Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C:2]([O:5][C:6]([NH:8][C@H:9]([C:17]([OH:19])=O)[CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)=[O:7])([CH3:4])[CH3:3].CN1CCOCC1.C(OC(Cl)=O)C(C)C.[N+:35](=[CH2:37])=[N-:36]>O1CCCC1.CCOCC.CO>[CH3:4][C:2]([O:5][C:6]([NH:8][C@@H:9]([CH2:10][C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1)[C:17](=[O:19])[CH:37]=[N+:35]=[N-:36])=[O:7])([CH3:1])[CH3:3]
Reactant: C=[N+]=[N-]
Reactant: CC(C)(C)OC(=O)N[C@@H](Cc1ccccc1)C(=O)O
Agent: CC(C)COC(=O)Cl
Solvent: CCOCC
Solvent: CO
Solvent: CN1CCOCC1
Product: CC(C)(C)OC(=O)N[C@@H](Cc1ccccc1)C(=O)C=[N+]=[N-]
Temperature: -25 °C
Reaction time: 0.17 h

Procedure:
A solution of N-[[(1,1-dimethylethyl)oxy]carbonyl]-L-phenylalanine (20.01 g., 75 mmol) in 150 mL of dry tetrahydrofuran was chilled to -25° C. and treated with N-methylmorpholine (8.3 mL, 75 mmol) and isobutylchloroformate (9.8 mL, 75 mmol) and then stirred at -25° C. for 10 minutes. The reaction mixture was then filtered into a flask containing a solution of diazomethane (prepared from 35.48 g., 240 mmol of N-methyl-N'-nitro-N-nitrosoguanidine) in 300 mL of anhydrous ether at -78° C. and then let warm to -5° C. and stirred overnight. The cold reaction mixture was then filtered and the filtrate was washed with water, saturated sodium bicarbonate, and brine. The organic layer was dried (MgSO4), filtered and concentrated in vacuo to yield a reddish brown oil. The oil was triturated with cold petroleum ether to yield 14.42 g. of a light tan solid. The mother liquors were concentrated and allowed to stand yielding a second crop of 1.96 g. of light yellow crystals for a total yield of 16.38 g. of the title A compound as a tannish solid; m.p. 87°-90° C. [α]D =-32.2° (c=1.15, methanol).
Reaction SMILES: [NH2:1][C:2]1[C:3]([F:10])=[C:4]([CH:7]=[CH:8][CH:9]=1)[C:5]#[N:6].[CH3:11][N:12]([CH3:22])[C:13]1[CH:21]=[CH:20][C:16]([C:17](Cl)=[O:18])=[CH:15][CH:14]=1.N1C=CC=CC=1>ClCCCl.C(OCC)(=O)C>[C:5]([C:4]1[C:3]([F:10])=[C:2]([NH:1][C:17](=[O:18])[C:16]2[CH:15]=[CH:14][C:13]([N:12]([CH3:11])[CH3:22])=[CH:21][CH:20]=2)[CH:9]=[CH:8][CH:7]=1)#[N:6]
Reactant: N#Cc1cccc(N)c1F
Reactant: CN(C)c1ccc(C(=O)Cl)cc1
Solvent: ClCCCl
Solvent: c1ccncc1
Solvent: CCOC(C)=O
Product: CN(C)c1ccc(C(=O)Nc2cccc(C#N)c2F)cc1
Temperature: 70 °C
Yield: 88.2 %

Procedure:
To a mixture of 3-amino-2-fluorobenzonitrile (2.24 g, 16.46 mmol) and 4-(dimethylamino)benzoyl chloride (3.46 g, 18.84 mmol) in 1,2-dichloroethane (50 mL) at rt was added pyridine (0.891 mL, 11.02 mmol). The resulting mixture was heated at 70° C. for 5 hr. On cooling to room temperature, the mixture was diluted with ethyl acetate (250 mL), washed with water (5×60 mL) and brine (60 mL), and dried over anhydrous MgSO4. The organic solution was concentrated under vacuum, and the residue was subjected to ISCO (2×330 g silica gel, 25-50% ethyl acetate/hexane) to afford the desired product (4.11 g, 14.51 mmol, 88% yield) as a white solid.
Reaction SMILES: [N:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[NH:3][CH:2]=1.[H-].[Na+].[Br:12][CH2:13][CH2:14][CH2:15]Br>CN(C=O)C>[Br:12][CH2:13][CH2:14][CH2:15][N:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[CH:2]1
Reactant: c1ccc2[nH]cnc2c1
Reactant: BrCCCBr
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: BrCCCn1cnc2ccccc21
Reaction time: 0.5 h
Yield: 73.9 %

Procedure:
To a solution of benzimidazol (355 mg, 3.00 mmol) in dry DMF (10 mL) was added NaH (83 mg, 3.3 mmol) at 20° C. under N2 atmosphere. The reaction mixture was stirred for 30 min, and then 1,3-dibromopropane (1.82 g, 9.00 mmol) was added and stirres for additional 15 h at 20° C. The reaction was quenched by addition of H2O, and the product was extracted with EtOAc. The organic solution was then washed with H2O and brine, dried over MgSO4, filtered and concentrated in vacuo. 1-(3-Bromo-1-propyl)benzimidazole (530 mg, 74%) was isolated by flash chromatography on a silica gel column by elution with EtOAc/Hexanes a pale yellow oil. 1H NMR (CDCl3, 300 MHz) δ2.40 (qu, 2H, J=6.6 Hz), 3.33 (t, 2H, J=6.2 Hz), 4.42 (t, 2H, J=6.6 Hz), 7.12-7.20 (m, 1H), 7.27-7.48 (m, 2H), 7.43-7.49 (m, 1H), 7.78-7.86 (m, 1H) ppm.
Reaction SMILES: [CH3:1][C:2]([CH3:23])([CH3:22])[C:3]([NH:5][C:6]1[CH:11]=[CH:10][C:9]([Cl:12])=[CH:8][C:7]=1[CH:13]1[CH2:21][C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[NH:14]1)=[O:4].CCN(CC)CC.[C:31](OC(=O)C)(=[O:33])[CH3:32]>C(Cl)Cl>[CH3:1][C:2]([CH3:23])([CH3:22])[C:3]([NH:5][C:6]1[CH:11]=[CH:10][C:9]([Cl:12])=[CH:8][C:7]=1[CH:13]1[CH2:21][C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[N:14]1[C:31](=[O:33])[CH3:32])=[O:4]
Reactant: CC(=O)OC(C)=O
Reactant: CC(C)(C)C(=O)Nc1ccc(Cl)cc1C1Cc2ccccc2N1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CC(=O)N1c2ccccc2CC1c1cc(Cl)ccc1NC(=O)C(C)(C)C
Temperature: 25 °C

Procedure:
To a solution of 3.38 g 2,2-dimethyl-N-[2-(2,3-dihydro-1H-indol-2-yl)-4-chlorophenyl]propanamide in 40 ml CH2Cl2 at 10° C. were added 12.7 ml Et3N and then dropwise 6.59 ml acetic anhydride. The resulting mixture was stirred twenty-four hours at room temperature. The reaction was quenched with water (30 ml). The organic phase was separated, washed with 5% HCl, water, 7.5% NaHCO3 and sat. NaCl (1×), and dried (MgSO4). Concentration, trituration with hexane and recrystallization from cyclohexane gave 2.10 g solid, m.p. 131°-134° C.
Reaction SMILES: [H-].[Na+].[Br:3][C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[NH:9][CH:8]=[CH:7]2.[CH3:13][Si:14]([CH3:21])([CH3:20])[CH2:15][CH2:16][O:17][CH2:18]Cl.[Cl-].[NH4+]>O1CCCC1.CCOCC>[Br:3][C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[N:9]([CH2:18][O:17][CH2:16][CH2:15][Si:14]([CH3:21])([CH3:20])[CH3:13])[CH:8]=[CH:7]2
Reactant: Brc1ccc2[nH]ccc2c1
Reactant: C[Si](C)(C)CCOCCl
Agent: [Cl-]
Agent: [H-]
Agent: [NH4+]
Solvent: C1CCOC1
Solvent: CCOCC
Product: C[Si](C)(C)CCOCn1ccc2cc(Br)ccc21
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 66.1 %

Procedure:
To a suspension of sodium hydride (0.27 g, 6.6 mmol) in tetrahydrofuran (10 mL) at 0° C. was added 5-bromoindole (1.0 g, 5.1 mmol). The reaction was stirred for 30 min at room temperature, then cooled to 0° C. and 2-(trimethylsilyl)ethoxymethyl chloride (1.0 mL, 5.6 mmol) was added. The solution was stirred for 2 h at room temperature. The reaction mixture was poured into saturated aqueous ammonium chloride solution and diluted with ether. The layers were separated and the aqueous layer was extracted (2×100 mL ether). The combined organic layers were washed with brine, dried (magnesium sulfate), filtered and concentrated in vacuo. Column chromatography (silica gel, 20:1 hexanes/ethyl acetate) gave 1.1 g (66%) of 5-bromo-1-({[2-(trimethylsilyl)ethyl]oxy}methyl)-1H-indole. 1H NMR (400 MHz, CDCl3): 7.81 (d, 1H), 7.42 (d, 1H), 7.38 (dd, 1H), 7.23 (d, 1H), 6.52 (dd, 1H), 5.51 (s, 2H), 3.60 (m, 2H), 0.93 (m, 2H), 0.00 (s, 9H); MS (EI) for C14H20NOSiBr: 209 (M-OCH2CH2Si(CH3)3).
Reaction SMILES: [CH3:1][O:2][CH2:3][O:4][CH2:5][C:6]1[N:7]=[C:8]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[O:9][CH:10]=1.C([Li])CCC.CN(C)[CH:24]=[O:25].Cl>CCCCCC.C(OCC)C>[CH3:1][O:2][CH2:3][O:4][CH2:5][C:6]1[N:7]=[C:8]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[O:9][C:10]=1[CH:24]=[O:25]
Reactant: CN(C)C=O
Reactant: COCOCc1coc(-c2ccccc2)n1
Agent: Cl
Agent: [Li]CCCC
Solvent: CCOCC
Solvent: CCCCCC
Product: COCOCc1nc(-c2ccccc2)oc1C=O
Temperature: -78 °C
Reaction time: 1.5 h
Yield: 52.7 %

Procedure:
To a mixture of 4-methoxymethoxymethyl-2-phenyloxazole (10.86 g) and diethyl ether (300 mL) was dropwise added a solution (1.6 M, 37 mL) of n-butyl lithium in hexane at −78° C., and the mixture was stirred at −78° C. for 1.5 hrs. A solution (10 mL) of N,N-dimethylformamide (6.50 g) in diethyl ether was added to the reaction mixture and the reaction mixture was allowed to warm to room temperature with stirring for 2 hrs. Dilute hydrochloric acid was added to the reaction mixture and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated. The obtained residue was subjected to silica gel column chromatography to give crystals (6.45 g, 53%) of 4-methoxymethoxymethyl-2-phenyl-5-oxazolecarbaldehyde from a fraction eluted with ethyl acetate-hexane (1:6, v/v). Recrystallization from ethyl acetate-hexane gave colorless prism crystals. melting point: 51-52° C.
Reaction SMILES: [C:1]1([CH2:7][N:8]2[CH2:13][CH2:12][NH:11][CH:10]([C:14]([NH2:16])=[O:15])[CH2:9]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl[CH2:18][CH2:19][CH2:20][CH:21]([C:29]1[CH:34]=[CH:33][C:32]([F:35])=[CH:31][CH:30]=1)[C:22]1[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=1.C(=O)([O-])[O-].[Na+].[Na+].[I-].[K+]>O.CC(C)CC(=O)C>[F:28][C:25]1[CH:24]=[CH:23][C:22]([CH:21]([C:29]2[CH:30]=[CH:31][C:32]([F:35])=[CH:33][CH:34]=2)[CH2:20][CH2:19][CH2:18][N:11]2[CH2:12][CH2:13][N:8]([CH2:7][C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)[CH2:9][CH:10]2[C:14]([NH2:16])=[O:15])=[CH:27][CH:26]=1
Reactant: Fc1ccc(C(CCCCl)c2ccc(F)cc2)cc1
Reactant: NC(=O)C1CN(Cc2ccccc2)CCN1
Agent: O=C([O-])[O-]
Agent: [I-]
Agent: [K+]
Solvent: CC(=O)CC(C)C
Solvent: O
Product: NC(=O)C1CN(Cc2ccccc2)CCN1CCCC(c1ccc(F)cc1)c1ccc(F)cc1
Temperature: 25 °C
Yield: 63.6 %

Procedure:
A mixture of 13.2 parts of 4-(phenylmethyl)-2-piperazinecarboxamide, 18.5 parts of 1,1'-(4-chlorobutylidene)bis[4-fluorobenzene], 14.8 parts of sodium carbonate, 0.1 parts of potassium iodide and 200 parts of 4-methyl-2-pentanone was stirred and refluxed for 72 hours using a water-separator. The reaction mixture was cooled to room temperature, filtered and the filtrate was evaporated. The oily residue was purified by column-chromatography over silica gel using a mixture of trichloromethane and methanol (97:3 by volume) as eluent. The pure fractions were collected and the eluent was evaporated. The residue was crystallized from 2,2'-oxybispropane. The product was filtered off and dried, yielding 17.7 parts (63.6%) of 1-[4,4-bis(4-fluorophenyl)butyl]-4-(phenylmethyl)-2-piperazinecarboxamide; mp. 79.2° C. (intermediate 46).
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]([NH:17][C:18]2[N:23]=[C:22]([C:24]([F:27])([F:26])[F:25])[CH:21]=[CH:20][N:19]=2)[CH:5]=[C:6](B2OC(C)(C)C(C)(C)O2)[CH:7]=1.Br[C:29]1[S:33][CH:32]=[N:31][CH:30]=1.C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH3:1][C:2]1[CH:3]=[C:4]([NH:17][C:18]2[N:23]=[C:22]([C:24]([F:26])([F:25])[F:27])[CH:21]=[CH:20][N:19]=2)[CH:5]=[C:6]([C:29]2[S:33][CH:32]=[N:31][CH:30]=2)[CH:7]=1
Reactant: Brc1cncs1
Reactant: Cc1cc(Nc2nccc(C(F)(F)F)n2)cc(B2OC(C)(C)C(C)(C)O2)c1
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: O=C([O-])[O-]
Solvent: C1COCCO1
Solvent: O
Product: Cc1cc(Nc2nccc(C(F)(F)F)n2)cc(-c2cncs2)c1
Temperature: 25 °C

Procedure:
To a solution of N-[3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-4-(trifluoromethyl)pyrimidin-2-amine (80 g, 211.08 mmol) in 1,4-dioxane (800 mL) was added 5-bromo-1,3-thiazole (28 g, 171.78 mmol), Pd(dppf)Cl2 (8 g, 10.62 mmol) and a solution of sodium carbonate (44.7 g, 421.70 mmol) in water (447 mL). The resulting solution was heated to reflux for 1 hour. Then it was allowed to cool to room temperature and was concentrated in vacuo. The residue was diluted with EtOAc (500 mL) and filtered. The filtrate was washed with brine (2×300 mL) and water (2×300 mL). The organic layer was dried over anhydrous sodium sulfate and concentrated in vacuo. The crude product was recrystallized from EtOAc:DCM in the ratio of 1:5 to afford a portion of product. The mother liquor was applied onto a silica gel column and eluted with dichloromethane/ethyl acetate (2:1) to afford N-[3-methyl-5-(1,3-thiazol-5-yl)phenyl]-4-(trifluoromethyl)pyrimidin-2-amine as a pale yellow solid. MS ESI calc'd for C15H12F3N4S [M+H]+ 337. found 337. 1H NMR (400 MHz, CD3COCD3) δ 9.21 (1H, s), 8.97 (1H, s), 8.84 (1H, d, J=4.8 Hz), 8.21 (2H, m), 7.64 (1H, s), 7.25-7.26 (2H, m), 2.41 (3H, s). rhSyk activity=+++.
Reaction SMILES: [OH:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6](=[O:24])[C:7]([C:16]3[CH:23]=[CH:22][C:19]([C:20]#[N:21])=[CH:18][CH:17]=3)=[C:8]([C:12]([F:15])([F:14])[F:13])[O:9]2)=[CH:4][CH:3]=1.[Si]([N:29]=[N+:30]=[N-:31])(C)(C)C>C1(C)C=CC=CC=1>[NH:29]1[C:20]([C:19]2[CH:22]=[CH:23][C:16]([C:7]3[C:6](=[O:24])[C:5]4[C:10](=[CH:11][C:2]([OH:1])=[CH:3][CH:4]=4)[O:9][C:8]=3[C:12]([F:15])([F:13])[F:14])=[CH:17][CH:18]=2)=[N:21][N:31]=[N:30]1
Reactant: N#Cc1ccc(-c2c(C(F)(F)F)oc3cc(O)ccc3c2=O)cc1
Reactant: C[Si](C)(C)N=[N+]=[N-]
Solvent: Cc1ccccc1
Product: O=c1c(-c2ccc(-c3nnn[nH]3)cc2)c(C(F)(F)F)oc2cc(O)ccc12

Procedure:
To a solution of 4-(7-hydroxy-4-oxo-2-(trifluoromethyl)-4H-chromen-3-yl)benzonitrile (50 mg, 0.15 mmol) in toluene (2 ml), was added TMSN3 (296 mg, 2.72 mmol) and Bu2SnO (10 mg, 0.045 mmol) at room temperature. The mixture was refluxed overnight. The volatiles were removed under reduced pressure. The residue was purified by prep-HPLC to afford desired product in Example 1 as a yellow powder (19.4 mg, 34.6%).
Reaction SMILES: [NH:1]1[CH2:5][CH2:4][C@@H:3]([NH:6][C:7](=[O:14])[O:8][C@H:9]2[CH2:13][CH2:12][O:11][CH2:10]2)[CH2:2]1.Cl[C:16]1[C:25]2[C:20](=[CH:21][CH:22]=[C:23]([F:26])[CH:24]=2)[N:19]=[C:18]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=2[OH:33])[N:17]=1.C(N(CC)CC)C>C(Cl)Cl>[F:26][C:23]1[CH:24]=[C:25]2[C:20](=[CH:21][CH:22]=1)[N:19]=[C:18]([C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=1[OH:33])[N:17]=[C:16]2[N:1]1[CH2:5][CH2:4][C@@H:3]([NH:6][C:7](=[O:14])[O:8][C@H:9]2[CH2:13][CH2:12][O:11][CH2:10]2)[CH2:2]1
Reactant: O=C(N[C@@H]1CCNC1)O[C@H]1CCOC1
Reactant: Oc1ccccc1-c1nc(Cl)c2cc(F)ccc2n1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: O=C(N[C@@H]1CCN(c2nc(-c3ccccc3O)nc3ccc(F)cc23)C1)O[C@H]1CCOC1
Temperature: 25 °C
Reaction time: 1 h
Yield: 66.3 %

Procedure:
A mixture of (S)-tetrahydrofuran-3-yl (R)-pyrrolidin-3-ylcarbamate (225 mg, 1.12 mmol), 2-(4-chloro-6-fluoroquinazolin-2-yl)phenol (250 mg, 0.86 mmol), and triethylamine (0.240 mL, 1.72 mmol) in CH2Cl2 (10 mL) was stirred at room temperature. The reaction was complete in one hour. The reaction was quenched with water, the aqueous layer was extracted twice with CH2Cl2, and the combined organic extracts were dried over MgSO4, filtered, and concentrated. Purification via silica gel chromatography using 0-10% EtOAc/CH2Cl2 gave (S)-tetrahydrofuran-3-yl (R)-1-(6-fluoro-2-(2-hydroxyphenyl)quinazolin-4-yl)pyrrolidin-3-ylcarbamate (250 mg, 66%). LC/MS: m/z 439.5 (M+H)+ at 2.40 min (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)). 1H NMR (400 MHz, DMSO-d6) δ 8.43 (dd, J=7.8, 1.5 Hz, 1H), 7.99 (d, J=2.6 Hz, 1H), 7.87-7.91 (m, 1H), 7.74-7.79 (m, 1H), 7.70 (d, J=6.2 Hz, 1H), 7.35-7.39 (m, 1H), 6.91-6.96 (m, 2H), 5.15 (s, 1H), 4.21-4.25 (m, 2H), 4.12-4.14 (m, 1H), 4.01-4.06 (m, 1H), 3.87-3.89 (m, 1H), 3.65-3.78 (m, 4H), 2.02-2.26 (m, 3H), 1.82-1.89 (m, 1H) ppm.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:14]=[CH:13][C:12]([S:15]([NH:18][CH:19]3[CH2:23][CH:22]([CH2:24][S:25][C:26]4[N:30]=[CH:29][NH:28][N:27]=4)[O:21][C:20]3=[O:31])(=[O:17])=[O:16])=[CH:11][CH:10]=2)=[CH:5][CH:4]=1.C[O:33]C1C=CC(C2C=CC(S(NC(CC3OC3)C(OC)=O)(=O)=O)=CC=2)=CC=1.CCN(CC)CC>C1C=CC=CC=1.O>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:10]=[CH:11][C:12]([S:15]([NH:18][CH:19]([CH2:23][CH:22]([OH:33])[CH2:24][S:25][C:26]3[N:30]=[CH:29][NH:28][N:27]=3)[C:20]([OH:21])=[O:31])(=[O:16])=[O:17])=[CH:13][CH:14]=2)=[CH:5][CH:4]=1
Reactant: COc1ccc(-c2ccc(S(=O)(=O)NC3CC(CSc4nc[nH]n4)OC3=O)cc2)cc1
Reactant: COC(=O)C(CC1CO1)NS(=O)(=O)c1ccc(-c2ccc(OC)cc2)cc1
Solvent: CCN(CC)CC
Solvent: O
Solvent: c1ccccc1
Product: COc1ccc(-c2ccc(S(=O)(=O)NC(CC(O)CSc3nc[nH]n3)C(=O)O)cc2)cc1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
3-[(4′-Methoxy[1,1′-biphenyl]-4-yl)sulfonyl]amino-2-oxo-5-[(1H-1,2,4-triazol-3-ylthio)methyl]-tetrahydrofuran: To a solution of methyl 2-[(4′-methoxy[1,1′-biphenyl]-4-yl)sulfonyl]amino-4,5-epoxypentanoate 1d (0.7 g, 1.79 mmol) in benzene (6 mL) and Et3N (0.33 mL, 2.3 mmol) at room temperature is added slowly 1H-1,2,4-mercaptotriazole (0.47 g, 4.48 mmol). The reaction mixture is stirred overnight at room temperature. Diluted with water, the mixture is extracted three times with EtOAc. The combined EtOAc layer is washed with water, brine, dried over MgSO4 and concentrated to an oil which is purified by column chromatography eluting with hexane/EtOAc (1:1) to give the desired product.
Reaction SMILES: [CH:1]1[CH:2]=[CH:3][C:4]([N:7]=[N:8][C:9]2[CH:10]=[CH:11][C:12]([OH:15])=[CH:13][CH:14]=2)=[CH:5][CH:6]=1.CCC(C(N)=O)(C(N)=O)C1C=CC=CC=1>>[CH:1]1[CH:2]=[CH:3][C:4]([NH:7][N:8]=[C:9]2[CH:10]=[CH:11][C:12](=[O:15])[CH:13]=[CH:14]2)=[CH:5][CH:6]=1
Reactant: Oc1ccc(N=Nc2ccccc2)cc1
Agent: CCC(C(N)=O)(C(N)=O)c1ccccc1
Product: O=C1C=CC(=NNc2ccccc2)C=C1

Procedure:
4-Phenylazophenol, [Solvent Yellow 7 (SY7)], a conventional yellow dye obtained from Aldrich Chemical Company in the amount of 10.3 mg was dissolved into a 10.01 g solution of monomers containing 66% PEA, 30.5% PEMA, and 3.3% BDDA by weight respectively giving a SY7 concentration of 0.103 wt %. After dissolving the SY7 into the monomer solution 52.3 mg of bis(4-tert-butylcyclohexylperoxy dicarbonate (Perkadox-16, AZKO Corp.) was added as the polymerization iniator (catalyst). One mm thick sheets were made by placing the SY7 monomer solution via syringe into a mold formed between two glass plates and a 1 mm Teflon gasket. The glass plates were held together with metal clips. Polymerization was effected by placing the mold into a 65° C. oven and curing for 17 hours. The temperature of the oven was raised to 100° C. and the mold heated for 3 hours to effect post-cure of the sheetstock. Approximately 1×2 cm. rectangles were cut from the sheet and the UV/visible measurements performed. The curve exhibited a strong attentuation of the short wavelengths of visible light in the 400 to 500 nm blue light region of the spectrum yielding a 50% transmission level at 473 nm. The rectangular samples were placed into individual tissue capsules and soxhlet extracted in acetone followed by drying in air then under vacuum at 50° C. Afterwards UV/visible measurements were performed again. The UV/visible transmission and absorption spectra were measured both before and after soxhlet extraction and drying. From the absorbance of the samples, at appropiate wavelengths between 400 and 500 nm, the percentage of the dye which is removed by soxhlet extraction was found to be 84%.
Reaction SMILES: [C:1]1([CH3:24])[CH:6]=[CH:5][C:4]([S:7][CH:8]([C:11]2[CH:16]=[CH:15][C:14]([C:17]([C:19]3[S:20][CH:21]=[CH:22][CH:23]=3)=[O:18])=[CH:13][CH:12]=2)[C:9]#[N:10])=[CH:3][CH:2]=1.[CH3:25][O-].[Na+].CI.[Cl-].[NH4+]>CO>[C:1]1([CH3:24])[CH:2]=[CH:3][C:4]([S:7][C:8]([C:11]2[CH:16]=[CH:15][C:14]([C:17]([C:19]3[S:20][CH:21]=[CH:22][CH:23]=3)=[O:18])=[CH:13][CH:12]=2)([CH3:25])[C:9]#[N:10])=[CH:5][CH:6]=1
Reactant: C[O-]
Reactant: Cc1ccc(SC(C#N)c2ccc(C(=O)c3cccs3)cc2)cc1
Agent: [Cl-]
Agent: [NH4+]
Agent: [Na+]
Solvent: CO
Solvent: CI
Product: Cc1ccc(SC(C)(C#N)c2ccc(C(=O)c3cccs3)cc2)cc1
Yield: 86 %

Procedure:
Anhydrous methanol (3 ml) was added to 351 mg of alpha-(p-tolylthio)[p-(2-thienylcabonyl)phenyl]acetonitrile, and the mixture was stirred in an argon atmosphere under ice cooling. Then, 0.45 ml of a 2.5 M methanol solution of sodium methoxide was added, and 0.10 ml of methyl iodide was added dropwise. The temperature was brought to room temperature and the mixture was stirred for 15 minutes. An aqueous solution of ammonium chloride (0.2 g/30 ml) was added, and the mixture was extracted with 20 ml of methylene chloride three times. The extract was washed with 20 ml of water, dried over anhydrous magnesium sulfate; and concentrated under reduced pressure. The residue was purified by column chromatography (silica gel; methylene chloride) to afford 314 mg (yield 86%) of alpha-(p-tolylthio)-alpha-[p-(2-thienylcabonyl)phenyl]-propionitrile as colorless crystals.
Reaction SMILES: Br[C:2]1[CH:11]=[CH:10][C:5]2[O:6][CH2:7][CH2:8][O:9][C:4]=2[CH:3]=1.C([Li])CCC.[CH3:17][O:18][C:19]1[CH:20]=[C:21]([CH:24]=[CH:25][CH:26]=1)[CH:22]=[O:23].C(O)(C)C>C1COCC1.O>[O:6]1[C:5]2[CH:10]=[CH:11][C:2]([CH:22]([C:21]3[CH:24]=[CH:25][CH:26]=[C:19]([O:18][CH3:17])[CH:20]=3)[OH:23])=[CH:3][C:4]=2[O:9][CH2:8][CH2:7]1
Reactant: Brc1ccc2c(c1)OCCO2
Reactant: COc1cccc(C=O)c1
Agent: [Li]CCCC
Solvent: O
Solvent: CC(C)O
Solvent: C1CCOC1
Product: COc1cccc(C(O)c2ccc3c(c2)OCCO3)c1
Temperature: -78 °C
Reaction time: 0.33 h

Procedure:
A stirred mixture of 6-bromo-2,3-dihydro-benzo[1,4]dioxine (1.59 g, 7.4 mmol) and dry TRF (10 mL) was cooled to −78° C., evacuated and refilled with nitrogen for 10 cycles. To this clear solution was slowly added n-butyllithium (3.0 mL, 7.4 mmol) and stirred for 20 min. Then a mixture of 3-methoxy-benzaldehyde (0.92 g, 6.7 mmol) in dry THF (10 mL) was added and stirred for 1 hour at −78° C. The mixture was quenched with isopropanol (3.1 mL, 40 mmol) and added water (10 mL). The mixture was extracted with EtOAc (3×30 mL). The combined organic phases were washed with water (2×30 mL), dried over MgSO4 and concentrated to give (2,3-dihydro-benzo[1,4]dioxin-6-yl)-(3-methoxy-phenyl)-methanol as an oil (2.09 g, 114% crude yield). The product was used in the next step without further purification.
Reaction SMILES: [H-].[Na+].C[O:4][C:5]1[C:6](=[CH:13][CH:14]=[CH:15][C:16]=1[Cl:17])[CH:7]=[CH:8][C:9]([O:11][CH3:12])=[O:10].C1C[O:21]CC1>>[C:9]([C:8]1[O:4][C:5]2[C:16]([Cl:17])=[CH:15][CH:14]=[CH:13][C:6]=2[C:7]=1[OH:21])([O:11][CH3:12])=[O:10]
Reactant: C1CCOC1
Reactant: COC(=O)C=Cc1cccc(Cl)c1OC
Agent: [H-]
Agent: [Na+]
Product: COC(=O)c1oc2c(Cl)cccc2c1O
Reaction time: 1 h
Yield: 80 %

Procedure:
According to the procedure of D. C. Schroeder, et al., J. Org. Chem., 27, 586 (1962) to a stirred suspension of NaH (50% dispersion in mineral oil, washed with hexane) (4.5 g, 0.093 mol) in THF (20 mL) was added a solution of methyl (methyl 3-chlorosalicylyl)acetate (24.1 g, 0.093 mol) in THF (50 mL). Additional THF (60 mL) was added. After 1 hour, the mixture was heated under reflux for 1 hour, cooled, and partitioned between ether and H2O. The aqueous phase was acidified with 1N HCl and the precipitate was collected by filtration. This material was dissolved in ether. The solution was washed with H2O, dried (MgSO4), and concentrated to give a yellow solid (16.9 g, 80%).
Reaction SMILES: C([N:4](C(=O)C)[C:5]1[NH:6][C:7](=[O:14])[C:8]2[NH:9][CH:10]=[N:11][C:12]=2[N:13]=1)(=O)C.C(O[CH2:22][O:23][CH2:24][CH2:25][O:26]C(=O)C)(=O)C.N>CS(C)=O>[CH:10]1[N:11]([CH2:22][O:23][CH2:24][CH2:25][OH:26])[C:12]2[N:13]=[C:5]([NH2:4])[N:6]=[C:7]([OH:14])[C:8]=2[N:9]=1
Reactant: CC(=O)N(C(C)=O)c1nc2nc[nH]c2c(=O)[nH]1
Reactant: CC(=O)OCCOCOC(C)=O
Agent: N
Solvent: CS(C)=O
Product: Nc1nc(O)c2ncn(COCCO)c2n1

Procedure:
Matsumoto in Chem Pharm Bull, 36(3), 1153-1157 and JP 63-107982 teaches a process for the synthesis of acyclovir(Ia) by condensation of diacetyl guanine (DAG Va) with 2-oxa-1,4-butanediol diacetate (OBDDA, VIIa) in DMSO in presence of an acid catalyst to get a mixture of N-9/N-7 isomer (66:26). The former is isolated by column chromatography and deacetylated with methanolic ammonia to give acyclovir. Overall yield of acyclovir from guanine is 42%
Reaction SMILES: [OH:1][C:2]1[CH:19]=[CH:18][C:5]2[S:6][C:7]3[CH:14]=[CH:13][CH:12]=[C:11]([C:15]([OH:17])=[O:16])[C:8]=3[CH2:9][CH2:10][C:4]=2[CH:3]=1.Cl.[CH2:21](O)[CH3:22]>C(OCC)(=O)C.C1C=CC=CC=1>[OH:1][C:2]1[CH:19]=[CH:18][C:5]2[S:6][C:7]3[CH:14]=[CH:13][CH:12]=[C:11]([C:15]([O:17][CH2:21][CH3:22])=[O:16])[C:8]=3[CH2:9][CH2:10][C:4]=2[CH:3]=1
Reactant: O=C(O)c1cccc2c1CCc1cc(O)ccc1S2
Reactant: CCO
Agent: Cl
Solvent: CCOC(C)=O
Solvent: c1ccccc1
Product: CCOC(=O)c1cccc2c1CCc1cc(O)ccc1S2
Yield: 85 %

Procedure:
An amount of 1.7 g of 2-hydroxy-9-carboxy-10,11-dihydrodibenzo[b,f]thiepin was dissolved in 50ml of anhydrous ethanol and the mixture was refluxed for 3 hours, while hydrogen chloride gas was bubbled into the mixture. The solvent was distilled off to obtain the residue which was dissolved in the mixed solvent of ethyl acetate-benzene. The solution was washed with saturated sodium chloride solution and freed of solvent by distillation to obtain 1.6 g (85%) of 2-hydroxy-9-ethoxycarbonyl-10,11-dihydrodibenzo[b,f]thiepin as brown crystals having a melting point of 125°-129° C.