Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C:2]1([CH3:36])[CH2:7][NH:6][CH2:5][CH2:4][N:3]1[CH2:8][C:9]1[N:10]([CH3:35])[C:11]2[C:16]([N:17]=1)=[C:15]([N:18]1[CH2:23][CH2:22][O:21][CH2:20][CH2:19]1)[N:14]=[C:13]([N:24]1[C:28]3[CH:29]=[CH:30][CH:31]=[CH:32][C:27]=3[N:26]=[C:25]1[CH2:33][CH3:34])[N:12]=2.[OH:37][C:38]([CH3:43])([CH3:42])[C:39](O)=[O:40].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>C(Cl)Cl>[CH2:33]([C:25]1[N:24]([C:13]2[N:12]=[C:11]3[C:16]([N:17]=[C:9]([CH2:8][N:3]4[CH2:4][CH2:5][N:6]([C:39](=[O:40])[C:38]([OH:37])([CH3:43])[CH3:42])[CH2:7][C:2]4([CH3:1])[CH3:36])[N:10]3[CH3:35])=[C:15]([N:18]3[CH2:23][CH2:22][O:21][CH2:20][CH2:19]3)[N:14]=2)[C:28]2[CH:29]=[CH:30][CH:31]=[CH:32][C:27]=2[N:26]=1)[CH3:34]
Reactant: CCc1nc2ccccc2n1-c1nc(N2CCOCC2)c2nc(CN3CCNCC3(C)C)n(C)c2n1
Reactant: CC(C)(O)C(=O)O
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: CCc1nc2ccccc2n1-c1nc(N2CCOCC2)c2nc(CN3CCN(C(=O)C(C)(C)O)CC3(C)C)n(C)c2n1
Temperature: 25 °C
Reaction time: 17 h
Yield: 47.8 %

Procedure:
A mixture of 8-(2,2-dimethylpiperazin-1-ylmethyl)-2-(2-ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purine (100 mg, 0.20 mmol), 2-hydroxyisobutyric acid (24 mg, 0.23 mmol), HATU (85 mg, 0.22 mmol) and DIPEA (40 μL, 0.23 mmol) in DCM (2 mL) was allowed to stir at r.t. for 17 h. The reaction mixture was loaded onto an Isolute® SCX-2 cartridge which was washed with MeOH and the product eluted with 2M NH3/MeOH. The resulting residue was purified by column chromatography (Si-PCC, MeOH:DCM, 0-3%) affording 741 as a white solid (55 mg, 46%). LCMS (method I): RT 2.89 min, [M+H]+ 576.3. 1H NMR (CDCl3, 400 MHz): δ 8.02-8.02 (1 H, m), 7.76-7.75 (1 H, m), 7.33-7.22 (2 H, m), 4.40-4.20 (5 H, m), 3.92 (3 H, s), 3.88-3.83 (5 H, m), 3.63 (2 H, s), 3.53 (2 H, s), 3.36 (2 H, q, J=7.48 Hz), 2.59-2.53 (2 H, m), 1.50 (6 H, s), 1.45 (3 H, t, J=7.48 Hz), 1.23 (6 H, s)
Reaction SMILES: [NH2:1][C@@H:2]1[N:8]=[C:7]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[C:6]2[CH:15]=[CH:16][CH:17]=[CH:18][C:5]=2[N:4]([CH3:19])[C:3]1=[O:20].[CH3:21][C:22]1[CH:27]=[CH:26][C:25]([N:28]=[C:29]=[O:30])=[CH:24][CH:23]=1>O1CCCC1>[CH3:19][N:4]1[C:5]2[CH:18]=[CH:17][CH:16]=[CH:15][C:6]=2[C:7]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)=[N:8][C@@H:2]([NH:1][C:29]([NH:28][C:25]2[CH:26]=[CH:27][C:22]([CH3:21])=[CH:23][CH:24]=2)=[O:30])[C:3]1=[O:20]
Reactant: Cc1ccc(N=C=O)cc1
Reactant: CN1C(=O)[C@H](N)N=C(c2ccccc2)c2ccccc21
Solvent: C1CCOC1
Product: Cc1ccc(NC(=O)N[C@@H]2N=C(c3ccccc3)c3ccccc3N(C)C2=O)cc1
Reaction time: 8 h

Procedure:
Equimolar amounts of 3(R)-amino-1,3-dihydro-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one and 4-methylphenylisocyanate were mixed in 8 ml of dry tetrahydrofuran at room temperature. The reaction mixture was allowed to stand for 8 hours and was then filtered. The collected solids were washed with tetrahydrofuran and dried in vacuo over P2O5 to give the analytical product: m.p. 233°-235° C.
Reaction SMILES: [CH2:1]([C:13]1[CH:18]=[C:17]([CH2:19][CH3:20])[C:16]([NH2:21])=[C:15]([CH2:22][CH3:23])[CH:14]=1)[C:2]1[CH:7]=[C:6]([CH2:8][CH3:9])[C:5]([NH2:10])=[C:4]([CH2:11][CH3:12])[CH:3]=1>[Pt].C(C(C)=O)C>[CH:1]([NH:21][C:16]1[C:17]([CH2:19][CH3:20])=[CH:18][C:13]([CH2:1][C:2]2[CH:7]=[C:6]([CH2:8][CH3:9])[C:5]([NH:10][CH:4]([CH2:5][CH3:6])[CH3:11])=[C:4]([CH2:11][CH3:12])[CH:3]=2)=[CH:14][C:15]=1[CH2:22][CH3:23])([CH2:2][CH3:3])[CH3:13]
Reactant: CCc1cc(Cc2cc(CC)c(N)c(CC)c2)cc(CC)c1N
Agent: [Pt]
Solvent: CCC(C)=O
Product: CCc1cc(Cc2cc(CC)c(NC(C)CC)c(CC)c2)cc(CC)c1NC(C)CC
Temperature: 95 °C
Reaction time: 0.08 h
Yield: 94 %

Procedure:
4,4′-Methylenebis(2,6-diethylbenzeneamine) (4.0 g), Pt(S)/C (0.2 g), sulfonated divinylbenzene/styrene copolymer (0.2 g; H ion form, sold as Amberlyst-15 by Rohm and Haas Company, Philadelphia, Pa.), and methyl ethyl ketone (50 g) were charged into a 100 mL metal autoclave at 22° C. The closed autoclave was purged 3 times with 125 psig (9.63×105 Pa) of H2 at 22° C. to remove traces of air. The reaction mixture was then heated at 95° C. under 125 psig (9.63×105 Pa) of H2 for 3 hours (until no further H2 uptake was observed). The product mixture was cooled to 22° C. and degassed. A diluted product sample was analyzed by gas chromatography (GC; 180° C. for 5 minutes at 10° C. per minute rate; final temperature, 270° C.). The GC data (normalization method) showed 100% conversion of 4,4′-methylenebis(2,6-diethylbenzeneamine) and a 94% yield of N,N′-di-sec-butyl-4,4′-methylenebis(2,6-diethylbenzeneamine). NMR analysis (with internal standard) of a neat product sample showed a purity of 94.75%.
Reaction SMILES: [OH:1][C:2]1[CH:7]=[C:6]([CH3:8])[O:5][C:4](=[O:9])[C:3]=1[SH:10].Cl[CH2:12][C:13]1[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[CH:16]=[CH:15][CH:14]=1.Cl>N1C=CC=CC=1>[OH:1][C:2]1[CH:7]=[C:6]([CH3:8])[O:5][C:4](=[O:9])[C:3]=1[S:10][CH2:12][C:13]1[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[CH:16]=[CH:15][CH:14]=1
Reactant: ClCc1cccc2ccccc12
Reactant: Cc1cc(O)c(S)c(=O)o1
Agent: Cl
Solvent: c1ccncc1
Product: Cc1cc(O)c(SCc2cccc3ccccc23)c(=O)o1

Procedure:
A solution of 15.8 g. (0.100 mole) of 4-hydroxy-3-mercapto-6-methyl-2-pyrone in 100 ml. of pyridine was cooled in an ice bath to about 15°C., and 17.7 g. (0.100 mole) of 1-chloromethylnaphthalene was added in one portion. The flask was then heated at 90°-95°C. on the steam plate for four hours. The reaction mixture was cooled and poured into 200 ml. of concentrated hydrochloric acid and about 400 g. of ice. A gummy solid was formed and was extracted with methylene chloride. The wet extract was treated with Darco and dried over anhydrous sodium sulfate. The solvent was removed by evaporation in vacuo, leaving a brown gum, which was crystallized (Darco) from ethanol to give 9.8 g. (33 percent) of tan crystals m.p. 155.5°-157.5°C. Recrystallization from ethanol gave the pure 4-hydroxy-6-methyl-3-(1-naphthylmethylthio)-2-pyrone as cream colored crystals, m.p. 169.5°-170.5°C.
Reaction SMILES: C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O.[F:32][C:33]1[C:38]([F:39])=[CH:37][CH:36]=[C:35]([N+:40]([O-:42])=[O:41])[C:34]=1[OH:43].[O:44]1[CH2:49][CH2:48][CH2:47][CH2:46][CH:45]1[O:50][CH:51]([CH3:54])[CH2:52]O>O1CCCC1>[F:32][C:33]1[C:38]([F:39])=[CH:37][CH:36]=[C:35]([N+:40]([O-:42])=[O:41])[C:34]=1[O:43][CH2:52][CH:51]([O:50][CH:45]1[CH2:46][CH2:47][CH2:48][CH2:49][O:44]1)[CH3:54]
Reactant: O=[N+]([O-])c1ccc(F)c(F)c1O
Reactant: CC(CO)OC1CCCCO1
Agent: CCOC(=O)N=NC(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: CC(COc1c([N+](=O)[O-])ccc(F)c1F)OC1CCCCO1
Yield: 97.2 %

Procedure:
To a solution of 2.04 g of triphenylphosphine in 10 ml of anhydrous tetrahydrofuran was added dropwise 1.36 g of diethyl azodicarboxylate with stirring under cooling with ice, and the resulting mixture was stirred at the same temperature for 30 minutes. To this solution was added dropwise a solution of 1.05 g of 2,3-difluoro-6- nitrophenol (IV, Xa=Xb=F), 1.01 g of 2-O-(tetra-hydropyran-2-yl)propane-1,2-diol (III, Rc=THP) in 5 ml of anhydrous tetrahydrofuran and then the mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and to the residue was added benzene and a saturated sodium bicarbonate aqueous solution. After the mixture was shaken, the organic layer was separated and washed successively with water and a saturated sodium chloride aqueous solution. The organic layer was dried over anhydrous magnesium sulfate, and then the solvent was removed under reduced pressure. The residue was purified through silica gel column to yield 1.85 g of the titled compound.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[C:14](=[O:18])[N:13]([C:19]1[CH:24]=[CH:23][C:22]([O:25][CH2:26][C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)=[CH:21][CH:20]=1)[C:12]2=[O:33])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:34]([Mg]Br)[CH3:35].[Cl-].[NH4+]>C1COCC1>[CH2:1]([O:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[C:14](=[O:18])[N:13]([C:19]1[CH:24]=[CH:23][C:22]([O:25][CH2:26][C:27]3[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=3)=[CH:21][CH:20]=1)[C:12]2([CH2:34][CH3:35])[OH:33])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CC[Mg]Br
Reactant: O=C1c2ccc(OCc3ccccc3)cc2C(=O)N1c1ccc(OCc2ccccc2)cc1
Agent: [Cl-]
Agent: [NH4+]
Solvent: C1CCOC1
Product: CCC1(O)c2cc(OCc3ccccc3)ccc2C(=O)N1c1ccc(OCc2ccccc2)cc1
Temperature: 3 °C
Reaction time: 0.25 h

Procedure:
To a cooled (3° C.) solution containing 5-benzyloxy-2-(4-benzyloxyphenyl)-isoindoline-1,3-dione (870 mg) in THF (25 mL) under nitrogen atmosphere was added ethylmagnesium bromide (4 mL, 3M solution in THF) dropwise. The mixture was stirred at 3° C. for 15 min then allowed to warm to room temperature for 2 h. The mixture was cooled, poured into saturated ammonium chloride and extracted with ethyl acetate. The organic layer was washed with brine. Evaporation of the solvent yielded the title compound (900 mg) as a tan solid. MS: 466 (MH+).
Reaction SMILES: [CH2:1]([O:8][NH:9][C:10](=[O:19])[CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17]Br)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH:20][C:21]1[CH:33]=[CH:32][C:31]2[C:30]3[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=3)[NH:24][C:23]=2[CH:22]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[CH2:1]([O:8][NH:9][C:10](=[O:19])[CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][O:20][C:21]1[CH:33]=[CH:32][C:31]2[C:30]3[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=3)[NH:24][C:23]=2[CH:22]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: Oc1ccc2c(c1)[nH]c1ccccc12
Reactant: O=C(CCCCCCCBr)NOCc1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: O=C(CCCCCCCOc1ccc2c(c1)[nH]c1ccccc12)NOCc1ccccc1

Procedure:
In a manner analogous to that of example 1(b), 8-bromo-octanoic acid benzyloxy-amide (example 1(a); 0.3 g, 1.1 mmol) was reacted with 2-hydroxy-9H-carbazol (0.3 g, 1.1 mmol) in the presence of potassium carbonate (0.15 g, 1.1 mmol) and DMF as solvent to give 8-(9H-carbazol-2-yloxy)-octanoic acid benzyloxyamide as an almost colorless wax (yield 0.1 g, 20%; purified by column chromatography using silica gel and ethyl acetate as eluent). MS (M+H+)=483.
Reaction SMILES: [NH2:1][C:2]1[C:7]([Br:8])=[CH:6][C:5]([C:9]2[O:10][C:11]3[C:19]([F:20])=[CH:18][C:17]([F:21])=[C:16]([NH:22]C(=O)C(C)(C)C)[C:12]=3[C:13](=[O:15])[CH:14]=2)=[CH:4][C:3]=1[Br:29]>S(=O)(=O)(O)O>[NH2:22][C:16]1[C:12]2[C:13](=[O:15])[CH:14]=[C:9]([C:5]3[CH:6]=[C:7]([Br:8])[C:2]([NH2:1])=[C:3]([Br:29])[CH:4]=3)[O:10][C:11]=2[C:19]([F:20])=[CH:18][C:17]=1[F:21]
Reactant: CC(C)(C)C(=O)Nc1c(F)cc(F)c2oc(-c3cc(Br)c(N)c(Br)c3)cc(=O)c12
Agent: O=S(=O)(O)O
Product: Nc1c(Br)cc(-c2cc(=O)c3c(N)c(F)cc(F)c3o2)cc1Br
Temperature: 100 °C
Reaction time: 1.3 h
Yield: 44.8 %

Procedure:
20 ml of concentrated sulfuric acid was added to the resulting 1.00 g (1.89 mmol) of 2-(4-amino-3,5-dibromophenyl)-6,8-difluoro-5-pivaloylamino-4H-1-benzopyran-4-one and the mixture was stirred at 100° C. for 1.3 hours. The reaction solution was adjusted to pH 9 by addition of ice and a 10N aqueous solution of sodium hydroxide thereto and the precipitated crystals were collected by filtration. The crystals were purified by silica gel column chromatography (chloroform:acetonitrile=40:1) and triturated with chloroform to give 378 mg (45%) of Compound 36.
Reaction SMILES: [Cl:1][C:2]1[C:7]([OH:8])=[CH:6][C:5]([N+:9]([O-:11])=[O:10])=[C:4]([NH2:12])[CH:3]=1.C(=O)([O-])[O-].[Ca+2].Cl[C:19]([O:21][CH2:22][CH2:23][CH2:24][Cl:25])=[O:20]>C(COC)OC>[Cl:1][C:2]1[C:7]([OH:8])=[CH:6][C:5]([N+:9]([O-:11])=[O:10])=[C:4]([NH:12][C:19](=[O:20])[O:21][CH2:22][CH2:23][CH2:24][Cl:25])[CH:3]=1
Reactant: O=C(Cl)OCCCCl
Reactant: Nc1cc(Cl)c(O)cc1[N+](=O)[O-]
Agent: O=C([O-])[O-]
Agent: [Ca+2]
Solvent: COCCOC
Product: O=C(Nc1cc(Cl)c(O)cc1[N+](=O)[O-])OCCCCl
Reaction time: 1 h

Procedure:
37.7 g (0.2 mole) of 6-chloro-3-nitro-4-aminophenol are dissolved in 120 ml of dimethoxyethane, 11 g of calcium carbonate are added and 32 g of γ-chloropropyl chloroformate are added dropwise at 70° C. After 1 hour at 90° C., the mixture is filtered hot and the filtrate is stirred into 300 ml of ice-water. The initially oily product crystallises after a short time.
Reaction SMILES: [F:1][C:2]1[CH:12]=[CH:11][CH:10]=[C:9]([F:13])[C:3]=1[C:4]([N:6]=[C:7]=[O:8])=[O:5].[Cl:14][C:15]1[CH:16]=[C:17]([NH2:29])[CH:18]=[C:19]([Cl:28])[C:20]=1[O:21][C:22]([F:27])([F:26])[CH:23]([Cl:25])[F:24]>C1(C)C=CC=CC=1>[Cl:14][C:15]1[CH:16]=[C:17]([NH:29][C:7]([NH:6][C:4](=[O:5])[C:3]2[C:2]([F:1])=[CH:12][CH:11]=[CH:10][C:9]=2[F:13])=[O:8])[CH:18]=[C:19]([Cl:28])[C:20]=1[O:21][C:22]([F:27])([F:26])[CH:23]([Cl:25])[F:24]
Reactant: Nc1cc(Cl)c(OC(F)(F)C(F)Cl)c(Cl)c1
Reactant: O=C=NC(=O)c1c(F)cccc1F
Solvent: Cc1ccccc1
Product: O=C(NC(=O)c1c(F)cccc1F)Nc1cc(Cl)c(OC(F)(F)C(F)Cl)c(Cl)c1
Reaction time: 1 h
Yield: 57.9 %

Procedure:
2,6-Difluorobenzoyl isocyanate (5.5 g, 0.03 mole) was added to a solution of 3,5-dichloro-4-(2-chloro-1,1,2-trifluoroethoxy)benzenamine (8.8 g, 0.03 mole) in 150 ml toluene and heated under reflux with stirring for one hour giving a clear solution. Toluene was removed by evaporation in a rotary evaporator. The residue was recrystallized from aqueous acetic acid and then from acetonitrile giving a white solid (8.3 g, 58 percent yield), melting at 178°-180° C.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:17])[C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([CH2:10][N:11]2[CH:15]=[C:14](Br)[CH:13]=[N:12]2)[CH:5]=1.[C:18]([C:20]1[CH:25]=[CH:24][C:23](B(O)O)=[CH:22][CH:21]=1)#[N:19].C(=O)([O-])[O-].[K+].[K+]>>[CH3:1][O:2][C:3](=[O:17])[C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([CH2:10][N:11]2[CH:15]=[C:14]([C:23]3[CH:24]=[CH:25][C:20]([C:18]#[N:19])=[CH:21][CH:22]=3)[CH:13]=[N:12]2)[CH:5]=1
Reactant: COC(=O)c1cccc(Cn2cc(Br)cn2)c1
Reactant: N#Cc1ccc(B(O)O)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Product: COC(=O)c1cccc(Cn2cc(-c3ccc(C#N)cc3)cn2)c1
Yield: 31.5 %

Procedure:
Charge a microwave vial with 3-(4-bromo-pyrazol-1-ylmethyl)-benzoic acid methyl ester (0.60 g, 2.00 mmol), 4-cyanophenylboronic acid (0.35 g, 2.40 mmol), potassium carbonate (0.50 g, 4.80 mmol) and tetrakistriphenylphosphine palladium (0) (0.23 g, 0.2 mmol). Flush the vessel with inert gas and seal. Dissolve the contents of the vial in 10 mL of a 4:1 dioxane-water mixture and microwave at 150° C. for 5 minutes. Dilute the reaction mixture with EtOAc, dry over sodium sulfate, filter and concentrate to give an oil. Purify the residue by flash chromatography using a gradient of 0-50% EtOAc/hexanes to afford 0.20 g, 32% yield of 3-[4-(4-cyano-phenyl)-pyrazol-1-ylmethyl]-benzoic acid methyl ester as a solid.
Reaction SMILES: [NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH:32]3[CH2:36][CH2:35][NH:34][CH2:33]3)[N:9]=[C:10]([C:11]3[CH:16]=[CH:15][C:14]([NH:17][C:18]([C:20]4[N:21]([CH3:29])[C:22]5[C:27]([CH:28]=4)=[CH:26][CH:25]=[CH:24][CH:23]=5)=[O:19])=[C:13]([O:30][CH3:31])[CH:12]=3)[C:3]=12.[CH3:37][C:38]1[C:42]([CH:43]=O)=[CH:41][NH:40][N:39]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[OH-].[Na+]>ClC(Cl)C>[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH:32]3[CH2:36][CH2:35][N:34]([CH2:43][C:42]4[C:38]([CH3:37])=[N:39][NH:40][CH:41]=4)[CH2:33]3)[N:9]=[C:10]([C:11]3[CH:16]=[CH:15][C:14]([NH:17][C:18]([C:20]4[N:21]([CH3:29])[C:22]5[C:27]([CH:28]=4)=[CH:26][CH:25]=[CH:24][CH:23]=5)=[O:19])=[C:13]([O:30][CH3:31])[CH:12]=3)[C:3]=12
Reactant: Cc1n[nH]cc1C=O
Reactant: COc1cc(-c2nn(C3CCNC3)c3ncnc(N)c23)ccc1NC(=O)c1cc2ccccc2n1C
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Agent: [OH-]
Solvent: CC(Cl)Cl
Product: COc1cc(-c2nn(C3CCN(Cc4c[nH]nc4C)C3)c3ncnc(N)c23)ccc1NC(=O)c1cc2ccccc2n1C
Temperature: 25 °C
Reaction time: 24 h
Yield: 44.3 %

Procedure:
A suspension of N2-[4-(4-amino-1-tetrahydro-1H-3-pyrrolyl-1H-pyrazolo[3,4-d]pyrimidin-3-yl)-2-methoxyphenyl]-1-methyl-1H-2-indolecarboxamide (0.200 g, 0.415 mmol) in dichloroethane (5 mL) was treated with 3-methyl-1H-pyrazol-4-carboxaldehyde (0.091 g, 0.83 mmol) and sodium triacetoxy borohydride (0.176 g, 0.83 mmol). The reaction mixture was stirred at room temperature for 24 h under a nitrogen atmosphere. Sodium hydroxide (1N, 15 mL) was added to the reaction mixture and was stirred for 1 h. The organic layer was removed under reduced pressure and dichloromethane was added. The layers were partitioned and the aqueous layer was extracted with dichloromethane (100 mL) and ethyl acetate (100 mL). The combined organic layers were dried over magnesium sulfate, filtered and evaporated under reduced pressure. The crude material was purified by flash chromatography on silica gel using 10% methanol in dichloromethane (15 min), 15% methanol in dichloromethane (10 min), 20% methanol in dichloromethane (10 min) and 50% methanol in dichloromethane (8 min) as the eluent. The column afforded 0.106 g (44%) of pure N2-[4-(4-amino-1-{1-[(3-methyl-1H-4-pyrazolyl)methyl]tetrahydro-1H-3-pyrrolyl}-1H-pyrazolo[3,4-d]pyrimidin-3-yl)-2-methoxyphenyl]-1-methyl-1H-2-indolecarboxamide. 1H NMR (DMSO-d6, 400 MHz) δ 9.446 (s, 1H), 8.247 (s, 1H), 8.1275-8.1071 (d, 1H, J=8.16 Hz), 7.72-7.7003 (d, 1H, J=7.96 Hz), 7.6004-7.5793 (d, 1H, J=8.44 Hz), 7.398-7.286 (m, 5H), 7.172-7.134 (m, 1H), 5.379 (m, 1H), 4.0443 (s, 3H), 3.962 (s, 3H), 3.492 (m, 2H), 3.1 (m, 1H), 2.75 (m, 3H), 2.352-2.335 (m, 2H), 1.909 (s, 3H); LCMS (Thermoquest AQA single-quad MS, Genesis C18 column, 3 μm particle size, 33×4.6 mm; 70% 50 mM ammonium acetate in water to 95% acetonitrile over 6 min, 0.8 to 0.5 mL/min) Rt 2.17 min (100%), MH+ 577.3.
Reaction SMILES: CO[C:3](=[O:24])[CH2:4][CH:5]([NH:20]C(=O)C)[CH2:6][CH:7]([OH:19])[CH2:8][CH:9]([NH:15]C(=O)C)[CH2:10][C:11]([O:13][CH3:14])=[O:12].[ClH:25].Cl.[CH3:27][O:28][C:29](=[O:44])[CH2:30][CH:31]([NH2:43])[CH2:32][C:33](=[O:42])[CH2:34][CH:35]([NH2:41])[CH2:36]C(OC)=O>>[ClH:25].[ClH:25].[ClH:25].[ClH:25].[CH3:27][O:28][C:29](=[O:44])[CH2:30][CH:31]([NH2:43])[CH2:32][CH:33]([OH:42])[CH2:34][CH:35]([NH2:41])[CH2:36][C:3](=[O:24])[CH2:4][CH:5]([NH2:20])[CH2:6][CH:7]([OH:19])[CH2:8][CH:9]([NH2:15])[CH2:10][C:11]([O:13][CH3:14])=[O:12]
Reactant: COC(=O)CC(CC(O)CC(CC(=O)OC)NC(C)=O)NC(C)=O
Reactant: COC(=O)CC(N)CC(=O)CC(N)CC(=O)OC
Agent: Cl
Product: COC(=O)CC(N)CC(O)CC(N)CC(=O)CC(N)CC(O)CC(N)CC(=O)OC

Procedure:
When an equivalent quantity of 3,7-diacetylamino-5-hydroxy-1,9-nonanedioic acid dimethyl ester is substituted for the N-acetyl-3-aminoglutaric acid dimethyl ester of Example 6 and the procedures detailed therein substantially repeated there is obtained 3,7,11,15-tetramino-5,13-dihydroxy-9-oxo-1,17 heptadecanedioic acid dimethyl ester tetrahydrochloride which has the following structural formula ##STR28##
Reaction SMILES: [C:1]1([CH2:7][C:8](NC2C(=O)N3C2CCOC3(C)C)=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[O:22]1[CH2:27][CH2:26][CH2:25][CH2:24][CH:23]1[N:28]1[CH:31]([CH2:32][CH2:33][O:34][CH:35]2[CH2:40][CH2:39][CH2:38][CH2:37][O:36]2)[CH:30]([NH2:41])[C:29]1=[O:42]>>[O:22]1[CH2:27][CH2:26][CH2:25][CH2:24][CH:23]1[N:28]1[CH:31]([CH2:32][CH2:33][O:34][CH:35]2[CH2:40][CH2:39][CH2:38][CH2:37][O:36]2)[CH:30]([NH:41][C:8](=[O:9])[CH2:7][C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[C:29]1=[O:42]
Reactant: CC1(C)OCCC2C(NC(=O)Cc3ccccc3)C(=O)N21
Reactant: NC1C(=O)N(C2CCCCO2)C1CCOC1CCCCO1
Product: O=C(Cc1ccccc1)NC1C(=O)N(C2CCCCO2)C1CCOC1CCCCO1

Procedure:
Following the procedure described for the preparation of 7-phenylacetamido-8-oxo-2,2-dimethyl-3-oxa-1-azabicyclo[4.2.0]octane from 7-amino-8-oxo-2,2-dimethyl-3-oxa-1-azabicyclo[4.2.0]octane (Example 6) and using 1-(2-tetrahydropyranyl)-3-amino-4-[2-(2-tetrahydropyranyl)oxyethyl]-2-azetidinone there is obtained 1-(2-tetrahydropyranyl)-3-phenylacetamido-4-[2-(2-tetrahydropyranyl)oxyethyl]-2-azetidinone.
Reaction SMILES: [C:1]([NH:4][CH:5]([CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([O:18][CH3:19])[CH:13]=1)[CH2:6][CH2:7][C:8]([OH:10])=[O:9])(=[O:3])[CH3:2].[CH2:20]=[CH:21][C@@H:22]1[C@@H:27]2[CH2:28][C@H:29]([C@@H:30]([OH:41])[C:31]3[C:40]4[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=4)[N:34]=[CH:33][CH:32]=3)[N:24]([CH2:25][CH2:26]2)[CH2:23]1>O1CCOCC1>[C:1]([NH:4][C@H:5]([CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([O:18][CH3:19])[CH:13]=1)[CH2:6][CH2:7][C:8]([OH:10])=[O:9])(=[O:3])[CH3:2].[CH2:20]=[CH:21][C@@H:22]1[C@@H:27]2[CH2:28][C@H:29]([C@@H:30]([OH:41])[C:31]3[C:40]4[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=4)[N:34]=[CH:33][CH:32]=3)[N:24]([CH2:25][CH2:26]2)[CH2:23]1
Reactant: COc1cccc(CC(CCC(=O)O)NC(C)=O)c1
Agent: C=C[C@H]1CN2CC[C@H]1C[C@@H]2[C@@H](O)c1ccnc2ccccc12
Solvent: C1COCCO1
Product: COc1cccc(C[C@H](CCC(=O)O)NC(C)=O)c1

Procedure:
A mixture of 4-acetylamino-5-(3-methoxyphenyl)valeric acid (151 mg) and (+)-cinchonine (110 mg) in 1,4-dioxane (2.6 ml) was refluxed and the solution was allowed to cool. The resulting precipitates were collected by filtration and dried to give a salt of (S)-4-acetylamino-5-(3-methoxyphenyl)valeric acid and (+)-cinchonin (117 mg). This compound was recrystallized from 1,4-dioxane to give the pure salt (61 mg).
Reaction SMILES: [CH2:1]([N:4]1[C:16]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[C:10]2[C:5]1=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:2]#[CH:3].O.[OH-].[Na+].[I:20]I>CO.O1CCCC1>[I:20][C:3]#[C:2][CH2:1][N:4]1[C:16]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[C:10]2[C:5]1=[CH:6][CH:7]=[CH:8][CH:9]=2
Reactant: II
Reactant: C#CCn1c2ccccc2c2ccccc21
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: O
Solvent: C1CCOC1
Product: IC#CCn1c2ccccc2c2ccccc21
Temperature: 4 °C
Yield: 63 %

Procedure:
Procedure: To a solution of 1.23 g (0.006 mol) of N-(2-propynyl)carbazole in 19.2 mL of methanol 4.8 mL of water and 0.48 g of NaOH were added while stirring at 4° C. Addition of 6 mL of tetrahydrofurane (THF) to the turbid suspension resulted in a homogeneous solution. Then 1.52 g of crystalline iodine was added portion-wise. After 10 min of stirring the iodine color disappeared and the product started to separate as a dense white precipitate. Over 8 hrs of stirring at room temperature the product was filtered, washed with distilled water and air dried. 1.25 g (Yield 65%) of N-(3-Iodo-2-propynyl)carbazole has been obtained as crystals having m.p. 151-152° C. When applied onto a printing paper and analyzed according to Example 1, the compound gave an intense NIR FT-Raman spectrum in some features similar, but clearly not identical, to that shown in FIG. 1(A) for copper phenylacetylide (exemplary Compound #26 of the invention).
Reaction SMILES: [Cl:1][C:2]1[C:7]([C:8]([O:10][CH3:11])=[O:9])=[C:6]([N+:12]([O-])=O)[CH:5]=[CH:4][CH:3]=1.[H][H]>[Ni].CO>[Cl:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]([NH2:12])[C:7]=1[C:8]([O:10][CH3:11])=[O:9]
Reactant: COC(=O)c1c(Cl)cccc1[N+](=O)[O-]
Reactant: [H][H]
Agent: [Ni]
Solvent: CO
Product: COC(=O)c1c(N)cccc1Cl

Procedure:
4.5 gm (0.212 mol) of methyl 6-chloro-2-nitro-benzoate were hydrogenated with Raney nickel in 1.8 liters of methanol until the calculated amount of hydrogen was absorbed. The filtered reaction mixture was evaporated in vacuo, and the residue was distilled in vacuo.
Reaction SMILES: [I:1][C:2]1[CH:3]=[C:4]([CH:7]=[C:8]([CH3:11])[C:9]=1[OH:10])[CH:5]=[O:6].[H-].[Na+].I[CH3:15]>C1COCC1>[I:1][C:2]1[CH:3]=[C:4]([CH:7]=[C:8]([CH3:11])[C:9]=1[O:10][CH3:15])[CH:5]=[O:6]
Reactant: Cc1cc(C=O)cc(I)c1O
Reactant: CI
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: COc1c(C)cc(C=O)cc1I
Temperature: 60 °C
Reaction time: 0.5 h
Yield: 60.1 %

Procedure:
At 5° C., to a stirred solution of 3-iodo-4-hydroxy-5-methylbenzaldehyde (3.53 g, 13.5 mmol) in THF (67.4 mL) was added 60% sodium hydride/mineral oil (0.701 g, 17.5 mmol). After 0.5 h, to the reaction was added dropwise iodomethane (1.34 mL, 21.6 mmol). After 2 h, the reaction was heated at 60° C. After 3 days, the reaction was cooled to ambient temperature, quenched with H2O (100 mL) and extracted with ether. The ethereal extracts were washed with 1N NaOH (3×), with brine (3×), dried (K2CO3) and concentrated. Purification on Biotage KP-Sil eluting with 15% acetone/hexane gave 2.24 g (60%) of the title compound. 1H NMR (DMSO-d6) δ2.37 (s, 3 H), 3.77 (s, 3 H), 7.78 (s, 1 H), 8.17 (s, 1 H), 9.86 (s, 1 H).