Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: OCCO[CH:5]([CH2:9]OC(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[CH2:6][CH2:7][OH:8].C(N(CC)CC)C.[CH3:37][S:38](Cl)(=[O:40])=[O:39]>C(Cl)Cl>[CH3:37][S:38]([O:8][CH2:7][CH2:6][CH2:5][CH3:9])(=[O:40])=[O:39]
Reactant: CS(=O)(=O)Cl
Reactant: OCCOC(CCO)COC(c1ccccc1)(c1ccccc1)c1ccccc1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CCCCOS(C)(=O)=O
Temperature: 0 °C

Procedure:
3-(2-hydroxyethoxy)-4-(triphenylmethoxy)-1-butanol (14.0 g, 35.7 mmol) was dissolved in 140 mL of CH2Cl2, was cooled to 0° C. under N2, and triethylamine (10.8 g, 14.9 mL, 0.107 mol. 3.0 eq.) was added. Methanesulfonyl chloride (11.0 g, 7.46 mL, 96.4 mmol, 2.7 eq.) was then added dropwise at <5° C. The resultant reaction mixture was diluted with additional CH2Cl2 (300 mL) and was washed with 200 mL of water and 200 mL of an aqueous saturated solution of ammonium chloride. The aqueous layers were back-extracted with 50 mL of CH2Cl2 and the combined organic layer was washed with 100 mL of brine and was dried (MgSO4) and evaporated in vacuo to give 18.4 g (94%) of 3-(2-[(methylsulfonyl)oxy]ethoxy]-4-triphenylmethoxy)-1-butanol methane sulfonate as a white solid.
Reaction SMILES: CC(C)[O-].[Al+3].CC(C)[O-].CC(C)[O-].[Cl:14][C:15]([Cl:22])=[CH:16][C:17](=[O:21])[CH:18]([CH3:20])[CH3:19]>>[Cl:14][C:15]([Cl:22])=[CH:16][CH:17]([OH:21])[CH:18]([CH3:20])[CH3:19]
Reactant: CC(C)C(=O)C=C(Cl)Cl
Agent: CC(C)[O-]
Agent: [Al+3]
Product: CC(C)C(O)C=C(Cl)Cl
Yield: 94.8 %

Procedure:
The reaction vessel containing the aluminum isopropoxide was fitted with a condenser, and 1737 gm (10.60 moles) of 1,1-dichloro-4-methyl-1-penten-3-one was added. The reaction mixture was heated to reflux, and the evolved acetone was removed by distillation over a 19.25 hour period. The isopropanol was then removed by distillation, and the residue was separated into two portions of 1100 ml and 1900 ml respectively. The 1100 ml portion was hydrolyzed in 3000 ml of aqueous hydrochloric acid and then washed three times with 900 ml of benzene. For the 1900 ml portion, 5100 ml of aqueous hydrochloric acid and 1500 ml of benzene were used. The benzene washes were combined and washed with 4000 ml of water. The organic layer was separated and dried over magnesium sulfate. Most of the benzene was removed by distillation under atmospheric pressure. The residue was filtered, and the last trace of solvent was removed by distillation under reduced pressure. The residue was distilled under reduced pressure to give 1698 gm (94.8% yield) of 1,1-dichloro-3-hydroxy-4-methyl-1-pentene; b.p., 67°-83°/4-7mm.
Reaction SMILES: [C-:1]#[N:2].[Na+].F[B-](F)(F)F.[Cl:9][C:10]1[CH:15]=[CH:14][C:13]([N+]#N)=[CH:12][CH:11]=1>O>[Cl:9][C:10]1[CH:15]=[CH:14][C:13]([C:1]#[N:2])=[CH:12][CH:11]=1
Reactant: N#[N+]c1ccc(Cl)cc1
Reactant: [C-]#N
Agent: F[B-](F)(F)F
Agent: [Na+]
Solvent: O
Product: N#Cc1ccc(Cl)cc1
Yield: 75 %

Procedure:
Sodium cyanide (2.94 g; 0.06 mol) was added to water and stirred. Cuprous cyanide (2.7 g; 0.03 mol) was added to the mixture stirred until it became homogeneous. 4-chlorobenzenediazonium tetrafluoroborate (5.66 g; 0.025 mol) in water (10 ml) was added to one portion. The mixture was allowed to react at room temperature. The mixture was extracted by ethyl acetate and the extract analysed by means of gas chromatography which indicated that 4-chlorobenzonitrile had been formed in 75% yield.
Reaction SMILES: C(N(CC)CC)C.[OH:8][C:9]1[CH:22]=[C:21]([OH:23])[CH:20]=[CH:19][C:10]=1[C:11]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)=O.ClC(OCC)=O.O>C1COCC1>[CH2:11]([C:10]1[CH:19]=[CH:20][C:21]([OH:23])=[CH:22][C:9]=1[OH:8])[C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1
Reactant: O=C(c1ccccc1)c1ccc(O)cc1O
Agent: CCOC(=O)Cl
Solvent: O
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: Oc1ccc(Cc2ccccc2)c(O)c1
Temperature: 0 °C
Reaction time: 0.5 h

Procedure:
Triethyl amine (10 ml, 72.2 mmol) was added to a solution of 2,4-dihydroxybenzophenone (1) (5.4 g, 23.3 mmol) in THF (50 ml) and the solution cooled to 0° C. Ethyl chloroformate (6.9 ml, 72.2 mmol) was added slowly and the suspension stirrred for ˜30 mins at 0° C., and for ˜3 hrs at room temperature. Water (150 ml) was added and the mixture extracted with diethyl ether (150 ml). The extracts were washed with water (2×150 ml) and saturated aqueous sodium chloride solution (100 ml). The solution was dried over anhydrous magnesium sulphate and concentrated to give 4-benzyl-benzene-1,3-diol as a pale green gum, solidified on standing, (8.2 g).
Reaction SMILES: Cl.[F:2][C:3]1[CH:8]=[CH:7][C:6]([S:9]([CH2:12][CH:13]2[CH2:16][NH:15][CH2:14]2)(=[O:11])=[O:10])=[CH:5][CH:4]=1.CCN(CC)CC.Br[CH2:25][C:26]([C:28]1[CH:33]=[CH:32][C:31]([F:34])=[CH:30][C:29]=1[CH3:35])=[O:27]>CC#N>[F:34][C:31]1[CH:32]=[CH:33][C:28]([C:26](=[O:27])[CH2:25][N:15]2[CH2:16][CH:13]([CH2:12][S:9]([C:6]3[CH:7]=[CH:8][C:3]([F:2])=[CH:4][CH:5]=3)(=[O:11])=[O:10])[CH2:14]2)=[C:29]([CH3:35])[CH:30]=1
Reactant: Cc1cc(F)ccc1C(=O)CBr
Reactant: O=S(=O)(CC1CNC1)c1ccc(F)cc1
Agent: Cl
Solvent: CC#N
Solvent: CCN(CC)CC
Product: Cc1cc(F)ccc1C(=O)CN1CC(CS(=O)(=O)c2ccc(F)cc2)C1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 56.5 %

Procedure:
A mixture of 3-{[(4-fluorophenyl)sulfonyl]methyl}azetidine hydrochloride (75 mg, 0.28 mmol) in MeCN (5 mL) was treated with Et3N (97 μL, 0.7 mmol) and 2-bromo-1-(4-fluoro-2-methylphenyl)ethanone (72 mg, 0.31 mmol) and stirred for 30 min at room temperature. The reaction was evaporated and the residue dissolved in DCM and purified using 10 g silica bond-elute cartridge on the personal flash master. The column was eluted with 0.5% MeOH/DCM then 1% MeOH/DCM to give the title compound as a cream solid (60 mg, 56%). 1H NMR (500 MHz, CDCl3)δ2.49 (3H, s), 2.93–2.98 (1H, m), 3.08 (2H, t, J=7.4 Hz), 3.41 (2H, d, J=7.4 Hz), 3.62 (2H, t, J=7.4 Hz), 3.77 (2H, s), 6.89–6.95 (2H, m), 7.23–7.27 (2H, t, J=8.8 Hz), 7.61 (1H, dd, J=5.8 & 8.5 Hz), 7.90–7.92 (2H, dd, J=5.2 & 8.8 Hz). m/z (ES+) 380 (M+H)+.
Reaction SMILES: [OH:1][C:2]1[C:7]2[S:8][C:9]3[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=3[C:6]=2[S:5](=[O:16])(=[O:15])[N:4]([CH3:17])[C:3]=1[C:18](OC)=[O:19].[NH2:22][C:23]1[N:28]=[CH:27][CH:26]=[CH:25][N:24]=1>>[OH:1][C:2]1[C:7]2[S:8][C:9]3[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=3[C:6]=2[S:5](=[O:16])(=[O:15])[N:4]([CH3:17])[C:3]=1[C:18]([NH:22][C:23]1[N:28]=[CH:27][CH:26]=[CH:25][N:24]=1)=[O:19]
Reactant: Nc1ncccn1
Reactant: COC(=O)C1=C(O)c2sc3ccccc3c2S(=O)(=O)N1C
Product: CN1C(C(=O)Nc2ncccn2)=C(O)c2sc3ccccc3c2S1(=O)=O
Yield: 39 %

Procedure:
Prepared analogous to Example 1 from methyl 4-hydroxy-2-methyl-2H[1] benzothieno [2,3-e]-1,2-thiazine-3-carboxylate-1,1-dioxide and 2-amino-pyrimidine with a yield of 39% of theory.
Reaction SMILES: [CH2:1]([N:3]([C:10]1[CH:15]=[CH:14][C:13]([C:16]2[CH:17]=[CH:18][C:19]3[N:25]([CH:26]=[O:27])[CH2:24][CH2:23][C:22]([C:28]([OH:30])=O)=[CH:21][C:20]=3[CH:31]=2)=[CH:12][CH:11]=1)[CH2:4][CH2:5][O:6][CH2:7][CH2:8][CH3:9])[CH3:2].S(Cl)(Cl)=O.[CH3:36][N:37]([CH:39]=O)[CH3:38]>>[CH2:1]([N:3]([C:10]1[CH:11]=[CH:12][C:13]([C:16]2[CH:17]=[CH:18][C:19]3[N:25]([CH:26]=[O:27])[CH2:24][CH2:23][C:22]([C:28]([NH:3][C:10]4[CH:15]=[CH:14][C:13]([CH2:39][N:37]([CH3:36])[CH:38]5[CH2:8][CH2:7][O:6][CH2:5][CH2:4]5)=[CH:12][CH:11]=4)=[O:30])=[CH:21][C:20]=3[CH:31]=2)=[CH:14][CH:15]=1)[CH2:4][CH2:5][O:6][CH2:7][CH2:8][CH3:9])[CH3:2]
Reactant: CCCOCCN(CC)c1ccc(-c2ccc3c(c2)C=C(C(=O)O)CCN3C=O)cc1
Reactant: CN(C)C=O
Solvent: O=S(Cl)Cl
Product: CCCOCCN(CC)c1ccc(-c2ccc3c(c2)C=C(C(=O)Nc2ccc(CN(C)C4CCOCC4)cc2)CCN3C=O)cc1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
In DMF (7 ml) was dissolved 7-[4-[N-ethyl-N-(2-propoxyethyl)amino]phenyl]-1-formyl-2,3-dihydro-1H-1-benzazepine-4-carboxylic acid (0.25 g). To the solution was added, under ice-cooling, thionyl chloride (0.11 ml), and the mixture was stirred at room temperature for 30 minutes. Under reduced pressure, the solvent was evaporated, and the residue was dissolved in THF (25 ml). The solution was added dropwise to a solution of 4-[N-methyl-N-(tetrahydro-2H-pyran-4-yl)aminomethyl]aniline (0.16 g) and triethylamine (0.41 ml) in THF (5 ml), under ice-cooling, and the mixture was stirred under nitrogen atmosphere at room temperature overnight. Under reduced pressure, the solvent was evaporated. To the residue was added water, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine and dried with anhydrous magnesium sulfate, and the solvent was evaporated to give crude crystals, which were recrystallized from ethyl acetate/hexane to give 7-[4-[N-ethyl-N-(2-propoxyethyl)amino]phenyl]-1-formyl-N-[4-[[N-methyl-N-(tetrahydro-2H-pyran-4-yl)amino]methyl]phenyl]-2,3-dihydro-1H-1-benzazepine-4-carboxamide (Compound 6) (0.27 g) as pale yellow crystals.
Reaction SMILES: [CH3:1][NH:2][C:3]1[S:4][CH:5]=[C:6]([C:8]([O:10]CC)=O)[N:7]=1.C(O)(C)C.[CH3:17][N:18]([CH3:22])[CH2:19][CH2:20][NH2:21]>>[CH3:1][NH:2][C:3]1[S:4][CH:5]=[C:6]([C:8]([NH:21][CH2:20][CH2:19][N:18]([CH3:22])[CH3:17])=[O:10])[N:7]=1
Reactant: CN(C)CCN
Reactant: CCOC(=O)c1csc(NC)n1
Solvent: CC(C)O
Product: CNc1nc(C(=O)NCCN(C)C)cs1
Temperature: 100 °C
Reaction time: 6 h
Yield: 54.8 %

Procedure:
In 3.5 g of N,N-dimethylethylenediamine, 2.5 g of 2-(N-methylamino)-4-(ethoxycarbonyl)-1,3-thiazole was dissolved, followed by stirring at 100° C. for 6 hours. The reaction mixture was poured into isopropyl alcohol and the crystals so precipitated were collected by filtration, whereby 1.68 g of the title compound was obtained. Yield: 51.5%.
Reaction SMILES: [CH3:1][C:2]1([CH3:16])[CH2:14][C:5]2[S:6][C:7]([C:9]([O:11]CC)=[O:10])=[CH:8][C:4]=2[C:3]1=[O:15].C1COCC1.C(O)C.[OH-].[Li+]>O>[CH3:1][C:2]1([CH3:16])[CH2:14][C:5]2[S:6][C:7]([C:9]([OH:11])=[O:10])=[CH:8][C:4]=2[C:3]1=[O:15]
Reactant: CCOC(=O)c1cc2c(s1)CC(C)(C)C2=O
Agent: [Li+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CCO
Solvent: O
Product: CC1(C)Cc2sc(C(=O)O)cc2C1=O
Temperature: 50 °C
Reaction time: 2 h
Yield: 106.8 %

Procedure:
A 50-mL single-neck round-bottomed flask equipped with a magnetic stirrer and reflux condenser was charged with 8 (310 mg, 1.30 mmol), THF (2 mL) and ethanol (2 mL). A solution of lithium hydroxide (125 mg, 5.21 mmol) in water (2 mL) was added, and the mixture was stirred at 50° C. for 2 h. After this time, the organic solvents were removed under reduced pressure, water (6 mL) was added, and the pH was adjusted to 3.0 with 2 N hydrochloric acid. The resulting suspension was filtered and the filter cake washed with water (2 mL). The filter cake was dried to constant weight under vacuum at 40° C. to afford a 100% yield (292 mg) of 9 as a white solid: mp 124-125° C.; 1H NMR (500 MHz, CDCl3) δ 7.93 (s, 1H), 3.10 (s, 2H), 1.34 (5, 6H); MS (ESI+) m/z 211.0 (M+H).
Reaction SMILES: [CH3:1][N:2]([CH2:4][C:5]1[CH:15]=[CH:14][C:8]([CH2:9][S:10][CH2:11][CH2:12][NH2:13])=[CH:7][CH:6]=1)[CH3:3].[N+](N[C:20]1[NH:25][C:24](=[O:26])[C:23]([CH2:27][C:28]2[CH:29]=[N:30][CH:31]=[CH:32][CH:33]=2)=[CH:22][N:21]=1)([O-])=O>>[CH3:3][N:2]([CH2:4][C:5]1[CH:15]=[CH:14][C:8]([CH2:9][S:10][CH2:11][CH2:12][NH:13][C:20]2[NH:25][C:24](=[O:26])[C:23]([CH2:27][C:28]3[CH:29]=[N:30][CH:31]=[CH:32][CH:33]=3)=[CH:22][N:21]=2)=[CH:7][CH:6]=1)[CH3:1]
Reactant: CN(C)Cc1ccc(CSCCN)cc1
Reactant: O=c1[nH]c(N[N+](=O)[O-])ncc1Cc1cccnc1
Product: CN(C)Cc1ccc(CSCCNc2ncc(Cc3cccnc3)c(=O)[nH]2)cc1

Procedure:
Reaction of 2-[4-(dimethylaminomethyl)benzylthio]-ethylamine (1.7 g) with 2-nitroamino-5-(3-pyridylmethyl)-4-pyrimidone (1.7 g) in a similar manner to Example 7(iv) gave 2-[2-(4-(dimethylaminomethyl)benzylthio)ethylamino]-5-(3-pyridylmethyl)-4-pyrimidone m.p. 127°-130°. A sample recrystallised a further time from acetonitrile had m.p. 124°-126°.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:7])[C:5]#[CH:6])[CH3:2].[CH2:8]([OH:18])[CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH:16]=[CH2:17].CN1CCOCC1>C(OCC)C>[CH2:1]([O:3][C:4](=[O:7])/[CH:5]=[CH:6]/[O:18][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH:16]=[CH2:17])[CH3:2]
Reactant: C#CC(=O)OCC
Reactant: C=CCCCCCCCCO
Solvent: CCOCC
Solvent: CN1CCOCC1
Product: C=CCCCCCCCCO/C=C/C(=O)OCC
Temperature: 25 °C
Reaction time: 24 h
Yield: 91.2 %

Procedure:
The reaction was performed in standard glassware under an atmosphere of N2. To 150 ml of diethylether were added 9.8 g (0.1 mol) propiolic acid ethyl ester, 15.6g (0.1 mol) dec-9-en-1-ol and 10.1 g (0.1 mol) N-methylmorpholine. This solution was kept without stirring at room temperature for 24 hours. The mixture was evaporated under vacuum and the residue purified by bulb to bulb distillation (bp: 85-90° C.; 0.006 mbar) to yield 23.2 g (916%) of an oil.
Reaction SMILES: [Br:1][C:2]1[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][CH:6]=[C:7]2[CH2:16][OH:17].C1C=C[NH+]=CC=1.[O-][Cr](Cl)(=O)=O>>[Br:1][C:2]1[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][CH:6]=[C:7]2[CH:16]=[O:17]
Reactant: OCc1cccc2c(Br)c3ccccc3cc12
Agent: O=[Cr](=O)([O-])Cl
Agent: c1cc[nH+]cc1
Product: O=Cc1cccc2c(Br)c3ccccc3cc12

Procedure:
Using the procedure outlined in 2D, oxidation of (10-bromo-1-anthryl)-methanol with PCC gave 10-bromo-1-anthracenecarbaldehyde mp 134.5°-135.5°, (PhCH3 /hexane), (C, H, Br).
Reaction SMILES: [C:1]1([S:7]([NH:10][C:11]2[S:15][C:14]3[CH2:16][CH2:17][CH2:18][CH2:19][C:13]=3[C:12]=2[C:20]([O:22][CH2:23][CH3:24])=[O:21])(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.NC1SC2CCCCC=2C=1C(OCC)=O.[F:40]C1C=CC(S(Cl)(=O)=O)=CC=1>>[F:40][C:4]1[CH:3]=[CH:2][C:1]([S:7]([NH:10][C:11]2[S:15][C:14]3[CH2:16][CH2:17][CH2:18][CH2:19][C:13]=3[C:12]=2[C:20]([O:22][CH2:23][CH3:24])=[O:21])(=[O:9])=[O:8])=[CH:6][CH:5]=1
Reactant: O=S(=O)(Cl)c1ccc(F)cc1
Reactant: CCOC(=O)c1c(NS(=O)(=O)c2ccccc2)sc2c1CCCC2
Agent: CCOC(=O)c1c(N)sc2c1CCCC2
Product: CCOC(=O)c1c(NS(=O)(=O)c2ccc(F)cc2)sc2c1CCCC2

Procedure:
Prepared by proceeding in a similar manner to Intermediate 1, starting from ethyl 2-amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate and 4-fluorobenzene-sulphonyl chloride
Reaction SMILES: [NH2:1][C:2]1[C:3]([I:9])=[N:4][CH:5]=[N:6][C:7]=1I.[Cl:10][C:11]1[CH:12]=[C:13]([CH:15]=[CH:16][C:17]=1[O:18][CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[C:22]([F:26])[CH:21]=1)[NH2:14].O>CN1CCCC1=O>[Cl:10][C:11]1[CH:12]=[C:13]([NH:14][C:7]2[C:2]([NH2:1])=[C:3]([I:9])[N:4]=[CH:5][N:6]=2)[CH:15]=[CH:16][C:17]=1[O:18][CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[C:22]([F:26])[CH:21]=1
Reactant: Nc1ccc(OCc2cccc(F)c2)c(Cl)c1
Reactant: Nc1c(I)ncnc1I
Solvent: O
Solvent: CN1CCCC1=O
Product: Nc1c(I)ncnc1Nc1ccc(OCc2cccc(F)c2)c(Cl)c1
Yield: 81 %

Procedure:
A solution of 5-amino-4,6-diiodopyrimidine (3.83 g) and 3-chloro-4-[(3-fluorobenzyl)oxy]aniline (2.78 g) in 1-methyl-2-pyrrolidone (30 mL) was stirred at 70° C. for 14 hrs. Water was added to the reaction system and the mixture was extracted with ethyl acetate. The organic layer washed with water and saturated brine and dried over magnesium sulfate. After concentration under reduced pressure, the residue was separated and purified by column chromatography (eluent, ethyl acetate:hexane=1:4→2:3→1:1) to give the title compound (4.21 g) as brown powder crystals.
Reaction SMILES: [CH2:1]([C:3]1[N:7]([C:8]2[N:16]=[C:15]3[C:11]([N:12]=[C:13]([CH:18]=O)[N:14]3[CH3:17])=[C:10]([N:20]3[CH2:25][CH2:24][O:23][CH2:22][CH2:21]3)[N:9]=2)[C:6]2[CH:26]=[CH:27][CH:28]=[CH:29][C:5]=2[N:4]=1)[CH3:2].[NH:30]1[CH2:33][CH:32]([CH:34]([OH:38])[CH:35]([CH3:37])[CH3:36])[CH2:31]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[CH2:1]([C:3]1[N:7]([C:8]2[N:16]=[C:15]3[C:11]([N:12]=[C:13]([CH2:18][N:30]4[CH2:33][CH:32]([CH:34]([OH:38])[CH:35]([CH3:37])[CH3:36])[CH2:31]4)[N:14]3[CH3:17])=[C:10]([N:20]3[CH2:25][CH2:24][O:23][CH2:22][CH2:21]3)[N:9]=2)[C:6]2[CH:26]=[CH:27][CH:28]=[CH:29][C:5]=2[N:4]=1)[CH3:2]
Reactant: CCc1nc2ccccc2n1-c1nc(N2CCOCC2)c2nc(C=O)n(C)c2n1
Reactant: CC(C)C(O)C1CNC1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: ClCCCl
Product: CCc1nc2ccccc2n1-c1nc(N2CCOCC2)c2nc(CN3CC(C(O)C(C)C)C3)n(C)c2n1
Temperature: 25 °C
Reaction time: 5 h
Yield: 37.2 %

Procedure:
A mixture of 2-(2-ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purine-8-carbaldehyde (125 mg, 0.32 mmol), 1-azetidin-3-yl-2-methylpropan-1-ol (50 mg, 0.38 mmol) and 4 Å molecular sieves (1.0 g) in 1,2-dichloroethane (5 mL) was stirred at RT under nitrogen atmosphere for 5 h. Sodium triacetoxyborohydride (102 mg, 0.48 mmol) was added and the resulting reaction mixture was stirred at RT for 16 h. The solvent was reduced in vacuo and the residue was loaded onto an Isolute® SCX-2 cartridge (10 g). The cartridge was washed with DCM/MeOH, the desired product was subsequently eluted using a mixture of 2M NH3 in MeOH and DCM. The solvents were reduced in vacuo to afford 313 as an off-white foam (60 mg, 37%). LCMS (Method G): RT 6.95 min, [M+H]+ 505. 1H NMR (400 MHz, CDCl3): δ 7.99-7.95 (1 H, m), 7.72-7.71 (1 H, m), 7.23 (2 H, m), 4.32 (4 H, br s), 3.85-3.78 (9 H, m), 3.47-3.45 (3 H, m), 3.32 (2 H, q, J=7.48 Hz), 3.25 (1 H, t, J=6.66 Hz), 3.13 (1 H, t, J=6.66 Hz), 2.66-2.65 (1 H, m), 1.62-1.60 (2 H, m), 1.41 (3 H, t, J=7.48 Hz), 0.87 (6 H, dd, J=11.85, 6.78 Hz)
Reaction SMILES: [CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[C:11]1[C:19]2[C:14](=[N:15][CH:16]=[N:17][C:18]=2[NH2:20])[NH:13][N:12]=1.C([O-])([O-])=O.[K+].[K+].[CH:27]1(Br)[CH2:31][CH2:30][CH2:29][CH2:28]1.O>CN(C=O)C>[CH:27]1([N:13]2[C:14]3=[N:15][CH:16]=[N:17][C:18]([NH2:20])=[C:19]3[C:11]([C:2]3[CH:3]=[CH:4][C:5]4[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=4)[CH:1]=3)=[N:12]2)[CH2:31][CH2:30][CH2:29][CH2:28]1
Reactant: Nc1ncnc2[nH]nc(-c3ccc4ccccc4c3)c12
Reactant: BrC1CCCC1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: Nc1ncnc2c1c(-c1ccc3ccccc3c1)nn2C1CCCC1
Temperature: 60 °C

Procedure:
3-(naphthalen-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine (100 mg, 0.42 mmol) was dissolved in DMF (3 mL) and K2CO3 (220 mg, 1.6 mmol) and cyclopentyl bromide (49.5 μL, 0.46 mmol) were added. The reaction was heated to 60° C. overnight, then cooled to RT and poured into water (30 mL). The precipitate was collected by filtration. ESI-MS (M+H)− m/z calcd 330.2, found 330.2.
Reaction SMILES: [C:1]([CH:4]([CH2:16][CH2:17][CH2:18][CH:19]([OH:29])[CH2:20][O:21][C:22]1[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=1)[CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][C:11]([O:13]CC)=[O:12])(=[O:3])[CH3:2].[OH-].[Na+]>O.CO>[C:1]([CH:4]([CH2:16][CH2:17][CH2:18][CH:19]([OH:29])[CH2:20][O:21][C:22]1[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=1)[CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][C:11]([OH:13])=[O:12])(=[O:3])[CH3:2]
Reactant: CCOC(=O)CCCCCCC(CCCC(O)COc1ccc(F)cc1)C(C)=O
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CO
Product: CC(=O)C(CCCCCCC(=O)O)CCCC(O)COc1ccc(F)cc1
Reaction time: 69 h

Procedure:
Ethyl 8-Acetyl-12-hydroxy-13-(4-fluorophenoxy)-tridecanoate (4.67 g.; 0.0113 mole) is added to a solution of sodium hydroxide (0.68 g.; 0.0170 mole) in water (6.3 ml.) and methanol (56.7 ml.). The resulting solution is allowed to stand for 69 hours at 25°.
Reaction SMILES: [CH3:1][C:2]([C:4]1[O:5][C:6]2[CH:12]=[CH:11][CH:10]=[CH:9][C:7]=2[CH:8]=1)=[O:3].[Br:13]Br>CCOCC.C(=O)([O-])O.[Na+]>[Br:13][CH2:1][C:2]([C:4]1[O:5][C:6]2[CH:12]=[CH:11][CH:10]=[CH:9][C:7]=2[CH:8]=1)=[O:3]
Reactant: BrBr
Reactant: CC(=O)c1cc2ccccc2o1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCOCC
Product: O=C(CBr)c1cc2ccccc2o1
Temperature: 25 °C
Yield: 64.9 %

Procedure:
Benzofuran-2-yl methyl ketone (1.60 g, 10 mM) was dissolved in ether (20 mL). Under stirring of the mixture at room temperature, bromine (1.60 g) was added thereto. The resultant mixture was stirred for 10 minutes at room temperature, and poured in saturated sodium hydrogencarbonate solution, followed by extraction with ether (80 mL). The extract was washed with saturated brine and dried over magnesium sulfate, and the solvent was removed. Hexane was added to the residue and crystals were collected through filtration. The crystals were washed with hexane and dried, whereby 1.55 g of the product of interest was obtained (yield 69.4%).
Reaction SMILES: [C:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1)(=O)[CH3:2].[CH2:10]([N:12]([CH2:21][CH3:22])[C:13]1[CH:18]=[CH:17][C:16]([Mg]Br)=[CH:15][CH:14]=1)[CH3:11].[Mg].BrC1C=CC(N(CC)CC)=CC=1.[Cl-].[NH4+]>O1CCCC1.C1C=CC=CC=1>[CH2:10]([N:12]([CH2:21][CH3:22])[C:13]1[CH:18]=[CH:17][C:16]([C:1]([C:4]2[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=2)=[CH2:2])=[CH:15][CH:14]=1)[CH3:11]
Reactant: CC(=O)c1ccccc1
Reactant: CCN(CC)c1ccc([Mg]Br)cc1
Agent: CCN(CC)c1ccc(Br)cc1
Agent: [Cl-]
Agent: [Mg]
Solvent: c1ccccc1
Solvent: C1CCOC1
Product: C=C(c1ccccc1)c1ccc(N(CC)CC)cc1

Procedure:
After adding dropwise 100 ml of a benzene solution containing 8 g of acetophenone to a tetrahydrofuran solution of 4-diethylaminophenylmagnesium bromide prepared from 2 g of magnesium, 16 g of 4-bromodiethylaniline, and 100 ml of tetrahydrofuran, stirring was continued under reflux for 5 hours. After cooling, 200 ml of a saturated aqueous ammonium chloride solution was added thereto. The mixture was subjected to hydrolysis, and an organic layer was separated and washed with water. After distilling off the solvent, the residue was dissolved in benzene, and the solution was stirred and refluxed with the addition of 0.1 g of p-toluenesulfonic acid for one hour. After distilling off the solvent, the residue was dissolved in benzene, and the product was separated and purified by silica gel column chromatography.
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH:10]([CH3:14])[C:11]([OH:13])=[O:12])=[CH:6][CH:5]=1)([O-])=O>C(OCC)(=O)C.[Pd]>[NH2:1][C:4]1[CH:5]=[CH:6][C:7]([CH:10]([CH3:14])[C:11]([OH:13])=[O:12])=[CH:8][CH:9]=1
Reactant: CC(C(=O)O)c1ccc([N+](=O)[O-])cc1
Agent: [Pd]
Solvent: CCOC(C)=O
Product: CC(C(=O)O)c1ccc(N)cc1
Reaction time: 8 h

Procedure:
2-(4-nitrophenyl) propionic acid (5 g, 25.6 mmol) was dissolved in ethyl acetate (50 ml) and palladium on carbon (1 g, 9.40 mmol) was added then stirred under hydrogen balloon overnight. The product precipitated out. Added methanol to dissolved product then filtered off the palladium catalyst. The filtrate was concentrated and the residue was triturated with ethyl acetate to yield 2-(4-aminophenyl) propionic acid. LC-MS (IE, m/z): 166 [M+1]+;
Reaction SMILES: [C:1]1([CH:7]2[CH2:11][NH:10][C:9](=[O:12])[CH2:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[H-].[Na+].[CH2:15](I)[CH3:16]>O1CCCC1>[CH2:15]([N:10]1[CH2:11][CH:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[CH2:8][C:9]1=[O:12])[CH3:16]
Reactant: O=C1CC(c2ccccc2)CN1
Reactant: CCI
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: CCN1CC(c2ccccc2)CC1=O
Yield: 57 %

Procedure:
A mixture of 4-phenyl-pyrrolidin-2-one (24.2 g; 0.15 mole) and sodium hydride (80% oil suspension)(5.4 g; 0.18 mole) in tetrahydrofuran (150 ml) is refluxed for 2.5 hrs. After cooling, ethyl iodide (29 g; 0.185 mole) is added thereto, and the resulting material is refluxed for another 5 hrs. The solvent is then evaporated off; the residue is taken up into chloroform, washed with water, dried and distilled. B.p.(0.2 mm Hg)=124°-126° C. Yield: 57%.
Reaction SMILES: C([O-])(=O)C.[Na+].[Cl:6][C:7]1[CH:12]=[C:11]([O:13][S:14]([CH3:17])(=[O:16])=[O:15])[CH:10]=[CH:9][C:8]=1[C:18](=[O:29])[C:19](=[CH:25]OCC)[C:20]([CH:22]1[CH2:24][CH2:23]1)=[O:21].Cl.[NH2:31]O.O>C(O)C>[Cl:6][C:7]1[CH:12]=[C:11]([O:13][S:14]([CH3:17])(=[O:16])=[O:15])[CH:10]=[CH:9][C:8]=1[C:18]([C:19]1[CH:25]=[N:31][O:21][C:20]=1[CH:22]1[CH2:24][CH2:23]1)=[O:29]
Reactant: CCOC=C(C(=O)c1ccc(OS(C)(=O)=O)cc1Cl)C(=O)C1CC1
Reactant: NO
Agent: CC(=O)[O-]
Agent: Cl
Agent: [Na+]
Solvent: O
Solvent: CCO
Product: CS(=O)(=O)Oc1ccc(C(=O)c2cnoc2C2CC2)c(Cl)c1
Reaction time: 0.75 h
Yield: 89.6 %

Procedure:
Sodium acetate (1.52 g) was added to a stirred mixture of 1-[2-chloro-4-(methylsulphonyloxy)phenyl]-3-cyclopropyl-2-ethoxymethylenepropan-1,3-dione (5.6 g) and hydroxylamine hydrochloride (1.3 g) in ethanol. The mixture was stirred for 0.75 hours. Water was added and the mixture was extracted with dichloromethane. The organic layer was washed with water, dried (MgSO4) and filtered. The filtrate was evaporated to dryness and the residue was purified by chromatography eluted with a mixture of ethyl acetate and dichloromethane to give 4-[2-chloro-4-(methylsulphonyloxy)benzoyl]-5-cyclopropylisoxazole (compound 1, 4.60 g) as a brown oil, NMR (CDCl3) 1.25-1.35(m,2H), 1,4-1.5 (m,2H), 2.6-2.7(m, 1H), 3.2(s, 1H), 7.3(d, 1H), 7.4(s, 1H), 7.45 (d, 1H), 8.15 (s, 1H).