Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: N#N.[CH2:3]([N:10]1[CH2:15][CH2:14][CH:13]([C:16]2[CH:21]=[CH:20][C:19](Br)=[CH:18][CH:17]=2)[CH2:12][CH2:11]1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.C([Li])CCC.[CH3:28][C:29]1[NH:30][C:31]([CH3:40])=[CH:32][C:33]=1[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][N:35]=1>CCCCCC.CCOCC>[CH2:3]([N:10]1[CH2:15][CH2:14][CH:13]([C:16]2[CH:21]=[CH:20][C:19]([C:36]3[N:35]=[C:34]([C:33]4[CH:32]=[C:31]([CH3:40])[NH:30][C:29]=4[CH3:28])[CH:39]=[CH:38][CH:37]=3)=[CH:18][CH:17]=2)[CH2:12][CH2:11]1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1
Reactant: Brc1ccc(C2CCN(Cc3ccccc3)CC2)cc1
Reactant: Cc1cc(-c2ccccn2)c(C)[nH]1
Agent: N#N
Agent: [Li]CCCC
Solvent: CCCCCC
Solvent: CCOCC
Product: Cc1cc(-c2cccc(-c3ccc(C4CCN(Cc5ccccc5)CC4)cc3)n2)c(C)[nH]1
Temperature: -70 °C
Reaction time: 0.08 h
Yield: 32.3 %

Procedure:
To a 125 mL three-necked round-bottomed flask equipped with septum and N2 inlet were added 2.93 g (8.88 mmol) N-benzyl-4-(4-bromophenyl)piperidine and 30 mL dry ether. The solution was cooled to −70° C., and 6.66 mL (10.65 mmol) of a 1.6 N solution of butyl lithium in hexane added dropwise over 5 minutes. After stirring a further 5 minutes at −70° C., the solution was warmed slowly to room temperature over 25 minutes. A solution of 1.83 g (10.65 mmol) 2-(2,5-dimethylpyrrolyl)pyridine in 10 mL dry ether was then added dropwise over 5 minutes, and the reaction, which turned slowly dark red, stirred at room temperature for 3 hours. The reaction was quenched with aqueous ammonium chloride solution, partitioned between ethyl acetate and water, and the organic layer separated, washed with brine, and dried over sodium sulfate, allowing it to stand overnight to effect rearomatization of the pyridine ring. After evaporation of the solvent, the residue was chromatographed on silica gel using ethyl acetate/hexane followed by methanol/methylene chloride as eluant to afford 1.21 g (32%) of an oil.
Reaction SMILES: Cl.[CH3:2][O:3][C:4](=[O:7])[CH2:5][NH2:6].[C:8]([O:12][C:13]([NH:15][C@H:16]([CH:21]=O)[C@H:17]([CH2:19][CH3:20])[CH3:18])=[O:14])([CH3:11])([CH3:10])[CH3:9].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(N(CC)CC)C>ClCCCl.CN(C=O)C>[CH3:2][O:3][C:4](=[O:7])[CH2:5][NH:6][CH2:21][C@@H:16]([NH:15][C:13]([O:12][C:8]([CH3:11])([CH3:10])[CH3:9])=[O:14])[C@@H:17]([CH3:18])[CH2:19][CH3:20]
Reactant: COC(=O)CN
Reactant: CC[C@H](C)[C@@H](C=O)NC(=O)OC(C)(C)C
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: Cl
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: ClCCCl
Solvent: CCN(CC)CC
Product: CC[C@H](C)[C@@H](CNCC(=O)OC)NC(=O)OC(C)(C)C
Temperature: 0 °C

Procedure:
Glycine methyl ester hydrochloride (4.41 g, 0.035 mol) was dissolved in 1,2-dichloroethane (50 mL) and DMF (5 mL) and treated with 3A molecular sieves (10 g) and N-t-butoxycarbonyl-isoleucinal (6.3 g, 0.029 mol) with stirring at 0° C. Sodium triacetoxyborohydride (9.27 g, 0.044 mol) was added, and the pH of the mixture was adjusted to 6 with triethylamine (3 mL, 0.022 mol). After stirring for 18 h the mixture was filtered, concentrated to a small volume and partitioned between EtOAc and water. The aqueous layer was extracted with EtOAc (2×50 mL). The combined organic phase was washed with aqueous saturated NaHCO3 solution, brine, and dried (Na2SO4). Filtration and concentration afforded a residue which was purified by flash chromatography (SiO2, EtOAc:hexane, 1:3) to give (6).
Reaction SMILES: Cl.[Cl:2][C:3]1[N:8]=[C:7]([CH3:9])[N:6]=[C:5]([NH2:10])[C:4]=1[CH2:11][CH2:12][CH:13]1[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]1.C(N(C(C)C)CC)(C)C.F[P-](F)(F)(F)(F)F.CN(C(=[N+](C)C)ON1C2=NC=CC=C2N=N1)C.[C:52]([O:56][C:57]([NH:59][C@@H:60]([CH3:64])[C:61](O)=[O:62])=[O:58])([CH3:55])([CH3:54])[CH3:53]>CN(C=O)C>[NH2:10][C:5]1[C:4]([CH2:11][CH2:12][CH:13]2[CH2:18][CH2:17][N:16]([C:61](=[O:62])[C@@H:60]([NH:59][C:57](=[O:58])[O:56][C:52]([CH3:54])([CH3:53])[CH3:55])[CH3:64])[CH2:15][CH2:14]2)=[C:3]([Cl:2])[N:8]=[C:7]([CH3:9])[N:6]=1
Reactant: C[C@H](NC(=O)OC(C)(C)C)C(=O)O
Reactant: Cc1nc(N)c(CCC2CCNCC2)c(Cl)n1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: Cl
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: Cc1nc(N)c(CCC2CCN(C(=O)[C@H](C)NC(=O)OC(C)(C)C)CC2)c(Cl)n1
Reaction time: 0.08 h
Yield: 153.2 %

Procedure:
Into each of two round bottom flasks add 6-chloro-2-methyl-5-[2-(4-piperidyl)ethyl]pyrimidin-4-amine hydrochloride (12.50 g, 42.92 mmol), diisopropylethylamine (22.46 mL, 128.7 mmol) and DMF (100 mL). Cool the two mixtures in a cold water bath and stir for 5 min. Add to each of the mixtures [dimethylamino(triazolo[4,5-b]pyridin-3-yloxy)methylene]-dimethyl-ammonium hexafluorophosphate (17.95 g, 47.21 mmol) and (2S)-2-(tert-butoxycarbonylamino)propanoic acid (8.93 g, 47.21 mmol) in one portion. Stir the mixtures at RT for 90 min Pour the mixtures into separate separatory funnels along with water (300 mL) and EtOAc (400 mL), shake and partition. Extract the aqueous layers with EtOAc (3×300 mL), wash the respective organic layers with water (4×250 mL), saturated aqueous NaCl (200 mL) and dry over MgSO4, filter and concentrate under reduced pressure. Purify the combined materials via silica gel chromatography eluting with 70% to 100% EtOAc in hexanes. Combine and concentrate the purified fractions under reduced pressure. Dilute the residue with EtOAc (500 mL) and wash with saturated aqueous NH4Cl (100 mL), saturated aqueous NaHCO3 (100 mL), water (100 mL) and saturated aqueous NaCl (100 mL). Dry the organics over MgSO4, filter, and concentrate under reduced pressure to give the title compound as a white solid (28.00 g, 76%). LC-ES/MS m/z (35Cl/37Cl) 426.2/428.2 (M+1).
Reaction SMILES: [Br:1][C:2]1[CH:14]=[CH:13][C:5]([O:6][CH:7]2[CH2:12][CH2:11][NH:10][CH2:9][CH2:8]2)=[CH:4][CH:3]=1.C([O-])([O-])=O.[Na+].[Na+].[O:21](C(OC(C)(C)C)=O)[C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=O>O1CCOCC1.O>[C:25]([O:24][C:22]([N:10]1[CH2:9][CH2:8][CH:7]([O:6][C:5]2[CH:13]=[CH:14][C:2]([Br:1])=[CH:3][CH:4]=2)[CH2:12][CH2:11]1)=[O:21])([CH3:28])([CH3:27])[CH3:26]
Reactant: CC(C)(C)OC(=O)OC(=O)OC(C)(C)C
Reactant: Brc1ccc(OC2CCNCC2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: C1COCCO1
Solvent: O
Product: CC(C)(C)OC(=O)N1CCC(Oc2ccc(Br)cc2)CC1
Reaction time: 48 h
Yield: 86.4 %

Procedure:
To a solution of 4-(4-Bromo-phenoxy)-piperidine (1 g, 3.9 mmol) in dioxane (20 ml), water (20 ml) added Na2CO3 (1.6 g, 18.9 mmol) and (BOC)2O (1.3 g, 5.9 mmol). Reaction stirred at ambient for 48 hours, solvent was removed under reduced pressure and residue partitioned between EtOAc and water the layers were separated. The organic layer was washed with brine, dried (MgSO4), and concentrated under reduced pressure to give (1.2 g) of product.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([N:11]([S:15]([C:18]2[CH:23]=[CH:22][C:21]([Cl:24])=[C:20]([C:25]([F:28])([F:27])[F:26])[CH:19]=2)(=[O:17])=[O:16])[CH2:12][O:13][CH3:14])[C:5]([C:8](Cl)=[O:9])=[N:6][CH:7]=1.[CH3:29][C@H:30]1[O:35][C@@H:34]([CH3:36])[CH2:33][NH:32][CH2:31]1.C(N(C(C)C)CC)(C)C>C(Cl)Cl>[Cl:24][C:21]1[CH:22]=[CH:23][C:18]([S:15]([N:11]([C:4]2[C:5]([C:8]([N:32]3[CH2:31][C@H:30]([CH3:29])[O:35][C@H:34]([CH3:36])[CH2:33]3)=[O:9])=[N:6][CH:7]=[C:2]([Cl:1])[CH:3]=2)[CH2:12][O:13][CH3:14])(=[O:17])=[O:16])=[CH:19][C:20]=1[C:25]([F:28])([F:27])[F:26]
Reactant: COCN(c1cc(Cl)cnc1C(=O)Cl)S(=O)(=O)c1ccc(Cl)c(C(F)(F)F)c1
Reactant: C[C@@H]1CNC[C@H](C)O1
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: COCN(c1cc(Cl)cnc1C(=O)N1C[C@@H](C)O[C@@H](C)C1)S(=O)(=O)c1ccc(Cl)c(C(F)(F)F)c1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
A mixture of 5-chloro-3-[(4-chloro-3-trifluoromethyl-benzenesulfonyl)-methoxymethyl-amino]-pyridine-2-carbonyl chloride (50mg, 0.11 mmol), cis-2,6-dimethylmorpholine (50 mg, 0.40 mmol) and di-isopropylethylamine (DIEA, 0.07 mL, 0.40 mmol) in CH2Cl2 (1.5 mL) was stirred at room temperature overnight. The mixture was concentrated to provide 4-chloro-N[5-chloro-2-(cis-2,6-dimethyl-morpholine-4-carbonyl)-pyridin-3-yl]-N-methoxymethyl-3-trifluoromethyl-benzenesulfonamide, which was directly used in the next step without any purification.
Reaction SMILES: Cl.[N:2]1([CH:7]2[CH2:12][CH2:11][CH2:10][NH:9][CH2:8]2)[CH:6]=[N:5][CH:4]=[N:3]1.C1CCN2C(=NCCC2)CC1.[CH:24]1([N:27]2[C:36]3[C:31](=[CH:32][C:33]([F:39])=[C:34](F)[C:35]=3[F:37])[C:30](=[O:40])[C:29]([C:41]([OH:43])=[O:42])=[CH:28]2)[CH2:26][CH2:25]1>C(#N)C>[CH:24]1([N:27]2[C:36]3[C:31](=[CH:32][C:33]([F:39])=[C:34]([N:9]4[CH2:10][CH2:11][CH2:12][CH:7]([N:2]5[CH:6]=[N:5][CH:4]=[N:3]5)[CH2:8]4)[C:35]=3[F:37])[C:30](=[O:40])[C:29]([C:41]([OH:43])=[O:42])=[CH:28]2)[CH2:25][CH2:26]1
Reactant: O=C(O)c1cn(C2CC2)c2c(F)c(F)c(F)cc2c1=O
Reactant: c1ncn(C2CCCNC2)n1
Agent: Cl
Solvent: CC#N
Solvent: C1CCC2=NCCCN2CC1
Product: O=C(O)c1cn(C2CC2)c2c(F)c(N3CCCC(n4cncn4)C3)c(F)cc2c1=O
Temperature: 90 °C

Procedure:
3-(1,2,4-triazol-1-yl)piperidine hydrochloride (300 mg, 1.59 mmol) and DBU (0.48 g, 3.18 mmol) were added to a suspension of 1-cyclopropyl-6,7,8-trifluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic acid (180 mg, 0.63 mmol) in acetonitrile (15 ml). The reaction mixture was refluxed at 90° C. for 48 hrs and then concentrated under vacuum. The residue was diluted with water and aqueous solution was extracted with chloroform. The organic layer dried over Na2SO4, concentrated and the residue was diluted with water. The separated solid was filtered and washed with 2 ml of acetonitrile. Yield 13 mg, m.p. 217° C.; 1H NMR (TFA) δ: 9.75 (s, 1H), 9.40 (s, 1H), 8.78 (s, 1H), 8.20 (d, 1H), 5.10 (m, 1H), 4.58 (m, 1H), 3.52-4.40 (m, 4H), 2.55 (m, 2H), 2.20 (m, 2H), 1.30-1.70 (m, 4H).
Reaction SMILES: C1(C([O:20][CH2:21][CH2:22][C@H:23]2[O:27][C:26](=[O:28])[N:25]([CH2:29][CH:30]3[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]3)[CH:24]2[C:36]2[CH:41]=[CH:40][C:39]([Cl:42])=[C:38]([Cl:43])[CH:37]=2)(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.Cl.C(N(CC)CC)C.[CH3:52][S:53](Cl)(=[O:55])=[O:54]>O1CCOCC1.C(Cl)Cl>[CH3:52][S:53]([O:20][CH2:21][CH2:22][C@H:23]1[O:27][C:26](=[O:28])[N:25]([CH2:29][CH:30]2[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]2)[CH:24]1[C:36]1[CH:41]=[CH:40][C:39]([Cl:42])=[C:38]([Cl:43])[CH:37]=1)(=[O:55])=[O:54]
Reactant: CS(=O)(=O)Cl
Reactant: O=C1O[C@H](CCOC(c2ccccc2)(c2ccccc2)c2ccccc2)C(c2ccc(Cl)c(Cl)c2)N1CC1CCCCC1
Agent: Cl
Solvent: ClCCl
Solvent: C1COCCO1
Solvent: CCN(CC)CC
Product: CS(=O)(=O)OCC[C@H]1OC(=O)N(CC2CCCCC2)C1c1ccc(Cl)c(Cl)c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 83.2 %

Procedure:
An alcohol derivative (930 mg, 91%) was prepared according to the procedures described in Example 12(d) using 2-[3-(cyclohexylmethyl)-(5R)-(3,4-dichlorophenyl)-2-oxooxazolidin-5-yl]ethanol triphenylmethylether (1.69 g, 2.75 mmol) and a solution of hydrogen chloride in dioxane (4N, 6.9 ml). The alcohol derivative (880 mg, 2.36 mmol) was dissolved in methylene chloride (18 ml), and triethylamine (0.50 ml, 3.55 mmol) and methanesulfonyl chloride (0.22 ml, 2.84 mmol) were added to the solution. The mixture was stirred at room temperature overnight. To the reaction mixture, methylene chloride was added, and this was washed with water and then with a saturated aqueous solution of sodium chloride. The organic layer was dried over anhydrous magnesium sulfate and the solvent was distilled off under reduced pressure. The residue was purified by flash chromatography on a silica gel column using n-hexane/ethyl acetate=4/1−1/1 as an eluant to afford the title compound (1.03 g, 97%).
Reaction SMILES: Cl.[CH:2]1([N:5]([CH:19]2[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]2)[C:6](=[O:18])[C:7]2[CH:12]=[CH:11][C:10]([C:13]3[O:17][CH:16]=[N:15][CH:14]=3)=[CH:9][CH:8]=2)[CH2:4][CH2:3]1.[CH3:25][O:26][C:27]([C:29]1[CH:34]=[N:33][C:32](Cl)=[CH:31][N:30]=1)=[O:28]>CN1CCCC1=O>[CH3:25][O:26][C:27]([C:29]1[CH:34]=[N:33][C:32]([N:22]2[CH2:23][CH2:24][CH:19]([N:5]([CH:2]3[CH2:4][CH2:3]3)[C:6](=[O:18])[C:7]3[CH:8]=[CH:9][C:10]([C:13]4[O:17][CH:16]=[N:15][CH:14]=4)=[CH:11][CH:12]=3)[CH2:20][CH2:21]2)=[CH:31][N:30]=1)=[O:28]
Reactant: COC(=O)c1cnc(Cl)cn1
Reactant: O=C(c1ccc(-c2cnco2)cc1)N(C1CCNCC1)C1CC1
Agent: Cl
Solvent: CN1CCCC1=O
Product: COC(=O)c1cnc(N2CCC(N(C(=O)c3ccc(-c4cnco4)cc3)C3CC3)CC2)cn1

Procedure:
The title compound is prepared from N-cyclopropyl-4-oxazol-5-yl-N-piperidin-4-yl-benzamide hydrochloride and 5-chloro-pyrazine-2-carboxylic acid methyl ester following a procedure analogous to that described in Example 19 using N-methylpyrrolidinone as solvent. LC (method 16): tR=0.44 min; Mass spectrum (ESI+): m/z=448 [M+H]+.
Reaction SMILES: CS([O:5][CH:6]([CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH3:20])[CH3:7])(=O)=O.[I:21][C:22]1[CH:27]=[CH:26][C:25](O)=[CH:24][CH:23]=1.C(=O)([O-])[O-].[K+].[K+].IC1C=CC(OC(CCCCCCCC)C)=CC=1>CN(C=O)C>[I:21][C:22]1[CH:27]=[CH:26][C:25]([O:5][CH:6]([CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH3:20])[CH3:7])=[CH:24][CH:23]=1
Reactant: Oc1ccc(I)cc1
Reactant: CCCCCCCCCCCCCC(C)OS(C)(=O)=O
Agent: CCCCCCCCC(C)Oc1ccc(I)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CCCCCCCCCCCCCC(C)Oc1ccc(I)cc1
Temperature: 80 °C
Reaction time: 24 h
Yield: 43.1 %

Procedure:
The 2-methanesulfonyloxypentadecane (34.4 g, 102 mmol) was reacted with 4-iodophenol (22.7 g, 103 mmol) and potassium carbonate (14.3 g, 103 mmol) in DMF (200 ml) as per 2-(4-iodophenoxy)decane except that the temperature of the oil bath was maintained at 80° C. for 15 hrs and increased to 86° C. with stirring for an additional 24 hrs. At the end of this period, NMR spectral analysis indicated that the reaction was complete. The reaction mixture was processed as for 2-(4-iodophenoxy)decane except with four times the volumes to provide a light yellow oil. Flash column chromatography (silica, hexanes) yielded 2-(4-iodophenoxy)pentadecane (18.9 g, 43.0%) as a clear oil. Title Compound: 1H (300 MHz) and 13C (75 MHz) NMR spectra were consistent with the desired structure. FAB/MS: M+, 430. Calculated for C21H35IO: C, 58.47; H, 8.41; I, 29.42. Found: C, 58.91, H, 8.36; I, 29.26.
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[C:11](Br)=[CH:10][CH:9]=[C:8]([CH3:13])[N:7]=1)=[O:5])[CH3:2].[NH2:14][C:15]1[CH:16]=[N:17][N:18]([CH3:20])[CH:19]=1>[Pd]>[CH2:1]([O:3][C:4]([C:6]1[C:11]([NH:14][C:15]2[CH:16]=[N:17][N:18]([CH3:20])[CH:19]=2)=[CH:10][CH:9]=[C:8]([CH3:13])[N:7]=1)=[O:5])[CH3:2]
Reactant: Cn1cc(N)cn1
Reactant: CCOC(=O)c1nc(C)ccc1Br
Agent: [Pd]
Product: CCOC(=O)c1nc(C)ccc1Nc1cnn(C)c1

Procedure:
The Pd catalyzed coupling of 3-Bromo-6-methyl-pyridine-2-carboxylic acid ethyl ester and 4-Amino-1-methyl-pyrazole was performed in accordance with the general method of Example 78, step 3 to yield the title compound as an orange solid, MS (ISP): m/e=261.0 (M+H+).
Reaction SMILES: Cl[C:2]1[C:7]([C:8]#[N:9])=[CH:6][N:5]=[CH:4][CH:3]=1.[CH2:10]([Sn](CCCC)(CCCC)C=C)[CH2:11]CC>CN(C)C=O.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>[CH:10]([C:2]1[C:7]([C:8]#[N:9])=[CH:6][N:5]=[CH:4][CH:3]=1)=[CH2:11]
Reactant: N#Cc1cnccc1Cl
Reactant: C=C[Sn](CCCC)(CCCC)CCCC
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Solvent: CN(C)C=O
Product: C=Cc1ccncc1C#N
Temperature: 120 °C
Reaction time: 1 h
Yield: 99.1 %

Procedure:
To a solution of compound (20)(1.00 g, 7.21 mmol) in dimethylformamide (15 ml) were added tributyl(vinyl)tin (2.50 ml, 8.65 mmol) and dichlorobis(triphenylphosphine)palladium (0.40 g, 0.58 mmol), and the mixture was stirred at 120° C. under an argon atmosphere for one hr. The reaction mixture was poured into ice water and extracted with ethyl acetate. The extract was combined and washed with brine and dried (MgSO4). The solvent was evaporated under reduced pressure and the obtained residue was purified by silica gel column chromatography to give a white powder (0.93 g, 99%).
Reaction SMILES: [CH2:1]([C:3]1[CH:8]=[CH:7][CH:6]=[C:5]([CH:9]([CH3:11])[CH3:10])[C:4]=1[N:12]=[C:13]=[S:14])[CH3:2].Cl.C([O:18][C:19](=O)[CH2:20][NH:21][CH3:22])C.C(N(CC)CC)C>C(Cl)(Cl)Cl>[CH2:1]([C:3]1[CH:8]=[CH:7][CH:6]=[C:5]([CH:9]([CH3:11])[CH3:10])[C:4]=1[N:12]1[C:19](=[O:18])[CH2:20][N:21]([CH3:22])[C:13]1=[S:14])[CH3:2]
Reactant: CCc1cccc(C(C)C)c1N=C=S
Reactant: CCOC(=O)CNC
Agent: Cl
Solvent: ClC(Cl)Cl
Solvent: CCN(CC)CC
Product: CCc1cccc(C(C)C)c1N1C(=O)CN(C)C1=S
Yield: 64.9 %

Procedure:
The title compound was prepared by the procedure described in Example 1 using 10.25 g of 2-ethyl-6-isopropylphenyl-isothiocyanate, 7.68 g of sarcosine ethyl ester hydrochloride, 14.8 g of triethyl amine, and 200 mL of chloroform. Crystallization from diethyl ether/hexane mixture afforded the title compound (8.95 g) as a tan solid, m.p. 132°-134° C. Anal. Calcd. for C15H20N2O S: C, 65.18; H, 7.29; N, 10.13. Found: C, 65.11; H, 7.31; N, 10.05. Mass spectrum (PBEI, M.+) m/z 276.
Reaction SMILES: O=O.[CH2:3]([SH:7])[CH2:4][CH2:5][CH3:6].CO.[OH-].[Na+]>O>[CH2:3]([S:7][S:7][CH2:3][CH2:4][CH2:5][CH3:6])[CH2:4][CH2:5][CH3:6]
Reactant: CCCCS
Agent: O=O
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: O
Product: CCCCSSCCCC
Reaction time: 1 h

Procedure:
This example illustrates the invention and shows that when the reaction liquid is circulated through a restricted area (aspirator) such that a more intimate contact with oxygen is made, the rate of reaction (rate of mercaptan conversion) is greatly increased. A 10-gallon glass-lined reactor, equipped with a Scott oxygen analyzer, reflux condenser, stirrer, thermocouple and circulating inlet tube as shown in FIG. 1 was charged with 38 pounds (0.42 pound moles) of n-butyl mercaptan, 17.2 pounds (0.432 pound moles) of methyl alcohol and 0.91 pounds (0.023 pound moles) of sodium hydroxide. The reactor was sealed and pressured with nitrogen to 220 psig. The stirrer was started and the liquid externally circulated at 1.5-2 gallons per minute using a Lawrence can pump by first passage through a heat exchanger and then being passed through an Ametex water jet exhauster (aspirator) having a 1.27 cm (0.50 in.) opening on the circulated side and a 0.635 cm (0.25 in.) opening on the suction side. The liquid was then returned to the vapor phase of the reactor. Oxygen was then added such that entry was made through the aspirator (see FIG. 1). The system was pressured to about 280 psig with the additional oxygen and the amount of oxygen present in the vapor phase of the reactor monitored by a Scott analyzer and maintained at about 20 mole percent. The reaction temperature immediately began to slowly rise such that after about 1 hour the temperature in the liquid phase of the reactor was about 60° C. (140° F.). The temperature was maintained between about 49° C.-60° C. (120° F.-140° F.) throughout the run. After 1 hour analysis indicated the reaction was 65 percent complete and after 2 hours the reaction was complete as determined by GLC. The product was separated and dried as previously described to give 33.3 pounds (88.6 mole percent yield) of essentially pure di-n-butyl disulfide. A comparison of the rates of reaction carried out by the closed system (Example I) and the circulating-intimate mixing system (Example II) is shown in Table I and FIG. II. When another run employing the method described in Example II was carried out wherein the separated oil was distilled rather than air dried at 100° C.-120° C., the yield of di-n-butyl disulfide was increased giving 35 pounds (93.1 mole percent) of product.
Reaction SMILES: [CH2:1]([O:5][C:6]1[N:14]=[C:13]2[C:9]([N:10]=[C:11]([O:23]C)[N:12]2[CH2:15][CH2:16][CH:17]2[CH2:22][CH2:21][O:20][CH2:19][CH2:18]2)=[C:8]([NH2:25])[N:7]=1)[CH2:2][CH2:3][CH3:4].Cl.O.[OH-].[Na+]>CO.O1CCOCC1>[NH2:25][C:8]1[N:7]=[C:6]([O:5][CH2:1][CH2:2][CH2:3][CH3:4])[N:14]=[C:13]2[C:9]=1[NH:10][C:11](=[O:23])[N:12]2[CH2:15][CH2:16][CH:17]1[CH2:18][CH2:19][O:20][CH2:21][CH2:22]1
Reactant: CCCCOc1nc(N)c2nc(OC)n(CCC3CCOCC3)c2n1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: O
Solvent: C1COCCO1
Product: CCCCOc1nc(N)c2[nH]c(=O)n(CCC3CCOCC3)c2n1
Reaction time: 4 h
Yield: 77.7 %

Procedure:
2-Butoxy-8-methoxy-9-[2-(tetrahydro-2H-pyran-4-yl)ethyl]-9H-purin-6-amine (0.11 g) was dissolved in methanol (2 mL) and treated with 4N hydrogen chloride in 1,4-dioxane (1 mL). The reaction mixture was stirred for 4 hours and was stripped to dryness. Water (2 mL) and methanol (15 mL) were added to the residue and then neutralised by the addition of 2N sodium hydroxide solution. The above was stripped to near dryness (small quantity of water remaining) and the solid thus obtained was filtered (transferred and washed the solid with water (3 mL)). The solid was dried under suction before being dried further in vacuo to afford the title compound as a white solid (82 mg).
Reaction SMILES: [H-].[Na+].[C:3]([CH2:6][C:7](=[O:9])[CH3:8])(=[O:5])[CH3:4].[CH2:10]([N:14]([CH2:58][CH2:59][CH2:60][CH3:61])[C:15]1[CH:20]=[CH:19][C:18]([C:21]([C:50]2[CH:55]=[CH:54][C:53]([O:56][CH3:57])=[CH:52][CH:51]=2)(O)[CH:22]=[CH:23][CH:24]=[C:25]([C:34]2[CH:39]=[CH:38][C:37]([N:40]([CH2:45][CH2:46][CH2:47][CH3:48])[CH2:41][CH2:42][CH2:43][CH3:44])=[CH:36][CH:35]=2)[C:26]2[CH:31]=[CH:30][C:29]([O:32][CH3:33])=[CH:28][CH:27]=2)=[CH:17][CH:16]=1)[CH2:11][CH2:12][CH3:13].Cl([O-])(=O)(=O)=O>CN(C)C=O>[CH2:45]([N:40]([CH2:41][CH2:42][CH2:43][CH3:44])[C:37]1[CH:36]=[CH:35][C:34]([C:25]([C:26]2[CH:31]=[CH:30][C:29]([O:32][CH3:33])=[CH:28][CH:27]=2)=[CH:24][CH2:23][CH:22]=[C:21]([C:18]2[CH:17]=[CH:16][C:15]([N:14]([CH2:10][CH2:11][CH2:12][CH3:13])[CH2:58][CH2:59][CH2:60][CH3:61])=[CH:20][CH:19]=2)[C:50]2[CH:55]=[CH:54][C:53]([O:56][CH3:57])=[CH:52][CH:51]=2)=[CH:39][CH:38]=1)[CH2:46][CH2:47][CH3:48].[C:3]([CH2:6][C:7](=[O:9])[CH3:8])(=[O:5])[CH3:4]
Reactant: CCCCN(CCCC)c1ccc(C(=CC=CC(O)(c2ccc(OC)cc2)c2ccc(N(CCCC)CCCC)cc2)c2ccc(OC)cc2)cc1
Agent: [H-]
Agent: [Na+]
Agent: [O-][Cl+3]([O-])([O-])[O-]
Solvent: CC(=O)CC(C)=O
Solvent: CN(C)C=O
Product: CCCCN(CCCC)c1ccc(C(=CCC=C(c2ccc(OC)cc2)c2ccc(N(CCCC)CCCC)cc2)c2ccc(OC)cc2)cc1
Temperature: 0 °C
Reaction time: 1 h
Yield: 63.7 %

Procedure:
1.2 g of a 60% sodium hydride was dispersed in 200 ml of well-dried N,N-dimethylformamide (DMF) in a 300-ml. Erlenmeyer flask. To this dispersion, 3.00 g of acetylacetone was slowly added at room temperature and the mixture was stirred for 1 hour. To this mixture, 15.71 g of 1,5-bis-(p-di-n-butylaminophenyl)-1,5-bis-(p-methoxyphenyl)-2,4-pentadiene-1-ol-perchlorate prepared in Synthesis Example 2,5 was slowly added. This reaction mixture was stirred at room temperature for 1 hour. Then the reaction mixture was poured into 1 l of ice water. As a result, solids separated from the reaction mixture. The solids were washed with water and dried under reduced pressure. After the completion of drying, the solids were subjected to column chromatography, so that 10.0 g of 1,5-bis-(p-di-n-butylaminophenyl)-1,5-bis-(p-methoxyphenyl)-1,4-pentadiene-3-acetylacetone (Leuco Dye No. 26 ) according to the present invention was obtained in the form of light yellow viscous material. The yield was 63.7%. The characteristics absorption bands in the infrared spectrum of the thus obtained product were as follows:
Reaction SMILES: [CH2:1]([O:8][CH2:9][N:10]1[C:18]2[C:17](Cl)=[N:16][C:15]([CH2:20][CH2:21][CH2:22][CH3:23])=[N:14][C:13]=2[C:12]([I:24])=[CH:11]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH3:25]>CC(O)C.CO.ClCCl>[CH2:1]([O:8][CH2:9][N:10]1[C:18]2[C:17]([NH2:25])=[N:16][C:15]([CH2:20][CH2:21][CH2:22][CH3:23])=[N:14][C:13]=2[C:12]([I:24])=[CH:11]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: N
Reactant: CCCCc1nc(Cl)c2c(n1)c(I)cn2COCc1ccccc1
Solvent: CC(C)O
Solvent: CO
Solvent: ClCCl
Product: CCCCc1nc(N)c2c(n1)c(I)cn2COCc1ccccc1
Temperature: 120 °C
Reaction time: 1.5 h

Procedure:
5-((Benzyloxy)methyl)-2-butyl-4-chloro-7-iodo-5H-pyrrolo[3,2-d]pyrimidine (1 g, 2.2 mmol) was suspended in 2-propanol (5 mL) and 35% (0.88) ammonia solution (4 mL). The reaction was stirred at 120° C. for 90 minutes in a Biotage Initiator microwave. A further 1 mL of 35% (0.88) ammonia solution was added to the reaction. The reaction was stirred at 120° C. for 90 minutes in a Biotage Initiator microwave. The reaction was evaporated in vacuo to yield a pale yellow oil. The oil was dissolved in the minimum volume of 20% methanol in dichloromethane and purified by chromatography on silica using a gradient of 0-100% ethyl acetate in cyclohexane gradient over 80 minutes. Fractions were combined and evaporated in vacuo to yield the title compound as a colourless oil (768 mg).