Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH:1]([N:4]=[C:5]=[S:6])([CH3:3])[CH3:2].[NH2:7][C:8]1[C:17]2[N:18]=[C:19]([CH2:29][O:30][CH2:31][CH3:32])[N:20]([CH2:21][C:22]([NH:25][C:26](=[O:28])[CH3:27])([CH3:24])[CH3:23])[C:16]=2[C:15]2[CH:14]=[CH:13][C:12]([O:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][NH2:40])=[CH:11][C:10]=2[N:9]=1>ClCCl>[NH2:7][C:8]1[C:17]2[N:18]=[C:19]([CH2:29][O:30][CH2:31][CH3:32])[N:20]([CH2:21][C:22]([NH:25][C:26](=[O:28])[CH3:27])([CH3:24])[CH3:23])[C:16]=2[C:15]2[CH:14]=[CH:13][C:12]([O:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][NH:40][C:5]([NH:4][CH:1]([CH3:3])[CH3:2])=[S:6])=[CH:11][C:10]=2[N:9]=1
Reactant: CCOCc1nc2c(N)nc3cc(OCCCCCCN)ccc3c2n1CC(C)(C)NC(C)=O
Reactant: CC(C)N=C=S
Solvent: ClCCl
Product: CCOCc1nc2c(N)nc3cc(OCCCCCCNC(=S)NC(C)C)ccc3c2n1CC(C)(C)NC(C)=O
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 34.7 %

Procedure:
Isopropyl isothiocyanate (255 μL, 2.38 mmol) was added to a stirred suspension of N-{2-[4-amino-7-(6-aminohexyloxy)-2-ethoxymethyl-1H-imidazo[4,5-c]quinolin-1-yl]-1,1-dimethylethyl}acetamide (prepared as described in Part I of Example 49, 1.02 g, 2.17 mmol) in dichloromethane (100 mL) at 0° C. The mixture was stirred for 30 minutes at 0° C., then was allowed to warm to room temperature and was stirred over the weekend. The solution was concentrated under reduced pressure. The crude product was purified by flash chromatography (silica gel, gradient elution with 7.5-10% methanol in dichloromethane) followed by recrystallization from acetonitrile. The crystals were dissolved in 1:1 dichloromethane/methanol and the resulting solution was concentrated under reduced pressure to afford a white powder that was dried under vacuum at 60° C. to yield 0.43 g of N-(2-{4-amino-2-(ethoxymethyl)-7-[(6-{[(isopropylamino)carbonothioyl]amino}hexyl)oxy]-1H-imidazo[4,5-c]quinolin-1-yl}-1,1-dimethylethyl)acetamide as a white powder, mp 110-120° C.
Reaction SMILES: Cl.[NH2:2][OH:3].C(=O)(O)[O-].[K+].[CH2:9]([C:12]1[CH:24]=[CH:23][CH:22]=[CH:21][C:13]=1[O:14][CH2:15][CH:16]([OH:20])[CH2:17][C:18]#[N:19])[CH:10]=[CH2:11]>O.C(O)CCC>[NH2:2][OH:3].[CH2:9]([C:12]1[CH:24]=[CH:23][CH:22]=[CH:21][C:13]=1[O:14][CH2:15][CH:16]([OH:20])[CH2:17][C:18](=[N:2][OH:3])[NH2:19])[CH:10]=[CH2:11]
Reactant: C=CCc1ccccc1OCC(O)CC#N
Agent: Cl
Agent: NO
Agent: O=C([O-])O
Solvent: CCCCO
Solvent: O
Product: C=CCc1ccccc1OCC(O)CC(N)=NO
Temperature: 94 °C
Reaction time: 2 h
Yield: 86.1 %

Procedure:
An aqueous solution of hydroxylamine is prepared from 39.06 g (0.562 mol) of hydroxylamine hydrochloride in 150 ml of water and from 56.2 g (0.562 mol) of potassium bicarbonate. 48.9 g (0.225 mol) of 4-(o-allylphenoxy)-3-hydroxy-butyronitrile previously dissolved in 250 ml of n-butanol are then added. The resulting mixture is taken to 80° C. in about 2 hours, then taken to reflux (94° C.) which is maintained for 5 hours. The mixture is cooled, the H2O--CH3 (CH2)2CH2OH mixture is evaporated, the residue of evaporation is taken up with ether, washed several times in water, dried and the ether is evaporated under reduced pressure. 48.5 g (yield 86%) of 4-(o-allyl-phenoxy)-3-hydroxy-butyramidoxime are obtained in the form of a brown oil.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5](/[CH:8]=[CH:9]/[N:10]2CCCC2)=[C:4]([N+:15]([O-:17])=[O:16])[CH:3]=1.Cl.N[NH:20][C:21]([NH2:23])=[O:22]>CO.O>[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8]/[CH:9]=[N:10]/[NH:20][C:21]([NH2:23])=[O:22])=[C:4]([N+:15]([O-:17])=[O:16])[CH:3]=1
Reactant: NNC(N)=O
Reactant: O=[N+]([O-])c1cc(F)ccc1/C=C/N1CCCC1
Agent: Cl
Solvent: CO
Solvent: O
Product: NC(=O)N/N=C/Cc1ccc(F)cc1[N+](=O)[O-]
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a stirred solution of 1-[(E)-2-(4-fluoro-2-nitrophenyl)ethenyl]pyrrolidine (77.25 g, 0.327 mol) in warm MeOH (500 mL) was added a solution of semicarbazide HCl (38.3 g, 0.343 mol) in warm water (200 mL). The reaction mixture was stirred at room temperature for 1 h and was then cooled in ice and filtered. The solid was washed with cold 1:1 MeOH/water (2×30 mL) and dried to give 71 g (90% over two steps) of the title compound.
Reaction SMILES: [F:1][C:2]1[CH:14]=[CH:13][CH:12]=[C:11]([F:15])[C:3]=1[CH2:4][N:5]1[CH2:9][CH:8]=[CH:7][N:6]1O.P(Br)(Br)([Br:18])=O>C(Cl)(Cl)Cl>[Br:18][C:9]1[N:5]([CH2:4][C:3]2[C:2]([F:1])=[CH:14][CH:13]=[CH:12][C:11]=2[F:15])[N:6]=[CH:7][CH:8]=1
Reactant: ON1C=CCN1Cc1c(F)cccc1F
Reactant: O=P(Br)(Br)Br
Solvent: ClC(Cl)Cl
Product: Fc1cccc(F)c1Cn1nccc1Br
Temperature: 25 °C
Yield: 96.3 %

Procedure:
2-(2,6-Difluorobenzyl)-1-hydroxy-1H-pyrazole (81.2 mg, 0.386 mmol, 1.0 eq) and 5 of anhydrous CHCl3 were combined in a flame-dried 25 mL round-bottom flask under argon and cooled in an ice/water bath. A solution of POBr3 (398.1 mg, 1.39 mmol, 3.60 eq) in 3 mL of CHCl3 was added using a syringe in aliquots over an hour period with stirring. The reaction solution was warmed to room temperature and stirred for 16 hours. The CHCl3 was removed in vacuo and the resulting orange mixture was neutralized with saturated aqueous NaHCO3 and extracted with 3×30 mL of diethyl ether. The combined ether fractions were washed with brine, dried over Na2SO4 and concentrated in vacuo to yield 101.5 mg (96.7% yield) of 5-bromo-1-(2,6-difluorobenzyl)-1H-pyrazole as a hygroscopic orange-tan colored solid. 1H NMR (CDCl3 300 MHz) δ 7.51 (d, 1H), 7.34 (m, 1H), 6.94 (t, 2H), 6.29 (d, 1H), 5.50 (s, 2H). LC/MS (ES) M+1=273.1, 275.1
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[OH:12])[O:8][CH:7]=[C:6]([C:13]1[CH:22]=[CH:21][C:16]3[O:17][CH2:18][CH2:19][O:20][C:15]=3[CH:14]=1)[C:5]2=O.O.[NH2:25][NH2:26]>C(O)C>[Cl:1][C:2]1[CH:3]=[C:4]([C:5]2[C:6]([C:13]3[CH:22]=[CH:21][C:16]4[O:17][CH2:18][CH2:19][O:20][C:15]=4[CH:14]=3)=[CH:7][NH:26][N:25]=2)[C:9]([OH:8])=[CH:10][C:11]=1[OH:12]
Reactant: NN
Reactant: O=c1c(-c2ccc3c(c2)OCCO3)coc2cc(O)c(Cl)cc12
Solvent: CCO
Solvent: O
Product: Oc1cc(O)c(-c2n[nH]cc2-c2ccc3c(c2)OCCO3)cc1Cl

Procedure:
This compounds was synthesised in the same manner as described above. 6-Chloro-3-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-7-hydroxy-chromen-4-one (0.1 g, 0.30 mmol), hydrazine hydrate (4 ml), ethanol (10 ml). The quenched reaction was extracted into ethyl acetate (2×30 ml), washed (water), dried (MgSO4), and the solvent remove to give 4-Chloro-6-[4-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-1H-pyrazol-3-yl]-benzene-1,3-diol as an off white solid (0.031 g, 30%); Rf 0.6 Cf SM 0.8 ethyl acetate/hexane (75/25).
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[C:6](Cl)[CH:5]=[CH:4][N:3]=1.[F:9][C:10]1[CH:15]=[C:14]([N+:16]([O-:18])=[O:17])[CH:13]=[CH:12][C:11]=1[OH:19].C(N(CC)C(C)C)(C)C.C(OCC)(=O)C>CN1CCCC1=O>[NH2:1][C:2]1[CH:7]=[C:6]([O:19][C:11]2[CH:12]=[CH:13][C:14]([N+:16]([O-:18])=[O:17])=[CH:15][C:10]=2[F:9])[CH:5]=[CH:4][N:3]=1
Reactant: Nc1cc(Cl)ccn1
Reactant: O=[N+]([O-])c1ccc(O)c(F)c1
Solvent: CCN(C(C)C)C(C)C
Solvent: CCOC(C)=O
Solvent: CN1CCCC1=O
Product: Nc1cc(Oc2ccc([N+](=O)[O-])cc2F)ccn1
Temperature: 160 °C
Reaction time: 41 h
Yield: 19.5 %

Procedure:
2-Amino-4-chloropyridine (8.00 g) was dissolved in N-methylpyrrolidone (65 ml), and then 2-fluoro-4-nitrophenol (19.55 g) and N,N-diisopropylethylamine (43.36 ml) were added thereto, followed by stirring at 160° C. for 41 hrs. The reaction mixture was cooled down to room temperature, and partitioned between ethyl acetate-tetrahydrofuran (1:1) and a 2 N aqueous solution of sodium hydroxide. The organic layer was washed with water and brine in this order. The aqueous layer was extracted again with ethyl acetate. The combined organic layer was dried over anhydrous sodium sulfate. The solvent was evaporated under a reduced pressure to give a residue, which was purified by silica gel column chromatography (eluent; hexane:ethyl acetate=1:2, then ethyl acetate). Fractions containing the target compound were concentrated to provide a residue, to which ethyl acetate was added to precipitate crystals. The crystals were filtered, and dried under aeration to provide the titled compound (3.02 g, 20%) as opaline crystals.
Reaction SMILES: C1[O:20][C:19]2[C:3](=[C:4]3[C:16](=[CH:17][CH:18]=2)[CH:8]2[CH2:9][NH:10][CH2:11][C:12]4[CH:13]=[CH:14][CH:15]=[C:6]([C:7]=42)[CH2:5]3)[O:2]1.C([C@](C(O)=O)(O)[C@](C(=O)C1C=CC=CC=1)(O)C(O)=O)(=O)C1C=CC=CC=1.[OH-].[K+].C(O)(=O)[C@H]([C@@H](C(O)=O)O)O>C(O)C.CO>[OH:2][C:3]1[C:19]([OH:20])=[CH:18][CH:17]=[C:16]2[C:4]=1[CH2:5][C:6]1[C:7]3[C@@H:8]2[CH2:9][NH:10][CH2:11][C:12]=3[CH:13]=[CH:14][CH:15]=1
Reactant: c1cc2c3c(c1)Cc1c(ccc4c1OCO4)C3CNC2
Agent: O=C(O)[C@@H](O)[C@H](O)C(=O)O
Agent: O=C(O)[C@](O)(C(=O)c1ccccc1)[C@](O)(C(=O)O)C(=O)c1ccccc1
Agent: [K+]
Solvent: CCO
Solvent: CO
Product: Oc1ccc2c(c1O)Cc1cccc3c1[C@@H]2CNC3
Reaction time: 4 h

Procedure:
A solution of racemic (±)-8,9-methylenedioxy-2,3,7,11b-tetrahydro-1H-napth[1,2,3-de]isoquinoline (3.0 gm, 11.3 mmol) in 100 mL of 95% ethyl alcohol at room temperature was mixed with a warm solution of (+)-dibenzoyl-D-tartaric acid in 40 mL of 95% ethyl alcohol. The solution was allowed to stand at room temperature for 4 hours and the grayish off-white crystals were collected by filtration and subsequently dried in a vacuum oven at 35° C. to give 1.3 gm (melting point: 175–176° C., 35.7%). The enantiomeric purity was determined by the same chiral HPLC conditions described above in Example 8: the salt was neutralized with 2M potassium hydroxide solution and the organic materials extracted with methylene chloride. The organic layers were combined and concentrated under reduced pressure to give a white solid which was redissolved in methanol prior to injection into HPLC Chiral column. The ratio of the second peak to the first was determined to be greater than 40:1. The identical resolution may also be. carried out using the unnatural D-tartaric acid. Melting points are uncorrected for the desired tartaric salts of the title compound.
Reaction SMILES: O([C:8]([N:10]([CH2:12][C:13]#[C:14][C:15]1[CH:19]=[C:18]([C:20]2[CH:25]=[CH:24][C:23]([CH3:26])=[CH:22][CH:21]=2)[N:17]([C:27]2[CH:32]=[CH:31][C:30]([O:33][CH3:34])=[CH:29][CH:28]=2)[N:16]=1)[OH:11])=[O:9])C1C=CC=CC=1.[NH3:35]>CO>[OH:11][N:10]([CH2:12][C:13]#[C:14][C:15]1[CH:19]=[C:18]([C:20]2[CH:21]=[CH:22][C:23]([CH3:26])=[CH:24][CH:25]=2)[N:17]([C:27]2[CH:28]=[CH:29][C:30]([O:33][CH3:34])=[CH:31][CH:32]=2)[N:16]=1)[C:8]([NH2:35])=[O:9]
Reactant: N
Reactant: COc1ccc(-n2nc(C#CCN(O)C(=O)Oc3ccccc3)cc2-c2ccc(C)cc2)cc1
Solvent: CO
Product: COc1ccc(-n2nc(C#CCN(O)C(N)=O)cc2-c2ccc(C)cc2)cc1
Reaction time: 8 h

Procedure:
Alternatively, N-phenoxycarbonyl-N-(1(1-(4-methoxyphenyl)-5-(4-methylphenyl)-3-pyrazolyl)-1-propyn-3-yl)hydroxylamine (4.67 mmol, 2.12 g) was dissolved in 20 mL of 14% w/w solution of ammonia in MeOH and stirred overnight in a stoppered round-bottomed flask. The solution was concentrated to give 2.2 g of orange oil which was purified by MPLC to give 0.89 g (51%) of Cpd. 1 as an off white solid. Tables I & J list the analytical data for Cpd. 1 as well as other compounds which were prepared in this manner.
Reaction SMILES: [CH3:1][C:2]1[CH:8]=[CH:7][C:6]([N+:9]([O-:11])=[O:10])=[CH:5][C:3]=1[NH2:4].[N:12]#[C:13][NH2:14].Cl.[N+:16]([O-:19])([OH:18])=[O:17]>C(O)(C)C>[N+:16]([O-:19])([OH:18])=[O:17].[CH3:1][C:2]1[CH:8]=[CH:7][C:6]([N+:9]([O-:11])=[O:10])=[CH:5][C:3]=1[NH:4][C:13]([NH2:14])=[NH:12]
Reactant: Cc1ccc([N+](=O)[O-])cc1N
Reactant: N#CN
Agent: Cl
Solvent: CC(C)O
Solvent: O=[N+]([O-])O
Product: Cc1ccc([N+](=O)[O-])cc1NC(=N)N
Temperature: 80 °C
Reaction time: 1 h
Yield: 81.5 %

Procedure:
20 g of 2-Methyl-5-nitroaniline (0.131 mol; 1 eq.), 11.05 g of cyanamide (0.263 mol; 2 eq.) and 80 mL of isopropyl alcohol were placed in a reactor flask. The reaction mixture was heated to 80° C., and 18 mL of concentrated hydrochloric acid was slowly added dropwise within 80 minutes. The reaction mixture was stirred for 1 hour while maintaining the temperature at 80° C. Next, 6 mL of concentrated hydrochloric acid was added dropwise and the reaction mixture was kept at 80° C. for 2 hours. The reaction mixture was cooled down to 60° C. and 10 mL of 65% nitric acid (0.142 mol, 1.08 eq.) was added dropwise and the mixture was left with stirring until it was cooled down to room temperature. The solid product was filtered off, washed with 50 mL of isopropyl alcohol and dried in the air to afford 27.45 g (yield 81.1%) of 1-(2-methyl-5-nitrophenyl)guanidine nitrate, m.p. 203-206° C.; 1H NMR (DMSO-d6, 200 MHz): 2.32 (3H, s, CH3), 7.44 (4H, m, 4×NH), 7.64 (1H, d, J=8.2 Hz, 3-H), 8.09 (1H, d, J=2.5 Hz, 6-H), 8.15 (1H, dd, J=8.2 i 2.5 Hz, 4-H), 9.51 (1H, m, NH+).
Reaction SMILES: [NH2:1][C:2]1[N:6]([C:7]2[CH:16]=[CH:15][C:10]3[NH:11][C:12]([CH3:14])=[N:13][C:9]=3[CH:8]=2)[N:5]=[CH:4][C:3]=1[C:17]([C:19]1[N:20]([S:29]([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)(=[O:31])=[O:30])[C:21]2[C:26]([CH:27]=1)=[CH:25][C:24](I)=[CH:23][CH:22]=2)=[O:18].[Cu][C:39]#[N:40].CN1CCCC1=O.O.N>CO.C(OCC)(=O)C>[NH2:1][C:2]1[N:6]([C:7]2[CH:16]=[CH:15][C:10]3[NH:11][C:12]([CH3:14])=[N:13][C:9]=3[CH:8]=2)[N:5]=[CH:4][C:3]=1[C:17]([C:19]1[N:20]([S:29]([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)(=[O:31])=[O:30])[C:21]2[C:26]([CH:27]=1)=[CH:25][C:24]([C:39]#[N:40])=[CH:23][CH:22]=2)=[O:18]
Reactant: Cc1nc2cc(-n3ncc(C(=O)c4cc5cc(I)ccc5n4S(=O)(=O)c4ccccc4)c3N)ccc2[nH]1
Reactant: N#C[Cu]
Agent: N
Solvent: CO
Solvent: CCOC(C)=O
Solvent: CN1CCCC1=O
Product: Cc1nc2cc(-n3ncc(C(=O)c4cc5cc(C#N)ccc5n4S(=O)(=O)c4ccccc4)c3N)ccc2[nH]1
Yield: 88.7 %

Procedure:
A mixture of 2-[5-amino-1-(2-methyl-1H-benzimidazol-5-yl)-1H-pyrazole-4-carbonyl]-1-(benzenesulfonyl)-5-iodo-1H-indole (117 mg), copper (I) cyanide (84 mg), and 1-methyl-2-pyrrolidinone was reacted in a microwave reactor (190° C., 20 minutes). The reaction mixture was poured into a mixed solution of 2 M ammonia water (40 ml), ethyl acetate (60 ml), and methanol (7 ml), and sonicated for five minutes. After ethyl acetate extraction, the extract was washed with water and then dried over anhydrous sodium sulfate. The desiccant was removed by filtration. The filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (methanol/dichloromethane=0/100 to 20/100) to give 2-[5-amino-1-(2-methyl-1H-benzimidazol-5-yl)-1H-pyrazole-4-carbonyl]-1-(benzenesulfonyl)-1H-indole-5-carbonitrile (87 mg, 89%).
Reaction SMILES: [F:1][C:2]1[CH:24]=[N:23][C:5]2[N:6](COCC[Si](C)(C)C)[C:7]3[CH:12]=[N:11][C:10]([C:13]#[N:14])=[CH:9][C:8]=3[C:4]=2[C:3]=1[N:25]1[CH2:29][CH2:28][C@H:27]([N:30]([CH2:38][CH3:39])C(=O)OC(C)(C)C)[CH2:26]1.Br.[OH-].[Na+].Cl>O1CCOCC1>[F:1][C:2]1[CH:24]=[N:23][C:5]2[NH:6][C:7]3[CH:12]=[N:11][C:10]([C:13]#[N:14])=[CH:9][C:8]=3[C:4]=2[C:3]=1[N:25]1[CH2:29][CH2:28][C@H:27]([NH:30][CH2:38][CH3:39])[CH2:26]1
Reactant: CCN(C(=O)OC(C)(C)C)[C@H]1CCN(c2c(F)cnc3c2c2cc(C#N)ncc2n3COCC[Si](C)(C)C)C1
Agent: Br
Agent: Cl
Agent: [Na+]
Solvent: C1COCCO1
Product: CCN[C@H]1CCN(c2c(F)cnc3[nH]c4cnc(C#N)cc4c23)C1
Temperature: 55 °C
Yield: 77.1 %

Procedure:
(S)-tert-butyl 1-(3-fluoro-6-cyano-9-((2-(trimethylsilyl)ethoxy)methyl)-9H-dipyrido[2,3-b;4′,3′-d]pyrrol-4-yl)pyrrolidin-3-yl(ethyl)carbamate (120 mg, 0.2 mmol) was dissolved in 1,4-dioxane (0.3 mL) and then treated with 48% HBr(aq) (0.3 mL) and heated at 55° C. for 20 minutes. The cooled reaction mixture was then basified to pH ˜12 by dropwise addition of 6N sodium hydroxide and then immediately acidified to pH ˜8-9 by dropwise addition of concentrated hydrochloric acid, producing a cloudy precipitate. The solid was collected by centrifugation, dissolved in dimethylsulfoxide (2 mL), and purified by preparative HPLC [5-85% methanol in water (0.1% ammonium hydroxide) over 30 min, 35 mL/min] to afford the title compound as a pale yellow solid (50 mg, 30% over two steps). 1H NMR (500 MHz, d6-DMSO) δ 8.87 (s, 1H), 8.49 (s, 1H), 8.32 (d, J=7.0, 1H), 3.91-3.84 (m, 1H), 3.83-3.76 (m, 2H), 3.58 (m, 1H), 3.43 (m, 1H), 2.67-2.56 (m, 2H), 2.19 (m, 1H), 1.83 (m, 1H), 1.07 (t, J=7.1, 3H), NH signal not observed. LCMS (Method D): RT=6.033 min, M+H+=325.1.
Reaction SMILES: C[O:2][C:3](=[O:34])[CH2:4][O:5][C:6]1[CH:14]=[CH:13][CH:12]=[C:11]2[C:7]=1[C:8]([C:29](=[O:33])[C:30]([NH2:32])=[O:31])=[C:9]([CH3:28])[N:10]2[CH2:15][C:16]1[CH:17]=[C:18]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH:19]=[CH:20][CH:21]=1.CO.[Na]>[OH-].[Na+]>[NH2:32][C:30](=[O:31])[C:29]([C:8]1[C:7]2[C:11](=[CH:12][CH:13]=[CH:14][C:6]=2[O:5][CH2:4][C:3]([OH:34])=[O:2])[N:10]([CH2:15][C:16]2[CH:17]=[C:18]([C:22]3[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=3)[CH:19]=[CH:20][CH:21]=2)[C:9]=1[CH3:28])=[O:33]
Reactant: COC(=O)COc1cccc2c1c(C(=O)C(N)=O)c(C)n2Cc1cccc(-c2ccccc2)c1
Agent: [Na+]
Agent: [Na]
Agent: [OH-]
Solvent: CO
Product: Cc1c(C(=O)C(N)=O)c2c(OCC(=O)O)cccc2n1Cc1cccc(-c2ccccc2)c1
Yield: 43.4 %

Procedure:
Using the procedure described in Example 2, Part E, 956 mg (2.1 mmol) of [[3-(2-amino-1,2-dioxoethyl)-1-([1,1′-biphenyl]-3-ylmethyl)-2-methyl-1H-indol-4-yl]oxy]acetic acid methyl ester was hydrolyzed in 10 mL of 1N NaOH and 20 mL of MeOH to give 403 mg (41% yield) of [[3-(2-amino-1,2-dioxoethyl)-1-([1,1-biphenyl]-3-ylmethyl)-2-methyl-1H-indol-4-yl]oxy]acetic acid, sodium salt, mp, >265° C.
Reaction SMILES: [CH2:1]([C:3]1[N:4]=[C:5]([C@@H:8]([NH2:19])[CH2:9][C:10]2[CH:15]=[CH:14][C:13]([N+:16]([O-:18])=[O:17])=[CH:12][CH:11]=2)[O:6][CH:7]=1)[CH3:2].[C:20]1([CH2:26][C:27](O)=[O:28])[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.ON1C2C=CC=CC=2N=N1.CN(C)CCCN=C=NCC.C(N(CC)CC)C>CN(C=O)C.O>[CH2:1]([C:3]1[N:4]=[C:5]([CH:8]([NH:19][C:27](=[O:28])[CH2:26][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH2:9][C:10]2[CH:15]=[CH:14][C:13]([N+:16]([O-:18])=[O:17])=[CH:12][CH:11]=2)[O:6][CH:7]=1)[CH3:2]
Reactant: O=C(O)Cc1ccccc1
Reactant: CCc1coc([C@@H](N)Cc2ccc([N+](=O)[O-])cc2)n1
Agent: CCN=C=NCCCN(C)C
Agent: On1nnc2ccccc21
Solvent: O
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: CCc1coc(C(Cc2ccc([N+](=O)[O-])cc2)NC(=O)Cc2ccccc2)n1
Temperature: 0 °C
Reaction time: 0.5 h

Procedure:
To a solution of (S)-1-(4-ethyloxazol-2-yl)-2-(4-nitrophenyl)ethanamine, 65, (2.9 g, 11 mmol), phenylacetic acid (1.90 g, 14 mmol) and 1-hydroxybenzotriazole (HOBt) (0.94 g, 7.0 mmol) in DMF (100 mL) at 0° C., is added 1-(3-dimethylamino-propyl)-3-ethylcarbodiimide (EDCI) (2.68 g, 14 mmol) followed by triethylamine (6.0 mL, 42 mmol). The mixture is stirred at 0° C. for 30 minutes then at room temperature overnight. The reaction mixture is diluted with water and extracted with EtOAc. The combined organic phase is washed with 1 N aqueous HCl, 5% aqueous NaHCO3, water and brine, and dried over Na2SO4. The solvent is removed in vacuo to afford the desired product which is used without further purification.
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([NH:8][CH3:9])[C:5]([N+:10]([O-:12])=[O:11])=[CH:4][N:3]=1.[NH2:13][C:14]1[CH:19]=[CH:18][C:17]([N:20]2[CH2:25][CH2:24][O:23][CH2:22][CH2:21]2)=[CH:16][CH:15]=1>C1COCC1.CC(O)C.O>[CH3:9][NH:8][C:6]1[C:5]([N+:10]([O-:12])=[O:11])=[CH:4][N:3]=[C:2]([NH:13][C:14]2[CH:15]=[CH:16][C:17]([N:20]3[CH2:25][CH2:24][O:23][CH2:22][CH2:21]3)=[CH:18][CH:19]=2)[N:7]=1
Reactant: Nc1ccc(N2CCOCC2)cc1
Reactant: CNc1nc(Cl)ncc1[N+](=O)[O-]
Solvent: CC(C)O
Solvent: O
Solvent: C1CCOC1
Product: CNc1nc(Nc2ccc(N3CCOCC3)cc2)ncc1[N+](=O)[O-]
Temperature: 50 °C
Reaction time: 0.5 h
Yield: 98.1 %

Procedure:
To a room temperature solution of 0.943 g (5 mmol) of 2-chloro-4-(methylamino)-5-nitropyrimidine in 25 mL THF is added a solution of 1.96 g (11 mmol) of 4-(4-aminophenyl)morpholine in 100 mL of 2-propanol, and the resulting mixture is heated and stirred at 50° C. for 30 minutes. The mixture is then diluted with water, the solid precipitate is collected, washed with water, and dried, to give 1.62 g (98%) of the title compound: mp (EtOH) 240–241° C.
Reaction SMILES: I([O-])(=O)(=O)=O.[Na+].[CH3:7][C:8]1[CH:9]=[C:10]([OH:23])[CH:11]=[CH:12][C:13]=1[B:14]1[O:18]C(C)(C)C(C)(C)[O:15]1.C([O-])(=O)C.[NH4+]>CC(C)=O.O>[OH:23][C:10]1[CH:11]=[CH:12][C:13]([B:14]([OH:18])[OH:15])=[C:8]([CH3:7])[CH:9]=1
Reactant: Cc1cc(O)ccc1B1OC(C)(C)C(C)(C)O1
Agent: CC(=O)[O-]
Agent: [NH4+]
Agent: [Na+]
Solvent: CC(C)=O
Solvent: O
Product: Cc1cc(O)ccc1B(O)O
Yield: 48.8 %

Procedure:
Sodium periodate (2.39 g, 11.15 mmol) was added to 3-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol (870.4 mg, 3.72 mmol) and ammonium acetate (859.8 mg, 11.15 mmol) in acetone and water (2:1, 36 mL) at room temperature. The mixture was stirred for sixty-eight hours, then filtered, and concentrated. Sodium chloride was added to the filtrate, and it was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, then filtered and concentrated. The residue was purified by silica gel chromatography eluting with 1:4 ethyl acetate:hexanes to give 275.7 mg (49%) of (4-hydroxy-2-methylphenyl)boronic acid as a solid. 1H NMR (400 MHz, d6-DMSO): δ 9.28 (s, 1H), 7.70 (d, J=9 Hz, 1H), 6.56-6.52 (m, 2H), 2.55 (s, 3H). ESI-LCMS m/z 151 (M−H)−.
Reaction SMILES: CCN(C1C=CC(N=NC2C(C(O)=O)=CC=CC=2)=CC=1)CC.CCN1C2C(=CC=CC=2)C=C/C/1=C\C1C2C(=CC=CC=2)[N+](CC)=CC=1.[I-].CO[C:51]1[C:56](F)=[C:55](F)[C:54]([C:59]([C:67]([C:81]2[CH:86]=[CH:85][CH:84]=[CH:83][CH:82]=2)([C:69]2[C:74](F)=[C:73](F)[C:72](OC)=[C:71](F)[C:70]=2F)[OH:68])([C:61]2[CH:66]=[CH:65][CH:64]=[CH:63][CH:62]=2)[OH:60])=[C:53](F)[C:52]=1F>CC(C)=O.COCCO>[C:69]1([C:67]([C:59]([C:61]2[CH:66]=[CH:65][CH:64]=[CH:63][CH:62]=2)([C:54]2[CH:53]=[CH:52][CH:51]=[CH:56][CH:55]=2)[OH:60])([C:81]2[CH:86]=[CH:85][CH:84]=[CH:83][CH:82]=2)[OH:68])[CH:74]=[CH:73][CH:72]=[CH:71][CH:70]=1
Reactant: COc1c(F)c(F)c(C(O)(c2ccccc2)C(O)(c2ccccc2)c2c(F)c(F)c(OC)c(F)c2F)c(F)c1F
Agent: CCN(CC)c1ccc(N=Nc2ccccc2C(=O)O)cc1
Agent: CCN1/C(=C/c2cc[n+](CC)c3ccccc23)C=Cc2ccccc21
Agent: [I-]
Solvent: CC(C)=O
Solvent: COCCO
Product: OC(c1ccccc1)(c1ccccc1)C(O)(c1ccccc1)c1ccccc1
Temperature: 160 °C

Procedure:
Ethyl red (2.0 mg), 1,1'-diethyl-2,4'-cyanine iodide, was dissolved in 2.0 ml. of acetone/2-methoxyethanol. Then, 50 mg of 4,4"-dimethoxy-2,3,5,6,2",3",5",6"-octafluorobenzopinacol was added. The solution was mixed with 1.0 ml of 20 percent polysulfonamide polymer solution (acetone/2-methoxyethanol (1:1)). The solution was mixed and coated on poly(ethylene terephthalate) film base at a wet thickness of 0.098 mm. It was allowed to dry at 49° C. for 15 minutes. The dye in the film had λ max at 565 nm, and at 530 nm, the optical density was 1.8 and 0.93, respectively. The film was heated at 160° C. for 10 seconds. The optical density of the heated film was 0.20 at λ=565 and 0.18 at 530 nm. The reduction in the dye density was 89 percent and 81 percent, at the two wavelengths. The same results were obtained after the film had been held in storage at room temperature for 6 months.
Reaction SMILES: [Cl:1][C:2]1[C:15]([Cl:16])=[CH:14][CH:13]=[CH:12][C:3]=1[C:4](=O)[CH2:5][NH:6][CH:7]=[CH:8][C:9]#[N:10].CC[O-].[Na+]>C(O)C>[Cl:1][C:2]1[C:15]([Cl:16])=[CH:14][CH:13]=[CH:12][C:3]=1[C:4]1[C:8]([C:9]#[N:10])=[CH:7][NH:6][CH:5]=1
Reactant: N#CC=CNCC(=O)c1cccc(Cl)c1Cl
Agent: CC[O-]
Agent: [Na+]
Solvent: CCO
Product: N#Cc1c[nH]cc1-c1cccc(Cl)c1Cl

Procedure:
4.2 g of the 3-(2,3-dichlorophenacylamino)acrylonitrile obtained in (a) are reacted in 50 ml of ethanol with 0.5 g of sodium ethylate as described in Example P5 b), affording the title compound in quantitative yield. Melting point: 150°-152° C.
Reaction SMILES: C(C1C=CC(C#C)=CC=1)(C)(C)C.C[Si]([C:17]#[C:18][C:19]1[CH:24]=[CH:23][C:22]([C:25]([CH3:32])([CH3:31])[CH2:26][CH2:27][CH:28]([CH3:30])[CH3:29])=[CH:21][CH:20]=1)(C)C>>[CH3:32][C:25]([C:22]1[CH:21]=[CH:20][C:19]([C:18]#[CH:17])=[CH:24][CH:23]=1)([CH3:31])[CH2:26][CH2:27][CH:28]([CH3:30])[CH3:29]
Reactant: CC(C)CCC(C)(C)c1ccc(C#C[Si](C)(C)C)cc1
Agent: C#Cc1ccc(C(C)(C)C)cc1
Product: C#Cc1ccc(C(C)(C)CCC(C)C)cc1

Procedure:
Using the same general procedure as described for Compound 19, but using instead trimethylsilyl[4-(1,1,4-trimethylpentyl)]phenylethyne (Compound 34), the title compound was synthesized as a colorless oil. PMR (CDCl3): & 0.81 (6H, d, J-6.6 Hz), 0.85-0.96 (2H, m), 1.29 (6H, s), 1.32-1.48 (1H, m). 1.55-1.66 (2H, m)., 3.04 (1H, s), 7.29 (2H, d, J-8.4 Hz), 7.44 (2H, d, J-8.4 Hz).