Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C(OC([N:11]1[C@H:33]([CH2:34][OH:35])[C@@H:24]([O:25]CC2C=CC=CC=2)[C@H:22]([OH:23])[C@@H:13]([O:14]CC2C=CC=CC=2)[CH2:12]1)=O)C1C=CC=CC=1.C(OCC)C>C(O)(=O)C.[Pd]>[NH:11]1[C@H:33]([CH2:34][OH:35])[C@@H:24]([OH:25])[C@H:22]([OH:23])[C@@H:13]([OH:14])[CH2:12]1
Reactant: O=C(OCc1ccccc1)N1C[C@H](OCc2ccccc2)[C@@H](O)[C@H](OCc2ccccc2)[C@H]1CO
Agent: [Pd]
Solvent: CC(=O)O
Solvent: CCOCC
Product: OC[C@H]1NC[C@H](O)[C@@H](O)[C@@H]1O
Yield: 96 %

Procedure:
The diol (17) (580 mg, 1.2 mmol) was stirred in glacial acetic acid (30 ml) in the presence of palladium black (100 mg) under hydrogen for 3 days, by which time no starting material (Rf 0.2) remained by t.l.c. (diethyl ether). Filtration and removal of the solvent then gave a gum which was purified by ion exchange chromatography with Dowex 50(H+) followed by Amberlite CC-400(Cl-) resins to give 1,5-dideoxy-1,5-imino-D-glucitol (3) (188 mg, 95%), which was crystallized as its hydrochloride salt. m.p. 204°-205° C. (lit.* 203°-206° C.). All spectroscopic data were identical to that of authentic material. 13C NMR (D2O) free base δ: 79.0, 72.1, 71.1 (3d, C-2, C-3, C-4), 61.9 (t, C-6), 61.0 (d, C-5), 49.2 (t, C-1). Hydrogen chloride salt δ: 77.1, 68.6, 67.8 (3d, C-2, C-3, C-4), 60.8 (d, C-5), 58.5 (t, C-6), 46.7 (t, C-1). [*Fleet et al., Tetrahedron 43, 979 (1987)].
Reaction SMILES: [Br:1][C:2]1[N:7]=[CH:6][C:5]([C:8](=[O:12])[CH2:9][O:10][CH3:11])=[CH:4][CH:3]=1.O1CCCC1.[BH4-].[Na+].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C(O)C>[Br:1][C:2]1[N:7]=[CH:6][C:5]([CH:8]([OH:12])[CH2:9][O:10][CH3:11])=[CH:4][CH:3]=1
Reactant: COCC(=O)c1ccc(Br)nc1
Agent: O=C(O)CC(O)(CC(=O)O)C(=O)O
Agent: [BH4-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CCO
Product: COCC(O)c1ccc(Br)nc1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 95.4 %

Procedure:
To a mixture of 1-(6-bromopyridin-3-yl)-2-methoxyethanone (15.85 g), tetrahydrofuran (15 mL) and ethanol (15 mL) was slowly added sodium borohydride (0.97 g) at room temperature, and the mixture was stirred at room temperature for 30 min. To the reaction mixture was added 10% aqueous citric acid solution, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine, dried (MgSO4) and concentrated. The obtained residue was subjected to silica gel column chromatography, and the title compound (15.26 g, yield 96%) was obtained as a yellow oil from a fraction eluted with ethyl acetate. MS: 234 (MH+).
Reaction SMILES: [NH:1]([C:3]1[CH:8]=[C:7]([S:9][CH3:10])[N:6]=[C:5]([CH3:11])[N:4]=1)[NH2:2].[C:12](OCC)(OCC)(OCC)[CH3:13]>>[CH3:12][C:13]1[N:4]2[C:5]([CH3:11])=[N:6][C:7]([S:9][CH3:10])=[CH:8][C:3]2=[N:1][N:2]=1
Reactant: CSc1cc(NN)nc(C)n1
Reactant: CCOC(C)(OCC)OCC
Product: CSc1cc2nnc(C)n2c(C)n1

Procedure:
A mixture of 2.5 g (0.015 mole) of 4-hydrazino-2-methyl-6-methythiopyrimidine and 50 ml of triethyl orthoacetate was heated at its reflux temperature for five days, and was then cooled. The solid was separated by filtration and recrystallized with treatment with decolorizing charcoal from first an ethyl acetate-hexane mixture, and then a benzene-hexane mixture to provide 3,5-dimethyl-7-methythio-1,2,4-triazolo[4,3-c]pyrimidine, m.p. 201°-203° C. Calculated for C8H10N4S: %C, 49.5; %H, 5.2; %N, 28.8; Found: %C, 49.6; %H, 5.2; % N, 28.9.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:30]=[C:29]([O:31][CH2:32][C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[C:28]([C:39]([CH3:41])=[CH2:40])=[CH:27][C:10]=1[C:11]([NH:13][C:14]1[CH:19]=[CH:18][C:17]([CH2:20][N:21]2[CH2:26][CH2:25][O:24][CH2:23][CH2:22]2)=[CH:16][CH:15]=1)=[O:12])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].[CH2:44](Br)[C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1>CN(C=O)C.CCOC(C)=O.O>[CH2:44]([N:13]([C:14]1[CH:15]=[CH:16][C:17]([CH2:20][N:21]2[CH2:26][CH2:25][O:24][CH2:23][CH2:22]2)=[CH:18][CH:19]=1)[C:11](=[O:12])[C:10]1[CH:27]=[C:28]([C:39]([CH3:41])=[CH2:40])[C:29]([O:31][CH2:32][C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)=[CH:30][C:9]=1[O:8][CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)[C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1
Reactant: BrCc1ccccc1
Reactant: C=C(C)c1cc(C(=O)Nc2ccc(CN3CCOCC3)cc2)c(OCc2ccccc2)cc1OCc1ccccc1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Solvent: CCOC(C)=O
Product: C=C(C)c1cc(C(=O)N(Cc2ccccc2)c2ccc(CN3CCOCC3)cc2)c(OCc2ccccc2)cc1OCc1ccccc1
Reaction time: 0.25 h
Yield: 69.6 %

Procedure:
2,4-Bis-benzyloxy-5-isopropenyl-N-(4-morpholin-4-ylmethyl-phenyl)-benzamide (0.245 g, 0.45 mmol) [prepared using Method A2 from (2,4-bis-benzyloxy-5-isopropenyl)-benzoic acid (Preparation B5) and 4-morpholin-4-yl-methyl-phenylamine] dissolved in DMF (3 ml), was treated with 60% NaH in mineral oil (27 mg, 1.5 eq) and stirred for 15 minutes followed by the addition of benzyl bromide (0.052 ml, 0.45 mmol), then stirred for a further 2 hours at room temperature. The reaction was diluted with EtOAc and water. The EtOAc layer was separated, washed with brine, dried (MgSO4) and evaporated to afford 0.2 g of the title compound as a yellow oil. MS: [M+H]+ 639
Reaction SMILES: Br[CH2:2][C:3]1[N:8]([C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([C:15]([F:18])([F:17])[F:16])[CH:10]=2)[C:7](=[O:19])[NH:6][CH:5]([C:20]2[CH:25]=[CH:24][C:23]([C:26]#[N:27])=[CH:22][C:21]=2[S:28]([CH3:31])(=[O:30])=[O:29])[C:4]=1[C:32](OCC)=[O:33].[CH3:37][NH:38][NH2:39]>O1CCOCC1>[CH3:37][N:38]1[CH2:2][C:3]2[N:8]([C:9]3[CH:14]=[CH:13][CH:12]=[C:11]([C:15]([F:18])([F:16])[F:17])[CH:10]=3)[C:7](=[O:19])[NH:6][CH:5]([C:20]3[CH:25]=[CH:24][C:23]([C:26]#[N:27])=[CH:22][C:21]=3[S:28]([CH3:31])(=[O:30])=[O:29])[C:4]=2[C:32](=[O:33])[NH:39]1
Reactant: CCOC(=O)C1=C(CBr)N(c2cccc(C(F)(F)F)c2)C(=O)NC1c1ccc(C#N)cc1S(C)(=O)=O
Reactant: CNN
Solvent: C1COCCO1
Product: CN1CC2=C(C(=O)N1)C(c1ccc(C#N)cc1S(C)(=O)=O)NC(=O)N2c1cccc(C(F)(F)F)c1

Procedure:
Ethyl 6-(bromomethyl)-4-[4-cyano-2-(methylsulphonyl)phenyl]-2-oxo-1-[3-(trifluoromethyl)-phenyl]-1,2,3,4-tetrahydropyrimidine-5-carboxylate (150 mg, 0.256 mmol; Example 19A) was initially charged in dioxane (3.5 ml). Methylhydrazine (35.4 mg, 0.767 mmol) was added dropwise to the reaction mixture, and the mixture was then stirred at boiling point for 3 h. The reaction mixture was then separated directly by preparative HPLC (Method 12). This gave 55 mg (39% of theory) of the target compound.
Reaction SMILES: [C:1]([C:4]1[CH:5]=[C:6]([CH:29]=[CH:30][CH:31]=1)[C:7]([N:9]([CH2:11][CH2:12][O:13][CH2:14][CH2:15][O:16][CH2:17][CH2:18][O:19][CH2:20][CH2:21][C:22]([O:24]C(C)(C)C)=[O:23])[CH3:10])=[O:8])(=[O:3])[NH2:2].FC(F)(F)C(O)=O>ClCCl>[C:1]([C:4]1[CH:5]=[C:6]([CH:29]=[CH:30][CH:31]=1)[C:7]([N:9]([CH2:11][CH2:12][O:13][CH2:14][CH2:15][O:16][CH2:17][CH2:18][O:19][CH2:20][CH2:21][C:22]([OH:24])=[O:23])[CH3:10])=[O:8])(=[O:3])[NH2:2]
Reactant: CN(CCOCCOCCOCCC(=O)OC(C)(C)C)C(=O)c1cccc(C(N)=O)c1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: CN(CCOCCOCCOCCC(=O)O)C(=O)c1cccc(C(N)=O)c1
Yield: 84.1 %

Procedure:
To a solution of tert-butyl 3-(2-(2-(2-(3-(carbamoyl)-N-methylbenzamido)ethoxy)ethoxy)ethoxy)propanoate (120 mg, 0.14 mmol, 1.00 equiv, 90%) in dichloromethane (10 mL) was added trifluoroacetic acid (2 mL) dropwise with stirring and the resulting solution was stirred for 2 h at room temperature. The reaction progress was monitored by LCMS. The resulting mixture was concentrated under vacuum and the crude product (100 mg) was purified by reverse phase HPLC eluting with a water/CH3CN gradient containing 0.05% TFA to afford 45 mg (45%) of a yellow solid. 1H-NMR (300 MHz, DMSO, ppm): 10.95 (s, 1H), 10.87 (s, 1H), 9.19 (s, 2H), 8.35-8.38 (t, 2H), 8.04-8.07 (d, J=9 Hz, 1H), 7.93 (s, 1H), 7.89 (s, 1H), 7.51-7.60 (m, 5H), 7.34 (s, 1H), 3.43-3.62 (m, 17H), 3.98 (s, 3H), 2.38-2.42 (t, J=6, 6 Hz, 2H), 1.51-1.71 (m, 6H). MS (ES, m/z): 739 [M+11]+.
Reaction SMILES: [CH2:1]([OH:6])[CH2:2][C@@H:3]([OH:5])[CH3:4].C(N(CC)CC)C.[C:14]1([CH3:24])[CH:19]=[CH:18][C:17]([S:20](Cl)(=[O:22])=[O:21])=[CH:16][CH:15]=1>ClCCl>[C:14]1([CH3:24])[CH:19]=[CH:18][C:17]([S:20]([O:6][CH2:1][CH2:2][C@@H:3]([OH:5])[CH3:4])(=[O:22])=[O:21])=[CH:16][CH:15]=1
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Reactant: C[C@H](O)CCO
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: Cc1ccc(S(=O)(=O)OCC[C@H](C)O)cc1
Temperature: 25 °C
Reaction time: 3 h
Yield: 83.4 %

Procedure:
To a solution of (S)-1,3-butanediol (1.0 g) and triethylamine (1.12 g) in dichloromethane (30 ml) was added portionwise p-toluenesulfonyl chloride (2.12 g) at 0° C., and then the mixture was stirred at ambient temperature for 3hours and stand overnight. The resulting solution was dilueted with dichloromethane (30 ml) and the organic layer was washed successively with 1 N hydrochloric acid, saturated sodium bicarbonate aqueous solution and brine. Drying, filtering and removal of solvents afforded (S)-3-hyrdoxybutyl p-toluenesulfonate (2.26 g).
Reaction SMILES: CO[C:3]([CH:5]1[C:10]2[S:11][CH:12]=[CH:13][C:9]=2[S:8](=[O:15])(=[O:14])[NH:7][C:6]1=[O:16])=[O:4].[NH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][N:19]=1.[C:24]1(C)C(C)=CC=CC=1>>[CH3:24][N:7]1[C:6](=[O:16])[CH:5]([C:3](=[O:4])[NH:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][N:19]=2)[C:10]2[S:11][CH:12]=[CH:13][C:9]=2[S:8]1(=[O:14])=[O:15]
Reactant: Cc1ccccc1C
Reactant: Nc1ccccn1
Reactant: COC(=O)C1C(=O)NS(=O)(=O)c2ccsc21
Product: CN1C(=O)C(C(=O)Nc2ccccn2)c2sccc2S1(=O)=O

Procedure:
0.3 G. of 3,4-dihydro-4-methoxycarbonyl-3-oxo-2H-thieno[ 2,3-e] 1,2-thiazine 1,1-dioxide and 0.13 g. of 2-aminopyridine are dissolved in 30 ml. of absolute xylene and the solution is heated for 1 hour under reflux. After cooling, the crystals are removed by filtration and recrystallized from glacial acetic acid. 3,4-Dihydro-2-methyl-3-oxo-4-(2-pyridyl-carbamoyl)-2H-thieno [2,3-e] 1,2-thiazine 1,1-dioxide, melting point 225° C. to 256° C. (decomposition), is obtained.
Reaction SMILES: C([CH:3]1[CH2:11][C:10]2[C:5](=[CH:6][CH:7]=[C:8]([N+:12]([O-])=O)[CH:9]=2)[CH:4]1[C:15]1[N:16]=[CH:17][NH:18][CH:19]=1)C.[H][H].[CH2:22](O)[CH3:23]>O=[Pt]=O>[NH2:12][C:8]1[CH:9]=[C:10]2[C:11](=[CH:6][CH:7]=1)[CH2:3][C:4]([C:15]1[N:16]=[CH:17][NH:18][CH:19]=1)([CH2:22][CH3:23])[CH2:5]2
Reactant: [H][H]
Reactant: CCO
Reactant: CCC1Cc2cc([N+](=O)[O-])ccc2C1c1c[nH]cn1
Agent: O=[Pt]=O
Product: CCC1(c2c[nH]cn2)Cc2ccc(N)cc2C1
Yield: 91 %

Procedure:
A solution of 4-(2-ethyl-2,3-dihydro-5-nitro-1H-inden-1-yl)-1H-imidazole (10.25 g, 0.03988 mol) in ethanol (150 ml) was hydrogenated over PtO2 (1 g) at 3 atm pressure. When the uptake of hydrogen ceased the reaction mixture was filtered and evaporated to dryness to give 4-(5-amino-2-ethyl-2,3-dihydro-1H-inden-2-yl)-1H-imidazole (8.2 g, 91%).
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][C:5]([SH:8])=[CH:4][CH:3]=1.[NH2:9][CH2:10][CH2:11][CH2:12]O.[C:14]([OH:18])(=O)[CH2:15][CH3:16]>>[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([S:8][CH2:12][CH2:11][CH2:10][NH:9][C:14](=[O:18])[CH2:15][CH3:16])=[CH:4][CH:3]=1
Reactant: NCCCO
Reactant: Cc1ccc(S)cc1
Reactant: CCC(=O)O
Product: CCC(=O)NCCCSc1ccc(C)cc1

Procedure:
The experiment of Example 1A was repeated in all essential details except that p-thiocresol, 3-aminopropanol and propionic acid in equimolar amounts were used as the reactants. There was obtained N-[3-(p-methylphenylthio)-propyl]propionamide, m.p. 55.5°-56.5° C., designated P-2142. The nmr spectrum was consistent with the proposed structure. P-2142 was generally ineffective for controlling the growth of seven species of bacteria but was effective (MIC-100-500) for controlling the growth of four species of fungi.
Reaction SMILES: N[C:2]1[C:3]([O:17][CH3:18])=[C:4]([NH:12][S:13]([CH3:16])(=[O:15])=[O:14])[CH:5]=[C:6]([C:8]([CH3:11])([CH3:10])[CH3:9])[CH:7]=1.[H+].[B-](F)(F)(F)F.N([O:27][CH2:28]CC(C)C)=O.C1C[O:36][CH2:35]C1>>[CH3:35][O:36][C:28](=[O:27])[C:2]1[CH:7]=[C:6]([C:8]([CH3:11])([CH3:10])[CH3:9])[CH:5]=[C:4]([NH:12][S:13]([CH3:16])(=[O:15])=[O:14])[C:3]=1[O:17][CH3:18]
Reactant: CC(C)CCON=O
Reactant: C1CCOC1
Reactant: COc1c(N)cc(C(C)(C)C)cc1NS(C)(=O)=O
Agent: F[B-](F)(F)F
Agent: [H+]
Product: COC(=O)c1cc(C(C)(C)C)cc(NS(C)(=O)=O)c1OC
Reaction time: 2 h

Procedure:
To a 0° C. solution of 1.34 g (4.92 mmol) of N-(3-amino-5-tert-butyl-2-methoxy-phenyl)-methanesulfonamide and 1.3 mL (10 mmol) of 48% aqueous HBF4 in 10 mL of THF was added 586 mg (5 mmol) of isoamyl nitrite. The mixture was stirred 2 h, then the solvent was removed and the resulting orange semi-solid triturated with MTBE (3×10 mL). The resulting residue was taken up in MeOH and while CO was bubbled through, 60 mg of Pd(OAc)2 was added, and the mixture was stirred with continuous CO bubbling for 1 h. The solution was filtered, concentrated, and purified by chromatography (0 to 50% EtOAc in hexanes) to provide the title compound as a white solid (752 mg).
Reaction SMILES: C([N:11]=[C:12]=[O:13])CCCCCCCCC.Cl.C(O[NH:23][CH2:24][CH2:25][CH2:26][C:27]([O:29][CH2:30][CH3:31])=[O:28])C1C=CC=CC=1.C(N(CC)CC)C>C1(C)C=CC=CC=1.CN(C=O)C>[CH2:30]([O:29][C:27]([CH2:26][CH2:25][CH2:24][NH:23][C:12](=[O:13])[NH2:11])=[O:28])[CH3:31]
Reactant: CCOC(=O)CCCNOCc1ccccc1
Reactant: CCCCCCCCCCN=C=O
Agent: Cl
Solvent: Cc1ccccc1
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: CCOC(=O)CCCNC(N)=O
Reaction time: 1 h
Yield: 180.7 %

Procedure:
Using the method of Example 2 above, but using ethyl 4-bromobutyrate, t-butyl N-[3-(ethoxycarbonyl)propyl]-N-benzyloxy carbamate was obtained as a colorless oil. This carbamate (6.17 g, 18.8 mmol) was dissolved in 3.3M HCl in ethyl acetate (50 ml) at room temperature under nitrogen. After one hour, the turbid solution was evaporated, and the residue was triturated with hexane. Filtration gave ethyl 4-(benzyloxyamino)butyrate hydrochloride as a white solid (4.59 g, 93% yield). To a solution of decyl isocyanate (0.92 g) in toluene (50 ml) was added this hydrochloride (1.40 g) in DMF (5 ml). Triethylamine (0.75 ml) was added, and the solution was stirred for one hour. The mixture was washed with 10% aqueous citric acid, and the organic solution was dried (MgSO4), filtered and evaporated. Purification by chromatography on silica gave N'-decyl-N-benzyloxy-N-[3-(ethoxycarbonylpropyl]urea as a colorless oil (1.58 g, 58% yield).
Reaction SMILES: [Na].[NH:2]1[CH:6]=[CH:5][CH:4]=[N:3]1.[CH2:7](Br)[CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1>CCO.[Na+].[I-]>[CH2:7]([N:2]1[CH:6]=[CH:5][CH:4]=[N:3]1)[CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1
Reactant: BrCCc1ccccc1
Reactant: c1cn[nH]c1
Agent: [I-]
Agent: [Na+]
Agent: [Na]
Solvent: CCO
Product: c1ccc(CCn2cccn2)cc1
Temperature: 50 °C
Yield: 24.7 %

Procedure:
To a solution prepared by dissolving sodium (1.01 g, 44.07 mmol) in absolute EtOH (25 mL), was added 1H-pyrazole (2.5 g, 36.72 mmol). The solution was heated to gentle reflux, then allowed to cool to about 50° C. and treated with a catalytic amount of NaI (25 mg) followed by a slow addition of phenethyl bromide (6.0 mL, 44.07 mmol). The reaction was returned to reflux and after a few min, a white solid precipitated out of solution. After refluxing for 16 h, the solvent was removed by evaporation and the residue dissolved in water (30 mL) and extracted with EtOAc (4×50 mL). The combined organic extracts were washed with water and brine, dried (Na2SO4), filtered and concentrated. The crude product was purified by flash chromatography (Isco CombiFlash) 0-20% EtOAc/heptane to afford 1-phenethyl-1H-pyrazole (1.56 g, 25%). 1H NMR (400 MHz, CDCl3) δ ppm 3.18 (t, J=7.28 Hz, 2H), 4.34-4.39 (m, 2H), 6.18 (t, J=2.06 Hz, 1H), 7.07-7.11 (m, 2H), 7.17 (d, J=2.20 Hz, 1H), 7.20-7.31 (m, 3H), 7.55 (d, J=1.74 Hz, 1H); LCMS-MS (ESI+) 172.86 (M+H).
Reaction SMILES: [CH3:1][NH:2][S:3]([CH3:6])(=[O:5])=[O:4].C(#N)C.[F:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]2[C:22]([C:23]([O:25][CH3:26])=[O:24])=[C:21]([CH:27]([CH3:29])[CH3:28])[N:20]=[C:19](OS(C3C=CC(C)=CC=3)(=O)=O)[N:18]=2)=[CH:13][CH:12]=1>O>[F:10][C:11]1[CH:12]=[CH:13][C:14]([C:17]2[C:22]([C:23]([O:25][CH3:26])=[O:24])=[C:21]([CH:27]([CH3:29])[CH3:28])[N:20]=[C:19]([N:2]([CH3:1])[S:3]([CH3:6])(=[O:5])=[O:4])[N:18]=2)=[CH:15][CH:16]=1
Reactant: COC(=O)c1c(-c2ccc(F)cc2)nc(OS(=O)(=O)c2ccc(C)cc2)nc1C(C)C
Reactant: CNS(C)(=O)=O
Solvent: O
Solvent: CC#N
Product: COC(=O)c1c(-c2ccc(F)cc2)nc(N(C)S(C)(=O)=O)nc1C(C)C
Temperature: 81.5 °C
Yield: 74.8 %

Procedure:
In a 25 mL-volume glass flask equipped with a stirrer, a thermometer and a reflux condenser were placed 196 mg (1.8 mmol.) of N-methylmethanesulfonamide, 198 mg (1.8 mmol.) of sodium t-pentoxide, 7.5 mL of acetonitrile, and 667 mg (1.5 mmol.) of 4-(4-fluorophenyl)-6-isopropyl-5-methoxycarbonyl-2-(p-toluenesulfonyloxy)pyrimidine. The mixture was heated to 81-82° C. for 1.5 hours under refluxing, to carry out reaction. After the reaction was complete, the reaction mixture was cooled to room temperature. To the cooled mixture was added 10 mL of water, and the aqueous mixture was extracted with ethyl acetate. The ethyl acetate portion was separated, and dried over anhydrous magnesium sulfate. The dried ethyl acetate portion was filtered and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (column: Wako Gel C-200, eluent: hexane/ethyl acetate (2:1, volume ratio)). There was obtained 428 mg of 4-(4-fluorophenyl)-6-isopropyl-5-methoxycarbonyl-2-(N-methyl-N-methanesul-fonylamino)-pyrimidine. The yield was 75% (based on the amount of 4-(4-fluorophenyl)-6-isopropyl-5-methoxycarbonyl-2-(p-toluenesulfonyloxy)pyrimidine).
Reaction SMILES: CN(C=O)C.[CH:6]([CH:8]([C:11]#[C:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[CH2:9][NH2:10])=[CH2:7].Cl[C:20]1[C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[N:23]=[CH:22][N:21]=1.C(N(CC)CC)C>O>[CH:6]([CH:8]([C:11]#[C:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[CH2:9][NH:10][C:20]1[C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[N:23]=[CH:22][N:21]=1)=[CH2:7]
Reactant: C=CC(C#Cc1ccccc1)CN
Reactant: Clc1ncnc2ccccc12
Solvent: O
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: C=CC(C#Cc1ccccc1)CNc1ncnc2ccccc12
Temperature: 80 °C
Reaction time: 5 h
Yield: 82.5 %

Procedure:
To 15 ml of DMF were added 550 mg of 2-vinyl-4-phenyl-3-butynylamine, 500 mg of 4-chloroquinazoline, and 636 μl of triethylamine, and the mixture was stirred at 80° C. for 5 hours. After cooling the reaction mixture, 20 ml of water was added and two extractions were conducted with 50 ml of ethyl acetate. After being washed twice with 50 ml of saturated brine, the organic layer was dried over sodium sulfate. After filtering the sodium sulfate, the organic layer was concentrated and purified by means of flash chromatography (Isolera™ manufactured by Biotage AB) to give 750 mg of the end product.
Reaction SMILES: [Si:1]([O:8][CH2:9][C:10]1([CH2:27][O:28][Si:29]([C:32]([CH3:35])([CH3:34])[CH3:33])([CH3:31])[CH3:30])[O:15][C:14]2[CH:16]=[CH:17][C:18]([N+:20]([O-:22])=[O:21])=[CH:19][C:13]=2[N:12]2[C:23](=[O:26])[NH:24][N:25]=[C:11]12)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].IC.[C:38](=O)([O-])[O-].[Cs+].[Cs+].O>CN(C=O)C>[Si:29]([O:28][CH2:27][C:10]1([CH2:9][O:8][Si:1]([C:4]([CH3:5])([CH3:6])[CH3:7])([CH3:3])[CH3:2])[O:15][C:14]2[CH:16]=[CH:17][C:18]([N+:20]([O-:22])=[O:21])=[CH:19][C:13]=2[N:12]2[C:23](=[O:26])[N:24]([CH3:38])[N:25]=[C:11]12)([C:32]([CH3:35])([CH3:34])[CH3:33])([CH3:31])[CH3:30]
Reactant: O=C([O-])[O-]
Reactant: CC(C)(C)[Si](C)(C)OCC1(CO[Si](C)(C)C(C)(C)C)Oc2ccc([N+](=O)[O-])cc2-n2c1n[nH]c2=O
Agent: [Cs+]
Solvent: CN(C)C=O
Solvent: O
Solvent: CI
Product: Cn1nc2n(c1=O)-c1cc([N+](=O)[O-])ccc1OC2(CO[Si](C)(C)C(C)(C)C)CO[Si](C)(C)C(C)(C)C
Temperature: 25 °C
Reaction time: 8 h

Procedure:
4,4-Bis(((tert-butyldimethylsilyl)oxy)methyl)-8-nitro-2,4-dihydro-1H-benzo[b][1,2,4]triazolo[4,3-d][1,4]oxazin-1-one and iodomethane (0.626 mL) were dissolved in DMF. Cesium carbonate (4.13 g) was added to the solution. The reaction mixture was stirred at room temperature overnight. Water (250 mL) was added to the reaction. The aqueous solution was extracted with EtOAc (2×200 mL). The organic layers were evaporated to give 4,4-bis(((tert-butyldimethylsilyl)oxy)methyl)-2-methyl-8-nitro-2,4-dihydro-1H-benzo[b][1,2,4]triazolo[4,3-d][1,4]oxazin-1-one.
Reaction SMILES: [C:1]([C:5]1[CH:6]=[C:7]([S:16][C:17]#[N:18])[CH:8]=[C:9]([C:12]([CH3:15])([CH3:14])[CH3:13])[C:10]=1[OH:11])([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.[SH2:26]>C(OCC)C>[C:17](=[S:26])([S:16][C:7]1[CH:6]=[C:5]([C:1]([CH3:4])([CH3:2])[CH3:3])[C:10]([OH:11])=[C:9]([C:12]([CH3:15])([CH3:14])[CH3:13])[CH:8]=1)[NH2:18]
Reactant: CC(C)(C)c1cc(SC#N)cc(C(C)(C)C)c1O
Reactant: S
Solvent: CCN(CC)CC
Solvent: CCOCC
Product: CC(C)(C)c1cc(SC(N)=S)cc(C(C)(C)C)c1O

Procedure:
3,5-Di-tert-butyl-4-hydroxyphenyl thiocyanate (8.7 g) and 0.3 g of triethylamine were dissolved in 80 ml of diethyl ether, and hydrogen sulfide was blown into the solution at room temperature over 4.5 hours. The reaction mixture was concentrated, and the crude product thus obtained was washed with diethyl ether to give 7.5 g of the desired compound as a colorless solid.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]2[O:10][CH2:9][O:8][C:5]2=[N:6][CH:7]=1.C([Sn](CCCC)(CCCC)[C:16]([O:18]CC)=[CH2:17])CCC.O.CCOC(C)=O>CN(C=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>[O:10]1[C:4]2[C:5](=[N:6][CH:7]=[C:2]([C:16](=[O:18])[CH3:17])[CH:3]=2)[O:8][CH2:9]1
Reactant: Brc1cnc2c(c1)OCO2
Reactant: C=C(OCC)[Sn](CCCC)(CCCC)CCCC
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: CN(C)C=O
Solvent: O
Solvent: CCOC(C)=O
Product: CC(=O)c1cnc2c(c1)OCO2
Temperature: 65 °C
Reaction time: 8 h

Procedure:
A round-bottomed flask was charged with 6-Bromo-[1,3]dioxolo[4,5-b]pyridine IM13 (1.74 g, 8.61 mmol) in DMF (25 ml) under N2 and tributyl(1-ethoxyvinyl)tin (3.65 ml, 10.8 mmol) was added. Tetrakistriphenylphosphinepalladium(0) (0.50 g, 0.43 mmol) was added and the solution was stirred at 65° C. overnight. The mixture was added to water and EtOAc and the phases were separated. The org phase was washed with brine, dried (MgSO4) filtered and was rotovaped. The residue was dissolved in THF (100 ml), and a mixture of water (15 ml) and conc. HCl (2.5 ml) was added and the solution was stirred at rt 5 min. The solution was added to brine and sat NaHCO3 solution was added until the solution was slightly alkaline. The org Phase was extracted with EtOAc and the phases were separated. The org phase was washed with brine, dried (MgSO4) filtered and was rotovaped. The residue was redissolved in THF (10 ml) EtOAc (20 ml) and heptanes (20 ml). The mixture was concentrated until 25 ml remained and cooled in ice. A solid precipitated and was collected by filtration. Yield: 0.942 g (66%) of IM21. 1H-NMR (500 MHz, DMSO) δ 8.47 (s, 1H), 8.54 (s, 1H), 6.27 (s, 2H), 2.53 (s, 3H).
Reaction SMILES: I[C:2]([F:21])([F:20])[C:3]([O:6][C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([O:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH:8]=1)([F:5])[F:4].I[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.CS(C)=O.Cl>O.[Cu]>[O:13]([C:9]1[CH:8]=[C:7]([CH:12]=[CH:11][CH:10]=1)[O:6][C:3]([F:5])([F:4])[C:2]([C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)([F:21])[F:20])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1
Reactant: FC(F)(I)C(F)(F)Oc1cccc(Oc2ccccc2)c1
Reactant: Ic1ccccc1
Agent: [Cu]
Agent: Cl
Solvent: CS(C)=O
Solvent: O
Product: FC(F)(Oc1cccc(Oc2ccccc2)c1)C(F)(F)c1ccccc1
Temperature: 120 °C
Reaction time: 16 h

Procedure:
The 1-iodo-2-(m-phenoxyphenoxy)-1,1,2,2-tetrafluoroethane (2.06 g, 5 mmoles) is then mixed with iodobenzene (1.12 g, 5.5 mmoles), activated copper (0.7 g, 11 mmoles) and 20 ml dimethyl sulfoxide (DMSO) and heated to 120° C. The mixture is heated and stirred at 120° C. for 16 hours and then cooled, diluted with 100 ml water, acidified with HCl and the product is extracted with ethyl acetate (2×40 ml). A colorless oil, 1-(m-phenoxyphenoxy)-2-phenyl-1,1,2,2-tetrafluoroethane, is recovered in a yield of 69 percent based on 1-iodo-2-(m-phenoxyphenoxy)-1,1,2,2-tetrafluoroethane (1.3 g). The identity of the product is confirmed by mass spectrometry. The 1-(m-phenoxyphenoxy)-2-phenyl-1,1,2,2-tetrafluoroethane has a pour point of -23° C.