Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C[S-].[Na+].BrCCCC[N:9]1[C:13](=[O:14])[C:12]2=[CH:15][CH:16]=[CH:17][CH:18]=[C:11]2[C:10]1=[O:19]>CO>[C:13]1(=[O:14])[NH:9][C:10](=[O:19])[C:11]2=[CH:18][CH:17]=[CH:16][CH:15]=[C:12]12
Reactant: O=C1c2ccccc2C(=O)N1CCCCBr
Agent: C[S-]
Agent: [Na+]
Solvent: CO
Product: O=C1NC(=O)c2ccccc21
Temperature: 65 °C
Reaction time: 18 h
Yield: 149.2 %

Procedure:
Sodium thiomethoxide (300 mg) was dissolved in methanol (20 ml), N-(4-bromobutyl)phthalimide (1.0 g) was added to the solution, and the resulting mixture was stirred at 65° C. for 18 hours. The reaction mixture was concentrated under reduced pressure, ethyl acetate and distilled water were added to the resulting residue, and the layers were separated. The organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous sodium sulfate, and filtered, and then the filtrate was concentrated under reduced pressure to obtain a phthalimide compound (778 mg). (2) The compound obtained in (1) mentioned above (775 mg) was dissolved in methylene chloride (23 ml), m-chloroperbenzoic acid (2.06 g) was added to the solution under ice cooling, and the resulting mixture was stirred at room temperature for 17 hours. 10% Aqueous sodium thiosulfate was added to the reaction mixture, the layers were separated, and the organic layer was washed with 10% aqueous sodium thiosulfate, saturated aqueous sodium hydrogencarbonate, distilled water, and saturated aqueous sodium chloride. The organic layer was dried over anhydrous sodium sulfate, and filtered, and then the filtrate was concentrated under reduced pressure to obtain an oxidized compound (854 mg). (3) By using the compound obtained in (2) mentioned above (850 mg) as a starting material, the title compound (256 mg) was obtained in the same manner as that of Reference Example 9, (2).
Reaction SMILES: Br[C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][N:3]=1.[F:10][C:11]([F:17])([F:16])[O:12][CH2:13][CH2:14][OH:15]>>[F:10][C:11]([F:17])([F:16])[O:12][CH2:13][CH2:14][O:15][C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][N:3]=1
Reactant: N#Cc1ccc(Br)nc1
Reactant: OCCOC(F)(F)F
Product: N#Cc1ccc(OCCOC(F)(F)F)nc1
Yield: 95 %

Procedure:
The title compound is prepared in 95% yield (509 mg, colorless oil) from 6-bromonicotinonitrile (422 mg, 2.31 mmol) and 2-(trifluoromethoxy)ethanol (300 mg, 2.31 mmol) by the similar manner in Step-1 of Amine-101.
Reaction SMILES: [NH2:1][C@H:2]([C:9]([OH:11])=[O:10])[CH2:3][C:4]1[N:8]=[CH:7][NH:6][CH:5]=1.C[O-].[Na+].O.O.C([O-])(=O)C.[Zn+2:21].C([O-])(=O)C>CO>[Zn:21].[NH2:1][C@H:2]([C:9]([OH:11])=[O:10])[CH2:3][C:4]1[N:8]=[CH:7][NH:6][CH:5]=1
Reactant: [Zn+2]
Agent: CC(=O)[O-]
Agent: C[O-]
Agent: N[C@@H](Cc1c[nH]cn1)C(=O)O
Solvent: CO
Solvent: O
Product: [Zn]

Procedure:
L-histidine (2.00 g, 12.8 mmol) was added to an MeOH solution of NaOMe (prepared with Na: 0.30 g, MeOH: 50 ml) at 0° C. and stirred. An MeOH solution (30 ml) of zinc acetate dihydrate (1.41 g) was then slowly dropwise added thereto at room temperature. After stirring for 3 hours, the precipitated crystal (in suspension) was recovered by filtration, washed with water, air dried, and then concentrated under a reduced pressure (5 mmHg, 80° C.).
Reaction SMILES: [C:1]1([Mg]Br)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[O:9]=[C:10]1[CH2:19][CH2:18][CH2:17][C:16]2[N:15]=[C:14]([CH3:20])[CH:13]=[CH:12][C:11]1=2.N1C2C(=CC=CC=2)CCC1C.[Cl-].[NH4+]>C(OCC)C>[OH:9][C:10]1([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[CH2:19][CH2:18][CH2:17][C:16]2[N:15]=[C:14]([CH3:20])[CH:13]=[CH:12][C:11]1=2
Reactant: Br[Mg]c1ccccc1
Reactant: Cc1ccc2c(n1)CCCC2=O
Agent: CC1CCc2ccccc2N1
Agent: [Cl-]
Agent: [NH4+]
Solvent: CCOCC
Product: Cc1ccc2c(n1)CCCC2(O)c1ccccc1

Procedure:
To a stirred solution of 0.155 moles of phenylmagnesium bromide in 250 ml of diethyl ether was added dropwise a solution of 2.0 g (0.124 mole) of 5-keto-5,6,7,8-tetrahydroquinaldine in 100 ml of diethyl ether. After all of the tetrahydroquinaldine had been added the mixture was then treated with an excess of a saturated aqueous ammonium chloride solution. The ether layer was separated, dried and evaporated to prevent a residue. This residue was dissolved in dilute hydrochloric acid and the aqueous acid layer was then extracted sequentially with diethyl ether and hexane. The acid layer was then basified with aqueous sodium hydroxide. Filtration provided yellow solid 5-hydroxy-5-phenyl-5,6,7,8-tetrahydroquinaldine, which had a m.p. of 130°-134° C. after recrystallization from a dichloromethane-hexane mixture. Analysis: Calculated for C16H17NO: %C, 80.3; %H, 7.2; %N, 5.9; Found: %C, 80.2; %H, 7.2; %N, 5.5. The structural assignment was confirmed by infrared and nuclear magnetic resonance spectral analyses.
Reaction SMILES: C([O:4][C:5]1[CH:10]=[C:9]([F:11])[C:8]([F:12])=[CH:7][C:6]=1[C:13](Cl)=[O:14])(=O)C.[NH2:16][C:17]1[CH:26]=[CH:25][C:20]([C:21]([O:23][CH3:24])=[O:22])=[CH:19][CH:18]=1>>[F:11][C:9]1[C:8]([F:12])=[CH:7][C:6]([C:13]([NH:16][C:17]2[CH:18]=[CH:19][C:20]([C:21]([O:23][CH3:24])=[O:22])=[CH:25][CH:26]=2)=[O:14])=[C:5]([OH:4])[CH:10]=1
Reactant: COC(=O)c1ccc(N)cc1
Reactant: CC(=O)Oc1cc(F)c(F)cc1C(=O)Cl
Product: COC(=O)c1ccc(NC(=O)c2cc(F)c(F)cc2O)cc1
Yield: 71.2 %

Procedure:
Analogous to the method described in Example 1, 2-(chlorocarbonyl)-4,5-difluorophenyl acetate (0.2 g, 0.85 mmol) and methyl 4-aminobenzoate (0.174 g, 1.1 mmol) were coupled to yield methyl 4-(4,5-difluoro-2-hydroxybenzamido)benzoate (0.186 g, 64%). RP-HPLC: 2.61 min; ES-MS (M+H)+=308.0.
Reaction SMILES: [CH2:1]([O:4][C:5]([N:7]1[CH2:11][C@H:10]([O:12][S:13]([CH3:16])(=[O:15])=[O:14])[CH2:9][C@H:8]1[CH2:17][CH2:18]OS(C)(=O)=O)=[O:6])[CH:2]=[CH2:3].[NH:24]1[CH:28]=[CH:27][N:26]=[CH:25]1.CC(C)([O-])C.[K+].O>CN(C)C=O>[CH2:1]([O:4][C:5]([N:7]1[CH2:11][C@H:10]([O:12][S:13]([CH3:16])(=[O:14])=[O:15])[CH2:9][C@H:8]1[CH2:17][CH2:18][N:24]1[CH:28]=[CH:27][N:26]=[CH:25]1)=[O:6])[CH:2]=[CH2:3]
Reactant: c1c[nH]cn1
Reactant: C=CCOC(=O)N1C[C@H](OS(C)(=O)=O)C[C@H]1CCOS(C)(=O)=O
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: C=CCOC(=O)N1C[C@H](OS(C)(=O)=O)C[C@H]1CCn1ccnc1

Procedure:
To a solution of (2R,4R)-1-allyloxycarbonyl-4-methanesulfonyloxy-2-(2-methanesulfonyloxyethyl)pyrrolidine (5.35 g) in N,N-dimethylformamide (54 ml) were added imidazole (1.18 g) and potassium t-butoxide (1.78 g) with stirring under ice-cooling. The mixture was stirred at 40°-45° C. for 40 minutes. The reaction mixture was poured into water (100 ml) and extracted with dichloromethane (80 ml). The extract was washed in turn with water (50 ml) and 10% aqueous sodium chloride (50 ml), dried over anhydrous magnesium sulfate and evaporated in vacuo to give (2R,4R)-1-allyloxycarbonyl-2-[2-(imidazol-1-yl)ethyl]-4-methanesulfonyloxypyrrolidine.
Reaction SMILES: [CH3:1][C:2]1[NH:6][CH:5]=[N:4][C:3]=1[C:7]1[CH:12]=[CH:11][C:10]([N+:13]([O-])=O)=[CH:9][CH:8]=1.[H][H]>CO.[Pd]>[CH3:1][C:2]1[NH:6][CH:5]=[N:4][C:3]=1[C:7]1[CH:12]=[CH:11][C:10]([NH2:13])=[CH:9][CH:8]=1
Reactant: [H][H]
Reactant: Cc1[nH]cnc1-c1ccc([N+](=O)[O-])cc1
Agent: [Pd]
Solvent: CO
Product: Cc1[nH]cnc1-c1ccc(N)cc1
Yield: 88 %

Procedure:
Sixty grams of 5-methyl-4-(4-nitrophenyl)-1-H-imidazole dissolved in methanol was hydrogenated in the presence of 0.7 gm of 5% Pd catalyst at atmospheric pressure and at room temperature. When the calculated amount of hydrogen was taken up, the catalyst was filtered off, and the solution was evaporated to dryness to yield 45 gm of 5-methyl-4-(4-aminophenyl)-1-H-imidazole.
Reaction SMILES: C1(C)C=CC(S(O)(=O)=O)=CC=1.[NH2:12][C@@H:13]1[CH2:18][CH2:17][N:16]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:15][C@H:14]1[C:26]1[CH:31]=[CH:30][C:29]([Cl:32])=[C:28]([Cl:33])[CH:27]=1.[F:34][C:35]([F:50])([F:49])[C:36]1[CH:37]=[C:38]([CH:42]=[C:43]([C:45]([F:48])([F:47])[F:46])[CH:44]=1)[C:39](O)=[O:40].CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1>C(#N)C.O.CCN(CC)CC>[F:34][C:35]([F:49])([F:50])[C:36]1[CH:37]=[C:38]([C:39]([NH:12][C@@H:13]2[CH2:18][CH2:17][N:16]([C:19]([O:21][C:22]([CH3:25])([CH3:23])[CH3:24])=[O:20])[CH2:15][C@H:14]2[C:26]2[CH:31]=[CH:30][C:29]([Cl:32])=[C:28]([Cl:33])[CH:27]=2)=[O:40])[CH:42]=[C:43]([C:45]([F:46])([F:47])[F:48])[CH:44]=1
Reactant: O=C(O)c1cc(C(F)(F)F)cc(C(F)(F)F)c1
Reactant: CC(C)(C)OC(=O)N1CC[C@@H](N)[C@H](c2ccc(Cl)c(Cl)c2)C1
Agent: CCN=C=NCCCN(C)C
Agent: Cc1ccc(S(=O)(=O)O)cc1
Agent: Cl
Solvent: CC#N
Solvent: O
Solvent: CCN(CC)CC
Product: CC(C)(C)OC(=O)N1CC[C@@H](NC(=O)c2cc(C(F)(F)F)cc(C(F)(F)F)c2)[C@H](c2ccc(Cl)c(Cl)c2)C1
Temperature: 25 °C
Reaction time: 14 h
Yield: 98.6 %

Procedure:
To a solution of the compound (1.48 g) obtained in step 4, 3,5-bis(trifluoromethyl)benzoic acid (1.10 g) and Et3N (0.40 mL) in acetonitrile (15 mL) were added WSC.HCl (1.10 g) and HOBt (0.88 g), and the mixture was stirred at room temperature for 14 hr. The reaction mixture was poured into water, and the resultant product was extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium hydrogen carbonate solution and brine and dried, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (solvent gradient; 10→33% ethyl acetate/hexane) to give the title compound (1.65 g, 98%) as a white powder.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([CH:9]=[C:10]([CH2:12][OH:13])[CH:11]=1)[C:5]([O:7][CH3:8])=[O:6]>[O-2].[Mn+4].[O-2].C(Cl)Cl>[Br:1][C:2]1[CH:3]=[C:4]([CH:9]=[C:10]([CH:12]=[O:13])[CH:11]=1)[C:5]([O:7][CH3:8])=[O:6]
Reactant: COC(=O)c1cc(Br)cc(CO)c1
Agent: [Mn+4]
Agent: [O-2]
Solvent: ClCCl
Product: COC(=O)c1cc(Br)cc(C=O)c1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
A mixture of methyl 3-bromo-5-(hydroxymethyl)benzoate (149 mg, 0.61 mmol) and manganese(IV) oxide (529 mg, 6.08 mmol), and CH2Cl2 (3 mL) was stirred at rt overnight. The mixture was filtered through Celite and the filter cake was washed with CH2Cl2. The filtrate was concentrated to afford the title compound.
Reaction SMILES: [F:1][C:2](=[C:12]([F:14])[F:13])[CH2:3][CH2:4][S:5][CH:6]1[NH:10][C:9](=[O:11])[CH2:8][O:7]1.C(N(CC)CC)C.[CH3:22][S:23](Cl)(=[O:25])=[O:24]>O1CCCC1>[CH3:22][S:23]([O:11][C:9]1[N:10]=[C:6]([S:5][CH2:4][CH2:3][C:2]([F:1])=[C:12]([F:13])[F:14])[O:7][CH:8]=1)(=[O:25])=[O:24]
Reactant: O=C1COC(SCCC(F)=C(F)F)N1
Reactant: CS(=O)(=O)Cl
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: CS(=O)(=O)Oc1coc(SCCC(F)=C(F)F)n1
Temperature: 50 °C
Reaction time: 8 h
Yield: 18.7 %

Procedure:
1 g of 2-(3,4,4-trifluoro-3-butenylthio)oxazolidin-4-one and 0.9 g of triethylamine were dissloved in 30 ml of tetrahydrofuran, to which 0.56 g of methanesulfonic chloride was added dropwise under ice cooling and stirred at 50° C. for 8 hours. After distilling off the solvent under reduced pressure, the residue was dissolved in ether. After washing with 1N hydrochloric acid and water, it was dried with anhydrous sodium sulfate and the solvent was distilled off under reduced pressure. The residue was purified by column chromatography (eluent: hexane:dichloromethane=1:1) to obtain 0.25 g of 4-methylsulfonyloxy-2-(3,4,4-trifluoro-3-butenylthio)oxazole (yield 19%). n20D=1.4830.
Reaction SMILES: [CH2:1]1[O:9][CH:2]1[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[H][H]>>[C:3]1([CH2:2][CH2:1][OH:9])[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1
Reactant: [H][H]
Reactant: c1ccc(C2CO2)cc1
Product: OCCc1ccccc1
Yield: 78.4 %

Procedure:
Recently, gas phase hydrogenation of styrene oxide over pentasile type zeolite phosphate doped with a metal as a catalyst to give 2-phenyl ethanol has been reported. The styrene oxide and hydrogen were passed through a tube reactor packed with catalyst prepared by calcining a borosilicate with Cu(NO3)2 at 540° C. to give 78.4% 2-phenyl ethanol. [Holderich Wolfgang, Goelz Narbert, Hupfer Leopold (BASF) Ger offen DE 3,801,106,(1989)].
Reaction SMILES: [NH:1]([CH2:5][CH2:6][OH:7])[CH2:2][CH2:3][OH:4].[Cl:8][C:9]1[CH:16]=[CH:15][C:12]([CH2:13]Cl)=[CH:11][CH:10]=1>>[Cl:8][C:9]1[CH:16]=[CH:15][C:12]([CH2:13][N:1]([CH2:5][CH2:6][OH:7])[CH2:2][CH2:3][OH:4])=[CH:11][CH:10]=1
Reactant: ClCc1ccc(Cl)cc1
Reactant: OCCNCCO
Product: OCCN(CCO)Cc1ccc(Cl)cc1

Procedure:
2-[(4-chlorobenzyl)-(2-hydroxy-ethyl)-amino]-ethanol was prepared according to the general method as outlined in Example 1 (Step 4). Starting from diethanolamine (14.3 g, 95 mmol), and 4-chlorobenzyl chloride (10.2 g, 63 mmol). Yield 12.1 g, (84%); yellow oil; MS: 230 (M+H)+.
Reaction SMILES: Cl[C:2]1[N:11]=[CH:10][C:9]2[N:8]([CH3:12])[C:7](=[O:13])[C@@H:6]([CH2:14][CH3:15])[N:5]([CH:16]([CH3:18])[CH3:17])[C:4]=2[N:3]=1.[C:19]([C:21]1[CH:22]=[C:23]([C:27]2[NH:28][CH:29]=[CH:30][N:31]=2)[CH:24]=[CH:25][CH:26]=1)#[N:20]>>[CH2:14]([C@H:6]1[N:5]([CH:16]([CH3:18])[CH3:17])[C:4]2[N:3]=[C:2]([N:28]3[CH:29]=[CH:30][N:31]=[C:27]3[C:23]3[CH:22]=[C:21]([CH:26]=[CH:25][CH:24]=3)[C:19]#[N:20])[N:11]=[CH:10][C:9]=2[N:8]([CH3:12])[C:7]1=[O:13])[CH3:15]
Reactant: N#Cc1cccc(-c2ncc[nH]2)c1
Reactant: CC[C@@H]1C(=O)N(C)c2cnc(Cl)nc2N1C(C)C
Product: CC[C@@H]1C(=O)N(C)c2cnc(-n3ccnc3-c3cccc(C#N)c3)nc2N1C(C)C

Procedure:
The title compound was prepared similarly to the methods described in Example 26, with Intermediate C instead of Intermediate B and with 2-(3-cyanophenyl)-1H-imidazole instead of 2-phenyl-1H-imidazole. LCMS: 402.2 m/z (M+H)+; ret. Time: 5.97 min (Analytical Method C).
Reaction SMILES: [NH2:1][CH2:2][CH2:3][N:4]1[C:13]2[C:8](=[N:9][CH:10]=[C:11]([CH2:14][C:15]3[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=3)[CH:12]=2)[C:7]([OH:22])=[C:6]([C:23]([NH:25][CH2:26][CH2:27][O:28][CH2:29][CH2:30][OH:31])=[O:24])[C:5]1=[O:32].C(N(C(C)C)CC)(C)C.[CH3:42][N:43]([CH:45]=[O:46])[CH3:44]>>[CH3:42][N:43]([CH3:44])[C:45]([NH:1][CH2:2][CH2:3][N:4]1[C:13]2[C:8](=[N:9][CH:10]=[C:11]([CH2:14][C:15]3[CH:16]=[CH:17][C:18]([F:21])=[CH:19][CH:20]=3)[CH:12]=2)[C:7]([OH:22])=[C:6]([C:23]([NH:25][CH2:26][CH2:27][O:28][CH2:29][CH2:30][OH:31])=[O:24])[C:5]1=[O:32])=[O:46]
Reactant: CN(C)C=O
Reactant: NCCn1c(=O)c(C(=O)NCCOCCO)c(O)c2ncc(Cc3ccc(F)cc3)cc21
Solvent: CCN(C(C)C)C(C)C
Product: CN(C)C(=O)NCCn1c(=O)c(C(=O)NCCOCCO)c(O)c2ncc(Cc3ccc(F)cc3)cc21

Procedure:
A solution of 1-(2-aminoethyl)-7-[(4-fluorophenyl)methyl]-4-hydroxy-N-{2-[(2-hydroxyethyl)oxy]ethyl}-2-oxo-1,2-dihydro-1,5-naphthyridine-3-carboxamide (0.025 g, 0.057 mmol) and diisopropyl ethylamine (0.05 mL, 0.29 mmol) in DMF (3 mL) under nitrogen was treated with N,N-dimethyl carbonyl chloride (0.0055 mL, 0.06 mmol) (40° C. After 2½ h the reaction was cooled, concentrated in vacuo, and the resulting residue treated with 1N NaHSO4, filtered, washed with water, and dried in vacuo to provide the title compound as a pale yellow solid: 1H NMR (300 MHz, DMSO-d6) δ ppm 1.73 (s, 1 H), 2.70 (s, 6 H), 3.24-3.30 (m, 3 H), 3.46-3.62 (m, 7 H), 4.12 (s, 2 H), 4.25 (t, J=6.32 Hz, 2 H), 4.62 (t, J=5.19 Hz, 1 H), 6.56 (t, J=5.76 Hz, 1 H), 7.10-7.18 (m, 2 H), 7.37-7.44 (m, 2 H), 8.30 (s, 1 H), 8.53 (d, J=1.69 Hz, 1 H), 10.41 (t, J=5.26 Hz, 1 H); ES+ MS: 516 (M+H+).
Reaction SMILES: [C:1]([C:3]1[O:10][C:9]2[CH:8]=[C:7]([C:11]([OH:13])=O)[NH:6][C:5]=2[CH:4]=1)#[N:2].Cl.[NH2:15][C@@H:16]([CH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)[C:17]([N:19]1[CH2:22][CH:21]([OH:23])[CH2:20]1)=[O:18]>>[CH2:24]([C@H:16]([NH:15][C:11]([C:7]1[NH:6][C:5]2[CH:4]=[C:3]([C:1]#[N:2])[O:10][C:9]=2[CH:8]=1)=[O:13])[C:17]([N:19]1[CH2:22][CH:21]([OH:23])[CH2:20]1)=[O:18])[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1
Reactant: N#Cc1cc2[nH]c(C(=O)O)cc2o1
Reactant: N[C@@H](Cc1ccccc1)C(=O)N1CC(O)C1
Agent: Cl
Product: N#Cc1cc2[nH]c(C(=O)N[C@@H](Cc3ccccc3)C(=O)N3CC(O)C3)cc2o1

Procedure:
2-Cyano-4H-furo[3,2-b]pyrrole-5-carboxylic acid and (2S)-amino-1-(3-hydroxy-azetidin-1-yl)-3-phenyl-propan-1-one hydrochloride were coupled according to Procedure B (reaction mixture partitioned between ethyl acetate and water prior to acidic washing).
Reaction SMILES: [C:1]([C:5]1[CH:15]=[CH:14][C:8](/[CH:9]=[CH:10]/[C:11]([OH:13])=[O:12])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].C(Cl)(=O)C(Cl)=O.[CH3:22][O:23][C:24]1[CH:25]=[C:26](O)[CH:27]=[CH:28][CH:29]=1.C([O-])([O-])=O.[K+].[K+].Cl>C1COCC1.CN(C=O)C.C(Cl)Cl>[C:1]([C:5]1[CH:6]=[CH:7][C:8](/[CH:9]=[CH:10]/[C:11]([O:13][C:28]2[CH:27]=[CH:26][CH:25]=[C:24]([O:23][CH3:22])[CH:29]=2)=[O:12])=[CH:14][CH:15]=1)([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)c1ccc(/C=C/C(=O)O)cc1
Reactant: COc1cccc(O)c1
Agent: Cl
Agent: O=C(Cl)C(=O)Cl
Agent: O=C([O-])[O-]
Solvent: ClCCl
Solvent: C1CCOC1
Solvent: CN(C)C=O
Product: COc1cccc(OC(=O)/C=C/c2ccc(C(C)(C)C)cc2)c1

Procedure:
To a 100 mL round-bottomed flask equipped with magnetic stirring was added 4-tert-butyl-trans-cinnamic acid (500 mg, 2.45 mmol, EMKA-Chemie), CH2Cl2 (10 mL), and DMF (10 uL) under N2. The solution was treated dropwise with oxalyl chloride (4.0 mL, 8.0 mmol, 2.0 M in CH2Cl2, Aldrich) then stirred at 25° C. for 1 h. The reaction mixture was concentrated in vacuo and the residue treated with 3-methoxyphenol (269 uL, 2.45 mmol, Aldrich), THF (20 mL) and satd K2CO3 (15 mL). The reaction mixture was stirred at 25° C. overnight, then acidified to pH 4.5 with 1 N HCl. The mixture was extracted with EtOAc (2×30 mL), the combined organic extract was dried and concentrated in vacuo. Purification by silica gel chromatography (5:1 hexane:EtOAc) provided the title product as a white solid. MP 83° C. MS (ESI, pos. ion) m/z: 311 (M+1).
Reaction SMILES: [CH2:1]([O:4][CH2:5][CH:6]([NH2:9])[C:7]#[N:8])[CH:2]=[CH2:3].[OH:10][N:11]=[C:12]([CH2:16][CH:17]([CH3:19])[CH3:18])[C:13](O)=[O:14].C1(N=C=NC2CCCCC2)CCCCC1.C1(NC(NC2CCCCC2)=O)CCCCC1>O1CCOCC1>[CH2:1]([O:4][CH2:5][CH:6]([NH:9][C:13](=[O:14])[C:12](=[N:11][OH:10])[CH2:16][CH:17]([CH3:19])[CH3:18])[C:7]#[N:8])[CH:2]=[CH2:3]
Reactant: CC(C)CC(=NO)C(=O)O
Reactant: C=CCOCC(N)C#N
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: O=C(NC1CCCCC1)NC1CCCCC1
Solvent: C1COCCO1
Product: C=CCOCC(C#N)NC(=O)C(CC(C)C)=NO
Yield: 96 %

Procedure:
In 750 ml of dioxane were dissolved 52 g of 3-allyloxy-2-aminopropionitrile, 40 g of α-hydroxyiminoisocaproic acid and 34.9 g of N-hdyroxysuccinimide. Thereto was added 59.7 g of N,N'-dicyclohexylcarbodiimide. The mixture was subjected to a reaction for 16 hours at room temperature. After completion of the reaction, N,N'-dicyclohexylurea was removed by filtration. The filtrate was concentrated to remove dioxane. The resulting residue was mixed with 800 ml of ethyl acetate. The mixture was washed with an aqueous sodium hydrogen carbonate solution and dried over magnesium sulfate. The solvent was removed by evaporation. The residue was purified by a silica gel column chromatography (eluting solvent: 40% by volume of ethyl acetate-n-hexane) to obtain 67 g of 3-allyloxy-2-(α-hydroxyiminoisocaproylamino)propionitrile (Compound B-2) as white crystals.
Reaction SMILES: [NH2:1][C:2]1[N:7]([CH2:8][CH2:9][CH2:10][CH3:11])[C:6](=[O:12])[NH:5][C:4](=[O:13])[CH:3]=1.Cl.[N:15]([O-])=[O:16].[Na+]>O>[NH2:1][C:2]1[N:7]([CH2:8][CH2:9][CH2:10][CH3:11])[C:6](=[O:12])[NH:5][C:4](=[O:13])[C:3]=1[N:15]=[O:16]
Reactant: CCCCn1c(N)cc(=O)[nH]c1=O
Reactant: O=N[O-]
Agent: Cl
Agent: [Na+]
Solvent: O
Product: CCCCn1c(N)c(N=O)c(=O)[nH]c1=O

Procedure:
To 50.6 g (0.276 mol) of 6-amino-1-butyl-2,4-(1H,3H)-pyrimidinedione (VIII) dissolved in 1.8 l of water at 80° C. was added 60 ml of 5 N HCl and 20 g (0.29 mol) of NaNO2 which were dissolved in water. After cooling the red crystals were filtered off and washed with water. Yield 52.8 g (97%) (IX), NMR.
Reaction SMILES: [CH3:1][C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][C:6]([CH2:12][CH2:13][OH:14])=[CH:7][CH:8]=2)[N:3]=1.[O:15]1CCOCC1>O>[OH:14][CH2:13][CH2:12][C:6]1[CH:5]=[C:4]2[C:9]([CH:10]=[CH:11][C:2]([CH:1]=[O:15])=[N:3]2)=[CH:8][CH:7]=1
Reactant: Cc1ccc2ccc(CCO)cc2n1
Reactant: C1COCCO1
Solvent: O
Product: O=Cc1ccc2ccc(CCO)cc2n1
Temperature: 25 °C
Yield: 89 %

Procedure:
2-(2-methylquinolin-7-yl)ethanol (0.220 g, 1.17 mmol) was dissolved in dioxane (5 mL) and water (0.05 mL). The reaction was treated with SeO2 (0.156 g, 1.41 mmol) and the mixture was heated to reflux for 2 hours. After cooling to ambient temperature, the solid was removed by filtration and washed with DCM. The filtrate was concentrated and the residue was purified by flash chromatography on silica gel (ethyl acetate/hexanes 5:1) to give 7-(2-hydroxyethyl)quinoline-2-carbaldehyde (0.21 g, 1.04 mmol, 89% yield) as a solid.
Reaction SMILES: C([Li])CCC.[CH2:6]([N:9]1[C:13]([SH:14])=[N:12][N:11]=[N:10]1)[CH:7]=[CH2:8].[C:15](=[O:17])=[O:16].O>CCCCCC.O1CCCC1>[C:15]([CH2:8][CH:7]=[CH:6][N:9]1[C:13]([SH:14])=[N:12][N:11]=[N:10]1)([OH:17])=[O:16]
Reactant: C=CCn1nnnc1S
Reactant: O=C=O
Agent: [Li]CCCC
Solvent: CCCCCC
Solvent: C1CCOC1
Solvent: O
Product: O=C(O)CC=Cn1nnnc1S
Temperature: -20 °C
Reaction time: 0.5 h

Procedure:
15% solution of n-butyl lithium in hexane (371 ml) was dissolved in dry tetrahydrofuran (150 ml) and cooled to -20° C. To the solution was added dropwise a solution of 1-allyl-1H-tetrazole-5-thiol (38.7 g) in tetrahydrofuran (220 ml) with stirring under a stream of nitrogen gas during a period of 30 minutes. After the addition of solid carbon dioxide, the mixture was stirred for 30 minutes at -10° C. To the mixture was added water (275 ml) and then the resulting mixture was stirred. The aqueous layer was separated adjusted to pH 4.5, washed with ethyl acetate, adjusted to pH 3.8 to 4.0 and extracted with ethyl acetate. The extract was washed with a saturated aqueous solution of sodium chloride, dried over magnesium sulfate and then evaporated. The residue was washed with diisopropyl ether to give an oil of 1-(3-carboxy-1-propenyl)-1H-tetrazole-5-thiol (5.5 g).
Reaction SMILES: [CH2:1]([C:9]1[CH:19]=[CH:18][C:12]([CH:13]=[CH:14][C:15](O)=[O:16])=[CH:11][CH:10]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8].S(Cl)([Cl:22])=O>>[CH2:1]([C:9]1[CH:19]=[CH:18][C:12]([CH:13]=[CH:14][C:15]([Cl:22])=[O:16])=[CH:11][CH:10]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8]
Reactant: CCCCCCCCc1ccc(C=CC(=O)O)cc1
Reactant: O=S(Cl)Cl
Product: CCCCCCCCc1ccc(C=CC(=O)Cl)cc1

Procedure:
1.8 G. of p-n-octylcinnamic acid, prepared in a manner analogous to that described in Example 1, are boiled in 25 ml. of thionyl chloride for 30 minutes. The excess thionyl chloride is removed by distillation. The residue is taken up twice in absolute toluene, concentrated on a rotary evaporator and dried. There is thus obtained crude p-n-octylcinnamic acid chloride.
Reaction SMILES: [Si:1]([O:18][CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=1[CH2:26]O)([C:14]([CH3:17])([CH3:16])[CH3:15])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(Br)(Br)(Br)[Br:29].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CCCCCC>ClCCl.C(OCC)(=O)C>[Br:29][CH2:26][C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][C:20]=1[CH2:19][O:18][Si:1]([C:14]([CH3:17])([CH3:16])[CH3:15])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CC(C)(C)[Si](OCc1ccccc1CO)(c1ccccc1)c1ccccc1
Reactant: BrC(Br)(Br)Br
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Solvent: CCOC(C)=O
Solvent: CCCCCC
Product: CC(C)(C)[Si](OCc1ccccc1CBr)(c1ccccc1)c1ccccc1
Temperature: 25 °C
Reaction time: 14 h
Yield: 89.1 %

Procedure:
In dichloromethane (50 ml) were dissolved [2-[(t-butyldiphenylsilyloxy)methyl]phenyl]methanol (3.00 g, 7.97 mmol) and carbon tetrabromide (3.40 g, 10.3 mmol). Under ice cooling, a dichloromethane solution (5 ml) of triphenylphosphine (2.70 g, 10.3 mmol) was added dropwise. After stirring at room temperature for 14 hours, the reaction mixture was concentrated under reduced pressure. The residue thus obtained was subjected to silica gel chromatography. The fraction obtained from the hexane:ethyl acetate=30:1 eluate was concentrated under reduced pressure, whereby the title compound (3.12 g, 7.10 mmol, 89%) was obtained as a colorless oil.