Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH:1]1([CH2:4][NH:5][S:6]([C:9]2[CH:14]=[CH:13][C:12]([NH:15][C:16]3[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][C:17]=3[Cl:23])=[CH:11][C:10]=2[C:24]([F:27])([F:26])[F:25])(=[O:8])=[O:7])[CH2:3][CH2:2]1.CI.[CH2:30]([N+](CCCC)(CCCC)CCCC)CCC.[OH-].[Na+]>ClCCl.O>[CH:1]1([CH2:4][N:5]([CH3:30])[S:6]([C:9]2[CH:14]=[CH:13][C:12]([NH:15][C:16]3[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][C:17]=3[Cl:23])=[CH:11][C:10]=2[C:24]([F:26])([F:27])[F:25])(=[O:7])=[O:8])[CH2:3][CH2:2]1
Reactant: O=S(=O)(NCC1CC1)c1ccc(Nc2ccc(Cl)cc2Cl)cc1C(F)(F)F
Reactant: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [Na+]
Agent: [OH-]
Solvent: ClCCl
Solvent: CI
Solvent: O
Product: CN(CC1CC1)S(=O)(=O)c1ccc(Nc2ccc(Cl)cc2Cl)cc1C(F)(F)F
Reaction time: 3 h
Yield: 97 %

Procedure:
To a solution of N-Cyclopropylmethyl-4-(2,4-dichloro-phenylamino)-2-trifluoromethyl-benzenesulfonamide, (256 mg. 0.58 mmol), methyl iodide (92 mg, 0.65 mmol) and tetrabutylammonium hydrosulfate (38 mg, 0.11 mmol) in 15 ml dichloromethane 3 ml 25% solution of NaOH was added and mixture was stirred for 3 hours. Water was added and mixture was washed twice with 1 N HCl and brine. After drying over sodium sulfate solvent was evaporated and crude solid used in the next stage. Yield 97%.
Reaction SMILES: [CH3:1][N:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([OH:11])[CH:9]=2)[C:4]([CH2:12][C:13]2[CH:18]=[CH:17][C:16]([Cl:19])=[CH:15][CH:14]=2)=[C:3]1[CH2:20][C:21]([CH3:27])([CH3:26])[C:22]([O:24][CH3:25])=[O:23].C([O-])([O-])=O.[K+].[K+].Br[CH2:35][C:36]1[CH:45]=[CH:44][C:43]2[C:38](=[CH:39][CH:40]=[CH:41][CH:42]=2)[N:37]=1>CN(C=O)C>[CH3:1][N:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([O:11][CH2:35][C:36]3[CH:45]=[CH:44][C:43]4[C:38](=[CH:39][CH:40]=[CH:41][CH:42]=4)[N:37]=3)[CH:9]=2)[C:4]([CH2:12][C:13]2[CH:18]=[CH:17][C:16]([Cl:19])=[CH:15][CH:14]=2)=[C:3]1[CH2:20][C:21]([CH3:27])([CH3:26])[C:22]([O:24][CH3:25])=[O:23]
Reactant: BrCc1ccc2ccccc2n1
Reactant: COC(=O)C(C)(C)Cc1c(Cc2ccc(Cl)cc2)c2ccc(O)cc2n1C
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: COC(=O)C(C)(C)Cc1c(Cc2ccc(Cl)cc2)c2ccc(OCc3ccc4ccccc4n3)cc2n1C
Temperature: 25 °C
Reaction time: 18 h

Procedure:
To a solution of 315 mg of the ester from Step B in 3 mL of DMF were added 225 mg of milled K2CO3 and 272 mg of 2-(bromomethyl)quinoline. The mixture was stirred at R.T. for 18 h, poured into 25% aq NH4OAc, and extracted with ethyl acetate. The organic extract was dried over Na2SO4 and evaporated to dryness to give an oil which was chromatographed on flash silica gel using ethyl acetate:hexane (30:70) as eluant to give the title compound as a foam.
Reaction SMILES: Cl.CN(C)CCCCl.[CH3:9][N:10]([CH3:42])[CH2:11][CH2:12][CH2:13][O:14][CH2:15][C:16]1[N:17](COCC[Si](C)(C)C)[N:18]=[C:19]2[C:25]=1[C:24]1[CH:26]=[CH:27][CH:28]=[CH:29][C:23]=1[S:22][C:21]1[CH:30]=[CH:31][CH:32]=[CH:33][C:20]2=1>>[CH3:42][N:10]([CH3:9])[CH2:11][CH2:12][CH2:13][O:14][CH2:15][C:16]1[NH:17][N:18]=[C:19]2[C:25]=1[C:24]1[CH:26]=[CH:27][CH:28]=[CH:29][C:23]=1[S:22][C:21]1[CH:30]=[CH:31][CH:32]=[CH:33][C:20]2=1
Reactant: CN(C)CCCOCc1c2c(nn1COCC[Si](C)(C)C)-c1ccccc1Sc1ccccc1-2
Agent: CN(C)CCCCl
Agent: Cl
Product: CN(C)CCCOCc1[nH]nc2c1-c1ccccc1Sc1ccccc1-2

Procedure:
By the reaction of alcohol 19B (0.15 mmole) and 3-dimethylaminopropylchloride-hydrochloride (1.8 mmole), dimethyl-{3-[2-(2-trimethylsilyl-ethoxymethyl)-2H-8-thia-1,2-diaza-dibenzo[e,h]azulene-3-ylmethoxy]-propyl}-amine in the form of an oily product was obtained.
Reaction SMILES: [C:1]([C:3]1[CH:4]=[C:5]([CH:12]=[CH:13][CH:14]=1)[O:6][CH2:7][CH:8]([OH:11])[CH2:9][NH2:10])#[N:2].O1CCCC1.C(=O)(O)[O-].[Na+].[C:25](Br)([CH3:28])([CH3:27])[CH3:26]>CN(C)C=O>[C:1]([C:3]1[CH:4]=[C:5]([CH:12]=[CH:13][CH:14]=1)[O:6][CH2:7][CH:8]([OH:11])[CH2:9][NH:10][C:25]([CH3:28])([CH3:27])[CH3:26])#[N:2]
Reactant: CC(C)(C)Br
Reactant: N#Cc1cccc(OCC(O)CN)c1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: C1CCOC1
Product: CC(C)(C)NCC(O)COc1cccc(C#N)c1

Procedure:
9.6 gm (0.05 mol) of 1-(3-cyanophenoxy)-2-hydroxy-3-amino propane were dissolved in 40 ml of dimethylformamide and 100 ml of tetrahydrofuran and 4.2 gm (0.05 mol) of pulverized sodium bicarbonate were added thereto. Then, 6.9 gm (0.05 mol) of tert.-butylbromide were added and the mixture was refluxed for 24 hours. After the mixture had been cooled, the inorganic solid was filtered off and the solvent mixture was distilled off in vacuo. The residue was dissolved by heating in ethyl acetate and the insoluble inorganic portions were vacuum filtered off and the filtrate was admixed with petroleum ether. The base precipitated in solid form and was isolated and recrystallized from ethyl acetate with an addition of petroleum ether to obtain 1-(3-cyanophenoxy)-2-hydroxy-3-tert.-butylamino propane having a melting point of 108° - 110°C.
Reaction SMILES: [CH2:1]([CH2:6][NH2:7])[CH2:2][C:3]([OH:5])=[O:4].[NH2:8][CH2:9][C:10]([NH:12][CH2:13][C:14]([NH:16][CH2:17][C:18]([NH:20][CH2:21][CH2:22][C:23]([O:25]C(C)(C)C)=[O:24])=[O:19])=[O:15])=[O:11].O>FC(F)(F)C(O)=O>[CH2:1]([CH2:6][NH2:7])[CH2:2][C:3]([OH:5])=[O:4].[NH2:8][CH2:9][C:10]([NH:12][CH2:13][C:14]([NH:16][CH2:17][C:18]([NH:20][CH2:21][CH2:22][C:23]([OH:25])=[O:24])=[O:19])=[O:15])=[O:11]
Reactant: CC(C)(C)OC(=O)CCNC(=O)CNC(=O)CNC(=O)CN
Agent: NCCCC(=O)O
Solvent: O=C(O)C(F)(F)F
Solvent: O
Product: NCC(=O)NCC(=O)NCC(=O)NCCC(=O)O
Yield: 100 %

Procedure:
820 mg (1.7 mmol) of Mal-Gaba-Gly-Gly-Gly-β-Ala-OtBu was disolved in 9.0 mL of 95:5 trifluoroacetic acid: deionized water and magnetically stirred for 3 hours. Solvent was removed by rotary evaporation under vacuum to give 730 mg (100%) of the title compound. 1H NMR (d6-DMSO) 12.1 (bs, 1H), 8.05-8.20 (m, 3H), 7.82 (t, J=6.0 Hz, 1H), 7.00 (s, 2H), 3.71 (t, J=6.0 Hz, 4H), 3.65 (d, J=6.0 Hz, 2H), 3.41 (t, J=7.2 Hz, 2H), 3.26 (q, J=5.6 Hz, 2H), 2.38 (t, J=7.2 Hz, 2H,), 2.14 (q, J=8.0 Hz, 2H), 1.67-1.77 (m, 2H). 13C NMR (d6-DMSO) 172.70, 171.83, 171.01, 169.50, 168.99, 168.51, 134.38, 42.07, 41.84, 36.75, 34.70, 33.69, 32.28, 23.97 HRMS (M+Na+) Calc. 448.1444 found 448.1465
Reaction SMILES: [CH3:1][O:2][C:3](=[O:21])[CH:4]([NH:13][C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:5][C:6]1[CH:11]=[CH:10][C:9](I)=[CH:8][CH:7]=1.[CH:22]1[C:30]2[C:29]3[CH:31]=[CH:32][CH:33]=[CH:34][C:28]=3[O:27][C:26]=2[C:25]([C:35]2[CH:40]=[CH:39][C:38](B(O)O)=[CH:37][CH:36]=2)=[CH:24][CH:23]=1.C([O-])([O-])=O.[K+].[K+]>C1(C)C=CC=CC=1.C(O)C.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>[CH3:1][O:2][C:3](=[O:21])[CH:4]([NH:13][C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:5][C:6]1[CH:11]=[CH:10][C:9]([C:38]2[CH:39]=[CH:40][C:35]([C:25]3[C:26]4[O:27][C:28]5[CH:34]=[CH:33][CH:32]=[CH:31][C:29]=5[C:30]=4[CH:22]=[CH:23][CH:24]=3)=[CH:36][CH:37]=2)=[CH:8][CH:7]=1
Reactant: COC(=O)C(Cc1ccc(I)cc1)NC(=O)OC(C)(C)C
Reactant: OB(O)c1ccc(-c2cccc3c2oc2ccccc23)cc1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCO
Solvent: Cc1ccccc1
Solvent: CCOC(C)=O
Product: COC(=O)C(Cc1ccc(-c2ccc(-c3cccc4c3oc3ccccc34)cc2)cc1)NC(=O)OC(C)(C)C
Temperature: 25 °C
Yield: 70.3 %

Procedure:
A solution of 2-tert-Butoxycarbonylamino-3-(4-iodophenyl)-propanoic acid methyl ester (1.22 g, 3 mmol), 4-(4-dibenzofuranyl)benzeneboronic acid (0.906 g, 3.15 mmol) and Pd(PPh3)4 (160 mg, 5 mol %) in toluene (25 mL) and ethanol (6.0 mL) was treated with 2 M K2CO3 (4.5 mL). The reaction mixture was heated to reflux for 2 h, cooled to room temperature, diluted with ethyl acetate (100 mL). The organic layer was washed successively with 2% aq HCl and sat. aq NaCl, dried over MgSO4 and concentrated. Purification by flash column chromatography (2-10% ethyl acetate in heptane) gave 2-tert-Butoxycarbonylamino-3-(4′-dibenzofuran-4-yl-biphen-4-yl)-propanoic acid methyl ester (1.1 g, 70%) as an oil. 1H NMR (CDCl3), δ 7.98 (d, J=9 Hz, 2 H), 7.96 (d, J=8 Hz, 2 H), 7.74 (d, J=9, 2H), 7.66 (m, 4 H), 7.42 (m, 5 H), 5.04 (d, J=9 Hz, 1 H), 4.66 (m, 1 H), 3.73 (s, 3 H), 3.15 (m, 2 H), 1.57 (s, 9 H). LCMS 422 (M+−100).
Reaction SMILES: [Cl-].[CH3:2][O:3][CH2:4][P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.CC([O-])(C)C.[K+].[Br:30][C:31]1[C:32]([O:39][CH3:40])=[N:33][CH:34]=[C:35]([CH:38]=1)[CH:36]=O>C1COCC1>[Br:30][C:31]1[C:32]([O:39][CH3:40])=[N:33][CH:34]=[C:35](/[CH:36]=[CH:2]/[O:3][CH3:4])[CH:38]=1
Reactant: COc1ncc(C=O)cc1Br
Reactant: COC[P+](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: CC(C)(C)[O-]
Agent: [Cl-]
Agent: [K+]
Solvent: C1CCOC1
Product: CO/C=C/c1cnc(OC)c(Br)c1
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 84.8 %

Procedure:
A solution of (methoxymethyl)triphenylphosphonium chloride (737 mg, 2.15 mmol) in THF (10 mL) at −78° C. was added t-BuOK (1 M in THF, 2.15 mL, 2.15 mmol) and stirred at 0° C. for 30 mins, then added dropwisely a solution of 5-bromo-6-methoxynicotinaldehyde (310 mg, 1.435 mmol) in THF (6 mL) at 0° C. via cannulation. The mixture was stirred and gradually warmed to rt overnight. The mixture was concentrated and the residue was purified via a flash column using 50% ethyl acetate in hexanes as an eluent. The product containing fractions were concentrated to give (E)-3-bromo-2-methoxy-5-(2-methoxyvinyl)pyridine (296.9 mg, 85% yield).
Reaction SMILES: Cl[C:2]1[N:3]([C:13]2[CH:18]=[C:17]([O:19][CH:20]([CH3:22])[CH3:21])[C:16]([Cl:23])=[CH:15][C:14]=2[F:24])[C:4](=[O:12])[CH:5]=[C:6]([C:8]([F:11])([F:10])[F:9])[N:7]=1.[CH3:25][CH2:26][O-:27].[Na+]>C(O)C>[CH2:26]([O:27][C:2]1[N:3]([C:13]2[CH:18]=[C:17]([O:19][CH:20]([CH3:22])[CH3:21])[C:16]([Cl:23])=[CH:15][C:14]=2[F:24])[C:4](=[O:12])[CH:5]=[C:6]([C:8]([F:11])([F:10])[F:9])[N:7]=1)[CH3:25]
Reactant: CC(C)Oc1cc(-n2c(Cl)nc(C(F)(F)F)cc2=O)c(F)cc1Cl
Reactant: CC[O-]
Agent: [Na+]
Solvent: CCO
Product: CCOc1nc(C(F)(F)F)cc(=O)n1-c1cc(OC(C)C)c(Cl)cc1F

Procedure:
using 2-chloro-1-(4-chloro-2-fluoro-5-isopropoxyphenyl)-4-trifluoromethyl-6(1H)-pyrimidinone and sodium ethylate in ethanol there is obtained 2-ethoxy-1-(4-chloro-2-fluoro -5-isopropoxyphenyl)-4-trifluoromethyl-6(1H)-pyrimidinone, m.p. 101°-103° C.;
Reaction SMILES: CO[C:3](=[O:24])[C:4]1[CH:9]=[CH:8][C:7]([O:10][CH2:11][C:12]2[C:13]([C:17]3[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=3)=[N:14][O:15][CH:16]=2)=[N:6][CH:5]=1.[NH2:25][CH2:26][CH:27]1[CH2:29][CH2:28]1>>[CH:27]1([CH2:26][NH:25][C:3](=[O:24])[C:4]2[CH:9]=[CH:8][C:7]([O:10][CH2:11][C:12]3[C:13]([C:17]4[CH:18]=[CH:19][C:20]([F:23])=[CH:21][CH:22]=4)=[N:14][O:15][CH:16]=3)=[N:6][CH:5]=2)[CH2:29][CH2:28]1
Reactant: NCC1CC1
Reactant: COC(=O)c1ccc(OCc2conc2-c2ccc(F)cc2)nc1
Product: O=C(NCC1CC1)c1ccc(OCc2conc2-c2ccc(F)cc2)nc1
Yield: 31 %

Procedure:
As described for example 324, 6-[3-(4-fluoro-phenyl)-isoxazol-4-ylmethoxy]-nicotinic acid methyl ester (200 mg, 0.61 mmol) was converted, using aminomethylcyclopropane instead of 4-aminotetrahydropyran, to the title compound (70 mg, 31%) which was obtained as a white solid. MS: m/e=368.1 [M+H]+.
Reaction SMILES: [NH2:1][C:2]1[C:3]([C:14]([O:16]C)=[O:15])=[N:4][C:5]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)=[CH:6][N:7]=1.[OH-].[Na+].Cl>CO>[NH2:1][C:2]1[C:3]([C:14]([OH:16])=[O:15])=[N:4][C:5]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)=[CH:6][N:7]=1
Reactant: COC(=O)c1nc(-c2ccccc2)cnc1N
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: Nc1ncc(-c2ccccc2)nc1C(=O)O
Reaction time: 3 h
Yield: 52.1 %

Procedure:
To a solution of methyl 3-amino-6-phenylpyrazine-2-carboxylate (1.2 g, 5.26 mmol) in methanol (5 mL) was added 6.0 N aqueous sodium hydroxide (6 mL) at room temperature. The solution was stirred at 50 C. for 3 h. The reaction was neutralized slowly by adding 2.0 N hydrochloric acid until the pH of the solution became in the 2-3 range at 0° C. The solution was extracted with ethyl acetate (50 mL). The organic layer was washed with saturated aqueous sodium chloride (50 mL) and dried over magnesium sulfate. Filtration and concentration at reduced pressure afforded 3-amino-6-phenylpyrazine-2-carboxylic acid (0.59 g, 52% yield): MS (EI) for C11H9O2: 216 (MH+)
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([C:14]([O:16][CH3:17])=[O:15])[CH:9]=2)[CH:5]=[CH:6][CH:7]=1.Br[CH2:19][CH2:20][NH:21][C:22](=[O:28])[O:23][C:24]([CH3:27])([CH3:26])[CH3:25]>CN(C=O)C>[CH3:17][O:16][C:14]([C:10]1[CH:9]=[C:8]([C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([NH:1][CH2:19][CH2:20][NH:21][C:22]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:28])[CH:3]=2)[CH:13]=[CH:12][CH:11]=1)=[O:15]
Reactant: CC(C)(C)OC(=O)NCCBr
Reactant: COC(=O)c1cccc(-c2cccc(N)c2)c1
Solvent: CN(C)C=O
Product: COC(=O)c1cccc(-c2cccc(NCCNC(=O)OC(C)(C)C)c2)c1
Temperature: 55 °C
Yield: 16.3 %

Procedure:
A mixture of methyl 3′-aminobiphenyl-3-carboxylate (3.0 g, 13.22 mmol, 1.00 equiv.), tert-butyl 2-bromoethylcarbamate (3.0 g, 13.22 mmol, 1.00 equiv.) potassium carbonate (3.6 g, 26.09 mmol, 2.00 equiv.), and N,N′-dimethylformamide (20 mL) was heated at 50-60° C. for about 16 hours. Additional tert-butyl 2-bromoethylcarbamate (3.0 g, 13.22 mmol, 1.00 equiv) was added and the mixture was heated an additional 14 hours. The mixture was cooled to ambient temperature and partitioned between ethyl acetate and water. The organic layer was separated, washed with water, dried over sodium sulfate, filtered, and concentrated to afford a crude product that was purified by silica gel chromatography (petroleum ether/ethyl acetate (8:1) to give the title product as light-yellow oil (800 mg; yield=16%).
Reaction SMILES: [OH:1][CH:2]1[CH2:7][CH2:6][NH:5][CH2:4][CH2:3]1.[Cl:8][C:9]1[CH:10]=[C:11]([C:15]2[O:19][N:18]=[CH:17][C:16]=2[CH2:20][CH2:21][C:22](O)=[O:23])[CH:12]=[CH:13][CH:14]=1.N=C=N>ClCCl>[Cl:8][C:9]1[CH:10]=[C:11]([C:15]2[O:19][N:18]=[CH:17][C:16]=2[CH2:20][CH2:21][C:22]([N:5]2[CH2:6][CH2:7][CH:2]([OH:1])[CH2:3][CH2:4]2)=[O:23])[CH:12]=[CH:13][CH:14]=1
Reactant: O=C(O)CCc1cnoc1-c1cccc(Cl)c1
Reactant: OC1CCNCC1
Agent: N=C=N
Solvent: ClCCl
Product: O=C(CCc1cnoc1-c1cccc(Cl)c1)N1CCC(O)CC1
Temperature: 25 °C
Reaction time: 8 h
Yield: 46 %

Procedure:
A mixture of 4-hydroxypiperidine (10 mg), 3-[5-(3-chlorophenyl)-4-isoxazolyl]propionic acid (25 mg), PS-carbodiimide (100 mg, manufactured by Argonaut Technologies) and dichloromethane (1 ml) was shaken at room temperature overnight. The reaction mixture was filtrated and the filtrate was concentrated. The obtained residue was purified by preparative HPLC to give 1-{3-[5-(3-chlorophenyl)-4-isoxazolyl]propanoyl}-4-piperidinol.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][C:10]2[N:11]=[C:12]([NH:15][C:16](=[O:25])[O:17][CH2:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[S:13][CH:14]=2)=[CH:4][CH:3]=1.[N:26]#[C:27][NH2:28].Cl>C(OCC)(=O)C.C(O)C>[NH2:28][C:27]([NH:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][C:10]2[N:11]=[C:12]([NH:15][C:16]([O:17][CH2:18][C:19]3[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=3)=[O:25])[S:13][CH:14]=2)=[CH:4][CH:3]=1)=[NH:26]
Reactant: Nc1ccc(CCc2csc(NC(=O)OCc3ccccc3)n2)cc1
Reactant: N#CN
Agent: Cl
Solvent: CCO
Solvent: CCOC(C)=O
Product: N=C(N)Nc1ccc(CCc2csc(NC(=O)OCc3ccccc3)n2)cc1
Temperature: 100 °C
Reaction time: 72 h
Yield: 53.6 %

Procedure:
A mixture of benzyl 4-[2-(4-aminophenyl)ethyl]-1,3-thiazol-2-ylcarbamate (25 mg), cyanamide (6.0 mg), 4N hydrogen chloride in ethyl acetate (0.018 ml) and ethanol (1 ml) was stirred at 100° C. for 72 hours. The reaction mixture was concentrated in vacuo. To the residue was added ethyl acetate (5 ml) and saturated aqueous sodium hydrogen bicarbonate (5 ml). The precipitated solid was filtered and washed with ethylacetate and water to give benzyl 4-[2-(4-{[amino(imino)methyl]amino}phenyl)ethyl]-1,3-thiazol-2-carbamate (15 mg).
Reaction SMILES: [CH2:1]([Sn:5](=[O:10])[CH2:6][CH2:7][CH2:8][CH3:9])[CH2:2][CH2:3][CH3:4].[CH2:11]([OH:15])[CH2:12][CH2:13][CH3:14]>>[CH2:1]([Sn:5]([CH2:6][CH2:7][CH2:8][CH3:9])([O:15][CH2:11][CH2:12][CH2:13][CH3:14])[O:10][Sn:5]([CH2:6][CH2:7][CH2:8][CH3:9])([CH2:1][CH2:2][CH2:3][CH3:4])[O:15][CH2:11][CH2:12][CH2:13][CH3:14])[CH2:2][CH2:3][CH3:4]
Reactant: CCCCO
Reactant: CCCC[Sn](=O)CCCC
Product: CCCCO[Sn](CCCC)(CCCC)O[Sn](CCCC)(CCCC)OCCCC
Reaction time: 0.5 h
Yield: 99 %

Procedure:
692 g (2.78 mol) of dibutyltin oxide (made by Sankyo Organic Chemicals Co., Ltd., Japan) and 2000 g (27 mol) of 1-butanol (made by Wako, Japan) were put into a 3000 mL flask. The flask containing the mixture, which was a white slurry, was attached to an evaporator (R-144, made by Sibata, Japan) having a temperature regulator-equipped oil bath (OBH-24, made by Masuda Corporation, Japan), a vacuum pump (G-50A, made by Ulvac, Japan) and a vacuum controller (VC-10S, made by Okano Works Ltd., Japan) connected thereto. The outlet of a purge valve of the evaporator was connected to a line for nitrogen gas flowing at normal pressure. The purge valve of the evaporator was closed, and the pressure in the system was reduced, and then the purge valve was gradually opened, so as to pass nitrogen into the system, and thus return the system to normal pressure. The oil bath temperature was set to 126° C., and the flask was immersed in the oil bath and rotation of the evaporator was commenced. With the purge valve of the evaporator left open, rotational stirring and heating were carried out for approximately 30 minutes at normal pressure, whereupon the liquid mixture boiled, and hence distilling off of a low boiling component began. This state was maintained for 8 hours, and then the purge valve was closed, and the pressure in the system was gradually reduced, and residual low boiling component was distilled off with the pressure in the system at from 76 to 54 kPa. Once low boiling component stopped coming off, the flask was lifted out from the oil bath. The reaction liquid was a transparent liquid. After lifting the flask out from the oil bath, the purge valve was gradually opened, so as to return the pressure in the system to normal pressure. 952 g of reaction liquid was obtained in the flask. According to 119Sn—, 1H—, and 13C-NMR analysis results, the product 1,1,3,3-tetrabutyl-1,3-di(butyloxy)-distannoxane was obtained at a yield of 99% based on the dibutyltin oxide. The same procedure was carried out so as to produce 1,1,3,3-tetrabutyl-1,3-di(butyloxy)-distannoxane to be used in the following step B.
Reaction SMILES: [Si]([O:8][CH2:9][CH2:10][N:11]([CH3:41])[C:12]([C:14]1[C:19]([O:20][CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)=[C:18]([OH:28])[N:17]=[C:16]([CH2:29][C:30]2([C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][N:36]=3)[CH2:34][CH2:33][CH2:32][CH2:31]2)[N:15]=1)=[O:13])(C(C)(C)C)(C)C.Cl>O1CCCC1>[OH:8][CH2:9][CH2:10][N:11]([CH3:41])[C:12]([C:14]1[C:19]([O:20][CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)=[C:18]([OH:28])[N:17]=[C:16]([CH2:29][C:30]2([C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][N:36]=3)[CH2:34][CH2:33][CH2:32][CH2:31]2)[N:15]=1)=[O:13]
Reactant: CN(CCO[Si](C)(C)C(C)(C)C)C(=O)c1nc(CC2(c3ccccn3)CCCC2)nc(O)c1OCc1ccccc1
Agent: Cl
Solvent: C1CCOC1
Product: CN(CCO)C(=O)c1nc(CC2(c3ccccn3)CCCC2)nc(O)c1OCc1ccccc1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a stirred solution 5-benzyloxy-6-hydroxy-2-(1-pyridin-2-yl-cyclopentylmethyl)-pyrimidine-4-carboxylic acid [2-(tert-butyl-dimethylsilanyloxy)-ethyl]-methyl-amide (442) (180 mg, 0.313 mmol) of in tetrahydrofuran (10 mL), was added 1N HCl (2 mL), then this reaction mixture was stirred for 1 h, at room temperature, After completion of the reaction, volatiles were removed from the reaction mixture and the residue was diluted with water (10 mL) and pH was adjusted with NaHCO3 to 8. The quenched mass was extracted with ethyl acetate (2×50 mL). The combined extracts were dried and concentrated. The resulting crude product was purified by normal silica gel (100-200 mesh) column chromatography using 50-60% ethyl acetate in hexane as a gradient polarity mobile phase to get 5-benzyloxy-6-hydroxy-2-(1-pyridin-2-yl-cyclopentylmethyl)-pyrimidine-4-carboxylic acid (2-hydroxyethyl)-methyl-amide (443).
Reaction SMILES: Cl.[CH:2]1([C:5]2[N:10]=[CH:9][C:8]([C:11]3[CH:12]=[C:13]4[C:18](=[CH:19][N:20]=3)[CH2:17][NH:16][CH2:15][CH2:14]4)=[CH:7][N:6]=2)[CH2:4][CH2:3]1.[CH3:21][C@@:22]1([CH2:29][S:30](Cl)(=[O:32])=[O:31])[C:26](=[O:27])[NH:25][C:24](=[O:28])[NH:23]1>C(Cl)Cl.C1COCC1>[CH:2]1([C:5]2[N:6]=[CH:7][C:8]([C:11]3[CH:12]=[C:13]4[C:18](=[CH:19][N:20]=3)[CH2:17][N:16]([S:30]([CH2:29][C@@:22]3([CH3:21])[NH:23][C:24](=[O:28])[NH:25][C:26]3=[O:27])(=[O:31])=[O:32])[CH2:15][CH2:14]4)=[CH:9][N:10]=2)[CH2:4][CH2:3]1
Reactant: c1nc(C2CC2)ncc1-c1cc2c(cn1)CNCC2
Reactant: C[C@]1(CS(=O)(=O)Cl)NC(=O)NC1=O
Agent: Cl
Solvent: C1CCOC1
Solvent: ClCCl
Product: C[C@]1(CS(=O)(=O)N2CCc3cc(-c4cnc(C5CC5)nc4)ncc3C2)NC(=O)NC1=O
Temperature: 25 °C
Reaction time: 8 h
Yield: 67.8 %

Procedure:
To a stirred solution of 6-(2-cyclopropylpyrimidin-5-yl)-1,2,3,4-tetrahydro-2,7-naphthyridine hydrochloride (0.12 g, 0.42 mmol) in DCM (10 mL) was added TEA (0.12 mL, 0.84 mmol) followed by the dropwise addition of [(4S)-4-methyl-2,5-dioxoimidazolidin-4-yl]methanesulfonyl chloride (0.090 g, 0.40 mmol) in THF (10 mL) at −10° C. The mixture was stirred at RT overnight, concentrated, taken up in water (10 mL) and extracted four times with EtOAc. The combined organic phases were dried, filtered and concentrated. Purification by prep-HPLC gave 0.12 g (64%) of the title compound as a white solid.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[N:4][C:5]2[N:6]([N:8]=[C:9]([C:11]([OH:13])=O)[CH:10]=2)[CH:7]=1.[O:14]1[CH:18]=[CH:17][C:16]([C:19]2[CH:20]=[C:21]3[C:26](=[CH:27][CH:28]=2)[CH:25]([CH3:29])[NH:24][CH2:23][CH2:22]3)=[CH:15]1>>[Br:1][C:2]1[CH:3]=[N:4][C:5]2[N:6]([N:8]=[C:9]([C:11]([N:24]3[CH2:23][CH2:22][C:21]4[C:26](=[CH:27][CH:28]=[C:19]([C:16]5[CH:17]=[CH:18][O:14][CH:15]=5)[CH:20]=4)[CH:25]3[CH3:29])=[O:13])[CH:10]=2)[CH:7]=1
Reactant: CC1NCCc2cc(-c3ccoc3)ccc21
Reactant: O=C(O)c1cc2ncc(Br)cn2n1
Product: CC1c2ccc(-c3ccoc3)cc2CCN1C(=O)c1cc2ncc(Br)cn2n1

Procedure:
In close analogy to the procedure described in Example 1, 6-bromo-pyrazolo[1,5-a]pyrimidine-2-carboxylic acid is reacted with 6-Furan-3-yl-1-methyl-1,2,3,4-tetrahydro-isoquinoline to provide the title compound in moderate yield.
Reaction SMILES: [OH:1][OH:2].[C:3]([O:6][OH:7])(=[O:5])[CH3:4].[C:8]([OH:11])(=[O:10])[CH3:9]>>[C:3]([O:6][OH:7])(=[O:5])[CH3:4].[OH:1][OH:2].[C:8]([O:11][C:3](=[O:5])[CH3:4])(=[O:10])[CH3:9]
Reactant: CC(=O)O
Agent: CC(=O)OO
Agent: OO
Product: CC(=O)OC(C)=O

Procedure:
Referring to FIG. 1 an arrangement useful for epoxidizing an olefin in a batchwise manner is illustated. Epoxidation reactor 1 initially is filled with an unsaturated hydrocarbon compound such as an olefin via conduit 10. An acid stream comprising an aqueous mixture of hydrogen peroxide, acetic acid and peracetic acid then is introduced into reactor 1 through conduit 11 for contacting the oil phase. The acid stream flows through reactor 1; is separately recovered from the oil phase in conduit 12, and is deliverd by circulating pump 5 to regeneration stage 2. In regeneration stage 2, peracetic acid is formed by the catalytic reaction between hydrogen peroxide and acetic acid or acetic anhydride. Additional hydrogen peroxide and acetic acid or acetic anhydride are added to the recirculating acid in conduit 12 via pumps 3 and 4 respectively. A quantity of liquid necessary to balance the addition of new components to the acid stream is removed through conduit 13. The regenerated aqueous acid phase then is returned to reactor 1 through conduit 11. Once the oil phase has been completely epoxidized, the epoxide product is removed from reactor 1 through valved conduit 27.