Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C(OC([N:8]([C:16]1[C:21]([C:22]#[CH:23])=[N:20][C:19]([C:24]2[CH:29]=[CH:28][C:27]([S:30]([CH:33]([CH3:35])[CH3:34])(=[O:32])=[O:31])=[CH:26][CH:25]=2)=[CH:18][N:17]=1)C(=O)OC(C)(C)C)=O)(C)(C)C.[C:36](Cl)(=[O:43])[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(O)(C(F)(F)F)=O>C1COCC1.C(Cl)Cl.Cl[Pd]Cl.[Cu]I>[NH2:8][C:16]1[C:21]([C:22]#[C:23][C:36]([C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)=[O:43])=[N:20][C:19]([C:24]2[CH:29]=[CH:28][C:27]([S:30]([CH:33]([CH3:34])[CH3:35])(=[O:32])=[O:31])=[CH:26][CH:25]=2)=[CH:18][N:17]=1
Reactant: O=C(Cl)c1ccccc1
Reactant: C#Cc1nc(-c2ccc(S(=O)(=O)C(C)C)cc2)cnc1N(C(=O)OC(C)(C)C)C(=O)OC(C)(C)C
Agent: Cl[Pd]Cl
Agent: [Cu]I
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: O=C(O)C(F)(F)F
Solvent: C1CCOC1
Solvent: ClCCl
Product: CC(C)S(=O)(=O)c1ccc(-c2cnc(N)c(C#CC(=O)c3ccccc3)n2)cc1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
tert-butyl N-tert-butoxycarbonyl-N-[3-ethynyl-5-(4-isopropylsulfonylphenyl)pyrazin-2-yl]carbamate (200 mg, 0.3987 mmol), benzoyl chloride (56.04 mg, 46.28 μL, 0.3987 mmol), TEA (44.38 mg, 61.13 μL, 0.4386 mmol) was added to a solution of dichloropalladium; triphenylphosphane (27.98 mg, 0.03987 mmol) and CuI (15.19 mg, 0.07974 mmol) in degassed THF (4 mL). The reaction mixture was stirred overnight at ambient temperature. The reaction mixture was concentrated in vacuo. The residue was partitioned between DCM and NaHCO3 aq sat. The combined organic extract was dried (MgSO4) and concentrated in vacuo yielding an oil that was dissolved in DCM (10 mL). TFA (1 mL) was added and the mixture was stirred at ambient temperature for 30 min. The mixture was concentrated in vacuo to provide the sub-titled product which was used in the next reaction without further purification. LC/MS m/z 406.1 [M+H]+.
Reaction SMILES: [CH3:1][C:2]1[O:3][C:4]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)=[CH:5][C:6](=[O:8])[CH:7]=1.[Na].[Cl:16][C:17]1[CH:24]=[CH:23][C:20]([CH:21]=O)=[CH:19][CH:18]=1>[O-]CC.[Na+].C(O)C>[Cl:16][C:17]1[CH:24]=[CH:23][C:20]([CH:21]=[CH:1][C:2]2[O:3][C:4]([C:9]3[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=3)=[CH:5][C:6](=[O:8])[CH:7]=2)=[CH:19][CH:18]=1
Reactant: Cc1cc(=O)cc(-c2ccccc2)o1
Reactant: O=Cc1ccc(Cl)cc1
Agent: CC[O-]
Agent: [Na+]
Agent: [Na]
Solvent: CCO
Product: O=c1cc(C=Cc2ccc(Cl)cc2)oc(-c2ccccc2)c1
Temperature: 25 °C
Reaction time: 24 h

Procedure:
2-Methyl-6-phenyl-4H-pyran-4-one (3.7 g) was dissolved in sodium ethoxide solution prepared by dissolving sodium (0.46 g) in ethanol (50 ml). A solution of 4-chlorobenzaldehyde (5.6 g) in ethanol (50 ml) was added and the mixture was stirred at room temperature for 24 hours. The solid which formed was recrystallised from ethanol to give the title product (mp 169°-171° C.).
Reaction SMILES: [F:1][CH:2]1[C:11]2[C:6](=[C:7]([C:12](OC)=[O:13])[CH:8]=[CH:9][CH:10]=2)[CH2:5][N:4]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:3]1.C(=O)=O.CC(C)=O.CC(C[AlH]CC(C)C)C>C1COCC1>[F:1][CH:2]1[C:11]2[C:6](=[C:7]([CH2:12][OH:13])[CH:8]=[CH:9][CH:10]=2)[CH2:5][N:4]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:3]1
Reactant: COC(=O)c1cccc2c1CN(C(=O)OC(C)(C)C)CC2F
Agent: CC(C)C[AlH]CC(C)C
Agent: O=C=O
Solvent: C1CCOC1
Solvent: CC(C)=O
Product: CC(C)(C)OC(=O)N1Cc2c(CO)cccc2C(F)C1
Temperature: 25 °C

Procedure:
To a flask containing 2-tert-butyl 8-methyl 4-fluoro-3,4-dihydroisoquinoline-2,8(1H)-dicarboxylate (24-6) (214 mg, 0.692 mmol), was added anhydrous THF (3.5 ml) then cooled to −78 C (dry ice/acetone bath) while stirring under an atmosphere of N2. Then added DIBAL-H (2.4 ml, 2.400 mmol) dropwise. The reaction mixture was then stirred at −78 C for ˜20 minutes, then warmed to room temperature. Followed by LC/MS. After 10 minutes at room temperature quenched by dropwise addition of saturated solution of Rochelle's Salt (Na+/K+ Tartrate) in water, then suspended in EtOAc, washed with saturated NaHCO3, then H2O, then brine; organics dried over Na2SO4, filtered & concentrated. Purification by silica gel chromatography (0-40%; isocratic @ 30% EtOAc/Hex; 24 g ISCO); desired fractions concentrated to yield tert-butyl 4-fluoro-8-(hydroxymethyl)-3,4-dihydroisoquinoline-2(1H)-carboxylate (24-7). HRMS [M+H]; calculated; 282.1500, observed; 282.1491.
Reaction SMILES: [N+:1]([O-:4])(O)=[O:2].S(=O)(=O)(O)O.[CH3:10][C:11]1([CH3:21])[C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[NH:13][C:12]1=[O:20]>>[CH3:10][C:11]1([CH3:21])[C:19]2[C:14](=[CH:15][CH:16]=[C:17]([N+:1]([O-:4])=[O:2])[CH:18]=2)[NH:13][C:12]1=[O:20]
Reactant: CC1(C)C(=O)Nc2ccccc21
Reactant: O=[N+]([O-])O
Agent: O=S(=O)(O)O
Product: CC1(C)C(=O)Nc2ccc([N+](=O)[O-])cc21
Reaction time: 0.5 h

Procedure:
A solution of 22 ml. fuming nitric acid in 200 ml. 80% sulphuric acid is added dropwise, with cooling, to a solution of 100 g. (0.62 mol) 3,3-dimethylindolin-2-one in 500 ml. 80% sulphuric acid. The reaction mixture is then stirred for about 30 minutes, poured on to ice, filtered with suction, washed with water and dried. Yield: 100 g. (78% of theory); m.p. 192°-196° C. (ethyl acetate/heptane).
Reaction SMILES: [Y:1].[H][H].[CH:4]([OH:7])([CH3:6])[CH3:5]>[Zn]>[CH3:5][CH:4]([CH3:6])[O-:7].[Y+3:1].[CH3:5][CH:4]([CH3:6])[O-:7].[CH3:5][CH:4]([CH3:6])[O-:7]
Reactant: CC(C)O
Reactant: [H][H]
Reactant: [Y]
Agent: [Zn]
Product: CC(C)[O-]
Product: [Y+3]
Yield: 10 %

Procedure:
The same reaction was done exactly the same way except no zinc was milled with the yttrium. The milled yttrium was reacted with isopropanol in the same way. There was very little evolution of hydrogen and work-up of the reaction solutions gave a yield of less than 10% for yttrium isopropoxide.
Reaction SMILES: [Cl:1][C:2]1[CH:18]=[CH:17][C:5]([CH2:6][C:7]2[C:8](=[O:16])[NH:9][C:10](SC)=[N:11][C:12]=2[CH3:13])=[CH:4][CH:3]=1.[CH3:19][C:20]1[NH:24][CH:23]=[N:22][C:21]=1[CH2:25][S:26][CH2:27][CH2:28][NH2:29]>>[ClH:1].[ClH:1].[CH3:19][C:20]1[NH:24][CH:23]=[N:22][C:21]=1[CH2:25][S:26][CH2:27][CH2:28][NH:29][C:10]1[NH:9][C:8](=[O:16])[C:7]([CH2:6][C:5]2[CH:4]=[CH:3][C:2]([Cl:1])=[CH:18][CH:17]=2)=[C:12]([CH3:13])[N:11]=1
Reactant: CSc1nc(C)c(Cc2ccc(Cl)cc2)c(=O)[nH]1
Reactant: Cc1[nH]cnc1CSCCN
Product: Cc1nc(NCCSCc2nc[nH]c2C)[nH]c(=O)c1Cc1ccc(Cl)cc1
Product: Cl

Procedure:
Reaction of 5-(4-chlorobenzyl)-6-methyl-2-methylthio-4-pyrimidone (1.95 g) with 2-(5-methyl-4-imidazolylmethylthio)ethylamine (1.19 g) by the method described in Example 1(ii) gave the title compound, m.p. 203°-206.5°. (Crystallised from ethanol).
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([CH:11]3[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]3)=[CH:7][NH:8]2)=[CH:4][CH:3]=1.[O:17]1[CH2:19][C@H:18]1[CH2:20][O:21][C:22]1[CH:30]=[CH:29][CH:28]=[C:27]2[C:23]=1[CH:24]=[CH:25][NH:26]2>CO.CS(C)=O>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([CH:11]3[CH2:16][CH2:15][N:14]([CH2:19][C@H:18]([OH:17])[CH2:20][O:21][C:22]4[CH:30]=[CH:29][CH:28]=[C:27]5[C:23]=4[CH:24]=[CH:25][NH:26]5)[CH2:13][CH2:12]3)=[CH:7][NH:8]2)=[CH:4][CH:3]=1
Reactant: c1cc(OC[C@@H]2CO2)c2cc[nH]c2c1
Reactant: Clc1ccc2c(C3CCNCC3)c[nH]c2c1
Solvent: CS(C)=O
Solvent: CO
Product: O[C@H](COc1cccc2[nH]ccc12)CN1CCC(c2c[nH]c3cc(Cl)ccc23)CC1

Procedure:
The title compound was prepared in a fashion similar to that described in Example 193 from 6-chloro-3-(piperidin-4-yl)-1H-indole (1.00 g, 4.3 mmol) and (S)-(+)-4-(oxiranylmethoxy)-1H-indole (0.81 g, 4.3 mmol). The product was isolated as a white foam. Yield 1.15 g (64%). mp 90°-95° C. FDMS m/e=423 (M+ of free base). α[D]589 =+8.81 (c=0.98, methanol/dimethylsulfoxide).
Reaction SMILES: [H-].[Na+].[CH3:3][O:4][C:5]1[C:11]2[S:12][CH:13]=[CH:14][C:10]=2[C:9](=O)[C:8]2[CH:16]=[CH:17][CH:18]=[CH:19][C:7]=2[CH:6]=1.O.Cl.[CH2:22]([O:24][C:25](=[O:27])[CH3:26])[CH3:23]>CS(C)=O.CN(C)C=O>[CH2:22]([O:24][C:25](=[O:27])[CH:26]=[C:9]1[C:10]2[CH:14]=[CH:13][S:12][C:11]=2[C:5]([O:4][CH3:3])=[CH:6][C:7]2[CH:19]=[CH:18][CH:17]=[CH:16][C:8]1=2)[CH3:23]
Reactant: CCOC(C)=O
Reactant: COc1cc2ccccc2c(=O)c2ccsc12
Agent: Cl
Agent: [H-]
Agent: [Na+]
Solvent: CS(C)=O
Solvent: O
Solvent: CN(C)C=O
Product: CCOC(=O)C=C1c2ccccc2C=C(OC)c2sccc21
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
21.6 g pre-dried NaH are suspended in 0.9 l dimethylsulfoxide and 200 g ethoxycarbonylmethylen-diethylphosphonate [(C2H5O)2POCH2COOC2H5 ] are added drop-wise over ca. 1 hour, the temperature being maintained at ca. 25°-30° C. by light cooling. The obtained mixture is then stirred for 30 minutes at room temperature and 121 g 10-methoxy-4H-benzo[4,5]cyclohepta[1,2-b]thiophen-4-one dissolved with warming in 0.9 l dimethylformamide are then added in a single portion. The obtained reaction mixture is stirred for ca. 17 hours at ca. 95° C. under argon, and then stirred into a mixture of 7 l H2O/3 kg ice and 50 ml conc. HCl covered with a layer of 2 l ethylacetate. The organic phase is separated off and the aqueous phase extracted 3× with 2 l and 3× with 1 l ethyl acetate. The combined organic phases are washed 3× with 2 l H2O and 3× with 2 l saline, dried with MgSO4, filtered under suction and concentrated on a rotary evaporator to yield the title compound as a (Z,E)-isomer mixture: m.p.=91°-93° C.
Reaction SMILES: [Cl:1][C:2]1[C:7]([O:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)=[CH:6][CH:5]=[CH:4][C:3]=1[C:15]1[O:16][CH2:17][C:18]([CH3:21])([CH3:20])[N:19]=1.C[I:23].[CH3:24]COCC>[N+](C)([O-])=O>[I-:23].[Cl:1][C:2]1[C:7]([O:8][C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=2)=[CH:6][CH:5]=[CH:4][C:3]=1[C:15]1[O:16][CH2:17][C:18]([CH3:21])([CH3:20])[N+:19]=1[CH3:24]
Reactant: CI
Reactant: CCOCC
Reactant: CC1(C)COC(c2cccc(Oc3ccccc3)c2Cl)=N1
Solvent: C[N+](=O)[O-]
Product: C[N+]1=C(c2cccc(Oc3ccccc3)c2Cl)OCC1(C)C
Product: [I-]

Procedure:
2-(2-Chloro-3-phenoxyphenyl)-4,4-dimethyl-4,5-dihydrooxazole (2.80 g, 9.28 mmol) was heated with methyl iodide (1.8 mL) in nitromethane (4.0 mL) for 24 hr, (bath temp ca 70° C.). The brown solution was allowed to cool and Et2O was added until a slight cloudiness was observed. Crystallization commenced almost immediately and the mixture was allowed to stand in the freezer overnight. Large off-white crystals of the product: 2-(2-chloro-3-phenoxyphenyl)-3,4,4-trimethyl-4,5-dihydrooxazolium iodide were obtained. 3.51 g, (85%).
Reaction SMILES: C(Cl)(Cl)Cl.Cl.[CH3:6][O:7][C:8]1[CH:9]=[C:10]([CH:15]=[CH:16][C:17]=1[O:18][CH2:19][C:20]1[CH:25]=[CH:24][C:23]([CH2:26][N:27]2[C:31](=[O:32])[C:30]3=[CH:33][CH:34]=[CH:35][CH:36]=[C:29]3[C:28]2=[O:37])=[CH:22][CH:21]=1)[C:11](=[NH:14])OC.[NH3:38]>CO>[CH3:6][O:7][C:8]1[CH:9]=[C:10]([CH:15]=[CH:16][C:17]=1[O:18][CH2:19][C:20]1[CH:25]=[CH:24][C:23]([CH2:26][N:27]2[C:28](=[O:37])[C:29]3=[CH:36][CH:35]=[CH:34][CH:33]=[C:30]3[C:31]2=[O:32])=[CH:22][CH:21]=1)[C:11]([NH2:14])=[NH:38]
Reactant: COC(=N)c1ccc(OCc2ccc(CN3C(=O)c4ccccc4C3=O)cc2)c(OC)c1
Reactant: N
Agent: Cl
Solvent: ClC(Cl)Cl
Solvent: CO
Product: COc1cc(C(=N)N)ccc1OCc1ccc(CN2C(=O)c3ccccc3C2=O)cc1
Reaction time: 24 h

Procedure:
To a mixture of 100 ml of chloroform and 100 ml of anhydrous methanol, was added 3.0 g of methyl 3-methoxy-4-(4-phthalimidomethylbenzyloxy)benzimidate hydrochloride followed by 16 ml of a methanol solution of anhydrous ammonia (22 mg/ml). The mixture was stirred for 24 hours and then evaporated to dryness. The residue was dissolved in methanol, then poured into a large volume of chloroform, and filtered from precipitated colorless solids. The filtrate was evaporated to dryness and the residue was recrystallized from methanol to yield 1.4 g of 3-methoxy-4-(4-phthalimidomethylbenzyloxy)benzamidine; m.p. 228°-230° C. To obtain a methanesulfonate, the above benzamidine compound was suspended in methanol and admixed with an excess of methanesulfonic acid. Upon addition of ether to the resulting solution, there was obtained a colorless solid which was recrystallized from methanol to yield colorless needle crystals of 3-methoxy-4-(4-phthalimidomethylbenzyloxy)benzamidine methanesulfonate; m.p. 174°-176° C.
Reaction SMILES: [H-].[Na+].[CH:3]1([OH:9])[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1.Br[CH2:11][C:12]([OH:14])=[O:13].O>O1CCCC1>[CH:3]1([O:9][CH2:11][C:12]([OH:14])=[O:13])[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1
Reactant: O=C(O)CBr
Reactant: OC1CCCCC1
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: O
Product: O=C(O)COC1CCCCC1
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 842.1 %

Procedure:
To a suspension of 60% sodium hydride (8.79 g) in tetrahydrofuran (500 mL) was added cyclohexanol (10 g) and the mixture was stirred at 0° C. for 0.5 hour. To the mixture was added bromoacetic acid (13.9 g) under ice-water cooling and the mixture was heated under reflux for 2 hours. After adding water to the mixture and organic solvent was evaporated in vacuo. The aqueous solution was diluted with water, washed with ether, acidified with 1 N hydrochloric acid, and extracted with ether. The organic layer was separated, dried over magnesium sulfate, and evaporated in vacuo to give (cyclohexyloxy)acetic acid as colorless oil (133 g).
Reaction SMILES: Cl.[Cl-].[N:3]1[CH:8]=[CH:7][CH2+:6]=[CH:5][CH:4]=1.[CH3:9][O:10][C:11]1[CH:16]=[CH:15][C:14]([NH2:17])=[CH:13][CH:12]=1>N1C=CC=CC=1>[CH3:9][O:10][C:11]1[CH:16]=[CH:15][C:14]([NH:17][C:6]2[CH:7]=[CH:8][N:3]=[CH:4][CH:5]=2)=[CH:13][CH:12]=1
Reactant: COc1ccc(N)cc1
Reactant: C1=CN=CC=[CH2+]1
Agent: Cl
Agent: [Cl-]
Solvent: c1ccncc1
Product: COc1ccc(Nc2ccncc2)cc1
Temperature: 25 °C

Procedure:
A mixture of 1-(4-pyridinium chloride hydrochloride (10.0 g, 0.04 mol) and p-anisidine (4.9 g, 0.04 mol) is heated at 150° C. until the pyridine stops distilling. The resulting black oil is allowed to cool to room temperature during which time it solidifies. The solid is broken into a powder and repeatedly washed with acetone until the color is light brown. Recrystallization from isopropanol gives the product as a yellow powder, mp 129°-134° C.
Reaction SMILES: Cl.[C@H:2]12[CH2:8][C@H:5]([NH:6][CH2:7]1)[CH2:4][N:3]2[CH2:9][C:10]1[CH:25]=[CH:24][C:13]([O:14][C:15]2[S:16][C:17]3[CH:23]=[CH:22][CH:21]=[CH:20][C:18]=3[N:19]=2)=[CH:12][CH:11]=1.[C:26](O)(=[O:29])[CH2:27][OH:28].Cl.CN(C)CCCN=C=NCC.CCN(CC)CC>C(Cl)Cl>[S:16]1[C:17]2[CH:23]=[CH:22][CH:21]=[CH:20][C:18]=2[N:19]=[C:15]1[O:14][C:13]1[CH:12]=[CH:11][C:10]([CH2:9][N:3]2[CH2:4][C@@H:5]3[CH2:8][C@H:2]2[CH2:7][N:6]3[C:27](=[O:28])[CH2:26][OH:29])=[CH:25][CH:24]=1
Reactant: O=C(O)CO
Reactant: c1ccc2sc(Oc3ccc(CN4C[C@@H]5C[C@H]4CN5)cc3)nc2c1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: O=C(CO)N1C[C@@H]2C[C@H]1CN2Cc1ccc(Oc2nc3ccccc3s2)cc1
Temperature: 25 °C
Reaction time: 16 h
Yield: 55.3 %

Procedure:
To a stirred suspension of (S,S)-2-[4-(2,5-diaza-bicyclo[2.2.1]hept-2-ylmethyl)-phenoxy]-benzothiazole hydrochloride (1.6 g, 3.9 mmol), glycolic acid (600 mg, 7.8 mmol), and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (1.5 g, 7.8 mmol) in CH2Cl2 (15 mL) was added Et3N (2.7 mL, 19.5 mmol). The resulting solution was then stirred at rt for 16 h. The resulting white suspension was partitioned between CH2Cl2 (600 mL) and satd. aq. NaHCO3 (100 mL). The organic layer was separated, dried (Na2SO4), filtered and concentrated. Purification by silica gel flash chromatography (0% to 5% CH3OH in CH2Cl2) afforded the title compound as a white solid (853 mg, 55%). MS (ESI): mass calcd. for C21H21N3O3S, 395.13; m/z found, 396.2 [M+H]+. 1H NMR (500 MHz, CDCl3, mixture of rotamers): 7.73 (d, J=8.5 Hz, 1H), 7.67 (d, J=8.0 Hz, 1H), 7.41 (m, 2H), 7.38 (m, 1H), 7.32 (br m, 2H), 7.28 (m, 1H), 4.83 (br m, 0.5H), 4.21 (br d, J=14.5 Hz, 0.5H), 4.10-3.99 (br m, 2H), 3.80 (br d, J=11.7 Hz, 0.5H), 3.76 (d, J=13.8 Hz, 2H), 3.61 (br s, 1H), 3.50 (br s, 0.5H), 3.48-3.45 (m, 0.5H), 3.42 (br s, 0.5H), 3.39-3.35 (m, 0.5H), 3.23 (dd, J=9.2, 2.3 Hz, 0.5H), 3.01 (dd, J=9.7, 2.1 Hz, 0.5H), 2.90 (dd, J=9.8, 2.2 Hz, 0.5H), 2.81-2.77 (m, 0.5H), 2.58 (dd, J=9.7, 1.2 Hz, 0.5H), 2.07-2.01 (m, 0.5H), 2.00-1.96 (m, 0.5H), 1.80 (d, J=9.8 Hz, 0.5H), 1.70 (d, J=10.0 Hz, 0.5H).
Reaction SMILES: [C:1]([O:4][C@H:5]1[C@H:9]([O:10][C:11](=[O:13])[CH3:12])[C@@H:8]([CH2:14][O:15][Si:16]([CH:23]([CH3:25])[CH3:24])([CH:20]([CH3:22])[CH3:21])[CH:17]([CH3:19])[CH3:18])[O:7][C@H:6]1[N:26]1[CH:34]=[N:33][C:32]2[C:27]1=[N:28][CH:29]=[N:30][C:31]=2N)(=[O:3])[CH3:2].C[Si]([Br:40])(C)C.C(ON=O)(C)(C)C.C(=O)(O)[O-].[Na+]>BrCBr.ClCCl>[C:1]([O:4][C@H:5]1[C@H:9]([O:10][C:11](=[O:13])[CH3:12])[C@@H:8]([CH2:14][O:15][Si:16]([CH:23]([CH3:25])[CH3:24])([CH:20]([CH3:22])[CH3:21])[CH:17]([CH3:19])[CH3:18])[O:7][C@H:6]1[N:26]1[CH:34]=[N:33][C:32]2[C:27]1=[N:28][CH:29]=[N:30][C:31]=2[Br:40])(=[O:3])[CH3:2]
Reactant: CC(=O)O[C@H]1[C@H](OC(C)=O)[C@@H](CO[Si](C(C)C)(C(C)C)C(C)C)O[C@H]1n1cnc2c(N)ncnc21
Reactant: C[Si](C)(C)Br
Agent: CC(C)(C)ON=O
Agent: O=C([O-])O
Agent: [Na+]
Solvent: BrCBr
Solvent: ClCCl
Product: CC(=O)O[C@H]1[C@H](OC(C)=O)[C@@H](CO[Si](C(C)C)(C(C)C)C(C)C)O[C@H]1n1cnc2c(Br)ncnc21
Reaction time: 2.5 h
Yield: 59.1 %

Procedure:
(2R,3S,4R,5R)-2-(6Amino-9H-purin-9-yl)-5-{[(triisopropylsilyl)oxy]methyl}-tetrahydrofuran-3,4-diyl diacetate (0.605 g, 1.19 mmol) was dissolved in dibromomethane (24 mL). Trimethylsilyl bromide (0.17 mL, 1.35 mmol) was added dropwise followed by tert-butylnitrite (0.97 mL, 8.12 mmol). The orange solution was stirred for 2.5 hours then slowly poured into a 1:1 mixture of saturated sodium bicarbonate and dichloromethane and extracted. The pale yellow organic layer was washed with water and brine, dried (Na2SO4), filtered and concentrated. The yellow solid was purified by flash chromatography eluting with 25% ethyl acetate/hexanes to give the title compound as a yellow solid (0.402 g, 52%).
Reaction SMILES: [H-].[Na+].[C:3]([O:7][C:8](=[O:29])[NH:9][C:10]1[S:11][C:12]([C:15]2[CH:20]=[CH:19][N:18]=[C:17]([NH:21][C:22]3[CH:23]=[C:24]([CH3:28])[CH:25]=[CH:26][CH:27]=3)[N:16]=2)=[CH:13][CH:14]=1)([CH3:6])([CH3:5])[CH3:4].[CH3:30]I>C1COCC1>[C:3]([O:7][C:8](=[O:29])[N:9]([CH3:30])[C:10]1[S:11][C:12]([C:15]2[CH:20]=[CH:19][N:18]=[C:17]([NH:21][C:22]3[CH:23]=[C:24]([CH3:28])[CH:25]=[CH:26][CH:27]=3)[N:16]=2)=[CH:13][CH:14]=1)([CH3:6])([CH3:5])[CH3:4]
Reactant: CI
Reactant: Cc1cccc(Nc2nccc(-c3ccc(NC(=O)OC(C)(C)C)s3)n2)c1
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: Cc1cccc(Nc2nccc(-c3ccc(N(C)C(=O)OC(C)(C)C)s3)n2)c1
Reaction time: 0.25 h

Procedure:
Sodium hydride (60% disersion in mineral oil) (21.4 mg, 0.535 mmol) was added to a solution of [5-(2-m-tolylamino-pyrimidin-4-yl)-thiophen-2-yl]-carbamic acid tert-butyl ester (186 mg, 0.486 mmol) in anhydrous THF (5 mL) at ice bath temperature. After 15 minutes, MeI was added and the mixture was removed from the ice bath. Additional NaH (7.7 mg, 0.19 mmol) and MeI (9.0 uL, 0.145 mmol) were added after 5 hours and the reaction was stirred 3 days. The reaction was quenched by addition of a few drops of water and was concentrated to dryness and taken to the next step without further purification. MS: m/z 397 (M+H+).
Reaction SMILES: O1[CH:7]2[CH:2]1[C:3]([CH3:18])([CH3:17])[O:4][C:5]1[CH:11]=[CH:10][C:9]([CH:12]3CCCC3)=[CH:8][C:6]=12.C([N:21](CC)CC)C.[Cl:26][CH2:27][C:28](Cl)=[O:29]>ClCCl>[Cl:26][CH2:27][C:28]([NH:21][CH:7]1[C:6]2[CH:8]=[C:9]([CH3:12])[CH:10]=[CH:11][C:5]=2[O:4][C:3]([CH3:17])([CH3:18])[CH2:2]1)=[O:29]
Reactant: CCN(CC)CC
Reactant: O=C(Cl)CCl
Reactant: CC1(C)Oc2ccc(C3CCCC3)cc2C2OC21
Solvent: ClCCl
Product: Cc1ccc2c(c1)C(NC(=O)CCl)CC(C)(C)O2
Reaction time: 16 h
Yield: 78 %

Procedure:
To a solution of 4-amino-3,4-dihydro-2,2,6-dimethyl-2H-1-benzopyran (1.63 g, described in Khim. Geterot. Soed. 5 (3), 434, 1969) in 40 ml dichloromethane at 0° C. was added triethylamine (1.2 ml) followed by chloroacetyl chloride (0.96 g). The solution was stirred for 16 h then washed with saturated brine solution, separated, dried (MgSO4) and concentrated to a cream solid. Chromatography (silica, CH2Cl2 eluent) provided 4-chloroacetamido-3,4-dihydro-2,2,6-trimethyl-2H-1-benzopyran (1.78 g, 78%) as a white solid. m.p. 147°-148° C.
Reaction SMILES: [N:1]1([C:7](=[O:31])[CH:8]=[CH:9][C:10]2[CH:15]=[CH:14][C:13]([NH:16][CH2:17][C:18]3[CH:23]=[CH:22][C:21]([O:24][CH:25]4[CH2:30][CH2:29][CH2:28][CH2:27][O:26]4)=[CH:20][CH:19]=3)=[CH:12][CH:11]=2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.C(N(CC)CC)C.[CH3:39][O:40][C:41]1[CH:46]=[CH:45][C:44]([S:47](Cl)(=[O:49])=[O:48])=[CH:43][CH:42]=1.O>C(Cl)Cl>[CH3:39][O:40][C:41]1[CH:42]=[CH:43][C:44]([S:47]([N:16]([C:13]2[CH:12]=[CH:11][C:10]([CH:9]=[CH:8][C:7]([N:1]3[CH2:6][CH2:5][O:4][CH2:3][CH2:2]3)=[O:31])=[CH:15][CH:14]=2)[CH2:17][C:18]2[CH:23]=[CH:22][C:21]([O:24][CH:25]3[CH2:30][CH2:29][CH2:28][CH2:27][O:26]3)=[CH:20][CH:19]=2)(=[O:49])=[O:48])=[CH:45][CH:46]=1
Reactant: O=C(C=Cc1ccc(NCc2ccc(OC3CCCCO3)cc2)cc1)N1CCOCC1
Reactant: COc1ccc(S(=O)(=O)Cl)cc1
Solvent: O
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: COc1ccc(S(=O)(=O)N(Cc2ccc(OC3CCCCO3)cc2)c2ccc(C=CC(=O)N3CCOCC3)cc2)cc1
Temperature: 25 °C
Reaction time: 60 h

Procedure:
To a solution of 1-morpholin-4-yl-3-{4-[4-(tetrahydro-pyran-2-yloxy)benzylamino]-phenyl}-prop-2-en-1-one (0.115 g, 0.27 mmol) and triethylamine (0.100 mL, 0.72 mmol) in 3 mL methylene chloride was added 4-methoxybenzenesulfonyl chloride (0.065 g, 0.31 mmol). The reaction mixture was stirred at room temperature for 60 h. Water was added and the aqueous solution was washed with methylene chloride (3×). The combined organic layers were dried (magnesium sulfate) and concentrated. Medium pressure silica gel chromatography (50% ethyl acetate/hexanes) gave the title compound of Step B.
Reaction SMILES: [C:1]([O:12][CH3:13])(=[O:11])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH:9]=[CH2:10].[C:14]([O:27][CH3:28])(=[O:26])[CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21]C=CCC.OCP(CO)CO>C1(C)C=CC=CC=1>[C:14]([O:27][CH3:28])(=[O:26])[CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH:10]=[CH:9][CH2:8][CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2][C:1]([O:12][CH3:13])=[O:11]
Reactant: CCC=CCCCCCCCC(=O)OC
Reactant: C=CCCCCCCCC(=O)OC
Agent: OCP(CO)CO
Solvent: Cc1ccccc1
Product: COC(=O)CCCCCCCC=CCCCCCCCC(=O)OC
Temperature: 60 °C
Reaction time: 0.29 h

Procedure:
A dibasic ester composition is produced in accordance with the exemplary procedure below, including a cross-metathesis reaction between methyl 9-decenoate (9-decenoic acid methyl ester, 9-DAME) and methyl 9-dodecenoate (9-dodecenoic acid methyl ester, 9-DDAME). A 1.0:1.0 mole ratio mixture of 9-DAME and 9-DDAME (332 g) is charged to a 1 L round bottom flask and heated to 60° C. Pressure is adjusted to 100 mg Hg with ChemGlass diaphragm vacuum pump model CG-4812-30/and J-Kem Scientific Digital Vacuum Regulator Model 200 and stirring is initiated with a magnetic stir bar. After the system stabilizes at desired conditions, 80 ppm of C-827 (as toluene solution) is added (t=0 min). At approximately 15-20 min, the reaction starts bubbling vigorously and the pressure rises to approximately 500 mm Hg. Pressure restabilizes at 100 mm Hg after approximately 5-10 more minutes. At 180 min, an additional 40 ppm of the catalyst C-827 (as toluene solution) is added. Subsequently, the catalyst is deactivated with 25 equivalents tris hydroxymethyl phosphine (THMP) to C-827 at 80° C. for 120 min, THMP. The catalyst is then removed by water extraction (5:1 oil to water). The composition is dried with MgSO4. Then, light FAME stripping is conducted at 1 mm Hg and approximately 100° C. The products from this reaction include a large fraction of 18:1 dibasic ester.