Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C[O:2][C:3]([C@H:5]1[CH2:10][CH2:9][C@H:8]([C:11]2[N:15]3[CH:16]=[CH:17][N:18]=[C:19]([NH2:20])[C:14]3=[C:13]([C:21]3[CH:30]=[C:29]4[C:24]([CH:25]=[CH:26][C:27]([C:31]5[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=5)=[N:28]4)=[CH:23][CH:22]=3)[N:12]=2)[CH2:7][CH2:6]1)=O.[H-].[H-].[H-].[H-].[Li+].[Al+3]>C1COCC1>[NH2:20][C:19]1[C:14]2[N:15]([C:11]([C@H:8]3[CH2:7][CH2:6][C@H:5]([CH2:3][OH:2])[CH2:10][CH2:9]3)=[N:12][C:13]=2[C:21]2[CH:30]=[C:29]3[C:24]([CH:25]=[CH:26][C:27]([C:31]4[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=4)=[N:28]3)=[CH:23][CH:22]=2)[CH:16]=[CH:17][N:18]=1
Reactant: COC(=O)[C@H]1CC[C@H](c2nc(-c3ccc4ccc(-c5ccccc5)nc4c3)c3c(N)nccn32)CC1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Product: Nc1nccn2c1c(-c1ccc3ccc(-c4ccccc4)nc3c1)nc2[C@H]1CC[C@H](CO)CC1
Temperature: 25 °C
Reaction time: 4 h

Procedure:
A THF solution (8 mL) of trans-4-[8-amino-1-(2-phenylquinolin-7-yl)-imidazo[1,5-a]pyrazin-3-yl]-cyclohexanecarboxylic acid methyl ester was cooled to −78° C. and charged with 1M LiAlH4 in THF (1.5 mL, 1.5 mmol) dropwise; the reaction vessel was removed from the −78° C. cooling bath and stirred at rt for 4 h. The reaction mixture was charged with EtOAc, Na2SO4.10H2O, and silica gel and concentrated in vacuo to yellow solids. The crude material was purified by silica gel column chromatography [Jones Flashmaster, 10 g/70 mL cartridge, eluting with 1%˜7N NH3 in MeOH/CH2Cl2] to afford the desired product as a yellow solid; 1H NMR (CDCl3, 400 MHz) δ 1.17-1.29 (m, 2H), 1.63-1.73 (m, 2H), 1.87-2.07 (m, 4H), 2.12-2.23 (m, 2H), 2.92-3.02 (m, 1H), 3.56 (d, 2H, J=6.0 Hz), 5.25 (s, 2H), 7.13 (d, 1H, J=4.8 Hz), 7.27-7.28 (m, 1H), 7.46-7.50 (m, 1H), 7.52-7.57 (m, 2H), 7.89-7.96 (m, 3H), 8.18-8.21 (m, 2H), 8.27 (d, 1H, J=8.8 Hz), 8.40-8.42 (m, 1H); MS (ES+): m/z 450.0 [MH+]; HPLC: tR=2.4 min (Micromass Platform H, polar—5 min).
Reaction SMILES: [CH3:1][N:2]([C:4](=[O:41])[C:5]([N:7]([CH3:40])[CH:8]1[CH2:14][N:13](C(OC(C)(C)C)=O)[CH2:12][CH2:11][N:10]2[C:22](=[O:39])[C:23]([OH:38])=[C:24]([C:26]([NH:28][CH2:29][C:30]3[CH:35]=[CH:34][C:33]([F:36])=[C:32]([CH3:37])[CH:31]=3)=[O:27])[N:25]=[C:9]12)=[O:6])[CH3:3]>ClCCl.FC(F)(F)C(O)=O>[F:36][C:33]1[CH:34]=[CH:35][C:30]([CH2:29][NH:28][C:26]([C:24]2[N:25]=[C:9]3[CH:8]([N:7]([CH3:40])[C:5](=[O:6])[C:4]([N:2]([CH3:1])[CH3:3])=[O:41])[CH2:14][NH:13][CH2:12][CH2:11][N:10]3[C:22](=[O:39])[C:23]=2[OH:38])=[O:27])=[CH:31][C:32]=1[CH3:37]
Reactant: Cc1cc(CNC(=O)c2nc3n(c(=O)c2O)CCN(C(=O)OC(C)(C)C)CC3N(C)C(=O)C(=O)N(C)C)ccc1F
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: Cc1cc(CNC(=O)c2nc3n(c(=O)c2O)CCNCC3N(C)C(=O)C(=O)N(C)C)ccc1F

Procedure:
The compound of Step 6 was stirred in dichloromethane/trifluoroacetic acid (8/2 v/v) for 1 hour, then concentrated under reduced pressure and purified by RP HPLC (C18, 5 μM, H2O/MeCN with 1% of TFA as eluant) affording desired compound as trifluoroacetic salt. 1H NMR (300 MHz, CD3CN) δ 12.68 (bs, 1H), 9.96 (bs, 1H), 7.50 (d, J=7.51 Hz, 1H), 7.45-7.41 (m, 1H), 7.21 (t, J=8.62 Hz, 1H), 5.55-5.46 (m, 2H), 4.75 (dd, J=14.6 Hz, J=6.8 Hz, 1H), 4.67 (dd, J=14.6 Hz, J=6.3 Hz, 1H), 4.24-4.05 (m, 3H), 3.96-3.92 (m, 1H), 3.39-3.36 (m, 1H), 3.24 (s, 3H), 3.19 (s, 3H), 3.18 (s, 3H), 2.46 (s, 3H); MS (ES) C22H27FN6O5 requires 474. Found: 475 (M+H+).
Reaction SMILES: [C:1]([N:5]1[C:9]([CH2:10][CH2:11][CH:12]=O)=[CH:8][C:7]([CH2:14][CH2:15][CH3:16])=[N:6]1)([CH3:4])([CH3:3])[CH3:2].[F:17][C:18]1[CH:23]=[CH:22][C:21]([CH:24]([C:31]2[CH:36]=[CH:35][C:34]([F:37])=[CH:33][CH:32]=2)[N:25]2[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]2)=[CH:20][CH:19]=1.CCN(C(C)C)C(C)C.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>>[C:1]([N:5]1[C:9]([CH2:10][CH2:11][CH2:12][N:28]2[CH2:27][CH2:26][N:25]([CH:24]([C:31]3[CH:36]=[CH:35][C:34]([F:37])=[CH:33][CH:32]=3)[C:21]3[CH:20]=[CH:19][C:18]([F:17])=[CH:23][CH:22]=3)[CH2:30][CH2:29]2)=[CH:8][C:7]([CH2:14][CH2:15][CH3:16])=[N:6]1)([CH3:4])([CH3:3])[CH3:2]
Reactant: CCCc1cc(CCC=O)n(C(C)(C)C)n1
Reactant: Fc1ccc(C(c2ccc(F)cc2)N2CCNCC2)cc1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: CCN(C(C)C)C(C)C
Product: CCCc1cc(CCCN2CCN(C(c3ccc(F)cc3)c3ccc(F)cc3)CC2)n(C(C)(C)C)n1

Procedure:
239 mg (97%) of target compound was obtained by using a method same as in Example 1 by using 3-(1-tert-butyl-3-propyl-1H-pyrazol-5-yl)propanal (100 mg, 0.450 mmol), 1-(bis(4-fluorophenyl)methyl)piperazine (130 mg, 0.450 mmol), DIPEA (0.118 mL, 0.675 mmol) and NaBH(OAc)3 (286 mg, 1.350 mmol).
Reaction SMILES: [Cl:1][C:2]1[CH:9]=[C:8]([O:10][C:11](=[O:25])[C:12]2[CH:17]=[CH:16][C:15]([CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH3:24])=[CH:14][CH:13]=2)[CH:7]=[CH:6][C:3]=1[CH:4]=[O:5].CC(C)=[O:28].OS(O)(=O)=O.O=[Cr](=O)=O>CC(C)=O>[Cl:1][C:2]1[CH:9]=[C:8]([O:10][C:11](=[O:25])[C:12]2[CH:13]=[CH:14][C:15]([CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH3:24])=[CH:16][CH:17]=2)[CH:7]=[CH:6][C:3]=1[C:4]([OH:28])=[O:5]
Reactant: CCCCCCCc1ccc(C(=O)Oc2ccc(C=O)c(Cl)c2)cc1
Reactant: CC(C)=O
Agent: O=[Cr](=O)=O
Agent: O=S(=O)(O)O
Product: CCCCCCCc1ccc(C(=O)Oc2ccc(C(=O)O)c(Cl)c2)cc1
Reaction time: 1 h

Procedure:
The resulting, crude 2-chloro-4-[(p-heptylbenzoyl)oxy]benzaldehyde is dissolved in 350 ml of acetone. Within 40 minutes there are added dropwise thereto 30 ml of Jones' reagent, the mixture warming slightly. The mixture is stirred for a further 1 hour, precipitated inorganic material is then filtered off under suction, the filtrate is diluted with 300 ml of water (the product precipitating), concentrated on a rotary evaporator to about 300 ml and the suspension obtained is suction filtered. The suction filter material is washed three times with 50 ml of 10% aqueous acetone, dried and recrystallized from about 60 ml of benzene. There are obtained 13.8 g of 2-chloro-4-[(p-heptylbenzoyl)oxy]benzoic acid, m.p. 108° C. (nematic).
Reaction SMILES: [CH2:1]([C:3]1([CH2:15][CH3:16])[CH:8]=[CH:7][C:6]2[CH:9]=[C:10]([C:13]#[N:14])[CH:11]=[CH:12][C:5]=2[O:4]1)[CH3:2].C(=O)(O)[O-:18].[Na+].ClC1C=CC=C(C(OO)=O)C=1>ClCCl>[CH2:15]([C:3]1([CH2:1][CH3:2])[CH:8]2[O:18][CH:7]2[C:6]2[CH:9]=[C:10]([C:13]#[N:14])[CH:11]=[CH:12][C:5]=2[O:4]1)[CH3:16]
Reactant: O=C([O-])O
Reactant: CCC1(CC)C=Cc2cc(C#N)ccc2O1
Agent: O=C(OO)c1cccc(Cl)c1
Agent: [Na+]
Solvent: ClCCl
Product: CCC1(CC)Oc2ccc(C#N)cc2C2OC21

Procedure:
12 g of the above chromene are dissolved in 400 ml of abs. dichloromethane, the obtained solution is mixed with anhydrous sodium bicarbonate and oxidized during 3 days with 31 mg of m-chloroperbenzoic acid. The slightly yellow suspension is partitioned between an aq. ammoniumhydroxide solution (5%) and dichlormethane, the organic phases are washed with water and dried over sodiumsulphate. The oil, obtained after concentration, is purified by flash-chromatography (silica gel/dichloromethane, hexane 2:3). Besides of educt, 2,2-diethyl-3,4-epoxy-3,4-dihydro-2H-1-benzopyran-6-carbonitrile is obtained as colorless oil.
Reaction SMILES: [Si:1]([O:8][CH:9]1[CH:14]([NH:15][C:16](=[O:22])[O:17][C:18]([CH3:21])([CH3:20])[CH3:19])[CH2:13][CH2:12][N:11]([C:23]2[CH:28]=[CH:27][N:26]=[CH:25][C:24]=2[N+:29]([O-])=O)[CH2:10]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]>C(O)C.C(OCC)(=O)C>[NH2:29][C:24]1[CH:25]=[N:26][CH:27]=[CH:28][C:23]=1[N:11]1[CH2:12][CH2:13][CH:14]([NH:15][C:16](=[O:22])[O:17][C:18]([CH3:20])([CH3:21])[CH3:19])[CH:9]([O:8][Si:1]([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2])[CH2:10]1
Reactant: CC(C)(C)OC(=O)NC1CCN(c2ccncc2[N+](=O)[O-])CC1O[Si](C)(C)C(C)(C)C
Solvent: CCO
Solvent: CCOC(C)=O
Product: CC(C)(C)OC(=O)NC1CCN(c2ccncc2N)CC1O[Si](C)(C)C(C)(C)C
Yield: 99 %

Procedure:
Following Method 2 of Example 49, (+/−)-tert-butyl 3-(tert-butyldimethylsilyloxy)-1-(3-nitropyridin-4-yl)piperidin-4-ylcarbamate in ethanol and ethyl acetate (1:1, 0.1 M solution) was reduced yielding (+/−)-tert-butyl 1-(3-aminopyridin-4-yl)-3-(tert-butyldimethylsilyloxy)piperidin-4-ylcarbamate, (>99%). LCMS (m/z): 423.3 (MH+); LC Rt=3.62 min.
Reaction SMILES: [NH2:1][C:2]1[N+:7]([O-:8])=[C:6]([NH2:9])[CH:5]=[C:4](Cl)[N:3]=1.CC1C=CC=CC=1C.[NH:19]1[CH2:24][CH2:23][CH:22]=[CH:21][CH2:20]1.[OH-].[Na+]>O>[NH2:1][C:2]1[N+:7]([O-:8])=[C:6]([NH2:9])[CH:5]=[C:4]([N:19]2[CH2:20][CH:21]=[CH:22][CH2:23][CH2:24]2)[N:3]=1
Reactant: Nc1cc(Cl)nc(N)[n+]1[O-]
Reactant: C1=CCNCC1
Agent: [Na+]
Agent: [OH-]
Solvent: Cc1ccccc1C
Solvent: O
Product: Nc1cc(N2CC=CCC2)nc(N)[n+]1[O-]
Temperature: 5 °C

Procedure:
155 G. of 2,4-diamino-6-chloropyrimidine-3-oxide are mixed under an argon atmosphere with 640 ml. of o-xylene and 260 ml. of 1,2,5,6-tetrahydropyridine and the mixture is stirred. The mixture is then heated to reflux for 30 minutes, the internal temperature rising from 115° C. to 123° C. The mixture is then cooled to 5° C., treated with 40 g. of sodium hydroxide in 400 ml. of water and stirred at 5° C. for 1 hour. The precipitate formed is filtered off, washed with 200 ml. of water and recrystallized from 3000 ml. of water, there being obtained pure 2,4-diamino-6-[3,6-dihydro-1(2H)-pyridyl]pyrimidine-3-oxide, having a melting point of 263°-265° C. (decomposition).
Reaction SMILES: C[N:2]1[CH:6]=[C:5]([C:7]2[CH:12]=[CH:11][N:10]=[CH:9][CH:8]=2)[C:4]([C:13]2[CH:30]=[CH:29][C:16]([O:17][CH2:18][C:19]3[CH:28]=[CH:27][C:26]4[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=4)[N:20]=3)=[CH:15][CH:14]=2)=[N:3]1.[CH:31](NN)([CH3:33])[CH3:32]>>[CH:31]([N:3]1[C:4]([C:13]2[CH:14]=[CH:15][C:16]([O:17][CH2:18][C:19]3[CH:28]=[CH:27][C:26]4[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=4)[N:20]=3)=[CH:29][CH:30]=2)=[C:5]([C:7]2[CH:12]=[CH:11][N:10]=[CH:9][CH:8]=2)[CH:6]=[N:2]1)([CH3:33])[CH3:32]
Reactant: CC(C)NN
Reactant: Cn1cc(-c2ccncc2)c(-c2ccc(OCc3ccc4ccccc4n3)cc2)n1
Product: CC(C)n1ncc(-c2ccncc2)c1-c1ccc(OCc2ccc3ccccc3n2)cc1

Procedure:
Following the procedure for the preparation of 2-[4-(1-Methyl-4-pyridin-4-yl-1H-pyrazol-3-yl)-phenoxymethyl]-quinoline but substituting isopropyl hydrazine provided the title compound. 1H NMR (400 MHz, CDCl3) δ 8.33 (bs, 2 H), 8.24 (d, J=8.3 Hz, 1 H), 8.08 (d, J=8.3 Hz, 1H), 7.86 (s, 1H) 7.83 (m, 1 H), 7.72 (m 2H), 7.58 (t, J=7.9 Hz, 1H), 7.20 (d, J=8.7 Hz, 2H), 7.15 (d, J=9.1 Hz, 2H) 7.04 (m, 2H), 5.43 (s, 2H), 4.31 (m, 1H), 1.43 (d, J=6.6 Hz), 6H); MS: (M+H m/z=421.2).
Reaction SMILES: [N:1]1([C:6]2[CH:7]=[C:8]([C:12]([C:17]3[N:25](S(C4C=CC=CC=4)(=O)=O)[C:20]4=[N:21][CH:22]=[CH:23][CH:24]=[C:19]4[CH:18]=3)=[CH:13][CH:14]([CH3:16])[CH3:15])[CH:9]=[CH:10][CH:11]=2)[CH:5]=[CH:4][CH:3]=[N:2]1.[OH-].[Na+]>C(O)C.O1CCCC1>[N:1]1([C:6]2[CH:7]=[C:8]([C:12]([C:17]3[NH:25][C:20]4=[N:21][CH:22]=[CH:23][CH:24]=[C:19]4[CH:18]=3)=[CH:13][CH:14]([CH3:16])[CH3:15])[CH:9]=[CH:10][CH:11]=2)[CH:5]=[CH:4][CH:3]=[N:2]1
Reactant: CC(C)C=C(c1cccc(-n2cccn2)c1)c1cc2cccnc2n1S(=O)(=O)c1ccccc1
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Solvent: C1CCOC1
Product: CC(C)C=C(c1cccc(-n2cccn2)c1)c1cc2cccnc2[nH]1
Temperature: 85 °C
Reaction time: 16 h
Yield: 69.4 %

Procedure:
A solution of 2-(1-(3-(1H-pyrazol-1-yl)phenyl)-3-methylbut-1-enyl)-1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridine (3.4 g, 7.2 mmol) in ethanol (50 mL) and tetrahydrofuran (100 mL) was treated with an aqueous sodium hydroxide solution (10%, 20 mL). The reaction was stirred at 85° C. for 16 h. At this time, the reaction mixture was cooled to 25° C., concentrated in vacuo, diluted with water (100 mL) and then extracted with ethyl acetate (3×150 mL). The organic layers were washed with a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The resulting solid was washed with ethanol (15 mL), and dried to afford 2-(1-(3-(1H-pyrazol-1-yl)phenyl)-3-methylbut-1-enyl)-1H-pyrrolo[2,3-b]pyridine (1.64 g, 68.9%) as a white solid: 1H NMR (300 MHz, CDCl3) δ ppm 11.64 (s, 1H), 8.52 (d, 1H, J=2.1 Hz), 8.19 (dd, 1H, J1=4.5 Hz, J2=1.8 Hz), 7.95 (dd, 2H, J1=7.8 Hz, J2=1.2 Hz), 7.75-7.69 (m, 3H), 7.42 (t, 1H, J=8.1 Hz), 7.13-7.05 (m, 2H), 6.52 (t, 1H, J=2.1 Hz), 6.44 (d, 1H, J=1.8 Hz), 6.27 (d, 1H, J=9.9 Hz), 2.70-2.57 (m, 1H), 1.17 (s, 3H), 1.15 (s, 3H).
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][C:10]([OH:12])=O)=[CH:4][CH:3]=1.[NH2:13][C@H:14]1[CH2:19][CH2:18][C@H:17]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH2:16][CH2:15]1.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1>CN(C=O)C>[OH:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:8][CH2:9][C:10]([NH:13][C@H:14]2[CH2:15][CH2:16][C@H:17]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[CH2:18][CH2:19]2)=[O:12])=[CH:6][CH:7]=1
Reactant: O=C(O)CCc1ccc(O)cc1
Reactant: N[C@H]1CC[C@H](c2ccccc2)CC1
Agent: On1nnc2ccccc21
Solvent: ClCCCl
Solvent: CN(C)C=O
Product: O=C(CCc1ccc(O)cc1)N[C@H]1CC[C@H](c2ccccc2)CC1
Reaction time: 8 h

Procedure:
A mixture of 3-(4-hydroxyphenyl)propionic acid 7 (0.48 g, 2.9 mmol), amine 5 (0.50 g, 2.9 mmol), EDC (0.67 g, 3.5 mmol), and HOBT (0.39 g, 2.9 mmol) in DMF (5 mL) was stirred under an atmosphere of nitrogen overnight. The reaction mixture was partitioned between H2O (25 mL) and EtOAc (50 mL). The organic layer was washed with H2O, 3N HCl (25 mL), H2O (25 mL), and saturated NaCl (25 mL). After drying (Na2SO4), concentration under reduced pressure gave (a) trans-3-(4-hydroxyphenyl)-N-(4-phenylcyclohexyl)propionamide (0.65 g, 69%) which was used without further purification: 1H NMR (300 MHz, CD3OD) δ 7.28-7.06 (m, 5H), 3.74-3.60 (m, 1H), 2.80 (t, J=4 Hz, 2H), 2.51-2.36 (m, 3H), 1.97-1.82 (m, 4H), 1.67-1.51 (m, 2H), 1.40-1.21 (m, 2H).
Reaction SMILES: [CH3:1][C:2]([O:5][C:6]([NH:8][C@@H:9]([CH2:13][CH:14]=[CH2:15])[C:10]([OH:12])=O)=[O:7])([CH3:4])[CH3:3].C(Cl)CCl.C[CH:21]=[CH:22][CH2:23][NH2:24]>CN(C1C=CN=CC=1)C>[CH2:23]([NH:24][C:10]([C@@H:9]([NH:8][C:6](=[O:7])[O:5][C:2]([CH3:1])([CH3:3])[CH3:4])[CH2:13][CH:14]=[CH2:15])=[O:12])[CH:22]=[CH2:21]
Reactant: CC=CCN
Reactant: C=CC[C@H](NC(=O)OC(C)(C)C)C(=O)O
Agent: CN(C)c1ccncc1
Solvent: ClCCCl
Product: C=CCNC(=O)[C@H](CC=C)NC(=O)OC(C)(C)C
Reaction time: 72 h
Yield: 28.4 %

Procedure:
To a stirred solution of (2S)-2-({[(1,1-dimethylethyl)oxy]carbonyl}amino)-4-pentenoic acid (2.82 g, 13 mmol), DMAP (1.9 g, 16 mmol) and EDC (3.1 g, 16 mmol) was added N-methylallylamine (1.38 mL, 14 mmol). The reaction was stirred for 72 hours before being quenched by the addition of 1 M HCl (15 mL). The resulting biphasic mixture was separated and the aqueous phase was extracted once with DCM. The combined organics were dried over sodium sulfate and concentrated to yield 1,1-dimethylethyl {(1S)-1-[(2-propen-1-ylamino)carbonyl]-3-buten-1-yl}carbamate (0.94 g, 28%). LCMS: (M−tBut)+: 238.1.
Reaction SMILES: Cl[C:2]([C:28](=[O:37])[C:29]1[CH:34]=[CH:33][C:32]([O:35][CH3:36])=[CH:31][CH:30]=1)([Cl:27])[C:3]([N:5]([C:12]([O:14][CH:15]([CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH3:26])[CH2:16][CH2:17][CH2:18][CH3:19])=[O:13])[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)=[O:4].[C:38]([C:41]1[CH:46]=[CH:45][C:44]([N:47]2[C:51]([SH:52])=[N:50][N:49]=[N:48]2)=[CH:43][CH:42]=1)([OH:40])=[O:39].C(N(CC)CC)C>C(Cl)(Cl)Cl>[CH3:36][O:35][C:32]1[CH:31]=[CH:30][C:29]([C:28]([C:2]([S:52][C:51]2[N:47]([C:44]3[CH:43]=[CH:42][C:41]([C:38]([OH:40])=[O:39])=[CH:46][CH:45]=3)[N:48]=[N:49][N:50]=2)([Cl:27])[C:3]([N:5]([C:12]([O:14][CH:15]([CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH3:26])[CH2:16][CH2:17][CH2:18][CH3:19])=[O:13])[C:6]2[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=2)=[O:4])=[O:37])=[CH:34][CH:33]=1
Reactant: CCCCCCCC(CCCC)OC(=O)N(C(=O)C(Cl)(Cl)C(=O)c1ccc(OC)cc1)c1ccccc1
Reactant: O=C(O)c1ccc(-n2nnnc2S)cc1
Solvent: CCN(CC)CC
Solvent: ClC(Cl)Cl
Product: CCCCCCCC(CCCC)OC(=O)N(C(=O)C(Cl)(Sc1nnnn1-c1ccc(C(=O)O)cc1)C(=O)c1ccc(OC)cc1)c1ccccc1
Yield: 93.3 %

Procedure:
33 g of α-chloro-α-(4-methoxybenzoyl)-2-chloro-5-dodecyloxycarbonylacetanilide and 16 g of 1-(4-carboxyphenyl)-5-mercaptotetrazole were dispersed in 200 ml of chloroform to which was added dropwise 10 ml of triethylamine at room temperature over a period of about 30 minutes. After stirring for 3 hours the chloroform solution was washed with water and concentrated under reduced pressure. The residue was recrystallized from methanol to obtain 41.2 g of α-(4-methoxybenzoyl)-α-[1-(4-carboxyphenyl)-5-tetrazolylthio]-2-chloro-5-dodecyloxycarbonylacetanilide. Yield: 93%. Melting Point: 172° to 174° C.
Reaction SMILES: Cl[S:2]([C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[NH:10][C:9](=[O:14])[CH2:8]2)(=[O:4])=[O:3].[CH:15]([NH2:18])([CH3:17])[CH3:16].N1C=CC=CC=1>ClCCl>[CH:15]([NH:18][S:2]([C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[NH:10][C:9](=[O:14])[CH2:8]2)(=[O:4])=[O:3])([CH3:17])[CH3:16]
Reactant: CC(C)N
Reactant: O=C1Cc2cc(S(=O)(=O)Cl)ccc2N1
Solvent: ClCCl
Solvent: c1ccncc1
Product: CC(C)NS(=O)(=O)c1ccc2c(c1)CC(=O)N2
Temperature: 25 °C
Reaction time: 4 h
Yield: 45.5 %

Procedure:
A suspension of 3 g 5-chlorosulfonyl-2-oxindole, 1.15 g isopropylamine and 1.2 mL of pyridine in 50 mL of dichloromethane was stirred at room temperature for 4 hours during which time a white solid formed. The solid was collected by vacuum filtration, slurry-washed with hot ethanol, cooled, collected by vacuum filtration and dried under vacuum at 40° C. overnight to give 1.5 g (45%) of 5-isopropylaminosulfonyl-2-oxindole.
Reaction SMILES: [O:1]([CH2:8][C@H:9]([NH2:11])[CH3:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([O:20][C@@H:21]1[C@H:25]([O:26]C(=O)C2C=CC=CC=2)[C@@H:24]([CH2:35][O:36]C(=O)C2C=CC=CC=2)[O:23][C@H:22]1[N:45]1[CH:53]=[N:52][C:51]2[C:46]1=[N:47][C:48]([Cl:55])=[N:49][C:50]=2Cl)(=O)C1C=CC=CC=1.C(N(C(C)C)CC)(C)C>O1CCOCC1>[Cl:55][C:48]1[N:49]=[C:50]([NH:11][C@H:9]([CH3:10])[CH2:8][O:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[C:51]2[N:52]=[CH:53][N:45]([C:46]=2[N:47]=1)[C@@H:22]1[O:23][C@H:24]([CH2:35][OH:36])[C@@H:25]([OH:26])[C@H:21]1[OH:20]
Reactant: C[C@@H](N)COc1ccccc1
Reactant: O=C(OC[C@H]1O[C@@H](n2cnc3c(Cl)nc(Cl)nc32)[C@H](OC(=O)c2ccccc2)[C@@H]1OC(=O)c1ccccc1)c1ccccc1
Solvent: CCN(C(C)C)C(C)C
Solvent: C1COCCO1
Product: C[C@H](COc1ccccc1)Nc1nc(Cl)nc2c1ncn2[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O
Temperature: 25 °C
Reaction time: 18 h
Yield: 53.5 %

Procedure:
(R)-1-phenoxy-2-propylamine (4.3 g, 23 mmol) was reacted with 9-(2,3,5-tri- O-benzoyl-β-D-ribofuranosyl)-2,6-dichloro-9H-purine (11.2 g, 18 mmol) in dioxan (150 ml) in the presence of diisopropylethylamine (5.3 g, 41 mmol). The reaction mixture was stirred at room temperature for 18 h, heated at 50° C. for 4 h, and stirred at room temperature for 60 h before being filtered and evaporated. The product (after purification by flash chromatography) was debenzoylated with methanolic ammonia to provide the title 2-chloro- N-[(R)-1-phenoxy-2-propyl]adenosine (after column chromatography) as a foam (4.2 g, 64%), 1H NMR (DMSO-d6)δ 1.31 (3H, d, --CH3), 3.52-3.59 (1H, m, H-5'a), 3.63-3.72 (1H, m, H-5'b), 3.92-3.99 and 4.10-4.21 (4H, 2 m, H-3', H-4' and --CH2 --), 4.52 (1H, dd, H-2'), 4.65 (1H, m, --CH3C H--), 5.07 (1H, t, 5'-OH), 5.22, 5.49 (2H, 2d, 2' and 3'-OH), 5.84 (1H, d, H-1 '), 6.88-7.02 (3H, m, Ar--H), 7.24-7.33 (2H, dd, Ar--H), 8.32-8.45 (2H, s & m, H-8 and N--H).
Reaction SMILES: [F:1][C:2]1[C:7]([NH:8][CH2:9][C:10]2[CH:15]=[C:14]([C:16]3[CH:21]=[CH:20][CH:19]=[C:18]([F:22])[CH:17]=3)[CH:13]=[CH:12][C:11]=2[F:23])=[C:6]([F:24])[C:5]([CH3:25])=[CH:4][C:3]=1[OH:26].C([O-])([O-])=O.[Cs+].[Cs+].Br[CH2:34][C:35]([O:37][CH:38]([CH3:40])[CH3:39])=[O:36].O>CN(C=O)C>[F:1][C:2]1[C:7]([NH:8][CH2:9][C:10]2[CH:15]=[C:14]([C:16]3[CH:21]=[CH:20][CH:19]=[C:18]([F:22])[CH:17]=3)[CH:13]=[CH:12][C:11]=2[F:23])=[C:6]([F:24])[C:5]([CH3:25])=[CH:4][C:3]=1[O:26][CH2:34][C:35]([O:37][CH:38]([CH3:40])[CH3:39])=[O:36]
Reactant: CC(C)OC(=O)CBr
Reactant: Cc1cc(O)c(F)c(NCc2cc(-c3cccc(F)c3)ccc2F)c1F
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: O
Solvent: CN(C)C=O
Product: Cc1cc(OCC(=O)OC(C)C)c(F)c(NCc2cc(-c3cccc(F)c3)ccc2F)c1F
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 76 %

Procedure:
2,4-difluoro-3-[[2-fluoro-5-(3-fluorophenyl)phenyl]methylamino]-5-methyl-phenol (206 mg, 0.57 mmol, 1.0 eq) was dissolved in DMF (15 mL). Cs2CO3 (279 mg, 0.86 mmol, 1.5 eq) was added and the reaction mixture stirred for 30 min at room temperature. Isopropyl bromoacetate (124 mg, 0.68 mmol, 1.2 eq) was added and the reaction stirred a further 1 h at room temperature. The resulting mixture was poured into water and extracted with EtOAc. The organic extract was washed with water and brine, dried (Na2SO4), filtered and evaporated in vacuo. The residue was purified by column chromatography (petroleum ether: EtOAc, 50:1 to 30:1) to give the title compound as a colorless oil (200 mg, 76%).
Reaction SMILES: [CH3:1][S:2][C:3]1[CH:8]=[CH:7][C:6]([OH:9])=[CH:5][CH:4]=1.Cl[CH2:11][CH2:12][OH:13].C(=O)([O-])[O-].[K+].[K+]>>[CH3:1][S:2][C:3]1[CH:8]=[CH:7][C:6]([O:9][CH2:11][CH2:12][OH:13])=[CH:5][CH:4]=1
Reactant: OCCCl
Reactant: CSc1ccc(O)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Product: CSc1ccc(OCCO)cc1
Yield: 28.5 %

Procedure:
A mixture of 105.46 g (0.753 mole) of 4-(methylthio)phenol, 62.0 g (0.772 mole) of 2-chloroethanol and 105 g (0.761 mole) of potassium carbonate in approximately one liter of acetonitrite was refluxed overnight. The cooled mixture was filtered, and the solvent was removed in vacuo to give a solid. This was recrystallized from diethyl ether-hexane to give 39.59 g (28.6%) of the product as a white, crystalline solid, mp 55°-56° C.
Reaction SMILES: [C:1]([C:4]1[CH:15]=[CH:14][C:7]([O:8][CH2:9][CH:10]([OH:13])[CH2:11][NH2:12])=[CH:6][CH:5]=1)(=[O:3])[CH3:2].OC(COC1C2C(=CC=CC=2)C=CC=1)CN[C:20]1[N:28]=[CH:27][N:26]=[C:25]2[C:21]=1[N:22]=[CH:23][NH:24]2>>[C:1]([C:4]1[CH:15]=[CH:14][C:7]([O:8][CH2:9][CH:10]([OH:13])[CH2:11][NH:12][C:20]2[N:28]=[CH:27][N:26]=[C:25]3[C:21]=2[N:22]=[CH:23][NH:24]3)=[CH:6][CH:5]=1)(=[O:3])[CH3:2]
Reactant: OC(CNc1ncnc2[nH]cnc12)COc1cccc2ccccc12
Reactant: CC(=O)c1ccc(OCC(O)CN)cc1
Product: CC(=O)c1ccc(OCC(O)CNc2ncnc3[nH]cnc23)cc1

Procedure:
By substituting 3-(4-acetylphenoxy)-2-hydroxypropylamine (3.65 g, 0.0174 moles) for the starting material of Example 2 and following the method of Example 2, the desired compound is obtained.
Reaction SMILES: [CH3:1][CH:2]([NH2:4])[CH3:3].[C:5]1([O:15][CH2:16][CH:17]2[O:19][CH2:18]2)[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[CH:8]=[CH:7][CH:6]=1>O>[CH3:1][CH:2]([NH:4][CH2:18][CH:17]([OH:19])[CH2:16][O:15][C:5]1[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[CH:8]=[CH:7][CH:6]=1)[CH3:3]
Reactant: c1ccc2c(OCC3CO3)cccc2c1
Reactant: CC(C)N
Solvent: O
Product: CC(C)NCC(O)COc1cccc2ccccc12

Procedure:
2.55 ml of (1-methylethyl)amine (0.0297 mol) are mixed with 1.25 ml of H2O and the mixture is then stirred with 5 g of 1-(1-naphthyloxy)-2,3-epoxypropane (0.0249 mol) and reacted at room temperature for 23 hours.
Reaction SMILES: Cl[CH2:2][C:3]1[N:7]2[CH:8]=[CH:9][CH:10]=[CH:11][C:6]2=[N:5][C:4]=1[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[N+:18]([O-])=O.C(N(CC)CC)C.[C:28]([N:35]1[CH2:40][CH2:39][NH:38][CH2:37][CH2:36]1)([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29]>C(Cl)Cl>[C:31]([O:30][C:28]([N:35]1[CH2:40][CH2:39][N:38]([CH2:2][C:3]2[N:7]3[CH:8]=[CH:9][CH:10]=[CH:11][C:6]3=[N:5][C:4]=2[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[NH2:18])[CH2:37][CH2:36]1)=[O:29])([CH3:34])([CH3:32])[CH3:33]
Reactant: CC(C)(C)OC(=O)N1CCNCC1
Reactant: O=[N+]([O-])c1ccccc1-c1nc2ccccn2c1CCl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CC(C)(C)OC(=O)N1CCN(Cc2c(-c3ccccc3N)nc3ccccn23)CC1
Temperature: 0 °C
Reaction time: 48 h
Yield: 66.7 %

Procedure:
To 3-Chloromethyl-2-(2-nitro-phenyl)-imidazo[1,2-a]pyridine (298 mg, 0.92 mmol) suspended in CH2Cl2 (15 ml) cooled to 0° C. was added dropwise triethylamine (279 mg, 3 eq), followed by 1-Boc-piperazine (1.3 eq, 221 mg) in two portions over a 24 hour period. The reaction mixture was concentrated to dryness and purified by chromatography using a 9:1 mixture of CH2Cl2 to MeOH. The fractions were concentrated, dissolved in Ethanol (20 ml), and stirred over H2 atmosphere with 10% Pd/C (10 mg) for 48 hours. The reaction mixture was filtered through Celite and concentrated, and dried under high vacuum to obtain 250 mg of the desired product. (MS, M++H=408.2)