Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([N:4]1[C:12]2[C:7](=[CH:8][C:9]([C:13](=[O:15])[CH3:14])=[CH:10][CH:11]=2)[CH2:6][C:5]1=[O:16])(=[O:3])[CH3:2].[F:17][C:18]([F:29])([F:28])[C:19]1[CH:27]=[CH:26][C:22]([C:23](O)=[O:24])=[CH:21][CH:20]=1>>[C:1]([N:4]1[C:12]2[C:7](=[CH:8][C:9]([C:13](=[O:15])[CH3:14])=[CH:10][CH:11]=2)[C:6](=[C:23]([C:22]2[CH:21]=[CH:20][C:19]([C:18]([F:17])([F:28])[F:29])=[CH:27][CH:26]=2)[OH:24])[C:5]1=[O:16])(=[O:3])[CH3:2]
Reactant: O=C(O)c1ccc(C(F)(F)F)cc1
Reactant: CC(=O)c1ccc2c(c1)CC(=O)N2C(C)=O
Product: CC(=O)c1ccc2c(c1)C(=C(O)c1ccc(C(F)(F)F)cc1)C(=O)N2C(C)=O

Procedure:
Prepared from 1,5-diacetyl-2-indolinone and 4-trifluoromethyl-benzoic acid
Reaction SMILES: [Br:1][C:2]1[C:3]2[CH:13]=[CH:12][CH:11]=[CH:10][C:4]=2[S:5][C:6]=1[CH2:7][CH2:8][OH:9].[H-].[Na+].[CH2:16](Br)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1>CN(C=O)C>[CH2:16]([O:9][CH2:8][CH2:7][C:6]1[S:5][C:4]2[CH:10]=[CH:11][CH:12]=[CH:13][C:3]=2[C:2]=1[Br:1])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1
Reactant: BrCc1ccccc1
Reactant: OCCc1sc2ccccc2c1Br
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: Brc1c(CCOCc2ccccc2)sc2ccccc12
Temperature: 0 °C
Reaction time: 0.33 h
Yield: 87.6 %

Procedure:
To a cooled solution (0° C.) of 2-(3-bromo-benzo[b]thiophen-2-yl)-ethanol (7.7 g, 29.9 mmol) in DMF (40 mL), NaH (1.44 g, 59.8 mmol, 95%) was added and the mixture was stirred for 20 min at 0° C. Subsequently benzylbromide (5.3 mL, 45 mmol) was added and the mixture was stirred overnight while the temperature gradually reached room temperature. After quenching with MeOH, the mixture was concentrated in vacuo, dissolved in EtOAc, washed with sat NaHCO3, brine, dried (Na2SO4) and concentrated in vacuo. Purification by silica gel column chromatography (eluent: EtOAc/Hexanes=1/1) afforded 9.1 g of 2-(2-benzyloxy-ethyl)-3-bromo-benzo[b]thiophene (87% yield).
Reaction SMILES: [C:1]1([C:7]2([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[CH2:12][CH2:11][N:10]([CH2:13][CH2:14][CH2:15][OH:16])[CH2:9][CH2:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH2:23]=[C:24]1[O:28][C:26](=[O:27])[CH2:25]1>C1(C)C=CC=CC=1.CC(C)=O>[C:1]1([C:7]2([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[CH2:8][CH2:9][N:10]([CH2:13][CH2:14][CH2:15][O:16][C:26](=[O:27])[CH2:25][C:24]([CH3:23])=[O:28])[CH2:11][CH2:12]2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: OCCCN1CCC(c2ccccc2)(c2ccccc2)CC1
Reactant: C=C1CC(=O)O1
Solvent: CC(C)=O
Solvent: Cc1ccccc1
Product: CC(=O)CC(=O)OCCCN1CCC(c2ccccc2)(c2ccccc2)CC1

Procedure:
23.6 g of 3-(4,4-diphenylpiperid-1-yl)-propanol were dissolved in 100 ml of absolute toluene, and 16 ml of a 50% strength solution of diketene in acetone were added with stirring. After standing for several days at room temperature (monitored by thin layer chromatography), the mixture was concentrated, and the residue was dried under high vacuum. The pale yellow, viscous oil which remains was employed without further purification for the next stage.
Reaction SMILES: [C:1]([O:5][C:6](=[O:30])[NH:7][C@@H:8]([CH2:26][CH:27]([CH3:29])[CH3:28])[CH2:9][O:10][C:11]1[CH:12]=[CH:13][C:14]2[C:24]3[C:19](=[CH:20][N:21]=[CH:22][CH:23]=3)[CH:18]([CH3:25])[O:17][C:15]=2[CH:16]=1)([CH3:4])([CH3:3])[CH3:2].C1C(=O)N([I:38])C(=O)C1>C(#N)C>[C:1]([O:5][C:6](=[O:30])[NH:7][C@@H:8]([CH2:26][CH:27]([CH3:29])[CH3:28])[CH2:9][O:10][C:11]1[C:12]([I:38])=[CH:13][C:14]2[C:24]3[C:19](=[CH:20][N:21]=[CH:22][CH:23]=3)[CH:18]([CH3:25])[O:17][C:15]=2[CH:16]=1)([CH3:3])([CH3:2])[CH3:4]
Reactant: O=C1CCC(=O)N1I
Reactant: CC(C)C[C@@H](COc1ccc2c(c1)OC(C)c1cnccc1-2)NC(=O)OC(C)(C)C
Solvent: CC#N
Product: CC(C)C[C@@H](COc1cc2c(cc1I)-c1ccncc1C(C)O2)NC(=O)OC(C)(C)C
Temperature: 80 °C
Yield: 48.9 %

Procedure:
To a solution of tert-butyl((2S)-4-methyl-1-((5-methyl-5H-chromeno[3,4-c]pyridin-8-yl)oxy)pentan-2-yl)carbamate (200 mg, 0.485 mmol) in acetonitrile (4 mL) was added NIS (654 mg, 2.91 mmol) and the mixture refluxed at 80° C. for 12 h. The volatiles were removed under reduced pressure. The residue was dissolved in water (10 mL) and the aqueous layer was extracted with ethyl acetate (3×10 mL). The combined organic layers were washed with brine (15 mL). The organic layer was dried over Na2SO4 and concentrated under reduced pressure. The crude product was purified by silica gel chromatography (pet ether: ethyl acetate) to afford tert-butyl((2S)-1-((9-iodo-5-methyl-5H-chromeno[3,4-c]pyridin-8-yl)oxy)-4-methylpentan-2-yl)carbamate (150 mg, 0.237 mmol, 49% yield) as a dark brown oil. LCMS (ESI) m/e 539.0 [(M+H)+, calcd for C24H32IN2O4 539.1]; LC/MS retention time (method D): tR=1.84 min.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH:11]([C:12]3[CH:17]=[CH:16][C:15]([O:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26]I)=[CH:14][CH:13]=3)[CH:10]([CH2:28][CH2:29][CH:30]([C:32]3[CH:37]=[CH:36][C:35]([F:38])=[CH:34][CH:33]=3)[OH:31])[C:9]2=[O:39])=[CH:4][CH:3]=1.[CH3:40][NH:41][CH2:42][CH:43]([OH:52])[CH:44]([OH:51])[CH:45]([OH:50])[CH:46]([OH:49])[CH2:47][OH:48]>CN(C)C=O>[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH:11]([C:12]3[CH:17]=[CH:16][C:15]([O:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][N:41]([CH3:40])[CH2:42][CH:43]([OH:52])[CH:44]([OH:51])[CH:45]([OH:50])[CH:46]([OH:49])[CH2:47][OH:48])=[CH:14][CH:13]=3)[CH:10]([CH2:28][CH2:29][CH:30]([C:32]3[CH:37]=[CH:36][C:35]([F:38])=[CH:34][CH:33]=3)[OH:31])[C:9]2=[O:39])=[CH:4][CH:3]=1
Reactant: CNCC(O)C(O)C(O)C(O)CO
Reactant: O=C1C(CCC(O)c2ccc(F)cc2)C(c2ccc(OCCCCCCCCI)cc2)N1c1ccc(F)cc1
Solvent: CN(C)C=O
Product: CN(CCCCCCCCOc1ccc(C2C(CCC(O)c3ccc(F)cc3)C(=O)N2c2ccc(F)cc2)cc1)CC(O)C(O)C(O)C(O)CO
Temperature: 50 °C
Reaction time: 2 h

Procedure:
150 mg of 1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3-hydroxypropyl]-4-[4-(8-iodooctyloxy)phenyl]azetidin-2-one are dissolved in 5 ml of absolute dimethylformamide. 180 mg of 6-methylaminohexane-1,2,3,4,5-pentaol are then added, and the reaction solution is stirred at 50° C. for 2 h. After concentration using a rotary evaporator and oil pump vacuum at 40° C., the residue is purified by preparative HPLC. The product is obtained as an oil. C39H52F2N2O8 (714) MS (ESI): M+
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[C:10]3[C:17]([CH3:18])=[C:16]([C:19]([O:21]C)=[O:20])[S:15][C:11]=3[N:12]=[CH:13][N:14]=2)=[C:4]([O:23][CH:24]2[CH2:28][CH2:27][CH:26]([OH:29])[CH2:25]2)[CH:3]=1.Cl>CO.C1COCC1.[OH-].[Na+]>[F:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[C:10]3[C:17]([CH3:18])=[C:16]([C:19]([OH:21])=[O:20])[S:15][C:11]=3[N:12]=[CH:13][N:14]=2)=[C:4]([O:23][CH:24]2[CH2:28][CH2:27][CH:26]([OH:29])[CH2:25]2)[CH:3]=1
Reactant: COC(=O)c1sc2ncnc(Nc3ccc(F)cc3OC3CCC(O)C3)c2c1C
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: C1CCOC1
Product: Cc1c(C(=O)O)sc2ncnc(Nc3ccc(F)cc3OC3CCC(O)C3)c12

Procedure:
Methyl 4-(4-fluoro-2-(3-hydroxycyclopentyloxy)phenylamino)-5-methylthieno[2,3-d]pyrimidine-6-carboxylate (150 mg) in methanol (2.0 ml), THF (2.0 ml) and 2M aq. sodium hydroxid (0.9 ml) was stirred at reflux for 40 min. After addition of 2 M aq. HCl (8.0 ml) the reaction mixture was concentrated in vacuo. The aqueous layer was filtered and washed with water. The crude was re-evaporated from EtOH to give the desired product.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([C:12]([CH:14]2[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]2)=[O:13])[CH:5]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:7]=1.[CH2:20]=O>C(O)=O>[Br:1][C:2]1[CH:3]=[C:4]([C:12]([CH:14]2[CH2:15][CH2:16][N:17]([CH3:20])[CH2:18][CH2:19]2)=[O:13])[CH:5]=[C:6]([C:8]([F:10])([F:11])[F:9])[CH:7]=1
Reactant: O=C(c1cc(Br)cc(C(F)(F)F)c1)C1CCNCC1
Reactant: C=O
Solvent: O=CO
Product: CN1CCC(C(=O)c2cc(Br)cc(C(F)(F)F)c2)CC1
Yield: 77 %

Procedure:
Stir the mixture of (3-bromo-5-(trifluoromethyl)phenyl)(piperidin-4-yl)methanone (400 mg, 0.96 mmol), formic acid (1 mL) and formaldehyde (1 mL) at 100° C. overnight. Upon the reaction completion, concentrate under reduced pressure to provide the crude product (250 mg, 77%) which is used in next step without further purification.
Reaction SMILES: Cl.[CH2:2]([O:9][C:10](=[O:20])[C@@H:11]1[CH2:15][CH2:14][CH2:13][N:12]1[C:16](=[O:19])[CH2:17][NH2:18])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.C(N(CC)CC)C.[C:28]1([S:34](Cl)(=[O:36])=[O:35])[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1>C(Cl)Cl>[CH2:2]([O:9][C:10](=[O:20])[C@@H:11]1[CH2:15][CH2:14][CH2:13][N:12]1[C:16](=[O:19])[CH2:17][NH:18][S:34]([C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)(=[O:36])=[O:35])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1
Reactant: NCC(=O)N1CCC[C@H]1C(=O)OCc1ccccc1
Reactant: O=S(=O)(Cl)c1ccccc1
Agent: Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: O=C(OCc1ccccc1)[C@@H]1CCCN1C(=O)CNS(=O)(=O)c1ccccc1
Reaction time: 1 h
Yield: 94.9 %

Procedure:
Glycyl-L-proline benzylester hydrochloride (1.49 g, 5 mmole) was dissolved in methylene chloride (30 ml), and triethylamine (1.11 g, 11 mmole) was added thereto at -30° C., and then methylene chloride (10 ml) solution of benzenesulfonylchloride (0.86 g, 5 mmole) was added dropwise. The mixture was stirred for 1 hour at less than 0° C, and then for 5 hours at room temperature, and methylene chloride (60 ml) was added. The mixture thus obtained was washed with 5% aqueous sodium bicarbonate (100 ml, twice), 1N aqueous hydrochloric acid (100 ml, twice) and water (100 ml) in the order given, and dried over anhydrous magnesium sulfate. The solvent was distilled under reduced pressure to give N-benzenesulfonylglycyl-L-proline benzylester (yield: 1.91 g, 94.9%).
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]([C:8](=O)[CH2:9][C:10](=O)[C:11]([F:14])([F:13])[F:12])[CH:5]=[CH:6][CH:7]=1.[NH2:17][C:18]1[N:19]=[CH:20][NH:21][C:22]=1[C:23]#[N:24]>>[CH3:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:9]=[C:10]([C:11]([F:14])([F:13])[F:12])[N:19]3[CH:20]=[N:21][C:22]([C:23]#[N:24])=[C:18]3[N:17]=2)[CH:5]=[CH:6][CH:7]=1
Reactant: N#Cc1[nH]cnc1N
Reactant: Cc1cccc(C(=O)CC(=O)C(F)(F)F)c1
Product: Cc1cccc(-c2cc(C(F)(F)F)n3cnc(C#N)c3n2)c1
Yield: 53.3 %

Procedure:
Reaction of 1-(3-methyl-phenyl)-4,4,4-trifluoro-butane-1,3-dione (230 mg, 1.0 mmol), prepared from commercially available 3-methyl-acetophenone according to general procedure A, and 4-amino-5-cyano-1H-imidazole (108 mg, 1.0 mmol) according to general procedure B yielded the title compound as a yellow solid (161 mg, 53%). MS (ISP) 302.9 [(M+H)+]; mp 202° C.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:16]([CH2:17][C:18]([OH:20])=O)[C:11]3=[N:12][CH:13]=[CH:14][CH:15]=[C:10]3[N:9]=2)=[CH:4][CH:3]=1.C(N1C=CN=C1)(N1C=CN=C1)=O.[CH2:33]([N:35]1[CH2:39][CH2:38][CH:37]([NH2:40])[CH2:36]1)[CH3:34]>O1CCCC1>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[N:16]([CH2:17][C:18]([NH:40][CH:37]3[CH2:38][CH2:39][N:35]([CH2:33][CH3:34])[CH2:36]3)=[O:20])[C:11]3=[N:12][CH:13]=[CH:14][CH:15]=[C:10]3[N:9]=2)=[CH:6][CH:7]=1
Reactant: CCN1CCC(N)C1
Reactant: O=C(O)Cn1c(-c2ccc(Br)cc2)nc2cccnc21
Agent: O=C(n1ccnc1)n1ccnc1
Solvent: C1CCOC1
Product: CCN1CCC(NC(=O)Cn2c(-c3ccc(Br)cc3)nc3cccnc32)C1
Temperature: 25 °C
Reaction time: 3 h
Yield: 71.7 %

Procedure:
A suspension of 2-(4-bromophenyl)-3H-imidazo[4,5-b]pyridine-3-acetic acid (5.0 g, 0.0151 mole), 1,1'-carbonyldiimidazole (2.45 g, 0.0151 mole), and anhydrous tetrahydrofuran (100 ml) was stirred at room temperature with a stream of nitrogen bubbling through it for 3 hours. The nitrogen flow was stopped and a solution of 1-ethyl-3-aminopyrrolidine (1.89 g, 0.0166 mole) in dry tetrahydrofuran (25 ml) was added. The solution was stirred at room temperature under nitrogen for 2 hours. The reaction mixture was concentrated in vacuo and the residue triturated in water (100 ml) and filtered. The filter cake was recrystallized from isopropyl alcohol-isopropyl ether to give 4.64 g (72%) of white needles, mp 202.5°-204° C.
Reaction SMILES: [C:1]1([C:7]([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[S:8][C@H:9]2[NH:12][C:11](=[O:13])[C@@H:10]2[C@H:14]([O:16][Si:17]([C:20]([CH3:23])([CH3:22])[CH3:21])([CH3:19])[CH3:18])[CH3:15])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Br[CH2:37][C:38]([O:40][CH2:41][CH:42]=[CH2:43])=[O:39].[OH-].[K+].C1CC2OCCOCCOC3C(OCCOCCOC2CC1)CCCC3>C1C=CC=CC=1>[CH2:41]([O:40][C:38]([CH2:37][N:12]1[C@H:9]([S:8][C:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)([C:30]2[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=2)[C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[C@@H:10]([C@H:14]([O:16][Si:17]([C:20]([CH3:22])([CH3:23])[CH3:21])([CH3:19])[CH3:18])[CH3:15])[C:11]1=[O:13])=[O:39])[CH:42]=[CH2:43]
Reactant: C[C@@H](O[Si](C)(C)C(C)(C)C)[C@H]1C(=O)N[C@@H]1SC(c1ccccc1)(c1ccccc1)c1ccccc1
Reactant: C=CCOC(=O)CBr
Agent: C1CCC2OCCOCCOC3CCCCC3OCCOCCOC2C1
Agent: [K+]
Agent: [OH-]
Solvent: c1ccccc1
Product: C=CCOC(=O)CN1C(=O)[C@H]([C@@H](C)O[Si](C)(C)C(C)(C)C)[C@H]1SC(c1ccccc1)(c1ccccc1)c1ccccc1

Procedure:
The tritylthioazetidinone 2 is treated with 1.5 equivalents of allyl bromoacetate and powdered potassium hydroxide in benzene solvent at ambient temperature in the presence of dicyclohexyl-18-crown-6 for 4 hours. The resulting (3S,4R)-1-(allyloxycarbonyl)methyl-3-[(R)-1-(tert-butyldimethylsiloxy)ethyl]-4-triphenylmethylthio-2-azetidinone (3) is isolated by conventional means. Alternatively p-nitro-benzylbromoacetate may be substituted for allylbromoacetate.
Reaction SMILES: [OH:1][C:2]1[C:11]([N:12]2[CH2:17][CH2:16][O:15][CH2:14][CH2:13]2)=[C:10]([N+:18]([O-])=O)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]=1>CO.O1CCCC1.[Pd]>[NH2:18][C:10]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]=[C:2]([OH:1])[C:11]=1[N:12]1[CH2:13][CH2:14][O:15][CH2:16][CH2:17]1
Reactant: O=[N+]([O-])c1c(N2CCOCC2)c(O)nc2ccccc12
Agent: [Pd]
Solvent: C1CCOC1
Solvent: CO
Product: Nc1c(N2CCOCC2)c(O)nc2ccccc12

Procedure:
The 2-hydroxy-3-morpholino-4-nitroquinoline (1.5 g, 0.0054 mol) was dissolved in a mixed solvent of methanol and tetrahydrofuran and subjected to catalytic reduction in the presence of 10g palladium-on-carbon. After completion of the reaction, the palladium-on-carbon catalyst was filtered off and the mother liquor was concentrated. Following purification by chromatography on an alumina column using chloroform as a developing solvent, recrystallization from chloroform was conducted to obtain 4-amino-2-hydroxy-3-morpholinoquinoline in an amount of 0.9 g (yield, 63%).
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([NH:8][CH2:9][C:10]2[CH:11]=[N:12][CH:13]=[CH:14][CH:15]=2)[CH:5]=[CH:6][CH:7]=1.[C:16]1([O:23][CH3:24])[C:17](=[CH:19][CH:20]=[CH:21][CH:22]=1)[OH:18]>>[CH3:24][O:23][C:16]1[CH:22]=[CH:21][CH:20]=[CH:19][C:17]=1[O:18][C:2]1[CH:3]=[C:4]([NH:8][CH2:9][C:10]2[CH:11]=[N:12][CH:13]=[CH:14][CH:15]=2)[CH:5]=[CH:6][CH:7]=1
Reactant: Brc1cccc(NCc2cccnc2)c1
Reactant: COc1ccccc1O
Product: COc1ccccc1Oc1cccc(NCc2cccnc2)c1

Procedure:
Using the method of Example 342 using N-(3-bromophenyl)pyridin-3-ylmethylamine and guaiacol (Aldrich) and purifying via preparative HPLC eluting with 1:1 DCM/ethyl acetate gave N-(3-(2-Methoxyphenoxy)phenyl) pyrid-3-ylmethylamine. Anal Calcd for C19H18N2O2.0.5H2O: C, 72.36; H, 6.07; N, 8.88. Found: C, 72.43; H, 5.80; N, 8.96. MS found 307.2 [M+H]+
Reaction SMILES: [OH:1][CH:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4](=O)[N:3]1[CH2:12][S:13][C:14]1[CH:19]=[CH:18][N:17]=[CH:16][CH:15]=1.[BH4-].[Na+].O.N>FC(F)(F)C(O)=O>[C:2]1(=[O:1])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][N:3]1[CH2:12][S:13][C:14]1[CH:19]=[CH:18][N:17]=[CH:16][CH:15]=1
Reactant: O=C1c2ccccc2C(O)N1CSc1ccncc1
Agent: N
Agent: [BH4-]
Agent: [Na+]
Solvent: O
Solvent: O=C(O)C(F)(F)F
Product: O=C1c2ccccc2CN1CSc1ccncc1
Reaction time: 0.25 h
Yield: 54.6 %

Procedure:
To a solution of 681 mg (2.5 mmol) of 4-[(3-hydroxyisoindolin-1-on-2-yl)methylthio]pyridine in 6 ml of trifluoroacetic acid, 0.30 g (7.93 mmol) of sodium borohydride was added in small portions, and the mixture was stirred for 15 minutes. The reaction mixture was poured into cold water and aqueous ammonia was added to make the mixture basic, followed by extraction with methylene chloride. The extract was dried over anhydrous magnesium sulfate and the solvent was distilled off. The residue was purified by recrystallization (solvent: ethyl acetate) to give. 350 mg of the desired product (54.6% yield, colorless columns), mp. 131°-132° C.
Reaction SMILES: C[O:2][C:3]([C:5]1[CH:13]=[CH:12][C:8]2[N:9]=[CH:10][S:11][C:7]=2[CH:6]=1)=O.[H-].[Al+3].[Li+].[H-].[H-].[H-].[OH-].[Na+]>C1COCC1>[S:11]1[C:7]2[CH:6]=[C:5]([CH2:3][OH:2])[CH:13]=[CH:12][C:8]=2[N:9]=[CH:10]1
Reactant: COC(=O)c1ccc2ncsc2c1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Product: OCc1ccc2ncsc2c1
Temperature: -10 °C
Reaction time: 0.33 h
Yield: 93.5 %

Procedure:
Add slowly a solution of benzothiazole-6-carboxylic acid methyl ester (0.5 g, 2.59 mmol) in anhydrous THF (10 mL) to a suspension of lithium aluminum hydride (0.1 g, 2.85 mmol) in anhydrous THF (20 mL) at −10° C. and stir for 20 min at −10° C. Treat the reaction mixture with 2N aqueous NaOH until a granular precipitate starts to form and filter through a pad of Celite®. Evaporate the solvent and purify by chromatography on silica gel eluting with hexane/EtOAc (1:0, 9:1, 4:1, 7:3, 3:2 and 1:1) to obtain the desired intermediate as a yellow oil (0.4 g, 99%). MS (ES+) m/z: 166 (M+H)+.
Reaction SMILES: I([O-])(=O)(=O)=O.[Na+].Cl.Cl.[NH2:9][C:10]1[C:11]2[NH:18][CH:17]=[C:16]([C@H:19]3[C@H:23]([OH:24])[C@H:22]([OH:25])[C@@H:21]([CH2:26][S:27][CH3:28])[NH:20]3)[C:12]=2[N:13]=[CH:14][N:15]=1.[BH4-].[Na+]>O>[NH2:9][C:10]1[C:11]2[NH:18][CH:17]=[C:16]([C@H:19]([NH:20][C@H:21]([CH2:26][S:27][CH3:28])[CH2:22][OH:25])[CH2:23][OH:24])[C:12]=2[N:13]=[CH:14][N:15]=1
Reactant: CSC[C@H]1N[C@@H](c2c[nH]c3c(N)ncnc23)[C@H](O)[C@@H]1O
Agent: Cl
Agent: [BH4-]
Agent: [Na+]
Solvent: O
Product: CSC[C@H](CO)N[C@H](CO)c1c[nH]c2c(N)ncnc12
Temperature: 25 °C
Reaction time: 1 h
Yield: 47 %

Procedure:
Sodium periodate (0.070 g, 0.326 mmol) was added to a solution of (2S,3S,4R,5S)-2-(4-amino-5H-pyrrolo[3,2-d]pyrimidin-7-yl)-5-(methylthiomethyl)pyrrolidine-3,4-diol dihydrochloride (0.1 g, 0.272 mmol, prepared according to G. B. Evans, R. H. Furneaux, V. L. Schramm, V. Singh, P. C. Tyler, J. Med. Chem., 2004, 47, 3275) in water (3 ml) and stirred at rt for 1 h. Sodium borohydride (0.051 g, 1.358 mmol) was added in small portions (vigorous reaction). The solution, which momentarily darkened then became almost colourless, was stirred for 15 mins. Silica gel was added and the solvent evaporated. The residue was chromatographed on silica gel (CH2Cl2-MeOH-28% aq. NH4OH, 50:10:1) and the fractions containing product were evaporated to a gum (70 mg) which was dissolved in MeOH and passed through Amberlyst A26 (OH−) resin using MeOH as eluant. The solvent was evaporated to a yellow gum, dissolved in water and lyophilised to give (S)-2-((S)-1-(4-amino-5H-pyrrolo[3,2-d]pyrimidin-7-yl)-2-hydroxyethylamino)-3-(methylthio)propan-1-ol as a cream coloured solid (38 mg, 47%).
Reaction SMILES: [H-].[Na+].C(OP([CH2:11][C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])(OCC)=O)C.[F:19][C:20]1[CH:27]=[CH:26][C:23]([CH:24]=O)=[CH:22][C:21]=1[N+:28]([O-:30])=[O:29].O>C1(C)C=CC=CC=1.C1COCC1>[F:19][C:20]1[CH:27]=[CH:26][C:23](/[CH:24]=[CH:11]/[C:12]([O:14][C:15]([CH3:16])([CH3:17])[CH3:18])=[O:13])=[CH:22][C:21]=1[N+:28]([O-:30])=[O:29]
Reactant: O=Cc1ccc(F)c([N+](=O)[O-])c1
Reactant: CCOP(=O)(CC(=O)OC(C)(C)C)OCC
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: Cc1ccccc1
Solvent: O
Product: CC(C)(C)OC(=O)/C=C/c1ccc(F)c([N+](=O)[O-])c1
Temperature: 0 °C
Reaction time: 0.5 h

Procedure:
Under argon, 130.1 mg (3.25 mmol) of sodium hydride were initially charged in 2 ml of toluene and 2 ml of THF. The mixture was cooled to 0° C., and 857.7 mg (3.40 mmol) of tert-butyl (diethoxyphosphoryl)acetate were added slowly. The mixture was stirred for another 30 min, and 500 mg (2.96 mmol) of 4-fluoro-3-nitrobenzaldehyde were then added. The reaction mixture was slowly warmed to RT and stirred for 3 h. The reaction mixture was then added to water and extracted three times with ethyl acetate. The organic phase was concentrated under reduced pressure and the residue purified by chromatography on silica gel (mobile phase cyclohexane/ethyl acetate 30:1→10:1). This gave 543 mg (69% of theory) of the title compound.
Reaction SMILES: [NH2:1][C:2]1[C:3]([C:14]([NH:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][N:18]=2)=[O:15])=[N:4][C:5]([N:8]2[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]2)=[CH:6][N:7]=1.CCN(CC)CC.[CH2:30]([S:32](Cl)(=[O:34])=[O:33])[CH3:31]>C(Cl)Cl>[NH2:1][C:2]1[C:3]([C:14]([NH:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][N:18]=2)=[O:15])=[N:4][C:5]([N:8]2[CH2:9][CH2:10][N:11]([S:32]([CH2:30][CH3:31])(=[O:34])=[O:33])[CH2:12][CH2:13]2)=[CH:6][N:7]=1
Reactant: Nc1ncc(N2CCNCC2)nc1C(=O)Nc1ccccn1
Reactant: CCS(=O)(=O)Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CCS(=O)(=O)N1CCN(c2cnc(N)c(C(=O)Nc3ccccn3)n2)CC1
Reaction time: 2 h
Yield: 100 %

Procedure:
3-amino-6-piperazin-1-yl-N-(2-pyridyl)pyrazine-2-carboxamide (100 mg, 0.1896 mmol) was dissolved in DCM (5 mL) and treated with Et3N (57.56 mg, 79.28 μL, 0.5688 mmol) followed by ethanesulfonyl chloride (26.82 mg, 19.76 μL, 0.2086 mmol). The reaction mixture was allowed to stir for 2 hours and then diluted with dichloromethane and washed with water. The aqueous layer was extracted further with dichloromethane and the organics washed with saturated aqueous NaHCO3, dried and concentrated in vacuo. The residue was purified on silica gel by flash column chromatography (0-5% MeOH/DCM) to afford the title compound (74.2 mg, 37% Yield). 1H NMR (400.0 MHz, DMSO) d 1.24 (t, J=7.3 Hz, 3H), 3.13 (q, J=7.4 Hz, 2H), 3.34-3.38 (m, 4H), 3.52-3.54 (m, 4H), 7.04 (s, 2H), 7.18-7.21 (m, 1H), 7.88 (s, 1H), 8.21 (d, J=8.4 Hz, 1H), 8.38 (d, J=3.2 Hz, 2H) and 10.08 (s, 1H) ppm; MS (ES+) 392.0
Reaction SMILES: [CH3:1][N:2]1[C:6]([N+:7]([O-:9])=[O:8])=[CH:5][N:4]=[C:3]1[CH2:10][O:11][C:12]1[CH:17]=[CH:16][C:15]([S:18][CH3:19])=[CH:14][CH:13]=1.ClC1C=CC=C(C(OO)=[O:28])C=1.C(=O)([O-])[O-].[Na+].[Na+]>C(Cl)(Cl)Cl>[CH3:1][N:2]1[C:6]([N+:7]([O-:9])=[O:8])=[CH:5][N:4]=[C:3]1[CH2:10][O:11][C:12]1[CH:17]=[CH:16][C:15]([S:18]([CH3:19])=[O:28])=[CH:14][CH:13]=1
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: CSc1ccc(OCc2ncc([N+](=O)[O-])n2C)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: ClC(Cl)Cl
Product: Cn1c([N+](=O)[O-])cnc1COc1ccc(S(C)=O)cc1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
27.9 Grams (0.1 mol) of 1-methyl-2-(4-methylthiophenyloxymethyl)-5-nitro-imidazole are dissolved in 200 ml of chloroform, and the solution is added dropwise while stirring at 25° C. to a solution of 17.25 g (0.1 mol) of m-chloroperbenzoic acid in 70 ml of chloroform. The reaction mixture is stirred for 1 hour at 25° C., the solution is shaken with dilute sodium carbonate solution, the chloroform phase is separated, dried over sodium sulfate and evaporated. The residue is recrystallized from ethanol with the addition of charcoal.