Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][C@@H:2]1[CH2:7][CH2:6][C@H:5]([C:8]([OH:10])=[O:9])[CH2:4][CH2:3]1.O=S(Cl)Cl.[CH3:15]O>>[NH2:1][C@@H:2]1[CH2:7][CH2:6][C@H:5]([C:8]([O:10][CH3:15])=[O:9])[CH2:4][CH2:3]1
Reactant: CO
Reactant: N[C@H]1CC[C@@H](C(=O)O)CC1
Solvent: O=S(Cl)Cl
Product: COC(=O)[C@H]1CC[C@@H](N)CC1
Temperature: 25 °C

Procedure:
A suspension of cis-4-aminocyclohexanecarboxylic acid (5.0 g, 34.9 mmol) in methanol (50 mL) was stirred at room temperature and SOCl2 (7.1 mL, 98.4 mmol) was added dropwise over 20 minutes, causing the solid to dissolve. The solution was stirred overnight and the methanol was then removed under reduced pressure. The residual solid was triturated with diethyl ether and air-dried and the title compound obtained as an off-white powder (6.0 g).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[C:11](=O)[C:10](=[CH:13]N(C)C)[CH2:9][C:8](=[O:17])[NH:7][C:6]=2[CH:18]=1.[Cl:19][C:20]1[CH:25]=[CH:24][C:23]([NH:26][C:27]([NH2:29])=[NH:28])=[CH:22][CH:21]=1>>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[C:11]3[N:28]=[C:27]([NH:26][C:23]4[CH:22]=[CH:21][C:20]([Cl:19])=[CH:25][CH:24]=4)[N:29]=[CH:13][C:10]=3[CH2:9][C:8](=[O:17])[NH:7][C:6]=2[CH:18]=1
Reactant: N=C(N)Nc1ccc(Cl)cc1
Reactant: CN(C)C=C1CC(=O)Nc2cc(Cl)ccc2C1=O
Product: O=C1Cc2cnc(Nc3ccc(Cl)cc3)nc2-c2ccc(Cl)cc2N1

Procedure:
In a manner similar to that described for method I, 8-chloro-4-dimethylaminomethylene-3,4-dihydro-1H-benzo[b]azepine-2,5-dione (v-j) and 1-(4-chlorophenyl)guanidine were converted to I-11 (23%): HRMS Calcd. for C18H12Cl2N4O: 371.0466, Found 371.0471.
Reaction SMILES: [Cl:1][C:2]1[CH:19]=[CH:18][C:5]([CH2:6][C:7]2[C:8](=O)[CH2:9][C:10]([CH3:16])([CH3:15])[CH2:11][C:12]=2[O:13]C)=[CH:4][CH:3]=1.[H-].[Al+3].[Li+].[H-].[H-].[H-].[OH-].[Na+].[Cr](Cl)([O-])(=O)=O.[NH+]1C=CC=CC=1>C(OCC)C.O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][C:7]2[C:12](=[O:13])[CH2:11][C:10]([CH3:16])([CH3:15])[CH2:9][CH:8]=2)=[CH:18][CH:19]=1
Reactant: COC1=C(Cc2ccc(Cl)cc2)C(=O)CC(C)(C)C1
Agent: O=[Cr](=O)([O-])Cl
Agent: [Al+3]
Agent: [H-]
Solvent: CCOCC
Solvent: O
Product: CC1(C)CC=C(Cc2ccc(Cl)cc2)C(=O)C1
Reaction time: 0.08 h
Yield: 90.7 %

Procedure:
98 g (0.35 mol) of the 2-(4-chlorobenzyl)-3-methoxy-5,5-dimethylcyclohex-2-en-1-one obtained in (c) were added to a slurry of 6.65 g (0.175 mol) lithium aluminium hydride in 490 mls diethyl ether at a rate sufficient to maintain reflux and the final reaction mixture refluxed for a further 30 minutes. 5 ml water were then added, followed by 5 ml 15% aqueous sodium hydroxide and a further 15 ml water and the resulting precipitate was filtered off. The filtrate was then shaken in 200 ml 5M hydrochloric acid for five minutes and the organic layer then separated, washed twice with 100 ml aliquots of saturated sodium bicarbonate solution, dried over anhydrous magnesium sulphate and stripped. The resulting oil was then dissolved in 430 mls dichloromethane, 18 g (0.085 mols) pyridinium chlorochromate were added and the reaction mixture stirred for 3 hours. 600 ml diethyl ether were added and the solid was then filtered off. The filtrate was washed three times with 10% sodium hydroxide, once with 2.5M hydrochloric acid and once with saturated sodium bicarbonate solution. It was then dried over anhydrous magnesium sulphate and stripped to give 82 g of crude product. Distillation of the crude product under reduced pressure (0.15 mm mercury) gave 79 g 2-(4-chlorobenzyl)-5,5-dimethylcyclohex-2-en-1-one, b.pt. 130° C. at 0.15 mm mercury. Yield: 91%.
Reaction SMILES: [Cl:1][CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:11]=[CH:10][C:9]([NH2:12])=[CH:8][CH:7]=1.N1C=CC=CC=1.[CH3:19][S:20](Cl)(=[O:22])=[O:21]>C(Cl)Cl>[Cl:1][CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:11]=[CH:10][C:9]([NH:12][S:20]([CH3:19])(=[O:22])=[O:21])=[CH:8][CH:7]=1
Reactant: CS(=O)(=O)Cl
Reactant: Nc1ccc(OCCCCl)cc1
Solvent: ClCCl
Solvent: c1ccncc1
Product: CS(=O)(=O)Nc1ccc(OCCCCl)cc1
Temperature: 0 °C
Reaction time: 18 h
Yield: 89.6 %

Procedure:
To a cooled (0° C.), stirred solution of 1-chloro-3-(4-aminophenoxy)propane (680 mg, 3.66 mmol) and pyridine (319 mg, 4.03 mmol) in CH2Cl2 (10 mL) was added methanesulfonyl chloride (461 mg, 4.03 mmol). After 18 hours, the mixture was washed with 1N HCl and brine, dried (MgSO4), and concentrated to give 865 mg (90%) of product as an off-white solid m.p. 120°-122° C.
Reaction SMILES: [H-].[H-].[H-].[H-].[Li+].[Al+3].C([O:9][C:10](=O)[C:11]1[CH:16]=[CH:15][CH:14]=[C:13]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])[CH:12]=1)C>C(OCC)C>[C:18]([O:17][C:13]1[CH:12]=[C:11]([CH2:10][OH:9])[CH:16]=[CH:15][CH:14]=1)([CH3:21])([CH3:19])[CH3:20]
Reactant: CCOC(=O)c1cccc(OC(C)(C)C)c1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: CCOCC
Product: CC(C)(C)Oc1cccc(CO)c1
Temperature: 25 °C
Yield: 91.2 %

Procedure:
To a suspension of LiAlH4 (1.707 g, 0.045 mol) in anhydrous diethyl ether (80 mL) in a 3-necked rb flask equipped with addition funnel at 0° C. in an ice-water bath was added dropwise a solution of 3-tert-butoxy-benzoic acid ethyl ester (5.0 g, 0.0225 mol) in ether (20 mL). The reaction mixture was left to warm to rt over 15 min, then cooled in an ice-water bath and quenched by dropwise addition of H2O. The mixture was partitioned between ether and H2O, the aqueous layer washed with ether (2×30 mL), the organics combined, washed with brine, dried (MgSO4), filtered and concentrated to give 3.70 g (82%) of the title compound.
Reaction SMILES: Br[C:2]1[CH:3]=[N:4][CH:5]=[CH:6][CH:7]=1.[C:8]([N:12]1[CH:16]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH:15]([CH3:23])[N:14]([CH3:24])[C:13]1=[O:25])(=[O:11])[CH:9]=[CH2:10].CC1C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.CCN(C(C)C)C(C)C>CN(C=O)C.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH3:24][N:14]1[CH:15]([CH3:23])[CH:16]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[N:12]([C:8](=[O:11])/[CH:9]=[CH:10]/[C:2]2[CH:3]=[N:4][CH:5]=[CH:6][CH:7]=2)[C:13]1=[O:25]
Reactant: Brc1cccnc1
Reactant: C=CC(=O)N1C(=O)N(C)C(C)C1c1ccccc1
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: Cc1ccccc1P(c1ccccc1C)c1ccccc1C
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: CC1C(c2ccccc2)N(C(=O)/C=C/c2cccnc2)C(=O)N1C
Temperature: 110 °C

Procedure:
A solution of 3-bromopyridine (8.6 mL, 88.5 mmole), (4 R, 5 S)-1-acryloyl-3,4-dimethyl-5-phenylimidazolidin-2-one (14.4 g. 59 mmole), Pd(OAc)2 (662 mg, 2.95 mmole), P(o-tolyl)3 (1.80 g, 5.9 mmole), and (i-Pr)2NEt (22 mL, 124 mmole) in dry DMF (300 mL) was degassed (3×vacuum/N2 purge) then heated to 110° C. After 2 hr the mixture was cooled and poured into EtOAc. The resulting mixture was washed with H2O (3×), and the combined aqueous layers were back-extracted with EtOAc (2×). The combined organic layers were dried over MgSO4, filtered through a plug of silica gel, and concentrated. The residue was taken up in 1: EtOAc/hexanes and the solid was collected, washed with 1:1 EtOAc/hexanes, and dried in vacuo to afford a first crop of the title compound. The filtrate was concentrated and the crystallization process was repeated to afford a second crop. The total yield of the title compound was 17.53 g (92%): 1H NMR (400 MHz, CDCl3) δ 8.48-8.85 (m, 2H), 8.25 (d, J=15.9 Hz, 1 H), 7.89-7.97 (m, 1 H), 7.68 (d, J=15.9 Hz, 1 H), 7.15-7.38 (m, 6 H), 5.43 (d, J=8.5 Hz, 1 H), 3.90-4.02 (m, 1 H), 2.88 (s, 3H), 0.85 (d, J=6.6 Hz, 3 H); MS (ES) m/e 322 (M+H)+.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][C:3]=1[CH:9]([CH3:16])[CH2:10][SiH:11]([O:14][CH3:15])[O:12][CH3:13].[CH2:17]=[CH:18][CH2:19][CH2:20][CH2:21][CH3:22]>C(O)(C)C.[H+].[H+].Cl[Pt-2](Cl)(Cl)(Cl)(Cl)Cl>[CH3:13][O:12][Si:11]([O:14][CH3:15])([CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH3:22])[CH2:10][CH:9]([C:3]1[CH:4]=[C:5]([CH3:8])[CH:6]=[CH:7][C:2]=1[CH3:1])[CH3:16]
Reactant: CO[SiH](CC(C)c1cc(C)ccc1C)OC
Reactant: C=CCCCC
Agent: Cl[Pt-2](Cl)(Cl)(Cl)(Cl)Cl
Agent: [H+]
Solvent: CC(C)O
Product: CCCCCC[Si](CC(C)c1cc(C)ccc1C)(OC)OC
Yield: 59.5 %

Procedure:
In the same apparatus and procedures as EXAMPLE 1, 12.7 g (0.049 mole) of 3-(2,5-dimethylphenyl)-1,1-dimethoxy-1-silabutane, 13.1 g (0.15 mole) of 1-hexene, and 90 μl of 1% chloroplatinic acid in isopropanol were placed under the dry nitrogen atmosphere. The reactor was refluxed for 3 hours. Vacuum distillation of the reaction products gave 9.4 g (bp, 131°-3° C./0.6 mmHg) of 4,4-dimethoxy-2-(2,5-dimethylphenyl)-4-siladecane.
Reaction SMILES: [OH:1][C:2]1[CH:12]=[CH:11][C:5]2[NH:6][C:7](=[O:10])[CH2:8][S:9][C:4]=2[CH:3]=1.C(=O)([O-])[O-].[K+].[K+].Cl[CH2:20][CH2:21][CH2:22][N:23]1[CH2:28][CH2:27][N:26]([CH2:29][C:30]2[CH:39]=[CH:38][C:37]3[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=3)[N:31]=2)[CH2:25][CH2:24]1>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.CN(C)C=O>[N:31]1[C:32]2[C:37](=[CH:36][CH:35]=[CH:34][CH:33]=2)[CH:38]=[CH:39][C:30]=1[CH2:29][N:26]1[CH2:25][CH2:24][N:23]([CH2:22][CH2:21][CH2:20][O:1][C:2]2[CH:12]=[CH:11][C:5]3[NH:6][C:7](=[O:10])[CH2:8][S:9][C:4]=3[CH:3]=2)[CH2:28][CH2:27]1
Reactant: O=C1CSc2cc(O)ccc2N1
Reactant: ClCCCN1CCN(Cc2ccc3ccccc3n2)CC1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: O=C([O-])[O-]
Agent: [Br-]
Solvent: CN(C)C=O
Product: O=C1CSc2cc(OCCCN3CCN(Cc4ccc5ccccc5n4)CC3)ccc2N1
Temperature: 50 °C
Reaction time: 96 h
Yield: 26.5 %

Procedure:
After a mixture consisting of 7-hydroxy-3,4-dihydro-2H-1,4-benzothiazin-3-one (1.812 g, 10 mmol), tetra-n-butylammonium bromide (0.322 g, 1 mmol), potassium carbonate (2.764 g, 20 mmol), 1-(3-chloropropyl)-4-(2-quinolylmethyl)piperazine (3.039 g, 10 mmol) and N,N-dimethylformamide (40 ml) was stirred for 4 days at a bath temperature of 50° C. under an argon gas stream, the solvent was distilled off under reduced pressure. Water was added to the residue, followed by extraction with chloroform. The extract was washed with water and then dried over anhydrous magnesium sulfate. The extract was subjected to chromatography on a silica gel column (developer: chloroform/methanol=100/1 to 40/1) and then crystallized from ethyl acetate, whereby 1.188 g of the title compound were obtained as yellow prisms (yield: 26.5%).
Reaction SMILES: Cl[C:2]1[C:11]([C:12]([OH:14])=[O:13])=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([Cl:15])[CH:8]=2)[N:3]=1.[CH3:16][CH2:17][CH2:18][CH:19]([NH2:23])[C:20]([OH:22])=[O:21].CC#N>O>[C:20]([CH:19]([NH:23][C:2]1[C:11]([C:12]([OH:14])=[O:13])=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([Cl:15])[CH:8]=2)[N:3]=1)[CH2:18][CH2:17][CH3:16])([OH:22])=[O:21]
Reactant: O=C(O)c1cc2cc(Cl)ccc2nc1Cl
Reactant: CCCC(N)C(=O)O
Solvent: O
Solvent: CC#N
Product: CCCC(Nc1nc2ccc(Cl)cc2cc1C(=O)O)C(=O)O
Yield: 15 %

Procedure:
In close analogy to the procedure described in Example 1, 2,6-dichloroquinoline-3-carboxylic acid is reacted with DL-2-aminopentanoic acid to provide the title compound in 15% yield as yellow needles (flash chromatography on SiO2, eluent MeCN, H2O, AcOH-20, 1, 0.3).
Reaction SMILES: C(B(CC)CC)C.[OH:8][CH:9]([CH2:14][C:15](=[O:22])[CH2:16][C:17]([O:19][CH2:20][CH3:21])=[O:18])[C:10]([O:12][CH3:13])=[O:11].B.[BH4-].[Na+]>C1COCC1.O.C(O)(=O)C.CO>[OH:8][CH:9]([CH2:14][CH:15]([OH:22])[CH2:16][C:17]([O:19][CH2:20][CH3:21])=[O:18])[C:10]([O:12][CH3:13])=[O:11]
Reactant: CCOC(=O)CC(=O)CC(O)C(=O)OC
Agent: B
Agent: CCB(CC)CC
Agent: [BH4-]
Solvent: CO
Solvent: C1CCOC1
Solvent: O
Product: CCOC(=O)CC(O)CC(O)C(=O)OC
Temperature: -55 °C
Reaction time: 1 h
Yield: 69 %

Procedure:
A mixture of THF (2.5 ml), methanol (5 ml) and triethylborane (1M in THF) (12 ml) was stirred at a temperature from -50 to -60° C. for one hour in an argon atmosphere. A solution of 1-methyl 6-ethyl 2-hydroxy-4-oxoadipate (2.2 g, 10 mmol) in THF (2.5 ml) was dropwise added to the above borane solution at -60° C. After stirring at -78° C. for 60 minutes, sodium borohydride (378 mg, 10 mmol) was added in one portion, followed by stirring at -78° C. for 2 hours. After dropwise adding acetic acid (3 ml) to the reaction solution at -78° C., the solution was stirred for 15 minutes. After adding water (5 ml), THF was evaporated off. After adding ethanol (10 ml) and a 10 % hydrogen peroxide (1.5 ml) at room temperature, 1 N hydrochloric acid was added to adjust pH to 7, followed by stirring for one hour. After adding a 5 % aqueous solution of sodium sulfite (15 ml) and stirring the mixture at room temperature for 40 minutes, the mixture was extracted with methylene chloride and organic layers were combined, dried over sodium sulfate and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography (hexane:acetone=5:1) to give pure 1-methyl 6-ethyl 2,4-dihydroxyadipate (1.52 g, 6.9 mmol). Yield, 69 %.
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[C:2]1[C:10]1[C:18]2[C:13](=[CH:14][CH:15]=[C:16]([O:19]C3C=CC=CC=3)[CH:17]=2)[NH:12][N:11]=1.C([O-])=O.[NH4+]>C(O)C.[Pd]>[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[C:2]1[C:10]1[C:18]2[C:13](=[CH:14][CH:15]=[C:16]([OH:19])[CH:17]=2)[NH:12][N:11]=1
Reactant: c1ccc(Oc2ccc3[nH]nc(-c4cc5ccccc5[nH]4)c3c2)cc1
Agent: [Pd]
Agent: O=C[O-]
Agent: [NH4+]
Solvent: CCO
Product: Oc1ccc2[nH]nc(-c3cc4ccccc4[nH]3)c2c1
Yield: 89.4 %

Procedure:
A solution of 2.54 g of 3-(1H-indol-2-yl)-5-phenoxy-1H-indazole, of 2.83 g of ammonium formate and 2.54 g of palladium-on-charcoal at 10% in 150 ml of ethanol is refluxed for one hour. The catalyst is filtered through paper and rinsed with ethanol. The filtrate is concentrated to dryness to obtain 1.74 g of 3-(1H-indol-2-yl)-1H-indazol-5-ol.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[CH:4][C:5]([C:12]2[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=2)=[C:6]2[C:10]=1[C:9](=[O:11])[NH:8][CH2:7]2.[Si:19](Cl)([C:22]([CH3:25])([CH3:24])[CH3:23])([CH3:21])[CH3:20].C1CCN2C(=NCCC2)CC1>C(#N)C>[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([C:12]2[CH:17]=[CH:16][C:15]([O:18][Si:19]([C:22]([CH3:25])([CH3:24])[CH3:23])([CH3:21])[CH3:20])=[CH:14][CH:13]=2)=[C:6]2[C:10]=1[C:9](=[O:11])[NH:8][CH2:7]2
Reactant: CC(C)(C)[Si](C)(C)Cl
Reactant: Nc1ccc(-c2ccc(O)cc2)c2c1C(=O)NC2
Solvent: C1CCC2=NCCCN2CC1
Solvent: CC#N
Product: CC(C)(C)[Si](C)(C)Oc1ccc(-c2ccc(N)c3c2CNC3=O)cc1
Yield: 67.5 %

Procedure:
In a similar manner to Step 1 of Example 304, 7-amino-4-(4-hydroxyphenyl)isoindolinone (182 mg, 0.760 mmol) was dissolved in acetonitrile (9.1 mL), and the solution was treated with tert-butyldimethylsilyl chloride (206 mg, 1.37 mmol) and DBU (0.205 mL, 1.37 mmol), followed by purification by flash column chromatography (chloroform) to obtain 7-amino-4-(4-tert-butyldimethylsilyloxyphenyl)isoindolinone (182 mg, yield 68%).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:20]=[CH:19][C:6]([C:7]([O:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][N:16]=[N+]=[N-])=[O:8])=[CH:5][CH:4]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O>C1COCC1.CCOC(C)=O>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([C:7]([O:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][NH2:16])=[O:8])=[CH:19][CH:20]=1
Reactant: COc1ccc(C(=O)OCCCCCCN=[N+]=[N-])cc1
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Solvent: O
Product: COc1ccc(C(=O)OCCCCCCN)cc1
Temperature: 25 °C
Reaction time: 144 h
Yield: 7.8 %

Procedure:
A mixture of 4-methoxybenzoic acid, 6-azidohexyl ester (1.119 g, 4.035 mmol), triphenylphosphine (1.164 g, 4.439 mmol), and water (0.08 ml) in THF was stirred under nitrogen at room temperature. After ˜144 h, the reaction mixture was diluted with EtOAc (50 ml), dried over Na2SO4, filtered and the filtrate concentrated in vac and dried. The residue was purified by flash chromatography (2×)(alumina, chloroform to 10% MeOH/CHCl3 gradient) to give the desired product as a light yellow oil (.0796 g, 78%); 1H NMR (400 MHz, DMSO-d6) δ1.18-1.40 (m, 6H), 1.63-1.71 (m, 2H), 2.50 (t, J=6.4 Hz, 2H), 3.82 (s, 3H), 4.21 (t, J=6.6 Hz, 2H), 7.01-7.06 (m, 2H), 7.87-7.92 (m, 2H); IR (KBr) 3410 (broad), 2940, 1710, 1605, 1510, 1260 cm−1; mass spectrum[(+)ESI], m/z 252 (M+H)+.
Reaction SMILES: [C:1]([C:4]1[CH:5]=[C:6]([CH:9]=[CH:10][C:11]=1[OH:12])[C:7]#[N:8])(=[O:3])[CH3:2].[CH3:13][C:14]([CH:16]([O:19][CH3:20])[O:17][CH3:18])=O.N1CCCC1>C1(C)C=CC=CC=1>[CH3:18][O:17][CH:16]([O:19][CH3:20])[C:14]1([CH3:13])[CH2:2][C:1](=[O:3])[C:4]2[CH:5]=[C:6]([C:7]#[N:8])[CH:9]=[CH:10][C:11]=2[O:12]1
Reactant: CC(=O)c1cc(C#N)ccc1O
Reactant: COC(OC)C(C)=O
Solvent: C1CCNC1
Solvent: Cc1ccccc1
Product: COC(OC)C1(C)CC(=O)c2cc(C#N)ccc2O1
Yield: 85.7 %

Procedure:
In 100 ml of toluene were dissolved 8.06 g (50 mmole) of 3-acetyl-4-hydroxybenzonitrile and 7.68 g (65 mmole) of pyruvic aldehyde dimethyl acetal; and, 1.67 ml (20 mmole) of pyrrolidine was added at room temperature thereto. 30 Minutes thereafter, the reactants were heated to reflux for 8 hours using Dean-Stark apparatus. The solvent was removed under reduced pressure; and, 50 ml of 2N HCl solution was added to the residue so obtained. The resultant solution was stirred for 30 minutes at room temperature, extracted with ethyl acetate (100 ml×2), washed with 50 ml of water and then with 50 ml of saturated sodium chloride aqueous solution and purified by silica gel column chromatography using as an eluent a mixture of hexane and ethyl acetate (4:1) to obtain 11.19 g (yield 86%) of the title compound as a white solid.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:34]=[CH:33][C:12]([O:13][C:14]2[CH:19]=[CH:18][C:17]([C:20]3[NH:24][C:23]4[CH:25]=[C:26]([Br:29])[CH:27]=[CH:28][C:22]=4[N:21]=3)=[CH:16][C:15]=2[N+:30]([O-])=O)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Cl-].[NH4+]>O.C(O)C.C(OCC)(=O)C.[Fe]>[CH2:1]([O:8][C:9]1[CH:34]=[CH:33][C:12]([O:13][C:14]2[CH:19]=[CH:18][C:17]([C:20]3[NH:24][C:23]4[CH:25]=[C:26]([Br:29])[CH:27]=[CH:28][C:22]=4[N:21]=3)=[CH:16][C:15]=2[NH2:30])=[CH:11][CH:10]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: O=[N+]([O-])c1cc(-c2nc3ccc(Br)cc3[nH]2)ccc1Oc1ccc(OCc2ccccc2)cc1
Agent: [Fe]
Agent: [Cl-]
Agent: [NH4+]
Solvent: CCO
Solvent: CCOC(C)=O
Solvent: O
Product: Nc1cc(-c2nc3ccc(Br)cc3[nH]2)ccc1Oc1ccc(OCc2ccccc2)cc1
Temperature: 25 °C
Yield: 93 %

Procedure:
The product of Example 147B (374 mg, 0.723 mmol), iron powder (248 mg, 4.45 mmol), and ammonium chloride (253 mg, 4.74 mmol) in water (5 mL) and ethanol (10 mL) were heated at 80° for 45 minutes. The reaction mixture was cooled to room temperature, diluted with ethyl acetate (100 mL), and washed with water (2×50 mL) and brine (50 mL). The organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated by rotary evaporation under vacuum provided the title compound as a golden solid (327 mg, 93%).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][CH:10]=1)[C:5]([OH:7])=[O:6].[OH-].[Na+].Cl[C:14]([O:16][CH:17]([CH2:19][CH3:20])[CH3:18])=[O:15]>O>[C:14](=[O:15])([O:16][CH:17]([CH3:18])[CH2:19][CH3:20])[O:6][C:5](=[O:7])[C:4]1[CH:8]=[CH:9][CH:10]=[C:2]([Cl:1])[CH:3]=1
Reactant: CCC(C)OC(=O)Cl
Reactant: O=C(O)c1cccc(Cl)c1
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: CCC(C)OC(=O)OC(=O)c1cccc(Cl)c1
Yield: 97.4 %

Procedure:
To a well-stirred reaction vessel equipped with a thermometer and a pH electrode were added 39 g of water and 0.20 g of Arquad CB50 at 5° C. After the addition of 0.05 mole of 3-chlorobenzoic acid the pH was adjusted to 6 using a 10 wt % aqueous NaOH solution. Then, 0.05 mole of sec-butyl chloroformate was dosed within 5 min at 5° C. During this time and a post-reaction time of 165 min at 5° C. the pH was kept at a value between 6 and 9. The reaction mixture was allowed to separate, giving 12.5 g of 3-chlorobenzoyl 1-methyl-1-propyl carbonate having a content of 98% in a yield of 95%.
Reaction SMILES: [N:1]1[N:2]2[CH:10]=[CH:9][CH:8]=[C:3]2[C:4](O)=[N:5][CH:6]=1.C(N(C(C)C)CC)(C)C.P(Cl)(Cl)([Cl:22])=O.C([O-])(O)=O.[Na+]>C1(C)C=CC=CC=1>[Cl:22][C:4]1[C:3]2=[CH:8][CH:9]=[CH:10][N:2]2[N:1]=[CH:6][N:5]=1
Reactant: O=P(Cl)(Cl)Cl
Reactant: Oc1ncnn2cccc12
Agent: O=C([O-])O
Agent: [Na+]
Solvent: Cc1ccccc1
Solvent: CCN(C(C)C)C(C)C
Product: Clc1ncnn2cccc12
Temperature: 100 °C
Reaction time: 0.5 h
Yield: 97 %

Procedure:
To a solution of pyrrolo[2,1-f][1,2,4]triazin-4-ol (3.70 g, 27.4 mmol, see generally, PCT Appl. WO 2000/071129 the disclosure of which is herein incorporated by reference in its entirety) in 40 mL of toluene at room temperature was added 4.77 mL (27.4 mmol) of diisopropylethylamine followed by 7.70 mL (82.6 mmol) of phosphorus oxychloride. The reaction mixture was heated at 100° C. for 18 h. After cooling to room temperature, the reaction was slowly added to a solution of 5% aq NaHCO3 solution (100 mL) at 0° C. Upon completion of the addition, the biphasic mixture was allowed to stir at room temperature for 30 min. The aqueous layer was extracted with EtOAc (3×100 mL) and the pooled organic extracts were washed with brine (100 mL), dried over anhydrous MgSO4, and concentrated in vacuo to give the crude product (4.10 g, 97%) as a yellow solid. 1H NMR (CDCl3) δ 8.14 (s, 1H), 7.80 (dd, 1H, J=2.4, 1.5 Hz), 6.91 (m, 2H).
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]([C:9]1[CH:10]=[C:11](Br)[C:12](=[O:21])[N:13]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH:14]=1)=[O:8].[C:23]([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=1B1OC(C([O-])=O)C=CO1)#[N:24].C(=O)([O-])[O-].[Cs+].[Cs+].CN(C)C=O>C(OCC)(=O)C>[C:23]([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=1[C:11]1[C:12](=[O:21])[N:13]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH:14]=[C:9]([C:7]([C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=2)=[O:8])[CH:10]=1)#[N:24]
Reactant: O=C(c1cc(Br)c(=O)n(-c2ccccc2)c1)c1ccccn1
Reactant: N#Cc1ccccc1B1OC=CC(C(=O)[O-])O1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: N#Cc1ccccc1-c1cc(C(=O)c2ccccn2)cn(-c2ccccc2)c1=O
Temperature: 130 °C
Reaction time: 5 h
Yield: 21.2 %

Procedure:
To a mixed liquid of 200 mg of 5-(2-pyridinecarbonyl)-1-phenyl-3-bromo-1,2-dihydropyridin-2-one, 130 mg of 2-(2-cyanophenyl)-1,3,2-dioxaborinate, 400 mg of cesium carbonate and 6 ml of dimethylformamide was added 60 mg of tetrakistriphenylphosphine palladium, followed by stirring at 130° C. for 5 hours in nitrogen atmosphere. After cooling to room temperature, ethyl acetate was added thereto. The extract was washed with water and brine, and dried over magnesium sulfate. The solvent was evaporated, and the residue was purified by silica gel chromatography (ethyl acetate/hexane), to give 45 mg of the title compound as a pale yellow powder.
Reaction SMILES: [CH:1]1[C:14]2[CH2:13][C:12]3[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=3)[O:6][C:5]=2[CH:4]=[CH:3][C:2]=1[CH:15]([CH3:19])[C:16](O)=[O:17].[H-].[H-].[H-].[H-].[Li+].[Al+3].[OH-].[Na+]>C1COCC1.O>[CH:1]1[C:14]2[CH2:13][C:12]3[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=3)[O:6][C:5]=2[CH:4]=[CH:3][C:2]=1[CH:15]([CH3:19])[CH2:16][OH:17]
Reactant: CC(C(=O)O)c1ccc2c(c1)Cc1ccccc1O2
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Solvent: O
Product: CC(CO)c1ccc2c(c1)Cc1ccccc1O2

Procedure:
A solution of 2.54 g. of 2-(2-xanthenyl)-propionic acid in 20 ml. of absolute THF is added dropwise to a mixture of 0.57 g. of LiAlH4 in 20 ml. of absolute THF. The mixture is refluxed for 8 hours, 2 ml. of water in 3 ml. of THF, as well as 4 ml. of 25% sodium hydroxide solution are added thereto, the mixture is decanted and the residue washed with ether. After the drying, filtration, and evaporation of the combined organic phases, 2-(2-xanthenyl)-propanol is obtained, m.p. 86°-89°.