Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: B([O-])O[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH3:10].C=CCCCCCC.B1C2CCCC1CCC2.[OH-].[Na+].[C:31]([O:35][C:36]([N:38]1[C:46]2[C:41](=[CH:42][CH:43]=[C:44](Br)[CH:45]=2)[C:40]([CH2:48][OH:49])=[CH:39]1)=[O:37])([CH3:34])([CH3:33])[CH3:32]>C1COCC1>[C:31]([O:35][C:36]([N:38]1[C:46]2[C:41](=[CH:42][CH:43]=[C:44]([CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH3:10])[CH:45]=2)[C:40]([CH2:48][OH:49])=[CH:39]1)=[O:37])([CH3:34])([CH3:33])[CH3:32]
Reactant: CCCCCCCCOB[O-]
Reactant: CC(C)(C)OC(=O)n1cc(CO)c2ccc(Br)cc21
Agent: B1C2CCCC1CCC2
Agent: [Na+]
Agent: [OH-]
Solvent: C=CCCCCCC
Solvent: C1CCOC1
Product: CCCCCCCCc1ccc2c(CO)cn(C(=O)OC(C)(C)C)c2c1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
An octyl boronate intermediate is generated by adding 1-octene (1.38 g, 14.1 mmol) to a solution of 9-BBN in THF (28.3 mL of a 0.5 M solution, 14.1 mmol). The reaction mixture is stirred at room temperature overnight. An aqueous solution of sodium hydroxide (5.0 mL of a 3.0 M solution) is added, followed by the addition of compound 25 (3.10 g, 10.0 mmol) and Pd[P(Ph)3]4 (0.310 g, 0.270 mmol). The reaction is brought to reflux and maintained for 12 hours under an inert atmosphere. The reaction is cooled, filtered, concentrated in vacuo and the residue purified using silica gel chromatography with hexane/ethyl acetate (75:25) as solvent.
Reaction SMILES: C(N(CC)C(C)C)(C)C.F[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1[N+:17]([O-:19])=[O:18].[O:20]1[CH2:24][CH2:23][CH:22]([NH2:25])[CH2:21]1>C(O)CCC>[N+:17]([C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=1[NH:25][CH:22]1[CH2:23][CH2:24][O:20][CH2:21]1)([O-:19])=[O:18]
Reactant: NC1CCOC1
Reactant: O=[N+]([O-])c1ccccc1F
Solvent: CCCCO
Solvent: CCN(C(C)C)C(C)C
Product: O=[N+]([O-])c1ccccc1NC1CCOC1
Temperature: 180 °C
Reaction time: 0.33 h

Procedure:
N,N-Diisopropylethylamine (3.2 mL, 18.4 mmol) was added to a solution of 1-fluoro-2-nitrobenzene (0.484 mL, 4.6 mmol) and (±)-tetrahydrofuran-3-amine (400 mg, 4.6 mmol) in n-butanol (10 mL) and the mixture heated to 180° C. in a microwave reactor. After 20 min, the reaction was allowed to cool to ambient temperature and concentrated. Purification by silica gel chromatography, eluting with a gradient of hexane:EtOAc—100:0 to 0:100, gave the title compound. MS: m/z=209 (M+1).
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[CH:9]=[C:8](Br)[S:7][CH:6]=1)=[O:4].[C:11]1(B(O)O)[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.C(=O)([O-])[O-].[K+].[K+]>COCCOC.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]([C:5]1[CH:9]=[C:8]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[S:7][CH:6]=1)=[O:4]
Reactant: OB(O)c1ccccc1
Reactant: COC(=O)c1csc(Br)c1
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: COCCOC
Product: COC(=O)c1csc(-c2ccccc2)c1
Temperature: 80 °C
Yield: 51.6 %

Procedure:
Prepare a mixture of 5-bromo-thiophene-3-carboxylic acid methyl ester (1.86 g, 8.41 mmol), phenylboronic acid (2.05 g, 16.83 mmol), and 1 M aqueous potassium carbonate (12.5 mL, 25.23 mmol) in 1,2-dimethoxyethane (70 mL) and purge with nitrogen for 20 minutes. Add Pd(PPh3)4 (485 mg, 0.42 mmol) and again purge the mixture with nitrogen for 10 minutes. Heat to 80° C. for 24 hours. Evaporate the solvent and redissolve the residue in ethyl acetate. Extract the aqueous phase with ethyl acetate (2×20 mL), wash the combined organic phases brine (40 mL), dry (magnesium sulfate), filter and concentrate. Perform flash chromatography on silica-gel eluting with 10:1 hexane/ethyl acetate to afford 947 mg of 5-phenylthiophene-3-carboxylic acid methyl ester as a white solid. MS: m/e=219 [MH+].
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][CH:7]=[C:6]2[O:15][C:16]1[CH:22]=[CH:21][C:19]([NH2:20])=[C:18]([F:23])[CH:17]=1.C(O)C.[Cl:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=1[C:34]([N:36]=[C:37]=[S:38])=[O:35]>C1(C)C=CC=CC=1>[Cl:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=1[C:34]([NH:36][C:37]([NH:20][C:19]1[CH:21]=[CH:22][C:16]([O:15][C:6]2[C:5]3[C:10](=[CH:11][C:12]([O:13][CH3:14])=[C:3]([O:2][CH3:1])[CH:4]=3)[N:9]=[CH:8][CH:7]=2)=[CH:17][C:18]=1[F:23])=[S:38])=[O:35]
Reactant: O=C(N=C=S)c1ccccc1Cl
Reactant: COc1cc2nccc(Oc3ccc(N)c(F)c3)c2cc1OC
Solvent: CCO
Solvent: Cc1ccccc1
Product: COc1cc2nccc(Oc3ccc(NC(=S)NC(=O)c4ccccc4Cl)c(F)c3)c2cc1OC
Temperature: 25 °C
Reaction time: 2 h
Yield: 80 %

Procedure:
4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2-fluoroaniline (50 mg) was dissolved in toluene (5 ml) and ethanol (1 ml) to prepare a solution. Commercially available 2-chloro-1-benzenecarbonyl isothiocyanate (50 μl) was then added to the solution, and the mixture was stirred at room temperature for 2 hr. The reaction solution was concentrated, and the residue was purified by chromatography on silica gel using chloroform/acetone for development to give the title compound (63 mg, yield 80%).
Reaction SMILES: [CH3:1][O:2][C@@H:3]([C@@H:33]([N:38]([CH3:46])[C:39](=[O:45])[C@H:40]([CH:42]([CH3:44])[CH3:43])[NH2:41])[C@@H:34]([CH3:37])[CH2:35][CH3:36])[CH2:4][C:5]([N:7]1[CH2:11][CH2:10][CH2:9][C@H:8]1[C@H:12]([O:31][CH3:32])[C@@H:13]([CH3:30])[C:14](=[O:29])[NH:15][C@H:16]([C:24]1[S:25][CH:26]=[CH:27][N:28]=1)[CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)=[O:6].[C:47]([O:51][C:52]([N:54]1[CH2:58][CH2:57][C@:56]([F:62])([C:59](O)=[O:60])[CH2:55]1)=[O:53])([CH3:50])([CH3:49])[CH3:48].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C>ClCCl>[F:62][C@:56]1([C:59](=[O:60])[NH:41][C@@H:40]([CH:42]([CH3:44])[CH3:43])[C:39]([N:38]([C@@H:33]([C@@H:34]([CH3:37])[CH2:35][CH3:36])[C@H:3]([O:2][CH3:1])[CH2:4][C:5]([N:7]2[CH2:11][CH2:10][CH2:9][C@H:8]2[C@H:12]([O:31][CH3:32])[C@@H:13]([CH3:30])[C:14](=[O:29])[NH:15][C@H:16]([C:24]2[S:25][CH:26]=[CH:27][N:28]=2)[CH2:17][C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=2)=[O:6])[CH3:46])=[O:45])[CH2:57][CH2:58][N:54]([C:52]([O:51][C:47]([CH3:48])([CH3:49])[CH3:50])=[O:53])[CH2:55]1
Reactant: CC[C@H](C)[C@@H]([C@@H](CC(=O)N1CCC[C@H]1[C@H](OC)[C@@H](C)C(=O)N[C@@H](Cc1ccccc1)c1nccs1)OC)N(C)C(=O)[C@@H](N)C(C)C
Reactant: CC(C)(C)OC(=O)N1CC[C@](F)(C(=O)O)C1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: CC[C@H](C)[C@@H]([C@@H](CC(=O)N1CCC[C@H]1[C@H](OC)[C@@H](C)C(=O)N[C@@H](Cc1ccccc1)c1nccs1)OC)N(C)C(=O)[C@@H](NC(=O)[C@@]1(F)CCN(C(=O)OC(C)(C)C)C1)C(C)C
Yield: 40.5 %

Procedure:
According to the general procedure D, from #86 (300 mg, 0.45 mmol, 1 eq.), #168 (106 mg, 0.45 mmol, 1 eq.), dichloromethane (10 mL), HATU (194 mg, 0.54 mmol, 1.2 eq.) and diisopropylethylamine (117 mg, 0.9 mmol, 2 eq.) was synthesized the crude desired material, which was purified by reverse phase chromatography (Method P) to afford #191 (159 mg, 40%) as a white solid. HPLC (Protocol X): m/z 873.4 [M+H+], retention time=3.32 minutes (purity=99%).
Reaction SMILES: [CH2:1]([N:5]1[C:13]2[C:12]([OH:14])=[N:11][CH:10]=[N:9][C:8]=2[S:7]/[C:6]/1=[N:15]\[C:16](=[O:28])[C:17]1[CH:22]=[C:21]([C:23]([F:26])([F:25])[F:24])[CH:20]=[CH:19][C:18]=1F)[CH2:2][CH2:3][CH3:4].[CH2:29]([OH:33])[C@@H:30]([OH:32])[CH3:31].CC(C)([O-])C.[K+].C1COCC1>C(O)(=O)C>[CH2:1]([N:5]1[C:13]2[C:12]([OH:14])=[N:11][CH:10]=[N:9][C:8]=2[S:7]/[C:6]/1=[N:15]\[C:16](=[O:28])[C:17]1[CH:22]=[C:21]([C:23]([F:26])([F:25])[F:24])[CH:20]=[CH:19][C:18]=1[O:33][CH2:29][C@@H:30]([OH:32])[CH3:31])[CH2:2][CH2:3][CH3:4]
Reactant: CCCCn1/c(=N/C(=O)c2cc(C(F)(F)F)ccc2F)sc2ncnc(O)c21
Reactant: C[C@H](O)CO
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: CC(=O)O
Solvent: C1CCOC1
Product: CCCCn1/c(=N/C(=O)c2cc(C(F)(F)F)ccc2OC[C@H](C)O)sc2ncnc(O)c21
Yield: 66.4 %

Procedure:
A mixture of Example 1B (65 mg, 0.16 mmol), (S)-propane-1,2-diol (28 mg, 0.36 mmol) and 1N solution of potassium tert-butoxide in THF (0.33 mL, 0.33 mmol) was heated at 45° C. for 18 hours. The mixture was acidified to pH 5 with acetic acid then concentrated under reduced pressure. The residue was stirred with saturated aqueous NaHCO3, extracted with EtOAc, concentrated, and the residue was purified by chromatography (EtOAc-EtOH 19:1) to afford 50 mg of the title compound. 1H NMR (300 MHz, DMSO-d6) δ ppm 0.90-0.96 (m, 3H) 1.19 (d, J=5.76 Hz, 3H) 1.30-1.41 (m, 2H) 1.77-1.86 (m, 2H) 3.93-4.08 (m, 3H) 4.66-4.76 (m, 2H) 4.87 (d, J=4.07 Hz, 1H) 7.36 (d, J=8.82 Hz, 1H) 7.82 (dd, J=8.82, 2.03 Hz, 1H) 8.22 (s, 2H) 13.12 (s, 1H). MS (ESI) m/z 471 (M+H)+.
Reaction SMILES: [OH:1][CH2:2][C:3]1[CH:16]=[CH:15][C:14]2[O:13][C:12]3[C:7]4=[C:8]([C:17](=[O:20])[NH:18][N:19]=[C:6]4[C:5]=2[CH:4]=1)[CH:9]=[CH:10][CH:11]=3.[CH3:21][N:22]([CH3:27])[CH2:23][C:24](O)=[O:25].C(Cl)CCl>CN(C=O)C.CN(C1C=CN=CC=1)C>[O:20]=[C:17]1[C:8]2[CH:9]=[CH:10][CH:11]=[C:12]3[O:13][C:14]4[CH:15]=[CH:16][C:3]([CH2:2][O:1][C:24](=[O:25])[CH2:23][N:22]([CH3:27])[CH3:21])=[CH:4][C:5]=4[C:6]([C:7]=23)=[N:19][NH:18]1
Reactant: O=c1[nH]nc2c3c(cccc13)Oc1ccc(CO)cc1-2
Reactant: CN(C)CC(=O)O
Agent: CN(C)c1ccncc1
Solvent: ClCCCl
Solvent: CN(C)C=O
Product: CN(C)CC(=O)OCc1ccc2c(c1)-c1n[nH]c(=O)c3cccc(c13)O2
Temperature: 25 °C
Reaction time: 8 h
Yield: 30 %

Procedure:
To a solution of compound 57 (0.5 mmol) in anhydrous DMF was added dimethyl glycine (0.75 mmol) and EDC (0.75 mmol) and DMAP (catalytic amount). The reaction mixture was stirred at room temperature overnight. Solvent was removed in vacuo. To the residue, 100 mL of ethyl acetate was added. The organic layer was washed with water, and brine, then dried with MgSO4. The Solvents were removed to afford a colorless oil, which was re-crystallized in EtOAc/Hexanes to afford an off-white solid 59 in 30% yield. MS (ES+): 352; MP: 227-230° C.; 1H-NMR (CDCl3, 400 MHz): 10.15 (s, 1H), 8.14 (d, J=2.0 Hz, 1H), 8.06 (dd, J=8.0 and 1.0 Hz, 1H), 7.80 (t, J=8.0 Hz, 1H), 7.53 (dd, J=8.0 and 1.0 Hz, 1H), 7.47 (dd, J=8.5 and 2.0 Hz, 1H), 7.22 (d, J=8.5 Hz, 1H), 5.21 (s, 2H), 3.26 (s, 2H), 2.37 (s, 6H); Anal. Calcd. for C19H17N3O4: C, 64.95; H, 4.86; N, 11.96. Found: C, 64.95; H, 4.78; N, 12.14.
Reaction SMILES: F[C:2]1[C:24]([O:25][CH:26]([F:28])[F:27])=[C:23]([F:29])[C:22]([F:30])=[CH:21][C:3]=1[C:4]([C:6](=[CH:12][NH:13][CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][N:16]=1)[C:7]([O:9][CH2:10][CH3:11])=[O:8])=[O:5].C(=O)([O-])O.[Na+].O>CN(C)C=O>[F:30][C:22]1[CH:21]=[C:3]2[C:2](=[C:24]([O:25][CH:26]([F:28])[F:27])[C:23]=1[F:29])[N:13]([CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][N:16]=1)[CH:12]=[C:6]([C:7]([O:9][CH2:10][CH3:11])=[O:8])[C:4]2=[O:5]
Reactant: CCOC(=O)C(=CNCc1ccccn1)C(=O)c1cc(F)c(F)c(OC(F)F)c1F
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: CCOC(=O)c1cn(Cc2ccccn2)c2c(OC(F)F)c(F)c(F)cc2c1=O
Temperature: 120 °C
Reaction time: 0.5 h
Yield: 48.7 %

Procedure:
In 50 ml of N,N-dimethylformamide was dissolved 5.6 g (0.013 mole) of ethyl 2-(2,4,5-trifluoro-3-difluoromethoxybenzoyl)-3-(2-pyridylmethylamino)acrylate, and 2.2 g (0.026 mole) of sodium hydrogen carbonate was added thereto. The mixture was stirred at 120° C. for 30 minutes. Then, the reaction mixture was poured into 200 ml of water, and crystals precipitated were collected by filtration. The collected crystals were washed with water and ethanol and dried to obtain 2.6 g of ethyl 6,7-difluoro-8-difluoromethoxy-1-(2-pyridylmethyl)-1,4-dihydro-4-oxoquinoline-3-carboxylate as yellow crystals.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8][CH:9]2[CH2:12][N:11]([C:13](Cl)=[O:14])[CH2:10]2)=[CH:4][CH:3]=1.[OH-].[NH4+:17]>O1CCCC1.O>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8][CH:9]2[CH2:12][N:11]([C:13]([NH2:17])=[O:14])[CH2:10]2)=[CH:4][CH:3]=1
Reactant: [NH4+]
Reactant: O=C(Cl)N1CC(Sc2ccc(Cl)cc2)C1
Agent: [OH-]
Solvent: O
Solvent: C1CCOC1
Product: NC(=O)N1CC(Sc2ccc(Cl)cc2)C1
Temperature: 25 °C
Reaction time: 3 h
Yield: 82.4 %

Procedure:
A stirred solution of 2.6 g (0.01 mole) of 3-[(4-chlorophenyl)thio]-1-azetidinecarbonyl chloride in 20 ml of tetrahydrofuran was treated with 2 ml (0.02 mole) of 57% ammonium hydroxide. The slightly exothermic reaction mixture was stirred for 3 hr as it cooled to ambient temperature then diluted with 200 ml of water. The precipitated product was collected by filtration (2.4 g) and recrystallized from absolute ethanol to yield 2 g (83.3%) of fine white crystals, m.p. 210°-212° C.
Reaction SMILES: [NH2:1][C:2]1[C:3](=[O:8])[NH:4][CH:5]=[CH:6][CH:7]=1.C(O[CH:12]=[C:13]([C:19]([O:21][CH2:22][CH3:23])=[O:20])[C:14]([O:16][CH2:17][CH3:18])=[O:15])C.CCOCC>C(O)(C)C>[O:8]=[C:3]1[C:2]([NH:1][CH:12]=[C:13]([C:14]([O:16][CH2:17][CH3:18])=[O:15])[C:19]([O:21][CH2:22][CH3:23])=[O:20])=[CH:7][CH:6]=[CH:5][NH:4]1
Reactant: CCOC=C(C(=O)OCC)C(=O)OCC
Reactant: Nc1ccc[nH]c1=O
Solvent: CC(C)O
Solvent: CCOCC
Product: CCOC(=O)C(=CNc1ccc[nH]c1=O)C(=O)OCC
Temperature: 100 °C
Reaction time: 3 h
Yield: 63.3 %

Procedure:
3-Aminopyridin-2(1H)-one (9.00 g, 81.7 mmol) was treated with diethyl ethoxymethylenemalonate (24.6 ml, 123 mmol) and heated to 100° C. After 3 hours, the reaction was cooled down and diluted with isopropyl alcohol. The solid that crashed out was collected by suction filtration and washed well with IPA and then ether to give diethyl 2-((2-oxo-1,2-dihydropyridin-3-ylamino)methylene)malonate (14.5 g, 63.3% yield) as a greenish solid. MS(M+H)+ 281.
Reaction SMILES: [I:1]C1NC(C2(C)COC2)=NC=1C.[CH3:13][C:14]1([C:18]2[NH:19][CH:20]=[C:21]([C:23]([F:26])([F:25])[F:24])[N:22]=2)[CH2:17][O:16][CH2:15]1.CC1N=C(C2(C)COC2)NC=1>>[I:1][C:20]1[NH:19][C:18]([C:14]2([CH3:13])[CH2:17][O:16][CH2:15]2)=[N:22][C:21]=1[C:23]([F:26])([F:24])[F:25]
Reactant: CC1(c2nc(C(F)(F)F)c[nH]2)COC1
Reactant: Cc1nc(C2(C)COC2)[nH]c1I
Agent: Cc1c[nH]c(C2(C)COC2)n1
Product: CC1(c2nc(C(F)(F)F)c(I)[nH]2)COC1

Procedure:
The title compound was prepared using standard chemical manipulations and procedures similar to those used for the preparation of compound 175.2, except 2-(3-methyloxetan-3-yl)-4-(trifluoromethyl)-1H-imidazole (compound 202.1) was used in place of 4-methyl-2-(3-methyloxetan-3-yl)-1H-imidazole (compound 175.1). m/z (ES+) 333 (M+H)+.
Reaction SMILES: [CH2:1]([C:8]1[CH:9]=[C:10]([CH:13]=[CH:14][CH:15]=1)[CH:11]=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[I-].[C:17]([CH2:20][CH2:21][CH2:22][CH2:23][CH2:24]C[P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)([OH:19])=[O:18].CC([O-])(C)C.[K+]>C1(C)C=CC=CC=1>[CH2:1]([C:8]1[CH:9]=[C:10]([CH:11]=[CH:24][CH2:23][CH2:22][CH2:21][CH2:20][C:17]([OH:19])=[O:18])[CH:13]=[CH:14][CH:15]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=Cc1cccc(Cc2ccccc2)c1
Reactant: O=C(O)CCCCCC[P+](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: CC(C)(C)[O-]
Agent: [I-]
Agent: [K+]
Solvent: Cc1ccccc1
Product: O=C(O)CCCCC=Cc1cccc(Cc2ccccc2)c1

Procedure:
By using a similar procedure to that described in example 24 but with 1 g of 3-benzylbenzaldehyde, 5.5 g of (6-carboxy-hexyl)triphenylphosphonium iodide, 2.5 g of potassium ter-butylate and 40 cc of toluene as the starting material (1 hour; 50° C.), and after purification by flash chromatography on silica gel (30-60 Mm; eluent: 8:2:0.05 n-hexane/ethyl acetate/acetic acid), 7-(3-benzyl-phenyl)-6-heptenoic acid is obtained. (m.p.=68° C.)
Reaction SMILES: [NH:1]1[C:10](=[O:11])[C:9]2[NH:8][CH:7]=[N:6][C:5]=2[N:4]=[C:2]1[NH2:3].C[Si](C)(C)N[Si](C)(C)C.C(O[CH2:25][O:26][CH2:27][CH2:28][O:29][C:30](=[O:32])[CH3:31])(=O)C.O>CC(C)=O.S([O-])([O-])(=O)=O.[NH4+].[NH4+]>[C:30]([O:29][CH2:28][CH2:27][O:26][CH2:25][N:6]1[CH:7]=[N:8][C:9]2[C:10](=[O:11])[NH:1][C:2]([NH2:3])=[N:4][C:5]1=2)(=[O:32])[CH3:31]
Reactant: Nc1nc2nc[nH]c2c(=O)[nH]1
Reactant: CC(=O)OCCOCOC(C)=O
Agent: C[Si](C)(C)N[Si](C)(C)C
Agent: O=S(=O)([O-])[O-]
Agent: [NH4+]
Solvent: CC(C)=O
Solvent: O
Product: CC(=O)OCCOCn1cnc2c(=O)[nH]c(N)nc21
Temperature: 130 °C
Yield: 57.3 %

Procedure:
A mixture of 10 gms (66 mmoles) of guanine, 50 ml of hexamethyldisilazane, and 0.4 gms (3 mmmol) of ammonium sulfate was heated to 115°-118° C. for 18 hours. The ammonia gas was removed as it was formed. After 18 hours of heating, a solution was formed indicating the completion of silylation. To this solution was added 15 gms (85 mmol) of 2-oxa-1,4-butanediol diacetate and 0.1 ml of trimethylsilyl triftriflate. The mixture was heated to 130° C. for a period of 4.5 hours. The solution was cooled to 50° C. and 10 ml of water dissolved in 100 ml of acetone was added. The mixture was heated to reflux and a precipitate was formed immediately. The mixture was cooled and the solid was collected by filtration to yield 10.1 g (58% yield) of 9-(2-acetoxyethoxy)methylguanine, with a 13:1 ratio of N-9 to N-7 isomer. Characteristic analytical data are as follows: 1H NMR (DMSO-d6) δ1.90 (3H, singlet, --OAc) , 3.58 (2H, multiplet, --OCH2 --) , 4.0 (2H, multiplet, --CH2OAc) , 5.25 (2H, singlet, --NCH2O--), 6.5 (2H, br singlet, --NH2), 7.75 (1H, singlet, --N=CH--N--).
Reaction SMILES: [C:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][N:5]=1)(=O)[CH3:2].[CH:10]1([NH2:13])[CH2:12][CH2:11]1.O1CCCC1.C([BH3-])#N>C(O)(=O)C>[CH:10]1([NH:13][CH:1]([C:4]2[CH:9]=[CH:8][CH:7]=[CH:6][N:5]=2)[CH3:2])[CH2:12][CH2:11]1
Reactant: NC1CC1
Reactant: CC(=O)c1ccccn1
Agent: [BH3-]C#N
Solvent: C1CCOC1
Solvent: CC(=O)O
Product: CC(NC1CC1)c1ccccn1
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 77.8 %

Procedure:
A mixture of 2-acetylpyridine (250 mg, 2.06 mmol), cyclopropylamine (111 mg, 1.94 mmol), anhyd tetrahydrofuran (15 mL) and acetic acid (1.5 mL) is stirred at room temperature for 10 min. MP-cyanoborohydride (1.2 g, 2.82 mmol) is added and the mixture is stirred overnight. The reaction is filtered through a Varian mega bond elut SCX and the resin washed with methanol (20 mL). The resin is then washed with 7 N methanolic ammonia (60 mL) and the eluent is evaporated. The residue is purified by chromatography on an ISCO Redisep 10 g cartridge eluting with ethyl acetate to afford cyclopropyl(1-pyridin-2-yl)ethylamine (245 mg, 73% yield) as oil. A hydrochloride salt is prepared by dissolving the amine (50 mg, 0.308 mmol) in methanol (2 mL), adding 1 M ethereal hydrochloric acid (0.8 mL), some methanol is removed, more ether added and the hydrochloride salt is collected by filtration (50 mg, 69% yield as gray solid). RT=1.69 min; MS 163 (M+1); 1H NMR (δ, ppm): 9.5 (2H, br s), 8.69 (1H, d), 7.94 (1H, dd), 7.69 (1H, d), 7.47 (1H, m), 4.59 (1H, q), 1.58 (3H, d), 0.6-0.96 (4H, m).
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][C:10]=1[C:11]([F:14])([F:13])[F:12])[NH:7][C:6](C(O)=O)=[CH:5]2.[H-].[Na+].[CH3:20][C@@H:21]1[CH2:23][O:22]1>C1(OC2C=CC=CC=2)C=CC=CC=1.O1CCCC1>[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][C:10]=1[C:11]([F:12])([F:13])[F:14])[N:7]([CH2:20][C@H:21]([OH:22])[CH3:23])[CH:6]=[CH:5]2
Reactant: C[C@@H]1CO1
Reactant: O=C(O)c1cc2cc(F)c(C(F)(F)F)cc2[nH]1
Agent: [H-]
Agent: [Na+]
Solvent: c1ccc(Oc2ccccc2)cc1
Solvent: C1CCOC1
Product: C[C@@H](O)Cn1ccc2cc(F)c(C(F)(F)F)cc21
Reaction time: 4 h
Yield: 18.9 %

Procedure:
A suspension of 0.75 g of 5-fluoro-6-trifluoromethylindole-2-carboxylic acid in 16 ml of diphenyl ether was stirred at 260° for 4 hours and, after cooling to 0°, diluted with 16 ml of tetrahydrofuran. 113 mg of sodium hydride dispersion were added and the mixture was stirred for 1 hour. Subsequently, 0.43 ml of (R)-methyloxirane was added and the reaction mixture was stirred at room temperature for 60 hours. The mixture was extracted with diethyl ether, water and saturated sodium chloride solution and the organic phase was dried over sodium sulfate. The solvent was removed and the residue was chromatographed over 40 g of silica gel with hexane-toluene (1:1) and subsequently with toluene-ethyl acetate (15:1). There was obtained 0.15 g (18.9%) of (R)-1-(5-fluoro-6-trifluoromethyl-indol-1-yl)-propan-2-ol as light brown crystals.
Reaction SMILES: [Br:1][C:2]1[N:10]([CH2:11][O:12][CH2:13][CH3:14])[C:9]2[C:8](=[O:15])[NH:7][C:6](=[O:16])[N:5]([CH3:17])[C:4]=2[N:3]=1.[H-].[Na+].[C:20]([O:23][C@H:24]([CH3:30])[CH2:25][CH2:26][CH2:27][CH2:28]Cl)(=[O:22])[CH3:21]>CS(C)=O>[C:20]([O:23][C@H:24]([CH3:30])[CH2:25][CH2:26][CH2:27][CH2:28][N:7]1[C:8](=[O:15])[C:9]2[N:10]([CH2:11][O:12][CH2:13][CH3:14])[C:2]([Br:1])=[N:3][C:4]=2[N:5]([CH3:17])[C:6]1=[O:16])(=[O:22])[CH3:21]
Reactant: CC(=O)O[C@H](C)CCCCCl
Reactant: CCOCn1c(Br)nc2c1c(=O)[nH]c(=O)n2C
Agent: [H-]
Agent: [Na+]
Solvent: CS(C)=O
Product: CCOCn1c(Br)nc2c1c(=O)n(CCCC[C@@H](C)OC(C)=O)c(=O)n2C
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 82.2 %

Procedure:
To a stirring suspension of 8-bromo-7-ethoxymethyl-3-methylxanthine (1.52 g, 5.0 mmol) in anhydrous dimethylsulfoxide (20 ml) was added sodium hydride (144 mg, 6.0 mmol). The mixture was stirred at room temperature for 30 min and then (R)-5-acetoxy-1-chlorohexane (983 mg, 5.5 mmol) was added and the mixture was stirred at 70-75° C. After 12 hours, the mixture was cooled to room temperature, quenched with saturated aqueous sodium chloride solution (100 ml) and extracted with ethyl acetate (3×50 ml). The combined extracts were washed with water (2×25 ml), with saturated aqueous sodium chloride solution (25 ml) and dried over magnesium sulfate. After evaporation of the solvent under reduced pressure, the product was purified by flash chromatography over silica gel eluting with ethyl acetate to provide (R)-1-(5-acetoxyhexyl)-8-bromo-7-ethoxymethyl-3-methylxanthine (1.83 g, 82% yield) as a beige solid.
Reaction SMILES: C(O[CH:6](N(C)C)[N:7]([CH3:9])[CH3:8])(C)(C)C.[CH:13]([O:26][C:27]([C:29]1[N:30]2[CH:33]([S:34][CH2:35][C:36]=1[CH3:37])[CH:32]([NH:38][P:39]([O:44][CH2:45][CH3:46])([O:41][CH2:42][CH3:43])=[O:40])[C:31]2=[O:47])=[O:28])([C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.C(OCC)(=O)C>CN(C)C=O>[CH:13]([O:26][C:27]([C:29]1[N:30]2[CH:33]([S:34][CH2:35][C:36]=1[CH:37]=[CH:6][N:7]([CH3:9])[CH3:8])[CH:32]([NH:38][P:39]([O:41][CH2:42][CH3:43])([O:44][CH2:45][CH3:46])=[O:40])[C:31]2=[O:47])=[O:28])([C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1
Reactant: CCOP(=O)(NC1C(=O)N2C(C(=O)OC(c3ccccc3)c3ccccc3)=C(C)CSC12)OCC
Reactant: CN(C)C(OC(C)(C)C)N(C)C
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: CCOP(=O)(NC1C(=O)N2C(C(=O)OC(c3ccccc3)c3ccccc3)=C(C=CN(C)C)CSC12)OCC
Reaction time: 0.2 h

Procedure:
t-Butoxy-bis-dimethylaminomethane (6 cc) is added to a solution of 2-benzhydryloxycarbonyl-7-diethoxyphosphorylamino-3-methyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene (10 g) in dry N,N-dimethylformamide (100 cc) at 80° C. After 12 minutes at 80° C., the reaction mixture is poured into ethyl acetate (400 cc) and washed with distilled water (5×250 cc). After drying over magnesium sulphate and evaporation of the solvent under reduced pressure (30 mm Hg; 4 kPa) at 30° C., 2-benzhydryloxycarbonyl-3-(2-dimethylaminovinyl)-7-diethoxyphosphorylamino-8-oxo-5thia-1-azabicyclo[4.2.0]oct-2-ene (E isomer) (10.5 g) is obtained in the form of an orange crystalline solid. This product is purified by crystallisation from ethyl acetate (30 cc), and 2-benzhydryloxycarbonyl-3-(2-dimethylaminovinyl)-7-diethoxyphosphorylamino-8-oxo-5 -thia-1-azabicyclo [4.2.0]oct-2-ene (E isomer) (5.3 g) is obtained in the form of a yellow crystalline powder (m.p.=193°-194° C.).