Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]1([CH2:7][C:8](Cl)=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[OH-:11].[Ca+2].[OH-].[O:14]1[CH2:18]CCC1>O>[C:1]1([CH2:7][C:8](=[O:9])[C:18]([OH:14])=[O:11])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:1]1([CH2:7][C:8]([OH:9])=[O:14])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: [OH-]
Reactant: C1CCOC1
Reactant: O=C(Cl)Cc1ccccc1
Agent: [Ca+2]
Solvent: O
Product: O=C(O)C(=O)Cc1ccccc1
Product: O=C(O)Cc1ccccc1
Temperature: 5 °C
Yield: 71.1 %
Yield: 20.3 %

Procedure:
A 20 mL aliquot of 4.0 mmoles of potassium tricarbonyl [triphenylphosphine] cobaltate was charged to a 100 mL three-neck round bottom flask under nitrogen and cooled to 5° C. Phenylacetyl chloride (0.53 mL; 4 mmoles) was added to the flask, and the resultant solution containing the preformed cobaltate complex was charged into a 300 mL autoclave by means of a transfer needle under nitrogen. The autoclave had previously been charged with 16 mmoles (1.18 g) of calcium hydroxide as a suspension in 25 mLs tetrahydrofuran and 5 mLs water. The vessel was sealed, flushed with carbon monoxide, pressurized to 900 psig and heated to 50° C. for nine hours. The autoclave was vented and the contents were poured into a 250 mL separatory funnel. The reaction mixture was acidified with 10% hydrochloric acid and then treated with an excess of iodine. The organic phase was diluted with 100 mLs of diethyl ether and the lower aqueous phase was discarded. The organic phase was washed with saturated sodium thiosulfate until the color of iodine was dispelled. The resultant light yellow diethyl ether phase was washed with 10% sodium hydroxide (3×25 mLs) and the organic phase discarded. Acidification of the combined aqueous sodium hydroxide solution followed by re-extraction with diethyl ether (2×75 mLs) gave a clear solution. The solution was dried over MgSO4 and evaporated to give (0.81 mmoles; 20.3% yield) of phenylpyruvic acid and 2.84 mmoles (71.1% yield) of phenylacetic acid as identified by mass spectroscopy and comparison to an authentic sample.
Reaction SMILES: [CH3:1][C@@H:2]([CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:3](OC)=[O:4].C[O-].[Na+].O1CCCC1.[H][H]>C(OCC)C>[CH3:1][C@@H:2]([CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[CH2:3][OH:4]
Reactant: COC(=O)[C@@H](C)Cc1ccccc1
Reactant: [H][H]
Agent: C[O-]
Agent: [Na+]
Solvent: CCOCC
Solvent: C1CCOC1
Product: C[C@H](CO)Cc1ccccc1
Yield: 85.9 %

Procedure:
Methyl (S)-2-methyl-3-phenylpropionate (5 mmol, 78.4% ee), a dichlororuthenium complex 8 (0.05 mmol), sodium methoxide (5 mmol), and tetrahydrofuran (2 mL) were charged into a 100-mL autoclave equipped with a stirrer. Then, the mixture was subjected to hydrogenation at a hydrogen pressure of 5 MPa at 80° C. for 16 hours. The reaction solution was diluted with 20 mL of diethyl ether, and was passed through 8.9 g of silica gel. The silica gel was washed with diethyl ether. The solution thus obtained was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (silica gel 13.4 g, hexane/ethyl acetate=8/1). Thus, (S)-2-methyl-3-phenylpropanol (645 mg, 18.4% ee) was obtained.
Reaction SMILES: [OH:1][CH2:2][CH2:3][CH:4]1[CH2:9][CH2:8][N:7]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:6][CH2:5]1.CC1(C)N([O])C(C)(C)CCC1.C(O)(=O)C.C(O)(=O)C.IC1C=CC=CC=1.[O-]S([O-])(=S)=O.[Na+].[Na+]>C(Cl)Cl>[CH:2]([CH2:3][CH:4]1[CH2:5][CH2:6][N:7]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:8][CH2:9]1)=[O:1]
Reactant: CC(C)(C)OC(=O)N1CCC(CCO)CC1
Agent: CC1(C)CCCC(C)(C)N1[O]
Agent: O=S([O-])([O-])=S
Agent: [Na+]
Solvent: CC(=O)O
Solvent: Ic1ccccc1
Solvent: ClCCl
Product: CC(C)(C)OC(=O)N1CCC(CC=O)CC1
Reaction time: 3 h

Procedure:
To a flask containing tert-butyl 4-(2 hydroxyethyl)piperidine-1-carboxylate (4.4 g, 19.2 mmol) in CH2Cl2 (20 mL) was added TEMPO (300 mg, 1.92 mmol) followed by iodobenzene diacetate (6.8 g, 21.1 mmol). The reaction was stirred 3 hours and then diluted with CH2Cl2 (100 mL). Saturated aqueous solution of Na2S2O3 (100 mL) was added and extracted with CH2Cl2 (3×50 mL). The combined organics were washed with saturated aqueous NaHCO3 (150 mL) and brine (150 mL), dried over Na2SO4, and concentrated in vacuo. The resulting residue was purified by silica gel chromatography (40-70% Et2O/pentanes) to provide the title compound, which was identical to the reported literature compound (see Sato et al. (2001) Heterocycle 54: 747). 13C NMR (75 MHz, CDCl3) δ 201.5, 154.7, 79.4, 50.3, 43.7, 31.9, 30.6, 28.4.
Reaction SMILES: Cl[C:2]1[CH:7]=[CH:6][C:5]([Cl:8])=[CH:4][N:3]=1.[C:9]1(B(O)O)[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1>C1C=CC(P(C2C=CC=CC=2)CCCCP(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl>[Cl:8][C:5]1[CH:6]=[CH:7][C:2]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)=[N:3][CH:4]=1
Reactant: Clc1ccc(Cl)nc1
Reactant: OB(O)c1ccccc1
Agent: Cl[Pd]Cl
Agent: c1ccc(P(CCCCP(c2ccccc2)c2ccccc2)c2ccccc2)cc1
Product: Clc1ccc(-c2ccccc2)nc1
Temperature: 25 °C
Yield: 74.8 %

Procedure:
A 100-mL, round-bottomed flask, fitted with a reflux condenser was charged with 2,5-dichloropyridine (1.00 g, 6.76 mmol), phenylboronic acid (1.07 g, 8.78 mmol), [1,4-bis(diphenylphosphino)butane]palladium(II) dichloride (0.204 g, 0.338 mmol), argon-degassed toluene/ethanol (4:1, 17 mL) and argon-degassed aqueous 1 N sodium carbonate (6.6 mL). The mixture was heated to reflux for 3 h, cooled to room temperature and diluted with water (15 mL) and EtOAc (100 mL). The layers separated and the aqueous phase was extracted with EtOAc (100 mL). The combine organic extracts were dried over Na2SO4, filtered and concentrated. Purification by flash column chromatography (silica gel, 50:50 hexanes/CH2Cl2) provided 5-chloro-2-phenylpyridine (0.959 g, 75%) as a white solid.
Reaction SMILES: [O:1]=[C:2]=[N:3]C1CC(C)(C)CC(C)(CN=C=O)C1.C([C:21]1C=C(C)C=C(C(C)(C)C)[C:22]=1[OH:32])(C)(C)C.C1OC1C.C1OC1CC.OCC[O:45][C:46](=[O:49])[CH:47]=[CH2:48]>>[C:46]([OH:49])(=[O:45])[CH:47]=[CH2:48].[NH2:3][C:2]([O:32][CH2:22][CH3:21])=[O:1]
Reactant: C=CC(=O)OCCO
Reactant: CC1(C)CC(N=C=O)CC(C)(CN=C=O)C1
Reactant: Cc1cc(C(C)(C)C)c(O)c(C(C)(C)C)c1
Agent: CC1CO1
Agent: CCC1CO1
Product: C=CC(=O)O
Product: CCOC(N)=O
Reaction time: 5 h

Procedure:
To a reaction vessel equipped with a stirrer, 100 gm of ARONIX M113 manufactured by Toagousei Chemicals, 124.7 gm of isophorone diisocyanate, 1 gm of dibutyltindilaurate, and 0.3 gm of 2,6-di-t-butyl-4-methylphenol were added. To this, 842.7 gm of a copolymerization diol of 1,2-propylene oxide and 1,2-butylene oxide [1,2 propylene oxide: 1,2-butylene oxide=2:8 (by weight)] of a number average molecular weight of 2,000 was added while maintaining the temperature in the 40° to 50° C. range, and the mixture was reacted for 2 hours. Then 32.6 gm of hydroxyethylacrylate was added, after which the mixture was continuously stirred for 5 hours at 50° to 60° C. to complete the reaction. A urethane acrylate [C-2] of a number average molecular weight of about 7,120 was obtained.
Reaction SMILES: [CH:1]1[C:11]2[C:10]3=[CH:12][C:13]4[CH:14]=[CH:15][C:16]([C:19]([O:21]C)=[O:20])=[CH:17][C:18]=4[N:9]3[CH2:8][CH:7]=[CH:6][C:5]=2[CH:4]=[CH:3][CH:2]=1.N1(C2N=CC=CN=2)CCNCC1.C(N(CC)CC)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.O>[CH:1]1[C:11]2[C:10]3=[CH:12][C:13]4[CH:14]=[CH:15][C:16]([C:19]([OH:21])=[O:20])=[CH:17][C:18]=4[N:9]3[CH2:8][CH:7]=[CH:6][C:5]=2[CH:4]=[CH:3][CH:2]=1
Reactant: COC(=O)c1ccc2cc3n(c2c1)CC=Cc1ccccc1-3
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Agent: c1cnc(N2CCNCC2)nc1
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Solvent: O
Product: O=C(O)c1ccc2cc3n(c2c1)CC=Cc1ccccc1-3
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
To a stirred solution of methyl 7H-indolo[2,1-a][2]benzazepine-10-carboxylate, 13-cyclohexyl, 6-carboxylic acid (150 mg, 0.36 mmol), 2-(piperazin-1-yl)pyrimidine (76 mg, 0.38 mmol) and triethylamine (0.10 mL) in DMF (2 mL) was added HATU (160 mg, 0.42 mmol). The reaction mixture was stirred at rt for 15 min., diluted with H2O (˜4 mL) and the solids were collected, by filtration washed with H2O and dried under vacuum overnight to yield 7H-indolo[2,1-a][2]benzazepine-10-carboxylic acid, 13-cyclohexyl-6-[[4-(4-morpholinylcarbonyl)-1-piperazinyl]carbonyl]-, methyl ester (170 mg, 0.30 mmol, 83%) as a yellow solid. 1H NMR (500 MHz, CDCl3) δ 8.15 (s, 1H), 7.88 (d, J=8.5 Hz, 1H), 7.74 (br d, J=8.5 Hz, 1H), 7.58 (br d, J=7.6 Hz, 1H), 7.52-7.44 (m, 2H), 7.39 (br d, J=7.3 Hz, 1H), 6.85 (s, 1H), 5.12(br s, 1H), 4.40 (br s, 1H), 3.94 (s, 3H), 3.72-3.01 (m, 8H), 3.63 (dd, J=4.9, 4.3 Hz, 4H), 3.20 (dd, J=4.9, 4.3 Hz, 4H), 2.88-2.81 (m, 1H), 2.16-1.15 (m, 10H). LCMS: m/e 597 (M+H)+, ret time 1.82 min, column A, 2 minute gradient.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[CH:10]=[C:9]([Si](CC)(CC)CC)[NH:8][C:5]2=[N:6][CH:7]=1.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1.C(OCC)(=O)C>[Cl:1][C:2]1[CH:3]=[C:4]2[CH:10]=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1
Reactant: CC[Si](CC)(CC)c1cc2cc(Cl)cnc2[nH]1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: Clc1cnc2[nH]ccc2c1
Temperature: 25 °C
Reaction time: 5 h
Yield: 90 %

Procedure:
Compound 41 (4.37 g, 0.0164 mol) was dissolved in THF. Molecular sieve (10 g of 3A) was added followed by TBAF (32.75 mL, 0.0328). The reaction mixture was stirred for 5 h at rt. Diluted with ethyl acetate and washed several times with water, brine and the organic layer was dried and concentrated in vacuo to an oil that was subjected to flash chromatography (30% EtOAc-70% hexanes) to give 02.3 g (90%) of the desired material 42. 1H NMR DMSO d6 11.8 (bs, 1H), 8.2 (s, 1H), 8.1 (s, 1H), 7.5 (s, 1H), 6.5 (s, 1H).
Reaction SMILES: [N:1]([O-:3])=O.[Na+].[C:5]([CH2:7][C:8]([O:10][CH2:11][CH3:12])=[O:9])#[N:6].P(=O)(O)(O)O.Cl>O>[CH2:11]([O:10][C:8](=[O:9])[C:7]([C:5]#[N:6])=[N:1][OH:3])[CH3:12]
Reactant: O=N[O-]
Reactant: CCOC(=O)CC#N
Agent: Cl
Agent: O=P(O)(O)O
Agent: [Na+]
Solvent: O
Product: CCOC(=O)C(C#N)=NO
Temperature: 40 °C
Reaction time: 1 h
Yield: 59.3 %

Procedure:
A solution of sodium nitrite (57.30 g, 830.60 mmol) in water (710.00 ml) was treated with ethyl cyanoacetate (100.00 g, 884.00 mmol). 85% Orthophosphoric acid (36.60 ml, 540.00 mmol) was added dropwise over 45 min, while keeping the temperature of the reaction mixture below 35° C. with the aid of an ice bath. At the end of the addition, the mixture was warmed to 40° C. and stirred for 1 hour. The reaction was quenched at 45° C. with fuming HCl (73.90 ml, 880.00 mmol), and the mixture was then left to cool to room temperature and at 0° C. overnight to complete precipitation. The solid was filtered, the filtrate washed with water and dried under high vacuum overnight to yield 70 g of cyano-hydroxyimino-acetic acid ethyl ester as white crystals. A second batch was obtained by extracting the mother liquor with ether (44.00 g, total yield 91%).
Reaction SMILES: [CH:1]#[C:2][CH2:3][CH2:4][CH2:5][CH3:6].I[C:8]1[CH:14]=[CH:13][CH:12]=[CH:11][C:9]=1[NH2:10]>C(N(CC)CC)C.[Cu](I)I>[C:1]([C:8]1[CH:14]=[CH:13][CH:12]=[CH:11][C:9]=1[NH2:10])#[C:2][CH2:3][CH2:4][CH2:5][CH3:6]
Reactant: Nc1ccccc1I
Reactant: C#CCCCC
Agent: I[Cu]I
Solvent: CCN(CC)CC
Product: CCCCC#Cc1ccccc1N
Temperature: 25 °C
Reaction time: 15 h

Procedure:
32 mg of copper iodide, 140 mg of bistriphenyl phosphine palladium chloride and then 2.3 ml of 1-hexyne were added to a solution of 4.4 g of 2-iodo aniline in 100 ml of triethylamine. The mixture was stirred for 15 hours at ambient temperature, followed by evaporating to dryness and taking up in ether. The insoluble part was filtered off, washed with ether and the ethereal fractions were evaporated to dryness. The residue was chromatographed on silica (eluant: hexane--ethyl acetate (9-1)) to obtain 3.27 g of the desired product.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[CH:4][C:5]([F:15])=[C:6]([CH:8]([OH:14])[C:9]([F:13])([F:12])[CH2:10][OH:11])[CH:7]=1.N1C=CN=C1.[Si:21](Cl)([C:24]([CH3:27])([CH3:26])[CH3:25])([CH3:23])[CH3:22]>C(Cl)Cl.C(OC(=O)C)C.CCCCCC>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([F:15])=[C:6]([CH:8]([OH:14])[C:9]([F:13])([F:12])[CH2:10][O:11][Si:21]([C:24]([CH3:27])([CH3:26])[CH3:25])([CH3:23])[CH3:22])[CH:7]=1
Reactant: OCC(F)(F)C(O)c1cc(Br)ccc1F
Reactant: CC(C)(C)[Si](C)(C)Cl
Agent: c1c[nH]cn1
Solvent: CCCCCC
Solvent: ClCCl
Solvent: CCOC(C)=O
Product: CC(C)(C)[Si](C)(C)OCC(F)(F)C(O)c1cc(Br)ccc1F
Temperature: 0 °C
Reaction time: 2 h

Procedure:
To an ice cooled solution of 1-(5-bromo-2-fluorophenyl)-2,2-difluoropropane-1,3-diol (17.0 g, 59.8 mmol) in dry DCM (200 mL) was added imidazole (12.2 g, 179.2 mmol) at 0° C. and stirred for 15 min. tert-butyldimethylsilylchloride (13.5 g, 89.5 mmol) was added to the resultant reaction mixture portion wise for a period of 30 min. and stirring continued for 2 h. Reaction was monitored by TLC analysis. The solids formed in the reaction mixture were separated by filtration and filtrate was concentrated under reduced pressure to obtain crude product which was puirified by column chromatography on silica gel with 2% Ethylacetate in Hexane as eluent to furnish title compound as a colorless liquid. Yield=19 g (80%). TLC (20% ethyl acetate in Hexane): Rf=0.75),
Reaction SMILES: [Cl:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=O)=[C:4]([OH:10])[CH:3]=1.[H-].[Na+].C(OP([C:21](=[CH2:27])[C:22]([O:24][CH2:25][CH3:26])=[O:23])(OCC)=O)C.O>O1CCCC1.C(OCC)C>[Cl:1][C:2]1[CH:3]=[C:4]2[C:5]([CH:6]=[C:21]([C:22]([O:24][CH2:25][CH3:26])=[O:23])[CH2:27][O:10]2)=[CH:8][CH:9]=1
Reactant: O=Cc1ccc(Cl)cc1O
Reactant: C=C(C(=O)OCC)P(=O)(OCC)OCC
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: C1CCOC1
Solvent: CCOCC
Product: CCOC(=O)C1=Cc2ccc(Cl)cc2OC1
Temperature: 25 °C
Reaction time: 2 h
Yield: 31.8 %

Procedure:
4-Chloro-2-hydroxybenzaldehyde (Acta. Chem. Scand., Vol. 53, p. 258, 1999) (510 mg) was dissolved in tetrahydrofuran (40 ml), sodium hydride (60% in oil, 157 mg) was added, and the mixture was stirred at room temperature for 2 hours. A tetrahydrofuran solution (10 ml) of ethyl 2-diethylphosphonoacrylate (J. Org. Chem., Vol. 43, P. 1256, 1978) (769 mg) was added to the reaction mixture, and the resultant mixture was stirred at room temperature for 2 hours and then heated overnight under reflux. After the reaction mixture was cooled to room temperature, water and diethyl ether were added to conduct liquid separation. After the resultant organic layer was dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure, and the residue was purified by column chromatography on silica gel (hexane:ethyl acetate=10:1) to obtain the title compound (247 mg).
Reaction SMILES: [C:1]([O:4][CH2:5][C@H:6]([N:8]1[CH:17]=[CH:16][C:15]2[C:10](=[CH:11][CH:12]=[C:13]([Cl:21])[C:14]=2[N+:18]([O-])=O)[C:9]1=[O:22])[CH3:7])(=[O:3])[CH3:2].C(O)C.[Cl-].[NH4+].O>[Fe].ClCCl>[C:1]([O:4][CH2:5][C@H:6]([N:8]1[CH:17]=[CH:16][C:15]2[C:10](=[CH:11][CH:12]=[C:13]([Cl:21])[C:14]=2[NH2:18])[C:9]1=[O:22])[CH3:7])(=[O:3])[CH3:2]
Reactant: CC(=O)OC[C@@H](C)n1ccc2c([N+](=O)[O-])c(Cl)ccc2c1=O
Agent: [Fe]
Agent: [Cl-]
Agent: [NH4+]
Solvent: O
Solvent: ClCCl
Solvent: CCO
Product: CC(=O)OC[C@@H](C)n1ccc2c(N)c(Cl)ccc2c1=O
Temperature: 85 °C

Procedure:
A round bottom flask was charged with (R)-2-(6-chloro-5-nitro-1-oxoisoquinolin-2(1H)-yl)propyl acetate (160.0 mg, 0.0004927 mol) and ethanol (7 mL, 0.1 mol) and the reaction heated at 85° C. Ammonium chloride (264 mg, 0.00493 mol) in water (7 mL, 0.4 mol) was then added followed by the addition of iron (110 mg, 0.0020 mol) in two portions. The reaction was heated at that temperature for another hour. The reaction mixture was poured into dichloromethane (60 mL) and extracted. The extracts were washed with brine, dried over sodium sulfate and the solvent removed under reduced pressure to obtain the product as a colorless solid. MS m/z=295.5 (M+H).
Reaction SMILES: [Cl:1][C:2]1[N:7]=[CH:6][C:5]([CH:8]=O)=[CH:4][CH:3]=1.[O-]S([O-])(=O)=O.[Na+].[Na+].[CH3:17][NH2:18].[O-]S([O-])(=O)=O.[Mg+2]>C1(C)C=CC=CC=1>[Cl:1][C:2]1[N:7]=[CH:6][C:5]([CH:8]=[N:18][CH3:17])=[CH:4][CH:3]=1
Reactant: CN
Reactant: O=Cc1ccc(Cl)nc1
Agent: O=S(=O)([O-])[O-]
Agent: [Mg+2]
Agent: [Na+]
Solvent: Cc1ccccc1
Product: CN=Cc1ccc(Cl)nc1
Reaction time: 8 h
Yield: 35.3 %

Procedure:
In 30 ml of toluene, 0.8 g (5.7×10-1 moles) of 6-chloropyridine-3-aldehyde and 10 g of Na2SO4 were mixed and while the mixtures was stirred, a 40% aqueous solution of methylamine (1.4 g, 1.1×10-2 mole) was added dropwise over 30 minutes, followed by addition of 10 g of MgSO4. The mixture was allowed to stand at room temperature overnight, after which it was filtered. The filtrate was concentrated to give 0.6 g (yield 68%) of N-(6-chloro-3-pyridylmethylidene)methylamine as crystals.
Reaction SMILES: Cl[C:2]([O:4][CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)=[O:3].[NH2:12][CH2:13][CH2:14][CH2:15][C:16]([OH:18])=[O:17].[OH-].[Na+]>C1COCC1.O>[C:2]([NH:12][CH2:13][CH2:14][CH2:15][C:16]([OH:18])=[O:17])([O:4][CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)=[O:3]
Reactant: O=C(Cl)OCc1ccccc1
Reactant: NCCCC(=O)O
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: O
Product: O=C(O)CCCNC(=O)OCc1ccccc1
Reaction time: 3 h

Procedure:
Benzyl chloroformate (0.630 mL, 753 mg, 4.4 mmol, 1 equiv) and 4-aminobutyric acid (440 mg, 4.3 mmol, 1 equiv) were added to a solution of NaOH (188 mg, 4.7 mmol, 1.1 equiv) in THF-water (25 mL each). More NaOH (175 mg, 4.4 mmol, 1 equiv) was added to make pH>7. The solution was stirred for 3 h. The solution was concentrated in vacuo. Water was added and the solution was washed three times each with dichloromethane and ethyl acetate. The aqueous layer was concentrated in vacuo to yield N-Cbz-4-aminobutyric acid. To a solution of mono-Boc p-xylylene diamine (271 mg, 1.1 mmol, 1 equiv) in dichloromethane (25 mL) was added N-Cbz-4-aminobutyric acid (258 mg, 1.1 mmol, 1 equiv). The mixture was cooled to 0° C. HOBT (165 mg, 1.2 mmol, 1.1 equiv) and EDC (233 mg, 1.2 mmol, 1.1 equiv) were added. NMM (30 drops) was added to adjust pH. The solution was stirred at 0° C. for 1 h and at r.t. over the weekend. Dichloromethane was added, and the solution was washed with 0.05N HCl, saturated aqueous sodium bicarbonate, and brine. The organic layer was dried over MgSO4, filtered, and concentrated in vacuo. Ethanol (30 mL) and palladium (270 mg, 5%/C) were added to the residue (432 mg) and the mixture was stirred under hydrogen (1 atm) for 20 h. The mixture was filtered, and the ethanol was removed in vacuo. To the residue (206 mg, 0.64 mmol, 2.1 equiv) was added dichloromethane (25 mL) and DMF (2 mL). Triethylamine (0.091 mL, 66 mg, 0.65 mmol, 2.2 equiv) and terephthaloyl dichloride (60 mg, 0.3 mmol, i equiv) were added and the solution was stirred overnight. The solution was washed with 0.05N HCl, saturated aqueous sodium bicarbonate, and brine. The organic layer was concentrated in vacuo. TFA and dichloromethane (10 mL each) were added and the solution was stirred for 1 h. The solution was concentrated under vacuum and rinsed twice with ether. The crude product was purified on the Waters LC (2-30% gradient) to yield 50 mg of >95% pure bis TFA salt of the title compound.
Reaction SMILES: [H-].[K+].[NH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][S:14]([OH:17])(=[O:16])=[O:15].[C:18](=[S:20])=[S:19].[CH3:21]I>C(O)C.O>[S:14]([CH2:13][CH2:12][CH2:11][CH2:10][CH2:9][CH2:8][CH2:7][CH2:6][CH2:5][CH2:4][NH:3][C:18](=[S:20])[S:19][CH3:21])([OH:17])(=[O:15])=[O:16]
Reactant: S=C=S
Reactant: CI
Reactant: NCCCCCCCCCCS(=O)(=O)O
Agent: [H-]
Agent: [K+]
Solvent: CCO
Solvent: O
Product: CSC(=S)NCCCCCCCCCCS(=O)(=O)O
Reaction time: 12 h

Procedure:
A suspension of 56 g. (1.0 mol.) of potassium hydride and 118.7 g. (0.5 mol.) of 10 -aminodecanesulfonic acid in 170 ml. of water is stirred for 30 minutes at 25°, then 40 g. (0.52 mol.) of carbon disulfide and 80 ml. of ethanol are added and the reaction mixture is stirred at 25° for 12 hours. The mixture is refluxed gently for 2 hours and cooled. Methyl iodide (71 g., 0.3 mol.) and 130 ml. of ethanol are added to the mixture and it is stirred at 25° for 12 hours. The mixture is evaporated to remove the ethanol and the solid residue is collected by filtration to give methyl 10-sulfodecyldithiocarbamate.
Reaction SMILES: C(OC([N:8]1[CH2:14][CH2:13][C:12](=[O:15])[N:11]([CH2:16][CH2:17][CH2:18][N:19]2[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]2)[CH2:10][CH2:9]1)=O)(C)(C)C.[ClH:25].CO>C(Cl)Cl.O1CCOCC1>[ClH:25].[ClH:25].[N:19]1([CH2:18][CH2:17][CH2:16][N:11]2[C:12](=[O:15])[CH2:13][CH2:14][NH:8][CH2:9][CH2:10]2)[CH2:20][CH2:21][CH2:22][CH2:23][CH2:24]1
Reactant: CC(C)(C)OC(=O)N1CCC(=O)N(CCCN2CCCCC2)CC1
Agent: Cl
Solvent: ClCCl
Solvent: CO
Solvent: C1COCCO1
Product: O=C1CCNCCN1CCCN1CCCCC1
Temperature: 0 °C
Reaction time: 3 h

Procedure:
A solution of 7.3 g (21.50 mmol) of 5-oxo-4-(3-piperidin-1-yl-propyl)-[1,4]diazepane-1-carboxylic acid tert-butyl ester was dissolved in 140 ml CH2Cl2, cooled to 0° C. and treated with 54 ml (215.03 mmol) of 4M HCl in dioxane, then warmed to RT. After 3 h, 40 ml of MeOH were added to dissolve the precipitation and stirring was continued over night. The solution was evaporated, dissolved in toluene and evaporated (2×) to yield 7.71 g (quantitative) of the title compound as a white solid. MS: 240.1 (MH+).
Reaction SMILES: [CH2:1]([OH:6])[C:2]#[C:3][CH2:4][OH:5].[O:7]1[CH:12]=[CH:11][CH2:10][CH2:9][CH2:8]1>C1(C)C=CC(S(O)(=O)=O)=CC=1.CCOCC>[O:7]1[CH2:12][CH2:11][CH2:10][CH2:9][CH:8]1[O:5][CH2:4][C:3]#[C:2][CH2:1][OH:6]
Reactant: OCC#CCO
Reactant: C1=COCCC1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: CCOCC
Product: OCC#CCOC1CCCCO1
Yield: 68.8 %

Procedure:
To a mixture of 5.0 g of 2-butyne-l,4-diol and 10 milligrams of p-toluenesulfonic acid and 150 ml of dry ether there was added dropwise with stirring at room temperature 4.9 g of 3,4-dihydro-2H-pyran. After stirring overnight at ambient temperature the ether was evaporated and the residue was poured into 200 ml of water. The aqueous solution was extracted with hexane (2×100 ml) and then re-extracted with ether (3×100 ml). The combined ether extracts were washed with 100 ml of brine, dried over magnesium sulfate and evaporated to yield 6.8 g of 4-tetrahydropyranoxy-2-butyn-1-ol.
Reaction SMILES: [CH3:1]/[C:2](/[O:8][Si](C)(C)C)=N\[Si](C)(C)C.N1C=[CH:19][C:17](=[O:18])NC1=O.[Si](OS(C(F)(F)F)(=O)=O)(C)(C)C.CC[O:35][C:36]([CH3:38])=[O:37]>C(#N)C.O>[CH3:1][C:2]([CH2:19][C:17]([CH2:38][C:36]([OH:35])=[O:37])=[O:18])=[O:8]
Reactant: CCOC(C)=O
Reactant: C/C(=N\[Si](C)(C)C)O[Si](C)(C)C
Reactant: O=c1cc[nH]c(=O)[nH]1
Agent: C[Si](C)(C)OS(=O)(=O)C(F)(F)F
Solvent: O
Solvent: CC#N
Product: CC(=O)CC(=O)CC(=O)O
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
N,O-Bis(trimethylsilyl)acetamide (BSA, 54.7 mL, 224 mmol) was added to a stirred suspension of uracil (10.2 g, 90.7 mmol) and Compound 54 (31.1 g, 60.4 mmoles) in dry acetonitrile (300 mL). After stirring at rt for 30 min a clear solution was observed, and the reaction was cooled to 0° C. under nitrogen. Trimethylsilyfluoromethanesulfonate (TMSOTf, 21.9 mL, 121 mmol) was added and after the reaction was stirred at rt for 15 min, it was transferred to a preheated oil bath at 80° C. After stirring for 4 h at 80° C., the reaction was cooled to rt and MeO H (20 mL), EtOAc (250 mL) and H2O (400 mL) were added. The organic phase was then sequentially washed with sat. NaHCO3, brine, dried (Na2SO4) and concentrated to provide the crude triacetate. TLC (Rf═0.60, 80% EtOAc/hexanes). LCMS (Method m/z═567.1 (M+H).