cc(Cl)nc2=O
Reactant: COc1ccc(CCO)cc1
Agent: [H-]
Agent: [Na+]
Solvent: CS(C)=O
Product: COc1ccc(CCOc2cc3n(c(=O)n2)CCCN3C)cc1
Temperature: 25 °C
Reaction time: 2 h
Yield: 47.5 %

Procedure:
To a solution of 2-(4-methoxyphenyl)ethanol (183 mg, 1.202 mmol) and 8-chloro-1-methyl-3,4-dihydro-1H-pyrimido[1,6-a]pyrimidin-6(2H)-one (200 mg, 1.002 mmol) in dimethyl sulfoxide (DMSO) (5 mL) stirred at room temp was added NaH (100 mg, 2.505 mmol) portionwise. The reaction mixture was stirred at room temp for 2 hr. The reaction was quenched with water and purified by prep-HPLC to give the title product as a white solid (150 mg).
Reaction SMILES: C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.BrN1C(=O)CCC1=O.[CH:28]1([CH2:33][CH:34]([C:38]2[CH:43]=[CH:42][C:41]([S:44]([C:47]([F:50])([F:49])[F:48])(=[O:46])=[O:45])=[CH:40][CH:39]=2)[C:35]([OH:37])=O)[CH2:32][CH2:31][CH2:30][CH2:29]1.[NH2:51][C:52]1[S:53][CH:54]=[C:55]([CH2:57][C:58]([O:60][CH2:61][CH3:62])=[O:59])[N:56]=1>C(Cl)Cl>[CH2:61]([O:60][C:58](=[O:59])[CH2:57][C:55]1[N:56]=[C:52]([NH:51][C:35](=[O:37])[CH:34]([C:38]2[CH:39]=[CH:40][C:41]([S:44]([C:47]([F:49])([F:48])[F:50])(=[O:45])=[O:46])=[CH:42][CH:43]=2)[CH2:33][CH:28]2[CH2:29][CH2:30][CH2:31][CH2:32]2)[S:53][CH:54]=1)[CH3:62]
Reactant: O=C(O)C(CC1CCCC1)c1ccc(S(=O)(=O)C(F)(F)F)cc1
Reactant: CCOC(=O)Cc1csc(N)n1
Agent: O=C1CCC(=O)N1Br
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Product: CCOC(=O)Cc1csc(NC(=O)C(CC2CCCC2)c2ccc(S(=O)(=O)C(F)(F)F)cc2)n1
Temperature: 0 °C
Reaction time: 0.33 h
Yield: 72.4 %

Procedure:
A solution of triphenylphosphine (97 mg, 0.371 mmol) in methylene chloride (1.5 mL) was cooled to 0° C. and then slowly treated with N-bromosuccinimide (66 mg, 0.371 mmol). The reaction mixture was stirred at 0° C. for 20 min and then treated with 3-cyclopentyl-2-(4-trifluoromethanesulfonyl-phenyl)propionic acid (100 mg, 0.285 mmol). The resulting reaction mixture was stirred at 0° C. for 10 min, allowed to warm to 25° C., and then treated with ethyl 2-amino-4-thiazoleacetate (123 mg, 0.657 mmol). The resulting reaction mixture was stirred at 25° C. for 3 d. The reaction mixture was then concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 3/1 hexanes/ethyl acetate) afforded {2-[3-cyclopentyl-2-(4-trifluoromethanesulfonyl-phenyl)-propionyl-amino]-thiazol-4-yl}-acetic acid ethyl ester (107 mg, 72%) as a yellow foam: mp 48-51° C.; EI-HRMS m/e calcd for C22H25F3N2O5S2 (M+) 518.1157, found 518.1157.
Reaction SMILES: C(Cl)(=O)C(Cl)=O.[CH3:7][O:8][C:9](=[O:19])[C:10]1[CH:18]=[CH:17][C:13]([C:14]([OH:16])=O)=[CH:12][CH:11]=1.[C:20]([NH:23][NH2:24])(=[O:22])[CH3:21].CCN(CC)CC>C(Cl)Cl.O>[CH3:7][O:8][C:9](=[O:19])[C:10]1[CH:11]=[CH:12][C:13]([C:14]([NH:24][NH:23][C:20](=[O:22])[CH3:21])=[O:16])=[CH:17][CH:18]=1
Reactant: CC(=O)NN
Reactant: COC(=O)c1ccc(C(=O)O)cc1
Agent: O=C(Cl)C(=O)Cl
Solvent: ClCCl
Solvent: O
Solvent: CCN(CC)CC
Product: COC(=O)c1ccc(C(=O)NNC(C)=O)cc1
Reaction time: 4 h
Yield: 76.3 %

Procedure:
Oxalyl chloride (1.05 g, 8.3 mmol) was added to a stirred solution of terephthalic acid monomethyl ester (1 g, 5.55 mmol) in DCM (12 mL) and stirring was continued at ambient temperature for 4 hr. The reaction mixture was concentrated under reduced pressure to afford the residue. The residue was dissolved in DCM (4 mL) and to the resulting solution was added, acetic acid hydrazide (490 mg, 6.66 mmol), Et3N (670 mg, 6.66 mmol) and stirring was continued at temperature overnight. The reaction mixture was diluted with water and extracted with ethylacetate, dried over sodium sulfate and concentrated under reduced pressure to afford 1 g (76.39% Yield) of 4-(N′-acetyl-hydrazinocarbonyl)-benzoic acid methyl ester. A stirred solution of 4-(N′-acetyl-hydrazinocarbonyl)-benzoic acid methyl ester (500 mg, 5.55 mmol) in POCl3 (12 mL) was heated at 100° C. for 3 hr. The reaction mixture was concentrated under reduced pressure to afford the residue. The residue was diluted with cold water, extracted with ethyl acetate, washed the organic layer with sodium bicarbonate solution, saturated brine solution and dried over sodium sulfate. The organic layer was concentrated under reduced pressure to 350 mg (75.92% Yield) of afford 4-(5-methyl-[1,3,4]oxadiazol-2-yl)-benzoic acid methyl ester. LiOH.H2O (330 mg, 8 mmol) was added to a solution of 4-(5-methyl-[1,3,4]oxadiazol-2-yl)-benzoic acid methyl ester (350 mg, 1.6 mmol) in the mixture of methanol (4 mL), THF (10 mL) and H2O (4 mL). The resulting reaction mixture was stirred at ambient temperature for 2 hrs. The reaction mixture was concentrated The residue was diluted with water, acidified with aqueous citric acid solution, extracted with ethyl acetate and dried over sodium sulfate. The organic layer was concentrated under reduced pressure to afford 280 mg (87.46% Yield) of 4-(5-methyl-[1,3,4]oxadiazol-2-yl)-benzoic acid.
Reaction SMILES: [I:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6](=[O:11])[C:5]2=O.C(O)(C(F)(F)F)=O.[CH2:20]([C@H:27]([O:38][C:39]1[CH:55]=[CH:54][C:42]([C:43]([NH:45][NH:46]C(OC(C)(C)C)=O)=[O:44])=[CH:41][CH:40]=1)[C:28]([O:30][CH2:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)=[O:29])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1>C(O)(=O)C>[I:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6](=[O:11])[C:5]2=[N:46][NH:45][C:43]([C:42]1[CH:54]=[CH:55][C:39]([O:38][C@@H:27]([CH2:20][C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=2)[C:28]([O:30][CH2:31][C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)=[O:29])=[CH:40][CH:41]=1)=[O:44]
Reactant: O=C1Nc2ccc(I)cc2C1=O
Reactant: CC(C)(C)OC(=O)NNC(=O)c1ccc(O[C@@H](Cc2ccccc2)C(=O)OCc2ccccc2)cc1
Solvent: CC(=O)O
Solvent: O=C(O)C(F)(F)F
Product: O=C1Nc2ccc(I)cc2C1=NNC(=O)c1ccc(O[C@@H](Cc2ccccc2)C(=O)OCc2ccccc2)cc1
Temperature: 100 °C
Yield: 76 %

Procedure:
Following the general method as outlined in Example 1, into a suspension of 5-iodo-1H-indole-2,3-dione in acetic acid in the presence of 5% TFA was added tert-butyl 2-{4-[(1S)-1-benzyl-2-(benzyloxy)-2-oxoethoxy]benzoyl}hydrazinecarboxylate. After stirring at 100° C., the reaction mixture was cooled to rt and a yellow solid precipitated out. Filtration on a fritté, washing with AcOH, water and drying under vacuo at 60° C. for 15 hrs gave 164 mg of the title compound (76%) as a yellow solid in 98.8% purity by HPLC (MaxPlot detection between 230 and 400 nm).
Reaction SMILES: O=O.C1C=C(C=O)OC=1.[O:10]1[CH:14]=[CH:13][CH:12]=[C:11]1[CH:15]=[CH:16]C(O)=O.C(O)(=O)CC(O)=O.N1CCCCC1.O1C=CC=C1C=C[C:40]([N:42]=[N+]=[N-])=[O:41].C1C=CC(P(N=[N+]=[N-])(C2C=CC=CC=2)=O)=CC=1>C(N(CC)CC)C>[O:10]1[C:11]2[CH:15]=[CH:16][NH:42][C:40](=[O:41])[C:12]=2[CH:13]=[CH:14]1
Reactant: O=C(O)C=Cc1ccco1
Reactant: [N-]=[N+]=NC(=O)C=Cc1ccco1
Agent: O=C(O)CC(=O)O
Agent: O=O
Agent: [N-]=[N+]=NP(=O)(c1ccccc1)c1ccccc1
Solvent: CCN(CC)CC
Solvent: O=Cc1ccco1
Solvent: C1CCNCC1
Product: O=c1[nH]ccc2occc12

Procedure:
For example, in making a compound of formula I in which Y is oxygen, Scheme A can be followed. Briefly, 2-furfural (1) is converted under heating into 3-furan-2-yl-acrylic acid (2) using malonic acid and a suitable base such as piperidine. 3-(Furan-2-yl)-acrylic acid (2) is converted into 3-(furan-2-yl)-acryloyl azide (3) using DPPA and a suitable base such as triethylamine. The azide (3) was cyclized to afford 5H-furo[3,2-c]pyridin-4-one (4) upon heating and a catalytic amount of iodine. 5H-furo[3,2-c]pyridin-4-one is chlorinated on the 4th position with POCl3 to afford 4-chloro-furo[3,2-c]pyridine (5). 4-Chloro-furo[3,2-c]pyridine is treated with bromine, and subsequently with DBU to afford compound (6). The chlorine atom of compound (6) is replaced with an amino group by the action of aqueous ammonia to afford compound (7). Compound (7) is subsequently subjected to Pd(PPh3)4, sodium carbonate, R—B(OH)2 or a compound of formula R—B(OR′)2, in which the radical —B(OR′)2 can be represented as
Reaction SMILES: Cl.[Cl:2][C:3]1[C:12]2[C:7](=[CH:8][C:9]([O:15][CH3:16])=[C:10]([O:13][CH3:14])[CH:11]=2)[N:6]=[CH:5][N:4]=1.[Br:17][C:18]1[C:24]([OH:25])=[CH:23][C:21]([NH2:22])=[C:20]([F:26])[CH:19]=1>CC(O)CC>[OH2:13].[ClH:2].[Br:17][C:18]1[C:24]([OH:25])=[CH:23][C:21]([NH:22][C:3]2[C:12]3[C:7](=[CH:8][C:9]([O:15][CH3:16])=[C:10]([O:13][CH3:14])[CH:11]=3)[N:6]=[CH:5][N:4]=2)=[C:20]([F:26])[CH:19]=1
Reactant: Nc1cc(O)c(Br)cc1F
Reactant: COc1cc2ncnc(Cl)c2cc1OC
Agent: Cl
Solvent: CCC(C)O
Product: COc1cc2ncnc(Nc3cc(O)c(Br)cc3F)c2cc1OC
Product: O
Yield: 168.4 %

Procedure:
Isopropanolic hydrogen chloride (0.1 ml of a 5M solution) was added to a solution of 4-chloro-6,7-dimethoxyquinazoline (202 mg, 0.9 mmol) and 4-bromo-2-fluoro-5-hydroxyaniline (as described in EP 61741 A2) (206 mg, 1 mmol) in 2-butanol (8 ml). The mixture was heated at reflux for 45 minutes, then allowed to cool. The precipitated product was collected by filtration, washed with 2-butanol, and then with ether, and dried under vacuum to give 4-(4-bromo-2-fluoro-5-hydroxyanilino)-6,7-dimethoxyquinazoline hydrochloride hydrate (340 mg, 87%) as a white solid.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([OH:9])=[CH:5][CH:4]=1.[Br:10]Br>CN(C=O)C>[Br:10][C:7]1[CH:8]=[C:3]([O:2][CH3:1])[CH:4]=[CH:5][C:6]=1[OH:9]
Reactant: BrBr
Reactant: COc1ccc(O)cc1
Solvent: CN(C)C=O
Product: COc1ccc(O)c(Br)c1
Temperature: 25 °C
Reaction time: 2 h
Yield: 100 %

Procedure:
To a solution of 4methoxyphenol (13.00 g, 104.84 mmol) in DMF (50 mL) was added bromine (5.40 mL, 104.84 mmol) at 0° C. The reaction was allowed to warm room temperature. After stirring for 2 h the reaction was quenched with water and extracted with ethyl acetate (3×200 mL). The combined organic extracts were washed with brine and dried (Na2SO4). Removal of the solvent under reduced pressure gave 21.28 g of the crude title compound as a dark oil: 1H NMR (250 MHz, CDCl3) d 7.49 (b, 1H), 6.96 (d. 1H), 6.72-6.62 (m, 2H). 3.71 (s, 3H).
Reaction SMILES: [CH3:1][C:2]1[O:6][C:5]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)=[N:4][C:3]=1[CH2:13][O:14][C:15]1[CH:25]=[CH:24][C:18]2[CH:19]=[C:20]([CH:22]=O)[O:21][C:17]=2[CH:16]=1.[O:26]1[CH2:30][C:29](=[O:31])[NH:28][C:27]1=[O:32].N1CCCC1.C(O)C>O>[CH3:1][C:2]1[O:6][C:5]([C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=2)=[N:4][C:3]=1[CH2:13][O:14][C:15]1[CH:25]=[CH:24][C:18]2[CH:19]=[C:20]([CH2:22][CH:30]3[O:26][C:27](=[O:32])[NH:28][C:29]3=[O:31])[O:21][C:17]=2[CH:16]=1
Reactant: O=C1COC(=O)N1
Reactant: Cc1oc(-c2ccccc2)nc1COc1ccc2cc(C=O)oc2c1
Solvent: CCO
Solvent: C1CCNC1
Solvent: O
Product: Cc1oc(-c2ccccc2)nc1COc1ccc2cc(CC3OC(=O)NC3=O)oc2c1
Yield: 6.6 %

Procedure:
A mixture of 6-(5-methyl-2-phenyl-4-oxazolylmethoxy)-2-benzofurancarbaldehyde (1.70 g), 2,4-oxazolidinedione (1.55 g), pyrrolidine (0.365 g) and ethanol (40 ml) was heated under refluxing conditions for 3 hours. The reaction mixture was poured over water; the resulting crystals were collected by filtration. The crystals were dissolved in tetrahydrofuran (100 ml); after palladium-carbon (0.40 g) was added, the mixture was subjected to catalytic reduction at room temperature under an atmospheric pressure of 1 atm. After the catalyst was filtered off, the filtrate was concentrated under reduced pressure; the residue was subjected to silica gel column chromatography. From the fraction eluted with methanolchloroform (2:98, v/v), crystals of 5-[6-(5-methyl-2-phenyl-4-oxazolylmethoxy)-2-benzofuranylmethyl]-2,4-oxazolidinedione (0.14 g, 6.6%) were obtained, which was then recrystallized from dichloromethane-methanol to yield colorless prisms having a melting point of 172° to 173° C.
Reaction SMILES: [CH:1]1([CH2:7][NH2:8])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[CH3:9][O:10][C:11](=[O:16])[CH2:12][C:13](=O)[CH3:14].[CH3:17][O:18][C:19](=[O:22])[C:20]#[CH:21]>CO>[CH3:17][O:18][C:19](=[O:22])[CH:20]=[CH:21][C:12](=[C:13]([NH:8][CH2:7][CH:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1)[CH3:14])[C:11]([O:10][CH3:9])=[O:16]
Reactant: C#CC(=O)OC
Reactant: COC(=O)CC(C)=O
Reactant: NCC1CCCCC1
Solvent: CO
Product: COC(=O)C=CC(C(=O)OC)=C(C)NCC1CCCCC1
Temperature: 25 °C
Yield: 80.5 %

Procedure:
A mixture of cyclohexanemethylamine (3 g, 26.5 mmol) and 3-oxo-butyric acid methyl ester (3.5 mL, 31.8 mmol) in MeOH (100 mL) was refluxed for 2 h. Propynoic acid methyl ester (3.6 mL, 39.8 mmol) was added, and the resulting mixture was refluxed for 2 days. After cooling to r.t., the solvent was evaporated, and the crude oil was recrystallized from MeOH to give 6.3 g of the title compound as a light tan solid. 1H NMR (CDCl3, 200 MHz): δ=10.73 (br s, 1H), 7.76 (d, 1H, J=15.4 Hz), 6.06 (d, 1H, J=15.4 Hz), 3.77 (s, 3H), 3.72 (s, 3H), 3.18 (t, 2H, J=6.2 Hz), 2.25 (s, 3H), 0.80-1.90 (m, 11H).
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[C:9]([C:11]2[N:15]=[C:14]([C:16]3[CH:21]=[CH:20][C:19]([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=4[CH3:28])=[C:18]([CH2:29][O:30][CH3:31])[CH:17]=3)[O:13][N:12]=2)[CH:8]=[CH:7][C:3]=1[C:4](O)=[O:5].Cl.[CH3:33][O:34][C:35](=[O:39])[CH2:36][CH2:37][NH2:38]>>[Cl:1][C:2]1[CH:10]=[C:9]([C:11]2[N:15]=[C:14]([C:16]3[CH:21]=[CH:20][C:19]([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=4[CH3:28])=[C:18]([CH2:29][O:30][CH3:31])[CH:17]=3)[O:13][N:12]=2)[CH:8]=[CH:7][C:3]=1[C:4]([NH:38][CH2:37][CH2:36][C:35]([O:34][CH3:33])=[O:39])=[O:5].[Cl:1][C:2]1[CH:10]=[C:9]([C:11]2[N:15]=[C:14]([C:16]3[CH:21]=[CH:20][C:19]([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=4[CH3:28])=[C:18]([CH2:29][O:30][CH3:31])[CH:17]=3)[O:13][N:12]=2)[CH:8]=[CH:7][C:3]=1[C:4]([NH:38][CH2:37][CH2:36][C:35]([OH:34])=[O:39])=[O:5]
Reactant: COC(=O)CCN
Reactant: COCc1cc(-c2nc(-c3ccc(C(=O)O)c(Cl)c3)no2)ccc1-c1ccccc1C
Agent: Cl
Product: COCc1cc(-c2nc(-c3ccc(C(=O)NCCC(=O)O)c(Cl)c3)no2)ccc1-c1ccccc1C
Product: COCc1cc(-c2nc(-c3ccc(C(=O)NCCC(=O)OC)c(Cl)c3)no2)ccc1-c1ccccc1C

Procedure:
Methyl N-(2-chloro-4-{5-[2-(methoxymethyl)-2′-methylbiphenyl-4-yl]-1,2,4-oxadiazol-3-yl}benzoyl)-beta-alaninate was prepared following the general procedure 14, starting from 2-chloro-4-{5-[2-(methoxymethyl)-2′-methylbiphenyl-4-yl]-1,2,4-oxadiazol-3-yl}benzoic acid and beta-alanine methyl ester hydrochloride. It was hydrolyzed following general procedure 9, to afford the title compound as a white foam. 1H NMR (DMSO-d6, 300 MHz) δ 12.25 (brs, 1H), 8.71 (m, 1H), 8.34 (m, 1H), 8.22-8.08 (m, 3H), 7.64 (d, J=7.8 Hz, 1H), 7.44 (d, 7.9 Hz, 1H), 7.40-7.25 (m, 3H), 7.15 (m, 1H), 4.19 (m, 2H), 3.44 (m, 2H), 3.25 (s, 3H), 2.53 (m, 2H), 2.04 (s, 3H). LC/MS (Method B): 506.4 (M+H)+, 504.4 (M−H)−. HPLC (Method B) Rt 5.16 min (Purity: 97.9%).
Reaction SMILES: [C:1]([O:5][C:6](=[O:16])[NH:7][CH2:8][CH2:9][CH:10]1[CH2:15][CH2:14][CH2:13][NH:12][CH2:11]1)([CH3:4])([CH3:3])[CH3:2].[Br:17][C:18]1[CH:23]=[CH:22][C:21]([N+:24]([O-:26])=[O:25])=[C:20](F)[CH:19]=1.C(N(CC)C(C)C)(C)C>C(#N)C>[C:1]([O:5][C:6](=[O:16])[NH:7][CH2:8][CH2:9][CH:10]1[CH2:15][CH2:14][CH2:13][N:12]([C:22]2[CH:23]=[C:18]([Br:17])[CH:19]=[CH:20][C:21]=2[N+:24]([O-:26])=[O:25])[CH2:11]1)([CH3:4])([CH3:2])[CH3:3]
Reactant: O=[N+]([O-])c1ccc(Br)cc1F
Reactant: CC(C)(C)OC(=O)NCCC1CCCNC1
Solvent: CC#N
Solvent: CCN(C(C)C)C(C)C
Product: CC(C)(C)OC(=O)NCCC1CCCN(c2cc(Br)ccc2[N+](=O)[O-])C1
Temperature: 25 °C

Procedure:
A solution of (2-Piperidin-3-yl-ethyl)-carbamic acid tert-butyl ester (0.087 mmol, 0.020 g) and 4-Bromo-2-fluoronitrobenzene (1.0 eq, 0.019 g), N,N-diisopropylethylamine (1.2 eq, 13.5 μL) in ACN (2 mL) was irradiated using microwave for 18 minutes at a temperature of 130° C. The solution was then cooled to room temperature and concentrated in vacuo to provide {2-[1-(5-Bromo-2-nitro-phenyl)-piperidin-3-yl]-ethyl}-carbamic acid tert-butyl ester. HPLC-MS RT=2.37 min, mass calculated for formula C18H26BrN3O4 427.11, observed LCMS m/z 428.22 and 430.11 (M+H).
Reaction SMILES: [C:1]([O:4][CH2:5][CH2:6][CH2:7][S:8](Cl)(=[O:10])=[O:9])(=[O:3])[CH3:2].[CH3:12][NH2:13]>ClCCl>[C:1]([O:4][CH2:5][CH2:6][CH2:7][S:8]([NH:13][CH3:12])(=[O:10])=[O:9])(=[O:3])[CH3:2]
Reactant: CN
Reactant: CC(=O)OCCCS(=O)(=O)Cl
Solvent: ClCCl
Product: CNS(=O)(=O)CCCOC(C)=O

Procedure:
15 g of 3-acetoxy-1-propanesulfonylchloride was dissolved in 150 ml dichloromethane. To the mixture was added dropwise 11.6 g of methylamine (40% methanol solution) with stirring under ice coioling. The reaction mixture was stirred for 1.5 hours under ice cooling.
Reaction SMILES: [CH:1]([C:3]1[CH:4]=[C:5]2[C:11]3([CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:12]3)[CH2:10][N:9]([C:23]([O:25][CH2:26][CH2:27][Si:28]([CH3:31])([CH3:30])[CH3:29])=[O:24])[C:6]2=[CH:7][CH:8]=1)=C.I([O-])(=O)(=O)=[O:33].[Na+].N1C(C)=CC=CC=1C.S([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.[Os](=O)(=O)(=O)=O.O>[CH:1]([C:3]1[CH:4]=[C:5]2[C:11]3([CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]([CH3:21])([CH3:22])[CH3:20])=[O:17])[CH2:12]3)[CH2:10][N:9]([C:23]([O:25][CH2:26][CH2:27][Si:28]([CH3:31])([CH3:30])[CH3:29])=[O:24])[C:6]2=[CH:7][CH:8]=1)=[O:33]
Reactant: [O-][I+3]([O-])([O-])[O-]
Reactant: C=Cc1ccc2c(c1)C1(CCN(C(=O)OC(C)(C)C)C1)CN2C(=O)OCC[Si](C)(C)C
Agent: O=[Os](=O)(=O)=O
Agent: O=S([O-])[O-]
Agent: [Na+]
Solvent: Cc1cccc(C)n1
Solvent: O
Solvent: C1COCCO1
Product: CC(C)(C)OC(=O)N1CCC2(C1)CN(C(=O)OCC[Si](C)(C)C)c1ccc(C=O)cc12
Reaction time: 3 h
Yield: 81.5 %

Procedure:
1-(2-(Trimethylsilyl)ethyl) 1′-tert-butyl 5-vinylspiro[indoline-3,3′-pyrrolidine]-1,1′-dicarboxylate (674 mg, 1.52 mmol) was dissolved in dioxane (15 mL). Thereafter, sodium periodate (1.30 g, 6.08 mmol), water (5 mL), 2,6-lutidine (0.35 mL, 3.01 mmol), and osmium tetroxide (1% t-butanol aqueous solution, 1 mL) were added to the above obtained solution under cooling on ice, and the thus obtained mixture was then stirred at the same temperature as above for 3 hours. Thereafter, an aqueous solution of sodium sulfite was added to the reaction solution, and the mixture was then extracted with chloroform. The organic layer was washed with brine, and was then dried over anhydrous sodium sulfate, followed by concentration in vacuo. The obtained residue was purified by silica gel column chromatography (hexane ethyl acetate=5:1) to obtain 1-(2-(trimethylsilyl)ethyl) 1′-tert-butyl 5-formylspiro[indoline-3,3′-pyrrolidine]-1,1′-dicarboxylate (553 mg, 82%) in the form of a light yellow solid.
Reaction SMILES: [CH2:1]([S:3][C:4]1[CH:5]=[C:6]([S:13]([C:16]2[CH:21]=[CH:20][C:19]([NH2:22])=[CH:18][CH:17]=2)(=[O:15])=[O:14])[CH:7]=[C:8]([S:10][CH2:11][CH3:12])[CH:9]=1)[CH3:2].Cl[C:24]([O:26][CH2:27][CH3:28])=[O:25]>N1C=CC=CC=1>[CH2:11]([S:10][C:8]1[CH:7]=[C:6]([S:13]([C:16]2[CH:17]=[CH:18][C:19]([NH:22][C:24](=[O:25])[O:26][CH2:27][CH3:28])=[CH:20][CH:21]=2)(=[O:15])=[O:14])[CH:5]=[C:4]([S:3][CH2:1][CH3:2])[CH:9]=1)[CH3:12].[C:24](=[O:25])([O-:26])[NH2:22]
Reactant: CCSc1cc(SCC)cc(S(=O)(=O)c2ccc(N)cc2)c1
Reactant: CCOC(=O)Cl
Solvent: c1ccncc1
Product: CCOC(=O)Nc1ccc(S(=O)(=O)c2cc(SCC)cc(SCC)c2)cc1
Product: NC(=O)[O-]
Temperature: 5 °C
Reaction time: 0.5 h

Procedure:
4-[[3,5-Bis(ethylthio)phenyl]sulfonyl]benzenamine (0.1 mole) and pyridine (50 ml) are charged into a glass reaction vessel fitted with a mechanical stirrer and thermometer and are cooled to about 5° C. Ethyl chloroformate (0.125 mole) is added, with stirring, at about 5° C. Stirring is continued for a period of about 30 minutes at about 5° C., then for an additional 16 hours at room temperature. The mixture is then washed with 2 portions of water (50 ml), dried and the solvent is then removed to yield the desired product ethyl [4-[3,5-bis(ethylthio)phenyl]sulfonyl]phenyl]carbamate.
Reaction SMILES: [CH2:1]([N:6]=[C:7]=[N:8][C:9]1[CH:10]=[N:11][CH:12]=[CH:13][CH:14]=1)[C:2]([CH3:5])([CH3:4])[CH3:3].C([N:19]=[C:20]=[N:21]C1C=NC=CC=1)(C)(C)C>>[C:20]([N:21]=[C:7]([NH:8][C:9]1[CH:10]=[N:11][CH:12]=[CH:13][CH:14]=1)[NH:6][CH2:1][C:2]([CH3:5])([CH3:4])[CH3:3])#[N:19]
Reactant: CC(C)(C)CN=C=Nc1cccnc1
Reactant: CC(C)(C)N=C=Nc1cccnc1
Product: CC(C)(C)CNC(=NC#N)Nc1cccnc1

Procedure:
By following the procedure of Example 1, but substituting N-neopentyl-N'-3-pyridylcarbodiimide for the N-tert-butyl-N'-3-pyridylcarbodiimide, the N"-cyano-N-neopentyl-N'-3-pyridylguanidine was obtained with a melting point of 214.0°-215.0° C.
Reaction SMILES: [CH3:1][NH:2][CH2:3][CH3:4].[C:5]1([CH:11]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH:12]([OH:15])[CH2:13]Br)[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1>C(O)C>[CH3:1][N:2]([CH2:13][CH:12]([OH:15])[CH:11]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[CH2:3][CH3:4]
Reactant: OC(CBr)C(c1ccccc1)c1ccccc1
Reactant: CCNC
Solvent: CCO
Product: CCN(C)CC(O)C(c1ccccc1)c1ccccc1

Procedure:
Excess N methyl-N-ethylamine was added to a solution of 1,1-diphenyl-3-bromo-propan-2-ol (2g) in ethanol. After 60 hours the solution was evaporated and the residue dissolved in dilute hydrochloric acid and ether. Basificiation of the acid extract and subsequent isolation through ether in the usual manner gave 3-(N-methyl-N- ethylamino)-1,1-diphenyl-propan-2-ol isolated as the hydrochloride (1 25g, 60%), m.p. 159°- 161°.