Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [OH-].[Na+].NC1[S:5][C:6]2[C:12]3[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=3[CH:10]=[CH:9][C:7]=2[N:8]=1>O.C(O)CO>[NH2:8][C:7]1[CH:9]=[CH:10][C:11]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[C:6]=1[SH:5]
Reactant: Nc1nc2ccc3ccccc3c2s1
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: OCCO
Product: Nc1ccc2ccccc2c1S

Procedure:
To a solution of 30.0 g sodium hydroxide in 30 mL of water and 140 mL of ethylene glycol was added 18.0 g of 2-aminobenzo[g]benzothiazole. The mixture was heated at reflux under nitrogen for 20 hours and diluted with 80 mL of water. After cooling, the mixture was filtered, then the filtrate was chilled in an ice-bath and neutralized with acetic acid. The aqueous suspension was extracted with ether (3×200 mL) and the combined extracts were dried (magnesium sulfate). Removal of the solvent gave the product to which heptane (3×150 mL) was added and the solvent was removed under reduced pressure. (This step removed traces of acetic acid). The yield of the 2-aminonaphthalene-1-thiol was 15.4 g (97%), mp 108°-110°. A sample of this compound was recrystallized from ethanol, mp 109°-110°. This compound is sensitive to air and therefore was used immediately in the next step of the synthetic scheme.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:22])[C@@H:4]([NH:14]C(OC(C)(C)C)=O)[CH2:5][CH2:6][O:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.FC(F)(F)C(O)=O>ClCCl>[CH3:1][O:2][C:3](=[O:22])[C@@H:4]([NH2:14])[CH2:5][CH2:6][O:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1
Reactant: COC(=O)[C@H](CCOc1ccccc1)NC(=O)OC(C)(C)C
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: COC(=O)[C@@H](N)CCOc1ccccc1
Reaction time: 16 h

Procedure:
To a solution of (S)-2-tert-butoxycarbonylamino-4-phenoxy-butyric acid methyl ester (1.15 g) in dichloromethane (3 ml) was added under an argon atmosphere trifluoroacetic acid (4.2 ml). The mixture was stirred for 16 h. The mixture was concentrated. The residue was treated with sodium bicarbonate solution until the pH was basic and extracted with dichloromethane twice. The combined organic layers were dried (MgSO4) and evaporated. The product was used without purification for the next step, yellow oil. MS (ISP): 210.3 ([M+H]+)).
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:25]=[CH:24][CH:23]=[CH:22][C:10]=1[CH2:11][C:12]1[CH:21]=[CH:20][C:15]([C:16]([O:18]C)=[O:17])=[CH:14][CH:13]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH-].[Na+]>CO>[CH2:1]([O:8][C:9]1[CH:25]=[CH:24][CH:23]=[CH:22][C:10]=1[CH2:11][C:12]1[CH:13]=[CH:14][C:15]([C:16]([OH:18])=[O:17])=[CH:20][CH:21]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: COC(=O)c1ccc(Cc2ccccc2OCc2ccccc2)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: O=C(O)c1ccc(Cc2ccccc2OCc2ccccc2)cc1
Temperature: 60 °C
Reaction time: 5 h
Yield: 75.2 %

Procedure:
To a solution of methyl 4-(2-benzyloxybenzyl)benzoate (1.0 g) in methanol (20 mL) was added 2 mol/L aqueous sodium hydroxide solution (7.5 mL), and the mixture was stirred at 60° C. for-5 hours. The reaction mixture was concentrated under reduced pressure. After the residue was acidified by adding dilute hydrochloric acid, the resulting mixture was extracted with ethyl acetate. The organic layer was washed with brine, and dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure to give 4-(2-benzyloxybenzyl)benzoic acid (0.72 g).
Reaction SMILES: C(N(C(C)C)CC)(C)C.[Br:10][C:11]1[CH:12]=[C:13]([CH:16]([NH2:24])[CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[S:14][CH:15]=1.[CH3:25][C:26]([O:29][C:30]([NH:32][CH2:33][CH:34]1[CH2:39][CH2:38][CH:37]([C:40](O)=[O:41])[CH2:36][CH2:35]1)=[O:31])([CH3:28])[CH3:27].C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C>CN(C=O)C.C(OCC)(=O)C>[C:26]([O:29][C:30](=[O:31])[NH:32][CH2:33][C@H:34]1[CH2:35][CH2:36][C@H:37]([C:40](=[O:41])[NH:24][CH:16]([C:13]2[S:14][CH:15]=[C:11]([Br:10])[CH:12]=2)[CH2:17][C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=2)[CH2:38][CH2:39]1)([CH3:25])([CH3:28])[CH3:27]
Reactant: CC(C)(C)OC(=O)NCC1CCC(C(=O)O)CC1
Reactant: NC(Cc1ccccc1)c1cc(Br)cs1
Agent: CCN=C=NCCCN(C)C
Agent: On1nnc2ccccc21
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Solvent: CCOC(C)=O
Product: CC(C)(C)OC(=O)NC[C@H]1CC[C@H](C(=O)NC(Cc2ccccc2)c2cc(Br)cs2)CC1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
At 0° C. under N2, diisopropylethylamine (1.1 mL, 6.6 mmol) was added dropwise to a mixture of 1A (564 mg, 2.0 mmol), Boc-tranexamic acid (565 mg, 2.2 mmol), HOBt (297 mg, 2.2 mmol), and EDCI (422 mg, 2.2 mmol) in anhydrous DMF (15 mL). After addition, the mixture was slowly warmed to rt and stirred for 2 h. The reaction mixture was diluted with ethyl acetate, washed with water, 1.0 N HCl, sat. NaHCO3, and brine, dried over MgSO4, filtered, and concentrated. Chromatography on silica gel provided 1B as a light yellow solid. LC/MS m/z 521.1 (M+H)+. 1H NMR (400 MHz, CDCl3) δ: 0.8-0-1.0 (m, 2H), 1.45 (s, 9H), 1.25-1.45 (m, 2H), 1.70-1.85 (m, 2H), 1.90-2.05 (2H), 2.95 (2H), 3.05-3.25 (2H), 4.60 (s, broad, 1H), 5.55 (m, 1H), 5.75 (m, 1H), 6.8 (s, 1H), 7.1 (s, 1H), 7.15 (d, J=7.8 Hz, 2H), 7.2-7.35, (m, 3H).
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:20])[C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([O:11][C:12]2[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=2)[C:6]=1[CH3:19])[CH3:2].[Br:21]N1C(=O)CCC1=O>C(Cl)(Cl)(Cl)Cl.C(OOC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1>[CH2:1]([O:3][C:4](=[O:20])[C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([O:11][C:12]2[CH:13]=[CH:14][C:15]([F:18])=[CH:16][CH:17]=2)[C:6]=1[CH2:19][Br:21])[CH3:2]
Reactant: CCOC(=O)c1cccc(Oc2ccc(F)cc2)c1C
Reactant: O=C1CCC(=O)N1Br
Agent: O=C(OOC(=O)c1ccccc1)c1ccccc1
Solvent: ClC(Cl)(Cl)Cl
Product: CCOC(=O)c1cccc(Oc2ccc(F)cc2)c1CBr
Temperature: 25 °C
Yield: 101.5 %

Procedure:
A mixture of 3-(4-fluoro-phenoxy)-2-methyl-benzoic acid ethyl ester (2.63 g, 9.60 mmol), N-bromosuccinimide (1.79 g, 10.08 mmol) and benzoyl peroxide (116 mg, 0.48 mmol) in carbon tetrachloride (35 mL) was refluxed for 4 h before it was cooled to room temperature and partitioned between dichloromethane and water. The organic layer was washed with saturated aqueous sodium bicarbonate solution, brine, dried over anhydrous sodium sulfate and concentrated in vacuo to give the title compound as a yellow oil (3.44 g): 1H NMR (CDCl3, 200 MHz): δ=7.67 (m, 1H), 7.27 (m, 2H), 7.01 (m, 4H), 5.09 (s, 3H), 4.42 (q, J=7.2 Hz, 2H), 1.44 (t, J=7.2 Hz, 3H).
Reaction SMILES: [F:1][C:2]1[CH:21]=[CH:20][C:5]([NH:6][CH:7]([C:10]2[CH:15]=[CH:14][C:13]([S:16](=[O:19])(=[O:18])[NH2:17])=[CH:12][CH:11]=2)[C:8]#N)=[CH:4][CH:3]=1.[CH:22]([CH:24]=C)=O>>[F:1][C:2]1[CH:21]=[CH:20][C:5]([N:6]2[CH:24]=[CH:22][CH:8]=[C:7]2[C:10]2[CH:15]=[CH:14][C:13]([S:16](=[O:19])(=[O:18])[NH2:17])=[CH:12][CH:11]=2)=[CH:4][CH:3]=1
Reactant: C=CC=O
Reactant: N#CC(Nc1ccc(F)cc1)c1ccc(S(N)(=O)=O)cc1
Product: NS(=O)(=O)c1ccc(-c2cccn2-c2ccc(F)cc2)cc1

Procedure:
Following a procedure similar to that described in Example 1(iii), but using α-(4-fluoroanilino)-α-(4-sulfamoylphenyl)acetonitrile [prepared as described in step (ii) above] and acrolein as starting materials, the title compound was obtained as a white powder (yield 48%), melting at 160-161° C.
Reaction SMILES: Br[C:2]1[CH:3]=[CH:4][C:5]2[NH:11][CH2:10][CH2:9][N:8]=[C:7]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)[C:6]=2[CH:18]=1.CN(C)C=O.[F:24][C:25]1[CH:26]=[N:27][CH:28]=[CH:29][C:30]=1B(O)O.C(=O)([O-])[O-].[K+].[K+]>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O>[F:24][C:25]1[CH:26]=[N:27][CH:28]=[CH:29][C:30]=1[C:2]1[CH:3]=[CH:4][C:5]2[NH:11][CH2:10][CH2:9][N:8]=[C:7]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)[C:6]=2[CH:18]=1
Reactant: Brc1ccc2c(c1)C(c1ccccc1)=NCCN2
Reactant: OB(O)c1ccncc1F
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: Fc1cnccc1-c1ccc2c(c1)C(c1ccccc1)=NCCN2
Temperature: 150 °C

Procedure:
A 5 mL microwave tube was charged with 7-bromo-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepine (50 mg), dimethylformamide (3.5 mL), 3-fluoro-4-pyridylboronic acid (2 equiv), potassium carbonate (2 equiv), bis(triphenylphosphine)-palladiumdichloride (10 mol %), and water (0.7 mL). The mixture was heated in a microwave at 150° C. for 5 min, then cooled and concentrated to dryness. The residue was taken up in ethyl acetate and filtered through a Celite pad. The filtrate was concentrated to dryness and the residue was triturated in diethyl ether. The resulting solids were collected on filter then purified using preparative thin-layer chromatography. The plates were eluted with 12.5% methanol in chloroform, and the desired band was collected to provide 7-(3-fluoropyridin-4-yl)-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepine as a yellow powder. H1 NMR (d6-dmso): 8.45 (d, 1H), 8.32 (d, 1H), 7.52 (d, 1H), 7.46 (m, 2H), 7.36-7.42 (m, 4H), 7.21 (s, 1H), 6.91 (d, 1H), 6.78 (brt, 1H), 3.96 (m, 2H), 3.60 (m, 2H).
Reaction SMILES: [CH3:1][O:2][C:3]1[C:8]([O:9][CH3:10])=[C:7]([O:11][CH2:12][O:13][CH3:14])[C:6]([CH3:15])=[C:5]([CH:16]=[CH:17][CH:18]=[CH:19][CH2:20][OH:21])[C:4]=1[O:22][CH2:23][O:24][CH3:25]>C(Cl)Cl.[O-2].[O-2].[Mn+4]>[CH3:1][O:2][C:3]1[C:8]([O:9][CH3:10])=[C:7]([O:11][CH2:12][O:13][CH3:14])[C:6]([CH3:15])=[C:5]([CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=[O:21])[C:4]=1[O:22][CH2:23][O:24][CH3:25]
Reactant: COCOc1c(C)c(C=CC=CCO)c(OCOC)c(OC)c1OC
Agent: [Mn+4]
Agent: [O-2]
Solvent: ClCCl
Product: COCOc1c(C)c(C=CC=CC=O)c(OCOC)c(OC)c1OC
Yield: 93 %

Procedure:
The alcohol compound (4.85 g, 13.7 mmol) prepared as above was dissolved in methylene chloride and the mixture was oxidized with active manganese dioxide (14.6 g) at room temperature for 2 hours. Working up in usual way gave 2,3-dimethoxy-5-methyl-1,4-bismethoxymethyloxy-6-(4-formyl-1,3-butadienyl)benzene [oily substance, δ 2.30 (3H), 3.49 (3H), 3.58 (3H), 3.86 (3H), 3.89 (3H), 5.06 (4H), 6.23 (1H), 7.0-7.4 (3H), 9.65 (1H)]. Yield 93%.
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[C:7]([CH3:22])=[C:8](C(OC(C)(C)C)=O)[NH:9][C:10]=1[CH2:11][C:12]([OH:14])=[O:13])=[O:5])[CH3:2].FC(F)(F)C(O)=O.C(=O)=O.C(O)C.[OH-].[Na+]>ClCCl>[CH2:1]([O:3][C:4]([C:6]1[C:7]([CH3:22])=[CH:8][NH:9][C:10]=1[CH2:11][C:12]([OH:14])=[O:13])=[O:5])[CH3:2]
Reactant: CCOC(=O)c1c(CC(=O)O)[nH]c(C(=O)OC(C)(C)C)c1C
Agent: O=C=O
Agent: [Na+]
Agent: [OH-]
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Solvent: CCO
Product: CCOC(=O)c1c(C)c[nH]c1CC(=O)O
Temperature: -30 °C
Yield: 85.2 %

Procedure:
A solution of 5-carboxymethyl-3-methyl-1H-pyrrole-2,4-dicarboxylic acid 2-tert-butyl ester 4-ethyl ester (6.3 g, 20 mmol) in 600 ml of dichloromethane and trifluoroacetic acid (120 ml, 1.55 mol) was heated to reflux under a nitrogen atmosphere for 2.5 hours. The reaction mixture was stirred in the dry ice-ethanol bath and added with aqueous sodium hydroxide solution (1.55 mol sodium hydroxide in 100 ml of water) while maintaining the temperature at −30° C. Upon completion of the addition, the mixture was extracted with dichloromethane (100 ml×7). The combined organic extracts were washed with brine (100 ml), dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to give 2-carboxymethyl-4-methyl-1H-pyrrole-3-carboxylic acid ethyl ester (3.6 g, 85.7%) as a white solid.
Reaction SMILES: O1[CH2:5][CH2:4][CH2:3][CH2:2]1.[C@H]([C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([C@@H:16]([CH2:18][CH3:19])[CH3:17])[C:11]=1[O:20]C(=O)N[C@@H](C1C=CC=CC=1)C)(CC)C.[OH-].[Na+]>C(OC)(C)(C)C>[C@H:3]([C:13]1[C:12]([C@@H:16]([CH2:18][CH3:19])[CH3:17])=[C:11]([OH:20])[CH:10]=[CH:15][CH:14]=1)([CH2:4][CH3:5])[CH3:2]
Reactant: C1CCOC1
Reactant: CC[C@@H](C)c1cccc([C@H](C)CC)c1OC(=O)N[C@H](C)c1ccccc1
Agent: [Na+]
Agent: [OH-]
Solvent: COC(C)(C)C
Product: CC[C@@H](C)c1cccc(O)c1[C@H](C)CC
Temperature: 57.5 °C

Procedure:
To a 100-ml three-necked flask equipped with a magnetic stirrer, a reflux condenser, a thermocouple and an N2 inlet, was added tetrahydrofuran (THF) (9 ml), (R,R,R)-1-phenylethylcarbamic acid-2,6-di-sec-butylphenyl ester (1 g, 2.8 mmol), and 1.0 M sodium hydroxide (11.4 ml, 11.4 mmol). The resulting clear mixture was heated under N2 at 55-60° C. using a heating mantle and continued to stir at this temperature while monitoring the progress of the reaction by HPLC. After the reaction was finished (6-8 h) as judged by HPLC, the reaction mixture was cooled to 15° C. and filtered to remove precipitated urea. The filtered cake was washed with cold THF (5 ml). The filtrate and the wash were combined, acidified to pH 2-3 with 3.0 M hydrochloric acid (HCl) (3.5 ml). After stirring for 10 minutes (min), ether (10 ml) was added and then resulting mixture was vigorously stirred for 15 min after which layers were separated. The organic layer was washed with 3.0 M HCl (3 ml), brine (5 ml), dried magnesium sulfate (MgSO4), filtered to remove the drying agent, and then concentrated on a rotavap to give a semi solid yellow residue which was stirred with methyl tertiary butyl ether (MTBE) (3 ml) for 15 min and then filtered. The filtered cake was washed with MTBE (2 ml). The filtrate and the wash were combined, and then concentrated on a rotavap to give the title compound as a yellow oil (0.6 g, 100% crude yield) that was found to be greater than 93 A % pure by HPLC. The NMR (DMSO-d6) was found to be consistent with the structure.
Reaction SMILES: ClC1C=CC=C(Cl)C=1N.C(C(=COCC)C(NC(OCC)=O)=O)#N.CCCCCC.[C:31]([C:33](=[CH:42][NH:43][C:44]1[C:49]([Cl:50])=[CH:48][CH:47]=[CH:46][C:45]=1[Cl:51])[C:34]([NH:36][C:37](OCC)=[O:38])=[O:35])#[N:32]>C(O)C.C1C2C(=CC=CC=2)CCC1>[C:31]([C:33]1[C:34](=[O:35])[NH:36][C:37](=[O:38])[N:43]([C:44]2[C:49]([Cl:50])=[CH:48][CH:47]=[CH:46][C:45]=2[Cl:51])[CH:42]=1)#[N:32]
Reactant: CCOC(=O)NC(=O)C(C#N)=CNc1c(Cl)cccc1Cl
Agent: CCOC=C(C#N)C(=O)NC(=O)OCC
Agent: Nc1c(Cl)cccc1Cl
Solvent: CCCCCC
Solvent: c1ccc2c(c1)CCCC2
Solvent: CCO
Product: N#Cc1cn(-c2c(Cl)cccc2Cl)c(=O)[nH]c1=O

Procedure:
2,6-Dichloroaniline and α-cyano-β-ethoxy-N-ethoxycarbonylacrylamide in ethanol is refluxed 3 days and hexane added to prepare α-cyano-β-(2,6-dichloroanilino)-N-ethoxycarbonylacrylamide, which is cyclized by heating in tetralin to yield 5-cyano-1-(2,6-dichlorophenyl)uracil, m.p. 273°-274.5°.
Reaction SMILES: [OH-:1].[K+].[C:3]([C:5]1[CH:6]=[C:7]([C:11]2[CH:16]=[CH:15][C:14]([I:17])=[CH:13][C:12]=2[CH3:18])[CH:8]=[CH:9][CH:10]=1)#[N:4]>C(O)C.O>[C:3]([C:5]1[CH:6]=[C:7]([C:11]2[CH:16]=[CH:15][C:14]([I:17])=[CH:13][C:12]=2[CH3:18])[CH:8]=[CH:9][CH:10]=1)(=[O:1])[NH2:4]
Reactant: [OH-]
Reactant: Cc1cc(I)ccc1-c1cccc(C#N)c1
Agent: [K+]
Solvent: CCO
Solvent: O
Product: Cc1cc(I)ccc1-c1cccc(C(N)=O)c1
Yield: 23 %

Procedure:
Potassium hydroxide (1.21 gm, 21.6 mmol) was added to a solution of 1-(3-cyanophenyl)-4-iodo-2-methylbenzene (1.27 gm, 4.0 mmol) in ethanol (50 mL) and heated under reflux for 16 h. After being cooled, the mixture was diluted with water (100 mL) and extracted with ethyl acetate (3×50 mL). The combined organic extracts were dried (Na2SO4) and concentrated under reduced pressure to give crude product (1.08 gm). The crude product (540 mg) was purified by flash chromatography (gradient elution with dichloromethane:sat. methanolic ammonia 100:2.5 to dichloromethane:ethyl acetate 1:1 to dichloromethane:ethyl acetate:acetic acid 100:100:4), then azeotroped with ethanol, ethyl acetate and diethyl ether to give 1-(3-carbamoylphenyl)-4-iodo-2-methylbenzene (310 mg, 46%) as a buff solid.
Reaction SMILES: [C:1]([CH:6]1[CH2:11][CH2:10][CH2:9][CH2:8][C:7]1=[O:12])([O:3][CH2:4][CH3:5])=[O:2].C(=O)([O-])[O-].[K+].[K+].Br[CH2:20][CH:21]1[CH2:25][CH2:24][CH2:23][O:22]1.O>[I-].C([N+](CCCC)(CCCC)CCCC)CCC.CN(C=O)C>[O:22]1[CH2:23][CH2:24][CH2:25][CH:21]1[CH2:20][C:6]1([C:1]([O:3][CH2:4][CH3:5])=[O:2])[CH2:11][CH2:10][CH2:9][CH2:8][C:7]1=[O:12]
Reactant: BrCC1CCCO1
Reactant: CCOC(=O)C1CCCCC1=O
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: O=C([O-])[O-]
Agent: [I-]
Solvent: O
Solvent: CN(C)C=O
Product: CCOC(=O)C1(CC2CCCO2)CCCCC1=O
Temperature: 57.5 °C
Reaction time: 17 h

Procedure:
2-carboethoxycyclohexanone (1 mmol), finely powdered potassium carbonate (2 mmol), 2-bromomethyltetrahydrofuran (1.5 mmol), and tetrabutylammonium iodide (10 mg/mmol) are combined in dry DMF (1.25 mL/mmol) and stirred under N2 at 55 to 60° C. for 16 to 18 hours. The room temperature reaction mixture is poured into water and extracted with Et2O and EtOAc. The combined organics are washed with brine, dried, and stripped of all solvent under reduced pressure to provide 2-tetrahydrofuranylmethyl-2-carboethoxycyclohexanone. This material is combined with lithium chloride (5 mmol), water (1.05 mmol) and dimethyl sulfoxide (5 mL/mmol) and the mixture refluxed for approximately 4 hrs. The mixture is poured into water and extracted with Et2O and EtOAc. The combined organics are washed with brine, dried, and stripped of all solvent under reduced pressure to generate the title material.
Reaction SMILES: O[CH2:2][CH2:3][NH:4][CH2:5][C:6]([NH:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][N:10]=1)=[O:7].C(P(CCCC)CCCC)CCC.CC(OC(/N=N/C(OC(C)(C)C)=O)=O)(C)C.Cl>C1COCC1.C(OCC)C.CO.N>[N:10]1[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=1[N:8]1[CH2:2][CH2:3][NH:4][CH2:5][C:6]1=[O:7]
Reactant: O=C(CNCCO)Nc1ccccn1
Agent: CC(C)(C)OC(=O)/N=N/C(=O)OC(C)(C)C
Agent: CCCCP(CCCC)CCCC
Agent: Cl
Solvent: CCOCC
Solvent: C1CCOC1
Solvent: CO
Product: O=C1CNCCN1c1ccccn1
Temperature: 40 °C
Yield: 64.9 %

Procedure:
A stirred suspension of 2-(2-hydroxyethylamino)-N-pyridin-2-yl-acetamide (0.17 g, 0.87 mmol) under an inert atmosphere in THF (3 mL) was cooled to 0–5° C. Tributyl phosphine (0.32 mL, 1.15 mmol) was added followed by a solution of di-tert-butylazodicarboxylate (0.29 g, 1.23 mmol) in THF (3 mL) dropwise over 15 min. After a further 15 min. the mixture was warmed to 40° C. and a hydrogen chloride solution in diethylether (1M, 1.8 mL) added to produce a precipitate. The mixture was cooled to 0–5° C. and the solids filtered off to give a hydroscopic product. This was dissolved in MeOH—NH3 and chromatographed on silica gel, eluting with DCM:MeOH (100:0 to 90:10), to afford the title compound (100 mg, 65%) as a colourless solid. 1H NMR (360 MHz, d6-DMSO) δ 2.85 (1H, br s), 3.01 (2H, t, J=5.5 Hz), 3.44 (2H, s), 3.82 (2H, t, J=5.5 Hz), 7.17–7.22 (1H, m), 7.75–7.86 (2H, m), 8.41–8.45 (1H, m). MS (ES+) 178 (M+1).
Reaction SMILES: [S].[C:2]([OH:21])(=[O:20])[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9]/[CH:10]=[CH:11]\[CH2:12][CH2:13][CH2:14][CH2:15]CCCC.C=CCCCCCCCCCCCCCCCC.CCCCCCCCCCCCCCCCCC.O.O.O.O.[N+]([O-])([O-])=O.[Cd+2:66].[N+]([O-])([O-])=O.C(O)(=O)CCCCCCCCCCCCC.[N+]([O-])(O)=O.[OH-].[Na+]>C([O-])(=O)CCCCCCCCCCCCCCCCC.[Zn+2].C([O-])(=O)CCCCCCCCCCCCCCCCC.O.O.O.O.C([O-])(=O)C.[Mn+2].C([O-])(=O)C>[C:2]([O-:21])(=[O:20])[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH3:15].[Cd+2:66].[C:2]([O-:21])(=[O:20])[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH3:15]
Reactant: CCCCCCCC/C=C\CCCCCCCC(=O)O
Agent: [Mn+2]
Agent: C=CCCCCCCCCCCCCCCCC
Agent: CC(=O)[O-]
Solvent: O=[N+]([O-])O
Solvent: O
Product: CCCCCCCCCCCCCC(=O)[O-]

Procedure:
Sulfur powder (99.999%), oleic acid (OLA, 90%), 1-octadecene (ODE, 90%), octadecane (ODA, 99%), oleyamine (OAm, 70%), polystyrene-block-polybutadiene (C12H14, 30 wt % styrene, 80% diblock), cadmium nitrate tetrahydrate (Cd(NO3)2.4H2O, 99.99%), zinc stearate (count as ZnO %≈14%), myristic acid (MA, 99%), nitric acid (69.5%), manganese acetate tetrahydrate (99%), and sodium hydroxide (NaOH) were purchased from commercial sources and used as received without further purification. Cadmium myristate was synthesized according to a literature method.
Reaction SMILES: [NH2:1][C:2]1[N:7]=[C:6]([CH2:8]O)[CH:5]=[C:4]([S:10][CH3:11])[CH:3]=1.[Br:12]C(Br)(Br)Br.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>ClCCl>[Br:12][CH2:8][C:6]1[N:7]=[C:2]([NH2:1])[CH:3]=[C:4]([S:10][CH3:11])[CH:5]=1
Reactant: CSc1cc(N)nc(CO)c1
Reactant: BrC(Br)(Br)Br
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Product: CSc1cc(N)nc(CBr)c1
Temperature: 25 °C
Reaction time: 1 h
Yield: 54.8 %

Procedure:
To a solution of 0.10 g (6-amino-4-methylsulfanyl-pyridin-2-yl)-methanol in 6 ml dichloromethane was added 0.292 g tetrabromomethane and 0.231 g triphenylphosphin and the mixture was stirred at room temperature for 1 h. The reaction mixture was purified by chromatography on silica gel with heptan:ethyl acetate=1:1 to yield 0.075 g of the title compound as white crystals MS (ISP): 232.9; 234.9 [M+H]+.
Reaction SMILES: [C:1]([O:5][C:6](=[O:18])[NH:7][CH2:8][C:9]1[CH:14]=[C:13]([Br:15])[C:12]([OH:16])=[C:11]([NH2:17])[CH:10]=1)([CH3:4])([CH3:3])[CH3:2].[Cl-].Cl[C:21](=[N+:23]([CH3:25])[CH3:24])Cl>C(Cl)Cl>[C:1]([O:5][C:6](=[O:18])[NH:7][CH2:8][C:9]1[CH:14]=[C:13]([Br:15])[C:12]2[O:16][C:21]([N:23]([CH3:25])[CH3:24])=[N:17][C:11]=2[CH:10]=1)([CH3:4])([CH3:2])[CH3:3]
Reactant: C[N+](C)=C(Cl)Cl
Reactant: CC(C)(C)OC(=O)NCc1cc(N)c(O)c(Br)c1
Agent: [Cl-]
Solvent: ClCCl
Product: CN(C)c1nc2cc(CNC(=O)OC(C)(C)C)cc(Br)c2o1

Procedure:
A mixture of Tert-butylN—(3-amino-5-bromo-4-hydroxybenzyl)carbamate (300 mg, 0.95 mmol) and dichloromethylenedimethylammonium chloride (phosgene iminium chloride, 240 mg, 1.48 mmol) in 10 mL of dry CH2Cl2 was refluxed for 6 h. After cooling the solution was extracted with EtOAc, washed with NaHCO3, brine and dried (MgSO4). After purification by column chromatography (1% MeOH in CH2Cl2) 192 mg (55%) of the title compound were obtained. 1H NMR (CDCl3) δ 7.14 (s, 1H, H-6); 7.04 (s, 1H, H-4); 5.11 (bs, 1H, NH); 4.31 (d, 2H, J=5.6 Hz, CH2); 3.23, 3.22 (s, 6H, NCH3 2×); 1.48 (s, 9H, (CH3)3C); 13C NMR (CDCl3) δ 163.3 (C-2), 156.2 (CO), 146.6 (C-7a), 145.1 (C-3a), 137.0 (C-5), 122.8 (C-6), 114.3 (C-4), 100.6 (C-7), 79.9 ((CH3)3C), 44.7 (CH2), 38.1 (NCH3×2), 28.8 ((CH3) 3C).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:16]=[CH:15][C:6]([CH2:7][N:8]2[C:12]([CH2:13]O)=[N:11][CH:10]=[N:9]2)=[CH:5][CH:4]=1.[CH2:17]([N:19](CC)CC)C.CS(Cl)(=O)=O>ClCCl>[CH3:1][O:2][C:3]1[CH:16]=[CH:15][C:6]([CH2:7][N:8]2[C:12]([CH2:13][NH:19][CH3:17])=[N:11][CH:10]=[N:9]2)=[CH:5][CH:4]=1
Reactant: CCN(CC)CC
Reactant: COc1ccc(Cn2ncnc2CO)cc1
Agent: CS(=O)(=O)Cl
Solvent: ClCCl
Product: CNCc1ncnn1Cc1ccc(OC)cc1
Temperature: 25 °C
Reaction time: 2 h
Yield: 83.1 %

Procedure:
[2-(4-Methoxybenzyl)-2H-[1,2,4]triazol-3-yl]methanol (0.50 g, 2.28 mmol) was dissolved in dichloromethane (10 ml), then triethylamine (0.36 ml, 2.60 mmol) was added. With cooling with ice, methanesulfonyl chloride (0.20 ml, 2.58 mmol) was added, followed by stirring at room temperature for 2 hours. The reaction liquid was concentrated, ethyl acetate was added, followed by washing. After drying over anhydrous sodium sulfate, the solvent was evaporated away under reduced pressure, and the resulting residue was dissolved in tetrahydrofuran (25 ml), then aqueous methylamine solution (40%, 5 ml) was added. After stirring at room temperature for 3 days, the reaction liquid was concentrated. This was diluted with ethyl acetate, washed with water, and dried over anhydrous sodium sulfate. The solvent was evaporated away under reduced pressure to obtain a pale yellow oil (0.44 g, 83%).