Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: CC[C@@]1(O)C(=O)[O:7]CC2C(N3C(=CC1=2)C1N=C2C(C=CC=C2)=CC=1C3)=O.C(O)(=O)C1C=CC=CC=1.[CH2:36]1[CH2:41][CH2:40][CH:39]([N:42]=[C:43]=[N:44][CH:45]2[CH2:50][CH2:49][CH2:48][CH2:47][CH2:46]2)[CH2:38][CH2:37]1>CN(C1C=CN=CC=1)C.CN(C=O)C>[CH:45]1([NH:44][C:43]([NH:42][CH:39]2[CH2:38][CH2:37][CH2:36][CH2:41][CH2:40]2)=[O:7])[CH2:50][CH2:49][CH2:48][CH2:47][CH2:46]1
Reactant: C(=NC1CCCCC1)=NC1CCCCC1
Reactant: CC[C@@]1(O)C(=O)OCc2c1cc1n(c2=O)Cc2cc3ccccc3nc2-1
Agent: CN(C)c1ccncc1
Agent: O=C(O)c1ccccc1
Solvent: CN(C)C=O
Product: O=C(NC1CCCCC1)NC1CCCCC1
Temperature: 25 °C
Reaction time: 72 h
Yield: 38 %

Procedure:
Camptothecin (0.8 g, 0.0023 mol), benzoic acid (1.8 g, 0.014 mol), DCC (1.2 g, 0.0058 mol), and DMAP (0.3 g, 0.0025 mol) were added to 60 ml DMF in a 250 ml round-bottomed flask equipped with a mechanical stirrer. The mixture was stirred under N2 at room temperature for 72 hr. Dicyclohexyl urea formed during the reaction was removed by filtration. The filtrate was poured onto 600 ml ice water while stirring. The stirring was maintained for 30 min. The crude product was collected by filtration. The residue was chromatographically separated with THF-CH2Cl2 (1:15) as eluent. The pure product (0.4 g) was obtained as white powders by precipitation from petroleum ether. Yield 38%. Mass m/e (relative intensity): 452 (m+, 25), 330 (100), 315 (35), 302 (60), 287 (40), 169 (12), 122 (36), 105 (70), 77 (35), 69 (26); precise mass (C27H20N2O5): found, 452.137; required, 452.137.
Reaction SMILES: F[B-](F)(F)F.C([N+]1C=CN(C)C=1)CCC.F[C:17]1[CH:22]=[CH:21][C:20]([N+:23]([O-:25])=[O:24])=[CH:19][C:18]=1[CH3:26].[C:27]([N:30]1[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]1)(=[O:29])[CH3:28]>C(#N)C.CCOC(C)=O.O>[C:27]([N:30]1[CH2:35][CH2:34][N:33]([C:17]2[CH:22]=[CH:21][C:20]([N+:23]([O-:25])=[O:24])=[CH:19][C:18]=2[CH3:26])[CH2:32][CH2:31]1)(=[O:29])[CH3:28]
Reactant: CC(=O)N1CCNCC1
Reactant: Cc1cc([N+](=O)[O-])ccc1F
Agent: CCCC[n+]1ccn(C)c1
Agent: F[B-](F)(F)F
Solvent: CC#N
Solvent: CCOC(C)=O
Solvent: O
Product: CC(=O)N1CCN(c2ccc([N+](=O)[O-])cc2C)CC1
Temperature: 95 °C

Procedure:
1-Butyl-3-methylimidazolium tetrafluoroborate (1.75 g, 7.74 mmol) was added to a stirred solution of 1-fluoro-2-methyl-4-nitrobenzene (12 g, 77.35 mmol) and 1-acetylpiperazine (39.7 g, 309.4 mmol) in acetonitrile (3 ml). The reaction mixture was then heating at 95° C. overnight. The reaction mixture was allowed to cool down to room temperature. The solution was diluted with EtOAc and water. The precipitate formed was filtered off to give a solid corresponding to the required product. The organics were washed with water (4 times), brine, dried and evaporation of solvent to give a solid. Both solids were combined and after trituration with isohexane/ether and filtration, the title compound was obtained as a yellow solid which was dried in vac oven overnight at 50° C. (19.61 g, 96%). NMR (400 MHz) 2.06 (s, 3H), 2.38 (s, 3H), 2.99 (dt, 4H), 3.61 (m, 4H), 7.14 (d, 1H), 8.04 (dd, 1H), 8.07 (d, 1H); m/z 264.
Reaction SMILES: [N:1]([CH2:4][CH2:5][O:6][CH2:7][CH2:8][O:9][CH2:10][CH2:11][O:12][CH2:13][CH2:14][NH2:15])=[N+:2]=[N-:3].C(N(CC)CC)C.[Cl:23][C:24]1[CH:25]=[C:26]2[C:31](=[C:32]([Cl:34])[CH:33]=1)[CH2:30][N:29]([CH3:35])[CH2:28][CH:27]2[C:36]1[CH:37]=[C:38]([S:42](Cl)(=[O:44])=[O:43])[CH:39]=[CH:40][CH:41]=1>C(Cl)Cl>[N:1]([CH2:4][CH2:5][O:6][CH2:7][CH2:8][O:9][CH2:10][CH2:11][O:12][CH2:13][CH2:14][NH:15][S:42]([C:38]1[CH:39]=[CH:40][CH:41]=[C:36]([CH:27]2[C:26]3[C:31](=[C:32]([Cl:34])[CH:33]=[C:24]([Cl:23])[CH:25]=3)[CH2:30][N:29]([CH3:35])[CH2:28]2)[CH:37]=1)(=[O:44])=[O:43])=[N+:2]=[N-:3]
Reactant: CN1Cc2c(Cl)cc(Cl)cc2C(c2cccc(S(=O)(=O)Cl)c2)C1
Reactant: [N-]=[N+]=NCCOCCOCCOCCN
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CN1Cc2c(Cl)cc(Cl)cc2C(c2cccc(S(=O)(=O)NCCOCCOCCOCCN=[N+]=[N-])c2)C1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To 2-(2-(2-(2-azidoethoxy)ethoxy)ethoxy)ethanamine (1.5 g, 6.87 mmol, 1.79 equiv) in DCM (20 mL) was added triethylamine (1.5 g, 14.82 mmol, 3.86 equiv) and 3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)benzene-1-sulfonyl chloride (1.5 g, 3.84 mmol, 1.00 equiv). The reaction was stirred overnight at room temperature at which time the resulting mixture was concentrated under vacuum. The residue was dissolved in 100 mL of ethyl acetate and then was washed with 2×20 mL of water, dried over anhydrous sodium sulfate and concentrated under vacuum. This resulted in 1.8 g (85%) of N-(2-(2-(2-(2-azidoethoxy)ethoxy)ethoxy)ethyl)-3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)benzenesulfonamide as yellow oil.
Reaction SMILES: [Al+3].[Cl-].[Cl-].[Cl-].C(S)C.[CH:8]([C:11]1[CH:21]=[C:20]([O:22]C)[CH:19]=[C:18]2[C:12]=1[C:13](=[O:24])[NH:14][S:15]2(=[O:17])=[O:16])([CH3:10])[CH3:9].Cl>C(Cl)(Cl)Cl>[OH:22][C:20]1[CH:19]=[C:18]2[C:12]([C:13](=[O:24])[NH:14][S:15]2(=[O:17])=[O:16])=[C:11]([CH:8]([CH3:10])[CH3:9])[CH:21]=1
Reactant: COc1cc(C(C)C)c2c(c1)S(=O)(=O)NC2=O
Agent: Cl
Agent: [Al+3]
Agent: [Cl-]
Solvent: CCS
Solvent: ClC(Cl)Cl
Product: CC(C)c1cc(O)cc2c1C(=O)NS2(=O)=O
Temperature: 25 °C
Reaction time: 3.5 h
Yield: 97.8 %

Procedure:
An alternative procedure was also used. To a stirred suspension of 62.74 g (0.47 mol) of AlCl3 in 500 mL of chloroform at 0° C. was added 43.9 g (0.7 mol) of ethanethiol. Within minutes a clear solution formed. To this a solution of 20.0 g (0.078 mol) of 4-isopropyl-6-methoxysaccharin in 550 mL of chloroform was added over a 30-min period. This solution was allowed to warm to RT and stirred for 3-4 hrs. at 60° C. After cooling, the mixture was poured into ice-water and acidified with dilute HCl. The solid which separated was collected by filtration, washed with water and dried to give 18.4 g (97%) of 6-hydroxy-4-isopropylsaccharin.
Reaction SMILES: Br[C:2]1[CH:15]=[CH:14][C:5]([CH2:6][CH2:7][N:8]2[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)=[CH:4][CH:3]=1.[CH3:16][C:17]1([CH3:26])[C:21]([CH3:23])([CH3:22])[O:20][B:19]([CH:24]=[CH2:25])[O:18]1.CCN(CC)CC>CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C>[CH3:22][C:21]1([CH3:23])[C:17]([CH3:26])([CH3:16])[O:18][B:19](/[CH:24]=[CH:25]/[C:2]2[CH:15]=[CH:14][C:5]([CH2:6][CH2:7][N:8]3[CH2:13][CH2:12][O:11][CH2:10][CH2:9]3)=[CH:4][CH:3]=2)[O:20]1
Reactant: C=CB1OC(C)(C)C(C)(C)O1
Reactant: Brc1ccc(CCN2CCOCC2)cc1
Agent: CC(C)(C)[P]([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)(C(C)(C)C)C(C)(C)C
Solvent: CCN(CC)CC
Product: CC1(C)OB(/C=C/c2ccc(CCN3CCOCC3)cc2)OC1(C)C
Temperature: 80 °C
Yield: 76.8 %

Procedure:
To a mixture of 4-(4-bromophenethyl)morpholine (731 mg, 2.71 mmol) and 4,4,5,5-tetramethyl-2-vinyl-1,3,2-dioxaborolane (0.5 mL, 2.95 mmol, 1.1 eq.) in a 20 mL microwave vial was added Et3N (0.76 mL, 5.4 mmol, 2 eq.), followed by Pd(PtBu3)2 (14 mg, 0.027 mmol, 1 mol %). The resulting mixture was purged with argon, then capped and heated at 80° C. (oil temp.) for 2 h. After cooling to rt, the reaction was quenched with sat. NaHCO3 (10 mL), H2O (10 mL), extracted with EtOAc (30 mL×2) and dried over Na2SO4. After evaporation of the solvents, the residue was purified by Biotage column system (EtOAc/hex gradient: 0-100%) to give (E)-4-(4-(2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)vinyl)phenethyl)morpholine as a white solid (714 mg, 77%). 1H NMR (400 MHz, CDCl3) δ 7.42 (d, J=8.0 Hz, 2H), 7.38 (d, J=19.0 Hz, 1H), 7.19 (d, J=7.8 Hz, 2H), 6.13 (d, J=18.3 Hz, 1H), 3.75 (t, J=4.4 Hz, 4H), 2.84-2.77 (m, 2H), 2.63-2.56 (m, 2H), 2.53 (br, pseudo s, 4H), 1.32 (s, 12H).
Reaction SMILES: [OH:1][C@H:2]1[CH2:6][CH2:5][NH:4][CH2:3]1.C(N(CC)CC)C.[CH3:14][S:15](Cl)(=[O:17])=[O:16]>CN(C)C1C=CN=CC=1.ClCCl>[CH3:14][S:15]([O:1][C@H:2]1[CH2:6][CH2:5][N:4]([S:15]([CH3:14])(=[O:17])=[O:16])[CH2:3]1)(=[O:17])=[O:16]
Reactant: O[C@H]1CCNC1
Reactant: CS(=O)(=O)Cl
Agent: CN(C)c1ccncc1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CS(=O)(=O)O[C@H]1CCN(S(C)(=O)=O)C1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To a dichloromethane (200 mL) solution of (S)-3-hydroxypyrrolidine (5.0 g, 57 mmol) and triethylamine (24.0 mL, 172 mmol) at 0° C. was added methanesulfonyl chloride (7.23 g, 63.1 mmol). 4-(Dimethylamino)pyridine (0.70 g, 5.7 mmol) was then added, and the mixture was stirred at room temperature for 2 hours. It was diluted with dichloromethane (50 mL), and the combined organic layers were washed with aqueous 1 M hydrochloric acid (30 mL), water (30 mL), brine (30 mL), dried (magnesium sulfate), filtered and concentrated in vacuo to afford the title compound. The crude product was used in the subsequent step without further purification. 1H NMR (500 MHz, CDCl3) δ 5.28 (t, J=4.5 Hz, 1H), 3.71 (d, J=12.9 Hz, 1H), 3.64 (dd, J=12.7, 4.0 Hz, 1H), 3.59 (td, J=9.2, 2.3 Hz, 1H), 3.46 (td, J=10.1, 6.7 Hz, 1H), 3.07 (s, 3H), 2.89 (s, 3H), 2.39-2.33 (m, 1H), 2.29-2.19 (m, 1H); LC-MS: m/z 244.1 (M+H).
Reaction SMILES: Cl[C:2](=[CH2:12])[CH2:3][CH:4]([C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)[OH:5].[OH-].[K+].C(O)(=O)C>CN(C)C=O>[C:6]1([CH:4]([CH2:3][C:2]#[CH:12])[OH:5])[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1
Reactant: C=C(Cl)CC(O)c1ccccc1
Agent: [K+]
Agent: [OH-]
Solvent: CC(=O)O
Solvent: CN(C)C=O
Product: C#CCC(O)c1ccccc1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
40.00 Grams of 2-chloroallylphenylcarbinol were dissolved in 400 g of dimethylformamide, and 36.85 g of potassium hydroxide in a flake form were added. The mixture was stirred at room temperature for 2 hours and then neutralized with a 20% acetic acid aqueous solution. The resultant mixture was subjected to extraction with toluene. The toluene phase was washed with water and then dried over magnesium sulfate. The desiccant was filtered off, and the toluene was distilled off under reduced pressure to give 31.35 g of phenylpropargylcarbinol, nD20 =1.546, FI-MS m/e 146 (M+), propargyl compound/allene compound=92.3/7.7.
Reaction SMILES: [N+:1]([C:4]1[C:9]([Cl:10])=[C:8]([Cl:11])[C:7]([Cl:12])=[C:6]([Cl:13])[C:5]=1[N+:14]([O-])=O)([O-])=O.O.O.Cl[Sn]Cl.C(O)C.C([O-])(O)=O.[Na+]>C(OCC)(=O)C>[NH2:14][C:5]1[C:6]([Cl:13])=[C:7]([Cl:12])[C:8]([Cl:11])=[C:9]([Cl:10])[C:4]=1[NH2:1]
Reactant: O=[N+]([O-])c1c(Cl)c(Cl)c(Cl)c(Cl)c1[N+](=O)[O-]
Agent: Cl[Sn]Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O
Solvent: CCOC(C)=O
Solvent: CCO
Product: Nc1c(N)c(Cl)c(Cl)c(Cl)c1Cl
Temperature: 25 °C

Procedure:
1,2-Diamino-3,4,5,6-tetrachlorobenzene was prepared using an adaptation of the method of Bellamy et al. (Bellamy, F. D. et al., Tetrahedron Lett. 25: 839 (1984)). A mixture of 1,2-dinitro-3,4,5,6-tetrachlorobenzene (1.00 g, 3.27 mmol) and SnCl2.2H2O (3.69 g, 16.4 mmol) dissolved in 10 mL ethyl acetate and 5 mL absolute ethanol under N2 was heated at 80° C. for 1 h. The reaction was allowed to cool to room temperature and poured into 20 mL crushed ice. Sufficient sat'd NaHCO3 solution was adding (foaming!) to bring the pH to 6. The thick white emulsion was extracted with 3×25 mL ethyl acetate and the combined organic extracts washed with sat'd NaCl solution. The organic phase was dried (MgSO4), vacuum filtered and the solvent rotary evaporated to yield a brown solid 569 mg (71%). 1H NMR (CDCl3) δ 3.96 (br s, 2(NH2)). 13C NMR (CDCl3) δ 118.2, 127.0, 132.0.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]([F:9])=[C:6]([CH3:8])[CH:7]=1.[Br:10]N1C(=O)CCC1=O.CCCCCCC.C1(=O)NC(=O)CC1>C(OC(=O)C)C.C(OOC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([F:9])=[C:6]([CH:7]=1)[CH2:8][Br:10]
Reactant: Cc1cc(Cl)ccc1F
Reactant: O=C1CCC(=O)N1Br
Agent: O=C(OOC(=O)c1ccccc1)c1ccccc1
Agent: O=C1CCC(=O)N1
Solvent: CCCCCCC
Solvent: CCOC(C)=O
Product: Fc1ccc(Cl)cc1CBr
Temperature: 80 °C
Reaction time: 3 h
Yield: 104.8 %

Procedure:
5-Chloro-2-fluoro-toluene (100 g, 692 mmol) was dissolved in ethylacetate (300 ml) at 20° C. To this solution N-bromosuccinimide (147.7 g, 830 mmol) and dibenzoyl peroxide (2 g, 8.25 mmol) was added. The mixture was stirred at 80° C. for 3 hours. Heptane (300 ml) was added and the solution was cool to 0° C. whereupon succinimide precipitates. After filtration and washing with heptane, the residue was washed with water (1500 ml). The filtrate was concentrated in vacuo to dryness, yielding 162 grams of crude 5-chloro-2-fluoro-benzylbromide. Purification of the crude product (141 grams) was done by vacuum distillation at 99° C. and 33 mbar, this 5-chloro-2-fluoro-benzylbromide (99 grams, 75%). Purity according to GC is 87.1% a/a.
Reaction SMILES: CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH:25]([C:27]([CH:29]1[CH2:34][CH2:33][N:32]([C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH2:31][CH2:30]1)=[O:28])[NH2:26].[CH2:42]([O:49][N:50]1[C:56](=[O:57])[N:55]2[CH2:58][C@H:51]1[CH2:52][CH2:53][C@H:54]2[C:59](O)=[O:60])[C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1.CCN(C(C)C)C(C)C>C(Cl)Cl>[CH2:42]([O:49][N:50]1[C:56](=[O:57])[N:55]2[CH2:58][C@H:51]1[CH2:52][CH2:53][C@H:54]2[C:59]([NH:26][NH:25][C:27]([CH:29]1[CH2:34][CH2:33][N:32]([C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH2:31][CH2:30]1)=[O:28])=[O:60])[C:43]1[CH:44]=[CH:45][CH:46]=[CH:47][CH:48]=1
Reactant: O=C(O)[C@@H]1CC[C@@H]2CN1C(=O)N2OCc1ccccc1
Reactant: CC(C)(C)OC(=O)N1CCC(C(=O)NN)CC1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: CC(C)(C)OC(=O)N1CCC(C(=O)NNC(=O)[C@@H]2CC[C@@H]3CN2C(=O)N3OCc2ccccc2)CC1
Temperature: 0 °C
Reaction time: 12 h

Procedure:
HATU (3.3 g, 8.7 mmol) and tert-butyl 4-(hydrazinecarbonyl)piperidine-1-carboxylate (2.29 g, 9.42 mmol) were added to a 0° C. solution of (2S,5R)-6-(benzyloxy)-7-oxo-1,6-diaza-bicyclo[3.2.1]octane-2-carboxylic acid (2 g, 7.25 mmol) in CH2Cl2 (50 mL), followed by the addition of DIPEA (2.8 g, 21.8 mmol). The reaction mixture was stirred at 0° C. for 12 hrs then washed with water and saturated sodium chloride, dried over Na2SO4, and concentrated. The residue was purified by silica gel column chromatography (gradient elution 1%-10% MeOH/CH2Cl2) to give tert-butyl 4-(2-((2S,5R)-6-(benzyloxy)-7-oxo-1,6-diaza-bicyclo[3.2.1]octane-2-carbonyl)hydrazinecarbonyl)piperidine-1-carboxylate as a white solid. (2.2 g, 62%). ESI-MS (EI+, m/z): 502.2 [M+H]+.
Reaction SMILES: F[C:2]1[C:7](F)=[C:6](I)C=C[C:3]=1[C:10]1C=[CH:14][C:13](C2C=CC(CCC)=CC=2)=[CH:12][C:11]=1F.OCC(C)(CO)C.CC(C)=O>CC(O)C.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH3:6][CH2:7][CH2:2][CH2:3][CH2:10][CH2:11][CH2:12][CH2:13][CH3:14]
Reactant: CCCc1ccc(-c2ccc(-c3ccc(I)c(F)c3F)c(F)c2)cc1
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: CC(C)(CO)CO
Solvent: CC(C)=O
Solvent: CC(C)O
Product: CCCCCCCCC
Yield: 65 %

Procedure:
A solution of (0.1 mmol) of 10, (0.12 mmol) of 12, 14 mg (0.13 mmol) of neopentyl glycol, 95 mg (0.3 mmol) of Ba(OH)2. 8H2O, 80 μl (6.08 mmol, 5 mol %) of a 76 mM acetone solution of Pd(OAc)2 in 2 ml of 95% i-PrOH is stirred at 80° C. for 12 hours. The solvent is subsequently removed under reduced pressure. 2 ml of 2 M HCl are added to the residue, and the mixture is extracted with dichloromethane (3×2 ml). The combined organic phases are dried over MgSO4 and filtered through SiO2. The solvent is removed under reduced pressure, and the residue is purified by recrystallisation twice from nonane (yield: 65%).
Reaction SMILES: C([O:4][C:5]1[CH:10]=[CH:9][C:8]([CH:11]=[O:12])=[C:7]([N+:13]([O-:15])=[O:14])[C:6]=1[O:16][CH3:17])(=O)C.C(=O)([O-])[O-].[K+].[K+].Cl>CO.O>[OH:4][C:5]1[CH:10]=[CH:9][C:8]([CH:11]=[O:12])=[C:7]([N+:13]([O-:15])=[O:14])[C:6]=1[O:16][CH3:17]
Reactant: COc1c(OC(C)=O)ccc(C=O)c1[N+](=O)[O-]
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CO
Solvent: O
Product: COc1c(O)ccc(C=O)c1[N+](=O)[O-]
Temperature: 25 °C
Reaction time: 16 h
Yield: 89.3 %

Procedure:
A mixture of 4-formyl-2-methoxy-3-nitrophenyl acetate 438 g (1.8 mol) and potassium carbonate (506 g, 3.7 mol) in MeOH (4000 mL) was stirred at room temperature for 16 h. The reaction mixture was concentrated under reduced pressure to afford a viscous oil. This was dissolved in water, acidified using a solution of HCl (2 N) and extracted with EtOAc. The organic layer was washed with brine, dried (MgSO4) and filtered. The solvent was concentrated under reduced pressure to ⅓ volume and the resulting solids were filtered and air-dried to give the title compound (317 g, 88%): 1H NMR (DMSO-d6) δ: 9.69 (1H, s), 7.68 (1H, d), 7.19 (1H, d), 3.82 (3H, s).
Reaction SMILES: [Si:1]([N:8]1[C:16]2[C:11](=[CH:12][C:13]([F:17])=[CH:14][CH:15]=2)[CH:10]=[CH:9]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].CN(CCN(C)C)C.[Li]C(CC)C.[B:31](OC(C)C)([O:36]C(C)C)[O:32]C(C)C>C1COCC1.C1CCCCC1.O>[Si:1]([N:8]1[C:16]2[C:11](=[C:12]([B:31]([OH:36])[OH:32])[C:13]([F:17])=[CH:14][CH:15]=2)[CH:10]=[CH:9]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]
Reactant: CC(C)OB(OC(C)C)OC(C)C
Reactant: CC(C)(C)[Si](C)(C)n1ccc2cc(F)ccc21
Agent: CN(C)CCN(C)C
Agent: [Li]C(C)CC
Solvent: C1CCOC1
Solvent: C1CCCCC1
Solvent: O
Product: CC(C)(C)[Si](C)(C)n1ccc2c(B(O)O)c(F)ccc21
Temperature: -78 °C
Reaction time: 2 h
Yield: 20.5 %

Procedure:
To a mixture of the product of Step 1 (4.98 g, 20 mmol) and TMEDA (2.32 g, 20 mmol) in THF at −78° C. was slowly added a 1.3M solution of s-BuLi (15.4 mL, 20 mmol) in cyclohexane and the mixture was stirred for 2 h at −78° C. Triisopropyl borate (3.76 g, 20 mmol) was added to the mixture at −78° C. and stirred for another 1 h and then warmed to −20° C. Water was added and the mixture was extracted with EtOAc and the organic layer was dried over Na2SO4 and evaporated. The residue was re-crystallized (EtOAc and n-hexane) to give the title compound (1.2 g, 20.7%).
Reaction SMILES: [F:1][C:2]1[CH:10]=[CH:9][C:5]([C:6](O)=[O:7])=[CH:4][CH:3]=1.S(Cl)([Cl:13])=O>CN(C)C=O.C(Cl)(Cl)Cl>[F:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([Cl:13])=[O:7])=[CH:4][CH:3]=1
Reactant: O=S(Cl)Cl
Reactant: O=C(O)c1ccc(F)cc1
Solvent: ClC(Cl)Cl
Solvent: CN(C)C=O
Product: O=C(Cl)c1ccc(F)cc1
Yield: 82.8 %

Procedure:
A mixture of 4-fluorobenzoic acid (0.15 mol), thionyl chloride (0.45 mol) and dimethylformamide (5 drops) in chloroform (200 ml) was heated at reflux for 16 hours. Volatiles were removed from the cooled solution in vacuo. The residue was diluted with carbon tetrachloride (100 ml) and the mixture evaporated in vacuo to remove residual thionyl chloride. The residue was distilled affording 19.7 g of a clear oil (83% yield); bp 110°-112° C. at 40 mm of Hg. Spectral data are consistent with the assigned structure.
Reaction SMILES: [OH:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[CH:4][CH:3]=1.C(N(CC)CC)C.[C:18](Cl)(=[O:29])[CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH3:28].Cl>CN(C)C1C=CN=CC=1.ClCCl>[C:18]([O:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[CH:4][CH:3]=1)(=[O:29])[CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH3:28]
Reactant: CCCCCCCCCCC(=O)Cl
Reactant: O=C(O)c1ccc(O)cc1
Agent: CN(C)c1ccncc1
Agent: Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CCCCCCCCCCC(=O)Oc1ccc(C(=O)O)cc1

Procedure:
12.7 Grams (0.0917 mol) of p-hydroxybenzoic acid was added to 150 ml of dichloromethane, and to this suspension was added 10.2 g (0.0917 mol) of triethylamine. The mixture was stirred until a homogeneous solution was formed. 19.7 Grams (0.096 mol) of undecanoyl chloride was added to the solution at such a rate that the dichloromethane was not refluxed. Then, 1.0 g (0.0085 mol) of 4-dimethylaminopyridine was added, and the mixture was stirred at room temperature overnight. 1N Hydrochloric acid was added to the reaction mixture and the mixture was subjected to extraction with ether. The ether was distilled off, and the resultant crude product was washed with hexane.
Reaction SMILES: [NH2:1][C:2]1[C:7]([N+:8]([O-:10])=[O:9])=[CH:6][CH:5]=[CH:4][C:3]=1[OH:11].C(=O)([O-])[O-].[K+].[K+].[CH3:18][O:19][C:20]1[CH:27]=[CH:26][C:23]([CH2:24]Cl)=[CH:22][CH:21]=1.O>CN(C)C=O>[CH3:18][O:19][C:20]1[CH:27]=[CH:26][C:23]([CH2:24][O:11][C:3]2[CH:4]=[CH:5][CH:6]=[C:7]([N+:8]([O-:10])=[O:9])[C:2]=2[NH2:1])=[CH:22][CH:21]=1
Reactant: COc1ccc(CCl)cc1
Reactant: Nc1c(O)cccc1[N+](=O)[O-]
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: COc1ccc(COc2cccc([N+](=O)[O-])c2N)cc1
Reaction time: 0.5 h
Yield: 0.1 %

Procedure:
To a solution of 2-amino-3-nitrophenol (10 g) in dimethylformamide (100 ml) was added potassium carbonate (17.9 g) under ice-cooling, and the mixture was stirred for 30 minutes at the same temperature. To the mixture was added 4-methoxybenzyl chloride (10.7 g) at ambient temperature, and the mixture was stirred for 30 minutes under ice-cooling and then overnight at ambient temperature. To the reaction mixture was added water, and the mixture was extracted with dichloromethane, and purified by silica gel column chromatography (ethyl acetate-n-hexane). The residue was crystallized with ethanol to give 2-(4-methoxybenzyloxy)-6-nitroaniline (13.6 mg) as yellow needles.
Reaction SMILES: Cl[CH2:2][C:3]1[CH:8]=[CH:7][C:6]([O:9][CH3:10])=[CH:5][CH:4]=1.[N-:11]=[N+:12]=[N-:13].[Na+].C(Cl)Cl>C(O)C.O>[N:11]([CH2:2][C:3]1[CH:8]=[CH:7][C:6]([O:9][CH3:10])=[CH:5][CH:4]=1)=[N+:12]=[N-:13]
Reactant: COc1ccc(CCl)cc1
Reactant: [N-]=[N+]=[N-]
Agent: [Na+]
Solvent: ClCCl
Solvent: CCO
Solvent: O
Product: COc1ccc(CN=[N+]=[N-])cc1
Yield: 75 %

Procedure:
64 mmol 1-(chloromethyl)-4-methoxybenzene and 90 mmol sodium azide were dissolved in 20 ml ethanol and 5 ml water, and stirred overnight at room temperature. CH2Cl2 and water were added. The organic layer was separated, dried and evaporated to give 48 mmol 1-(azidomethyl)-4-methoxybenzene.
Reaction SMILES: I[C:2]1[C:3](=[O:17])[NH:4][C:5](=[O:16])[N:6]([CH:15]=1)[C@@H:7]1[O:14][C@H:11]([CH2:12][OH:13])[C@@H:9]([OH:10])[CH2:8]1.C(N(CC)CC)C.[C:25]1(=[O:39])[N:29]([CH2:30][CH2:31][C:32]#[CH:33])[C:28](=[O:34])[C:27]2=[CH:35][CH:36]=[CH:37][CH:38]=[C:26]12>CN(C)C=O.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>[C:28]1(=[O:34])[N:29]([CH2:30][CH2:31][C:32]#[C:33][C:2]2[C:3](=[O:17])[NH:4][C:5](=[O:16])[N:6]([CH:15]=2)[C@@H:7]2[O:14][C@H:11]([CH2:12][OH:13])[C@@H:9]([OH:10])[CH2:8]2)[C:25](=[O:39])[C:26]2=[CH:38][CH:37]=[CH:36][CH:35]=[C:27]12
Reactant: C#CCCN1C(=O)c2ccccc2C1=O
Reactant: O=c1[nH]c(=O)n([C@H]2C[C@H](O)[C@@H](CO)O2)cc1I
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: O=C1c2ccccc2C(=O)N1CCC#Cc1cn([C@H]2C[C@H](O)[C@@H](CO)O2)c(=O)[nH]c1=O
Reaction time: 3 h
Yield: 78.8 %

Procedure:
5-Iodo-2′-deoxyuridine (354 mg, 1 mmol) was dissolved in 10 mL of dimethylformamide. Cuprous iodide (76 mg, 0.4 mmol), tetrakis(triphenylphosphine)palladium(0) (230 mg, 0.2 mmol), and triethylamine (200 mg, 2.0 mmol) were added. 4-Phthalimidobut-1-yne (300 mg, 1.5 mmol) was added all at once and the reaction kept at 60° C. for three hours. The clear yellow reaction was then evaporated and methylene chloride was added. Scratching of the flask induced crystallization of nearly all of the product which was filtered and recrystallized from 95% ethanol to give 335 mg (78%) of title compound as fine, feathery needles.
Reaction SMILES: [CH:1]1([C:4]([OH:6])=O)[CH2:3][CH2:2]1.[CH2:7]([Li])[CH2:8][CH2:9][CH3:10].Cl>CCOCC>[CH:1]1([C:4]([CH2:7][CH2:8][CH2:9][CH3:10])=[O:6])[CH2:3][CH2:2]1
Reactant: [Li]CCCC
Reactant: O=C(O)C1CC1
Agent: Cl
Solvent: CCOCC
Product: CCCCC(=O)C1CC1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To a vigorously-stirred solution of 31.0 g of cyclopropanecarboxylic acid in 330 ml of ether is added a solution of n-butyllithium (748 mmoles) in about 750 ml of 2:1 ether-hexane during one hour at 5°-10° C. The resulting suspension is diluted with 300 ml of ether and stirred at room temperature for 2 hours and at reflux for 2 hours. The mixture is cooled and poured into several portions of 1:1 ice:4N hydrochloric acid. The ethereal phases are combined and washed with brine, sodium carbonate solution, and brine. The extract is dried over magnesium sulfate and concentrated. The residue is distilled to provide a liquid, bp-102°-104° C. (80 mm), pmr spectrum (CDCl3): δ 2.55 (triplet, -CH2CO-).